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Wahlin B, Braune A, Jönsson E, Wållberg-Jonsson S, Bengtsson C. Beneficial effects of hydroxychloroquine on blood lipids and glycated haemoglobin: A randomised interventional study in patients with rheumatoid arthritis and systemic lupus erythematosus. PLoS One 2024; 19:e0312546. [PMID: 39466791 PMCID: PMC11515954 DOI: 10.1371/journal.pone.0312546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 09/29/2024] [Indexed: 10/30/2024] Open
Abstract
INTRODUCTION Hydroxychloroquine (HCQ) exerts a large reduction of cardiovascular risk in patients with inflammatory diseases, but the mechanisms are not fully known. The aim of this study was to study potential mechanisms for this. METHODS This interventional study (EudraCT 2014-005418-45) in 30 patients (23 with rheumatoid arthritis, 7 with systemic lupus erythematosus) investigates the effects of HCQ on cardiovascular risk factors and arterial stiffness in patients with inflammatory disease. Blood lipids, blood pressure, blood glucose, glycated haemoglobin (HbA1c) and arterial stiffness was assessed at initiation, after four weeks of treatment and after eight weeks of treatment with 200 mg HCQ daily. RESULTS After four weeks of treatment with HCQ, total cholesterol had decreased from 5.4 mmol/L to 5.1 mmol/L (p<0.001), low-density lipoproteins from 3,0 mmol/L to 2.7 mmol/L (p<0.001) and apolipoprotein B from 0.96 g/L to 0.90 g/L (p<0.01). Those levels remained unchanged after eight weeks of treatment with HCQ. Levels of triglycerides, high-density lipoproteins and apolipoprotein A1 remained unchanged during the study. HbA1c decreased in most patients, especially in patients with high levels at start of HCQ, but increased HbA1c was seen in patients with low levels at start of treatment with HCQ. No significant effect was seen on blood pressure or any measure of arterial stiffness. CONCLUSION This study does not identify the mechanisms of cardiovascular risk reduction from HCQ. Arterial stiffness is not affected by HCQ. The impact of HCQ on HbA1c and blood lipids is rapid, but of modest magnitude, and these effects do not fully explain the reduced risk of cardiovascular disease seen in observational studies. The mechanisms of cardiovascular risk reduction from HCQ are yet not completely known.
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Affiliation(s)
- Bengt Wahlin
- Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden
| | - Antje Braune
- Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden
| | - Elias Jönsson
- Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden
| | | | - Christine Bengtsson
- Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden
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Qiu S, Liu X, Lei L, Liang H, Li X, Wang Y, Yu C, Li X, Tang Y, Wu J, Wang Y, Zha D, Liu X, Xiao M, Xiu J. Association between the stress-hyperglycemia ratio and all-cause mortality in community-dwelling populations: An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014. J Diabetes 2024; 16:e13567. [PMID: 38769875 PMCID: PMC11106591 DOI: 10.1111/1753-0407.13567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 02/01/2024] [Accepted: 04/01/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. METHODS A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. RESULTS A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. CONCLUSIONS The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.
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Affiliation(s)
- Shifeng Qiu
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Xiaocong Liu
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Li Lei
- Department of CardiologyShenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)ShenzhenChina
| | - Hongbin Liang
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Xue Li
- Department of GastroenterologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Yutian Wang
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Chen Yu
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Xiaobo Li
- Department of CardiologyXiangdong Hospital Affiliated to Hunan Normal UniversityZhuzhouChina
| | - Yongzhen Tang
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Juefei Wu
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Yuegang Wang
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Daogang Zha
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Department of General PracticeNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Xuewei Liu
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- The First School of Clinical MedicineSouthern Medical UniversityDongguanChina
| | - Min Xiao
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Jiancheng Xiu
- Department of CardiologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of Shock and MicrocirculationNanfang Hospital, Southern Medical UniversityGuangzhouChina
- State Key Laboratory of Organ Failure ResearchNanfang Hospital, Southern Medical UniversityGuangzhouChina
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Dreier J, Schernhammer E, Haslacher H, Stögmann E, Lehrner J. Hemoglobin A1c Serum Level Predicts 5-year Mortality in Patients with Cognitive Impairment. J Diabetes Metab Disord 2023; 22:1705-1714. [PMID: 37969915 PMCID: PMC10638249 DOI: 10.1007/s40200-023-01303-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 09/05/2023] [Indexed: 11/17/2023]
Abstract
Background Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) may occur as preclinical stages of Alzheimer's disease (AD), ultimately leading to dementia. Glycated hemoglobin A1c (HbA1c) is a diagnostic marker for diabetes mellitus and indicates mortality risk. Objectives This university-based, exploratory retrospective study examined the impact of HbA1c serum level on 5-year mortality among individuals with cognitive impairment. Methods Included were 1076 subjects aged at least 50 years who visited the Memory Outpatient Clinic of the Medical University of Vienna due to memory problems. Participants were diagnosed with SCD, MCI, or AD subsequent to neurological examination, standard laboratory blood tests, and neuropsychological testing. Survival was compared between diagnostic subgroups and with respect to HbA1c categories using log-rank tests based on Kaplan-Meier functions. The Neuropsychological Test Battery Vienna (NTBV) was dimensionally reduced, and a principal component analysis (PCA) was performed to further analyze results. Corresponding factor scores, HbA1c values, and baseline characteristics were included in Cox proportional hazards models to assess 5-year mortality risk. Results During the observation period, 323 patients (30%) died at a mean age comparable between diagnostic subgroups (SCD 84.2 ± 10.1, MCI 81.2 ± 8.3, AD 82.2 ± 7.4 years). Individuals with normal serum HbA1c levels had significant advantages in survival within the MCI (12.9 ± .3 vs. 10.0 ± .8 years) and the AD subgroups (8.2 ± .4 vs. 5.5 ± .6 years), and metric HbA1c predicted 5-year mortality (HR 1.24). Conclusion This study demonstrates an association between abnormal HbA1c serum levels and increased mortality.
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Affiliation(s)
- J. Dreier
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - E. Schernhammer
- Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria
| | - H. Haslacher
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - E. Stögmann
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - J. Lehrner
- Department of Neurology, Medical University of Vienna, Vienna, Austria
- Neurologische Universitätsklinik, Allgemeines Krankenhaus, Währinger Gürtel 18-20, 1097 Vienna, Austria
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Ho KM, Lee A, Wu W, Chan MT, Ling L, Lipman J, Roberts J, Litton E, Joynt GM, Wong M. Flattening the biological age curve by improving metabolic health: to taurine or not to taurine, that' s the question. J Geriatr Cardiol 2023; 20:813-823. [PMID: 38098466 PMCID: PMC10716614 DOI: 10.26599/1671-5411.2023.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2023] Open
Abstract
The aging population is an important issue around the world especially in developed countries. Although medical advances have substantially extended life span, the same cannot be said for the duration of health span. We are seeing increasing numbers of elderly people who are frail and/or have multiple chronic conditions; all of these can affect the quality of life of the elderly population as well as increase the burden on the healthcare system. Aging is mechanistically related to common medical conditions such as diabetes mellitus, ischemic heart disease, cognitive decline, and frailty. A recently accepted concept termed 'Accelerated Biological Aging' can be diagnosed when a person's biological age-as measured by biomarkers of DNA methylation-is older than their corresponding chronological age. Taurine, a conditionally essential amino acid, has received much attention in the past few years. A substantial number of animal studies have provided a strong scientific foundation suggesting that this amino acid can improve cellular and metabolic health, including blood glucose control, so much that it has been labelled one of the 'longevity amino acids'. In this review article, we propose the rationale that an adequately powered randomized-controlled-trial (RCT) is needed to confirm whether taurine can meaningfully improve metabolic and microbiome health, and biological age. This trial should incorporate certain elements in order to provide the much-needed evidence to guide doctors, and also the community at large, to determine whether this promising and inexpensive amino acid is useful in improving human metabolic health.
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Affiliation(s)
- Kwok M. Ho
- Department of Intensive Care Medicine, Fiona Stanley Hospital, Perth, Australia
- Medical School, The University of Western Australia, Perth, Australia
- School of Veterinary & Life Sciences, Murdoch University, Perth, Australia
| | - Anna Lee
- Department of Anaesthesia & Intensive Care, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China
| | - William Wu
- Department of Anaesthesia & Intensive Care, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China
| | - Matthew T.V. Chan
- Department of Anaesthesia & Intensive Care, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China
| | - Lowell Ling
- Department of Anaesthesia & Intensive Care, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China
| | - Jeffrey Lipman
- Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
- Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France
| | - Jason Roberts
- Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France
- University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia
- Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Australia
- Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Australia
| | - Edward Litton
- Department of Intensive Care Medicine, Fiona Stanley Hospital, Perth, Australia
- Medical School, The University of Western Australia, Perth, Australia
| | - Gavin M. Joynt
- Department of Anaesthesia & Intensive Care, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China
| | - Martin Wong
- JC School of Public Health and Primary Care, Centre for Health Education and Health Promotion, Chinese University of Hong Kong, Hong Kong, China
- School of Public Health, Peking University, Beijing, China
- School of Public Health, Fudan University, Shanghai, China
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Shen Q, He T, Li T, Szeto IMY, Mao S, Zhong W, Li P, Jiang H, Zhang Y. Synergistic effects of overweight/obesity and high hemoglobin A1c status on elevated high-sensitivity C-reactive protein in Chinese adults: a cross-sectional study. Front Nutr 2023; 10:1156404. [PMID: 37215204 PMCID: PMC10196946 DOI: 10.3389/fnut.2023.1156404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 03/31/2023] [Indexed: 05/24/2023] Open
Abstract
Background High-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker that has been suggested as a predictor of cardiovascular diseases. High glycated hemoglobin (HbA1c) levels and overweight/obesity are independently associated with elevated hs-CRP; meanwhile, high HbA1c levels are frequently accompanied by overweight or obesity. However, their joint effect on elevated hs-CRP levels has not been well-established. Therefore, we evaluated whether overweight/obesity modified the association between high HbA1c levels and elevated hs-CRP. Methods Based on cross-sectional data from the Chinese Urban Adults Diet and Health Study (CUADHS) in 2016, we included 1,630 adults aged 18-75 years (mean age 50.16 years and 33.6% male). Elevated hs-CRP was defined as serum hs-CRP ≥ 3 and <10 mg/L. The interactive effects of BMI and HbA1c levels on the risk of elevated hs-CRP levels were calculated by using multiple logistic regression models, followed by strata-specific analyses. Results Individuals with elevated hs-CRP had a higher rate of HbA1c level than those without elevated (25.3 vs. 11.3%, P < 0.001), as well as a higher rate of overweight/obesity (67.1 vs. 43.5%, P < 0.001). Higher HbA1c levels were independently associated with an increased risk of elevated hs-CRP [adjusted odds ratio (aOR) = 2.31, 95% confidence interval (CI): 1.47, 3.65], as well as overweight/obesity with the risk of elevated hs-CRP (aOR = .31, 95% confidenc-3.73). Furthermore, overweight/obesity showed a significant synergistic effect on high HbA1c levels with a higher aOR of 5.25 (2.77, 9.95) (Pinteraction < 0.001). This synergistic effect was more prominent when stratified by age (in 18-44 years old, aOR, 95% CI = 30.90, 4.40-236.47 for interaction vs. 6.46, 1.38-30.23 for high HbA1c only) and gender (in women, aOR, 95% CI = 8.33, 3.80-18.23 for interaction vs. 2.46,1.38-4.40 for high HbA1c only). Conclusion There are synergistic effects of high HbA1c levels and overweight/obesity on the risk of elevated hs-CRP in Chinese adults, with more significant effects in adults aged 18-44 years or females. Intervention strategies for preventing high blood glucose levels and body weight simultaneously may be important for reducing hs-CRP-related diseases. Further studies are needed to confirm this finding in other populations, and its molecular mechanisms need to be elucidated.
