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Umegaki H. Management of older adults with diabetes mellitus: Perspective from geriatric medicine. J Diabetes Investig 2024; 15:1347-1354. [PMID: 39115890 PMCID: PMC11442781 DOI: 10.1111/jdi.14283] [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: 06/30/2024] [Accepted: 07/22/2024] [Indexed: 10/02/2024] Open
Abstract
Advances in diabetes medication and population aging are lengthening the lifespans of people with diabetes mellitus (DM). Older patients with diabetes mellitus often have multimorbidity and tend to have polypharmacy. In addition, diabetes mellitus is associated with frailty, functional decline, cognitive impairment, and geriatric syndrome. Although the numbers of patients with frailty, dementia, disability, and/or multimorbidity are increasing worldwide, the accumulated evidence on the safe and effective treatment of these populations remains insufficient. Older patients, especially those older than 75 years old, are often underrepresented in randomized controlled trials of various treatment effects, resulting in limited clinical evidence for this population. Therefore, a deeper understanding of the characteristics of older patients is essential to tailor management strategies to their needs. The clinical guidelines of several academic societies have begun to recognize the importance of relaxing glycemic control targets to prevent severe hypoglycemia and to maintain quality of life. However, glycemic control levels are thus far based on expert consensus rather than on robust clinical evidence. There is an urgent need for the personalized management of older adults with diabetes mellitus that considers their multimorbidity and function and strives to maintain a high quality of life through safe and effective medical treatment. Older adults with diabetes mellitus accompanied by frailty, functional decline, cognitive impairment, and multimorbidity require special management considerations and liaison with both carers and social resources.
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Affiliation(s)
- Hiroyuki Umegaki
- Department of Community Healthcare and GeriatricsNagoya University Graduate School of MedicineAichiJapan
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2
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Ajjan RA, Seidu S, Riveline JP. Perspective of Continuous Glucose Monitoring-Based Interventions at the Various Stages of Type 2 Diabetes. Diabetes Ther 2024; 15:1657-1672. [PMID: 38907936 PMCID: PMC11263446 DOI: 10.1007/s13300-024-01607-5] [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: 04/11/2024] [Accepted: 06/03/2024] [Indexed: 06/24/2024] Open
Abstract
Continuous glucose monitoring (CGM) is now advocated for the clinical management of individuals with type 1 diabetes (T1D). However, this glucose monitoring strategy is not routinely used in type 2 diabetes (T2D), given the large population, significant cost implications and relatively limited supporting evidence. T2D is a more heterogenous condition compared with T1D with various glucose lowering therapies that do not necessarily require CGM to ensure within target glucose levels. While all individuals with T2D may benefit from CGM at certain time points, the whole T2D population does not necessarily require this technology continuously, which should be prioritized based on patient benefit and cost effectiveness. In this pragmatic opinion piece, we describe the rationale and evidence for CGM use in different subgroups of individuals with T2d, divided according to the stage of the condition, glycemic therapies, presence of diabetes complications, or associated co-morbidities. We discuss a total of 16 T2D subgroups and provide a clinical view on CGM use in each, based on current evidence while also highlighting areas of knowledge gaps. This work provides health care professionals with a simple guide to CGM use in different T2D groups and gives suggestion for future studies to justify expansion of this technology.
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Affiliation(s)
- R A Ajjan
- Leeds Institute for Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, LS2 9JT, UK.
- St James's University Hospital, Leeds Teaching Hospitals Trust, Leeds, LS9 7TF, UK.
| | - S Seidu
- Diabetes Research Centre, Applied Research Collaboration East Midlands, National Institute for Health Research, University of Leicester, Leicester, UK
- Diabetes Research Centre, University of Leicester, National Institute for Health Research Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - J P Riveline
- Lariboisière Hospital, 2 Rue Ambroise Paré, 75010, Paris, France
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Yun JS, Kim K, Ahn YB, Han K, Ko SH. Holistic and Personalized Strategies for Managing in Elderly Type 2 Diabetes Patients. Diabetes Metab J 2024; 48:531-545. [PMID: 39091004 PMCID: PMC11307114 DOI: 10.4093/dmj.2024.0310] [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: 06/14/2024] [Accepted: 07/11/2024] [Indexed: 08/04/2024] Open
Abstract
Due to increased life expectancy and lifestyle changes, the prevalence of diabetes among the elderly in Korea is continuously rising, as is the associated public health burden. Diabetes management in elderly patients is complicated by age-related physiological changes, sarcopenia characterized by loss of muscle mass and function, comorbidities, and varying levels of functional, cognitive, and mobility abilities that lead to frailty. Moreover, elderly patients with diabetes frequently face multiple chronic conditions that elevate their risk of cardiovascular diseases, cancer, and mortality; they are also prone to complications such as hyperglycemic hyperosmolar state, diabetic ketoacidosis, and severe hypoglycemia. This review examines the characteristics of and management approaches for diabetes in the elderly, and advocates for a comprehensive yet personalized strategy.
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Affiliation(s)
- Jae-Seung Yun
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyuho Kim
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yu-Bae Ahn
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Seung-Hyun Ko
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Toschi E, O’Neal D, Munshi M, Jenkins A. Glucose Targets Using Continuous Glucose Monitoring Metrics in Older Adults With Diabetes: Are We There Yet? J Diabetes Sci Technol 2024; 18:808-818. [PMID: 38715259 PMCID: PMC11307211 DOI: 10.1177/19322968241247568] [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] [Indexed: 07/02/2024]
Abstract
The older population is increasing worldwide and up to 30% of older adults have diabetes. Older adults with diabetes are at risk of glucose-related acute and chronic complications. Recently, mostly in type 1 diabetes (T1D), continuous glucose monitoring (CGM) devices have proven beneficial in improving time in range (TIR glucose, 70-180 mg/dL or glucose 3.9-10 mmol/L), glycated hemoglobin (HbA1c), and in lowering hypoglycemia (time below range [TBR] glucose <70 mg/dL or glucose <3.9 mmol/L). The international consensus group formulated CGM glycemic targets relating to older adults with diabetes based on very limited data. Their recommendations, based on expert opinion, were aimed at mitigating hypoglycemia in all older adults. However, older adults with diabetes are a heterogeneous group, ranging from healthy to very complex frail individuals based on chronological, biological, and functional aging. Recent clinical trial and real-world data, mostly from healthy older adults with T1D, demonstrated that older adults often achieve CGM targets, including TIR recommended for non-vulnerable groups, but less often meet the recommended TBR <1%. Existing data also support that hypoglycemia avoidance may be more strongly related to minimization of glucose variability (coefficient of variation [CV]) rather than lower TIR. Very limited data are available for glucose goals in older adults adjusted for the complexity of their health status. Herein, we review the bidirectional associations between glucose and health status in older adults with diabetes; use of diabetes technologies, and their impact on glucose control; discuss current guidelines; and propose a new set of CGM targets for older adults with insulin-treated diabetes that are individualized for health and living status.
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Affiliation(s)
- Elena Toschi
- Joslin Diabetes Center, Harvard Medical
School, Boston, MA, USA
| | - David O’Neal
- Department of Medicine, St Vincent’s
Hospital, The University of Melbourne, Melbourne, VIC, Australia
- Department of Diabetes and
Endocrinology, St Vincent’s Hospital, Melbourne, VIC, Australia
- Australian Centre for Accelerating
Diabetes Innovations, The University of Melbourne, Melbourne, VIC, Australia
| | - Medha Munshi
- Joslin Diabetes Center, Harvard Medical
School, Boston, MA, USA
| | - Alicia Jenkins
- Department of Medicine, St Vincent’s
Hospital, The University of Melbourne, Melbourne, VIC, Australia
- Department of Diabetes and
Endocrinology, St Vincent’s Hospital, Melbourne, VIC, Australia
- Australian Centre for Accelerating
Diabetes Innovations, The University of Melbourne, Melbourne, VIC, Australia
- Baker Heart & Diabetes Institute,
Melbourne, VIC, Australia
- Faculty of Medicine, Monash University,
Melbourne, VIC, Australia
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Liu D, Chihuri S, Andrews HF, Betz ME, DiGuiseppi C, Eby DW, Hill LL, Jones V, Mielenz TJ, Molnar LJ, Strogatz D, Lang BH, Li G. Diabetes mellitus and hard braking events in older adult drivers. Inj Epidemiol 2024; 11:22. [PMID: 38840227 DOI: 10.1186/s40621-024-00508-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 05/23/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Diabetes mellitus (DM) can impair driving safety due to hypoglycemia, hyperglycemia, diabetic peripheral neuropathy, and diabetic eye diseases. However, few studies have examined the association between DM and driving safety in older adults based on naturalistic driving data. METHODS Data for this study came from a multisite naturalistic driving study of drivers aged 65-79 years at baseline. Driving data for the study participants were recorded by in-vehicle recording devices for up to 44 months. We used multivariable negative binomial modeling to estimate adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (HBEs, defined as maneuvers with deceleration rates ≥ 0.4 g) associated with DM. RESULTS Of the 2856 study participants eligible for this analysis, 482 (16.9%) reported having DM at baseline, including 354 (12.4%) insulin non-users and 128 (4.5%) insulin users. The incidence rates of HBEs per 1000 miles were 1.13 for drivers without DM, 1.15 for drivers with DM not using insulin, and 1.77 for drivers with DM using insulin. Compared to drivers without DM, the risk of HBEs was 48% higher for drivers with DM using insulin (aIRR 1.48; 95% CI: 1.43, 1.53). CONCLUSION Older adult drivers with DM using insulin appear to be at increased proneness to vehicular crashes. Driving safety should be taken into consideration in DM care and management.
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Affiliation(s)
- Difei Liu
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA
| | - Stanford Chihuri
- Department of Anesthesiology, Vagelos College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, NY, PH5-534, 10032, USA
| | - Howard F Andrews
- Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA
| | - Marian E Betz
- Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA
- VA Eastern Colorado Geriatric Research Education and Clinical Center, Aurora, CO, 80045, USA
| | - Carolyn DiGuiseppi
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA
| | - David W Eby
- College of Engineering, University of Michigan Transportation Research Institute, Ann Arbor, MI, 48109, USA
| | - Linda L Hill
- School of Public Health, University of California San Diego, La Jolla, San Diego, CA, 92093, USA
| | - Vanya Jones
- Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA
| | - Thelma J Mielenz
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA
- Columbia Center for Injury Science and Prevention, Columbia University Irving Medical Center, New York, NY, 10032, USA
| | - Lisa J Molnar
- College of Engineering, University of Michigan Transportation Research Institute, Ann Arbor, MI, 48109, USA
| | - David Strogatz
- Bassett Research Institute, Bassett Healthcare Network, Cooperstown, NY, 13326, USA
| | - Barbara H Lang
- Department of Anesthesiology, Vagelos College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, NY, PH5-534, 10032, USA
| | - Guohua Li
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA.
- Department of Anesthesiology, Vagelos College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, NY, PH5-534, 10032, USA.
