Dr. Constantin Polychronakos

Untangling the genetic threads of diabetes

The fields of genetics and endocrinology owe much to a little girl called Marie. It was this patient, according to Dr. Constantin Polychronakos, that led him to apply himself to finding genetic answers to the puzzle of diabetes. Then three years old, Marie had just been diagnosed with juvenile (Type-1) diabetes, and Dr. Polychranakos was rushing to save her from the effects of diabetic ketoacidosis (toxic blood sugar).

"Between discussing lab results and IV orders with the intensive care team, I had occasion to reflect on how my life as a clinician connected with my research interests which, at the time, were in genomic imprinting and its role in foetal growth and in embryonal tumours", he wrote of this moment.

Marie, and rapid advances in our understanding of the human genome, changed the course of Dr. Polychronakos’ career forever.

Educated in his native Greece, Dr. Polychronakos came to Canada in 1972, practicing as a specialist physician and researcher as a professor at McGill and a physician at the Montreal Children’s Hospital since 1983. He is also the director of the Endocrine Genetics Laboratory in the hospital’s Research Institute, and a member of the Montreal Diabetes Research Centre.

Diabetes is a disorder in which the pancreas does not produce insulin; patients are therefore unable to control glucose levels in their blood. Type-1 diabetes usually manifests itself before the age of 30, often in very young children. There is no known cure, but it is thought to be the result of the body’s immune system attacking insulin-producing cells. Type-2 diabetes (sometimes called adult onset diabetes) is a metabolic disorder that can often be kept in check through diet and exercise.

Both kinds can be regulated through insulin treatments, but still people are at high risk for blindness, heart and kidney failure and other ailments. While diabetes can be managed, it cannot yet be cured. In an attempt to do so, Dr. Polychronakos has spent years trying to pin down the genetic roots of the disease, with some success.

Dr. Polychronakos has made significant discoveries linking specific genes to both Type-1 and Type-2 diabetes. He has helped draft one of the most cited scientific articles of 2007, a study that discovered two new genes with a strong correlation to Type-2 diabetes, and another two that also seem to have a role.

Of the four genes found in this study, one has a known role in producing zinc in pancreatic cells, itself an important ingredient in insulin. This knowledge might, several years down the road, lead to a new treatment for the ailment.

Dr. Polychronakos believes that discoveries like his are changing our perception of diabetes. A few years ago, there were only two genes linked to the disease. The number has grown since – the last four he found brought the total known to over fifty, and Dr. Polychronakos expects more to follow.

In all likelihood, this genetic complexity means that Type-1 and Type-2 are only broad categories of diabetes – in reality, there are probably many subtypes, with different genes interacting in different ways. To discover that the problem is much harder than it appeared might not seem like progress, but for Dr. Polychronakos, more genes means there are more avenues of treatment – and possibly cures – on the horizon. More importantly, there is hope that genetic profiling will allow physicians to choose the treatment best suited to the individual patient (personalized medicine).

Dr. Polychronakos has been the recipient of funding from Genome Canada, Genome Québec, the Juvenile Diabetes Foundation, the Ministère du Développement économique, de l'Innovation et de l'Exportation from Quebec, and the Canadian Institutes of Health Research.

For further information, please contact Dr. Constantin Polychronakos using the Email contact form or by phone at 514 934-1934