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Yang A, Yu J, Cheung JTK, Chan JCN, Chow E. Real world evidence of insulin and biosimilar insulin therapy-Opportunities to improve adherence, outcomes and cost-effectiveness. Diabetes Obes Metab 2025. [PMID: 40235124 DOI: 10.1111/dom.16386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 03/15/2025] [Accepted: 03/24/2025] [Indexed: 04/17/2025]
Abstract
Insulin has been discovered for more than a century; however, its benefits to people with diabetes are yet to be fully realized due to barriers related to access, quality of care and costs. Insulin therapy remains the cornerstone of diabetes management. The multicausality of diabetes and its subtypes calls for comprehensive phenotyping and use of biomarkers to ensure timely use of insulin to achieve early glycaemic control for long-term benefits. Biosimilar insulins are biologic products that closely resemble originator insulins without significant differences in safety or efficacy. The lower investment costs needed for research and development make biosimilar insulin more affordable to improve access. While the efficacy of insulin products is proven in controlled settings, real world evidence (RWE) from real world data (RWD) plays a crucial role in assessing the safety, efficacy, cost-effectiveness, adherence to and impacts of different insulin products, including biosimilars, on clinical outcomes. In this narrative review, we summarized the trends of insulin use and patterns of biosimilar insulin utilization in real world practice across different regions. We reviewed RWE on clinical safety, efficacy and cost-effectiveness of biosimilar insulin, as well as therapeutic inertia and non-adherence with insulin therapy. We also highlighted barriers to insulin adherence and enablers for persistence, along with potential solutions to promote the use of insulin and technologies for optimizing glycaemic control in different subtypes of diabetes. During our extensive literature review, we identified data gaps in the usage of biosimilar insulin in real world practice. We advocate for implementing a diabetes register designed fit-for-purpose, managed by a trained doctor-nurse team with system support, to generate RWE. By setting up registers with structured data collection, we can generate high quality data for integrative analysis with electronic health records (EHR) and health claims to evaluate the impacts of insulin products and other diabetes programmes on clinical outcomes, quality of life and healthcare costs to inform practice and policies. PLAIN LANGUAGE SUMMARY: Diabetes affects approximately 10.5% of the global population and insulin is a vital treatment for diabetes management. Insulin was discovered more than a century ago, although its benefits to people with diabetes are yet to be fully realized due to barriers related to access, quality of care, and costs. Real-world evidence from real-world data plays a crucial role in assessing the safety, efficacy, cost-effectiveness, adherence to, and impacts of different insulin products, including biosimilars, on clinical outcomes. In this publication, the authors provided a detailed review of the patterns of use and cost-effectiveness of biosimilar insulin, and identified major data gaps. The authors explained the methodology, utility, and limitations of generating real-world evidence based on real-world data from sources such as registers, electronic health records and health claims for assessing treatment effectiveness and safety. The authors proposed the implementation of a purpose-built diabetes register with structured data collection, managed by a trained doctor-nurse team with system support. These high-quality data can be integrated with electronic health records and health claims for evaluation of interventions, including insulin on outcomes, quality of life, and costs to inform practice and policy. Based on these premises and available data, the authors summarized trends in insulin use including biosimilar insulin, and reviewed real-world evidence on the safety, efficacy, and cost-effectiveness of these products. They also identified barriers like therapeutic inertia and non-adherence, discussed enablers for persistence, and proposed solutions to evaluate the impacts of insulin products and other diabetes programs on clinical outcomes, quality of life, and healthcare costs to inform practice and policies.
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Affiliation(s)
- Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
| | - Jiazhou Yu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
| | - Johnny T K Cheung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China
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Wang Y, Chin WY, Lam CLK, Wan EYF. Trajectory of haemoglobin A1c and incidence of cardiovascular disease in patients with type 2 diabetes mellitus. Diabetes Obes Metab 2024; 26:5138-5146. [PMID: 39161066 DOI: 10.1111/dom.15856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 07/17/2024] [Accepted: 07/21/2024] [Indexed: 08/21/2024]
Abstract
AIM To evaluate the association between changes in haemoglobin A1c (HbA1c) and the concurrent incidence of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) patients. METHOD We conducted a retrospective cohort study among T2DM patients with HbA1c measurement after T2DM diagnosis between August 2009 and September 2010. The patients were classified into six subgroups based on baseline HbA1c (<7%; 7%-7.9%; ≥8%) and age (<65; ≥65 years), and then clustered into classes by HbA1c trajectory and CVD incidence over the 12-year follow-up period using joint latent class mixture models. We explored the HbA1c trajectories and CVD incidences in each latent class. Multinomial logistic regression was used to compare the baseline characteristics among different latent classes. RESULTS A total of 128 843 T2DM patients were included with a median follow-up period of 11.7 years. Ten latent classes were identified in patients with baseline HbA1c ≥ 8% and age <65 years, while seven classes were identified in the other five groups. Among all the identified latent classes, patients with fluctuating HbA1c trajectories, characterized by alternating periods of increase and decrease, had higher CVD incidences. Male patients, and patients with higher baseline HbA1c and use of antidiabetic drugs were more likely to have a fluctuating HbA1c trajectory. More specifically, patients aged < 65 years with younger age or a smoking habit, and patients aged ≥ 65 years with a longer duration of T2DM were more likely to have a fluctuating HbA1c trajectory. CONCLUSION We found that T2DM patients with fluctuating HbA1c trajectories could have a higher CVD risk. Different trajectory-associated characteristics in age subgroups highlight the need for individualized management of T2DM patients.
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Affiliation(s)
- Yuan Wang
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Weng Yee Chin
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Cindy Lo Kuen Lam
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Family Medicine, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China
| | - Eric Yuk Fai Wan
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong SAR, China
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Ji L, Agesen RM, Bain SC, Fu F, Gabery S, Geng J, Li Y, Lu Y, Luo B, Pang W, Tao Y. Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial. Diabetologia 2024; 67:1800-1816. [PMID: 38985161 PMCID: PMC11410852 DOI: 10.1007/s00125-024-06133-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 01/22/2024] [Indexed: 07/11/2024]
Abstract
AIMS/HYPOTHESIS The aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. METHODS The Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS). RESULTS Of 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were -2 (-4, -1) mmol/mol, -8 (-9, -6) mmol/mol and -11 (-12, -9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were -0.2 (-0.3, -0.1), -0.7 (-0.8, -0.6) and -1.0 (-1.1, -0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] -0.9 [-1.4, -0.4] kg, -2.3 [-2.8, -1.8] kg and -3.3 [-3.8, -2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity. CONCLUSIONS/INTERPRETATION Significantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. TRIAL REGISTRATION ClinicalTrials.gov NCT04017832. FUNDING This trial was funded by Novo Nordisk A/S, Søborg, Denmark.
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Affiliation(s)
- Linong Ji
- Peking University People's Hospital, Beijing, China
| | | | - Stephen C Bain
- Diabetes Research Unit, Swansea University, Swansea, UK.
| | - Fangming Fu
- Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | | | - Jianlin Geng
- Harrison International Peace Hospital, Hengshui, China
| | - Yiming Li
- Huashan Hospital, Fudan University, Shanghai, China
| | - Yibing Lu
- Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Bifen Luo
- Novo Nordisk (China) Pharmaceuticals Co., Ltd., Beijing, China
| | - Wuyan Pang
- Huaihe Hospital of Henan University, Kaifeng, Henan, China
| | - Yi Tao
- Novo Nordisk (China) Pharmaceuticals Co., Ltd., Beijing, China
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Cheung JTK, Yang A, Wu H, Lau ESH, Lui J, Kong APS, Ma RCW, Luk AOY, Chow E, Chan JCN. Association of dipeptidyl peptidase-4 inhibitor initiation at glycated haemoglobin <7.5% with reduced major clinical events mediated by low glycated haemoglobin variability. Diabetes Obes Metab 2024; 26:3339-3351. [PMID: 38802991 DOI: 10.1111/dom.15662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 05/06/2024] [Accepted: 05/07/2024] [Indexed: 05/29/2024]
Abstract
AIM Therapeutic inertia, hypoglycaemia and poor treatment persistence can lead to glycaemic fluctuation and poor outcomes in type 2 diabetes (T2D). We compared glycated haemoglobin (HbA1c) variability, insulin initiation, severe hypoglycaemia and clinical events in patients with T2D initiated dipeptidyl peptidase-4 inhibitors (DPP4is) at low versus high HbA1c thresholds. METHODS Using territory-wide electronic medical records in Hong Kong, we curated a propensity score-matched cohort of patients initiated DPP4i at HbA1c <7.5% versus ≥7.5% in 2007-2019. We expressed the HbA1c variability score (HVS) as a proportion of HbA1c varied by ≥0.5% compared with preceding values. We used the Cox model to compare the risks of insulin initiation and clinical outcomes, adjusted for time-varying variables between the two groups. Mediation analysis estimated the effects of HbA1c variability on outcomes. RESULTS Among 6874 insulin-naïve patients who initiated DPP4i, 88.7% were treated with metformin and 79.6% with sulphonylureas at baseline (54.9% men; mean age 65.2 ± 11.4 years). After a median follow-up of 4.6 years, compared with the high-threshold plus high-HVS group (≥50%), the low-threshold plus low-HVS (<50%) group had reduced hazard ratios (95% confidence interval) of insulin initiation (0.35, 0.31-0.40), severe hypoglycaemia (0.38, 0.34-0.44), major adverse cardiovascular endpoints (0.76, 0.66-0.88), heart failure (0.42, 0.36-0.49), end-stage kidney disease (0.65, 0.36-0.49) and mortality (0.45, 0.35-0.57). Reduced HbA1c variability explained 31.1%-81.2% of the effect size of DPP4i initiation at HbA1c <7.5% versus ≥7.5% on outcomes. CONCLUSIONS In Chinese patients with T2D, avoiding therapeutic inertia with intensified glycaemic control at HbA1c <7.5% using drugs with low risk of hypoglycaemia and good tolerability, such as DPP4i, delayed insulin treatment, reduced HbA1c variability and improved clinical events.
