Habitual Intake of Dietary Dicarbonyls is Associated with Greater Insulin Sensitivity and Lower Prevalence of Type 2 Diabetes: The Maastricht Study

Background: Dicarbonyls are reactive precursors of advanced glycation end-products (AGEs). Dicarbonyls are formed endogenously, but also during food processing. Circulating dicarbonyls are positively associated with insulin resistance and type 2 diabetes, but the consequences of dietary dicarbonyls are unknown. Objectives: We aimed to examine the associations of dietary intake of dicarbonyls with insulin sensitivity, 13-cell function, and the prevalence of pre -diabetes or type 2 diabetes. Methods: In 6282 participants (aged 60 & PLUSMN; 9 y; 50% men, 23% type 2 diabetes [oversampled]) of the population-based cohort the Maastricht Study, we estimated the habitual intake of the dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) using food frequency question-naires. Insulin sensitivity (n = 2390), 13-cell function (n = 2336), and glucose metabolism status (n = 6282) were measured by a 7-point oral glucose tolerance test. Insulin sensitivity was assessed as the Matsuda index. Additionally, insulin sensitivity was measured as HOMA2-IR (n = 2611). 13-cell function was assessed as the C-peptidogenic index, overall insulin secretion, glucose sensitivity, potentiation factor, and rate sensitivity. Cross-sectional associations of dietary dicarbonyls with these outcomes were investigated using linear or logistic regression adjusting for age, sex, cardiometabolic risk factors, lifestyle, and dietary factors. Results: Higher dietary MGO and 3-DG intakes were associated with greater insulin sensitivity after full adjustment, indicated by both a higher Matsuda index (MGO: Std. 13 [95% CI] = 0.08 [0.04, 0.12]; 3-DG: 0.09 [0.05, 0.13]) and a lower HOMA2-IR (MGO: Std. 13 = -0.05 [-0.09, -0.01]; 3-DG: -0.04 [-0.08, -0.01]). Moreover, higher MGO and 3-DG intakes were associated with a lower prevalence of newly diagnosed type 2 diabetes (OR [95% CI] = 0.78 [0.65, 0.93] and 0.81 [0.66, 0.99]). There were no consistent associations of MGO, GO, and 3-DG intakes with 13-cell function. Conclusion: Higher habitual consumption of the dicarbonyls MGO and 3-DG was associated with better insulin sensitivity and lower prevalence of type 2 diabetes, after excluding individuals with known diabetes. These novel observations warrant further exploration in prospective cohorts and intervention studies.