treatment

New research finds genetic changes that could lead to better treatments for type 2 diabetes

by Barbara Hewitt on October 2, 2018

People with type 2 diabetes could benefit from new research which has found that inherited genetic changes could point to better treatments.

Currently most people diagnosed with type 2 diabetes are treated with a one size fits all approach that is not tailored to each person’s physiology and may leave many cases inadequately managed.

Scientists Lab

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But a new study by scientists at the Broad Institute of MIT and Harvard and Massachusetts General Hospital (MGH) in the United States suggests that inherited genetic changes may underlie the variability observed among patients in the clinic, with several pathophysiological processes potentially leading to high blood sugar and its resulting consequences.

Scientists analysed genomic data with a computational tool that incorporates genetic complexity, and they identified five distinct groups of DNA sites that appear to drive distinct forms of type 2 diabetes in unique ways.

The work represents a first step toward using genetics to identify subtypes of type 2 diabetes, which could help physicians prescribe interventions aimed at the cause of the disease, rather than just the symptoms.

‘When treating type 2 diabetes, we have a dozen or so medications we can use, but after you start someone on the standard algorithm, it’s primarily trial and error,’ said senior author Jose Florez, an endocrinologist at MGH, co-director of the Broad’s Metabolism Programme and professor at Harvard Medical School.

‘We need a more granular approach that addresses the many different molecular processes leading to high blood sugar,’ he added.

It is known that type 2 diabetes can be broadly grouped into cases driven either by the inability of pancreatic beta cells to make enough insulin, known as insulin deficiency, or by the inability of liver, muscle or fat tissues to use insulin properly, known as insulin resistance.

Previous research has attempted to define more subtypes of type 2 diabetes based on indicators such as beta-cell function, insulin resistance, or body mass index, but those traits can vary greatly through life and during the course of disease.

Now the research points out that inherited genetic differences are present at birth, and so a more reliable method would be to create subtypes based on DNA variations that have been associated with diabetes risk in large scale genetic studies.

These variations can be grouped into clusters based on how they impact diabetes related traits. For example, genetic changes linked to high triglyceride levels are likely to work through the same biological processes.

The new work has revealed five clusters of genetic variants distinguished by distinct underlying cellular processes, within the existing major divisions of insulin resistant and insulin deficient disease. Two of these clusters contain variants that suggest beta cells aren’t working properly, but that differ in their impacts on levels of the insulin precursor, proinsulin.

The other three clusters contain DNA variants related to insulin resistance, including one cluster mediated by obesity, one defined by disrupted metabolism of fats in the liver, and one driven by defects in the distribution of fat within the body, known as lipodystrophy.

‘The clusters from our study seem to recapitulate what we observe in clinical practice. Now we need to determine whether these clusters translate to differences in disease progression, complications, and response to treatment,’ said Florez.

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