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Affiliation(s)
- Qianqian Shen
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, China
| | - Tingchao He
- Inner Mongolia Dairy Technology Research Institute Co., Ltd., Hohhot, China
- Yili Maternal and Infant Nutrition Institute, Inner Mongolia Yili Industrial Group Co., Ltd., Hohhot, China
| | - Ting Li
- Inner Mongolia Dairy Technology Research Institute Co., Ltd., Hohhot, China
- Yili Maternal and Infant Nutrition Institute, Inner Mongolia Yili Industrial Group Co., Ltd., Hohhot, China
| | - Ignatius Man-Yau Szeto
- Inner Mongolia Dairy Technology Research Institute Co., Ltd., Hohhot, China
- National Center of Technology Innovation for Dairy, Hohhot, China
| | - Shuai Mao
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, China
| | - Wuxian Zhong
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, China
| | - Pin Li
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, China
| | - Hua Jiang
- School of Nursing, Peking University, Beijing, China
| | - Yumei Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, China
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Mei Y, Li A, Zhao J, Zhou Q, Zhao M, Xu J, Li R, Li Y, Li K, Ge X, Guo C, Wei Y, Xu Q. Association of long-term air pollution exposure with the risk of prediabetes and diabetes: Systematic perspective from inflammatory mechanisms, glucose homeostasis pathway to preventive strategies. ENVIRONMENTAL RESEARCH 2023; 216:114472. [PMID: 36209785 DOI: 10.1016/j.envres.2022.114472] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 08/29/2022] [Accepted: 09/28/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Limited evidence suggests the association of air pollutants with a series of diabetic cascades including inflammatory pathways, glucose homeostasis disorder, and prediabetes and diabetes. Subclinical strategies for preventing such pollutants-induced effects remain unknown. METHODS We conducted a cross-sectional study in two typically air-polluted Chinese cities in 2018-2020. One-year average PM1, PM2.5, PM10, SO2, NO2, and O3 were calculated according to participants' residence. GAM multinomial logistic regression was performed to investigate the association of air pollutants with diabetes status. GAM and quantile g-computation were respectively performed to investigate individual and joint effects of air pollutants on glucose homeostasis markers (glucose, insulin, HbA1c, HOMA-IR, HOMA-B and HOMA-S). Complement C3 and hsCRP were analyzed as potential mediators. The ABCS criteria and hemoglobin glycation index (HGI) were examined for their potential in preventive strategy. RESULTS Long-term air pollutants exposure was associated with the risk of prediabetes [Prevalence ratio for O3 (PR_O3) = 1.96 (95% CI: 1.24, 3.03)] and diabetes [PR_PM1 = 1.18 (95% CI: 1.05, 1.32); PR_PM2.5 = 1.08 (95% CI: 1.00, 1.16); PR_O3 = 1.35 (95% CI: 1.03, 1.74)]. PM1, PM10, SO2 or O3 exposure was associated with glucose-homeostasis disorder. For example, O3 exposure was associated with increased levels of glucose [7.67% (95% CI: 1.75, 13.92)], insulin [19.98% (95% CI: 4.53, 37.72)], HOMA-IR [34.88% (95% CI: 13.81, 59.84)], and decreased levels of HOMA-S [-25.88% (95% CI: -37.46, -12.16)]. Complement C3 and hsCRP played mediating roles in these relationships with proportion mediated ranging from 6.95% to 60.64%. Participants with HGI ≤ -0.53 were protected from the adverse effects of air pollutants. CONCLUSION Our study provides comprehensive insights into air pollutant-associated diabetic cascade and suggests subclinical preventive strategies.
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Affiliation(s)
- Yayuan Mei
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Ang Li
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Jiaxin Zhao
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Quan Zhou
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Meiduo Zhao
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Jing Xu
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Runkui Li
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China; State Key Laboratory of Resources and Environmental Information System, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, 100101, China
| | - Yanbing Li
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Kai Li
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Xiaoyu Ge
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Chen Guo
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environment Sciences, Beijing, 100012, China
| | - Yongjie Wei
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environment Sciences, Beijing, 100012, China.
| | - Qun Xu
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China.
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Ooi SW, Yeh ST, Chang YH, Li CY, Chen HF. Low mean HbA1c does not increase all-cause and cardiovascular mortality in patients with diabetes: Effect-modifications by anemia and chronic kidney disease stages. PLoS One 2022; 17:e0272137. [PMID: 35951657 PMCID: PMC9371313 DOI: 10.1371/journal.pone.0272137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 07/13/2022] [Indexed: 11/30/2022] Open
Abstract
Background Previous studies reported that low levels of glycated hemoglobin A1c (HbA1c) were associated with increased mortality. We investigated rates and risks of all-cause and cardiovascular mortality in association with mean HbA1c levels with stratification of anemia and chronic kidney disease (CKD) stages, major causes of low HbA1c. Methods 47,145 patients with prescription of antidiabetic agents >6 months in the outpatient visits (2003–2018) were linked to Taiwan’s National Death Registry to identify all-cause and cardiovascular mortality. Poisson assumption was used to estimate the mortality rates, and the Cox proportional hazard regression model was used to evaluate the relative hazards of respective mortality in relation to mean HbA1c in different statuses of anemia and CKD stages. Results All-cause and cardiovascular mortality rates were the lowest in non-anemic stages 1–2 CKD patients, and the highest in anemic stages 3–5 CKD patients. In stages 1–2 CKD, excessive HRs observed in those with mean HbA1c <6.0% (Hazard Ratio [HR]) 1.58; 95% Confidence Interval [CI] 1.18–2.12) became inconsequential after adjustment of medications and laboratory results (HR: 1.26; 95% CI 0.89–1.79). The similar patterns were observed in anemic stages 1–2 CKD, anemic or non-anemic stages 3–5 CKD. Low HbA1c was not related to cardiovascular mortality in any anemia status or CKD staging. Conclusions Higher risks associated with low mean HbA1c and all-cause mortality were attenuated by adjustment of medications and comorbidities. It is imperative for the diabetologists to consider confounding effects of underlying illness before concluding low HbA1c associated higher mortality.
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Affiliation(s)
- Seng-Wei Ooi
- Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Shu-Tin Yeh
- Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Ya-Hui Chang
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
| | - Hua-Fen Chen
- Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- School of Medicine and Department of Public Health, College of Medicine, Fujen Catholic University, New Taipei City, Taiwan
- * E-mail:
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Sinning C, Makarova N, Völzke H, Schnabel RB, Ojeda F, Dörr M, Felix SB, Koenig W, Peters A, Rathmann W, Schöttker B, Brenner H, Veronesi G, Cesana G, Brambilla P, Palosaari T, Kuulasmaa K, Njølstad I, Mathiesen EB, Wilsgaard T, Blankenberg S, Söderberg S, Ferrario MM, Thorand B. Association of glycated hemoglobin A 1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium. Cardiovasc Diabetol 2021; 20:223. [PMID: 34781939 PMCID: PMC8594211 DOI: 10.1186/s12933-021-01413-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 11/04/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. METHODS Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). RESULTS Kaplan-Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02-1.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03-1.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02-1.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01-1.25, p = 0.04) and HR 1.10; 95% CI 1.01-1.20, p = 0.02) respectively. HbA1c cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk. CONCLUSIONS HbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population.
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Affiliation(s)
- Christoph Sinning
- Department of Cardiology, University Heart & Vascular Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany.
