Patients with type 2 diabetes should be put on diets rich in either animal or plant protein to reduce not only liver fat, but insulin resistance and hepatic necroinflammation markers as well, according to a study published in the February issue of Gastroenterology (doi: 10.1053/j.gastro.2016.10.007 ).

“High-protein diets have shown variable and sometimes even favorable effects on glucose metabolism and insulin sensitivity in people with type 2 diabetes and it is unclear which metabolic pathways are involved,” wrote the authors of the study, led by Mariya Markova, MD, of the German Institute of Human Nutrition Potsdam-Rehbrücke in Nuthetal, Germany.

Obesity and insulin resistance have long been linked to liver fat, with excessive amounts of the latter causing nonalcoholic fatty liver disease (NAFLD), with a significant risk of nonalcoholic steatohepatitis (NASH) developing as well. Compounding this issue, at least in the United States, are widespread dietary and nutritional habits that promote consumption of animal protein, carbohydrates, and saturated fats. This “hypercaloric Western style diet,” as the authors call it, exacerbates the accumulation of fat deposits in the liver and complicates the health of patients across the country, regardless of weight.

“Remarkably, diets restricted in methionine were shown to prevent the development of insulin resistance and of the metabolic syndrome in animal models [so] the type of protein may elicit different metabolic responses depending on the amino acid composition,” Dr. Markova and her coinvestigators noted. “It is therefore hypothesized that high-plant-protein diets exert favorable effects on hepatic fat content and metabolic responses as compared to high intake of animal protein rich in BCAA [branched-chain amino acids] and methionine,” both of which can be found in suitably low levels via plant protein.

Dr. Markova and her team devised a prospective, randomized, open-label clinical trial involving 44 patients with type 2 diabetes and NAFLD, all of whom were recruited at the department of clinical nutrition of the German Institute of Human Nutrition Potsdam-Rehbrücke between June 2013 and March 2015. Subjects were randomized into one of two cohorts, each of which were assigned a diet rich in either animal protein (AP) or plant protein (PP) for a period of 6 weeks. Median body mass index in the AP cohort was 31.0 ± 0.8, and was 29.4 ± 1.0 in the PP cohort.

The AP cohort diet consisted mainly of meat and dairy products, while legumes constituted the bulk of the PP cohort diet. Both diets were isocaloric and had the same macronutrient makeup: 30% protein, 40% carbohydrates, and 30% fat. Seven subjects dropped out prior to completion of the study; of the 37 that remained all the way through – 19 in the AP cohort, 18 in the PP cohort – the age range was 49-78 years. Subjects maintained the same physical exercise regimens throughout the study that they had beforehand, and were asked not to alter them. Hemoglobin A1c levels ranged from 5.8% to 8.8% at baseline, and evaluations were carried out at fasting levels for each subject.

Patients in both cohorts saw significant decreases in intrahepatic fat content by the end of the trial period. Those in the AP cohort saw decreases of 48.0% (P = .0002), while those in the PP cohort saw a decrease of 35.7% (P = .001). Perhaps most importantly, the reductions in both cohorts were not correlated to body weight. In addition, levels of fibroblast growth factor 21 (FGF21), which has been shown to be a predictive marker of NAFLD, decreased by nearly 50% for both AP and PP cohorts (P less than .0002 for both).

“Despite the elevated intake and postprandial uptake of methionine and BCAA in the AP group, there was no indication of negative effects of these components,” the authors stated in the study. “The origin of protein – animal or plant – did not play a major role. Both high-protein diets unexpectedly induced strong reductions of FGF21, which was associated with metabolic improvements and the decrease of IHL.”

Despite these findings, however, the 6-week time span used here is not sufficient to determine just how viable this diet may be in the long term, according to the authors. Further studies will be needed, and will need to take place over longer periods of time, to “show the durability of the responses and eventual adverse effects of the diets.” Furthermore, different age groups must be examined to find out if the benefits observed by Dr. Markova and her coinvestigators were somehow related to the age of these subjects.

The study was funded by grants from German Federal Ministry of Food and Agriculture and German Center for Diabetes Research. Dr. Markova and her coauthors did not report any financial disclosures.


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