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Affiliation(s)
- Johnny T K Cheung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Eric S H Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Juliana Lui
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Alice P S Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Ronald C W Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Andrea O Y Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
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Chan JCN, Yang A, Chu N, Chow E. Current type 2 diabetes guidelines: Individualized treatment and how to make the most of metformin. Diabetes Obes Metab 2024; 26 Suppl 3:55-74. [PMID: 38992869 DOI: 10.1111/dom.15700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 05/24/2024] [Accepted: 05/24/2024] [Indexed: 07/13/2024]
Abstract
Evidence-based guidelines provide the premise for the delivery of quality care to preserve health and prevent disabilities and premature death. The systematic gathering of observational, mechanistic and experimental data contributes to the hierarchy of evidence used to guide clinical practice. In the field of diabetes, metformin was discovered more than 100 years ago, and with 60 years of clinical use, it has stood the test of time regarding its value in the prevention and management of type 2 diabetes. Although some guidelines have challenged the role of metformin as the first-line glucose-lowering drug, it is important to point out that the cardiovascular-renal protective effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were gathered from patients with type 2 diabetes, the majority of whom were treated with metformin. Most national, regional and international guidelines recommend metformin as a foundation therapy with emphasis on avoidance of therapeutic inertia and early attainment of multiple treatment goals. Moreover, real-world evidence has confirmed the glucose-lowering and cardiovascular-renal benefits of metformin accompanied by an extremely low risk of lactic acidosis. In patients with type 2 diabetes and advanced chronic kidney disease (estimated glomerular filtration rate 15-30 mL/min/1.73m2), metformin discontinuation was associated with an increased risk of cardiovascular-renal events compared with metformin persistence. Meanwhile, it is understood that microbiota, nutrients and metformin can interact through the gut-brain-kidney axis to modulate homeostasis of bioactive molecules, systemic inflammation and energy metabolism. While these biological changes contribute to the multisystem effects of metformin, they may also explain the gastrointestinal side effects and vitamin B12 deficiency associated with metformin intolerance. By understanding the interactions between metformin, foods and microbiota, healthcare professionals are in a better position to optimize the use of metformin and mitigate potential side effects. The United Kingdom Prospective Diabetes Study and the Da Qing Diabetes Prevention Program commenced 40 years ago provided the first evidence that type 2 diabetes is preventable and treatable. To drive real-world impact from this evidence, payors, practitioners and planners need to co-design and implement an integrated, data-driven, metformin-based programme to detect people with undiagnosed diabetes and prediabetes (intermediate hyperglycaemia), notably impaired glucose tolerance, for early intervention. The systematic data collection will create real-world evidence to bring out the best of metformin and make healthcare sustainable, affordable and accessible.
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Affiliation(s)
- Juliana C N Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| | - Natural Chu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
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Yang A, Shi M, Wu H, Lau ESH, Cheung JTK, Zhang X, Fan B, Chen T, Kong APS, Luk AOY, Ma RCW, Chan JCN, Chow E. Clinical outcomes following discontinuation of metformin in patients with type 2 diabetes and advanced chronic kidney disease in Hong Kong: a territory-wide, retrospective cohort and target trial emulation study. EClinicalMedicine 2024; 71:102568. [PMID: 38586590 PMCID: PMC10998090 DOI: 10.1016/j.eclinm.2024.102568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 02/26/2024] [Accepted: 03/12/2024] [Indexed: 04/09/2024] Open
Abstract
Background Current labelling advises discontinuation of metformin when estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 due to increased risk of lactic acidosis. However, in real-world practice, the risk-benefit ratios remain uncertain. We examined the risk associations of discontinued-metformin use with cardiorenal and clinical outcomes in patients with type 2 diabetes (T2D) and advanced chronic kidney disease. Methods In this territory-wide, retrospective cohort and target trial emulation study, we included Chinese patients attending the Hong Kong Hospital Authority (HA) and enrolled in the Risk-Assessment-and-Management-Programme-for-Diabetes-Mellitus (RAMP-DM) from 2002 to 2019. Patients were stratified by discontinuation of metformin within six months after reaching eGFR < 30 ml/min/1.73 m2 from January 1, 2002 to December 31, 2018, and followed up until December 31 2019. We excluded patients who had observational time <6 months from eGFR < 30 ml/min/1.73 m2, and had their eGFR measured during a hospitalisation episode due to acute kidney injury, or missing diagnosis date of diabetes. We compared the risk associations of metformin discontinuation with clinical outcomes. The primary outcomes were major adverse cardiovascular events (MACE), end-stage kidney disease (ESKD), cancer, and all-cause mortality. A Cox-model with time-dependent exposure and covariates was used to estimate the hazard ratio (HR) of outcomes in a propensity-score overlap-weighted cohort. The risk of occurrence of lactic acidosis (serum lactate > 5.0 mmol/L with a concomitant blood pH < 7.35 or ICD-9 codes of 276.2) in discontinued-metformin versus continued-metformin users was assessed in a separate register-based cohort. Findings A total of 33,586 metformin users with new-onset eGFR < 30 ml/min/1.73 m2 were included in the study, 7500 (22.3%) of whom discontinued metformin within 6 months whereas 26,086 (77.7%) continued use of metformin. During a median follow-up of 3.8 (IQR: 2.2-6.1) years, 16.4% (5505/33,586), 30.1% (10,113/33,586), and 7.1% (2171/30,682) had incident MACE, ESKD, and cancer respectively, and 44.4% (14,917/33,586) died. Compared to continued-metformin use, discontinuation was associated with higher risk of MACE (weighted and adjusted HR = 1.40, 95% CI: 1.29-1.52), ESKD (HR = 1.52, 1.42-1.62), and death (HR = 1.22, 1.18-1.27). No association was observed for cancer (HR = 0.93, 0.85-1.01). Discontinued-metformin users had higher change in HbA1c change at 6-month of follow-up versus continued-metformin users (weighted mean HbA1c level change: 0.5% [0.4-0.6%] versus 0.2% [0.1-0.2]). In the separate register-based cohort (n = 3235), null association was observed between metformin use and risk of lactic acidosis (weighted HR = 0.94 [0.53-1.64]). Interpretation Our results suggest that discontinuation of metformin in patients with T2D and chronic kidney disease may be associated with increased risk of cardiovascular-renal events. Use of metformin below eGFR of 30 ml/min/1.73 m2 may be associated with cardiovascular, renal, and mortality benefits that need to be weighed against the risk of lactic acidosis, but further research is needed to validate these findings. Funding CUHK Impact Research Fellowship Scheme.
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Affiliation(s)
- Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Mai Shi
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Eric SH. Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Johnny TK. Cheung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Xinge Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Baoqi Fan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Tingting Chen
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Alice PS. Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Andrea OY. Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Ronald CW. Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Juliana CN. Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
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7
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Chan JC, O CK, Luk AO. Young-Onset Diabetes in East Asians: From Epidemiology to Precision Medicine. Endocrinol Metab (Seoul) 2024; 39:239-254. [PMID: 38626908 PMCID: PMC11066447 DOI: 10.3803/enm.2024.1968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 03/13/2024] [Accepted: 03/20/2024] [Indexed: 05/03/2024] Open
Abstract
Precision diagnosis is the keystone of clinical medicine. In East Asians, classical type 1 diabetes is uncommon in patients with youngonset diabetes diagnosed before age of 40, in whom a family history, obesity, and beta-cell and kidney dysfunction are key features. Young-onset diabetes affects one in five Asian adults with diabetes in clinic settings; however, it is often misclassified, resulting in delayed or non-targeted treatment. Complex aetiologies, long disease duration, aggressive clinical course, and a lack of evidence-based guidelines have contributed to variable care standards and premature death in these young patients. The high burden of comorbidities, notably mental illness, highlights the numerous knowledge gaps related to this silent killer. The majority of adult patients with youngonset diabetes are managed as part of a heterogeneous population of patients with various ages of diagnosis. A multidisciplinary care team led by physicians with special interest in young-onset diabetes will help improve the precision of diagnosis and address their physical, mental, and behavioral health. To this end, payors, planners, and providers need to align and re-design the practice environment to gather data systematically during routine practice to elucidate the multicausality of young-onset diabetes, treat to multiple targets, and improve outcomes in these vulnerable individuals.
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Affiliation(s)
- Juliana C.N. Chan
- Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
| | - Chun-Kwan O
- Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
| | - Andrea O.Y. Luk
- Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
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8
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Shi M, Yang A, Lau ESH, Luk AOY, Ma RCW, Kong APS, Wong RSM, Chan JCM, Chan JCN, Chow E. A novel electronic health record-based, machine-learning model to predict severe hypoglycemia leading to hospitalizations in older adults with diabetes: A territory-wide cohort and modeling study. PLoS Med 2024; 21:e1004369. [PMID: 38607977 PMCID: PMC11014435 DOI: 10.1371/journal.pmed.1004369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 02/29/2024] [Indexed: 04/14/2024] Open
Abstract
BACKGROUND Older adults with diabetes are at high risk of severe hypoglycemia (SH). Many machine-learning (ML) models predict short-term hypoglycemia are not specific for older adults and show poor precision-recall. We aimed to develop a multidimensional, electronic health record (EHR)-based ML model to predict one-year risk of SH requiring hospitalization in older adults with diabetes. METHODS AND FINDINGS We adopted a case-control design for a retrospective territory-wide cohort of 1,456,618 records from 364,863 unique older adults (age ≥65 years) with diabetes and at least 1 Hong Kong Hospital Authority attendance from 2013 to 2018. We used 258 predictors including demographics, admissions, diagnoses, medications, and routine laboratory tests in a one-year period to predict SH events requiring hospitalization in the following 12 months. The cohort was randomly split into training, testing, and internal validation sets in a 7:2:1 ratio. Six ML algorithms were evaluated including logistic-regression, random forest, gradient boost machine, deep neural network (DNN), XGBoost, and Rulefit. We tested our model in a temporal validation cohort in the Hong Kong Diabetes Register with predictors defined in 2018 and outcome events defined in 2019. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) statistics, and positive predictive value (PPV). We identified 11,128 SH events requiring hospitalization during the observation periods. The XGBoost model yielded the best performance (AUROC = 0.978 [95% CI 0.972 to 0.984]; AUPRC = 0.670 [95% CI 0.652 to 0.688]; PPV = 0.721 [95% CI 0.703 to 0.739]). This was superior to an 11-variable conventional logistic-regression model comprised of age, sex, history of SH, hypertension, blood glucose, kidney function measurements, and use of oral glucose-lowering drugs (GLDs) (AUROC = 0.906; AUPRC = 0.085; PPV = 0.468). Top impactful predictors included non-use of lipid-regulating drugs, in-patient admission, urgent emergency triage, insulin use, and history of SH. External validation in the HKDR cohort yielded AUROC of 0.856 [95% CI 0.838 to 0.873]. Main limitations of this study included limited transportability of the model and lack of geographically independent validation. CONCLUSIONS Our novel-ML model demonstrated good discrimination and high precision in predicting one-year risk of SH requiring hospitalization. This may be integrated into EHR decision support systems for preemptive intervention in older adults at highest risk.
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Affiliation(s)
- Mai Shi
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Eric S. H. Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Andrea O. Y. Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Ronald C. W. Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Alice P. S. Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Raymond S. M. Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Jones C. M. Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Juliana C. N. Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
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9
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Vonna A, Salahudeen MS, Peterson GM. Medication-Related Hospital Admissions and Emergency Department Visits in Older People with Diabetes: A Systematic Review. J Clin Med 2024; 13:530. [PMID: 38256662 PMCID: PMC10817070 DOI: 10.3390/jcm13020530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/05/2024] [Accepted: 01/15/2024] [Indexed: 01/24/2024] Open
Abstract
Limited data are available regarding adverse drug reactions (ADRs) and medication-related hospitalisations or emergency department (ED) visits in older adults with diabetes, especially since the emergence of newer antidiabetic agents. This systematic review aimed to explore the nature of hospital admissions and ED visits that are medication-related in older adults with diabetes. The review was conducted according to the PRISMA guidelines. Studies in English that reported on older adults (mean age ≥ 60 years) with diabetes admitted to the hospital or presenting to ED due to medication-related problems and published between January 2000 and October 2023 were identified using Medline, Embase, and International Pharmaceutical Abstracts databases. Thirty-five studies were included. Medication-related hospital admissions and ED visits were all reported as episodes of hypoglycaemia and were most frequently associated with insulins and sulfonylureas. The studies indicated a decline in hypoglycaemia-related hospitalisations or ED presentations in older adults with diabetes since 2015. However, the associated medications remain the same. This finding suggests that older patients on insulin or secretagogue agents should be closely monitored to prevent potential adverse events, and newer agents should be used whenever clinically appropriate.
