Diurnal pattern to insulin secretion and insulin action in healthy individuals

Abstract

Evaluation of the existence of a diurnal pattern of glucose tolerance after mixed meals is important to inform a closed-loop system of treatment for insulin requiring diabetes. We studied 20 healthy volunteers with normal fasting glucose (4.8 ± 0.1 mmol/L) and HbA(1c) (5.2 ± 0.0%) to determine such a pattern in nondiabetic individuals. Identical mixed meals were ingested during breakfast, lunch, or dinner at 0700, 1300, and 1900 h in randomized Latin square order on 3 consecutive days. Physical activity was the same on all days. Postprandial glucose turnover was measured using the triple tracer technique. Postprandial glucose excursion was significantly lower (P < 0.01) at breakfast than lunch and dinner. β-Cell responsivity to glucose and disposition index was higher (P < 0.01) at breakfast than lunch and dinner. Hepatic insulin extraction was lower (P < 0.01) at breakfast than dinner. Although meal glucose appearance did not differ between meals, suppression of endogenous glucose production tended to be lower (P < 0.01) and insulin sensitivity tended to be higher (P < 0.01) at breakfast than at lunch or dinner. Our results suggest a diurnal pattern to glucose tolerance in healthy humans, and if present in type 1 diabetes, it will need to be incorporated into artificial pancreas systems.

FIG. 1.

A: Plasma glucose and insulin concentrations obtained after labeled breakfast, lunch, and dinner. B: Plasma C-peptide and glucagon concentrations obtained after labeled breakfast, lunch, and dinner.

FIG. 2.

A: R_a of meal glucose, rate of EGP, and rate of R_d obtained after labeled breakfast, lunch, and dinner. B: Percent suppression of EGP and percent increase in R_d obtained after labeled breakfast, lunch, and dinner. *P < 0.05 vs. breakfast.

FIG. 3.

A: Indices of β-cell responsiveness Φ_s, Φ_d, and Φ_total obtained after labeled breakfast, lunch, and dinner. *P < 0.05 vs. breakfast. B: Indices of hepatic insulin extraction (basal and total) were obtained after labeled breakfast, lunch, and dinner. *P < 0.05 vs. breakfast.

FIG. 4.

S_i, DI static, DI dynamic, and DI total obtained after labeled breakfast, lunch, and dinner. *P < 0.05 vs. breakfast.

FIG. 5.

A: Model-based S_i for all subjects for each meal shown individually with log-transformed data. The boldface line indicates the average estimates for each meal. B: Model-based DI total for all subjects for each meal shown individually with log-transformed data. The boldface line indicates the average estimates for each meal. (A high-quality color representation of this figure is available in the online issue.)