Dataset Information

Long-term variability of glycemic markers and risk of all-cause mortality in type 2 diabetes: the Look AHEAD study.

ABSTRACT:

Introduction

Glycemic variability may predict poor outcomes in type 2 diabetes. We evaluated the associations of long-term variability in glycosylated hemoglobin (HbA_1C) and fasting plasma glucose (FPG) with cardiovascular disease (CVD) and death among individuals with type 2 diabetes.

Research design and methods

We conducted a secondary, prospective cohort analysis of the Look AHEAD (Action for Health in Diabetes) data, including 3560 participants who attended four visits (baseline, 12 months, 24 months, and 36 months) at the outset. Variability of HbA_1C and FPG was assessed using four indices across measurements from four study visits. Participants without CVD during the first 36 months were followed for incident outcomes including a CVD composite (myocardial infarction, stroke, hospitalization for angina, and CVD-related deaths), heart failure (HF), and deaths.

Results

Over a median follow-up of 6.8 years, there were 164 deaths from any cause, 33 CVD-related deaths, 91 HF events, and 340 participants experienced the CVD composite. Adjusted HRs comparing the highest to lowest quartile of SD of HbA_1C were 2.10 (95% CI 1.26 to 3.51), 3.43 (95% CI 0.95 to 12.38), 1.01 (95% CI 0.69 to 1.46), and 1.71 (95% CI 0.69 to 4.24) for all-cause mortality, CVD mortality, CVD composite and HF, respectively. The equivalent HRs for highest versus lowest quartile of SD of FPG were 1.66 (95% CI 0.96 to 2.85), 2.20 (95% CI 0.67 to 7.25), 0.94 (95% CI 0.65 to 1.35), and 2.05 (95% CI 0.80 to 5.31), respectively.

Conclusions

A greater variability in HbA_1C was associated with elevated risk of mortality. Our findings underscore the need to achieve normal and consistent glycemic control to improve clinical outcomes among individuals with type 2 diabetes.

SUBMITTER: Kaze AD

PROVIDER: S-EPMC7705503 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Long-term variability of glycemic markers and risk of all-cause mortality in type 2 diabetes: the Look AHEAD study.

Kaze Arnaud D AD Santhanam Prasanna P Erqou Sebhat S Ahima Rexford S RS Echouffo-Tcheugui Justin Basile JB

BMJ open diabetes research & care 20201101 2

<h4>Introduction</h4>Glycemic variability may predict poor outcomes in type 2 diabetes. We evaluated the associations of long-term variability in glycosylated hemoglobin (HbA<sub>1C</sub>) and fasting plasma glucose (FPG) with cardiovascular disease (CVD) and death among individuals with type 2 diabetes.<h4>Research design and methods</h4>We conducted a secondary, prospective cohort analysis of the Look AHEAD (Action for Health in Diabetes) data, including 3560 participants who attended four vis ...[more]

PMID: 33257421

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Project description:BackgroundAtrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (T2DM). Glycemic variability (GV) is associated with risk of micro- and macrovascular diseases. However, whether the GV can increase the risk of AF remains unknown.MethodsThe cohort study used a database from National Taiwan University Hospital, a tertiary medical center in Taiwan. Between 2014 and 2019, a total of 27,246 adult patients with T2DM were enrolled for analysis. Each individual was assessed to determine the coefficients of variability of fasting glucose (FGCV) and HbA1c variability score (HVS). The GV parameters were categorized into quartiles. Multivariate Cox regression models were employed to estimate the relationship between the GV parameters and the risk of AF, transient ischemic accident (TIA)/ischemic stroke and mortality in patients with T2DM.ResultsThe incidence rates of AF and TIA/ischemic stroke were 21.31 and 13.71 per 1000 person-year respectively. The medium follow-up period was 70.7 months. In Cox regression model with full adjustment, the highest quartile of FGCV was not associated with increased risk of AF [Hazard ratio (HR): 1.12, 95% confidence interval (CI) 0.96-1.29, p = 0.148] or TIA/ischemic stroke (HR: 1.04, 95% CI 0.83-1.31, p = 0.736), but was associated with increased risk of total mortality (HR: 1.33, 95% CI 1.12-1.58, p < 0.001) and non-cardiac mortality (HR: 1.41, 95% CI 1.15-1.71, p < 0.001). The highest HVS was significantly associated with increased risk of AF (HR: 1.29, 95% CI 1.12-1.50, p < 0.001), total mortality (HR: 2.43, 95% CI 2.03-2.90, p < 0.001), cardiac mortality (HR: 1.50, 95% CI 1.06-2.14, p = 0.024) and non-cardiac mortality (HR: 2.80, 95% CI 2.28-3.44, p < 0.001) but was not associated with TIA/ischemic stroke (HR: 0.98, 95% CI 0.78-1.23, p = 0.846). The Kaplan-Meier analysis showed significantly higher risk of AF, cardiac and non-cardiac mortality according to the magnitude of GV (log-rank test, p < 0.001).ConclusionsOur data demonstrate that high GV is independently associated with the development of new-onset AF in patients with T2DM. The benefit of maintaining stable glycemic levels to improve clinical outcomes warrants further studies.