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Affiliation(s)
- Azizah Vonna
- School of Pharmacy and Pharmacology, College of Health and Medicine, University of Tasmania, Hobart 7005, Australia; (M.S.S.); (G.M.P.)
- Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Syiah Kuala, Banda Aceh 23111, Aceh, Indonesia
| | - Mohammed S. Salahudeen
- School of Pharmacy and Pharmacology, College of Health and Medicine, University of Tasmania, Hobart 7005, Australia; (M.S.S.); (G.M.P.)
| | - Gregory M. Peterson
- School of Pharmacy and Pharmacology, College of Health and Medicine, University of Tasmania, Hobart 7005, Australia; (M.S.S.); (G.M.P.)
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10
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Lee CH, Mak LY, Tang EHM, Lui DTW, Mak JHC, Li L, Wu T, Chan WL, Yuen MF, Lam KSL, Wong CKH. SGLT2i reduces risk of developing HCC in patients with co-existing type 2 diabetes and hepatitis B infection: A territory-wide cohort study in Hong Kong. Hepatology 2023; 78:1569-1580. [PMID: 37055020 DOI: 10.1097/hep.0000000000000404] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 03/12/2023] [Indexed: 04/15/2023]
Abstract
BACKGROUND AND AIMS Type 2 diabetes (T2D) and chronic hepatitis B infection (CHB) are risk factors of HCC. Sodium glucose co-transporter 2 inhibitors (SGLT2i) inhibit HCC oncogenesis in preclinical studies. However, clinical studies are lacking. This study aimed to evaluate the impact of SGLT2i use on incident HCC using a territory-wide cohort of exclusively patients with co-existing T2D and CHB. APPROACH AND RESULTS Patients with co-existing T2D and CHB between 2015 and 2020 were identified from the representative electronic database of the Hong Kong Hospital Authority. Patients with and without SGLT2i use were 1:1 matched by propensity score for their demographics, biochemistry results, liver-related characteristics, and background medications. Cox proportional hazards regression model was used to assess the association between SGLT2i use and incident HCC. A total of 2,000 patients with co-existing T2D and CHB (1,000 in each SGLT2i and non-SGLT2i group; 79.7% on anti-HBV therapy at baseline) were included after propensity-score matching. Over a follow-up of 3,704 person-years, the incidence rates of HCC were 1.39 and 2.52 cases per 100 person-year in SGLT2i and non-SGLT2i groups, respectively. SGLT2i use was associated with a significantly lower risk of incident HCC (HR 0.54, 95%CI: 0.33-0.88, p =0.013). The association remained similar regardless of sex, age, glycemic control, diabetes duration, presence of cirrhosis and hepatic steatosis, timing of anti-HBV therapy, and background antidiabetic agents including dipeptidyl peptidase-4 inhibitors, insulin, or glitazones (all p interaction>0.05). CONCLUSIONS Among patients with co-existing T2D and CHB, SGLT2i use was associated with a lower risk of incident HCC.
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Affiliation(s)
- Chi-Ho Lee
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China
| | - Lung-Yi Mak
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
| | - Eric Ho-Man Tang
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - David Tak-Wai Lui
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Jimmy Ho-Cheung Mak
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Lanlan Li
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Tingting Wu
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Wing Lok Chan
- Department of Clinical Oncology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
| | - Karen Siu-Ling Lam
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China
| | - Carlos King Ho Wong
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong SAR, China
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11
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Wang Y, Xu W, Mak IL, Chin WY, Yu EYT, Lam CLK, Wan EYF. Trends of clinical parameters and incidences of diabetes mellitus complications among patients with type 2 diabetes mellitus in Hong Kong, 2010-2019: a retrospective cohort study. EClinicalMedicine 2023; 60:101999. [PMID: 37234549 PMCID: PMC10206435 DOI: 10.1016/j.eclinm.2023.101999] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 04/17/2023] [Accepted: 04/20/2023] [Indexed: 05/28/2023] Open
Abstract
Background Diabetes mellitus-related characteristics, including available medications, onset ages, and newly-introduced management program, have been changing recently in Hong Kong, especially after the introduction of the Risk Assessment and Management Program-Diabetes Mellitus in all outpatient clinics in 2009. To understand the plural change and improve the management of patients with Type 2 Diabetes Mellitus (T2DM) based on the latest data, we examined the trends of clinical parameters, T2DM complications and mortality in patients with T2DM in Hong Kong from 2010 to 2019. Methods In this retrospective cohort study, we acquired data from the Clinical Management System of the Hospital Authority in Hong Kong. Among adults with T2DM diagnosed on or before Sept 30, 2010, and with at least one attendance in general outpatient clinics between Aug 1, 2009, to Sept 30, 2010, we investigated the age-standardised trends of clinical parameters including haemoglobin A1c, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C), body mass index and estimated glomerular filtration rate (eGFR), complications including cardiovascular disease (CVD), peripheral vascular disease (PVD), sight-threatening diabetic retinopathy (STDR), neuropathy, eGFR<45 mL/min/1.73 m2 and end-stage renal disease (ESRD), and all-cause mortality from 2010 to 2019 and tested the statistical significance of the trends using generalised estimating equation by sex, level of clinical parameters and age groups. Findings In total, 82,650 males and 97,734 females with T2DM were identified. LDL-C decreased from 3 to 2 mmol/L in both males and females, while other clinical parameters changed within 5% over the full decade from 2010 to 2019. CVD, PVD, STDR, and neuropathy had declining incidences, while ESRD and all-cause mortality had increasing incidences from 2010 to 2019. The incidence of eGFR<45 mL/min/1.73 m2 increased in males but decreased in females. The odds ratio (OR) of ESRD (1.13, 95% CI [1.12, 1.15]) was highest in both males and females while the ORs of STDR (0.94, 95% CI [0.92, 0.96]) and neuropathy (0.90, 95% CI [0.88, 0.92]) were lowest in males and females, respectively. Complications and all-cause mortality trends varied among baseline HbA1c, eGFR, and age subgroups. In contrast to the findings in other age groups, the incidence of any outcomes did not decrease in younger patients (<45 years) from 2010 to 2019. Interpretation Improvements were observed in LDL-C and incidences of most complications from 2010 to 2019. Worse performance in the younger age group and increasing incidence of renal complications and mortality need more attention in managing patients with T2DM. Funding The Health and Medical Research Fund, the Health Bureau, and Government of the Hong Kong Special Administrative Region.
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Affiliation(s)
- Yuan Wang
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Wanchun Xu
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Ivy Lynn Mak
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Weng Yee Chin
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Esther Yee Tak Yu
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Cindy Lo Kuen Lam
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Family Medicine, The University of Hong Kong - Shenzhen Hospital, Guangdong, China
| | - Eric Yuk Fai Wan
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Sha Tin, Hong Kong SAR, China
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12
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Hu S, Lin C, Cai X, Li Z, Lv F, Yang W, Ji L. Trends in baseline HbA1c and body-mass index in randomised placebo-controlled trials of type 2 diabetes from 1987 to 2022: a systematic review and meta-analysis. EClinicalMedicine 2023; 57:101868. [PMID: 36864984 PMCID: PMC9971277 DOI: 10.1016/j.eclinm.2023.101868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/27/2023] [Accepted: 01/27/2023] [Indexed: 02/18/2023] Open
Abstract
BACKGROUND Curbing or reversing high glycated hemoglobin (HbA1c) and body mass index (BMI) are two essential parts in the clinical management of type 2 diabetes (T2D). We delineated the changing patterns of the baseline HbA1c and BMI in patients with T2D from placebo-controlled randomised trials to reflect the unmet clinical needs. METHODS PubMed, Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception to December 19, 2022. Placebo-controlled trials of T2D with reports of baseline HbA1c and BMI were included, of which summary data from published reports were extracted. Pooled effect sizes of baseline HbA1c and BMI of from studies published in the same year were computed in Random-effects model due to the high level of heterogeneity among studies. The main outcome was correlations between the pooled baseline HbA1c, the pooled baseline BMI, and study years. This study was registered in PROSPERO as CRD42022350482. FINDINGS We identified 6102 studies, of which 427 placebo-controlled trials with 261, 462 participants were finally included in the study. Baseline HbA1c level declined with time (Rs = -0.665, P ＜ 0.0001, I2 = 99.4%). Baseline BMI increased over the past 35 years (R = 0.464, P = 0.0074, I2 = 99.4%), rising by around 0.70 kg/m2 per decade. Patients with BMI ≤25.0 kg/m2 dropped substantially from the half in 1996 to none in 2022. Patients with BMI ranging from 25 kg/m2 to 30 kg/m2 stabilized at 30-40% since 2000. INTERPRETATION A substantial decline in baseline HbA1c levels and a constant increase in baseline BMI levels was found in placebo-controlled trials through the past 35 years, which indicated the improvement in glycemic control and the urgency for the management of obesity in T2D. FUNDING National Natural Science Foundation of China (No.81970698), Beijing Natural Science Foundation (No.7202216) and National Natural Science Foundation of China (No.81970708).
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Affiliation(s)
| | | | - Xiaoling Cai
- Corresponding author. Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
| | | | | | | | - Linong Ji
- Corresponding author. Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
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13
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Shi M, Yang A, Chow E, Lau ESH, Tam CHT, Kong APS, Luk AOY, Ma RCW, Cheung CMT, Chan JCN, Chan AWS. Genetic susceptibility of dipeptidyl Peptidase-4 inhibitor associated bullous pemphigoid in Chinese patients with type 2 diabetes. J Eur Acad Dermatol Venereol 2023; 37:e375-e377. [PMID: 36394174 DOI: 10.1111/jdv.18762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 11/08/2022] [Indexed: 11/18/2022]
Affiliation(s)
- Mai Shi
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Aimin Yang
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Elaine Chow
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.,Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Eric S H Lau
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Claudia H T Tam
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Alice P S Kong
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Andrea O Y Luk
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Ronald C W Ma
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Christina M T Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.,Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Shatin, Hong Kong.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Agnes W S Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong
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14
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Chen L, Chen Q, Chen X, Zhu P, Chen M, Wang W, Ye S, Zheng M. Clinical Application of Metformin Use in Anhui Province, China: A Cross-Sectional Study. J Multidiscip Healthc 2023; 16:345-354. [PMID: 36776727 PMCID: PMC9912819 DOI: 10.2147/jmdh.s397061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 01/09/2023] [Indexed: 02/09/2023] Open
Abstract
Purpose Given the importance of metformin, reasonable utilization is essential. We designed a cross-sectional survey on physicians' attitude and clinical application of metformin in Anhui Province, China. Methods The survey was distributed via an electronic questionnaire among endocrinologists and general practitioners. Seven representative questions were used to evaluate professional levels. Results Among the 477 valid responses, 72.75% of the respondents preferred to prescribe metformin extended-release, while only 34.38% of them would prescribe metformin extended-release at the correct frequency. More than half of the respondents thought that estimated glomerular filtration rate ˂ 45 mL/min/1.73 m² should be the contraindication of metformin prescription. Less than 10% of the physicians selected correct responses for two questions regarding metformin usage and contrast agent. Physicians with higher levels of hospital grades, education background and professional titles as well as working in general hospitals and in the Department of Endocrinology achieved high scores (P˂0.05). Logistic regression showed that department was an independent predictor for high scores. Conclusion Physicians, especially non-endocrinologists, are not at a professional level for prescribing metformin. Physicians should be highly vigilant in terms of standardized prescription for metformin. The guidelines or consensuses about diabetes care for physicians should be promoted.
