A mixed meal tolerance test predicts onset of type 2 diabetes in Southwestern Indigenous adults.

Abstract Background/Objective: To identify predictors of incident type 2 diabetes using a mixed meal tolerance test (MMTT). Methods: Adult Indigenous Americans without diabetes (n=501) from a longitudinal cohort underwent at baseline a 4-hour MMTT, measures of body composition, an oral glucose tolerance test, an intravenous glucose tolerance test for acute insulin response (AIR), and a hyperinsulinemic-euglycemic clamp for insulin action (M). Plasma glucose responses from the MMTT were quantified by total and incremental area under the curve (AUC/iAUC). Results: At follow-up (median time 9.6 [inter-quartile range: 5.6-13.5] years), 169 participants were diagnosed with diabetes. Unadjusted Cox proportional hazards models, glucose AUC180-min (HR: 1.98, 95% CI: 1.67, 2.34, p<0.0001), AUC240-min (HR: 1.93, 95% CI: 1.62, 2.31, p<0.0001), and iAUC180-min (HR: 1.43, 95% CI: 1.20, 1.71, p<0.0001) were associated with an increased risk of diabetes. After adjustment for covariates (age, sex, body fat percentage, M, AIR, Indigenous American heritage) in three subsequent models, AUC180-min (HR: 1.44, 95% CI: 1.10, 1.88, p=0.007) and AUC240-min (HR: 1.41, 95% CI: 1.09, 1.84, p<0.01) remained associated with increased risk of diabetes. Conclusions: Glucose responses to a mixed meal predicted development of type 2 diabetes. This indicates that a mixed nutritional challenge provides important information on disease risk.