AACE 2011: How Genomics Will Drive Diabetes Prevention and Management


Eric Topol, MD, discusses pharmacogenetics, molecular medicine, genomics, and the future of diabetes treatment.

Eric Topol, MD, discusses pharmacogenetics, molecular medicine, genomics, and the future of diabetes treatment.

“There is a revolution in medicine involving genomics that will affect oncology and diabetes treatment,” said Eric Topol, MD, at the 20th Annual Meeting and Clinical Congress of the American Association of Clinical Endocrinologists. Topol is director of the Scripps Translations Science Institute, chief academic officer for Scripps Health, professor of Translational Genomics at The Scripps Research Institute, and senior consultant cardiologist at Scripps Clinic. His talk focused on current and future capabilities related to genomics and its role in treating diabetes.

“Medicine, including diabetes, will become Schumpetered,” he said, referring to the book Capitalism, Socialism, and Democracy by Joseph Schumpeter that describes creative destruction in terms of downsizing in order to increase the efficiency and energy of a company. There has been remarkable progress in the last several years, with the underpinnings of over 150 diseases identified in the human genome. By mapping the human genome, scientists will be able to determine who will get a disease and what is the best method for treating the disease in each individual.

Topol described three main areas of genomic research: GWAS (Genome-Wide Association Study), WES (Whole Exome Sequencing), and WGS (Whole Genome Sequencing). GWAS accounts for .03% of the genome and only describes the common variants. WES accounts for 1.5% of the genome and picks up rare or low frequency variants, and WGS picks up 98% of the genome, also focusing on rare and low frequency variants. When it comes to diabetes, “no other genetic loci are as impactful as TCF7L2,” he explained. “It is the most common variant and the most important because of its impact and penetrance.” Homozygous carriers of TCF7L2 are at increased risk of diabetes.

The clinical implications of genome sequencing were illustrated by a story of a five-year-old boy whose life was saved because of sequencing. At two years old, he had a golf-ball-sized abscess which burst and became a hole in his rectum. After over 100 operations, intermittent sepsis, constant hospitalization, and treatment in hyperbaric chambers, he was close to death. He had unrestrained inflammation in the GI tract that looked like Crohn’s disease, but doctors thought this couldn’t possible come from a normal genome. After sequencing researchers identified 16,124 variants, and finally found a mutation in an inhibitor of apoptosis gene. Based on this finding, the boy was given a bone marrow transplant and is now thriving.

Additional findings from gene sequencing research relevant to diabetes include MTNR1B, where variants influence fasting glucose levels and increase the risk for type 2 diabetes; WES as an alternative for molecular diagnosis of neonatal diabetes; higher genotype score (ie, number of risk alleles without weighting) creates greater risk of diabetes; ADRA2A overexpression can lead to diabetes; and ATM, a gene associated with cancer, predicts response to metformin where if a person has two copies of this allele, he/she has a three-fold response.

Another exciting development with economic implications is that insurance companies are starting to cover sequencing. It is a step in the right direction, but Topol emphasized that we can do better. “A lot of individuals are starting to get genomics direct-to-consumer,” he said. “Pharmacogenetic panels are currently available and may predict response to drugs.” We should be doing more screening for variants that predict risk for developing diabetes and other conditions, as well as for determining response to drugs.

Topol made a prediction: “In the future, sequencing will be done through our cell phones. A prototype is already available today.”

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