Plasma lactate and diabetes risk in 8045 participants of the atherosclerosis risk in communities study

Abstract

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 (≥ 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.

Keywords: ARIC; Cohort; Diabetes risk; Lactate.

Conflict of interest statement

Conflict of interest

The authors declare that there is no conflict of interest associated with this manuscript.

Copyright © 2013 Elsevier Inc. All rights reserved.

Figures

Figure 1

Adjusted hazard ratios (solid line) for incident self-reported diabetes between ARIC visit 4 and April, 2011 according to baseline concentrations of plasma lactate values from a restricted cubic spline model. Dashed lines are the 95% confidence intervals. The models were expressed relative to the 25th percentile of lactate with knots specified at the 25th, 50th, and 75th percentiles and were adjusted for age, gender, race-ARIC center, education, diagnosis of hypertension, prevalent coronary disease, smoking status, parental history of diabetes, body mass index, waist circumference, serum uric acid, log10-transformed triglycerides, low density lipoprotein cholesterol, and high density lipoprotein cholesterol. The plot was truncated at the 1st and 99th percentiles of lactate. The hazard ratios are shown on a natural log scale. In addition, overlaid are kernel density plots depicting the distribution plasma lactate by participants who did not develop diabetes (dash) and participants who did develop diabetes (solid).