Circulating Lactate Is Elevated in Prediabetes Phenotypes Compared with Normal Glucose Tolerant Counterparts: 1392 Board #154 May 30 10:30 AM - 12:00 PM

PURPOSE: Prediabetes can be characterized as impaired fasting glucose (IFG) with or without impaired glucose tolerance (IGT; 2-hr blood glucose). IFG is depicted by impaired liver insulin sensitivity, while IFG+IGT is related to reduced liver and muscle insulin sensitivity. Lactate is a byproduct of non-oxidative glycolysis that may mediate altered glucose regulation. However, whether people with IFG and/or IFG+IGT have elevated lactate concentrations compared to normal glucose tolerant (NGT) controls is unclear. We hypothesized that individuals with IFG and IFG+IGT would have higher lactate levels than NGT controls in relation to glucose metabolism. METHODS: Forty-one obese adults (Age: 54.8±2.0yrs; BMI: 36.0±1.0kg/m2; 34F/7M) were screened for NGT, IFG, or IFG+IGT (75g OGTT, ADA criteria) following an overnight fast. Plasma lactate, glucose, and insulin were measured during a 120min 75g OGTT. The oral minimal model was used as an estimate for insulin sensitivity. Aerobic fitness (VO2peak), fasting substrate oxidation (respiratory exchange ratio (RER), indirect calorimetry) and body composition (bioelectrical impedance) were also tested. RESULTS: There were no differences in VO2peak, body fat or fasting RER across groups. Individuals with IFG+IGT had lower insulin sensitivity compared with IFG and NGT (P<0.01). However, both IFG and IFG+IGT had increased lactate tAUC compared to NGT (P<0.01 and P=0.01, respectively). Increased lactate tAUC correlated with fasting glucose (r=0.33, P=0.03) and reduced VO2peak (r=-0.34, P=0.03). Fasting lactate also related to fasting RER (r=0.31, P=0.04). CONCLUSION: Despite no differences between prediabetes phenotypes, adults with IFG and IFG+IGT have elevated lactates compared to NGT controls. Lactate tAUC directly associates with fasting glucose and fitness, but not insulin sensitivity. These data suggest that fitness may mediate lactate metabolism via the liver. Future work is warranted to determine the mechanism by which lactate influences type 2 diabetes risk.