In type 2 diabetes, high blood glucose levels are associated with increased glucagon levels and insufficient suppression of endogenous glucose production (EGP). Notably, glutamine, a gluconeogenic amino acid, is decreased compared to healthy individuals.

We randomized 32 overweight patients with type 2 diabetes to either a Paleolithic diet (PD) or a Paleolithic diet combined with supervised exercise (PD-EX). Study duration was 12 weeks. Subjects conducted a solid mixed meal test: glucagon, insulin and glucose were measured at 0, 30, 60, 120 and 180 min with calculation of the total area under the curve for the response. On another study day, fasting glutamine was measured with GC-MS and suppression of EGP was examined with the hyperinsulinemic euglycemic clamp technique with [6,6-2H2]glucose as a tracer and with an insulin infusion of 40 mIU/m2/min.

Median weight loss was 7 kg in both study groups. Fasting glucose and fasting insulin decrease significantly only in the PD-EX group. Postprandial glucose decreased by 13% in the PD group (P<0.05) and by 26% in the PD-EX group (P<0.01), without difference between groups. Fasting glucagon tended to decrease in both study groups. Postprandial glucagon decreased by 22% in the PD-group (P<0.01) and by 21% in the PD-EX group (P=0.13). Fasting glutamine increased non-significantly in both groups. Suppression of EGP increased by 26% in the PD group (P<0.05) and by 10% in the PD-EX group (P=0.75). During the intervention, the increased suppression of EGP was associated with a) reduction of postprandial glucagon levels (rS=-0.65, P<0.01), b) decreasing fasting glucagon (rS=-0.51, P<0.05) and c) the increasing fasting glutamine levels (rS=0.51, P<0.05).

We conclude that glucagon, an activator of EGP, decreases in concert with improved suppression of EGP during weight loss in type 2 diabetes patients. An increase in plasma glutamine may be due to decreased gluconeogenesis.


J. Otten: None. A. Stomby: None. M. Waling: None. E. Chorell: None. M. Ryberg: None. M.B. Svensson: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Zealand Pharma A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., AstraZeneca. Research Support; Self; Danish Diabetes Academy, Novo Nordisk Foundation. Other Relationship; Self; Antag Therapeutics. Other Relationship; Spouse/Partner; Antag Therapeutics. T. Olsson: None.

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