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Fabricius TW, Verhulst CEM, Kristensen PL, Holst JJ, Tack CJ, McCrimmon RJ, Heller SR, Evans ML, de Galan BE, Pedersen-Bjergaard U. Counterregulatory hormone and symptom responses to hypoglycaemia in people with type 1 diabetes, insulin-treated type 2 diabetes or without diabetes: the Hypo-RESOLVE hypoglycaemic clamp study. Acta Diabetol 2024; 61:623-633. [PMID: 38376580 PMCID: PMC11055751 DOI: 10.1007/s00592-024-02239-8] [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: 10/09/2023] [Accepted: 01/13/2024] [Indexed: 02/21/2024]
Abstract
AIM The sympathetic nervous and hormonal counterregulatory responses to hypoglycaemia differ between people with type 1 and type 2 diabetes and may change along the course of diabetes, but have not been directly compared. We aimed to compare counterregulatory hormone and symptom responses to hypoglycaemia between people with type 1 diabetes, insulin-treated type 2 diabetes and controls without diabetes, using a standardised hyperinsulinaemic-hypoglycaemic clamp. MATERIALS We included 47 people with type 1 diabetes, 15 with insulin-treated type 2 diabetes, and 32 controls without diabetes. Controls were matched according to age and sex to the people with type 1 diabetes or with type 2 diabetes. All participants underwent a hyperinsulinaemic-euglycaemic-(5.2 ± 0.4 mmol/L)-hypoglycaemic-(2.8 ± 0.13 mmol/L)-clamp. RESULTS The glucagon response was lower in people with type 1 diabetes (9.4 ± 0.8 pmol/L, 8.0 [7.0-10.0]) compared to type 2 diabetes (23.7 ± 3.7 pmol/L, 18.0 [12.0-28.0], p < 0.001) and controls (30.6 ± 4.7, 25.5 [17.8-35.8] pmol/L, p < 0.001). The adrenaline response was lower in type 1 diabetes (1.7 ± 0.2, 1.6 [1.3-5.2] nmol/L) compared to type 2 diabetes (3.4 ± 0.7, 2.6 [1.3-5.2] nmol/L, p = 0.001) and controls (2.7 ± 0.4, 2.8 [1.4-3.9] nmol/L, p = 0.012). Growth hormone was lower in people with type 2 diabetes than in type 1 diabetes, at baseline (3.4 ± 1.6 vs 7.7 ± 1.3 mU/L, p = 0.042) and during hypoglycaemia (24.7 ± 7.1 vs 62.4 ± 5.8 mU/L, p = 0.001). People with 1 diabetes had lower overall symptom responses than people with type 2 diabetes (45.3 ± 2.7 vs 58.7 ± 6.4, p = 0.018), driven by a lower neuroglycopenic score (27.4 ± 1.8 vs 36.7 ± 4.2, p = 0.012). CONCLUSION Acute counterregulatory hormone and symptom responses to experimental hypoglycaemia are lower in people with type 1 diabetes than in those with long-standing insulin-treated type 2 diabetes and controls.
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Affiliation(s)
- Therese W Fabricius
- Department of Endocrinology and Nephrology, Nordsjællands Hospital, Hillerød, Denmark.
| | - Clementine E M Verhulst
- Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Peter L Kristensen
- Department of Endocrinology and Nephrology, Nordsjællands Hospital, Hillerød, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens J Holst
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Cees J Tack
- Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Rory J McCrimmon
- Systems Medicine, School of Medicine, University of Dundee, Dundee, UK
| | - Simon R Heller
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Mark L Evans
- Welcome MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - Bastiaan E de Galan
- Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
- Department of Internal Medicine, Maastricht UMC+, Maastricht, The Netherlands
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
| | - Ulrik Pedersen-Bjergaard
- Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Fløde M, Hermann M, Haugstvedt A, Søfteland E, Igland J, Åsberg A, Jenssen TG, Graue M. High number of hypoglycaemic episodes identified by CGM among home-dwelling older people with diabetes: an observational study in Norway. BMC Endocr Disord 2023; 23:218. [PMID: 37817166 PMCID: PMC10566065 DOI: 10.1186/s12902-023-01472-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 09/28/2023] [Indexed: 10/12/2023] Open
Abstract
BACKGROUND A scoping review from 2021 identified a lack of studies on the incidence, prevention and management of hypoglycaemia in home-dwelling older people with diabetes. The aim of this study was to investigate the frequency and duration of hypoglycaemic episodes measured by continuous glucose monitoring (CGM) in older people with diabetes who received home care and who were treated with glucose-lowering medications, and to compare the frequency and duration of hypoglycaemic episodes between subgroups of the study population according to demographic and clinical variables. METHODS This was an observational study investigating the occurrence of hypoglycaemia in people with diabetes aged ≥ 65 years. Data were collected using blinded continuous glucose monitoring (CGM, iPro2) for 5 consecutive days. Frequency and duration of hypoglycaemic episodes were assessed using a sensor glucose cut-off value of 3.9 mmol/L. A blood sample for measurement of HbA1c and creatinine-based eGFR (CKD-EPI) was obtained during the monitoring period. Demographic and clinical data were collected from electronic patient records. RESULTS Fifty-six individuals were enrolled (median age 82 years and 52% were men). Of the 36 participants who were treated with insulin, 33% had at least one hypoglycaemic episode during the five-day period. Among 18 participants who neither used insulin nor sulfonylurea, but other glucose-lowering medications, 44% had at least one hypoglycaemicepisode. Of those with hypoglycaemic episodes, 86% lived alone. The median duration of the hypoglycaemia was 1 h and 25 min, ranging from 15 min to 8 h and 50 min. CONCLUSION This study identified an unacceptably high number of unknown hypoglycaemic episodes among older home-dwelling people with diabetes receiving home care, even among those not using insulin or sulfonylurea. The study provides essential knowledge that can serve as a foundation to improve the treatment and care for this vulnerable patient group. The routines for glucose monitoring and other prevention tasks need to be considered more comprehensively, also, among those treated with glucose-lowering medications other than insulin.
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Affiliation(s)
- Mari Fløde
- Department of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Norway
| | - Monica Hermann
- Department of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Norway
| | - Anne Haugstvedt
- Department of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Norway
| | - Eirik Søfteland
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Jannicke Igland
- Department of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | - Anders Åsberg
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Department of Pharmacy, Section for Pharmacology and Pharmaceutical Biosciences, University of Oslo, Oslo, Norway
| | - Trond Geir Jenssen
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Marit Graue
- Department of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Norway.
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Maxwell H, Dubois S, Cottrell-Martin E, Regalado SM, Stinchcombe A, Migay M, Gibbons C, Weaver B, Bédard M. The association between diabetes and safe driving: A systematic search and review of the literature and cross-reference with the current guidelines. Diabet Med 2023; 40:e15175. [PMID: 37422905 DOI: 10.1111/dme.15175] [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: 02/07/2023] [Revised: 06/21/2023] [Accepted: 07/04/2023] [Indexed: 07/11/2023]
Abstract
AIMS We conducted this review to characterize the quality of evidence about associations between diabetes and safe driving and to evaluate how these findings are reflected within current guidelines available to support clinicians and their patients with diabetes. METHODS The first stage entailed a systematic search and review of the literature. Evidence surrounding harms associated with diabetes and driving was identified, screened, extracted and appraised for quality utilizing the Newcastle Ottawa Scales (NOS). Next, relevant guidelines regarding driving and diabetes were sourced and summarized. Finally, the identified guidelines were cross-referenced with the results of the systematic search and review. RESULTS The systematic search yielded 12,461 unique citations; 52 met the criteria for appraisal. Fourteen studies were rated as 'high', two as 'medium' and 36 as 'low'. Studies with ratings of 'high' or 'medium' were extracted, revealing a body of inconsistent methods and findings. These results, cross-referenced with the guidelines, suggest a lack of agreement and a limited evidence base to justify recommendations. CONCLUSIONS The results presented emphasize the need for a better understanding of the impacts of diabetes on safe driving to inform evidence-based guidelines.
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Affiliation(s)
- Hillary Maxwell
- Centre for Applied Health Research, St. Joseph's Care Group, Thunder Bay, Ontario, Canada
- Centre for Research on Safe Driving, Lakehead University, Thunder Bay, Ontario, Canada
- Department of Health Sciences, Lakehead University, Thunder Bay, Ontario, Canada
| | - Sacha Dubois
- Centre for Applied Health Research, St. Joseph's Care Group, Thunder Bay, Ontario, Canada
- Centre for Research on Safe Driving, Lakehead University, Thunder Bay, Ontario, Canada
- School of Nursing, Lakehead University, Thunder Bay, Ontario, Canada
- NOSM University, Thunder Bay, Ontario, Canada
| | - Elyse Cottrell-Martin
- Centre for Applied Health Research, St. Joseph's Care Group, Thunder Bay, Ontario, Canada
| | - Sophie M Regalado
- Centre for Applied Health Research, St. Joseph's Care Group, Thunder Bay, Ontario, Canada
- Centre for Research on Safe Driving, Lakehead University, Thunder Bay, Ontario, Canada
- NOSM University, Thunder Bay, Ontario, Canada
| | - Arne Stinchcombe
- Centre for Research on Safe Driving, Lakehead University, Thunder Bay, Ontario, Canada
- University of Ottawa, Ottawa, Ontario, Canada
- Bruyère Research Institute, Ottawa, Ontario, Canada
| | - Marcia Migay
- Centre for Applied Health Research, St. Joseph's Care Group, Thunder Bay, Ontario, Canada
| | - Carrie Gibbons
- Centre for Applied Health Research, St. Joseph's Care Group, Thunder Bay, Ontario, Canada
| | - Bruce Weaver
- Centre for Research on Safe Driving, Lakehead University, Thunder Bay, Ontario, Canada
| | - Michel Bédard
- Centre for Applied Health Research, St. Joseph's Care Group, Thunder Bay, Ontario, Canada
- Centre for Research on Safe Driving, Lakehead University, Thunder Bay, Ontario, Canada
- Department of Health Sciences, Lakehead University, Thunder Bay, Ontario, Canada
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9
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Boureau AS, Guyomarch B, Gourdy P, Allix I, Annweiler C, Cervantes N, Chapelet G, Delabrière I, Guyonnet S, Litke R, Paccalin M, Penfornis A, Saulnier PJ, Wargny M, Hadjadj S, de Decker L, Cariou B. Nocturnal hypoglycemia is underdiagnosed in older people with insulin-treated type 2 diabetes: The HYPOAGE observational study. J Am Geriatr Soc 2023. [PMID: 36965179 DOI: 10.1111/jgs.18341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 01/25/2023] [Accepted: 02/02/2023] [Indexed: 03/27/2023]
Abstract
BACKGROUND There is a lack of real-life data regarding the frequency and predictive factors of hypoglycemia in older patients with type 2 diabetes (T2D). This study aimed to determine the frequency and predictors of hypoglycemia in older patients with insulin-treated T2D. METHODS This prospective multicenter study included 155 insulin-treated T2D patients aged 75 years and older with ≥2 self-monitoring of blood glucose (SMBG) daily controls. Participants underwent a geriatric and diabetic assessment and received ambulatory blinded continuous glucose monitoring (CGM) for 28 consecutive days with FreeStyle Libre Pro® sensor. Study population (n = 141) has >70% CGM active time. Multivariable logistic regressions were used to identify factors associated with SMBG confirmed hypoglycemia (≥70 mg/dL) and with nocturnal level 2 time below range (glucose concentration <54 mg/dL during ≥15 consecutive min between 0.00 and 6.00 am). RESULTS The mean age of the 141 analyzed patients was 81.5 ± 5.3 years and 56.7% were male. The mean baseline HbA1c was 7.9% ± 1.0%. After geriatric assessment, 102 participants (72.3%) were considered as complex and 39 (27.7%) as healthy. The primary endpoint (confirmed SMBG <70 mg/dL) occurred in 37.6% patients. In multivariable analysis, the risk of SMBG-confirmed hypoglycemia was positively associated with a longer duration of diabetes (OR (+1 year) =1.04, (1.00-1.08), p = 0.04) and glycemic variability assessed by CGM (CV %) (OR (+1%) = 1.12, [1.05-1.19], p = <0.001). Nighty-two patients (65.2%) experienced nocturnal time in hypoglycemia (i.e., <54 mg/dL during ≥15 consecutive min between midnight and 6 a.m.). In multivariable analyses, cognitive impairment (OR: 9.31 [2.59-33.4]), heart failure (OR: 4.81 [1;48-15.6]), and depressive disorder (OR: 0.19 [0.06-0.53]) were associated with nocturnal time in hypoglycemia. CONCLUSION Nocturnal hypoglycemia is very common and largely underdiagnosed in older patients with insulin-treated T2D. CGM is a promising tool to better identify hypoglycemia and adapt diabetes management in this population.