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Affiliation(s)
- Li Chen
- Department of Endocrinology, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei City), Hefei, People's Republic of China
| | - Qin Chen
- Department of Pharmacy, Taihe County People's Hospital, Taihe, People's Republic of China
| | - Xueping Chen
- Department of Pharmacy, Hefei Fourth People's Hospital, Hefei, People's Republic of China.,Psychopharmacology Research Laboratory, Anhui Mental Health Center and Department of Pharmacy, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Pengli Zhu
- Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Meinan Chen
- Ethics Committee on Medical Research, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Wei Wang
- Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.,Laboratory of Diabetes, Department of Endocrinology, The First Affiliated Hospital of USTC, Hefei, People's Republic of China
| | - Shandong Ye
- Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.,Laboratory of Diabetes, Department of Endocrinology, The First Affiliated Hospital of USTC, Hefei, People's Republic of China
| | - Mao Zheng
- Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.,Laboratory of Diabetes, Department of Endocrinology, The First Affiliated Hospital of USTC, Hefei, People's Republic of China
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15
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Cheung JTK, Yang A, Wu H, Lau ESH, Shi M, Kong APS, Ma RCW, Luk AOY, Chan JCN, Chow E. Initiation of sodium-glucose cotransporter-2 inhibitors at lower HbA1c threshold attenuates eGFR decline in type 2 diabetes patients with and without cardiorenal disease: A propensity-matched cohort study. Diabetes Res Clin Pract 2023; 195:110203. [PMID: 36493912 DOI: 10.1016/j.diabres.2022.110203] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 11/27/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022]
Abstract
AIM To examine the association of initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) at lower glycemic threshold with decline in estimated-glomerular filtration rate (eGFR). METHODS We analyzed a prospective cohort of Chinese patients with type 2 diabetes from Hong Kong. Patients initiating SGLT2i at HbA1c < 7.5 % (lower-HbA1c) versus ≥ 7.5 % (higher-HbA1c) were matched using 1:1 propensity score. We compared annual eGFR changes in the lower-HbA1c and higher-HbA1c groups using linear mixed-effect models. Binary logistic regression was used to explore associations of SGLT2i initiation at lower HbA1c with odds of rapid eGFR decline (>4% per year). RESULTS Among 3384 patients with a median follow-up of 1.9 years, the mean age was 60.2 ± 11.5 years and 62.1 % were male. The lower-HbA1c and higher-HbA1c groups had baseline HbA1c (%) of 6.9 ± 0.5 and 9.0 ± 1.3 respectively, with similar pre-index annual eGFR decline. The lower-HbA1c group had a slower post-index annual eGFR decline than the higher-HbA1c group (-0.99 versus -1.63 mL/min/1.73 m2, p < 0.001). Overall, the lower-HbA1c group had lower odds of rapid eGFR decline (OR = 0.15, 95 % CI: 0.07-0.29). Greater renoprotection from SGLT2i initiation at lower-HbA1c was observed in those with baseline eGFR < 60 mL/min/1.73 m2, albuminuria and/or treatment with renin-angiotensin-system inhibitors or insulin. CONCLUSIONS In this real-world study, SGLT2i initiation at HbA1c < 7.5 % was associated with slower eGFR decline especially in high risk patients, supporting the potential renal benefits of SGLT2i initiation at lower glycemic thresholds.
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Affiliation(s)
- Johnny T K Cheung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Eric S H Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Mai Shi
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Alice P S Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Ronald C W Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Andrea O Y Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
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16
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Yang B, Yang J, Wong MMH, Rana J, Yang Q, Chan V, Khan MS, Yang A, Lo K. Trends in elevated waist-to-height ratio and waist circumference in U.S. adults and their associations with cardiometabolic diseases and cancer, 1999-2018. Front Nutr 2023; 10:1124468. [PMID: 37113294 PMCID: PMC10126508 DOI: 10.3389/fnut.2023.1124468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 03/22/2023] [Indexed: 04/29/2023] Open
Abstract
Introduction Although waist-to-height ratio (WHtR) has established association with cardiometabolic disease, the trend of changes in elevated WHtR among general population have not been examined adequately. Methods This study examined the prevalence of elevated WHtR and waist circumference (WC) and their trends over time using Joinpoint regression models among adults who participated in the United States National Health and Nutrition Examination Survey (U.S. NHANES) 1999-2018. We performed weighted logistic regression to identify the association between central obesity subtypes and the prevalence of comorbidities, including diabetes, chronic kidney disease, hypertension, cardiovascular disease, and cancer. Results The prevalence of elevated WHtR has increased from 74.8% in 1999-2000 to 82.7% in 2017-2018 while elevated WC also increased from 46.9% in 1999-2000 to 60.3% in 2017-2018. Men, older adults, former smokers, and people with lower education levels were more likely to have elevated WHtR. A total of 25.5% of American adults had normal WC but elevated WHtR, and they had a significantly higher chance of suffering from diabetes (odds ratio [OR] = 2.06 [1.66, 2.55]), hypertension (OR = 1.75 [1.58, 1.93]) and CVD (OR = 1.32 [1.11, 1.57]). Discussion In conclusion, the burden of elevated WHtR and WC have been increasing among U.S. adults throughout the years, and the changes have been more significant across most subgroups. It is also notable that approximately a quarter of the population had normal WC but elevated WHtR, which had increased likelihood of having cardiometabolic diseases, especially diabetes. Future clinical practices should pay more attention to this subgroup of the population with overlooked health risks.
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Affiliation(s)
- Bo Yang
- Department of Epidemiology and Center for Global Cardiometabolic Health, School of Public Health, Brown University, Providence, RI, United States
| | - Jingli Yang
- College of Earth and Environmental Sciences, Lanzhou University, Lanzhou, China
| | - Martin Ming-him Wong
- School of Professional and Continuing Education, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China
| | - Juwel Rana
- Department of Epidemiology, Biostatistics and Occupational Health, School of Medicine and Health Sciences, McGill University, Montreal, QC, Canada
- Department of Public Health, School of Health and Life Sciences, North South University, Dhaka, Bangladesh
| | - Qinghua Yang
- Department of Nephrology, Peking University International Hospital, Beijing, China
| | - Vicky Chan
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - Moyukh Shabon Khan
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
- *Correspondence: Aimin Yang,
| | - Kenneth Lo
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Research Institute for Smart Ageing, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Kenneth Lo,
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17
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Yang A, Shi M, Lau ES, Wu H, Zhang X, Fan B, Kong AP, Luk AO, Ma RC, Chan JC, Chow E. Clinical outcomes following discontinuation of renin-angiotensin-system inhibitors in patients with type 2 diabetes and advanced chronic kidney disease: A prospective cohort study. EClinicalMedicine 2023; 55:101751. [PMID: 36457651 PMCID: PMC9706514 DOI: 10.1016/j.eclinm.2022.101751] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 11/01/2022] [Accepted: 11/01/2022] [Indexed: 11/27/2022] Open
Abstract
Background Renin-angiotensin-system inhibitors (RASi), that include angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) reduce proteinuria, delay chronic kidney disease (CKD) progression, protect against cardiovascular events and heart failure hospitalizations. We examined the associations of discontinuation of ACEi/ARBs with risk of clinical outcomes in Chinese patients with type 2 diabetes (T2D) and advanced-CKD (estimated-glomerular filtration rate [eGFR] <30 ml/min/1.73 m2). Methods We conducted a prospective, population-based cohort study including 10,400 patients with T2D in Hong Kong stratified by continuation of ACEi/ARBs within 6 months after reaching eGFR <30 ml/min/1.73 m2 from January 01, 2002 to December 31, 2018 and observed until December 31, 2019. The primary outcomes were death, major-adverse cardiovascular events (MACE), heart failure, end-stage kidney disease (ESKD), and all-cause mortality. Cox-model with time-dependent exposure and covariates was used to estimate the hazard ratio (HR) of outcomes in a propensity-score overlap-weighted cohort. The risk of occurrence of hyperkalemia (plasma potassium >5.5 mmol/L) in discontinued-ACEi/ARBs versus continued-ACEi/ARBs users was assessed in a register-based cohort. Findings In the population-based cohort of 10,400 ACEi/ARBs users with new-onset eGFR<30 ml/min/1.73 m2, 1766 (17.0%) discontinued ACEi/ARBs and 8634 (83.0%) persisted with treatment. During a median follow-up of 3.6 (interquartile range, IQR: 2.11-5.8) years (41,623 person-years), 13.5%, 12.9%, and 27.6% had incident MACE, heart failure and ESKD respectively, and 35.8% died. Discontinued-ACEi/ARBs use was associated with higher risk of MACE (HR = 1.27, 95% CI: 1.08-1.49), heart failure (HR = 1.85, 95% CI: 1.53-2.25) and ESKD (HR = 1.30, 95% CI: 1.17-1.43), and neutral risk of all-cause mortality (HR = 0.93, 95% CI: 0.86-1.01) compared to counterparts with continued use. In the register-based cohort (583 discontinued-ACEi/ARBs users and 3817 continued-ACEi/ARBs users), discontinued-ACEi/ARBs had neutral risk of hyperkalemia (HR = 0.95, 95% CI: 0.84-1.08). Interpretation Discontinuation of ACEi/ARBs was associated with increased risk of cardiovascular-renal events supporting their continued use in patients with T2D and advanced-CKD. Funding CUHK Impact Research Fellowship Scheme.
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Affiliation(s)
- Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Mai Shi
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Eric S.H. Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Xinge Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Baoqi Fan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Alice P.S. Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Andrea O.Y. Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Ronald C.W. Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Juliana C.N. Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
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Sugimoto T, Noma H, Kuroda Y, Matsumoto N, Uchida K, Kishino Y, Saji N, Niida S, Sakurai T. Time trends (2012-2020) in glycated hemoglobin and adherence to the glycemic targets recommended for elderly patients by the Japan Diabetes Society/Japan Geriatrics Society Joint Committee among memory clinic patients with diabetes mellitus. J Diabetes Investig 2022; 13:2038-2046. [PMID: 36124721 PMCID: PMC9720221 DOI: 10.1111/jdi.13897] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 07/25/2022] [Accepted: 08/17/2022] [Indexed: 11/28/2022] Open
Abstract
AIMS/INTRODUCTION To investigate the changes in the glycated hemoglobin (HbA1c) levels and the relative status of the glycemic control related to the new glycemic targets recommended by the Japan Diabetes Society/Japan Geriatrics Society Joint Committee in 2016 in patients with diabetes mellitus visiting a memory clinic from 2012 to 2020. MATERIALS AND METHODS This cross-sectional study included 1,436 patients aged ≥65 years with diabetes. Patients were categorized into three categories as follows: category I, intact cognitive function and activities of daily living (ADL); category II, mild cognitive deficits or impaired instrumental ADL; and category III, moderate to severe cognitive impairment or impaired basic ADL. Trends in HbA1c levels, glycemic control status (optimally/poorly/excessively controlled) and proportion of individuals receiving drugs potentially associated with severe hypoglycemia among all patients and categories (I, II or III) from 2012 to 2020 were examined using linear, logistic and multinominal logistic regression models adjusted for confounding factors. RESULTS Between 2012 and 2020, the HbA1c levels, as well as the proportion of patients with poor glycemic control, increased, whereas the proportion of patients with excessive glycemic control and those receiving drugs potentially associated with severe hypoglycemia decreased. CONCLUSIONS Increased levels of HbA1c and decreased proportions of individuals under excessive glycemic control might reflect recent treatment strategies that avoid hypoglycemia in older patients. Given the adverse complications associated with hyperglycemia, more flexible and individualized glycemic targets based on comprehensive assessments, including vascular complications and comorbidities, might be necessary.
