Introduction and Objective: We previously (BMJ Open Diab: e004199, 2024) showed that a 10-day weight-maintaining ketogenic diet in individuals with type 2 diabetes did not change OGTT responses or insulin sensitivity (two-step euglycemic clamp) but increased insulin secretion.To examine the effect of the 10-day weight-maintaining ketogenic or standard diet on fasting plasma glucagon and OGTT glucagon responses.Methods: Ten individuals with type 2 diabetes (A1c = 8.0 ± 0.2%; BMI 33 ± 1.0 kg/m²) consumed a weight-maintaining ketogenic diet (80% fat, 15% protein, 5% carbohydrate) and eight individuals with type 2 diabetes (A1c = 8.0 ± 0.1%; BMI 34 ± 1.5 kg/m²) consumed a weight-maintaining standard diet (35% protein, 45% carbohydrate, 20% fat) for 10 days. Plasma glucagon was measured after an overnight fast and during a 2-hour 75g OGTT. Plasma Insulin, C-peptide, FFA, and beta-hydroxy-butyrate were measured.Results: Fasting plasma glucagon increased after the ketogenic diet (56 ± 8 to 89 ± 13 pg/mL, p < 0.05). Mean OGTT plasma glucagon increased from 60 ± 7 to 82 ± 12 pg/mL (p = 0.12). Mean OGTT plasma insulin and C-peptide responses increased from 35 ± 4 to 56 ± 9 µU/mL and from 7.8 ± 0.6 to 11.5 ± 0.9 ng/mL, respectively (both p < 0.05). In the control group, fasting and OGTT plasma glucagon concentrations were unchanged (both p > 0.05). Efficacy of the ketogenic diet was confirmed by elevated fasting BOHB and increased lipid oxidation/decreased carbohydrate oxidation (indirect calorimetry).Conclusion: A short-term ketogenic diet in obese type 2 diabetic subjects increases fasting plasma glucagon and glucagon and insulin responses during the OGTT, whereas no changes occurred with the standard diet. These findings suggest a dual-hormone regulatory pattern in which elevated glucagon and insulin coexist with enhanced ketone production.
M. Lalovich: None. A. Merovci: None. A.O. Chavez-Velazquez: Advisory Panel; Ended; Crinetics Pharmaceuticals, Inc. A.A. Hansis-Diarte: None. H. Zaitoon: None. E.Y. Feigin: None. R. Belfort DeAguiar: None. M. Abdul-Ghani: None. R.A. DeFronzo: Advisory Panel; Ended; AstraZeneca. Research Support; Current; AstraZeneca. Advisory Panel; Current; Novo Nordisk. Research Support; Current; Eli Lilly and Company. Advisory Panel; Current; Corcept Therapeutics. Speaker’s Bureau; Current; Corcept Therapeutics. Consultant; Current; Alnylam Pharmaceuticals, Inc. Advisory Panel; Current; Regeneron Pharmaceuticals Inc., Aardvark.
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