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Affiliation(s)
- Anne-Sophie Boureau
- Nantes Université, CHU Nantes, Pole de Gérontologie Clinique, Nantes, F-44000, France
| | - Béatrice Guyomarch
- Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, F-44000, France
| | - Pierre Gourdy
- CHU de Toulouse & UMR1297/I2MC, Université de Toulouse, Toulouse, France
| | - Ingrid Allix
- Département d'Endocrinologie, Diabétologie, Nutrition, CHU de Angers, Angers, France
| | - Cédric Annweiler
- Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, University Hospital, Angers, France
- UPRES EA 4638, University of Angers, Angers, France
- Gérontopôle Autonomie Longévité des Pays de la Loire, Nantes, France
- Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, the University of Western Ontario, London, Ontario, Canada
| | | | - Guillaume Chapelet
- Nantes Université, CHU Nantes, Pole de Gérontologie Clinique, Nantes, F-44000, France
| | | | - Sophie Guyonnet
- Gerontopole of Toulouse, Institute of Ageing, Toulouse University Hospital (CHU Toulouse), Toulouse, France
| | - Rachel Litke
- CHU Lille, Geriatric Department, Lille, 59000, France
| | - Marc Paccalin
- CHU de Poitiers, Pôle de gériatrie, Poitiers, 86021, France
- Université de Poitiers, INSERM, CHU Poitiers, Centre d'Investigation Clinique CIC 1402, Poitiers, France
| | - Alfred Penfornis
- Centre Hospitalier Sud Francilien, F-91100 Corbeil-Essonnes, Université Paris-Saclay, France
| | - Pierre-Jean Saulnier
- Université de Poitiers, INSERM, CHU Poitiers, Centre d'Investigation Clinique CIC 1402, Poitiers, France
| | - Matthieu Wargny
- Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, F-44000, France
- Nantes Université, CHU Nantes, Pôle Hospitalo-Universitaire 11: Santé Publique, Clinique des données, INSERM, CIC 1413, Nantes, F-44000, France
| | - Samy Hadjadj
- Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, F-44000, France
| | - Laure de Decker
- Nantes Université, CHU Nantes, Pole de Gérontologie Clinique, Nantes, F-44000, France
| | - Bertrand Cariou
- Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, F-44000, France
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10
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Weisman A. Mismatch between HbA 1c and time in range targets among older adults with type 1 diabetes. THE LANCET. HEALTHY LONGEVITY 2022; 3:e809-e810. [PMID: 36410367 DOI: 10.1016/s2666-7568(22)00271-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 11/10/2022] [Indexed: 11/21/2022] Open
Affiliation(s)
- Alanna Weisman
- Department of Medicine, University of Toronto, Toronto, ON M5T 3L9, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital. Toronto, ON, Canada; ICES, Toronto, ON, Canada.
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11
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Evans M, Morgan AR, Davies S, Beba H, Strain WD. The role of sodium-glucose co-transporter-2 inhibitors in frail older adults with or without type 2 diabetes mellitus. Age Ageing 2022; 51:6749364. [PMID: 36201329 PMCID: PMC9536439 DOI: 10.1093/ageing/afac201] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 06/13/2022] [Indexed: 01/27/2023] Open
Abstract
Sodium-glucose co-transporter-2 (SGLT2) inhibitors offer significant outcome benefits beyond glucose lowering, including reduced risk of cardiovascular death, all-cause mortality, major adverse cardiovascular events, hospitalisations for heart failure and progression of renal disease. Considering these therapeutic effects, minimal incremental risk for hypoglycaemia and simplicity of administration, this drug class appears to be an attractive therapeutic option for older adults, and post hoc analysis of trial data provides support for the use of SGLT2 inhibitors in this population. Nevertheless, despite favourable clinical trial data, there has been some hesitance in clinical practice prescribing these drugs to older frail adults due to the limited therapeutic experience in this population and insufficient long-term safety data. In this review article, we evaluate the risk-benefit profile for the use of SGLT2 inhibitors in this population and suggest that rather than being a treatment to avoid, SGLT2 inhibitors should be considered a valid therapeutic option for older frail adults with or without diabetes.
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Affiliation(s)
- Marc Evans
- Diabetes Resource Centre, University Hospital Llandough, Cardiff, UK
| | | | | | - Hannah Beba
- NHS Leeds Clinical Commissioning Group, Leeds, UK
| | - William David Strain
- Address correspondence to: D. Strain, Diabetes and Vascular Medicine, University of Exeter, College of Medicine and Health, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5AX, UK. Tel: (+44) 7540886072; Fax: (+44) 1392403027.
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12
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Verhulst CEM, Fabricius TW, Teerenstra S, Kristensen PL, Tack CJ, McCrimmon RJ, Heller S, Evans ML, Amiel SA, Pedersen-Bjergaard U, de Galan BE. Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review. Diabetologia 2022; 65:1601-1612. [PMID: 35867127 PMCID: PMC9477942 DOI: 10.1007/s00125-022-05749-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 05/06/2022] [Indexed: 02/05/2023]
Abstract
AIM/HYPOTHESIS The physiological counterregulatory response to hypoglycaemia is reported to be organised hierarchically, with hormone responses usually preceding symptomatic awareness and autonomic responses preceding neuroglycopenic responses. To compare thresholds for activation of these responses more accurately between people with or without type 1 diabetes, we performed a systematic review on stepped hyperinsulinaemic-hypoglycaemic glucose clamps. METHODS A literature search in PubMed and EMBASE was conducted. We included articles published between 1980 and 2018 involving hyperinsulinaemic stepped hypoglycaemic glucose clamps among people with or without type 1 diabetes. Key exclusion criteria were as follows: data were previously published; other patient population; a clamp not the primary intervention; and an inadequate clamp description. Glycaemic thresholds for counterregulatory hormone and/or symptom responses to hypoglycaemia were estimated and compared using generalised logrank test for interval-censored data, where the intervals were either extracted directly or calculated from the data provided by the study. A glycaemic threshold was defined as the glucose level at which the response exceeded the 95% CI of the mean baseline measurement or euglycaemic control clamp. Because of the use of interval-censored data, we described thresholds using median and IQR. RESULTS A total of 63 articles were included, whereof 37 papers included participants with type 1 diabetes (n=559; 67.4% male sex, aged 32.7±10.2 years, BMI 23.8±1.4 kg/m2) and 51 papers included participants without diabetes (n=733; 72.4% male sex, aged 31.1±9.2 years, BMI 23.6±1.1 kg/m2). Compared with non-diabetic control individuals, in people with type 1 diabetes, the median (IQR) glycaemic thresholds for adrenaline (3.8 [3.2-4.2] vs 3.4 [2.8-3.9 mmol/l]), noradrenaline (3.2 [3.2-3.7] vs 3.0 [2.8-3.1] mmol/l), cortisol (3.5 [3.2-4.2]) vs 2.8 [2.8-3.4] mmol/l) and growth hormone (3.8 [3.3-3.8] vs. 3.2 [3.0-3.3] mmol/l) all occurred at lower glucose levels in people with diabetes than in those without diabetes (all p≤0.01). Similarly, although both autonomic (median [IQR] 3.4 [3.4-3.4] vs 3.0 [2.8-3.4] mmol/l) and neuroglycopenic (median [IQR] 3.4 [2.8-N/A] vs 3.0 [3.0-3.1] mmol/l) symptom responses were elicited at lower glucose levels in people with type 1 diabetes, the thresholds for autonomic and neuroglycopenic symptoms did not differ for each individual subgroup. CONCLUSIONS/INTERPRETATION People with type 1 diabetes have glycaemic thresholds for counterregulatory hormone and symptom responses at lower glucose levels than people without diabetes. Autonomic and neuroglycopenic symptoms responses are generated at about similar levels of hypoglycaemia. There was a considerable variation in the methodology of the articles and the high insulin doses in most of the clamps may affect the counterregulatory responses. FUNDING This article has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement no. 777460. REGISTRATION This systematic review is registered in PROSPERO (CRD42019120083).
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Affiliation(s)
- Clementine E M Verhulst
- Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
| | - Therese W Fabricius
- Department of Endocrinology and Nephrology, Nordsjællands Hospital, Hillerød, Denmark.
| | - Steven Teerenstra
- Section Biostatistics, Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Peter L Kristensen
- Department of Endocrinology and Nephrology, Nordsjællands Hospital, Hillerød, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Cees J Tack
- Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands
| | | | - Simon Heller
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Mark L Evans
- Wellcome Trust/MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - Stephanie A Amiel
- Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Ulrik Pedersen-Bjergaard
- Department of Endocrinology and Nephrology, Nordsjællands Hospital, Hillerød, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Bastiaan E de Galan
- Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands
- Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Centre, Maastricht, the Netherlands
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands
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13
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Idrees T, Castro-Revoredo IA, Migdal AL, Moreno EM, Umpierrez GE. Update on the management of diabetes in long-term care facilities. BMJ Open Diabetes Res Care 2022; 10:10/4/e002705. [PMID: 35858714 PMCID: PMC9305812 DOI: 10.1136/bmjdrc-2021-002705] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 05/29/2022] [Indexed: 11/10/2022] Open
Abstract
The number of patients with diabetes is increasing among older adults in the USA, and it is expected to reach 26.7 million by 2050. In parallel, the percentage of older patients with diabetes in long-term care facilities (LTCFs) will also rise. Currently, the majority of LTCF residents are older adults and one-third of them have diabetes. Management of diabetes in LTCF is challenging due to multiple comorbidities and altered nutrition. Few randomized clinical trials have been conducted to determine optimal treatment for diabetes management in older adults in LTCF. The geriatric populations are at risk of hypoglycemia since the majority are treated with insulin and have different levels of functionality and nutritional needs. Effective approaches to avoid hypoglycemia should be implemented in these settings to improve outcome and reduce the economic burden. Newer medication classes might carry less risk of developing hypoglycemia along with the appropriate use of technology, such as the use of continuous glucose monitoring. Practical clinical guidelines for diabetes management including recommendations for prevention and treatment of hypoglycemia are needed to appropriately implement resources in the transition of care plans in this vulnerable population.
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Affiliation(s)
- Thaer Idrees
- Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia, USA
| | - Iris A Castro-Revoredo
- Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia, USA
| | - Alexandra L Migdal
- Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia, USA
| | - Emmelin Marie Moreno
- Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia, USA
| | - Guillermo E Umpierrez
- Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia, USA
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14
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Bellary S, Kyrou I, Brown JE, Bailey CJ. Type 2 diabetes mellitus in older adults: clinical considerations and management. Nat Rev Endocrinol 2021; 17:534-548. [PMID: 34172940 DOI: 10.1038/s41574-021-00512-2] [Citation(s) in RCA: 232] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/13/2021] [Indexed: 02/06/2023]
Abstract
The past 50 years have seen a growing ageing population with an increasing prevalence of type 2 diabetes mellitus (T2DM); now, nearly half of all individuals with diabetes mellitus are older adults (aged ≥65 years). Older adults with T2DM present particularly difficult challenges. For example, the accentuated heterogeneity of these patients, the potential presence of multiple comorbidities, the increased susceptibility to hypoglycaemia, the increased dependence on care and the effect of frailty all add to the complexity of managing diabetes mellitus in this age group. In this Review, we offer an update on the key pathophysiological mechanisms associated with T2DM in older people. We then evaluate new evidence relating particularly to the effects of frailty and sarcopenia, the clinical difficulties of age-associated comorbidities, and the implications for existing guidelines and therapeutic options. Our conclusions will focus on the effect of T2DM on an ageing society.
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Affiliation(s)
- Srikanth Bellary
- School of Life and Health Sciences, Aston University, Birmingham, UK.
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
- Aston Research Centre for Healthy Ageing (ARCHA), Aston University, Birmingham, UK.
| | - Ioannis Kyrou
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
- Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, UK
- Warwick Medical School, University of Warwick, Coventry, UK
- Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry, UK
| | - James E Brown
- School of Life and Health Sciences, Aston University, Birmingham, UK
- Aston Research Centre for Healthy Ageing (ARCHA), Aston University, Birmingham, UK
| | - Clifford J Bailey
- School of Life and Health Sciences, Aston University, Birmingham, UK
- Aston Research Centre for Healthy Ageing (ARCHA), Aston University, Birmingham, UK
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15
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Abstract
Hypoglycaemia (blood glucose concentration below the normal range) has been recognised as a complication of insulin treatment from the very first days of the discovery of insulin, and remains a major concern for people with diabetes, their families and healthcare professionals today. Acute hypoglycaemia stimulates a stress response that acts to restore circulating glucose, but plasma glucose concentrations can still fall too low to sustain normal brain function and cardiac rhythm. There are long-term consequences of recurrent hypoglycaemia, which are still not fully understood. This paper reviews our current understanding of the acute and cumulative consequences of hypoglycaemia in insulin-treated diabetes.
