New Delhi: A team of Indian scientists has for the first time identified a gene that could potentially provide a completely novel interpretation into the causes of type-2 diabetes.
The disease is understood to be a metabolic disorder, but the new study suggests a more complex provenance involving nerve cells and a potentially new mechanism.
The study, that tested nearly 6,000 diabetics, will appear this week in the American journal Diabetes and claims that a variant of a commonly-found gene, TMEM163, was significantly associated with type-2 diabetes, in a primarily north Indian population.
These genes weren’t significantly present in south Indians as well as Caucasian populations, the latter of which is the most intensely studied population as far as the relationship between genes and diabetes goes.
To be sure, the complexity of type-2 diabetes is such that though the underlying mechanism—insufficient insulin in the blood caused due to improperly functioning cells that are supposed to regulate insulin and thereafter, blood sugar—is well understood, there are several contentious opinions on the fundamental causative factors.
As of today, nearly 60 genes have been associated with the type-2 diabetes and, even cumulatively, they cannot explain more than 10% of the incidence of diabetes in a population. The TMEM163 variant, the discovery of which involves a combined effort using a technique called genome-wide association studies and nearly 40 scientists and a range of institutions such as the Institute of Genomics and Integrative Biology (IGIB), the All India Institute of Medical Sciences (AIIMS), the Indian Statistical Institute and Oxford University, is one more gene on that list.
Still, it is unique because it’s a gene that’s responsible in the development of nerve endings, and carrying this variant gene makes one 56% more likely to develop the disease than those who have the regular version of the gene.
Among all the 60 genes associated so far, this variant is the most significantly associated with diabetes in Indians, the study adds.
“Most genes that we know are in some way associated with the endocrine system, which isn’t very surprising as diabetes is a disease of the endocrine system,” said Nikhil Tandon, a doctor at AIIMS and a lead researcher in the study, “but this is a nerve-related gene. We don’t know how important this is and its role in how it relates to diabetes, but it certainly may hold some clues in pointing to a new way to understand the mechanism of type-2 diabetes.”
Dwaipayan Bharadwaj of IGIB and another key researcher associated with the study, said that it was possible that there could be an entirely different pathway that could explain diabetes. “Only two or three genes, with some neuronal connection, have been associated with diabetes. And it’s important that, as far as Indian populations go, this gene variant is far strongly associated with diabetes than any other similar gene,” he said.
India has the highest number of diabetics in the world—50.8 million—and type-2 is the more common and complicated avatar of the condition, affecting almost nine out of every 10 diabetics.
While no government figures exist, diabetes costs India about Rs.13,000 crore, according to a 2007 study by the Economist Intelligence Unit, mostly from lost earnings and productivity.
Genome-wide association studies harness computers and specially-designed microchips to see how different the genomes of diabetics look from those who don’t have the condition.
People with type-2 diabetes cannot use the insulin they produce effectively, but can often manage their condition through exercise and diet, although many require medication, including insulin, to properly control blood glucose levels. It is estimated that 60% or more instances of type-2 diabetes can be prevented.
Diabetes claims four million lives every year and is a leading cause of blindness, kidney failure, heart attack, stroke and amputation, according to a report by the Belgium-based International Diabetes Federation. The rarer type-1 diabetes arises from insulin deficiency, usually because of a disorder in the pancreas where this enzyme is produced.
Independent scientists say that while the findings themselves might not lead to an immediate change in the way type-2 diabetes is treated, it is significant because it addresses, for the first time, features of diabetes unique to Indian populations.
“All of our knowledge in diabetes is driven by the West, which is unfortunate because diabetes is too big a problem in India to ignore,” said M.N. Ghosh, a senior endocrinologist with the Indian Council of Medical Research. “Genes and diabetes have a distant link, and this could potentially change our understanding of the disease.”