- German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
| | - Nataliya Makarova
- Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Henry Völzke
- Department of Study of Health in Pomerania/Clinical-Epidemiological Research, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, Germany
| | - Renate B Schnabel
- Department of Cardiology, University Heart & Vascular Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
| | - Francisco Ojeda
- Department of Cardiology, University Heart & Vascular Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany
| | - Marcus Dörr
- German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, Germany
- Department of Internal Medicine B, University of Medicine Greifswald, Greifswald, Germany
| | - Stephan B Felix
- German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, Germany
- Department of Internal Medicine B, University of Medicine Greifswald, Greifswald, Germany
| | - Wolfgang Koenig
- German Heart Center Munich, Technical University, Munich, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
- Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
| | - Annette Peters
- German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
| | - Wolfgang Rathmann
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | - Ben Schöttker
- Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany
- Network Aging Research, University of Heidelberg, Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany
- Network Aging Research, University of Heidelberg, Heidelberg, Germany
| | - Giovanni Veronesi
- Department of Medicine and Surgery, EPIMED Research Center, University of Insubria at Varese, Varese, Italy
| | - Giancarlo Cesana
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Paolo Brambilla
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Tarja Palosaari
- Finnish Institute for Health and Welfare, Division Public Health and Welfare, Helsinki, Finland
| | - Kari Kuulasmaa
- Finnish Institute for Health and Welfare, Division Public Health and Welfare, Helsinki, Finland
| | - Inger Njølstad
- Department of Community Medicine, UiT The Arctic University of Norway, Tromsö, Norway
| | - Ellisiv Bøgeberg Mathiesen
- Brain and Circulation Research Group, UiT The Arctic University of Norway, Tromsö, Norway
- Neurological Department, University Hospital of North Norway, Tromsö, Norway
| | - Tom Wilsgaard
- Department of Community Medicine, UiT The Arctic University of Norway, Tromsö, Norway
| | - Stefan Blankenberg
- Department of Cardiology, University Heart & Vascular Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
| | - Stefan Söderberg
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Marco M Ferrario
- Department of Medicine and Surgery, EPIMED Research Center, University of Insubria at Varese, Varese, Italy
| | - Barbara Thorand
- German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
- German Center for Diabetes Research (DZD), Munich, Neuherberg, Germany
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9
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Luo S, Au Yeung SL, Schooling CM. Assessing the linear and non-linear association of HbA 1c with cardiovascular disease: a Mendelian randomisation study. Diabetologia 2021; 64:2502-2510. [PMID: 34345974 DOI: 10.1007/s00125-021-05537-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 05/19/2021] [Indexed: 10/20/2022]
Abstract
AIMS/HYPOTHESIS We aimed to evaluate whether genetically predicted HbA1c has an effect on the risk of cardiovascular diseases and investigate the shape of the relationship of genetically predicted HbA1c with cardiovascular diseases. METHODS We performed linear univariable, multivariable and non-linear Mendelian randomisation analyses in 373,571 white British participants (mean age 56.9) from the UK Biobank. RESULTS In univariable linear Mendelian randomisation analysis, a 1 mmol/mol increase in genetically predicted HbA1c was associated with higher risk of coronary artery disease (OR 1.03, 95% CI 1.02, 1.05), stroke (OR 1.02, 95% CI 1.00, 1.05) and hypertension (OR 1.02, 95% CI 1.01, 1.03). Multivariable Mendelian randomisation adjusted for the effect of haemoglobin gave a consistent conclusion for coronary artery disease. The associations with stroke and hypertension were directionally similar but with wider CI overlapping the null. Non-linear Mendelian randomisation indicated that the shape of the effect of genetically predicted HbA1c on cardiovascular outcomes was likely linear. CONCLUSIONS/INTERPRETATION The study suggests a detrimental effect of HbA1c on coronary artery disease in both men and women, and the effect is via a glycaemic characteristic. The shape of the genetic association of HbA1c with these cardiovascular outcomes, in particular coronary artery disease, is likely to be linear.
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Affiliation(s)
- Shan Luo
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China
| | - Shiu Lun Au Yeung
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
| | - C Mary Schooling
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China
- School of Public Health and Health Policy, City University of New York, New York, NY, USA
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10
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Inoue K, Nianogo R, Telesca D, Goto A, Khachadourian V, Tsugawa Y, Sugiyama T, Mayeda ER, Ritz B. Low HbA1c levels and all-cause or cardiovascular mortality among people without diabetes: the US National Health and Nutrition Examination Survey 1999-2015. Int J Epidemiol 2021; 50:1373-1383. [PMID: 33378417 DOI: 10.1093/ije/dyaa263] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/02/2020] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVE It is unclear whether relatively low glycated haemoglobin (HbA1c) levels are beneficial or harmful for the long-term health outcomes among people without diabetes. We aimed to investigate the association between low HbA1c levels and mortality among the US general population. METHODS This study includes a nationally representative sample of 39 453 US adults from the National Health and Nutrition Examination Surveys 1999-2014, linked to mortality data through 2015. We employed the parametric g-formula with pooled logistic regression models and the ensemble machine learning algorithms to estimate the time-varying risk of all-cause and cardiovascular mortality by HbA1c categories (low, 4.0 to <5.0%; mid-level, 5.0 to <5.7%; prediabetes, 5.7 to <6.5%; and diabetes, ≥6.5% or taking antidiabetic medication), adjusting for 72 potential confounders including demographic characteristics, lifestyle, biomarkers, comorbidities and medications. RESULTS Over a median follow-up of 7.5 years, 5118 (13%) all-cause deaths, and 1116 (3%) cardiovascular deaths were observed. Logistic regression models and machine learning algorithms showed nearly identical predictive performance of death and risk estimates. Compared with mid-level HbA1c, low HbA1c was associated with a 30% (95% CI, 16 to 48) and a 12% (95% CI, 3 to 22) increased risk of all-cause mortality at 5 years and 10 years of follow-up, respectively. We found no evidence that low HbA1c levels were associated with cardiovascular mortality risk. The diabetes group, but not the prediabetes group, also showed an increased risk of all-cause mortality. CONCLUSIONS Using the US national database and adjusting for an extensive set of potential confounders with flexible modelling, we found that adults with low HbA1c were at increased risk of all-cause mortality. Further evaluation and careful monitoring of low HbA1c levels need to be considered.
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Affiliation(s)
- Kosuke Inoue
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA
| | - Roch Nianogo
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA
| | - Donatello Telesca
- Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA, USA
| | - Atsushi Goto
- Department of Health Data Science, Graduate School of Data Science, Yokohama City University, Yokohama, Japan
| | - Vahe Khachadourian
- Gerald & Patricia Turpanjian School of Public Health, American University of Armenia, Yerevan, Armenia
| | - Yusuke Tsugawa
- Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.,Department of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA, USA
| | - Takehiro Sugiyama
- Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.,Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Elizabeth Rose Mayeda
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA
| | - Beate Ritz
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.,Department of Environmental Health Sciences, UCLA Fielding School of Public Health, Los Angeles, CA, USA.,Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA
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11
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Rodgers LR, Hill AV, Dennis JM, Craig Z, May B, Hattersley AT, McDonald TJ, Andrews RC, Jones A, Shields BM. Choice of HbA1c threshold for identifying individuals at high risk of type 2 diabetes and implications for diabetes prevention programmes: a cohort study. BMC Med 2021; 19:184. [PMID: 34412655 PMCID: PMC8377980 DOI: 10.1186/s12916-021-02054-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 07/07/2021] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Type 2 diabetes (T2D) is common and increasing in prevalence. It is possible to prevent or delay T2D using lifestyle intervention programmes. Entry to these programmes is usually determined by a measure of glycaemia in the 'intermediate' range. This paper investigated the relationship between HbA1c and future diabetes risk and determined the impact of varying thresholds to identify those at high risk of developing T2D. METHODS We studied 4227 participants without diabetes aged ≥ 40 years recruited to the Exeter 10,000 population cohort in South West England. HbA1c was measured at study recruitment with repeat HbA1c available as part of usual care. Absolute risk of developing diabetes within 5 years, defined by HbA1c ≥ 48 mmol/mol (6.5%), according to baseline HbA1c, was assessed by a flexible parametric survival model. RESULTS The overall absolute 5-year risk (95% CI) of developing T2D in the cohort was 4.2% (3.6, 4.8%). This rose to 7.1% (6.1, 8.2%) in the 56% (n = 2358/4224) of participants classified 'high-risk' with HbA1c ≥ 39 mmol/mol (5.7%; ADA criteria). Under IEC criteria, HbA1c ≥ 42 mmol/mol (6.0%), 22% (n = 929/4277) of the cohort was classified high-risk with 5-year risk 14.9% (12.6, 17.2%). Those with the highest HbA1c values (44-47 mmol/mol [6.2-6.4%]) had much higher 5-year risk, 26.4% (22.0, 30.5%) compared with 2.1% (1.5, 2.6%) for 39-41 mmol/mol (5.7-5.9%) and 7.0% (5.4, 8.6%) for 42-43 mmol/mol (6.0-6.1%). Changing the entry criterion to prevention programmes from 39 to 42 mmol/mol (5.7-6.0%) reduced the proportion classified high-risk by 61%, and increased the positive predictive value (PPV) from 5.8 to 12.4% with negligible impact on the negative predictive value (NPV), 99.6% to 99.1%. Increasing the threshold further, to 44 mmol/mol (6.2%), reduced those classified high-risk by 59%, and markedly increased the PPV from 12.4 to 23.2% and had little impact on the NPV (99.1% to 98.5%). CONCLUSIONS A large proportion of people are identified as high-risk using current thresholds. Increasing the risk threshold markedly reduces the number of people that would be classified as high-risk and entered into prevention programmes, although this must be balanced against cases missed. Raising the entry threshold would allow limited intervention opportunities to be focused on those most likely to develop T2D.
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Affiliation(s)
- Lauren R Rodgers
- Institute of Health Research, University of Exeter Medical School, South Cloisters, St Lukes Campus, Exeter, EX1 2LU, UK.
| | - Anita V Hill
- NIHR Exeter Clinical Research Facility, Royal Devon & Exeter NHS Foundation Trust & University of Exeter Medical School, Exeter, UK
| | - John M Dennis
- Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, EX2 5DW, UK
| | - Zoe Craig
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, West Yorkshire, UK
| | - Benedict May
- College of Mathematics Engineering and Physical Science, University of Exeter, Exeter, UK
| | - Andrew T Hattersley
- Department of Diabetes and Endocrinology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Timothy J McDonald
- Academic Department of Blood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Rob C Andrews
- Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, EX2 5DW, UK
| | - Angus Jones
- Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, EX2 5DW, UK
| | - Beverley M Shields
- Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, EX2 5DW, UK
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12
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Wium-Andersen IK, Hengeveld EM, Rungby J, Jørgensen MB, Osler M, Wium-Andersen MK. Hemoglobin A1c-levels and subsequent risk of depression in individuals with and without diabetes. J Diabetes Complications 2021; 35:107946. [PMID: 34053797 DOI: 10.1016/j.jdiacomp.2021.107946] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 04/15/2021] [Accepted: 05/02/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND It has been suggested that long-term glycemic load as reflected in plasma levels of Glycosylated Hemoglobin, Type A1C (HbA1c) is associated with higher risk of depression, however results have been conflicting. We examined the potential association between HbA1c and risk of depression in a large population-based cohort without baseline diabetes (the Glostrup cohort) defined by either self-reported diabetes, registry diagnosis of diabetes or use of antidiabetic medication at baseline and in a national diabetes cohort (the Danish Adult Diabetes Database). METHODS A total of 16,124 middle-aged individuals from the Glostrup cohort and 93,544 patients registered in the Danish Adult Diabetes Database were followed from the first registered HbA1c measurement (1999-2014) for subsequent diagnosis of depression or use of antidepressant medication in nation-wide Danish registers. The association was analyzed using a Cox proportional hazards regression model with HbA1c on both a continuous scale using restricted cubic splines and categorized based on the groups found in the spline model. We adjusted for relevant sociodemographic and clinical variables including previous depression and tested for interaction of both gender, insulin use and diabetes type. RESULTS During follow-up, 2694 (17%) in the Glostrup cohort and 29,234 (31%) in the diabetes cohort developed depression. In the Glostrup cohort, we found an indication of a positive linear association between HbA1c and depression in women, while no clear association was found in men. In patients with diabetes, we found a U-shaped association between HbA1c and depression in both men and women with the lowest risk estimates for HbA1c levels of 58 mmol/mol (7.5%) in men and of 60 mmol/mol (7.6%) in women. When HbA1c was categorized, men with the highest HbA1c-levels had significantly elevated risk of depression (HRHbA1c>9.4 1.16 (95%CI 1.10-1.23)) after multifactorial adjustment compared to the reference group with HbA1c of 42.1-56.2 mmol/mol (6.0-7.3%). Women in the lowest and highest category of HbA1c had significantly higher risk of depression HRHbA1c<6.0 1.15 (95% CI 1.09-1.22) and HRHbA1c>9.3 1.10 (95% CI 1.04-1.16), respectively, compared to the reference group with HbA1c 42.1-55.0 mmol/mol (7.2-9.3%). There was a significant interaction with gender, but no interaction for insulin use or diabetes type. CONCLUSIONS In a population without baseline diabetes, higher HbA1c levels seemed associated with higher depression risk in women, whereas a U-shaped association was found in patients with known diabetes.
