Despite comparable weight loss and gains in skeletal muscle insulin sensitivity across 3 dietary approaches, the very-low-carbohydrate ketogenic diet may have increased hepatic insulin sensitivity more among participants.
In a randomized clinical trial, investigators randomly assigned participants aged 18 to 55 years with obesity, prediabetes, and hepatic steatosis to follow the very-low-carbohydrate ketogenic, Mediterranean, or very-low-fat plant-forward diet. The diets provided 4%, 50%, and 70% of energy from carbohydrates, respectively. All food was provided to participants, who met with the study dietitian weekly.
Among 55 randomized participants, 42 completed the study. The participants achieved about 10% weight loss at a mean 4.6, 5.4, and 5.1 months in the ketogenic, Mediterranean, and plant-forward groups, respectively. Dietary adherence exceeded 95%.
The 2 prespecified primary outcomes were skeletal muscle and hepatic insulin sensitivity. The investigators assessed skeletal muscle insulin sensitivity using a hyperinsulinemic-euglycemic clamp procedure and assessed hepatic insulin sensitivity using an index based on basal endogenous glucose production and plasma insulin concentration. Secondary outcomes were considered exploratory and were evaluated without multiplicity adjustment.
Skeletal muscle insulin sensitivity increased by about 50% across all 3 groups, without a between-group difference. Hepatic insulin sensitivity index increased in all groups, but the increase was 2 to 3 times greater with the ketogenic diet compared with the Mediterranean and plant-forward diets. A sensitivity analysis using available data from all randomized participants yielded similar findings for both primary outcomes.
Among exploratory outcomes, intrahepatic triglyceride content decreased by 67% with the ketogenic diet compared with 45% with both the Mediterranean and plant-forward diets. Basal endogenous glucose production and hepatic de novo lipogenesis declined following weight loss with the ketogenic and Mediterranean diets but remained unchanged with the plant-forward diet, with greater reductions observed in the ketogenic group.
Prediabetes remission occurred in 50%, 29%, and 7% and 24-hour plasma glucose area under the curve decreased by 20%, 8%, and 8% in the ketogenic, Mediterranean, and plant-forward groups, respectively, while 24-hour plasma insulin area under the curve decreased by 74%, 44%, and 27%.
The investigators noted that the study achieved similar moderate weight loss across diet groups and high dietary adherence with all food provided to participants. They also noted that they comprehensively assessed clinically relevant metabolic outcomes. Limitations included the small sample size, which may have reduced the ability to detect some between-group differences. The study could not determine whether less-severe carbohydrate restriction without ketosis would have the same effects observed with the ketogenic diet or whether its hepatic effects depended on consuming the diet during weight loss rather than initiating it during weight maintenance.
“These results underscore the importance of dietary macronutrient composition, in addition to calorie restriction, in the clinical management of [patients] with metabolically unhealthy obesity,” wrote lead author Max C. Petersen, of the Center for Human Nutrition and the Division of Endocrinology, Metabolism, and Lipid Research at the Washington University School of Medicine, and colleagues.
The study was supported by grants from the National Institutes of Health and by the Foundation for Barnes-Jewish Hospital. Samuel Klein reported receiving scientific advisory board fees from AbbVie, 89Bio, and Boehringer Ingelheim; an investigator-initiated grant from Merck; and support for an industry-initiated multicenter clinical trial from Viking Therapeutics.
Source: Cell Metabolism
