New study raises hopes for reversing type 2 diabetes

A new study, which has succeeded in rapidly reversing type 2 diabetes in animal models through a very low calorie diet (VLCD), holds immense potential if confirmed in people. The study by a Yale-led research team and published in Cell Metabolism, investigated the effects of a 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 method, known as PINTA, allowed the investigators to perform a comprehensive set of analyses of key 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 VLCD’s dramatic effect of rapidly lowering blood glucose concentrations in the diabetic animals. In the liver, the VLCD lowers glucose production by: 1) decreasing the conversion of lactate and amino acids into glucose; 2) decreasing the rate of liver glycogen conversion to glucose; and 3) decreasing fat content, which in turn improves the liver’s response to insulin. These positive effects of the VLCD 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 hyperglycaemia following a very low calorie diet,” said senior author Dr Gerald I Shulman, the George R. Cowgill Professor of Medicine and Cellular and Molecular Physiology and an investigator at the Howard Hughes Medical Institute.
Type 2 diabetes occurs when your blood sugar is high, which is a result of your body either making too much or not enough insulin as the hormone helps glucose work properly. When this happens, not enough of the sugar reaches your cells to be used and stay in the blood. Genetics can play a role in the disease, but often extra weight and physical inactivity contribute. To lower your risk, doctors believe even losing 5 to 7% of your body weight can help, in addition to working out 30 minutes a day for five days out of the week.
According to the latest statistics from the World Health Organisation, the number of people with diabetes has risen from 108mn in 1980 to 422mn in 2014. The global prevalence of diabetes among adults over 18 years of age has risen from 4.7% in 1980 to 8.5% in 2014. Diabetes prevalence has been rising more rapidly in middle- and low-income countries. Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation. In 2015, an estimated 1.6mn deaths were directly caused by diabetes. Another 2.2mn deaths were attributable to high blood glucose in 2012.
The next step for the researchers will be to confirm whether the findings can be replicated in type 2 diabetic patients undergoing either 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 added.

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