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Affiliation(s)
- I K Wium-Andersen
- Psychiatric Center Copenhagen, Department O, Copenhagen, Denmark; Center for Clinical Research and Prevention, Frederiksberg Hospital, Denmark
| | - E M Hengeveld
- Center for Clinical Research and Prevention, Frederiksberg Hospital, Denmark
| | - J Rungby
- Department of Endocrinology and Copenhagen Center for Translational Research, Bispebjerg-Frederiksberg, Denmark
| | - M B Jørgensen
- Psychiatric Center Copenhagen, Department O, Copenhagen, Denmark
| | - M Osler
- Center for Clinical Research and Prevention, Frederiksberg Hospital, Denmark; Section for Epidemiology, Department of Public Health, University of Copenhagen, Denmark
| | - M K Wium-Andersen
- Center for Clinical Research and Prevention, Frederiksberg Hospital, Denmark.
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13
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Kowall B, Rathmann W, Kuß O, Herder C, Roden M, Stang A, Erbel R, Huth C, Thorand B, Meisinger C, Jöckel KH, Peters A. Associations between haemoglobin A 1c and mortality rate in the KORA S4 and the Heinz Nixdorf Recall population-based cohort studies. Diabetes Metab Res Rev 2021; 37:e3369. [PMID: 32558166 DOI: 10.1002/dmrr.3369] [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: 03/13/2020] [Revised: 05/30/2020] [Accepted: 06/12/2020] [Indexed: 11/06/2022]
Abstract
BACKGROUND There is limited knowledge about mortality risk in persons with increased haemoglobin A1c (HbA1c ) levels below the diabetes threshold. Moreover, little is known about how associations between increased HbA1c and mortality depend on the length of follow-up. Therefore, we studied associations between HbA1c and mortality over long-term follow-up in persons with and without known diabetes. METHODS We used data from two German population-based cohort studies: KORA S4 Study (Southern Germany, n = 1458, baseline visits in 1999 to 2001, baseline age 55 to 74 years, mortality follow-up 16.8 years) and Heinz Nixdorf Recall (HNR) Study (Ruhr area, n = 4613, baseline visits in 2000 to 2003, baseline age 45 to 75 years, mortality follow-up 17.8 years). Adjusted log-linear models were fitted to estimate relative risks (RRs) with 95% confidence intervals (CI). RESULTS In both cohorts, participants with HbA1c 39 to 41 mmol/mol (5.7%-5.9%) and HbA1c 42 to 46 mmol/mol (6.0% to 6.4%) did not have a larger overall mortality risk than participants with HbA1c < 39 mmol/mol (5.7%): the corresponding adjusted RRs were 1.00 (95% CI: 0.83-1.21) and 1.01 (0.80-1.27) in KORA and 0.99 (0.82-1.21) and 0.83 (0.65-1.07) in the HNR Study. For the pooled cohorts, the RR for HbA1c 39 to 46 mmol/mol (5.7%-6.4%) was 0.96 (0.85-1.07). Associations between newly detected diabetes (HbA1c ≥ 6.5%) and mortality were weak after 4 and 8 years of follow-up, but were stronger after 12 years of follow-up, whereas associations between previously known diabetes (baseline) and mortality decreased. CONCLUSIONS HbA1c -defined pre-diabetes is not associated with overall mortality. For newly detected and previously known diabetes, mortality risks vary with length of follow-up.
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Affiliation(s)
- Bernd Kowall
- Center of Clinical Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, Medical Faculty, University Duisburg-Essen, Essen, Germany
| | - Wolfgang Rathmann
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research, Düsseldorf, Germany
| | - Oliver Kuß
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research, Düsseldorf, Germany
| | - Christian Herder
- German Center for Diabetes Research, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Michael Roden
- German Center for Diabetes Research, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Andreas Stang
- Center of Clinical Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, Medical Faculty, University Duisburg-Essen, Essen, Germany
| | - Raimund Erbel
- Institute for Medical Informatics, Biometry and Epidemiology, University Clinic Essen, University Duisburg-Essen, Essen, Germany
| | - Cornelia Huth
- German Center for Diabetes Research, Düsseldorf, Germany
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Barbara Thorand
- German Center for Diabetes Research, Düsseldorf, Germany
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Christa Meisinger
- Department of Epidemiology, Ludwig-Maximilian-Universität München, UNIKA-T Augsburg, Augsburg, Germany
- Independent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Karl-Heinz Jöckel
- Institute for Medical Informatics, Biometry and Epidemiology, University Clinic Essen, University Duisburg-Essen, Essen, Germany
| | - Annette Peters
- German Center for Diabetes Research, Düsseldorf, Germany
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
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14
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Rooney MR, Tang O, Pankow JS, Selvin E. Glycaemic markers and all-cause mortality in older adults with and without diabetes: the Atherosclerosis Risk in Communities (ARIC) study. Diabetologia 2021; 64:339-348. [PMID: 32990802 PMCID: PMC7855037 DOI: 10.1007/s00125-020-05285-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 08/11/2020] [Indexed: 12/19/2022]
Abstract
AIMS/HYPOTHESIS There is controversy regarding the performance of HbA1c in old age. We evaluated the prognostic value of HbA1c and other glycaemic markers (fructosamine, glycated albumin, fasting glucose) with mortality risk in older adults (66-90 years). METHODS This was a prospective analysis of 5636 participants (31% with diagnosed diabetes, mean age 76, 58% female, 21% black) in the Atherosclerosis Risk in Communities (ARIC) study, baseline 2011-2013. We used Cox regression to examine associations of glycaemic markers (modelled in categories) with mortality risk, stratified by diagnosed diabetes status. RESULTS During a median of 6 years of follow-up, 983 deaths occurred. Among older adults with diabetes, 30% had low HbA1c (<42 mmol/mol [<6.0%]) and 10% had high HbA1c (≥64 mmol/mol [≥8.0%]); low (HR 1.32 [95% CI 1.04, 1.68]) and high (HR 1.86 [95% CI 1.32, 2.62]) HbA1c were associated with mortality risk vs HbA1c 42-52 mmol/mol (6.0-6.9%) after demographic adjustment. Low fructosamine and glycated albumin were not associated with mortality risk. Both low and high fasting glucose were associated with mortality risk. After further adjustment for lifestyle and clinical risk factors, high HbA1c (HR 1.81 [95% CI 1.28, 2.56]), fructosamine (HR 1.96 [95% CI 1.43-2.69]), glycated albumin (HR 1.81 [95% CI 1.33-2.47]) and fasting glucose (HR 1.81 [95% CI 1.24, 2.66]) were associated with mortality risk. Low HbA1c and fasting glucose were no longer significantly associated with mortality risk. Among participants without diabetes, associations of glycaemic markers with mortality risk were less robust. CONCLUSIONS/INTERPRETATION Elevated HbA1c, fructosamine, glycated albumin and fasting glucose were associated with risk of mortality in older adults with diabetes. Low HbA1c and fasting glucose may be markers of poor prognosis but are possibly confounded by health status. Our findings support the clinical use of HbA1c in older adults with diabetes. Graphical abstract.
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Affiliation(s)
- Mary R Rooney
- Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA.
| | - Olive Tang
- Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
| | - James S Pankow
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA
| | - Elizabeth Selvin
- Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
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15
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Wang XB, Cui NH, Liu X, Liu X. Mitochondrial 8-hydroxy-2'-deoxyguanosine and coronary artery disease in patients with type 2 diabetes mellitus. Cardiovasc Diabetol 2020; 19:22. [PMID: 32075646 PMCID: PMC7029479 DOI: 10.1186/s12933-020-00998-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 02/06/2020] [Indexed: 12/14/2022] Open
Abstract
Background Little is known about whether mitochondria 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of mitochondrial DNA (mtDNA) oxidative damage, contributes to the development of coronary artery disease (CAD) in diabetic patients. Here, we explored the associations of mtDNA 8-OHdG in leukocytes with obstructive CAD, coronary stenosis severity, cardiovascular biomarkers, and 1-year adverse outcomes after coronary revascularization in patients with type 2 diabetes mellitus (T2DM). Methods In a total of 1920 consecutive patients with T2DM who underwent coronary angiography due to symptoms of angina or angina equivalents, the presence of obstructive CAD, the number of diseased vessels with ≥ 50% stenosis, and modified Gensini score were cross-sectionally evaluated; the level of mtDNA 8-OHdG was quantified by quantitative PCR. Then, 701 of 1920 diabetic patients who further received coronary revascularization completed 1-year prospective follow-up to document major adverse cardiovascular and cerebral events (MACCEs). In vitro experiments were also performed to observe the effects of mtDNA oxidative damage in high glucose-cultured human umbilical vein endothelial cells (HUVECs). Results Cross-sectionally, greater mtDNA 8-OHdG was associated with increased odds of obstructive CAD (odds ratio [OR] 1.38, 95% CI confidence interval 1.24–1.52), higher degree of coronary stenosis (number of diseased vessels: OR 1.29, 95% CI 1.19–1.41; modified Gensini scores: OR 1.28, 95% CI 1.18–1.39), and higher levels of C-reactive protein (β 0.18, 95% CI 0.06–0.31) after adjusting for confounders. Sensitivity analyses using propensity score matching yielded similar results. Stratification by smoking status showed that the association between mtDNA 8-OHdG and obstructive CAD was most evident in current smokers (Pinteration < 0.01). Prospectively, the adjusted hazards ratio per 1-SD increase in mtDNA 8-OHdG was 1.59 (95% CI 1.33–1.90) for predicting 1-year MACCEs after revascularization. In HUVECs, exposure to antimycin A, an inducer for mtDNA oxidative damage, led to adverse alterations in markers of mitochondrial and endothelia function. Conclusion Greater mtDNA 8-OHdG in leukocytes may serve as an independent risk factor for CAD in patients with T2DM.
