Most patients diagnosed with type 2 diabetes are treated with a "one-size-fits-all" protocol that is not tailored to each person's physiology and may leave many cases inadequately managed. A new study by scientists at the Broad Institute of MIT and Harvard and Massachusetts General Hospital (MGH) indicates 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.
By analyzing genomic data with a computational tool that incorporates genetic complexity, the researchers identified five distinct groups of DNA sites that appear to drive distinct forms of the illness 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.
The study appears in PLOS Medicine.
"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 Program, and professor at Harvard Medical School. "We need a more granular approach that addresses the many different molecular processes leading to high blood sugar."
It's 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.
A recent op-ed by genetic counselor Laura Hercher illuminated a sticky situation in which more and more consumers find themselves. Matt Fender ordered a spit kit from direct-to-consumer (DTC) genetic testing company 23andMe, downloaded his raw data, and ran them through a third party service called Promethease, which can help consumers make sense of their raw data. Fender’s Promethease report highlighted a genetic variant in the raw data that, if truly present, would place him at very high risk to develop an early-onset form of Alzheimer disease and would alter the course of his life.
Fender found himself in a gap where thousands before him have fallen, and where even more will end up if the estimates that 100 million consumers will have DTC genetic testing by 2021 are correct. Namely, he had information in his hands that could be either accurate medical information or dead wrong. Why? At a consumer’s request, some DTC companies release raw genetic data that has not been verified under the umbrella of genetics ‘entertainment’ (or genutainment). This means that these raw data are not complete or ‘medical-grade’ genetic information; however, they can, and sometimes do, reveal serious and accurate medical information. Fender wanted to learn if his result was accurate, but he had a difficult time getting the confirmatory medical-grade test he needed because he had no personal or family history of this disease.
Health care providers, as a whole, do not have the time, training, or desire to wade through these lengthy reports to help consumers decipher if DTC test kits and raw data findings are accurate or not. And, importantly, insurance companies most often will not cover these consultations or repeat testing if, like Fender, the patient has no personal or family history of that disease. So, how do we throw down a line to consumers stuck in this abyss?
Since being blocked by the FDA from returning health information in 2013, some companies have worked with the agency on a process through which they can return some health information directly back to consumers. For example, 23andMe is again releasing the three common Jewish BRCA1 and BRCA2 variants (3 of thousands of pathogenic BRCA variants, also known as mutations) to consumers. They recommend that all consumers then repeat that testing through their health care provider in a medical-grade laboratory, which lands those consumers in the abyss. Until now.
Forward-thinking insurer Blue Shield of California has stepped up to the plate. Under the leadership of genetic counselor Stephanie Gandomi and Director of Enhanced Clinical Programs, Henry Garlich, Blueshield implemented a medical policy that covers confirmatory testing in a medical-grade laboratory for any insured who has received a positive Ashkenazi Jewish BRCA finding directly from 23andMe. Perhaps at some point in the future, they and other visionaries in the field will expand medical policies to include confirmatory testing for patients who learn of other potentially important genetic findings on their DTC raw data analysis.