Channing Diabetes and Obesity Research

The Examination and Analyses of Gene-lifestyle Interactions in the Development of Type 2 Diabetes and Obesity

Diabetes is a chronic metabolic disease characterized by elevated blood sugar. Type 2 diabetes (T2D) accounts for more than 90% of all diabetes cases and affects over 29 million Americans. With its numerous complications, diabetes results in excessive premature deaths and significant economic burden.

Excess body weight is the most important risk factor for developing T2D. In the U.S., more than two-thirds of adults are either overweight or obese. In addition, childhood obesity has become a significant public health issue, and its prevalence has been steadily increasing.

Through decades of research, it is clear that both obesity and T2D are mainly driven by unhealthy diets and lifestyle, and precipitated by complex and poorly understood interactions between genetic predisposition and environmental factors.

Current Research

At the Channing Division of Network Medicine (CDNM), investigators have performed extensive research to examine the role of genetic, dietary, lifestyle, and other risk factors in the development of obesity and T2D. In addition, we have also investigated modifiable risk factors for developing cardiovascular disease (CVD) and other complications among individuals with diabetes.

Achievements

CDNM investigators have uncovered important roles in T2D and obesity for many dietary factors, including glycemic index, glycemic load, sugar-sweetened beverages, coffee, whole grains, and red and processed meats. We estimated that up to 90% of T2D cases are potentially preventable by following a healthy diet and lifestyle.

We have also identified novel biomarkers for T2D, including adipokines, inflammatory cytokines, nutrition metabolites, and environmental pollutants, offering new insights into the pathophysiology of the disease.

Our analyses of gene-lifestyle interactions have shown that genetic factors predispose individuals to obesity, but that such susceptibility can be attenuated by healthy lifestyle choices.

Diet

Diet is among the most important modifiable factors for T2D incidence and weight gain. Our research:

• Uses validated food frequency questionnaires and other self-reported dietary instruments to assess human diet and evaluates diet-T2D/obesity associations at the levels of nutrients, foods, dietary patterns, and other dietary behaviors, such as cooking methods or frequencies of consuming meals cooked at home
• Quantifies dietary intake and evaluates associations of diet with T2D/obesity risk through the use of objective dietary biomarkers
• Illustrates potential pathways through which diet modulates T2D/obesity risk by examining diet in relation to intermediate outcomes, the human metabolome, and gut microbiomes

Genetics and gene-environment interactions

CDNM investigators have contributed to the understanding of genetic determinants of obesity and T2D through the following research:

• Conducting genome-wide association studies (GWAS) to identify and replicate novel genetic loci that predict higher body mass index (BMI) and T2D risk. We also participate in various consortia and share our data with investigators outside the CDNM community to enhance the ability to detect genetic loci with smaller effect size or lower frequency.
• Exploring gene-diet and gene-environment interactions on BMI and T2D
• Investigating other genetic factors, such as telomere length, in relation to obesity or T2D risk

Environmental pollutants

It is increasingly recognized that many environmental pollutants possess endocrine-disrupting properties and may promote excessive weight gain and T2D risk. Our research:

• Evaluates biomarkers of environmental pollutants, i.e., metabolites of pollutants in human biospecimens, in relation to body weight and risk of T2D
• Examines the role of environmental pollutants in relation to weight loss and weight regain in intentional weight-loss setting

Lifestyle and other factors

We are also interested in understanding physical activities, sleep duration, snoring, night-shift, smoking, and many other lifestyle-related risk factors in relation to obesity and T2D risk.

Study populations

Investigators at CDNM primarily use data collected in the well-established Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-Up Study. We also collaborate with numerous investigators nationally and internationally, and address search questions often in clinical trials, including the PREDIMED trial, the VITAL trial, and POUNDS-Lost Study.