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Affiliation(s)
- Xue-Bin Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road No. 1, Zhengzhou, 450000, Henan, China.
| | - Ning-Hua Cui
- Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Xia'nan Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road No. 1, Zhengzhou, 450000, Henan, China
| | - Xin Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road No. 1, Zhengzhou, 450000, Henan, China
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16
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Su WY, Chen SC, Huang YT, Huang JC, Wu PY, Hsu WH, Lee MY. Comparison of the Effects of Fasting Glucose, Hemoglobin A 1c, and Triglyceride-Glucose Index on Cardiovascular Events in Type 2 Diabetes Mellitus. Nutrients 2019; 11:nu11112838. [PMID: 31752391 PMCID: PMC6893677 DOI: 10.3390/nu11112838] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 11/12/2019] [Accepted: 11/15/2019] [Indexed: 02/06/2023] Open
Abstract
The triglyceride–glucose (TyG) index has been correlated with insulin resistance. We aim to investigate the role of the TyG index on cardiovascular (CV) events in type 2 diabetes mellitus and compare the roles of fasting glucose, hemoglobin A1c, and the TyG index in predicting CV events. This retrospective study enrolled 3524 patients with type 2 diabetes from the Kaohsiung Medical University Research Database in 2009 in this longitudinal study and followed them until 2015. The TyG index was calculated as log (fasting triglyceride level (mg/dL) × fasting glucose level (mg/dL)/2). CV events included myocardial infarction, unstable angina, stroke, hospitalization for coronary artery disease, peripheral artery disease, and CV-related death. The association between variables and CV events was assessed using a multivariable stepwise Cox proportional hazard analysis. Two hundred and fifteen CV events (6.1%) were recorded during a follow-up period of 5.93 years. The multivariable stepwise analysis showed that high fasting glucose (HR, 1.007; p < 0.001) and a high TyG index (HR, 1.521; p = 0.004) but not hemoglobin A1c or triglycerides were associated with a higher rate of CV events. Adding fasting glucose and the TyG index to the basic model improved the predictive ability of progression to a CV event (p < 0.001 and p = 0.018, respectively), over that of hemoglobin A1c (p = 0.084) and triglyceride (p = 0.221). Fasting glucose and the TyG index are useful parameters and stronger predictive factors than hemoglobin A1c and triglyceride for CV events and may offer an additional prognostic benefit in patients with type 2 diabetes.
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Affiliation(s)
- Wei-Yu Su
- Department of General Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan;
| | - Szu-Chia Chen
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (S.-C.C.); (J.-C.H.); (P.-Y.W.)
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan;
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Yu-Ting Huang
- Division of Medical Statistics and Bioinformatics, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Jiun-Chi Huang
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (S.-C.C.); (J.-C.H.); (P.-Y.W.)
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan;
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Pei-Yu Wu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (S.-C.C.); (J.-C.H.); (P.-Y.W.)
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan;
| | - Wei-Hao Hsu
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan;
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Mei-Yueh Lee
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Correspondence: ; Tel.: +886-7-803-6783-3441; Fax: +886-7-806-3346
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17
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Wiss DA. The Relationship Between Alcohol and Glycohemoglobin: A Biopsychosocial Perspective. Biores Open Access 2019; 8:146-154. [PMID: 31588381 PMCID: PMC6776959 DOI: 10.1089/biores.2019.0009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
With the rising prevalence of type 2 diabetes mellitus (T2DM), there is debate regarding biological and psychosocial risk factors. While it is well established that alcohol lowers glycohemoglobin (HbA1c) levels, it is less clear whether alcohol consumption is protective of T2DM. It is also unclear how gender and ethnicity influence the utility of HbA1c screening as a tool for T2DM diagnosis, particularly in the context of alcohol use. This cross-sectional study utilized the National Health and Nutrition Examination Survey 2013–2014 dataset and was restricted to adults 20 years and older, nonpregnant, and not on antihypertensive medication (n = 4299) to evaluate the relationship between alcohol use and HbA1c. A multilinear regression model controlled for gender, ethnicity, education level, body mass index, and age. After controlling for covariates, both moderate (β = −0.073; p = 0.033) and heavy drinking (β = −0.167; p < 0.001) are associated with reduced HbA1c levels. Additionally, female gender is a significant negative predictor of HbA1c (β = −0.052; p = 0.024) and all ethnic groups have higher levels of HbA1c compared with non-Hispanic whites. Plausible biological mechanisms are discussed. The clinical utility of HbA1c as a screening tool for T2DM without considering alcohol use, gender, and ethnicity may lead to diagnostic errors. Individualized approaches and focused efforts toward health equity are needed to address rising rates of T2DM.
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Affiliation(s)
- David A. Wiss
- Department of Community Health Sciences, Fielding School of Public Health, University of California Los Angeles, Los Angeles, California
- Address correspondence to: David A. Wiss, MS, RDN, Department of Community Health Sciences, Fielding School of Public Health, University of California Los Angeles, 650 Young Drive South, Los Angeles, CA 90025
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18
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Cai L, Wang S, Gao P, Shen X, Jalaludin B, Bloom MS, Wang Q, Bao J, Zeng X, Gui Z, Chen Y, Huang C. Effects of ambient particulate matter on fasting blood glucose among primary school children in Guangzhou, China. ENVIRONMENTAL RESEARCH 2019; 176:108541. [PMID: 31271922 DOI: 10.1016/j.envres.2019.108541] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 06/06/2019] [Accepted: 06/17/2019] [Indexed: 06/09/2023]
Abstract
BACKGROUND Exposure to ambient particulate matter (PM) has been linked with diabetes and elevated blood glucose in adults. However, there are few reports on the effects of PM on fasting blood glucose (FBG) among children. OBJECTIVES The study aimed to assess the associations between medium-term exposure of ambient particles with diameters ≤2.5 μm (PM2.5), and ≤10 μm (PM10) and FBG in a general population of children, and also to explore the modifying effects of diet. METHODS In this cross-sectional study, we enrolled 4234 children (aged 6-13 years) residing in Guangzhou, China, in 2017. Individual PM2.5 and PM10 exposures during the 186-day period before each physical examination were retrospectively estimated by an inverse distance weighting interpolation and time-weighted approach according to their home address, school address, and activity patterns. Linear mixed effect models were used to examine the relationships between PM2.5 and PM10 with FBG after adjusting for covariates. RESULTS We found that per 10 μg/m3 increase in PM2.5 and PM10 levels during the 186-day period were associated with 2.3% (95% CI: 1.0%, 3.8%) higher FBG and 0.9% (95% CI: 0.5%, 1.4%) higher FBG, respectively. Stronger effect estimates were observed among subgroups of children with a family history of diabetes, and higher intake of sugar-sweetened beverages (SSBs). Also, we found significant interactions between PM2.5 concentration and family history of diabetes and SSBs intake on FBG. CONCLUSIONS Medium-term exposure to ambient PM2.5 and PM10 were associated with higher FBG levels in children, and that higher SSBs intake might modify these associations.
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Affiliation(s)
- Li Cai
- Department of Maternal and Child Health, School of Public Health, Sun Yat-sen University, China
| | - Suhan Wang
- Department of Health Policy and Management, School of Public Health, Sun Yat-sen University, China; Laboratory of Meteorology and Health, Shanghai Meteorological Service, China
| | - Peng Gao
- Guangdong Province Key Laboratory for Climate Change and Natural Disaster Studies, School of Atmospheric Sciences, Sun Yat-sen University, China
| | - Xiaoting Shen
- Center for Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University, China
| | - Bin Jalaludin
- Population Health, South Western Sydney Local Health District, Liverpool, NSW, 2170, Australia
| | - Michael S Bloom
- Department of Environmental Health Sciences and Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, NY, 12144, USA
| | - Qiong Wang
- Department of Health Policy and Management, School of Public Health, Sun Yat-sen University, China; Laboratory of Meteorology and Health, Shanghai Meteorological Service, China
| | - Junzhe Bao
- Department of Health Policy and Management, School of Public Health, Sun Yat-sen University, China; Laboratory of Meteorology and Health, Shanghai Meteorological Service, China
| | - Xia Zeng
- Department of Maternal and Child Health, School of Public Health, Sun Yat-sen University, China
| | - Zhaohuan Gui
- Department of Maternal and Child Health, School of Public Health, Sun Yat-sen University, China
| | - Yajun Chen
- Department of Maternal and Child Health, School of Public Health, Sun Yat-sen University, China.
| | - Cunrui Huang
- Department of Health Policy and Management, School of Public Health, Sun Yat-sen University, China; Laboratory of Meteorology and Health, Shanghai Meteorological Service, China.
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19
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Li FR, Zhang XR, Zhong WF, Li ZH, Gao X, Kraus VB, Lv YB, Zou MC, Chen GC, Chen PL, Zhang MY, Kur AKA, Shi XM, Wu XB, Mao C. Glycated Hemoglobin and All-Cause and Cause-Specific Mortality Among Adults With and Without Diabetes. J Clin Endocrinol Metab 2019; 104:3345-3354. [PMID: 30896760 PMCID: PMC7328059 DOI: 10.1210/jc.2018-02536] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Accepted: 03/15/2019] [Indexed: 12/25/2022]
Abstract
CONTEXT The patterns of associations between glycated Hb (HbA1c) and mortality are still unclear. OBJECTIVE To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes. DESIGN, SETTING, AND PATIENTS This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for mortality. RESULTS A total of 2133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was <5.6% or >7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When the HbA1c level was <5.0%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 5.4%. However, we did not observe a statistically significant elevated risk of all-cause mortality above an HbA1c level of 5.4%. CONCLUSIONS A U-shaped and reverse J-shaped association for all-cause mortality was found among participants with and without diabetes. The corresponding optimal ranges for overall survival are predicted to be 5.6% and 7.4% and 5.0% and 6.5%, respectively.
