Pancreatic β-cell Hypersecretion Of Insulin In Intermediate Versus Morning Chronotype

Insulin resistance promotes hypersecretion of insulin from pancreatic β-cells to preserve normoglycemia. Declines in β-cell function over time, however, cause Type 2 Diabetes (T2D). Disruption of circadian rhythms is suggested to promote impaired β-cell function. While later chronotypes are suggested to have greater T2D risk, no data exist characterizing β-cell function among chronotypes. PURPOSE: To assess β-cell function in relation to incretin hormones in morning (MC) and intermediate (IC) chronotypes with obesity. METHODS: Adults with obesity (n = 46, 9 M, 55 ± 1.7y, 36.8 ± 1.0 kg/m2) were grouped as MC or IC per the Morningness-Eveningness Questionnaire (MEQ). Glucose, insulin, C-peptide, GIP, and GLP-1 were collected in 30 min intervals during a 120 min 75 g OGTT. Total area under the curve (tAUC) was calculated using the trapezoidal method. Early (0-30 min) and total-phase (0-120 min) glucose-stimulated insulin secretion (GSIS: C-peptide/Glucose) and β-cell function (disposition index (DI): GSIS scaled to insulin sensitivity) were determined. Peripheral insulin sensitivity (glucose infusion rate (GIR)) and hepatic insulin resistance (HOMA-IR) were assessed from a 120 min euglycemic hyperinsulinemic clamp (40 mU/m2/min, 90 mg/dl). Body composition (DXA) and aerobic fitness (VO2max) were also measured. RESULT: No difference in body composition, peripheral insulin sensitivity or incretins were seen. IC had higher hepatic insulin resistance (P = 0.03) and lower VO2max (P < 0.01) versus MC. However, IC had higher early phase C-peptide tAUC0-30min (P = 0.04) and DI0-30min when corrected to peripheral insulin sensitivity (P = 0.059). Early phase C-peptide tAUC0-30min associated with lower peripheral insulin sensitivity (r = -0.38, P < 0.01) and VO2max (r = -0.40, P < 0.01), but higher lean body mass (r = 0.47, P < 0.01). Hepatic insulin resistance correlated with early phase C-peptide tAUC0-30min (r = 0.35, P < 0.02) and lower total phase GLP tAUC0-120min (r = -0.40, P = 0.04). CONCLUSION: IC hypersecreted insulin to possibly compensate for peripheral and hepatic insulin resistance and regulate post-prandial glycemia compared to MC. Additional β-cell function investigation in chronotypes is needed to optimize fitness mediated T2D risk reduction. Supported by NIH RO1-HL130296 NIH RO1-HL130296