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Differential Islet and Incretin Hormone Responses in Morning Versus Afternoon after Standardized Meal in Healthy Men

Department of Clinical Sciences (O.L., M.S.W., J.V., B.A.), Lund University, SE-221 84 Lund, Sweden; National Research Council (A.M.), I-35127 Padua, Italy; Department of Biomedical Sciences (C.F.D.), Copenhagen University, DK-2300 Copenhagen, Denmark; and Merck A/S (R.D.C.), DK-2600 Glostrup, Denmark

Address all correspondence and requests for reprints to: Dr. Bo Ahrén, Department of Clinical Sciences, Lund, B11 BMC, SE-221 84 Lund, Sweden. E-mail: bo.ahren{at}med.lu.se.

Context: The insulin response to meal ingestion is more rapid in the morning than in the afternoon. Whether this is explained by a corresponding variation in the incretin hormones is not known.

Objective: Our objective was to assess islet and incretin hormones after meal ingestion in the morning vs. afternoon.

Design, Settings, and Participants: Ingestion at 0800 and 1700 h of a standardized meal (524 kcal) in healthy lean males (n = 12) at a University Clinical Research Unit.

Main Outcome Measures: We assessed early (30-min) area under the curve (AUC30) of plasma levels of insulin and intact (i) and total (t) glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) after meal ingestion and made an estimation of β-cell function by model analysis of glucose and C-peptide.

Results: Peak glucose was lower in the morning than in the afternoon (6.1 ± 0.2 vs. 7.4 ± 0.3 mmol/liter, P = 0.001). AUC30_insulin (4.9 ± 0.6 vs. 2.8 ± 0.4 nmol/liter · 30 min; P = 0.012), AUC30_tGLP-1 (300 ± 40 vs. 160 ± 30 pmol/liter · 30 min, P = 0.002), AUC30_iGIP (0.7 ± 0.1 vs. 0.3 ± 0.1 nmol/liter · 30 min, P = 0.002), and AUC30_tGIP (1.1 ± 0.1 vs. 0.6 ± 0.1nmol/liter · min, P = 0.007) were all higher in the morning. AUC30_iGLP-1 (r = 0.68; P = 0.021) and AUC30_iGIP (r = 0.78; P = 0.001) both correlated to AUC30_insulin. Model analysis of β-cell function showed a higher first-hour potentiation factor in the morning (P = 0.009). This correlated negatively with the 60-min glucose level (r = –0.63; P < 0.001).

Conclusions: The early release of GLP-1 and GIP are more pronounced in the morning than in the afternoon. This may contribute to the more rapid early insulin response, more pronounced potentiation of β-cell function, and lower glucose after the morning meal.