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Affiliation(s)
- Fu-Rong Li
- Department of Epidemiology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, China
| | - Xi-Ru Zhang
- Department of Epidemiology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, China
| | - Wen-Fang Zhong
- Department of Epidemiology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, China
| | - Zhi-Hao Li
- Department of Epidemiology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, China
| | - Xiang Gao
- Nutritional Epidemiology Laboratory, The Pennsylvania State University, Philadelphia, Pennsylvania
| | - Virginia Byers Kraus
- Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
| | - Yue-Bin Lv
- National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Meng-Chen Zou
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Guo-Chong Chen
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
| | - Pei-Liang Chen
- Department of Epidemiology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, China
| | - Min-Yi Zhang
- Department of Epidemiology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, China
| | - Akech Kuol Akech Kur
- Department of Epidemiology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, China
| | - Xiao-Ming Shi
- National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Xian-Bo Wu
- Department of Epidemiology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, China
- Correspondence and Reprint Requests: Chen Mao, PhD, or Xian-Bo Wu, PhD, Department of Epidemiology, School of Public Health, Southern Medical University, 510000 Guangzhou, Guangdong, China. E-mail: or
| | - Chen Mao
- Department of Epidemiology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, China
- Correspondence and Reprint Requests: Chen Mao, PhD, or Xian-Bo Wu, PhD, Department of Epidemiology, School of Public Health, Southern Medical University, 510000 Guangzhou, Guangdong, China. E-mail: or
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20
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Pappolla MA, Manchikanti L, Andersen CR, Greig NH, Ahmed F, Fang X, Seffinger MA, Trescot AM. Is insulin resistance the cause of fibromyalgia? A preliminary report. PLoS One 2019; 14:e0216079. [PMID: 31059525 PMCID: PMC6502334 DOI: 10.1371/journal.pone.0216079] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Accepted: 04/11/2019] [Indexed: 12/21/2022] Open
Abstract
Fibromyalgia (FM) is one of the most frequent generalized pain disorders with poorly understood neurobiological mechanisms. This condition accounts for an enormous proportion of healthcare costs. Despite extensive research, the etiology of FM is unknown and thus, there is no disease modifying therapy available for this condition. We show that most (if not all) patients with FM belong to a distinct population that can be segregated from a control group by their glycated hemoglobin A1c (HbA1c) levels, a surrogate marker of insulin resistance (IR). This was demonstrated by analyzing the data after introducing an age stratification correction into a linear regression model. This strategy showed highly significant differences between FM patients and control subjects (p < 0.0001 and p = 0.0002, for two separate control populations, respectively). A subgroup of patients meeting criteria for pre-diabetes or diabetes (patients with HbA1c values of 5.7% or greater) who had undergone treatment with metformin showed dramatic improvements of their widespread myofascial pain, as shown by their scores using a pre and post-treatment numerical pain rating scale (NPRS) for evaluation. Although preliminary, these findings suggest a pathogenetic relationship between FM and IR, which may lead to a radical paradigm shift in the management of this disorder.
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Affiliation(s)
- Miguel A. Pappolla
- Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America
- St. Michael’s Pain & Spine Clinics, Houston, Texas, United States of America
- * E-mail:
| | - Laxmaiah Manchikanti
- Department of Anesthesiology, LSU School of Medicine Health Sciences Center, New Orleans, Louisiana, United States of America
| | - Clark R. Andersen
- Office of Biostatistics, University of Texas Medical Branch, Galveston, Texas, United States of America
| | - Nigel H. Greig
- Drug Design and Development Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Fawad Ahmed
- St. Michael’s Pain & Spine Clinics, Houston, Texas, United States of America
| | - Xiang Fang
- Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America
| | - Michael A. Seffinger
- Department of Neuromusculoskeletal Medicine, College of Osteopathic Medicine of the Pacific, Pomona, California, United States of America
| | - Andrea M. Trescot
- Pain and Headache Center, Eagle River, Alaska, United States of America
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21
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Mongraw-Chaffin M, Bertoni AG, Golden SH, Mathioudakis N, Sears DD, Szklo M, Anderson CAM. Association of Low Fasting Glucose and HbA1c With Cardiovascular Disease and Mortality: The MESA Study. J Endocr Soc 2019; 3:892-901. [PMID: 31020054 PMCID: PMC6469950 DOI: 10.1210/js.2019-00033] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 02/26/2019] [Indexed: 12/12/2022] Open
Abstract
Trials of intensive glucose control have not improved cardiovascular disease (CVD) risk in populations with type 2 diabetes; however, in the general population, reports are inconsistent about the effects of maintaining lower glucose levels. Some speculate that low glycemic values are associated with increased glycemic variability, which is in turn associated with higher CVD risk. It has also been suggested that fasting glucose and hemoglobin A1c (HbA1c) in the lower ranges have a different relationship with CVD and mortality. In 4990 participants from the Multi-Ethnic Study of Atherosclerosis, we used logistic regression to investigate associations of low fasting glucose (<80 mg/dL) and HbA1c (<5.0%) from baseline and averaged across follow-up with incident CVD and mortality over 13 years. We used normal glycemic ranges (80 to <100 mg/dL and 5.0 to <5.7%) as references and analyzed glycemic levels with visit-matched covariates. We adjusted for potential confounding by age, sex, race/ethnicity, education, income, smoking status, body mass index, total cholesterol level, cholesterol medications, high-density lipoprotein cholesterol, and hypertension. Low baseline glucose and HbA1c were positively, but not significantly, associated with mortality, whereas low average fasting glucose and HbA1c were strongly and significantly associated with incident CVD [glucose OR, 2.04 (95% CI, 1.38-3.00); HbA1c OR, 2.01 (95% CI, 1.58-2.55)] and mortality [glucose OR, 1.93 (95% CI, 1.33-2.79); HbA1c OR, 2.51 (95% CI, 2.00-3.15)]. These results were not due to type 2 diabetes or medication use. Glucose variability did not explain CVD risk beyond average glucose levels. Chronic low fasting glucose and HbA1c may be better indicators of risk than a single low measurement.
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Affiliation(s)
- Morgana Mongraw-Chaffin
- Department of Epidemiology & Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Alain G Bertoni
- Department of Epidemiology & Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Sherita Hill Golden
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.,Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nestoras Mathioudakis
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dorothy D Sears
- Department of Medicine, University of California San Diego, La Jolla, California.,Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California
| | - Moyses Szklo
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Cheryl A M Anderson
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.,Department of Medicine, University of California San Diego, La Jolla, California.,Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California
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22
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Richter B, Hemmingsen B, Metzendorf M, Takwoingi Y. Development of type 2 diabetes mellitus in people with intermediate hyperglycaemia. Cochrane Database Syst Rev 2018; 10:CD012661. [PMID: 30371961 PMCID: PMC6516891 DOI: 10.1002/14651858.cd012661.pub2] [Citation(s) in RCA: 91] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Intermediate hyperglycaemia (IH) is characterised by one or more measurements of elevated blood glucose concentrations, such as impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and elevated glycosylated haemoglobin A1c (HbA1c). These levels are higher than normal but below the diagnostic threshold for type 2 diabetes mellitus (T2DM). The reduced threshold of 5.6 mmol/L (100 mg/dL) fasting plasma glucose (FPG) for defining IFG, introduced by the American Diabetes Association (ADA) in 2003, substantially increased the prevalence of IFG. Likewise, the lowering of the HbA1c threshold from 6.0% to 5.7% by the ADA in 2010 could potentially have significant medical, public health and socioeconomic impacts. OBJECTIVES To assess the overall prognosis of people with IH for developing T2DM, regression from IH to normoglycaemia and the difference in T2DM incidence in people with IH versus people with normoglycaemia. SEARCH METHODS We searched MEDLINE, Embase, ClincialTrials.gov and the International Clinical Trials Registry Platform (ICTRP) Search Portal up to December 2016 and updated the MEDLINE search in February 2018. We used several complementary search methods in addition to a Boolean search based on analytical text mining. SELECTION CRITERIA We included prospective cohort studies investigating the development of T2DM in people with IH. We used standard definitions of IH as described by the ADA or World Health Organization (WHO). We excluded intervention trials and studies on cohorts with additional comorbidities at baseline, studies with missing data on the transition from IH to T2DM, and studies where T2DM incidence was evaluated by documents or self-report only. DATA COLLECTION AND ANALYSIS One review author extracted study characteristics, and a second author checked the extracted data. We used a tailored version of the Quality In Prognosis Studies (QUIPS) tool for assessing risk of bias. We pooled incidence and incidence rate ratios (IRR) using a random-effects model to account for between-study heterogeneity. To meta-analyse incidence data, we used a method for pooling proportions. For hazard ratios (HR) and odds ratios (OR) of IH versus normoglycaemia, reported with 95% confidence intervals (CI), we obtained standard errors from these CIs and performed random-effects meta-analyses using the generic inverse-variance method. We used multivariable HRs and the model with the greatest number of covariates. We evaluated the certainty of the evidence with an adapted version of the GRADE framework. MAIN RESULTS We included 103 prospective cohort studies. The studies mainly defined IH by IFG5.6 (FPG mmol/L 5.6 to 6.9 mmol/L or 100 mg/dL to 125 mg/dL), IFG6.1 (FPG 6.1 mmol/L to 6.9 mmol/L or 110 mg/dL to 125 mg/dL), IGT (plasma glucose 7.8 mmol/L to 11.1 mmol/L or 140 mg/dL to 199 mg/dL two hours after a 75 g glucose load on the oral glucose tolerance test, combined IFG and IGT (IFG/IGT), and elevated HbA1c (HbA1c5.7: HbA1c 5.7% to 6.4% or 39 mmol/mol to 46 mmol/mol; HbA1c6.0: HbA1c 6.0% to 6.4% or 42 mmol/mol to 46 mmol/mol). The follow-up period ranged from 1 to 24 years. Ninety-three studies evaluated the overall prognosis of people with IH measured by cumulative T2DM incidence, and 52 studies evaluated glycaemic status as a prognostic factor for T2DM by comparing a cohort with IH to a cohort with normoglycaemia. Participants were of Australian, European or North American origin in 41 studies; Latin American in 7; Asian or Middle Eastern in 50; and Islanders or American Indians in 5. Six studies included children and/or adolescents.Cumulative incidence of T2DM associated with IFG5.6, IFG6.1, IGT and the combination of IFG/IGT increased with length of follow-up. Cumulative incidence was highest with IFG/IGT, followed by IGT, IFG6.1 and IFG5.6. Limited data showed a higher T2DM incidence associated with HbA1c6.0 compared to HbA1c5.7. We rated the evidence for overall prognosis as of moderate certainty because of imprecision (wide CIs in most studies). In the 47 studies reporting restitution of normoglycaemia, regression ranged from 33% to 59% within one to five years follow-up, and from 17% to 42% for 6 to 11 years of follow-up (moderate-certainty evidence).Studies evaluating the prognostic effect of IH versus normoglycaemia reported different effect measures (HRs, IRRs and ORs). Overall, the effect measures all indicated an elevated risk of T2DM at 1 to 24 years of follow-up. Taking into account the long-term follow-up of cohort studies, estimation of HRs for time-dependent events like T2DM incidence appeared most reliable. The pooled HR and the number of studies and participants for different IH definitions as compared to normoglycaemia were: IFG5.6: HR 4.32 (95% CI 2.61 to 7.12), 8 studies, 9017 participants; IFG6.1: HR 5.47 (95% CI 3.50 to 8.54), 9 studies, 2818 participants; IGT: HR 3.61 (95% CI 2.31 to 5.64), 5 studies, 4010 participants; IFG and IGT: HR 6.90 (95% CI 4.15 to 11.45), 5 studies, 1038 participants; HbA1c5.7: HR 5.55 (95% CI 2.77 to 11.12), 4 studies, 5223 participants; HbA1c6.0: HR 10.10 (95% CI 3.59 to 28.43), 6 studies, 4532 participants. In subgroup analyses, there was no clear pattern of differences between geographic regions. We downgraded the evidence for the prognostic effect of IH versus normoglycaemia to low-certainty evidence due to study limitations because many studies did not adequately adjust for confounders. Imprecision and inconsistency required further downgrading due to wide 95% CIs and wide 95% prediction intervals (sometimes ranging from negative to positive prognostic factor to outcome associations), respectively.This evidence is up to date as of 26 February 2018. AUTHORS' CONCLUSIONS Overall prognosis of people with IH worsened over time. T2DM cumulative incidence generally increased over the course of follow-up but varied with IH definition. Regression from IH to normoglycaemia decreased over time but was observed even after 11 years of follow-up. The risk of developing T2DM when comparing IH with normoglycaemia at baseline varied by IH definition. Taking into consideration the uncertainty of the available evidence, as well as the fluctuating stages of normoglycaemia, IH and T2DM, which may transition from one stage to another in both directions even after years of follow-up, practitioners should be careful about the potential implications of any active intervention for people 'diagnosed' with IH.
