News & Research

    Massachusetts General Hospital, Boston, Massachusetts

Genetics of type 2 diabetes quantitative traits

General Research Subject: Insulin Resistance Pre Diabetes

Focus: Genetics, Genetics\Type 2 Diabetes

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: January 1, 2010

Project End Date: December 31, 2013

Research Description

People get type 2 diabetes if they have genes that make them susceptible and especially if they have obesity. Obesity and consequently diabetes have become very common in recent years. Over the same time, new knowledge of diabetes genetics also has grown dramatically. Discovery of new diabetes genes and determining how to make this new knowledge useful for diabetes prevention and treatment is the aim of the research. Here there are two main goals. The first is to understand how genes cause type 2 diabetes by testing whether certain genetic differences between people called single nucleotide polymorphisms (SNPs) are associated with differences between people in levels of blood sugar, insulin resistance or risk to develop type 2 diabetes itself. Whether obesity weakens or strengthens these relationships will also be tested.

The second goal is to try and understand the health value of this new genetic information by testing if combinations of diabetes genes are useful for risk prediction, and whether such 'genotype scores' influence personal diabetes prevention behaviors. The research is conducted in collaboration with the Framingham Heart Study- SNP Health Association Resource Study, the Meta-Analyses of Glucose and Insulin-related traits Consortium and the Nurses Health/Health Professionals Follow Up Studies. These groups study diabetes genetics in over 100,000 European individuals who have detailed information on blood sugar, body mass index, and other measures. This project will support a research Fellow to train in a environment committed to identification of novel approaches for prevention of type 2 diabetes.

Reseacher Profile

Mentor: James B. Meigs, MD, MPH   Postdcotoral Fellow: Jonna Grimsby, PhD

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes? 

People get type 2 diabetes if they have genes that make them susceptible and especially if they have obesity. Obesity and consequently diabetes have become very common in recent years. Over the same time, new knowledge of type 2 diabetes genetics also has grown dramatically. Discovery of new diabetes genes and determining how to make this new knowledge useful for diabetes prevention and treatment is the aim of the research. Here there are two main goals. The first is to understand how genes cause type 2 diabetes by testing whether certain genetic differences between people called single nucleotide polymorphisms (SNPs) are associated with differences between people in levels of blood sugar, insulin resistance or risk to develop type 2 diabetes itself. Whether obesity weakens or strengthens these relationships will also be tested.

The second goal is to try and understand the health value of this new genetic information by testing if combinations of diabetes genes are useful for risk prediction, and whether such 'genotype scores' influence personal diabetes prevention behaviors. The research is conducted in collaboration with the Framingham Heart Study- SNP Health Association Resource Study, the Meta-Analyses of Glucose and Insulin-related traits Consortium and the Nurses Health/Health Professionals Follow Up Studies. These groups study diabetes genetics in over 120,000 European individuals who have detailed information on blood sugar, body mass index, and other measures. This project will support a research Fellow to train in a environment committed to identification of novel approaches for prevention of type 2 diabetes.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond? 

Type 2 diabetes runs in families, but the genes that are passed from parents to children that predispose to diabetes are only now becoming understood. Genes that are associated with differences between people in levels of glucose and insulin are largely unknown. The goal of the research is to identify these genes, understand the mechanisms whereby the genes act on glucose and insulin metabolism (these might turn out to be drug or prevention targets), and to understand how to use genetic information to prevent type 2 diabetes or improve its treatment. The project will help people with diabetes by leading to a greater understanding of the causes and best approaches to prevent type 2 diabetes.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts? 

I am both an adult medicine primary care physician and a type 2 diabetes clinical epidemiology researcher. As a clinician, I see type 2 diabetes every day in clinic and feel strongly that new approaches to better understanding of the causes and prevention of type 2 diabetes are needed. This motivated me to get involved in diabetes research over 15 years ago. As a clinical epidemiology researcher, this award will allow me to 1) train a new investigator to become involved (and ideally, eventually, a leader) in diabetes prevention research and 2) to expand my research capacity in genetic epidemiology by adding another capable investigator to my team. The support of the ADA has been invaluable at every stage in my career allowing continuation and expansion of my research directions.

In what direction do you see the future of diabetes research going? 

As knowledge of the genetic basis of type 2 diabetes continues to grow, diabetes research will go in several directions simultaneously. New genes related to type 2 diabetes will reveal previously unsuspected, novel pathways involved in type 2 diabetes pathogenesis.  Some of these pathways will offer novel targets for drug treatment and prevention interventions. Further, genetic differences between diabetes patients may allow tailored drug therapy, increasing efficacy and reducing side effects or secondary failure.

As sufficient numbers of genes related to risk of type 2 diabetes are discovered, they may offer improved capability to predict diabetes risk, especially in young persons in whom clinical risk factors (like obesity) have not yet developed. Diversity in the genetic architecture of diabetes among different race/ethnic groups will begin to explain some of the race/ethnic disparities that have been observed in risk of diabetes and its complications. Thus, the future of type 2 diabetes genetics research is likely to have important impacts on personalization, prediction, prevention and public health that may lower the burden of morbidity and mortality in type 2 diabetes in the U.S and worldwide.