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Affiliation(s)
- Taiki Sugimoto
- Department of Prevention and Care ScienceResearch Institute, National Center for Geriatrics and GerontologyObuJapan
- Center for Comprehensive Care and Research on Memory Disorders, HospitalNational Center for Geriatrics and GerontologyObuJapan
| | - Hisashi Noma
- Department of Data ScienceThe Institute of Statistical MathematicsTokyoJapan
| | - Yujiro Kuroda
- Department of Prevention and Care ScienceResearch Institute, National Center for Geriatrics and GerontologyObuJapan
| | - Nanae Matsumoto
- Center for Comprehensive Care and Research on Memory Disorders, HospitalNational Center for Geriatrics and GerontologyObuJapan
| | - Kazuaki Uchida
- Center for Comprehensive Care and Research on Memory Disorders, HospitalNational Center for Geriatrics and GerontologyObuJapan
- Department of Public Health, Graduate School of Health SciencesKobe UniversityKobeJapan
| | - Yoshinobu Kishino
- Center for Comprehensive Care and Research on Memory Disorders, HospitalNational Center for Geriatrics and GerontologyObuJapan
- Department of Cognition and Behavior ScienceNagoya University Graduate School of MedicineNagoyaJapan
| | - Naoki Saji
- Center for Comprehensive Care and Research on Memory Disorders, HospitalNational Center for Geriatrics and GerontologyObuJapan
| | - Shumpei Niida
- National Center for Geriatrics and GerontologyResearch InstituteObuJapan
| | - Takashi Sakurai
- Department of Prevention and Care ScienceResearch Institute, National Center for Geriatrics and GerontologyObuJapan
- Center for Comprehensive Care and Research on Memory Disorders, HospitalNational Center for Geriatrics and GerontologyObuJapan
- Department of Cognition and Behavior ScienceNagoya University Graduate School of MedicineNagoyaJapan
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Yang A, Lau ESH, Wu H, Ma RCW, Kong APS, So WY, Luk AOY, Fu AWC, Chan JCN, Chow E. Attenuated Risk Association of End-Stage Kidney Disease with Metformin in Type 2 Diabetes with eGFR Categories 1-4. Pharmaceuticals (Basel) 2022; 15:1140. [PMID: 36145361 PMCID: PMC9505840 DOI: 10.3390/ph15091140] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/07/2022] [Accepted: 08/19/2022] [Indexed: 11/16/2022] Open
Abstract
Type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) is a global burden, while the renoprotective effects of metformin remain controversial. In a population-based cohort (2002-2018) including 96,643 patients with T2D observed for 0.7 million person-years, we estimated the risk association of metformin and its dose-relationship with ESKD in a propensity-score overlap-weighting (PS-OW) cohort by eGFR categories. Amongst 96,643, 83,881 (86.8%) had eGFR-G1/G2 (≥60 mL/min/1.73 m2), 8762 (9.1%) had eGFR-G3a (≥45-60 mL/min/1.73 m2), 3051 (3.2%) had eGFR-G3b (≥30-45 mL/min/1.73 m2), and 949 (1.0%) had eGFR-G4 (≥15-30 mL/min/1.73 m2). The respective proportions of metformin users in these eGFR categories were 95.1%, 81.9%, 53.8%, and 20.8%. In the PS-OW cohort with 88,771 new-metformin and 7872 other oral glucose-lowering-drugs (OGLDs) users, the respective incidence rates of ESKD were 2.8 versus 22.4/1000 person-years. Metformin use associated with reduced risk of ESKD (hazard ratio (HR) = 0.43 [95% CI: 0.35-0.52] in eGFR-G1/G2, 0.64 [0.52-0.79] in eGFR-G3a, 0.67 [0.56-0.80] in eGFR-G3b, and 0.63 [0.48-0.83] in eGFR-G4). Metformin use was associated with reduced or neutral risk of major adverse cardiovascular events (MACE) (7.2 versus 16.0/1000 person-years) and all-cause mortality (14.6 versus 65.1/1000 person-years). Time-weighted mean daily metformin dose was 1000 mg in eGFR-G1/G2, 850 mg in eGFR-G3a, 650 mg in eGFR-G3b, and 500 mg in eGFR-G4. In a subcohort of 14,766 patients observed for 0.1 million person-years, the respective incidence rates of lactic acidosis and HR in metformin users and non-users were 42.5 versus 226.4 events/100,000 person-years (p = 0.03) for eGFR-G1/G2 (HR = 0.57, 0.25-1.30) and 54.5 versus 300.6 events/100,000 person-years (p = 0.01) for eGFR-G3/G4 (HR = 0.49, 0.19-1.30). These real-world data underscore the major benefits and low risk of lactic acidosis with metformin use down to an eGFR of 30 mL/min/1.73 m2 and possibly even 15 mL/min/1.73 m2, while reinforcing the importance of dose adjustment and frequent monitoring of eGFR.
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Affiliation(s)
- Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
| | - Eric S. H. Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Asia Diabetes Foundation, Hong Kong SAR 999077, China
| | - Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
| | - Ronald C. W. Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
| | - Alice P. S. Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
| | - Wing Yee So
- Hong Kong Hospital Authority Head Office, Hong Kong SAR 999077, China
| | - Andrea O. Y. Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
| | - Amy W. C. Fu
- Asia Diabetes Foundation, Hong Kong SAR 999077, China
| | - Juliana C. N. Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Asia Diabetes Foundation, Hong Kong SAR 999077, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR 999077, China
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Yang A, Wu H, Lau ESH, Shi M, Fan B, Kong APS, Ma RCW, Luk AOY, Chan JCN, Chow E. Effects of RAS inhibitors on all-site cancers and mortality in the Hong Kong diabetes surveillance database (2002-2019). EBioMedicine 2022; 83:104219. [PMID: 35970023 PMCID: PMC9399959 DOI: 10.1016/j.ebiom.2022.104219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 07/19/2022] [Accepted: 07/29/2022] [Indexed: 11/30/2022] Open
Abstract
Background Cancer is replacing cardiovascular-disease as a leading cause of death in type 2 diabetes (T2D). The association of RAS-inhibitors (RASi) and cancer, including differences between angiotensin-converting-enzyme-inhibitor (ACEi) and angiotensin-receptor-blocker (ARBs) as well as their associations independent of blood pressure lowering, remains inconclusive in T2D. Methods We conducted a cohort study with new-user design in 253,491 patients in the Hong-Kong-Diabetes-Surveillance-Database (HKDSD) in 2002-2019. We evaluated the associations of time-varying RASi use (ACEi and ARBs) with all-site cancer, diabetes-related cancers, and cancer-specific mortality including comparison with new-users of calcium-channel-blockers (CCBs) as an active-comparator group. Findings Of 253,491, 133,730 (52.8%) were new-RASi and 119,761 (47.2%) were non-RASi users with a median follow-up period of 6.3 (interquartile ragne: 3.4-9.2) years (1,678,719 patient-years). After propensity-score weighting and adjustment for time-varying covariables, RASi use was associated with lower risk of all-site cancer (HR=0.76, 95%CI: 0.74-0.79), diabetes-related cancer (HR=0.79, 95%CI: 0.75-0.84), cancer-specific mortality (HR=0.50, 95%CI: 0.47-0.53), and diabetes-related cancer mortality (HR=0.49, 95%CI: 0.45-0.54) versus non-RASi. Amongst RASi users, ARBs use was associated with lower risk of cancer-specific mortality versus ACEi (HR=0.77, 95%CI: 0.66-0.91). Use of RASi was associated with an estimated-prevention of 2.6 (95%CI: 2.3-3.0) all-site cancer per-1000-person-years and 2.2 (95%CI: 2.0-2.5) cancer-related mortality per-1000-person-years. Lower risk of cancer-specific mortality was similarly observed in new-RASi compared with new-CCBs users. Interpretation RASi use was independently associated with lower cancer risk in T2D with stronger associations in users of ARBs than ACEi. The benefits of RASi in patients with diabetes might go beyond cardiovascular-renal protection if confirmed by other real-world studies and trials. Funding Dr. Aimin Yang was supported by a CUHK Impact-Research-Fellowship Scheme.
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Affiliation(s)
- Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Eric S H Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Mai Shi
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Baoqi Fan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Alice Pik-Shan Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Ronald Ching-Wan Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Andrea On-Yan Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Juliana Chung-Ngor Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
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21
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Yang A, Wu H, Lau ES, Zhang X, Shi M, Fan B, Ma RC, Kong AP, Luk AO, Chan JC, Chow E. Glucose-lowering drug use, glycemic outcomes, and severe hypoglycemia: 18-Year trends in 0·9 million adults with Diabetes in Hong Kong (2002-2019). THE LANCET REGIONAL HEALTH. WESTERN PACIFIC 2022; 26:100509. [PMID: 35789825 PMCID: PMC9249907 DOI: 10.1016/j.lanwpc.2022.100509] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Background Improvements in glycemic outcomes have stalled since 2010 in several international surveys. We previously reported improvements in glycemic control in 2007-2014 in Hong Kong coinciding with primary care reforms, use of dipeptidyl-peptidase 4 inhibitors (DPP-4is) and metformin. The aim of this study was to estimate more recent trends in drug use and glycemic outcomes following introduction of newer classes of glucose-lowering drugs (GLDs). Methods Using population-based data from the Hong Kong Diabetes Surveillance Database, we explored age-specific trends in proportion of patients reaching glycemic targets and incidence rates of severe hypoglycemia (SH) in 963,612 adults with diabetes in 2002-2019. We further assessed patterns of GLDs utilisation by presence of atherosclerotic-cardiovascular disease (ASCVD), heart failure, and estimated-glomerular filtration rate (eGFR). Findings Following rapid decline in HbA1c from 7·7% to 7·2% in 2005-2014 (annual percentage change [APC]= -0·8, 95% CI:-1·0,-0·6), standardized mean HbA1c plateaued since 2014 (HbA1c 7·2% in 2019, APC=0·0, 95% CI:-0·2, 0·2). The incidence rates of SH declined from 3·4 to 0·7 events per 100-person years, but improvements levelled off since 2014. Use of metformin steadily increased (41·1 to 58·7%), sulfonylureas decreased (52·2 to 31·1%) while insulin remained static in 2002-2019. Adoption of DPP-4is slowed following initial rapid uptake in 2007-2011. DPP-4is remained the most widely prescribed newer GLD in all ages (14·3% in 2019). Use of glucagon-like-peptide 1 receptor agonists (GLP1-RAs) and sodium glucose co-transporter-2 inhibitors (SGLT2is) increased rapidly in 2015-2019 with 0·5% and 6% of users respectively in 2019. Interpretation Following rapid improvement in 2007-2014, glycemic control and SH rates had plateaued despite changing patterns of newer GLDs use in Hong Kong. Funding Dr. Aimin Yang was supported by a CUHK Impact Research Fellowship Scheme.