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Affiliation(s)
- Stephanie A Amiel
- Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
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16
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Hermann M, Heimro LS, Haugstvedt A, Hernar I, Sigurdardottir AK, Graue M. Hypoglycaemia in older home-dwelling people with diabetes- a scoping review. BMC Geriatr 2021; 21:20. [PMID: 33413148 PMCID: PMC7792330 DOI: 10.1186/s12877-020-01961-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 12/14/2020] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Hypoglycaemia is associated with cognitive and functional decline in older people with diabetes. Identification of individuals at risk and prevention of hypoglycaemia is therefore an important task in the management of diabetes in older home-dwelling individuals. The purpose of this scoping review was to map the literature on hypoglycaemia in home-dwelling older people with diabetes. METHODS This scoping review included original research articles on hypoglycaemia in older (≥ 65 years) individuals with diabetes from developed countries. A broad search of the databases Cinahl, Embase and Medline was performed in July 2018. The report of the scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews. RESULTS Our database search identified 577 articles of which 23 were eligible for inclusion. The identified literature was within four areas: 1) incidence of hypoglycaemia in older home-dwelling people with diabetes (11/23 articles), 2) risk factors of hypoglycaemia (9/23), 3) diabetes knowledge and self-management (6/23) and 4) consequences of hypoglycaemia for health care use (6/23). The majority of the literature focused on severe hypoglycaemia and the emergency situation. The literature on diabetes knowledge and management related to preventing adverse events relevant to older home-dwellers, was limited. We found no literature on long-term consequences of hypoglycaemia for the use of home health care services and the older persons' ability to remain home-dwelling. CONCLUSIONS We identified a lack of studies on prevention and management of hypoglycaemia in the older individuals' homes. Such knowledge is of utmost importance in the current situation where most western countries' governmental policies aim to treat and manage complex health conditions in the patient's home. Future studies addressing hypoglycaemia in older individuals with diabetes are needed in order to tailor interventions aiming to enable them to remain home-dwelling as long as possible.
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Affiliation(s)
- Monica Hermann
- Faculty of Health and Social Sciences, Institute of Health and Caring Sciences, Western Norway University of Applied Sciences, Stord, Norway.
| | - Lovise S Heimro
- Faculty of Health and Social Sciences, Institute of Health and Caring Sciences, Western Norway University of Applied Sciences, Stord, Norway
| | - Anne Haugstvedt
- Faculty of Health and Social Sciences, Institute of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Norway
| | - Ingvild Hernar
- Faculty of Health and Social Sciences, Institute of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Norway
| | - Arun K Sigurdardottir
- School of Health Sciences, University of Akureyri, Akureyri, Iceland
- Akureyri Hospital, Akureyri, Iceland
| | - Marit Graue
- Faculty of Health and Social Sciences, Institute of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Norway
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17
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Cheng AYY, Wong J, Freemantle N, Acharya SH, Ekinci E. The Safety and Efficacy of Second-Generation Basal Insulin Analogues in Adults with Type 2 Diabetes at Risk of Hypoglycemia and Use in Other Special Populations: A Narrative Review. Diabetes Ther 2020; 11:2555-2593. [PMID: 32975710 PMCID: PMC7547921 DOI: 10.1007/s13300-020-00925-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 09/03/2020] [Indexed: 12/16/2022] Open
Abstract
Hypoglycemia is a major barrier impeding glycemic control in persons with type 2 diabetes mellitus and creates a substantial burden on the healthcare system. Certain populations that require special attention, such as older adults and individuals with renal impairment, a longer duration of diabetes or those who have experienced prior hypoglycemia, may be at a higher risk of hypoglycemia, particularly with insulin treatment. Second-generation basal insulin analogues (insulin glargine 300 U/mL and degludec) have demonstrated reductions in hypoglycemia compared with insulin glargine 100 U/mL although evidence of this benefit across specific populations is less clear. In this review we summarize the literature with respect to the efficacy and safety data for second-generation basal insulin analogues in adults with type 2 diabetes mellitus who are at risk of hypoglycemia or who require special attention. Randomized controlled trials, meta-analyses and real-world evidence demonstrate that the use of second-generation basal insulin analogues is associated with less hypoglycemia compared with insulin glargine 100 U/mL without compromising glycated hemoglobin control. A reduced risk of hypoglycemia with second-generation basal insulin analogues was evident in older adults and in individuals with obesity, renal impairment, a history of cardiovascular disease or a long duration of insulin use. Further studies are needed in other populations, including those with more severe renal impairment or hepatic dysfunction, the hospitalized population and those with cognitive impairment. Overall, less hypoglycemia associated with second-generation basal insulin analogues may help reduce barriers for insulin use, improve adherence and offset the costs of hypoglycemia-related healthcare resource utilization.
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Affiliation(s)
- Alice Y Y Cheng
- Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
| | - Jencia Wong
- Diabetes Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Central Clinical School, Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
| | - Nick Freemantle
- Institute for Clinical Trials and Methodology, University College London, London, UK
| | - Shamasunder H Acharya
- Department of Diabetes, John Hunter Hospital, Hunter New England Health-University of Newcastle, New Lambton, NSW, Australia
| | - Elif Ekinci
- Department of Medicine, Austin Health-University of Melbourne, Melbourne, VIC, Australia
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18
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Jacob P, Chandran SR, Choudhary P. Treatment of type 1 diabetes complicated by problematic hypoglycemia. TRANSPLANTATION, BIOENGINEERING, AND REGENERATION OF THE ENDOCRINE PANCREAS 2020:391-406. [DOI: 10.1016/b978-0-12-814833-4.00032-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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19
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Hypoglycemia. Endocrinology 2020. [PMID: 31968189 DOI: 10.1007/978-3-030-36694-0_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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20
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Noma Y, Komatsu M, Miya K, Shima K. Cognitive dysfunction during hypoglycemia in an elderly subject without diabetes. Diabetol Int 2019; 11:150-154. [PMID: 32206485 DOI: 10.1007/s13340-019-00419-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 11/25/2019] [Indexed: 12/13/2022]
Abstract
The aim of the present study was to examine whether an elderly subject without diabetes experiences hypoglycemia during his daily life or after an oral glucose tolerance test (OGTT), and investigate whether hypoglycemic episodes affect cognitive function. The 85-year-old healthy subject, who is a sports enthusiast, showed lower than normal (< 80 mg/dl) blood glucose levels on two occasions over 6 days in the early morning. The subject also experienced hypoglycemic episodes and blood glucose levels of 65 and 74 mg/dl, respectively, during the 6-h OGTT given after a 13-h fast. Cognitive function, as assessed using a numeracy test and a driving simulator test, deteriorated during the hypoglycemic episodes but recovered 0.5 h after ingestion of a confectionary product (two pieces of Dorayaki containing 247 kcal and 51.5 g of carbohydrate each). Cognitive dysfunction caused by mild hypoglycemia can be involved in a part of traffic accidents in elderly drivers.
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Affiliation(s)
- Yoshihiko Noma
- Department of Diabetes Care Medicine, Kawashima Hospital, 1-39, Kitasako, Tokushima, 770-8548 Japan
| | - Machiko Komatsu
- Department of Diabetes Care Medicine, Kawashima Hospital, 1-39, Kitasako, Tokushima, 770-8548 Japan
| | - Keiko Miya
- Department of Internal Medicine, Kawashima Hospital, 1-39, Kitasako, Tokushima, 770-8548 Japan
| | - Kenji Shima
- Department of Diabetes Care Medicine, Kawashima Hospital, 1-39, Kitasako, Tokushima, 770-8548 Japan
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21
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Nwokolo M, Amiel SA, O'Daly O, Byrne ML, Wilson BM, Pernet A, Cordon SM, Macdonald IA, Zelaya FO, Choudhary P. Impaired Awareness of Hypoglycemia Disrupts Blood Flow to Brain Regions Involved in Arousal and Decision Making in Type 1 Diabetes. Diabetes Care 2019; 42:2127-2135. [PMID: 31455689 DOI: 10.2337/dc19-0337] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 08/07/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Impaired awareness of hypoglycemia (IAH) affects one-quarter of adults with type 1 diabetes and significantly increases the risk of severe hypoglycemia. Differences in regional brain responses to hypoglycemia may contribute to the susceptibility of this group to problematic hypoglycemia. This study investigated brain responses to hypoglycemia in hypoglycemia aware (HA) and IAH adults with type 1 diabetes, using three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) functional MRI to measure changes in regional cerebral blood flow (CBF). RESEARCH DESIGN AND METHODS Fifteen HA and 19 IAH individuals underwent 3D pCASL functional MRI during a two-step hyperinsulinemic glucose clamp. Symptom, hormone, global, and regional CBF responses to hypoglycemia (47 mg/dL [2.6 mmol/L]) were measured. RESULTS In response to hypoglycemia, total symptom score did not change in those with IAH (P = 0.25) but rose in HA participants (P < 0.001). Epinephrine, cortisol, and growth hormone responses to hypoglycemia were lower in the IAH group (P < 0.05). Hypoglycemia induced a rise in global CBF (HA P = 0.01, IAH P = 0.04) but was not different between groups (P = 0.99). IAH participants showed reduced regional CBF responses within the thalamus (P = 0.002), right lateral orbitofrontal cortex (OFC) (P = 0.002), and right dorsolateral prefrontal cortex (P = 0.036) and a lesser decrease of CBF in the left hippocampus (P = 0.023) compared with the HA group. Thalamic and right lateral OFC differences survived Bonferroni correction. CONCLUSIONS Responses to hypoglycemia of brain regions involved in arousal, decision making, and reward are altered in IAH. Changes in these pathways may disrupt IAH individuals' ability to recognize hypoglycemia, impairing their capacity to manage hypoglycemia effectively and benefit fully from conventional therapeutic pathways to restore awareness.
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Affiliation(s)
- Munachiso Nwokolo
- Department of Diabetes, School of Life Course Sciences, King's College London, London, U.K. .,King's College Hospital NHS Foundation Trust, London, U.K
| | - Stephanie A Amiel
- Department of Diabetes, School of Life Course Sciences, King's College London, London, U.K.,King's College Hospital NHS Foundation Trust, London, U.K
| | - Owen O'Daly
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, U.K
| | - Megan L Byrne
- Department of Diabetes, School of Life Course Sciences, King's College London, London, U.K
| | - Bula M Wilson
- Department of Diabetes, School of Life Course Sciences, King's College London, London, U.K
| | - Andrew Pernet
- Department of Diabetes, School of Life Course Sciences, King's College London, London, U.K
| | - Sally M Cordon
- School of Life Sciences, MRC Arthritis Research UK Centre of Excellence in Musculoskeletal Ageing, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, U.K
| | - Ian A Macdonald
- School of Life Sciences, MRC Arthritis Research UK Centre of Excellence in Musculoskeletal Ageing, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, U.K
| | - Fernando O Zelaya
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, U.K
| | - Pratik Choudhary
- Department of Diabetes, School of Life Course Sciences, King's College London, London, U.K.,King's College Hospital NHS Foundation Trust, London, U.K
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22
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Vandenberghe F, Challet C, Maitrejean M, Christin L, Schaad N. Impact of drugs on hypoglycaemia in hospitalised patients. Eur J Hosp Pharm 2019; 26:199-204. [PMID: 31338167 DOI: 10.1136/ejhpharm-2017-001375] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Revised: 02/01/2018] [Accepted: 02/20/2018] [Indexed: 11/04/2022] Open
Abstract
Objectives Hospital admission rates for hypoglycaemia now exceed those for hyperglycaemias among older adults. A growing number of reports associating hypoglycaemia with non-antidiabetic drugs have been published. Clinical pharmacists are often faced with hypoglycaemia in patients taking multiple medications. This study assessed the potential relationship between prescribed drugs and episodes of hypoglycaemia during hospitalisation. Methods Point-of-care blood glucose values and prescribed drugs were analysed in patients admitted to a regional hospital. Hypoglycaemia cases were defined as patients with at least one hypoglycaemic event (random glucose value ≤3.9 mmol/L), and normoglycaemic cases as those with random glucose concentrations within the range of 4.5-5.8 mmol/L. Analyses were carried out using multivariate logistic regressions and Cox proportional hazard models. Results 373 patients (53% males; median age=74 years) were included in the analysis and of these, 64 (17%) had at least one hypoglycaemic event. Patients who experienced a hypoglycaemic event had a longer length of stay (median=10 vs 7 days, p<0.01) and a higher rate of antidiabetic drugs prescription (83% vs 37%, p<0.01). The number of non-antidiabetic drugs was associated with an increased risk of hypoglycaemia during hospitalisation (HR 2.3, 95% CI 1.4 to 4, p<0.01). After adjusting by confounders, heparin and pantoprazole were found to be associated with hypoglycaemia. Conclusions The relationship between hypoglycaemia and polypharmacy reinforces the advice to limit polymedication as much as possible, especially in elderly patients. This result underlines the potential involvement of clinical pharmacists with the aim to reduce the risk of hypoglycaemia during hospitalisation.
