TOPLINE

In individuals with metabolically unhealthy obesity, moderate weight loss achieved through a very low-carbohydrate ketogenic diet led to greater improvements in hepatic insulin sensitivity and greater reductions in liver fat than moderate weight loss achieved through Mediterranean or very low-fat plant-forward diets.

METHODOLOGY

• Although weight loss plays a central role in addressing obesity-related insulin resistance, prediabetes, and metabolic dysfunction-associated steatotic liver disease, whether popular weight-loss diets offer metabolic benefits beyond weight loss alone remains unclear.
• Researchers conducted a randomized clinical trial that compared a very low-carbohydrate ketogenic diet, Mediterranean diet, and very low-fat plant-forward diet to evaluate the impact of dietary macronutrient composition on cardiometabolic effects in individuals with metabolically unhealthy obesity.
• The analysis included 42 individuals (mean age, 43.2 years; mean BMI, 38.9) with metabolically unhealthy obesity, who were randomly assigned to a very low-carbohydrate ketogenic diet, Mediterranean diet, or very low-fat plant-forward diet group. Each group included five men and nine women. 
• Participants across all diet groups achieved a moderate weight loss of approximately 10% over 4-5 months. 
• Primary outcomes were changes in skeletal muscle insulin sensitivity and hepatic insulin sensitivity after weight loss.

TAKEAWAY

• Weight loss increased skeletal muscle insulin sensitivity by approximately 50% in all groups without differences among diets, but the increase in hepatic insulin sensitivity was two- to threefold greater in the very low-carbohydrate ketogenic diet group than in the Mediterranean and very low-fat plant-forward diet groups (P < .001).
• Intrahepatic triglyceride content decreased by 67% in the very low-carbohydrate ketogenic group vs 45% in both the Mediterranean and very low-fat plant-forward diet groups (P < .05). Hepatic de novo lipogenesis declined to a greater extent in the very low-carbohydrate ketogenic group than in other diet groups.
• A1c levels decreased to a greater extent in the very low-carbohydrate ketogenic diet group than in other diet groups; prediabetes remission occurred in 50% of participants in the very low-carbohydrate ketogenic diet group vs 29% in the Mediterranean diet group and 7% in the very low-fat plant-forward diet group (P < .05 for all).
• No serious adverse events were reported, and no participant withdrew because of an adverse event. 

IN PRACTICE

"[The] results underscore the importance of dietary macronutrient composition, in addition to calorie restriction, in the clinical management of people with metabolically unhealthy obesity," the authors wrote.

SOURCE

The study was led by Max C. Petersen, MD, PhD, Washington University School of Medicine, St. Louis. It was published online in Cell Metabolism.

LIMITATIONS

The relatively small number of participants may have limited the ability to detect some differences between diet groups. The researchers did not determine whether a less restrictive carbohydrate-reduction strategy without ketosis would provide similar metabolic benefits. The researchers also did not determine whether the observed hepatic benefits required a ketogenic diet during active weight loss or could also be achieved when the diet was introduced during weight-loss maintenance.

DISCLOSURES

The study was supported by grants from the National Institutes of Health and the Foundation for Barnes-Jewish Hospital. One author disclosed receiving scientific advisory board fees from multiple companies, an investigator-initiated grant from a pharmaceutical company, and support from a company for an industry-initiated multicenter clinical trial.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.