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Affiliation(s)
- Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| | - Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
| | - Eric S.H. Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
| | - Xinge Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
| | - Mai Shi
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
| | - Baoqi Fan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
| | - Ronald C.W. Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| | - Alice P.S. Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| | - Andrea O.Y. Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Juliana C.N. Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region (SAR), China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
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22
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Lui DTW, Au ICH, Tang EHM, Cheung CL, Lee CH, Woo YC, Wu T, Tan KCB, Wong CKH. Kidney outcomes associated with sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide 1 receptor agonists: A real-world population-based analysis. EClinicalMedicine 2022; 50:101510. [PMID: 35784442 PMCID: PMC9241106 DOI: 10.1016/j.eclinm.2022.101510] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/24/2022] [Accepted: 05/25/2022] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Kidney benefits have been demonstrated for both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) compared with placebo in patients with type 2 diabetes. This study aimed to compare the impacts of SGLT2i and GLP1RA on the trend of estimated glomerular filtration rate (eGFR) and other kidney outcomes. METHODS Using a real-world population-based database, the Hong Kong Hospital Authority (HA) database, of patients with type 2 diabetes between January 2008 and December 2020, patients started on SGLT2i were compared with those started on GLP1RA, with one-to-one propensity-score matching. Primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), incident macroalbuminuria and kidney-related mortality. Secondary outcome was the rate of eGFR decline. FINDINGS A total of 2551 SGLT2i and 2551 GLP1RA new users were analyzed. At baseline, mean age was 56·2 years, with mean eGFR 78·0 mL/min/1·73m2 and 11·9% having macroalbuminuria. Upon median follow-up of 13 months (IQR: 5-27), SGLT2i users had a lower risk of composite kidney outcomes (HR=0·77, 95%CI 0·62-0·96, p = 0·02), mainly driven by a reduction in ESKD (HR=0·53, p = 0·01). SGLT2i users also tended to have a lower risk of incident macroalbuminuria (HR=0·74, p = 0·05). Subgroup analyses of the benefits of SGLT2i use on composite kidney outcomes did not reveal interaction by age, sex, baseline eGFR/albuminuria status, hemoglobin A1c (HbA1c) and renin-angiotensin-system inhibitor use. Furthermore, SGLT2i users had a slower eGFR decline than GLP1RA users (SGLT2i: -1·19 mL/min/1·73m2/year, GLP1RA: -1·95 mL/min/1·73m2/year, p < 0·01). INTERPRETATION Our results suggest that SGLT2i might be superior to GLP1RA in reducing kidney outcomes among patients with type 2 diabetes. Future trials are needed to corroborate our findings. FUNDING None.
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Affiliation(s)
- David Tak Wai Lui
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Ivan Chi Ho Au
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Eric Ho Man Tang
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Ching Lung Cheung
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health Limited (D4H), Hong Kong Science Park, New Territories, Hong Kong SAR, China
| | - Chi Ho Lee
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Yu Cho Woo
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Tingting Wu
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Kathryn Choon Beng Tan
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Corresponding author at: Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
| | - Carlos King Ho Wong
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health Limited (D4H), Hong Kong Science Park, New Territories, Hong Kong SAR, China
- Corresponding author at: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
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23
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Jin Q, Luk AO, Lau ESH, Tam CHT, Ozaki R, Lim CKP, Wu H, Jiang G, Chow EYK, Ng JK, Kong APS, Fan B, Lee KF, Siu SC, Hui G, Tsang CC, Lau KP, Leung JY, Tsang MW, Kam G, Lau IT, Li JK, Yeung VT, Lau E, Lo S, Fung S, Cheng YL, Chow CC, Huang Y, Lan HY, Szeto CC, So WY, Chan JCN, Ma RCW. Nonalbuminuric Diabetic Kidney Disease and Risk of All-Cause Mortality and Cardiovascular and Kidney Outcomes in Type 2 Diabetes: Findings From the Hong Kong Diabetes Biobank. Am J Kidney Dis 2022; 80:196-206.e1. [PMID: 34999159 DOI: 10.1053/j.ajkd.2021.11.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 11/24/2021] [Indexed: 01/27/2023]
Abstract
RATIONALE & OBJECTIVE Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing DKD phenotype. We compared the risks of adverse outcomes among patients with this phenotype compared with other DKD phenotypes. STUDY DESIGN Multicenter prospective cohort study. SETTINGS & PARTICIPANTS 19,025 Chinese adults with type 2 diabetes enrolled in the Hong Kong Diabetes Biobank. EXPOSURES DKD phenotypes defined by baseline estimated glomerular filtration rate (eGFR) and albuminuria: no DKD (no decreased eGFR or albuminuria), albuminuria without decreased eGFR, decreased eGFR without albuminuria, and albuminuria with decreased eGFR. OUTCOMES All-cause mortality, cardiovascular disease (CVD) events, hospitalization for heart failure (HF), and chronic kidney disease (CKD) progression (incident kidney failure or sustained eGFR reduction ≥40%). ANALYTICAL APPROACH Multivariable Cox proportional or cause-specific hazards models to estimate the relative risks of death, CVD, hospitalization for HF, and CKD progression. Multiple imputation was used for missing covariates. RESULTS Mean participant age was 61.1 years, 58.3% were male, and mean diabetes duration was 11.1 years. During 54,260 person-years of follow-up, 438 deaths, 1,076 CVD events, 298 hospitalizations for HF, and 1,161 episodes of CKD progression occurred. Compared with the no-DKD subgroup, the subgroup with decreased eGFR without albuminuria had higher risks of all-cause mortality (hazard ratio [HR], 1.59 [95% CI, 1.04-2.44]), hospitalization for HF (HR, 3.08 [95% CI, 1.82-5.21]), and CKD progression (HR, 2.37 [95% CI, 1.63-3.43]), but the risk of CVD was not significantly greater (HR, 1.14 [95% CI, 0.88-1.48]). The risks of death, CVD, hospitalization for HF, and CKD progression were higher in the setting of albuminuria with or without decreased eGFR. A sensitivity analysis that excluded participants with baseline eGFR <30 mL/min/1.73 m2 yielded similar findings. LIMITATIONS Potential misclassification because of drug use. CONCLUSIONS Nonalbuminuric DKD was associated with higher risks of hospitalization for HF and of CKD progression than no DKD, regardless of baseline eGFR.
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Affiliation(s)
- Qiao Jin
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Andrea O Luk
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Eric S H Lau
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Claudia H T Tam
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Chinese University of Hong Kong and Shanghai Jiao Tong University Joint Research Centre on Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Risa Ozaki
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Cadmon K P Lim
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Hongjiang Wu
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Guozhi Jiang
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Elaine Y K Chow
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Jack K Ng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Alice P S Kong
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Baoqi Fan
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Chinese University of Hong Kong and Shanghai Jiao Tong University Joint Research Centre on Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Ka Fai Lee
- Department of Medicine and Geriatrics, Kwong Wah Hospital, Hong Kong, China
| | - Shing Chung Siu
- Diabetes Centre, Tung Wah Eastern Hospital, Hong Kong, China
| | - Grace Hui
- Diabetes Centre, Tung Wah Eastern Hospital, Hong Kong, China
| | - Chiu Chi Tsang
- Diabetes and Education Centre, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China
| | - Kam Piu Lau
- Department of Medicine, North District Hospital, Hong Kong, China
| | - Jenny Y Leung
- Department of Medicine and Geriatrics, Ruttonjee Hospital, Hong Kong, China
| | - Man-Wo Tsang
- Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong, China
| | - Grace Kam
- Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong, China
| | - Ip Tim Lau
- Department of Medicine, Tseung Kwan O Hospital, Hong Kong, China
| | - June K Li
- Department of Medicine, Yan Chai Hospital, Hong Kong, China
| | - Vincent T Yeung
- Centre for Diabetes Education and Management, Our Lady of Maryknoll Hospital, Hong Kong, China
| | - Emmy Lau
- Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
| | - Stanley Lo
- Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
| | - Samuel Fung
- Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, China
| | - Yuk Lun Cheng
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China
| | - Chun Chung Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Yu Huang
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
| | - Hui-Yao Lan
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Cheuk Chun Szeto
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Wing Yee So
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Juliana C N Chan
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Chinese University of Hong Kong and Shanghai Jiao Tong University Joint Research Centre on Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Ronald C W Ma
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Chinese University of Hong Kong and Shanghai Jiao Tong University Joint Research Centre on Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
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24
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Ke C, Narayan KMV, Chan JCN, Jha P, Shah BR. Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations. Nat Rev Endocrinol 2022; 18:413-432. [PMID: 35508700 PMCID: PMC9067000 DOI: 10.1038/s41574-022-00669-4] [Citation(s) in RCA: 120] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/24/2022] [Indexed: 02/08/2023]
Abstract
Nearly half of all adults with type 2 diabetes mellitus (T2DM) live in India and China. These populations have an underlying predisposition to deficient insulin secretion, which has a key role in the pathogenesis of T2DM. Indian and Chinese people might be more susceptible to hepatic or skeletal muscle insulin resistance, respectively, than other populations, resulting in specific forms of insulin deficiency. Cluster-based phenotypic analyses demonstrate a higher frequency of severe insulin-deficient diabetes mellitus and younger ages at diagnosis, lower β-cell function, lower insulin resistance and lower BMI among Indian and Chinese people compared with European people. Individuals diagnosed earliest in life have the most aggressive course of disease and the highest risk of complications. These characteristics might contribute to distinctive responses to glucose-lowering medications. Incretin-based agents are particularly effective for lowering glucose levels in these populations; they enhance incretin-augmented insulin secretion and suppress glucagon secretion. Sodium-glucose cotransporter 2 inhibitors might also lower blood levels of glucose especially effectively among Asian people, while α-glucosidase inhibitors are better tolerated in east Asian populations versus other populations. Further research is needed to better characterize and address the pathophysiology and phenotypes of T2DM in Indian and Chinese populations, and to further develop individualized treatment strategies.