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Affiliation(s)
| | | | - Mathias Maitrejean
- Medical Analysis Laboratory, Groupement Hospitalier de l'Ouest Lémanique, Nyon, Switzerland, Nyon, Switzerland
| | - Laurent Christin
- Department of Internal Medicine, Groupement Hospitalier de l'Ouest Lémanique, Nyon, Switzerland., Nyon, Switzerland
| | - Nicolas Schaad
- Pharmacie Interhospitalière de la Cote, Morges, Switzerland.,Department of Basic Neurosciences, Geneva University Hospital, Geneva, Switzerland.,Department of Anaesthetics, Pharmacology and Intensive Care, Geneva University Hospital, Geneva, Switzerland
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Heller SR, DeVries JH, Wysham C, Hansen CT, Hansen MV, Frier BM. Lower rates of hypoglycaemia in older individuals with type 2 diabetes using insulin degludec versus insulin glargine U100: Results from SWITCH 2. Diabetes Obes Metab 2019; 21:1634-1641. [PMID: 30891886 PMCID: PMC6618254 DOI: 10.1111/dom.13708] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 03/06/2019] [Accepted: 03/16/2019] [Indexed: 01/09/2023]
Abstract
AIM This study aimed to investigate the safety of insulin degludec (degludec) in relation to age and risk of hypoglycaemia post hoc in individuals with type 2 diabetes (T2D) (SWITCH 2 trial). METHODS In this crossover study, individuals with T2D who were at risk of hypoglycaemia were randomized to double-blind treatment with degludec or insulin glargine 100 units/mL (glargine U100) ± oral antidiabetic drugs. After 32 weeks, patients crossed over to the other treatment. Primary endpoint was number of overall severe (positively adjudicated) or glucose-confirmed (plasma glucose <56 mg/dL; 3.1 mmol/L) symptomatic hypoglycaemia events during the two 16-week maintenance periods. RESULTS For individuals ≤65 (n = 450) and >65 (n = 270) years, baseline median (range) duration of diabetes was 12 (1-40) vs 15 (1-54) years, mean HbA1c was 7.7% vs 7.4% and mean estimated glomerular filtration rate was 87.0 vs 63.7 mL/min/1.73 m2 , respectively. No significant differences in HbA1c reduction were seen in individuals ≤65 or >65 years. During both maintenance periods, treatment with degludec lowered rates of hypoglycaemia (overall/nocturnal symptomatic) vs those with glargine U100 in individuals ≤65 (31% vs 43%) and >65 (30% vs 41%) years. With degludec and glargine U100, respectively, six vs nine severe hypoglycaemic events occurred in individuals ≤65 years and four vs eight events occurred in those >65 years. Adverse event rates were 3.2 and 3.3 events/patient-year for individuals ≤65 years and were 3.5 and 4.1 events/patient-year for individuals >65 years with degludec and glargine U100, respectively. CONCLUSION Treatment with degludec was safe and effective, with a frequency of hypoglycaemia lower than that with glargine U100 in both younger and older individuals (>65 years) with T2D.
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Affiliation(s)
- Simon R. Heller
- Academic Unit of Diabetes, Endocrinology and MetabolismUniversity of SheffieldSheffieldUK
| | - J. Hans DeVries
- Academic Medical CenterUniversity of AmsterdamAmsterdamthe Netherlands
| | - Carol Wysham
- School of MedicineUniversity of Washington/Multicare Rockwood ClinicSpokaneWashington
| | | | | | - Brian M. Frier
- The Queen's Medical Research CentreUniversity of EdinburghEdinburghUK
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Wu IC, Hsu CC, Chen CY, Chuang SC, Cheng CW, Hsieh WS, Wu MS, Liu YT, Liu YH, Tsai TL, Lin CC, Hsiung CA. Paradoxical Relationship Between Glycated Hemoglobin and Longitudinal Change in Physical Functioning in Older Adults: A Prospective Cohort Study. J Gerontol A Biol Sci Med Sci 2019; 74:949-956. [PMID: 31095709 DOI: 10.1093/gerona/gly147] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Hyperglycemia with high hemoglobin A1c (HbA1c) levels is associated with significant health risks. However, the relationship between HbA1c levels and the physical functioning status in later life remains uncertain and so is the possible underlying mechanism. METHODS We conducted a prospective study of 2,565 initially well-functioning community-dwelling older adult aged 55 years and older from the Healthy Aging Longitudinal Study in Taiwan. Each participant received baseline measurements of blood HbA1c and inflammatory markers levels and repeated assessments of physical functioning over a mean follow-up period of 5.3 years. We used generalized linear mixed-effects regression to estimate the adjusted changes in the odds ratio for self-reported physical functioning impairment and Short Physical Performance Battery (SPPB) score according to baseline HbA1c levels (categorized into 0.5% increments from <5.5% to ≥7.0%). RESULTS HbA1c levels showed a U-shaped relationship with changes in the odds ratio for physical functioning impairment and SPPB score (p for quadratic term < .001). Compared with participants with an HbA1c of 5.5% to <6.0%, those with an HbA1c of <5.5% or ≥7.0% had a higher annual increase in the odds ratio for physical functioning impairment (odds ratio [95% confidence interval] per year, 1.25 [1.04-1.50] and 1.21 [1.04-1.41]) and a higher annualized decrease in SPPB score (coefficient [95% confidence interval], -0.05 [-0.10 to 0.00] and -0.04 [-0.08 to 0.00]). These relationships were nonlinear only in participants with high soluble interleukin-6 receptor levels (>48,124 pg/mL; p for interaction < .05). CONCLUSIONS High and low HbA1c levels at baseline are associated with faster physical functioning decline, particularly among individuals with elevated circulating soluble interleukin-6 receptor, a sign of enhanced interleukin-6 trans-signaling.
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Affiliation(s)
- I-Chien Wu
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan.,2Department of Health Services Administration, China Medical University, Taichung, Taiwan
| | - Ching-Yu Chen
- Department of Family Medicine, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan
| | - Shu-Chun Chuang
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
| | - Chiu-Wen Cheng
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
| | - Wan-Shan Hsieh
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
| | - Ming-Shiang Wu
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
| | - Yen-Tze Liu
- Changhua Christian Hospital, Changhua County, Taiwan
| | - Yo-Hann Liu
- Hope Doctors Hospital, Miaoli County, Taiwan
| | - Tsung-Lung Tsai
- Puzi Hospital, Ministry of Health and Welfare, Chiayi County, Taiwan
| | | | - Chao A Hsiung
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
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Sugiyama K, Meguro S, Saisho Y, Irie J, Tanaka M, Itoh H. Efficacy and safety of switching to insulin glargine 300 U/mL from 100 U/mL in Japanese patients with type 2 diabetes: A 12-month retrospective analysis. Heliyon 2019; 5:e01257. [PMID: 30886921 PMCID: PMC6389521 DOI: 10.1016/j.heliyon.2019.e01257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 02/13/2019] [Accepted: 02/13/2019] [Indexed: 11/18/2022] Open
Abstract
Aims To evaluate the efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) from insulin glargine 100 U/mL (Gla-100) in Japanese patients with type 2 diabetes (T2DM). Methods This was a 12-month retrospective study comprising 109 patients. Primary endpoint was glycated hemoglobin (HbA1c) level at month 12. Secondary endpoints were hypoglycemia for the overall study period as well as body weight and insulin dose at month 12. Results Similar glycemic control was achieved with mean (standard deviation) HbA1c level of 7.7 (1.1)% (61 [12] mmol/mol) at baseline and 7.7 (1.3)% (61 [14] mmol/mol) at month 12. Fewer confirmed (<3.0 mmol/L [< 54 mg/dL]) or severe hypoglycemic events were observed (0.52 vs. 0.85 events per patient-year; rate ratio 0.61; 95% confidence interval 0.38–0.97; p = 0.037), but the percent of patients experiencing ≥1 hypoglycemic event did not differ. There was no difference in confirmed (≤3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemia and nocturnal hypoglycemia. Conclusions In Japanese patients with T2DM who switched to Gla-300 from Gla-100, similar glycemic control was achieved with fewer confirmed (<3.0 mmol/L [< 54 mg/dL]) or severe hypoglycemic events over a 12-month period, although the absolute benefit was marginal.
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Hypoglycemia. Endocrinology 2019. [DOI: 10.1007/978-3-319-27316-7_22-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Otsuka T, Okada Y, Torimoto K, Tanaka Y. Risk Factors for Hypoglycemic Coma: A Study of 33 Patients on Insulin Therapy Who Were Transported to the Hospital by Ambulance. Intern Med 2018; 57:2923-2927. [PMID: 29780121 PMCID: PMC6232023 DOI: 10.2169/internalmedicine.0535-17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Accepted: 03/05/2018] [Indexed: 11/28/2022] Open
Abstract
Objective Patients on outpatient insulin therapy are at a high risk of severe hypoglycemia and a high incidence of hypoglycemic coma. However, only a few studies have explored the risk factors for hypoglycemic coma in such patients. We retrospectively analyzed the clinical characteristics of diabetic patients who had developed hypoglycemic coma during outpatient insulin therapy. Methods This study included 33 diabetic patients on insulin therapy who were transported to the hospital by ambulance for severe hypoglycemia. Patients with a Japan Coma Scale score <100 were classified as the non-coma group (n=18), while those with a score ≥100 (n=15) were classified into the coma group. Results Patients in the coma group were significantly older, with a higher proportion of elderly patients ( ≥65 years of age), than those in the non-coma group. Although no marked difference in the basal insulin dose was observed between the two groups, the bolus insulin dose was significantly higher in the coma group. However, no marked differences in the disease type or renal function were noted between the two groups. Conclusion An advanced age and bolus insulin dose are risk factors for hypoglycemic coma in diabetic patients on insulin therapy. Bolus insulin dose minimization should be performed in order to prevent hypoglycemic coma, especially in elderly diabetic patients.
