Changes in isoleucine, sarcosine, and dimethylglycine during OGTT as risk factors for diabetes.

Abstract

Current metabolomics studies in diabetes have focused on the fasting state, while only few addressed the satiated state. We combined oral glucose tolerance test (OGTT) and metabolomics to examine metabolite level changes in populations with different glucose tolerance statuses and evaluate the potential risk of these changes for diabetes. We grouped participants into those with normal glucose tolerance (NGT), impaired glucose regulation (IGR), and newly diagnosed type 2 diabetes (NDM). During the OGTT, serum was collected at 0, 30, 60, 120, and 180 min. We evaluated the changes in metabolite levels during OGTT and compared metabolic profiles among the three groups. The relationship between metabolite levels during the OGTT and risk of diabetes and prediabetes was analyzed using generalized estimating equation (GEE). The regression results were adjusted for sex, body mass index, fasting insulin levels, heart rate, smoking status, and blood pressure. Glucose intake altered metabolic profile and induced an increase in glycolytic intermediates and decrease in amino acids, glycerol, ketone bodies, and triglycerides. Isoleucine levels differed between NGT and NDM groups and between NGT and IGR groups. Changes in sarcosine levels during OGTT in diabetes groups were opposite to those in glycine levels. GEE analysis revealed that during OGTT, isoleucine, sarcosine, and acetic acid levels were associated with NDM risks, while isoleucine and acetate levels with IGR risks. Metabolic profiles differ after glucose induction in individuals with different glucose tolerance statuses. Changes in metabolite levels during OGTT are potential risk factors for diabetes development.