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Affiliation(s)
- Calvin Ke
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
- Department of Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
- Centre for Global Health Research, Unity Health Toronto, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
- Asia Diabetes Foundation, Shatin, Hong Kong SAR, China.
| | - K M Venkat Narayan
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
- Nutrition and Health Sciences Program, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA
- Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
- Asia Diabetes Foundation, Shatin, Hong Kong SAR, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Prabhat Jha
- Centre for Global Health Research, Unity Health Toronto, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Baiju R Shah
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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25
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Yokoyama H, Araki SI, Yamazaki K, Kawai K, Shirabe SI, Oishi M, Kanatsuka A, Yagi N, Kabata D, Shintani A, Maegawa H. Trends in glycemic control in patients with insulin therapy compared with non-insulin or no drugs in type 2 diabetes in Japan: a long-term view of real-world treatment between 2002 and 2018 (JDDM 66). BMJ Open Diabetes Res Care 2022; 10:10/3/e002727. [PMID: 35504696 PMCID: PMC9066475 DOI: 10.1136/bmjdrc-2021-002727] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 03/06/2022] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION We investigated trends in the proportion of diabetes treatment and glycemic control, which may be altered by recent advances in insulin and non-insulin drugs, in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A serial cross-sectional study was performed using a multicenter large-population database from the Japan Diabetes Clinical Data Management study group. Patients with type 2 diabetes who attended clinics belonging to the study group between 2002 and 2018 were included to examine trends in glycated hemoglobin A1c (HbA1c) by treatment group using multivariable non-linear regression model. RESULTS The proportion of patients with insulin only decreased from 15.0% to 3.6%, patients with insulin+non-insulin drugs increased from 8.1% to 15.1%, patients with non-insulin drugs increased from 50.8% to 67.0%, and those with no drugs decreased from 26.1% to 14.4% from 2002 to 2018, respectively. The HbA1c levels of each group, except for no drugs, continued to decrease until 2014 (unadjusted mean HbA1c (%) from 2002 to 2014: from 7.89 to 7.45 for insulin only, from 8.09 to 7.63 for insulin+non-insulin, and from 7.51 to 6.98 for non-insulin) and remained unchanged thereafter. Among insulin-treated patients, use of human insulin decreased, use of long-acting analog insulin increased, and concomitant use of non-insulin drugs increased (from 35.1% in 2002 to 80.9% in 2018), which included increased use of dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists, and the persistently high use of metformin. CONCLUSIONS During the past two decades, combined use of insulin and non-insulin drugs increased and glycemic control improved and leveled off after 2014 in Japanese patients with type 2 diabetes. Further studies of the trend in association with age and factors related to metabolic syndrome are necessary to investigate strategies aiming at personalized medicine in diabetes care.
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Affiliation(s)
| | - Shin-Ichi Araki
- Department of Internal Medicine, Division of Nephrology, Wakayama Medical University, Wakayama, Japan
| | | | | | | | | | | | | | - Daijiro Kabata
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Ayumi Shintani
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hiroshi Maegawa
- Department of Medicine, Shiga University of Medical Science, Otsu, Japan
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26
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Chow E, Yang A, Chung CHL, Chan JCN. A Clinical Perspective of the Multifaceted Mechanism of Metformin in Diabetes, Infections, Cognitive Dysfunction, and Cancer. Pharmaceuticals (Basel) 2022; 15:ph15040442. [PMID: 35455439 PMCID: PMC9030054 DOI: 10.3390/ph15040442] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 03/30/2022] [Accepted: 03/30/2022] [Indexed: 12/16/2022] Open
Abstract
In type 2 diabetes, ecological and lifecourse factors may interact with the host microbiota to influence expression of his/her genomes causing perturbation of interconnecting biological pathways with diverse clinical course. Metformin is a plant-based or plant-derived medicinal product used for the treatment of type 2 diabetes for over 60 years and is an essential drug listed by the World Health Organization. By reducing mitochondrial oxidative phosphorylation and adenosine triphosphate (ATP) production, metformin increased AMP (adenosine monophosphate)-activated protein kinase (AMPK) activity and altered cellular redox state with reduced glucagon activity, endogenous glucose production, lipogenesis, and protein synthesis. Metformin modulated immune response by directly reducing neutrophil to lymphocyte ratio and improving the phagocytic function of immune cells. By increasing the relative abundance of mucin-producing and short-chain-fatty-acid-producing gut microbes, metformin further improved the host inflammatory and metabolic milieu. Experimentally, metformin promoted apoptosis and reduced proliferation of cancer cells by reducing their oxygen consumption and modulating the microenvironment. Both clinical and mechanistic studies support the pluripotent effects of metformin on reducing cardiovascular–renal events, infection, cancer, cognitive dysfunction, and all-cause death in type 2 diabetes, making this low-cost medication a fundamental therapy for individualization of other glucose-lowering drugs in type 2 diabetes. Further research into the effects of metformin on cognitive function, infection and cancer, especially in people without diabetes, will provide new insights into the therapeutic value of metformin in our pursuit of prevention and treatment of ageing-related as well as acute and chronic diseases beyond diabetes.
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Affiliation(s)
- Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China; (E.C.); (A.Y.); (C.H.L.C.)
- The Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China; (E.C.); (A.Y.); (C.H.L.C.)
- The Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China
| | - Colin H. L. Chung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China; (E.C.); (A.Y.); (C.H.L.C.)
| | - Juliana C. N. Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China; (E.C.); (A.Y.); (C.H.L.C.)
- The Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China
- Correspondence: ; Tel.: +852-3505-3138
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Morton JI, Lazzarini PA, Shaw JE, Magliano DJ. Trends in the Incidence of Hospitalization for Major Diabetes-Related Complications in People With Type 1 and Type 2 Diabetes in Australia, 2010-2019. Diabetes Care 2022; 45:789-797. [PMID: 35085387 DOI: 10.2337/dc21-2268] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 01/04/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To determine trends in the incidence of major diabetes-related complications in Australia. RESEARCH DESIGN AND METHODS This study included 70,885 people with type 1 and 1,089,270 people with type 2 diabetes registered on the Australian diabetes registry followed from July 2010 to June 2019. Outcomes (hospitalization for myocardial infarction [MI], stroke, heart failure [HF], lower-extremity amputation [LEA], hypoglycemia, and hyperglycemia) were obtained via linkage to hospital admissions databases. Trends over time in the age-adjusted incidence of hospitalizations were analyzed using joinpoint regression and summarized as annual percent changes (APCs). RESULTS In type 1 diabetes, the incidence of all complications remained stable, except for stroke, which increased from 2010-2011 to 2018-2019 (financial years; APC: +2.5% [95% CI 0.1, 4.8]), and hyperglycemia, which increased from 2010-2011 to 2016-2017 (APC: +2.7% [1.0, 4.5]). In type 2 diabetes, the incidence of stroke remained stable, while the incidence of MI decreased from 2012-2013 to 2018-2019 (APC: -1.7% [95% CI -2.8, -0.5]), as did the incidence of HF and hypoglycemia from 2010-2011 to 2018-2019 (APCs: -0.8% [-1.5, 0.0] and -5.3% [-6.7, -3.9], respectively); the incidence of LEA and hyperglycemia increased (APCs: +3.1% [1.9, 4.4], and +7.4% [5.9, 9.0]). Most trends were consistent by sex, but differed by age; in type 2 diabetes most improvements were confined to individuals aged ≥60 years. CONCLUSIONS Trends in admissions for diabetes-related complications were largely stable in type 1 diabetes. In type 2 diabetes, hospitalization rates for MI, HF, and hypoglycemia fell over time, while increasing for LEA and hyperglycemia.
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Affiliation(s)
- Jedidiah I Morton
- Baker Heart and Diabetes Institute, Melbourne, Australia.,School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Peter A Lazzarini
- School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia.,Australian Centre for Health Services Innovation & Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia.,Allied Health Research Collaborative, The Prince Charles Hospital, Brisbane, Australia
| | - Jonathan E Shaw
- Baker Heart and Diabetes Institute, Melbourne, Australia.,School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Dianna J Magliano
- Baker Heart and Diabetes Institute, Melbourne, Australia.,School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
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Yang A, Shi M, Wu H, Lau ES, Fan B, Kong AP, Ma RC, Luk AO, Chan JC, Chow E. Time-varying risk associations of renin angiotensin system inhibitors with pneumonia and related deaths in a cohort of 252,616 patients with diabetes (2002-2019). Diabetes Res Clin Pract 2022; 185:109233. [PMID: 35131377 DOI: 10.1016/j.diabres.2022.109233] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 01/06/2022] [Accepted: 01/31/2022] [Indexed: 02/06/2023]
Abstract
AIMS To evaluate the time-varying and cumulative risk associations of renin-angiotensin-system-inhibitors (RASi) with pneumonia and related deaths in people with diabetes. METHODS This was a prospective analysis with propensity-score overlap-weighting of a territory-wide cohort (n = 252,616, 1.7 million person-years) and a register-based cohort (n = 13,017, 0.1 million person-years) of patients with diabetes in Hong Kong. We compared risk of pneumonia and related death in new-users of angiotensin-converting-enzyme-inhibitor (ACEi) and angiotensin-receptor-blocker (ARBs) with non-RASi users and new-users of calcium-channel-blockers as active comparator. RESULTS Amongst 252,616 people with diabetes (99.3% type 2 diabetes) in the population-based cohort with a mean follow-up of 6.7 years, 73,161 were new-ACEi-only users; 20,907 new-ARBs-only users; 38,778 ACEi/ARBs users; and 119,770 never-ACEi/ARBs. Time-varying RASi exposure was associated with reduced risk of pneumonia (HR = 0.78, 95% CI: 0.75-0.82) and pneumonia-related death (HR = 0.49, 0.46-0.53). The respective HRs for ARBs-only were 0.70 (0.62-0.78) and 0.41 (0.33-0.52) and that of ACEi-only were 0.98 (0.91-1.05) and 0.77 (0.68-86). The attenuated risk association of RASi use was time-invariant for pneumonia (P = 0.340) and time-varying for related-death (P < 0.001) with prevention of 0.6 (0.2-0.9) and 1.4 (1.0-1.6) per-1000-person-years events and deaths, respectively. CONCLUSIONS Long-term use of RASi, notably ARBs, was associated with reduced risk of pneumonia and related deaths in Chinese people with diabetes.
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Affiliation(s)
- Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Mai Shi
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Eric Sh Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Baoqi Fan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Alice Ps Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Ronald Cw Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Andrea Oy Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Juliana Cn Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
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Nakhleh A, Shehadeh N. Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention. World J Diabetes 2021; 12:2036-2049. [PMID: 35047118 PMCID: PMC8696639 DOI: 10.4239/wjd.v12.i12.2036] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/16/2021] [Accepted: 12/07/2021] [Indexed: 02/06/2023] Open
Abstract
Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. Episodes of hypoglycemia are associated with physical and psychological morbidity. The fear of hypoglycemia constitutes a barrier that impairs the patient's ability to reach good glycemic control. To prevent hypoglycemia, much effort must be invested in patient education regarding risk factors, warning signs, and treatment of hypoglycemia at an early stage, together with setting personalized goals for glycemic control. In this review, we present a comprehensive update on the treatment and prevention of hypoglycemia in type 1 and type 2 diabetic patients.
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Affiliation(s)
- Afif Nakhleh
- Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa 3109601, Israel
| | - Naim Shehadeh
- Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa 3109601, Israel
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30
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Wu H, Lau ESH, Yang A, Zhang X, Ma RCW, Kong APS, Chow E, So WY, Chan JCN, Luk AOY. Data Resource Profile: The Hong Kong Diabetes Surveillance Database (HKDSD). Int J Epidemiol 2021; 51:e9-e17. [PMID: 34904159 DOI: 10.1093/ije/dyab252] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 11/29/2021] [Indexed: 02/01/2023] Open
Affiliation(s)
- Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China
| | - Eric S H Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China
| | - Xinge Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China
| | - Ronald C W Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China
| | - Alice P S Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China
| | - Wing-Yee So
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.,Hong Kong Hospital Authority, Hong Kong Special Administrative Region, P. R. China
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China
| | - Andrea O Y Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, P. R. China
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31
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Defining Potentially Inappropriate Prescriptions for Hypoglycaemic Agents to Improve Computerised Decision Support: A Study Protocol. Healthcare (Basel) 2021; 9:healthcare9111539. [PMID: 34828585 PMCID: PMC8622925 DOI: 10.3390/healthcare9111539] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 11/05/2021] [Accepted: 11/07/2021] [Indexed: 12/21/2022] Open
Abstract
In France, around 5% of the general population are taking drug treatments for diabetes mellitus (mainly type 2 diabetes mellitus, T2DM). Although the management of T2DM has become more complex, most of these patients are managed by their general practitioner and not a diabetologist for their antidiabetics treatments; this increases the risk of potentially inappropriate prescriptions (PIPs) of hypoglycaemic agents (HAs). Inappropriate prescribing can be assessed by approaches that are implicit (expert judgement based) or explicit (criterion based). In a mixed, multistep process, we first systematically reviewed the published definitions of PIPs for HAs in patients with T2DM. The results will be used to create the first list of explicit definitions. Next, we will complete the definitions identified in the systematic review by conducting a qualitative study with two focus groups of experts in the prescription of HAs. Lastly, a Delphi survey will then be used to build consensus among participants; the results will be validated in consensus meetings. We developed a method for determining explicit definitions of PIPs for HAs in patients with T2DM. The resulting explicit definitions could be easily integrated into computerised decision support tools for the automated detection of PIPs.