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Affiliation(s)
- Takashi Otsuka
- First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan
| | - Yosuke Okada
- First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan
| | - Keiichi Torimoto
- First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan
| | - Yoshiya Tanaka
- First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan
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Meneilly GS, Knip A, Miller DB, Sherifali D, Tessier D, Zahedi A. Diabetes in Older People. Can J Diabetes 2018; 42 Suppl 1:S283-S295. [PMID: 29650107 DOI: 10.1016/j.jcjd.2017.10.021] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Indexed: 12/15/2022]
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Chakera AJ, Hurst PS, Spyer G, Ogunnowo-Bada EO, Marsh WJ, Riches CH, Yueh CY, Markkula SP, Dalley JW, Cox RD, Macdonald IA, Amiel SA, MacLeod KM, Heisler LK, Hattersley AT, Evans ML. Molecular reductions in glucokinase activity increase counter-regulatory responses to hypoglycemia in mice and humans with diabetes. Mol Metab 2018; 17:17-27. [PMID: 30146176 PMCID: PMC6197723 DOI: 10.1016/j.molmet.2018.08.001] [Citation(s) in RCA: 35] [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: 07/24/2018] [Accepted: 08/02/2018] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE Appropriate glucose levels are essential for survival; thus, the detection and correction of low blood glucose is of paramount importance. Hypoglycemia prompts an integrated response involving reduction in insulin release and secretion of key counter-regulatory hormones glucagon and epinephrine that together promote endogenous glucose production to restore normoglycemia. However, specifically how this response is orchestrated remains to be fully clarified. The low affinity hexokinase glucokinase is found in glucose-sensing cells involved in glucose homeostasis including pancreatic β-cells and in certain brain areas. Here, we aimed to examine the role of glucokinase in triggering counter-regulatory hormonal responses to hypoglycemia, hypothesizing that reduced glucokinase activity would lead to increased and/or earlier triggering of responses. METHODS Hyperinsulinemic glucose clamps were performed to examine counter-regulatory responses to controlled hypoglycemic challenges created in humans with monogenic diabetes resulting from heterozygous glucokinase mutations (GCK-MODY). To examine the relative importance of glucokinase in different sensing areas, we then examined responses to clamped hypoglycemia in mice with molecularly defined disruption of whole body and/or brain glucokinase. RESULTS GCK-MODY patients displayed increased and earlier glucagon responses during hypoglycemia compared with a group of glycemia-matched patients with type 2 diabetes. Consistent with this, glucagon responses to hypoglycemia were also increased in I366F mice with mutated glucokinase and in streptozotocin-treated β-cell ablated diabetic I366F mice. Glucagon responses were normal in conditional brain glucokinase-knockout mice, suggesting that glucagon release during hypoglycemia is controlled by glucokinase-mediated glucose sensing outside the brain but not in β-cells. For epinephrine, we found increased responses in GCK-MODY patients, in β-cell ablated diabetic I366F mice and in conditional (nestin lineage) brain glucokinase-knockout mice, supporting a role for brain glucokinase in triggering epinephrine release. CONCLUSIONS Our data suggest that glucokinase in brain and other non β-cell peripheral hypoglycemia sensors is important in glucose homeostasis, allowing the body to detect and respond to a falling blood glucose.
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Affiliation(s)
- Ali J Chakera
- Institute of Clinical and Biomedical Sciences, University of Exeter, United Kingdom
| | - Paul S Hurst
- Wellcome Trust/ MRC Institute of Metabolic Science and Department of Medicine, University of Cambridge, United Kingdom
| | - Gill Spyer
- Institute of Clinical and Biomedical Sciences, University of Exeter, United Kingdom
| | - Emmanuel O Ogunnowo-Bada
- Wellcome Trust/ MRC Institute of Metabolic Science and Department of Medicine, University of Cambridge, United Kingdom
| | - William J Marsh
- Wellcome Trust/ MRC Institute of Metabolic Science and Department of Medicine, University of Cambridge, United Kingdom
| | - Christine H Riches
- Wellcome Trust/ MRC Institute of Metabolic Science and Department of Medicine, University of Cambridge, United Kingdom
| | - Chen-Yu Yueh
- Wellcome Trust/ MRC Institute of Metabolic Science and Department of Medicine, University of Cambridge, United Kingdom
| | - S Pauliina Markkula
- Wellcome Trust/ MRC Institute of Metabolic Science and Department of Medicine, University of Cambridge, United Kingdom
| | - Jeffrey W Dalley
- Behavioural and Clinical Neuroscience Institute and Departments of Psychology and Psychiatry, University of Cambridge, United Kingdom
| | - Roger D Cox
- MRC Harwell Institute, Mammalian Genetics Unit, Harwell Oxford, United Kingdom
| | - Ian A Macdonald
- MRC-ARUK Centre for Musculoskeletal Ageing and NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust/ University of Nottingham, Nottingham, United Kingdom
| | - Stephanie A Amiel
- Division of Diabetes and Nutritional Sciences, King's College London, United Kingdom
| | - Kenneth M MacLeod
- Institute of Clinical and Biomedical Sciences, University of Exeter, United Kingdom
| | - Lora K Heisler
- Rowett Institute, University of Aberdeen, United Kingdom
| | - Andrew T Hattersley
- Institute of Clinical and Biomedical Sciences, University of Exeter, United Kingdom.
| | - Mark L Evans
- Wellcome Trust/ MRC Institute of Metabolic Science and Department of Medicine, University of Cambridge, United Kingdom.
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Ritzel R, Harris SB, Baron H, Florez H, Roussel R, Espinasse M, Muehlen-Bartmer I, Zhang N, Bertolini M, Brulle-Wohlhueter C, Munshi M, Bolli GB. A Randomized Controlled Trial Comparing Efficacy and Safety of Insulin Glargine 300 Units/mL Versus 100 Units/mL in Older People With Type 2 Diabetes: Results From the SENIOR Study. Diabetes Care 2018; 41:1672-1680. [PMID: 29895556 DOI: 10.2337/dc18-0168] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Accepted: 05/07/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE SENIOR compared the efficacy and safety of insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in older people (≥65 years old) with type 2 diabetes. RESEARCH DESIGN AND METHODS SENIOR was an open-label, two-arm, parallel-group, multicenter phase 3b trial designed to enroll ∼20% of participants aged ≥75 years. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to a fasting self-monitored plasma glucose of 5.0-7.2 mmol/L (90-130 mg/dL). RESULTS In total, 1,014 participants were randomized (mean age: 71 years). Comparable reductions in HbA1c were observed from baseline to week 26 for Gla-300 (-0.89%) and Gla-100 (-0.91%) in the overall population (least squares mean difference: 0.02% [95% CI -0.092 to 0.129]) and for participants aged ≥75 years (-0.11% [-0.330 to 0.106]). Incidence and rates of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemia events were low and similar between both treatment groups, with lower rates of documented symptomatic hypoglycemia with Gla-300. The lower risk of hypoglycemia with Gla-300 versus Gla-100 was more apparent in the subgroup aged ≥75 years versus the overall population. Significantly lower annualized rates of documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) hypoglycemia were observed (Gla-300: 1.12; Gla-100: 2.71; rate ratio: 0.45 [95% CI 0.25-0.83]). CONCLUSIONS Efficacy and safety of Gla-300 was demonstrated in older people (≥65 years of age) with type 2 diabetes, with comparable reductions in HbA1c and similarly low or lower risk of documented symptomatic hypoglycemia versus Gla-100. A significant benefit in hypoglycemia reduction was seen in participants aged ≥75 years.
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Affiliation(s)
- Robert Ritzel
- Klinikum Schwabing and Klinikum Bogenhausen, Städtisches Klinikum München GmbH, Munich, Germany
| | | | - Helen Baron
- University of Southern California, Los Angeles, CA
| | - Hermes Florez
- Miller School of Medicine, University of Miami, Coral Gables, FL
| | | | | | | | | | | | | | - Medha Munshi
- Joslin Diabetes Center, Harvard University, Boston, MA
| | - Geremia B Bolli
- Department of Medicine, Perugia University Medical School, Perugia, Italy
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Heald AH, Anderson SG, Cortes GJ, Cholokova V, Narajos M, Khan A, Donnahey G, Livingston M. Hypoglycaemia in the over 75s: Understanding the predisposing factors in type 2 diabetes (T2DM). Prim Care Diabetes 2018; 12:133-138. [PMID: 28941578 DOI: 10.1016/j.pcd.2017.08.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2016] [Revised: 06/23/2017] [Accepted: 08/15/2017] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Hypoglycaemia has been recognised as a problem in the treatment for type 2 diabetes. Here we describe how levels of HbA1C and treatment with a sulphonylurea or insulin relate to risk of significant hypoglycaemia. METHODS Incident hypoglycaemia as recorded for the previous 10 years was determined from the GP records for patients with T2DM aged 75 years or more. RESULTS The anonymised GP records of 5974 T2DM patients (2934 men and 3040 women) aged 75 years or more were analysed. Mean age of the men was 81.0 (95% confidence interval (CI) 80.9-81.2) years and of the women was 82.2 (95% CI 82.0-82.4) years. Hypoglycaemic events of significance were recorded in 4.9% of men and 5.1% of women. The prevalence of hypoglycaemia was higher in those with a higher concurrent HbA1C. HbA1C for those people with a recorded significant hypoglycaemic attack(s) was 57.9 (95% CI 56.4-59.4) mmol/mol compared to those with no history of hypoglycaemic episodes at 51.6 (95% CI 51.3-52.0) mmol/mol (p<0.002). Even for those on sulphonylurea and/or insulin treatment, hypoglycaemia prevalence increased with HbA1C: for patients with an HbA1C of <48mmol/mol, age and gender adjusted hypoglycaemia prevalence was 11.1%, for HbA1C of 48-57mmol/mol, prevalence 9.9%, for HbA1C 58-67mmol/mol prevalence, 13.2% and for HbA1C 68mmol/mol or more, prevalence of hypoglycaemia was 16.1%. There was a slight fall in HbA1C by age (normalised β -0.069, p<0.001) and no difference by level of social disadvantage. Treatment with a sulphonylurea or insulin very significantly increased the likelihood of a hypoglycaemic episode: odds ratio (OR) 8.94 (95% CI 6.45-12.42), p<0.001, independent of age, BMI, Townsend index and gender. CONCLUSION Prevalence of hypoglycaemia was greater in those individuals with higher HbA1C and in those on sulphonylurea/insulin treatment. Our findings suggest that it is variance in blood glucose rather than overall lower blood glucose levels that predisposes older people to hypoglycaemia.
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Affiliation(s)
- Adrian Hugh Heald
- Department of Endocrinology and Diabetes, Salford Royal Hospital, Salford, United Kingdom; The School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom
| | | | - Gabriela Janet Cortes
- Obesity Clinic in the Medicine School of Instituto Politecnico Nacional, Mexico City, Mexico
| | | | - Marcos Narajos
- Green College, University of Oxford, Oxford, United Kingdom
| | - Adnan Khan
- Department of Medicine, Leighton Hospital, Crewe, United Kingdom
| | - Gemma Donnahey
- EMIS Health, Fulford Grange, Micklefield Ln, Rawdon, Leeds, United Kingdom
| | - Mark Livingston
- Department of Blood Sciences, Walsall Manor Hospital, Walsall, United Kingdom.
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Eliaschewitz FG, de Paula MA, Pedrosa HC, Pires AC, Salles JEN, Tambascia MA, A Turatti LA. Barriers to insulin initiation in elderly patients with type 2 diabetes mellitus in Brazil. Diabetes Metab Syndr 2018; 12:39-44. [PMID: 28864058 DOI: 10.1016/j.dsx.2017.08.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 08/20/2017] [Indexed: 12/25/2022]
Abstract
AIMS We aimed to explore insulin initiation barriers in the Brazilian Type 2 Diabetes Mellitus (T2DM) elderly population, according to the physician's perspective, and suggest strategies to overcome them. METHODS A 45-questions survey addressing issues as clinical characteristics, barriers to insulinization, and treatment strategies in elderly patients with T2DM, was sent to six endocrinologists from different Brazilian locations. Thereafter, all the respondents participated in a panel discussion to validate their responses and collect additional relevant data. RESULTS Endocrinologists had at least 15 years of experience, with a mean of 63 elderly patients per month. Nearly 25% of the elderly patients were treated in the Brazilian public healthcare system (SUS, Unified Health System); only a quarter presented proper glycemic control. In contrast, 55% of the patients from private healthcare system presented adequate glycemic control. The main barriers for insulin initiation for patients, according to physicians' perspective, are side effects and negative perception over treatment (100%). For endocrinologists, main barriers were lack of time to guide patients and concern over side effects (83%). Therefore, specialists considered education for both healthcare professionals and patients as one of the most important strategies to circumvent the current scenario related insulin therapy among elderly patients in the country. CONCLUSION Insulin therapy remains underused due to several barriers, such as concern over side effects and negative perception. Educational measures for patients and HCPs could improve the current scenario.
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Affiliation(s)
- Freddy G Eliaschewitz
- Centro de Pesquisas Clínicas, Rua Goias, 193, São Paulo, São Paulo, 01244-030, Brazil.
| | - Mauricio A de Paula
- Medical Manager at Sanofi, Avenida Major Sylvio de Magalhães Padilha, 5200, São Paulo, São Paulo, 05693-000, Brazil.
| | - Hermelinda C Pedrosa
- Unidade de Endocrinologia-Polo de Pesquisa, Hospital Regional de Taguatinga, Secretaria de Estado de Saúde do Distrito Federal, St. C Norte Área Especial 24, Taguatinga Norte, Brasília, Distrito Federal, 72120-970, Brazil.
| | - Antônio Carlos Pires
- Faculdade de Medicina de São José do Rio Preto, Avenida Brigadeiro Faria Lima, 5416, São José do Rio Preto, São Paulo, 15090-000, Brazil.
| | - João Eduardo N Salles
- Faculdade de Ciências Médicas da Santa Casa de São Paulo, Rua Doutor Cesário Motta Júnior, 61, São Paulo, São Paulo, 01221-020, Brazil.
| | - Marcos Antônio Tambascia
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Rua Tessália Vieira de Camargo, 126, Campinas, São Paulo, 13083-887, Brazil.
| | - Luiz Alberto A Turatti
- Sociedade Brasileira de Diabetes, Rua Afonso Braz, 579, São Paulo, São Paulo, 04511-011, Brazil.