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Affiliation(s)
- Bernd Richter
- Institute of General Practice, Medical Faculty of the Heinrich‐Heine‐University DüsseldorfCochrane Metabolic and Endocrine Disorders GroupPO Box 101007DüsseldorfGermany40001
| | - Bianca Hemmingsen
- Institute of General Practice, Medical Faculty of the Heinrich‐Heine‐University DüsseldorfCochrane Metabolic and Endocrine Disorders GroupPO Box 101007DüsseldorfGermany40001
| | - Maria‐Inti Metzendorf
- Institute of General Practice, Medical Faculty of the Heinrich‐Heine‐University DüsseldorfCochrane Metabolic and Endocrine Disorders GroupPO Box 101007DüsseldorfGermany40001
| | - Yemisi Takwoingi
- University of BirminghamInstitute of Applied Health ResearchEdgbastonBirminghamUKB15 2TT
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Lucht SA, Hennig F, Matthiessen C, Ohlwein S, Icks A, Moebus S, Jöckel KH, Jakobs H, Hoffmann B. Air Pollution and Glucose Metabolism: An Analysis in Non-Diabetic Participants of the Heinz Nixdorf Recall Study. ENVIRONMENTAL HEALTH PERSPECTIVES 2018; 126:047001. [PMID: 29616776 PMCID: PMC6071794 DOI: 10.1289/ehp2561] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 02/26/2018] [Accepted: 02/26/2018] [Indexed: 05/05/2023]
Abstract
BACKGROUND Despite the importance of understanding the connection between air pollution exposure and diabetes, studies investigating links between air pollution and glucose metabolism in nondiabetic adults are limited. OBJECTIVE We aimed to estimate the association of medium-term air pollution exposures with blood glucose and glycated hemoglobin A1c (HbA1c) among nondiabetics. METHODS This study included observations from nondiabetic participants (nobs=7,108) of the population-based Heinz Nixdorf Recall study at baseline (2000–2003) and follow-up examination (2006–2008). Daily fine particulate matter (aerodynamic diameter≤2.5 μm, PM2.5; aerodynamic diameter≤10 μm, PM10), accumulation mode particle number (PNAM), and nitrogen dioxide (NO2) exposures were estimated at participants’ residences using the spatiotemporal European Air Pollution Dispersion (EURAD) chemistry transport model. We evaluated the associations between medium-term air pollution exposures (28- and 91-d means) and glucose metabolism measures using mixed linear regression and adjusting for season, meteorology, and personal characteristics. A range of other exposure windows (1-, 2-, 3-, 7-, 14-, 45-, 60-, 75-, 105-, 120-, and 182-d means) were also evaluated to identify potentially relevant biological windows. RESULTS We observed positive associations between PM2.5 and PNAM exposures and blood glucose levels [e.g., 28-d PM2.5: 0.91 mg/dL (95% CI: 0.38, 1.44) per 5.7 μg/m3]. PM2.5, PM10, and PNAM exposures were positively associated with HbA1c [e.g., 91-d PM2.5: 0.07 p.p. (95% CI: 0.04, 0.10) per 4.0 μg/m3]. Mean exposures during longer exposure windows (75- to 105-d) were most strongly associated with HbA1c, whereas 7- to 45-d exposures were most strongly associated with blood glucose. NO2 exposure was not associated with blood glucose or with HbA1c. CONCLUSIONS Medium-term PM and PNAM exposures were positively associated with glucose measures in nondiabetic adults. These findings indicate that reducing ambient air pollution levels may decrease the risk of diabetes. https://doi.org/10.1289/EHP2561.
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Affiliation(s)
- Sarah A Lucht
- Environmental Epidemiology Group, Institute of Occupational, Social and Environmental Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Frauke Hennig
- Environmental Epidemiology Group, Institute of Occupational, Social and Environmental Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Clara Matthiessen
- Environmental Epidemiology Group, Institute of Occupational, Social and Environmental Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Simone Ohlwein
- Environmental Epidemiology Group, Institute of Occupational, Social and Environmental Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Andrea Icks
- Institute for Health Services Research and Health Economics, Centre for Health and Society, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
- Institute for Health Services Research and Health Economics, German Diabetes Center (DDZ), Düsseldorf, Germany
| | - Susanne Moebus
- Institute of Medical Informatics, University Hospital Essen, University of Duisburg-Essen, Biometry and Epidemiology (IMIBE), Essen, Germany
| | - Karl-Heinz Jöckel
- Institute of Medical Informatics, University Hospital Essen, University of Duisburg-Essen, Biometry and Epidemiology (IMIBE), Essen, Germany
| | - Hermann Jakobs
- Rhenish Institute for Environmental Research (RIU), University of Cologne, Cologne, Germany
| | - Barbara Hoffmann
- Environmental Epidemiology Group, Institute of Occupational, Social and Environmental Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
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Cucuzzella MT, Tondt J, Dockter NE, Saslow L, Wood TR. A low-carbohydrate survey: Evidence for sustainable metabolic syndrome reversal. JOURNAL OF INSULIN RESISTANCE 2017. [DOI: 10.4102/jir.v2i1.30] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background: Metabolic syndrome has become a significant problem, with the American Diabetes Association estimating the cost of diabetes and pre-diabetes in the United States alone to be $322 billion per year. Numerous clinical trials have demonstrated the efficacy of low-carbohydrate diets in reversing metabolic syndrome and its associated disorders.Aim: This study was designed to examine how voluntary adherents to a low-carbohydrate diet rate its effectiveness and sustainability using an online survey.Setting and methods: The 57-question survey was administered online and shared internationally via social media and ‘low-carb’ communities. Where appropriate, chi-squared tests and paired t-tests were used to analyse the responses.Results: There were 1580 respondents. The majority of respondents had consumed less than 100 g of carbohydrates per day for over a year, typically for reasons of weight loss or disease management. There was a reported decrease in waist circumference and weight with a simultaneous decrease in hunger and increase in energy level. Of those who provided laboratory values, the majority saw improvements in their HbA1c, blood glucose measurements, and lipid panel results. There was a reduction in usage of various medications, and 25% reported medication cost savings, with average monthly savings of $288 for those respondents. In particular, the usage of pain relievers and anti-inflammatories dropped with a simultaneous decreased rating of pain and increase in mobility.Conclusion: We conclude that low-carbohydrate diets are a sustainable method of metabolic syndrome reversal in a community setting.
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Boytsov S, Logunova N, Khomitskaya Y. Suboptimal control of lipid levels: results from the non-interventional Centralized Pan-Russian Survey of the Undertreatment of Hypercholesterolemia II (CEPHEUS II). Cardiovasc Diabetol 2017; 16:158. [PMID: 29246151 PMCID: PMC5732396 DOI: 10.1186/s12933-017-0641-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Accepted: 12/06/2017] [Indexed: 02/08/2023] Open
Abstract
Background Elevated levels of low-density lipoprotein cholesterol (LDL-C) and glycosylated hemoglobin (HbA1c) are risk factors for cardiovascular complications. This study evaluated LDL-C goal attainment in Russian clinical practice among patients with moderate to very high cardiovascular risk. The study also assessed LDL-C goal attainment in patients prescribed lipid-lowering therapy for primary compared with secondary cardiovascular disease (CVD) prevention, predictors of LDL-C goal attainment, and the proportion of individuals with diabetes mellitus who achieved HbA1c < 7%. Methods The Centralized Pan-Russian Survey on the Undertreatment of Hypercholesterolemia in Russia II (CEPHEUS II) was a multicenter, non-interventional, cross-sectional study conducted in the Russian Federation from September 2014 to November 2015. Participants were aged ≥ 18 years, were receiving a stable dose of lipid-lowering medication and had a moderate to very high cardiovascular risk. The primary variable was the proportion of patients reaching LDL-C goals established by the Fifth Joint European Task Force guidelines. Secondary analyses used McNemar and χ2 tests. Results Data from 2703 patients were analyzed; 91.2% had a very high cardiovascular risk and 24.0% had been diagnosed with diabetes mellitus. Overall, 17.4% of patients (95% confidence interval [CI] 15.9–18.8%) achieved LDL-C goals. Investigators estimated this proportion at 21.8% (95% CI 20.3–23.4%). LDL-C goals were achieved by more patients in the primary CVD prevention subgroup than in the secondary CVD prevention subgroup (19.7% vs 16.1%, p = 0.017). Patient-related factors associated with a decreased likelihood of achieving LDL-C goals included having ischemic heart disease or a family history of premature coronary heart disease, forgetting to take hypercholesterolemia treatment or considering it acceptable to miss prescribed doses more than once per week, and dissatisfaction with or concern about lipid-lowering therapy. Overall, 367/593 (61.9%) patients with diabetes mellitus and interpretable HbA1c results achieved HbA1c < 7%. Conclusions Hypercholesterolemia management is suboptimal in patients with moderate to very high cardiovascular risk in Russian clinical practice. Substantial opportunity remains to improve treatment target attainment and reduce the risk of cardiovascular complications. Lipid-modifying strategies may need to be intensified to reduce CVD risk in this setting. Trial registration ClinicalTrials.gov: NCT02230241 (registered 26 August 2014) Electronic supplementary material The online version of this article (10.1186/s12933-017-0641-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Sergey Boytsov
- The Russian Cardiology Research and Production Complex, Moscow, Russian Federation
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26
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Perreault L, Færch K, Gregg EW. Can Cardiovascular Epidemiology and Clinical Trials Close the Risk Management Gap Between Diabetes and Prediabetes? Curr Diab Rep 2017; 17:77. [PMID: 28766246 DOI: 10.1007/s11892-017-0899-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE OF REVIEW We reviewed published literature to determine the relationship between A1c and cardiovascular disease (CVD) and summarize the need and implications for CVD risk reduction with interventions, focusing in the prediabetic A1c range (<6.5%). RECENT FINDINGS Strong evidence supports a continuous relationship between A1c and CVD-even below the current levels of A1c-defined prediabetes and after adjustment for known risk factors for CVD. Clinical trials have demonstrated a reduction in CV morbidity and/or mortality when interventions are invoked in the prediabetic A1c range. Guidelines advocating CV risk factor management in prediabetes have not been widely adopted, subsequently leading to comparable coronary heart disease risk between people with prediabetes (HR = 1.9, 95% CI 1.7-2.1 vs normoglycemia) and diabetes itself (HR=2.0, 95% CI 1.8-2.2 vs no diabetes). This review highlights the missed opportunity to utilize multiple risk factor interventions to reduce CVD in high-risk people with prediabetes.