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32
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Feng L, Lam A, Carmody D, Lim CW, Tan G, Goh SY, Bee YM, Jafar TH. Trends in cardiovascular risk factors and treatment goals in patients with diabetes in Singapore-analysis of the SingHealth Diabetes Registry. PLoS One 2021; 16:e0259157. [PMID: 34748574 PMCID: PMC8575178 DOI: 10.1371/journal.pone.0259157] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/13/2021] [Indexed: 01/04/2023] Open
Abstract
Background Asian populations are at high risk of diabetes and related vascular complications. We examined risk factor control, preventive care, and disparities in these trends among adults with diabetes in Singapore. Methods The sample included 209,930 adults with diabetes aged≥18 years from a multi-institutional SingHealth Diabetes Registry between 2013 and 2019 in Singapore. We performed logistic generalized estimating equations (GEEs) regression analysis and used linear mixed effect modeling to evaluate the temporal trends. Results Between 2013 and 2019, the unadjusted control rates of glycated hemoglobin (4.8%, 95%CI (4.4 to 5.1) and low-density lipoprotein cholesterol (LDL-C) (11.5%, 95%CI (11.1 to 11.8)) improved, but blood pressure (BP) control worsened (systolic BP (SBP)/diastolic BP (DBP) <140/90 mmHg: -6.6%, 95%CI (-7.0 to -6.2)). These trends persisted after accounting for the demographics including age, gender, ethnicity, and housing type. The 10-year adjusted risk for coronary heart disease (CHD) (3.4%, 95% (3.3 to 3.5)) and stroke (10.4%, 95% CI (10.3 to 10.5)) increased. In 2019, the control rates of glycated hemoglobin, BP (SBP/DBP<140/90 mmHg), LDL-C, each, and all three risk factors together, accounted for 51.5%, 67.7%, 72.2%, and 24.4%, respectively. Conclusions Trends in risk factor control improved for glycated hemoglobin and LDL-C, but worsened for BP among diabetic adults in Singapore from 2013 to 2019. Control rates for all risk factors remain inadequate.
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Affiliation(s)
- Liang Feng
- Program in Health Services & Systems Research, Duke-NUS Medical School, Singapore, Singapore
| | - Amanda Lam
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - David Carmody
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Ching Wee Lim
- Program in Health Services & Systems Research, Duke-NUS Medical School, Singapore, Singapore
| | - Gilbert Tan
- SingHealth Polyclinics, Singapore, Singapore
| | - Su-Yen Goh
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Yong Mong Bee
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Tazeen H. Jafar
- Program in Health Services & Systems Research, Duke-NUS Medical School, Singapore, Singapore
- Duke Global Health Institute, Durham, NC, United States of America
- * E-mail:
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33
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Wang K, Yang A, Shi M, Tam CCH, Lau ESH, Fan B, Lim CKP, Lee HM, Kong APS, Luk AOY, Tomlinson B, Ma RCW, Chan JCN, Chow E. CYP2C19 Loss-of-function Polymorphisms are Associated with Reduced Risk of Sulfonylurea Treatment Failure in Chinese Patients with Type 2 Diabetes. Clin Pharmacol Ther 2021; 111:461-469. [PMID: 34656068 PMCID: PMC9297921 DOI: 10.1002/cpt.2446] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 10/08/2021] [Indexed: 01/14/2023]
Abstract
Sulfonylureas (SUs) are predominantly metabolized by cytochrome p450 2C9 (CYP2C9) and cytochrome p450 2C19 (CYP2C19) enzymes. CYP2C9 polymorphisms are associated with greater treatment response and hypoglycemic risk in SU users. However, there are no large scale pharmacogenetic studies investigating the effect of loss‐of‐function alleles CYP2C19*2 and CYP2C19*3, which occur frequently in East Asians. Retrospective pharmacogenetic analysis was performed in 11,495 genotyped patients who were enrolled in the Hong Kong Diabetes Register between 1995 and 2017, with follow‐up to December 31, 2019. The associations of CYP2C19 polymorphisms with SU treatment failure, early HbA1c response, and severe hypoglycemia were analyzed by Cox regression or logistic regression assuming an additive genetic model. There were 2341 incident SU users that were identified (mean age 59 years, median diabetes duration 9 years), of which 324 were CYP2C19 poor metabolizers (CYP2C19 *2/*2 or *2/*3 or *3/*3). CYP2C19 poor metabolizers had lower risk of SU treatment failure (hazard ratio 0.83, 95% confidence interval (CI) 0.72–0.97, P = 0.018) and were more likely to reach the HbA1c treatment target < 7% (odds ratio 1.52, 95% CI 1.02–2.27, P = 0.039) than wild‐type carriers (CYP2C19 *1/*1) following adjustment for multiple covariates. There were no significant differences in severe hypoglycemia rates among different CYP2C19 genotype groups. CYP2C19 polymorphisms should be considered during personalization of SU therapy.
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Affiliation(s)
- Ke Wang
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Aimin Yang
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| | - Mai Shi
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Claudia C H Tam
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| | - Eric S H Lau
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Baoqi Fan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| | - Cadmon K P Lim
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| | - Heung Man Lee
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| | - Alice P S Kong
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| | - Andrea O Y Luk
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.,Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| | - Brian Tomlinson
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Faculty of Medicine, Macau University of Science and Technology, Macau, China
| | - Ronald C W Ma
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.,Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.,Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
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Lee SE, Kim KA, Son KJ, Song SO, Park KH, Park SH, Nam JY. Trends and risk factors in severe hypoglycemia among individuals with type 2 diabetes in Korea. Diabetes Res Clin Pract 2021; 178:108946. [PMID: 34252506 DOI: 10.1016/j.diabres.2021.108946] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 07/02/2021] [Accepted: 07/06/2021] [Indexed: 11/24/2022]
Abstract
AIMS Because of the development of new classes of antidiabetic drugs, hypoglycemic events were expected to decrease. We investigated the trends and risk factors for severe hypoglycemia in subjects with type 2 diabetes in Korea. METHODS We conducted repeated cross-sectional analyses using a Korean National Health Insurance Service-National Sample Cohort from 2006 to 2015. Severe hypoglycemia was defined as hospitalization or a visit to an emergency department with diagnosis of hypoglycemia using ICD-10 codes. RESULTS During the study period, the prevalence of type 2 diabetes continuously increased. The percentage of patients prescribed metformin and dipeptidyl peptidase-4 inhibitor increased, while the use of sulfonylurea decreased considerably, especially since 2009. The proportion of patients prescribed ≥3 classes of drugs continually increased. Age-standardized incidence of severe hypoglycemia per 1000 patients with diabetes increased from 6.00 to 8.24 between 2006 and 2010, and then fell to 6.49 in 2015. Predictors of severe hypoglycemia included female, older age, comorbidities, polypharmacy, and sulfonylurea or insulin usage. CONCLUSIONS Trends of severe hypoglycemia were associated with changes in drug classes rather than number of antidiabetic drugs. Relentless efforts to reduce the prescription of drugs with a high risk of hypoglycemia should be implemented, particularly for older women with multiple comorbidities.
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Affiliation(s)
- Seung Eun Lee
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
| | - Kyoung-Ah Kim
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
| | - Kang Ju Son
- Department of Research and Analysis, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea; Department of Biostatistics and Computing, Yonsei University Graduate School, Seoul, Republic of Korea.
| | - Sun Ok Song
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea.
| | - Kyeong Hye Park
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea.
| | - Se Hee Park
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea.
| | - Joo Young Nam
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea.
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Wu H, Lau ESH, Yang A, Szeto CC, Ma RCW, Kong APS, Chow E, So WY, Chan JCN, Luk AOY. Trends in kidney failure and kidney replacement therapy in people with diabetes in Hong Kong, 2002-2015: A retrospective cohort study. LANCET REGIONAL HEALTH-WESTERN PACIFIC 2021; 11:100165. [PMID: 34327367 PMCID: PMC8315404 DOI: 10.1016/j.lanwpc.2021.100165] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 04/12/2021] [Accepted: 04/19/2021] [Indexed: 12/14/2022]
Abstract
Background There are limited population-wide trend data on kidney failure and kidney replacement therapy (KRT) in people with diabetes. We conducted a retrospective cohort study to report incidence trends of kidney failure and KRT and related mortality in people with diabetes in Hong Kong between 2002 and 2015. Methods We used territory-wide electronic medical records including laboratory, diagnostic and procedural data to identify people with kidney failure and KRT. We used Joinpoint regression models to estimate the average annual percent change (AAPC) of kidney failure and KRT incidence for entire study period, and annual percent change (APC) for each linear trend segment, along with 1-year and 5-year mortality rates. Findings During 4.9 million person-years of follow-up of 712,222 people with diabetes, 31,425 developed kidney failure, among whom 23.0% (n=7,233) received KRT. The incidence of kidney failure declined by 46.8% from 2002 to 2007 (APC: -11.6, 95% CI: -16.3, -6.7), then flattened from 2007 to 2015 (APC: -0.9, 95% CI: -3.1, 1.3). The incidence of KRT remained constant (AAPC: -1.6, 95% CI: -4.4, 1.2). The 1-year mortality rates declined statistically significantly after both kidney failure and KRT. The 5-year mortality rates declined after kidney failure but the decline was not statistically significant after KRT. Interpretation The findings of our study highlight the importance of developing new strategies to prevent a looming epidemic of kidney failure in people with diabetes in Hong Kong. Funding Asia Diabetes Foundation
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Key Words
- AAPC, Average annual percent change
- APC, Annual percent change
- EMR, Electronic medical record
- HA, Hospital Authority
- HD, Hemodialysis
- HKDSD, Hong Kong Diabetes Surveillance Database
- KRT, Kidney replacement therapy
- PD, Peritoneal dialysis
- RAAS, Renin-angiotensin-aldosterone system
- RAMP-DM, Risk Assessment and Management Programme-Diabetes Mellitus
- diabetes
- incidence
- kidney failure
- kidney replacement therapy
- mortality
- trend
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Affiliation(s)
- Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Eric S H Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Cheuk-Chun Szeto
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Ronald C W Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Alice P S Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Wing-Yee So
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Hospital Authority, Hong Kong Special Administrative Region, People's Republic of China
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Andrea O Y Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
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