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Hypoglycemia. Endocrinology 2018. [DOI: 10.1007/978-3-319-27316-7_22-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Cardona S, Gomez PC, Vellanki P, Anzola I, Ramos C, Urrutia MA, Haw JS, Fayfman M, Wang H, Galindo RJ, Pasquel FJ, Umpierrez GE. Clinical characteristics and outcomes of symptomatic and asymptomatic hypoglycemia in hospitalized patients with diabetes. BMJ Open Diabetes Res Care 2018; 6:e000607. [PMID: 30613402 PMCID: PMC6304102 DOI: 10.1136/bmjdrc-2018-000607] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 10/30/2018] [Accepted: 11/16/2018] [Indexed: 12/20/2022] Open
Abstract
IMPORTANCE The frequency and impact of asymptomatic hypoglycemia in hospitalized patients with diabetes is not known. OBJECTIVE We determined the clinical characteristics and hospital outcomes of general medicine and surgery patients with symptomatic and asymptomatic hypoglycemia. RESEARCH DESIGN AND METHODS Prospective observational study in adult patients with diabetes and blood glucose (BG) <70 mg/dL. Participants were interviewed about signs and symptoms of hypoglycemia using a standardized questionnaire. Precipitating causes, demographics, insulin regimen, and complications data during admission was collected. RESULTS Among 250 patients with hypoglycemia, 112 (44.8%) patients were asymptomatic and 138 (55.2%) had symptomatic hypoglycemia. Patients with asymptomatic hypoglycemia were older (59±11 years vs 54.8±13 years, p=0.003), predominantly males (63% vs 48%, p=0.014), and had lower admission glycosylated hemoglobin (8.2%±2.6 % vs 9.1±2.9%, p=0.006) compared with symptomatic patients. Compared with symptomatic patients, those with asymptomatic hypoglycemia had higher mean BG during the episode (60.0±8 mg/dL vs 53.8±11 mg/dL, p<0.001). In multivariate analysis, male gender (OR 2.08, 95% CI 1.13 to 3.83, p=0.02) and age >65 years (OR 4.01, 95% CI 1.62 to 9.92, p=0.02) were independent predictors of asymptomatic hypoglycemia. There were no differences in clinical outcome, composite of hospital complications (27% vs 22%, p=0.41) or in-hospital length of stay (8 days (IQR 4-14) vs 7 days (IQR 5-15), p=0.92)) between groups. CONCLUSIONS Asymptomatic hypoglycemia was common among insulin-treated patients with diabetes but was not associated with worse clinical outcome compared with patients with symptomatic hypoglycemia. Older age and male gender were independent risk factors for asymptomatic hypoglycemia.
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Affiliation(s)
- Saumeth Cardona
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Patricia C Gomez
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Priyathama Vellanki
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Isabel Anzola
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Clementina Ramos
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Maria A Urrutia
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Jeehea Sonya Haw
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Maya Fayfman
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Heqiong Wang
- Rollins School of Public Health, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Rodolfo J Galindo
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Francisco J Pasquel
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
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de Decker L, Hanon O, Boureau AS, Chapelet G, Dibon C, Pichelin M, Berrut G, Cariou B. Association Between Hypoglycemia and the Burden of Comorbidities in Hospitalized Vulnerable Older Diabetic Patients: A Cross-Sectional, Population-Based Study. Diabetes Ther 2017; 8:1405-1413. [PMID: 29086351 PMCID: PMC5688985 DOI: 10.1007/s13300-017-0319-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Indexed: 01/16/2023] Open
Abstract
INTRODUCTION From a patient-centered perspective, the assessment of risk factors of hypoglycemia is of critical importance for the management of type 2 diabetes (T2D). However, the association between the occurrence of hypoglycemia and high burden of comorbidities has been poorly studied in vulnerable older patients. Here, we aimed to determine whether a high burden of comorbidities is associated with hypoglycemia in very old patients with T2D. METHODS A total of 1552 elderly (age ≥ 80 years old) patients with T2D were recruited in a nationwide cross-sectional study performed in French geriatric care units. Hypoglycemia was defined as a confirmed blood glucose value level ≤ 70 mg/dL. Comorbidities were assessed using the Charlson Comorbidity Index (CCI). RESULTS Amongst the 1552 recruited patients (mean age 86.4 years), 415 (26.7%) had documented hypoglycemia. Compared to patients in whom hypoglycemia was not reported, they have a lower body weight (p = 0.004), a reduced eGFR (p < 0.001), a greater level of dependency (p < 0.001) as well as history of dementia (p = 0.006) and cardiovascular disease (p < 0.001), and a higher CCI (4.7 vs 3.8, p < 0.001). Patients with hypoglycemia had a higher frequency of daily self-monitoring blood glucose (SMBG) (p < 0.001) and insulin use (p < 0.001), with reduced sulfonylurea use (p < 0.001). In multivariate logistic regression analysis, insulin therapy (OR 3.32, p < 0.001), daily SMBG (OR 1.79, p = 0.02), CCI (OR 1.24, p = 0.01), and age (OR 0.96, p = 0.03) were independently associated with the risk of hypoglycemia. CONCLUSION In addition to insulin therapy, a high burden of comorbidities was independently associated with hypoglycemia in older vulnerable patients with T2D.
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Affiliation(s)
- Laure de Decker
- Laboratory of clinical and experimental therapeutics of infections, EA 3628, Nantes University, 44000, Nantes, France
- Department of Geriatrics, Nantes University Hospital, 44000, Nantes, France
| | - Olivier Hanon
- Department of Geriatrics, Broca Hospital, Public Hospital of Paris, 75013 Paris, France
- Laboratory of Alzheimer disease : genetic and vascular markers, neuropsychology, psychosocial interventions and technologies, EA 4468, Paris Descartes University, Sorbonne Paris Cité, 75006 Paris, France
| | | | - Guillaume Chapelet
- Laboratory of clinical and experimental therapeutics of infections, EA 3628, Nantes University, 44000, Nantes, France
- Department of Geriatrics, Nantes University Hospital, 44000, Nantes, France
| | - Christelle Dibon
- Department of Geriatrics, Nantes University Hospital, 44000, Nantes, France
| | - Matthieu Pichelin
- Department of Endocrinology, l'institut du thorax, Nantes University Hospital, 44000, Nantes, France
| | - Gilles Berrut
- Department of Geriatrics, Nantes University Hospital, 44000, Nantes, France
| | - Bertrand Cariou
- Department of Endocrinology, l'institut du thorax, Nantes University Hospital, 44000, Nantes, France.
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Abstract
PURPOSE OF REVIEW The purpose of this review is to discuss strategies to reduce rates of hypoglycemia in the non-critical care setting. RECENT FINDINGS Strategies to reduce hypoglycemia rates should focus on the most common causes of iatrogenic hypoglycemia. Creating a standardized insulin order set with built-in clinical decision support can help reduce rates of hypoglycemia. Coordination of blood glucose monitoring, meal tray delivery, and insulin administration is an important and challenging task. Protocols and processes should be in place to deal with interruptions in nutrition to minimize risk of hypoglycemia. A glucose management page that has all the pertinent information summarized in one page allows for active surveillance and quick identification of patients who may be at risk of hypoglycemia. Finally, education of prescribers, nurses, food and nutrition services, and patients is important so that every member of the healthcare team can work together to prevent hypoglycemia. By implementing strategies to reduce hypoglycemia, we hope to lower rates of adverse events and improve quality of care while also reducing hospital costs. Future research should focus on the impact of an overall reduction in hypoglycemia to determine whether the expected benefits are achieved.
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Affiliation(s)
- Kristen Kulasa
- Division of Endocrinology, Diabetes, and Metabolism, University of California, San Diego, 200 West Arbor Drive, MC#8409, San Diego, CA, 92103, USA.
| | - Patricia Juang
- Division of Endocrinology, Diabetes, and Metabolism, University of California, San Diego, 200 West Arbor Drive, MC#8409, San Diego, CA, 92103, USA
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Forlenza GP, Argento NB, Laffel LM. Practical Considerations on the Use of Continuous Glucose Monitoring in Pediatrics and Older Adults and Nonadjunctive Use. Diabetes Technol Ther 2017; 19:S13-S20. [PMID: 28585878 PMCID: PMC5467117 DOI: 10.1089/dia.2017.0034] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Clinical use of continuous glucose monitoring (CGM) devices has grown over the past 15 years from a niche concept to becoming standard of care for patients with type 1 diabetes (T1D). With the December 2016 Food and Drug Administration approval for diabetes treatment decisions directly from CGM values (nonadjunctive use) without finger-stick confirmation, the uptake and scope of CGM use will likely further expand. With this expansion, it is important to consider the role and impact of CGM technology in specific settings and high-risk populations, such as the young and the elderly. In pediatric patients, CGM concerns include limited body surface area, difficulty keeping sensors adhered, and the role of nonadjunctive use in the school setting. In older adults, Medicare did not, until very recently, cover CGM devices and as such, their use had been limited by lack of reimbursement. As CGM use will likely expand in clinical practice given the nonadjunctive indication, guidelines and recommendations for clinical practice are warranted. In this article, we discuss recent research on CGM use in the special populations of children and older adults and provide initial guidelines for nonadjunctive use in clinical practice.
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Affiliation(s)
| | | | - Lori M. Laffel
- Pediatric, Adolescent and Young Adult Section, The Section on Clinical, Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts
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Glucose concentrations of less than 3.0 mmol/l (54 mg/dl) should be reported in clinical trials: a joint position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2017; 60:3-6. [PMID: 27872948 PMCID: PMC6518070 DOI: 10.1007/s00125-016-4146-6] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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Glucose Concentrations of Less Than 3.0 mmol/L (54 mg/dL) Should Be Reported in Clinical Trials: A Joint Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2017; 40:155-157. [PMID: 27872155 DOI: 10.2337/dc16-2215] [Citation(s) in RCA: 441] [Impact Index Per Article: 55.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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Hizel C, Tremblay J, Bartlett G, Hamet P. Introduction. PROGRESS AND CHALLENGES IN PRECISION MEDICINE 2017:1-34. [DOI: 10.1016/b978-0-12-809411-2.00001-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Chen AX, Thynne T. Sodium-glucose co-transporter 2 inhibitors: a review of their use in older people with type 2 diabetes mellitus. JOURNAL OF PHARMACY PRACTICE AND RESEARCH 2016. [DOI: 10.1002/jppr.1296] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Angela X. Chen
- Southern Adelaide Diabetes and Endocrine Service; Flinders Medical Centre; Adelaide Australia
| | - Tilenka Thynne
- Southern Adelaide Diabetes and Endocrine Service; Flinders Medical Centre; Adelaide Australia
- Department of Clinical Pharmacology; Flinders Medical Centre and Flinders University; Adelaide Australia
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Nassar DT, Habib OS, Mansour AA. Predictors of hypoglycemia in insulin-treated patients with type 2 diabetes mellitus in Basrah. World J Diabetes 2016; 7:470-480. [PMID: 27795821 PMCID: PMC5065667 DOI: 10.4239/wjd.v7.i18.470] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2016] [Revised: 05/23/2016] [Accepted: 08/18/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To measure the incidence and determinants (predictors) of hypoglycemia among patients with type 2 diabetes mellitus (T2DM) who were on insulin treatment for at least one year.
METHODS The present study is an out-patients based inquiry about the risk and predictors of hypoglycemia among patients with T2DM seeking care at the Al-Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah over a period of 7 mo (from 15th of April, 2013 to 15th of October, 2013). The data used in the study were based on all detailed interview and selected laboratory investigations. A total of 336 patients could be included in the study.
