13 Nov 2017 --- A very low-calorie diet can rapidly reverse Type 2 diabetes in animal models, suggests a new study from a Yale-led research team in the US. If confirmed in people, the insight provides potential new drug targets for treating the common chronic disease, note the researchers, whose study is published in Cell Metabolism.
One in three Americans will develop Type 2 diabetes by 2050, according to projections by the Center for Disease Control and Prevention. Reports indicate that the disease goes into remission in many patients who undergo bariatric weight-loss surgery, which significantly restricts caloric intake prior to clinically significant weight loss, the Yale University press release notes. The Yale-led team's study focused on understanding the mechanisms by which caloric restriction rapidly reverses Type 2 diabetes.
Rodent model indicates reversal The research team investigated the effects of a very low calorie diet (VLCD), consisting of one-quarter the normal intake, on a rodent model of Type 2 diabetes. Using a novel stable (naturally occurring) isotope approach, which they developed, the researchers tracked and calculated a number of metabolic processes that contribute to the increased glucose production by the liver.
The investigators’ method, known as PINTA, allowed them to carry out a comprehensive set of analyses of important metabolic fluxes within the liver that might contribute to insulin resistance and increased rates of glucose production by the liver – two key processes that cause increased blood-sugar concentrations in diabetes.
Using this approach, the researchers pinpointed three major mechanisms responsible for the very low-calorie diet’s dramatic effect of rapidly lowering blood glucose concentrations in the diabetic animals.
In the liver, the researchers found that the very low-calorie diet lowers glucose production by: decreasing the conversion of lactate and amino acids into glucose; decreasing the rate of liver glycogen conversion to glucose; and decreasing fat content, which in turn improves the liver's response to insulin. The researchers point out that these positive effects of the very low-calorie diet were observed in just three days.
“Using this approach to comprehensively interrogate liver carbohydrate and fat metabolism, we showed that it is a combination of three mechanisms that is responsible for the rapid reversal of hyperglycemia following a very low calorie diet,” says the study’s senior author Gerald I. Shulman, M.D., the George R. Cowgill Professor of Medicine and Cellular and Molecular Physiology and an investigator at the Howard Hughes Medical Institute.
The next step for the researchers will be to confirm whether the findings can be replicated in Type 2 diabetic patients who are either undergoing bariatric surgery or consuming very low-calorie diets. His team has already begun applying the PINTA methodology in humans.
“These results, if confirmed in humans, will provide us with novel drug targets to more effectively treat patients with Type 2 diabetes,” Shulman says.
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