Project description:Aims/hypothesisThe aim of this study was to evaluate the effects on diabetic peripheral neuropathy (DPN) of a long-term intensive lifestyle intervention (ILI) programme designed to achieve and maintain weight loss.MethodsBeginning in 2001, a total of 5145 overweight or obese people with type 2 diabetes, aged 45-76 years, participating in the multicentre Look AHEAD (Action for Health in Diabetes) study were randomised to ILI (n = 2570) or to a diabetes support and education (DSE) control group (n = 2575) using a web-based management system at the study coordinating centre at Wake Forest School of Medicine (Winston-Salem, NC, USA). Randomisation was stratified by clinical centre and was not revealed to the clinical staff responsible for obtaining data on study outcomes. Because of the nature of the study, patients and the local centre interventionists were not blinded to the study group assignments. In addition, the coordinating centre staff members responsible for data management and statistical analyses were not blinded to the study group assignments. The interventions were terminated in September 2012, 9-11 years after randomisation, but both groups continued to be followed for both primary and secondary outcomes. Neuropathy evaluations included the Michigan Neuropathy Screening Instrument (MNSI) questionnaire completed at baseline in 5145 participants (ILI n = 2570, DSE n = 2575) and repeated annually thereafter and the MNSI physical examination and light touch sensation testing conducted in 3775 participants (ILI n = 1905, DSE n = 1870) 1-2.3 years after discontinuation of the intervention.ResultsAt baseline, the MNSI questionnaire scores were 1.9 ± 0.04 and 1.8 ± 0.04 in the ILI and DSE groups, respectively (difference not statistically significant). After 1 year, when weight loss was maximal in the ILI group (8.6 ± 6.9%) compared with DSE (0.7 ± 4.8%), the respective MNSI scores were 1.7 ± 0.04 and 2.0 ± 0.04 (p ≤ 0.001). Subsequently, the scores increased gradually in both groups, but remained significantly lower in the ILI group for the first 3 years and at the end of follow-up. In both groups, there was a significant association between changes in the MNSI scores and changes in body weight, HbA1c and serum lipids. There were no significant between-group differences in the proportions of participants with MNSI physical examination scores ≥2.5, considered to be indicative of diabetic neuropathy. The light touch sensation measured separately in either the right or left big toes (halluces) did not differ between ILI and DSE, but when the data were combined for both toes, light touch was better preserved in the ILI group.Conclusions/interpretationILI resulted in a significant decrease in questionnaire-based DPN, which was associated with the magnitude of weight loss. In both the ILI and DSE groups, changes in the MNSI score were also related to changes in HbA1c and lipids. There were no significant effects of ILI on physical examination measures of DPN conducted 1-2.3 years after termination of the active intervention, except for light touch sensation, which was significantly better in the ILI group when measurements were combined for both toes. However, a potential limiting factor to the interpretation of the physical examination data is that no baseline studies are available for comparison.Trial registrationClinicalTrials.gov NCT00017953.FundingThis work was funded by the National Institutes of Health through cooperative agreements with the National Institute of Diabetes and Digestive and Kidney Diseases.

Dataset Information

Long-term variability of glycemic markers and risk of all-cause mortality in type 2 diabetes: the Look AHEAD study.

Introduction

Research design and methods

Results

Conclusions

Publications

Long-term variability of glycemic markers and risk of all-cause mortality in type 2 diabetes: the Look AHEAD study.

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