RESULTS The incidence of overall hypoglycemia among the studied patients was 75.3% within the last 3 mo preceding the interview. The incidence of hypoglycemia subtypes were 10.2% for severe hypoglycemia requiring medical assistance in the hospital, 44.36% for severe hypoglycemia treated at home by family; this includes both confirmed severe hypoglycemia with an incidence rate of 14.6% and unconfirmed severe hypoglycemia for which incidence rate was 29.76%. Regarding mild self-treated hypoglycemia, the incidence of confirmed mild hypoglycemia was 21.42%, for unconfirmed mild hypoglycemia the incidence rate was 50.0% and for total mild hypoglycemia, the incidence rate was 71.42%. The most important predictors of hypoglycemia were a peripheral residence, increasing knowledge of hypoglycemia symptoms, in availability and increasing frequency of self-monitoring blood glucose, the presence of peripheral neuropathy, higher diastolic blood pressure, and lower Hemoglobin A1c.
CONCLUSION Hypoglycemia is very common among insulin-treated patients with T2DM in Basrah. It was possible to identify some important predictors of hypoglycemia.
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Kim HM, Seong JM, Kim J. Risk of hospitalization for hypoglycemia among older Korean people with diabetes mellitus: Interactions between treatment modalities and comorbidities. Medicine (Baltimore) 2016; 95:e5016. [PMID: 27759630 PMCID: PMC5079314 DOI: 10.1097/md.0000000000005016] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
The objective of this study was to carry out a large population-based study to understand the factors associated with hypoglycemia-related hospitalizations among older Korean adults with diabetes mellitus.This study analyzed data from a subset of the 2013 Health Insurance and Review and Assessment service-Adult Patient Sample. A total of 307,170 subjects, comprising 41.7% men and 58.3% women, had diabetes mellitus. Hypertension (80.8%) was the most common comorbidity, and dyslipidemia (59.0%) and ischemic heart disease (21.3%) were also prevalent. Approximately half of the patients with diabetes had >2 comorbidities, and two-thirds of the patients had >3 comorbidities. The proportion of patients taking insulin or sulfonylureas was 54.9%, and 23.2% of the patients were taking other medications. About 21.9% of the patients were treated nonpharmacologically. A total of 2867 hypoglycemia-related admission occurred, the incident rate was 9.33 per 1000 person. The risk was higher among female patients and older patients with several comorbidities, including cardiovascular disease, cerebrovascular disease, chronic liver disease, chronic kidney disease, dementia, and malignancies. Treatment modalities, including insulin and sulfonylureas, were associated with a high risk of hypoglycemia. After adjustments for age, sex, the different comorbidities, and the treatment modalities, we determined that chronic kidney disease and dementia were associated with a high risk of hypoglycemia-related hospitalization (odds ratio [OR] = 2.52 and OR = 1.93, respectively). Furthermore, patients with chronic kidney disease or dementia who were treated with sulfonylureas and insulin had very high risks of hypoglycemia, and the incident rate was 66.6 and 63.75 per 1000 person, respectively.In conclusion, the presence of comorbidities, especially chronic kidney disease and dementia, increased the risk of hypoglycemia-associated hospitalization within this population of older patients with diabetes. The impact of the treatment modality, for example, insulin or sulfonylureas, on hypoglycemia was much greater among these patients.
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Affiliation(s)
- Hyun Min Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine
| | - Jong-Mi Seong
- Department of Pharmacy, Chung-Ang University College of Pharmacy, Seoul, Korea
| | - Jaetaek Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine
- Correspondence: Jaetaek Kim, Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea (e-mail: )
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May M, Schindler C. Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab 2016; 7:69-83. [PMID: 27092232 PMCID: PMC4821002 DOI: 10.1177/2042018816638050] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Patients with type 2 diabetes mellitus often require multifactorial pharmacological treatment due to different comorbidities. An increasing number of concomitantly taken medications elevate the risk of the patient experiencing adverse drug effects or drug interactions. Drug interactions can be divided into pharmacokinetic and pharmacodynamic interactions affecting cytochrome (CYP) enzymes, absorption properties, transporter activities and receptor affinities. Furthermore, nutrition, herbal supplements, patient's age and gender are of clinical importance. Relevant drug interactions are predominantly related to sulfonylureas, thiazolidinediones and glinides. Although metformin has a very low interaction potential, caution is advised when drugs that impair renal function are used concomitantly. With the exception of saxagliptin, dipeptidyl peptidase-4 (DPP-4) inhibitors also show a low interaction potential, but all drugs affecting the drug transporter P-glycoprotein should be used with caution. Incretin mimetics and sodium-glucose cotransporter-2 (SGLT-2) inhibitors comprise a very low interaction potential and are therefore recommended as an ideal combination partner from the clinical-pharmacologic point of view.
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Affiliation(s)
- Marcus May
- Hannover Medical School, MHH CRC Core Facility, Hannover, Germany
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Jafari B, Britton ME. Hypoglycaemia in elderly patients with type 2 diabetes mellitus: a review of risk factors, consequences and prevention. JOURNAL OF PHARMACY PRACTICE AND RESEARCH 2015. [DOI: 10.1002/jppr.1163] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- Badieh Jafari
- Department of General Medicine and Aged Care; Hervey Bay Hospital; Queensland Australia
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Muratli S, Tufan F, Soyluk O, Bahat G, Karan MA. Importance of hypoglycemia on the risk of Alzheimer's disease in elderly subjects with diabetes mellitus. Clin Interv Aging 2015; 10:1789-91. [PMID: 26622173 PMCID: PMC4639474 DOI: 10.2147/cia.s93925] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Affiliation(s)
- Sevilay Muratli
- Division of Geriatrics, Department of Internal Medicine, Istanbul University, Istanbul, Turkey
| | - Fatih Tufan
- Department of Gerontology, Faculty of Medical Sciences, Istanbul University, Istanbul, Turkey
| | - Ozlem Soyluk
- Department of Gerontology, Faculty of Medical Sciences, Istanbul University, Istanbul, Turkey
| | - Gulistan Bahat
- Division of Geriatrics, Department of Internal Medicine, Istanbul University, Istanbul, Turkey
| | - M Akif Karan
- Division of Geriatrics, Department of Internal Medicine, Istanbul University, Istanbul, Turkey
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Pilemann-Lyberg S, Thorsteinsson B, Snorgaard O, Zander M, Vestergaard H, Røder ME. Severe hypoglycaemia during treatment with sulphonylureas in patients with type 2 diabetes in the Capital Region of Denmark. Diabetes Res Clin Pract 2015; 110:202-7. [PMID: 26515912 DOI: 10.1016/j.diabres.2015.09.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Revised: 08/19/2015] [Accepted: 09/03/2015] [Indexed: 12/31/2022]
Abstract
AIMS Sulphonylureas (SU) are currently recommended as a well-established second line treatment in guidelines for type 2 diabetes (T2DM). In the Capital Region of Denmark 16,865 patients were given SU as part of their treatment of T2DM in 2010-2011. To what extent SU are associated with hospitalizations due to severe hypoglycaemic episodes, defined as episodes with a need for external assistance, was investigated. The prevalence and characteristics of these patients and potential risk factors were studied. METHODS ICD-10 diagnosis codes were used to identify patients hospitalized due to hypoglycaemia and T2DM for a period of 2 years (2010-2011). Inclusion criteria were T2DM, hospitalization due to hypoglycaemia and treatment with SU as monotherapy or in combination with other glucose-lowering drugs except insulin treatment. RESULTS We identified 161 patients fulfilling the inclusion criteria. Their mean age was 76 (53-97) years and 54% were males. Sixty percent of the patients had diabetic complications, including 19% with diabetic nephropathy. The major reason for severe hypoglycaemia was an unchanged dose of SU despite of a significant decline in food intake (45%). In 22% of the patients more than one reason was listed, most commonly a concomitant infection associated with decreased food intake and unchanged dose of SU. CONCLUSION The incidence of hospital admission-requiring severe hypoglycaemia in patients treated with SU was 0.48 episodes per 100 patient-years of SU-treated patients. It was mainly older patients with diminished food intake, excessive alcohol use or other medications, concomitant infection, and with diabetic complications.
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Affiliation(s)
- S Pilemann-Lyberg
- Center for Diabetes Research, Department of Medicine, Gentofte Hospital, Denmark; Steno Diabetes Center, Denmark
| | - B Thorsteinsson
- Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital Hillerød, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - O Snorgaard
- Department of Endocrinology, Hvidovre Hospital, Denmark
| | - M Zander
- Department of Endocrinology, Bispebjerg Hospital, Denmark
| | - H Vestergaard
- Department of Endocrinology, Herlev Hospital, Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research - Section of Metabolic Genetics, Denmark; Steno Diabetes Center, Denmark
| | - M E Røder
- Center for Diabetes Research, Department of Medicine, Gentofte Hospital, Denmark.
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Mathur S, Zammitt NN, Frier BM. Optimal glycaemic control in elderly people with type 2 diabetes: what does the evidence say? Drug Saf 2015; 38:17-32. [PMID: 25481812 DOI: 10.1007/s40264-014-0247-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The global prevalence of type 2 diabetes mellitus (T2DM) is rising in an ageing population through a combination of lifestyle changes and greater longevity. However, by excluding participants aged over 70 years, most major interventional trials on which current diabetes therapeutic guidelines are based have failed to provide specific evidence to support the prescribed management of diabetes in elderly people. While diabetes per se has a significant impact on the elderly person, the side effects of medications, particularly hypoglycaemia, prevent optimisation of diabetes treatment. Hypoglycaemia is associated with significant morbidity, to which elderly people are often more vulnerable because of factors such as the effects of ageing, progressive renal impairment, frailty, polypharmacy and cognitive decline. T2DM is associated with accelerated cognitive decline in some individuals, and recurrent severe hypoglycaemia has been implicated as a potential contributory factor. Although the evidence for selection of appropriate glycaemic targets in elderly patients is sparse, it is now acknowledged that prevention of hypoglycaemia must influence individualisation of treatment goals in this vulnerable group. This should also be reflected by the choice of anti-diabetes agents that are initiated when diet and lifestyle advice is ineffective. Recently developed international guidelines, which have specifically addressed the management of diabetes in elderly people, highlight the importance of a pragmatic management approach rather than attempting to achieve a generic glycated haemoglobin goal and are summarised in this article.
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Affiliation(s)
- Supriya Mathur
- Department of Diabetes, Royal Infirmary of Edinburgh, Edinburgh, Scotland, UK
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Lavernia F, Kushner P, Trence D, Rice D, Dailey G, Kuritzky L. Recognizing and minimizing hypoglycemia: The need for individualized care. Postgrad Med 2015; 127:801-7. [PMID: 26359949 DOI: 10.1080/00325481.2015.1086628] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Hypoglycemia is a condition known to disrupt many everyday activities and is associated with increased risks of hospitalization, falls, motor vehicle accidents and mortality. Many patients with diabetes have an increased risk of hypoglycemia due to interventions targeting glycemic control. In these patients, hypoglycemia and fear of hypoglycemia may further reduce adherence to glucose-lowering regimens, contributing to the further aggravation of diabetes-related complications. Avoiding hypoglycemia should be one of the principal goals of any treatment strategies employing agents that can induce hypoglycemia in order to prevent the occurrence of associated symptoms and consequences. The education of patients and their families is an important feature of individualized management strategies in order to prevent, mitigate and treat hypoglycemic episodes. Patients with diabetes need to be made aware of how to recognize the signs of hypoglycemia and of the simple, highly effective steps that they can take to self-manage hypoglycemic episodes. Clinicians should be familiar with the risk factors for hypoglycemia, especially the profiles of the different classes of glucose-lowering medications such as the sulfonylureas and insulin. This article aims to review the risk factors for hypoglycemia and its implications for patients and healthcare systems, and provide practical advice for minimizing the risk of hypoglycemia and its consequences.
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Affiliation(s)
- Frank Lavernia
- a 1 North Broward Diabetes Center , Coconut Creek, FL, USA
| | | | - Dace Trence
- c 3 University of Washington , Seattle, WA, USA
| | - Donna Rice
- d 4 Sanofi U.S., Inc. , Bridgewater, NJ, USA
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