Higher glucose and insulin responses to a mixed meal are associated with increased risk of diabetic retinopathy in Indigenous Americans

Purpose Prior research has focused on glucose/insulin responses to meal challenges to create personalized diets to improve health, though it is unclear if these responses predict chronic diseases. We aimed to identify glucose and insulin responses to a mixed meal tolerance test (MMTT) that predict the development of diabetic retinopathy (DR) and compare the predictive abilities with the oral glucose tolerance test (OGTT). Methods Indigenous American adults without diabetes (n = 168) underwent a 4-h MMTT, body composition assessment, and a 3-h OGTT at baseline. During follow-up (median 13.4 years), DR was diagnosed by direct ophthalmoscopy (n = 28) after onset of type 2 diabetes. Total and incremental area under the curve (AUC and iAUC) were calculated from glucose/insulin responses after the MMTT and OGTT. Results In separate Cox proportional hazards models adjusted for age, sex, and body fat (%), MMTT glucose AUCs (180-min and 240-min) and iAUC (180-min) predicted DR (HR 1.50, 95% CI 1.06, 2.12; HR 1.50, 95% CI 1.05, 2.14; HR 1.58, 95% CI 1.01, 2.46). The predictive abilities were better than the fasting OGTT glucose (p 0.05). Conclusions Higher MMTT glucose and insulin responses predicted DR and were comparable to the OGTT, supporting the use of a meal challenge for precision nutrition. Trial registrations : Clinical Trial Registry: ClinicalTrials.gov identifier: NCT00340132, NCT00339482.