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Affiliation(s)
- Leigh Perreault
- University of Colorado Anschutz Medical Campus, mailstop F8106, P.O. Box 6511, Aurora, CO, 80045, USA.
| | | | - Edward W Gregg
- Centers for Disease Control and Prevention, Atlanta, GA, USA
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27
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Richter B, Hemmingsen B, Metzendorf MI, Takwoingi Y. Intermediate hyperglycaemia as a predictor for the development of type 2 diabetes: prognostic factor exemplar review. Cochrane Database Syst Rev 2017. [DOI: 10.1002/14651858.cd012661] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Bernd Richter
- Institute of General Practice, Medical Faculty of the Heinrich-Heine-University Düsseldorf; Cochrane Metabolic and Endocrine Disorders Group; PO Box 101007 Düsseldorf Germany 40001
| | - Bianca Hemmingsen
- Herlev University Hospital; Department of Internal Medicine; Herlev Ringvej 75 Herlev Denmark DK-2730
| | - Maria-Inti Metzendorf
- Institute of General Practice, Medical Faculty of the Heinrich-Heine-University Düsseldorf; Cochrane Metabolic and Endocrine Disorders Group; PO Box 101007 Düsseldorf Germany 40001
| | - Yemisi Takwoingi
- University of Birmingham; Institute of Applied Health Research; Edgbaston Birmingham UK B15 2TT
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Mongraw-Chaffin M, LaCroix AZ, Sears DD, Garcia L, Phillips LS, Salmoirago-Blotcher E, Zaslavsky O, Anderson CAM. A prospective study of low fasting glucose with cardiovascular disease events and all-cause mortality: The Women's Health Initiative. Metabolism 2017; 70:116-124. [PMID: 28403935 PMCID: PMC5402725 DOI: 10.1016/j.metabol.2017.02.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 02/03/2017] [Accepted: 02/09/2017] [Indexed: 01/14/2023]
Abstract
BACKGROUND While there is increasing recognition of the risks associated with hypoglycemia in patients with diabetes, few studies have investigated incident cause-specific cardiovascular outcomes with regard to low fasting glucose in the general population. OBJECTIVE We hypothesized that low fasting glucose would be associated with cardiovascular disease risk and all-cause mortality in postmenopausal women. METHODS To test our hypothesis, we used both continuous incidence rates and Cox proportional hazards models in 17,287 participants from the Women's Health Initiative with fasting glucose measured at baseline. Participants were separated into groups based on fasting glucose level: low (<80mg/dL), normal/reference (80-99mg/dL), impaired (100-125mg/dL), and diabetic (≥126mg/dL). RESULTS Participants were free of cardiovascular disease at enrollment, had mean age of 62years, and were 52% Caucasian, 24% African American, 8% Asian, and 12% Hispanic. Median follow-up was 15years. Graphs of continuous incidence rates compared to fasting glucose distribution exhibited evidence of a weak J-shaped association with heart failure and mortality that was predominantly due to participants with treated diabetes. Impaired and diabetic fasting glucose were positively associated with all outcomes. Associations for low fasting glucose differed, with coronary heart disease (HR=0.64 (0.42, 0.98)) significantly inverse; stroke (0.73 (0.48, 1.13)), combined cardiovascular disease (0.91 (0.73, 1.14)), and all-cause mortality (0.97 (0.79, 1.20)) null or inverse and not significant; and heart failure (1.27 (0.80, 2.02)) positive and not significant. CONCLUSIONS Fasting glucose at the upper range, but not the lower range, was significantly associated with incident cardiovascular disease and all-cause mortality.
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Affiliation(s)
- Morgana Mongraw-Chaffin
- Department of Medicine, University of California San Diego, San Diego, CA; Department of Epidemiology & Prevention, Wake Forest School of Medicine, Winston-Salem NC.
| | - Andrea Z LaCroix
- Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA
| | - Dorothy D Sears
- Department of Medicine, University of California San Diego, San Diego, CA; Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA
| | - Lorena Garcia
- Department of Public Health Services, University of California Davis, Davis, CA
| | - Lawrence S Phillips
- Atlanta VA Medical Center, Decatur, GA and Division of Endocrinology and Metabolism, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Elena Salmoirago-Blotcher
- The Miriam Hospital Centers for Behavioral and Preventive Medicine at the Warren Alpert Medical School, Brown University, Providence, RI
| | - Oleg Zaslavsky
- School of Nursing, University of Washington, Seattle, WA
| | - Cheryl A M Anderson
- Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA
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Glycemic markers and relation with arterial stiffness in Caucasian subjects of the MARK study. PLoS One 2017; 12:e0175982. [PMID: 28414819 PMCID: PMC5393622 DOI: 10.1371/journal.pone.0175982] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 04/03/2017] [Indexed: 12/20/2022] Open
Abstract
Background Effect of prediabetes and normal glucose on arterial stiffness remains controversial. The primary aim of this study was to investigate the relationship of fasting plasma glucose (FPG), postprandial glucose (PG) and glycosylated haemoglobin (HbA1c) with brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) in Caucasian adults. The secondary aim was to analyse this relationship by glycaemic status. Methods Cross-sectional study. Setting: Primary care. Participants: 2,233 subjects, 35–74 years. Measures: FPG (mg/dL) and HbA1c (%) of all subjects were measured using standard automated enzymatic methods. PG (mg/dL) was self-measured at home two hours after meals (breakfast, lunch and dinner) for one day using an Accu-chek ® glucometer. CAVI was measured using a VaSera VS-1500® device (Fukuda Denshi), and baPWV was calculated using a validated equation. Results CAVI and baPWV values were significantly higher in subjects with diabetes mellitus than in glucose normal and prediabetes groups (p<0.001). FPG, PG and HbA1c were positively associated with CAVI and baPWV. The β regression coefficient for: HbA1c was 0.112 (CI 95% 0.068 to 0.155) with CAVI, 0.266 (CI 95% 0.172 to 0.359) with baPWV; for PG was 0.006 (CI 95% 0.004 to 0.009 and for FPG was 0.005 (CI 95% 0.002 to 0.008) with baPWV; and for PG was 0.002 (CI 95% 0.001 to 0.003) and 0.003 (CI 95% 0.002 to 0.004) with CAVI (p<0.01 in all cases). When analysing by hyperglycaemic status, FPG, PG and HbA1c were positively associated with CAVI and baPWV in subjects with type 2 diabetes mellitus. Conclusion FPG, PG and HbA1c show a positive association with CAVI and baPWV, in Caucasian adults with intermediate cardiovascular risk factors. When analysing by hyperglycaemic status, the association is only maintained in subjects with type 2 diabetes mellitus. Trial registration Clinical Trials.gov Identifier: NCT01428934. Registered 2 September 2011. Retrospectively registered. Last updated September 8, 2016.
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Di Pino A, Urbano F, Piro S, Purrello F, Rabuazzo AM. Update on pre-diabetes: Focus on diagnostic criteria and cardiovascular risk. World J Diabetes 2016; 7:423-432. [PMID: 27795816 PMCID: PMC5065662 DOI: 10.4239/wjd.v7.i18.423] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 06/24/2016] [Accepted: 08/15/2016] [Indexed: 02/05/2023] Open
Abstract
Pre-diabetes, which is typically defined as blood glucose concentrations higher than normal but lower than the diabetes threshold, is a high-risk state for diabetes and cardiovascular disease development. As such, it represents three groups of individuals: Those with impaired fasting glucose (IFG), those with impaired glucose tolerance (IGT) and those with a glycated haemoglobin (HbA1c) between 39-46 mmol/mol. Several clinical trials have shown the important role of IFG, IGT and HbA1c-pre-diabetes as predictive tools for the risk of developing type 2 diabetes. Moreover, with regard to cardiovascular disease, pre-diabetes is associated with more advanced vascular damage compared with normoglycaemia, independently of confounding factors. In view of these observations, diagnosis of pre-diabetes is mandatory to prevent or delay the development of the disease and its complications; however, a number of previous studies reported that the concordance between pre-diabetes diagnoses made by IFG, IGT or HbA1c is scarce and there are conflicting data as to which of these methods best predicts cardiovascular disease. This review highlights recent studies and current controversies in the field. In consideration of the expected increased use of HbA1c as a screening tool to identify individuals with alteration of glycaemic homeostasis, we focused on the evidence regarding the ability of HbA1c as a diagnostic tool for pre-diabetes and as a useful marker in identifying patients who have an increased risk for cardiovascular disease. Finally, we reviewed the current evidence regarding non-traditional glycaemic biomarkers and their use as alternatives to or additions to traditional ones.
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Altay S, Onat A, Kaya A, Tusun E. Modulators of J-Shaped Association of HbA<sub>1c</sub> Levels with Mortality in Adults. Cardiology 2016; 135:50-1. [DOI: 10.1159/000445797] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Accepted: 03/23/2016] [Indexed: 11/19/2022]
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