Obese women on a high-protein diet, most of whom lost significant weight, did so at a substantial cost — they did not obtain a corresponding improvement in skeletal muscle insulin sensitivity that would normally be expected with such a degree of weight loss, a randomized trial showed.
In contrast, improvement of 25% to 30% in insulin sensitivity was seen in a control group with similar weight loss on a diet with protein intake limited to the recommended daily allowance, reported Bettina Mittendorfer, PhD, Washington University School of Medicine in St. Louis, and colleagues online in Cell Reports.
The lack of improvement in muscle insulin sensitivity with high-protein weight-loss arm in this 34-patient study is clinically important because it reflects a failure to improve a major pathophysiological mechanism involved in the development of type 2 diabetes, Mittendorfer said in a statement.
“Changing the protein content has very big effects. It’s not that the metabolic benefits of weight loss were diminished — they were completely abolished in women who consumed high-protein diets, even though they lost the same, substantial amounts of weight as women who ate the diet that was lower in protein,” she said.
“This carefully conducted study adds to the growing body of evidence that the absolute level of dietary protein intake negatively correlates with metabolic health, particularly glucose control, independently from total caloric intake and even body weight,” Adam Rose, PhD, German Cancer Research Center (DKFZ) in Heidelberg, told MedPage Today in an email.
Participants included obese, sedentary (less than 1.5 hours of exercise per week) postmenopausal women ages 50-65 whose weight had been stable (within 2 kg) for at least 6 months. All had body mass index values of at least 30 and none had diabetes.
All participants received the same base diet with comparable amounts of fat and carbohydrates. Women were randomized to one of three groups for the 28-week study: a weight-maintenance control group, or one of the two weight-loss arms which provided a low-calorie diet containing either the standard recommended daily allowance of 0.8 g protein/kg body weight per day, or high-protein intake of 1.2 g protein/kg body weight per day.
The primary endpoint was rate of insulin-stimulated glucose uptake during an hyperinsulinemic-euglycemic clamp procedure (HECP). In addition, researchers assessed the muscle global transcriptome and a series of factors that can influence insulin action.
Body weight and body composition in the weight maintenance group did not change during the study. Both weight-loss groups lost an average of about 10% of their initial body weight, but the contribution of fat-free mass (FFM) to total weight loss was about 45% less in the high-protein group compared with the standard protein group (P=0.03). That translated into a difference of 700 grams of lean muscle mass preserved in the high-protein group versus the standard protein group.
Changes in other parameters, such as intrahepatic triglycerides, intra-abdominal adipose tissue, and basal insulin, did not differ between the two weight-loss groups.
“When you lose weight, about two-thirds of it tends to be fat tissue, and the other third is lean tissue,” Mittendorfer said in the statement. “The women who ate more protein did tend to lose a little bit less lean tissue, but the total difference was only about a pound. We question whether there’s a significant clinical benefit to such a small difference.”
High protein intake during weight loss is commonly believed to be important in order to preserve lean tissue mass and reduce the potential for adverse effects like sarcopenia in those at risk, including postmenopausal women. However, the trade-off in terms of lack of weight-loss-related improvements in insulin sensitivity may not support the benefit, the researchers suggested.
“Our data suggest that high protein intake causes alterations in muscle cell structure and organization and oxidative stress, which are involved in preventing the therapeutic effect of weight loss on muscle insulin action,” Mittendorfer and colleagues wrote, but they acknowledged that the study did not allow firm conclusions.
The study’s generalizability is limited by its small sample and restriction to women. “It’s not known whether the same results would occur in men or in women already diagnosed with type 2 diabetes,” Mittendorfer said.
Smith et al “High-protein intake during weight-loss therapy eliminates the weight-loss-induced improvement in insulin action in obese postmenopausal women” Cell Reports 2016; DOI: 10.1016/j.celrep.2016.09.047.