Effect of weight-maintaining ketogenic diet on glycemic control and insulin sensitivity in obese T2D subjects

• Published in: BMJ open diabetes research & care 2024-10, Vol.12 (5), p.e004199
• Main Authors: Merovci, Aurora, Finley, Brittany, Hansis-Diarte, Andrea, Neppala, Sivaram, Abdul-Ghani, Muhammad A, Cersosimo, Eugenio, Triplitt, Curtis, DeFronzo, Ralph A
• Format: Article
• Language: English
• Subjects: 3-Hydroxybutyric Acid - blood; Adult; Antidiabetics; Blood Glucose - analysis; Body fat; Body mass index; Carbohydrates; Catheters; Diabetes; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diet therapy; Diabetes Mellitus, Type 2 - metabolism; Diet; Diet, Ketogenic - methods; Female; Follow-Up Studies; Food; Glucagon; Glucose; Glucose Tolerance Test; Glycemic Control - methods; Humans; Insulin - blood; Insulin Resistance; Intervention; Ketones; Male; Metabolism; Middle Aged; Nutrition research; Obesity; Obesity - diet therapy; Obesity - metabolism; Obesity Studies; Original Research; Overweight; Peptides; Plasma; Proteins; Weight control; Weight Loss
• ISSN: 2052-4897; 2052-4897
• DOI: 10.1136/bmjdrc-2024-004199

IntroductionLow carbohydrate ketogenic diets have received renewed interest for the treatment of obesity and type 2 diabetes. These diets promote weight loss, improve glycemic control, and reduce insulin resistance. However, whether the improvements in glycemic control and insulin sensitivity are secondary to the weight loss or result from a direct effect of hyperketonemia is controversial.Research design and methods29 overweight obese subjects were randomized to one of three dietary interventions for 10 days: (1) Weight-maintaining standard diet; (2) Weight-maintaining ketogenic diet; (3) Weight-maintaining ketogenic diet plus supplementation with the ketone ester of beta-hydroxybutyrate (β-OH-B), 8 g every 8 hours. At baseline, all subjects had oral glucose tolerance test, 2-step euglycemic insulin clamp (20 mU/m2.min and 60 mU/m2.min) with titrated glucose and indirect calorimetry.ResultsBody weight, fat content, and per cent body fat (DEXA) remained constant over the 10-day dietary intervention period in all three groups. Plasma β-OH-B concentration increased twofold, while carbohydrate oxidation decreased, and lipid oxidation increased demonstrating the expected shifts in substrate metabolism with institution of the ketogenic diet. Glucose tolerance either decreased slightly or remained unchanged in the two ketogenic diet groups. Whole body (muscle), liver, and adipose tissue sensitivity to insulin remained unchanged in all 3 groups, as did the plasma lipid profile and blood pressure.ConclusionIn the absence of weight loss, a low carbohydrate ketogenic diet has no beneficial effect on glucose tolerance, insulin sensitivity, or other metabolic parameters.