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

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.