Plasma lactate and diabetes risk in 8045 participants of the Atherosclerosis Risk in Communities Study

Purpose: Determinants of oxidative capacity, such as fitness and level of adiposity, are strongly associated with type 2 diabetes. Whether decreased oxidative capacity itself is a cause or consequence of insulin resistance and diabetes is unknown. Methods: We examined the association of plasma lactate, a marker of oxidative capacity, with incident diabetes in 8045 participants from the Atherosclerosis Risk in Communities (ARIC) Study with no history of subclinical or diagnosed diabetes at baseline (1996-1998). Incident diabetes was self-reported during annual telephone calls. Results: During a median follow-up of 12 years, there were 1513 new cases of diabetes. In Cox proportional hazards models, baseline plasma lactate (per 10 mg/dL) was significantly associated with diabetes (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43), even after adjustment for diabetes risk factors, fasting glucose, and insulin. The upper quartile of baseline lactate (ge;8.1 mg/dL) was also significantly associated with diabetes risk (hazard ratio, 1.20; 95% confidence interval, 1.02-1.41) compared with the lowest quartile (≤5.1 mg/dL). Significant associations persisted among persons without insulin resistance (homeostatic model assessment insulin resistance index < 2.6 U) (P-trend < .01). Conclusions: These findings suggest that low oxidative capacity may precede diabetes. Future studies should evaluate the physiological origins of elevated lactate to better understand its possible role in the pathogenesis of diabetes.