Type-2 Diabetes Research

Type-2 diabetes is the most common form of diabetes, not only in America, but worldwide. Millions have been diagnosed but, many more are unaware they are at high risk. Some groups have a higher risk for developing type-2 diabetes than others.

Research to combat type-2 diabetes looks for a way to predict who will develop type-2 diabetes, how to successfully personalize treatment, and how to use this information to preempt the disease onset and the development of complications.

Research Highlights

Highlighted Projects

Inflammatory Precursors of Type-2 Diabetes

Principal Investigator: James S. Pankow
Mark Pereira
Funding Agency: NIH/NIDDK
This study will prospectively investigate the association between selected components of the inflammatory response (including cytokines, acute phase proteins, markers of endothelial activation and dysfunction, and chronic infections) and incident diabetes in the Atherosclerosis Risk in Communities (ARIC) Study, a large, population-based cohort of middle-aged men and women. Some of these components may explain the strong link between obesity and diabetes. Its population-based nature permits a characterization of the public health relevance of several apparently fundamental advances in the understanding of the molecular biology of diabetes pathogenesis, orienting future research and the application of such findings to public health measures.

Genetic and Environmental Determinants of Type 2 Diabetes in Singaporean Chinese

Principal Investigator: Mark A. Pereira
Myron Gross, Jian-Min Yuan, Andrew Odegaard
Funding Agency: National Institutes of Health / NIDDK
Southeast Asian populations have high rates of type-2 diabetes (T2D) despite low rates of obesity. This ‘Southeast Asian Paradox’ has caused an extremely high public health and economic burden. While Southeast Asian-specific lower thresholds for defining obesity, set by the World Health Organization, underscore the particular susceptibility of these ethnic groups to T2D, the underlying biological and environmental causes for the excess diabetes in these populations are unknown. To date, genome-wide association studies of T2D have been completed in European populations, with none in other ethnic groups. These recent genetic findings only add to a ‘Southeast Asian Paradox’ of T2D because several of the risk alleles found in Europeans have relatively low frequencies in the Asians. Our main aim is the identification of genetic susceptibility factors for T2D in Chinese living in Singapore, where there is a high prevalence of T2D. We are in a unique position of conducting a genome-wide association study like none other to date in the following respects:

  • 1) Very large size – 6,132 cases and 6,132 controls;
  • 2) Nested case-control design – allowing for gene x environment interactions;
  • 3) Unique, high risk population for which we currently have a weak understanding of T2DM etiology; and
  • 4) Replication of our findings in two external Asian cohort studies.

We believe this study will move the field forward in understanding the biological and environmental determinants of T2D in many Asian populations, and improve risk stratification so that those at greatest risk can be identified for early prevention or treatment.

Meta-analysis of Abdominal Obesity and Type 2 diabetes in Adults

Principal Investigator: Susan J. Duval
David Jacobs, Aaron Folsom
Funding Agency: Centers for Disease Control and Prevention
Collating an international data bank of prospective studies linking abdominal obesity and

Primary prevention of diabetes: population-based methods to identify people most likely to benefit from interventions

Principal Investigator: Susan J. Duval
David Jacobs, Michael Stern, Jaakko Tuomilehto, James Pankow, Jaana Lindstrom, Qing Qiao, Karri Silventoinen
Funding Agency: CDC
We will develop a non-invasive or minimally invasive screening tool to identify persons with impaired glucose metabolism. We will test the sensitivity and specificity of this tool in different subgroups, formed for example by sex, age, ethnicity and their combinations, and if needed modify the screening tool in the different subgroups. Our database includes sufficient ethnic variation and sample size to give precise estimates even for those subgroups, which are not adequately represented in any individual study. Our large international database includes more than 40 studies and 500, 000 participants.

Television Viewing and Risk of Injury and Chronic Disease Morbidity

Principal Investigator: Mark A. Pereira
Darin Erickson, David Jacobs, Anthony Fabio (PI at University of Pittsburgh)
Funding Agency: Pending Award from National Institutes of Health / National Institute of Aging
The CARDIA Study data will be used to evaluate the propensity that television exposure may increase the risk for intentional and unintentional injuries, as well as obesity and chronic diseases through a variety of plausible and interrelated mechanisms. We aim to explore the possibility of an interaction between television viewing and the hostility trait in predicting a variety of important health outcomes over this large 20-year prospective study in Caucasians and African Americans from the four U.S. metropolitan areas.

Effects of Dietary Composition on Exercise Tolerance in Obese Adults

Principal Investigator: Mark A. Pereira
Susan Raatz, Bruce Redmon, Alexander Rothman, Donald Dengel
Funding Agency: American Heart Association
We believe people’s physiological responses to exercise have an important systematic influence on their psychological response to exercise, which we refer to as “exercise tolerance”. We theorize that the composition of the diet may affect exercise tolerance through its known impact on metabolic fuels (i.e. glucose and fatty acid. Specifically, typical high carbohydrate diets may have a deleterious impact on exercise tolerance through effects of postprandial hyperinsulinemia on the partitioning of metabolic fuels from oxidation to storage. Our research has shown that high carbohydrate diets, relative to energy-matched moderate carbohydrate diets, result in reactive hypoglycemia, an augmented drop in resting energy expenditure during weight loss, and greater perceived hunger. We theorize that the proposed interplay between the physiological and the psychological systems may have implications for the maintenance of a physically active lifestyle. To this end, we use a randomized crossover design to compare the effects of two dietary patterns — Control (high carbohydrate) v. Experimental (lower in carbohydrate, more slowly digested carbohydrates) — on obese individuals. A second version of the Experimental diet is high in protein. Specifically, we examine the relative effect of the diets on metabolic fuels during standardized exercise testing; perceived exertion, energy, and mood during standardized exercise testing; and free-living day-to-day reported energy levels, mood, and well being. By addressing these aims, the study will contribute to our understanding of the interplay between the physiological and psychological systems that regulate people’s exercise behavior. Moreover, if the composition of the diet is shown to have a causal influence on exercise physiology and, in turn, on how people think and feel about exercise, it will provide the basis for new directions in the design of interventions to promote physical activity and prevent obesity.

Effects of Breakfast on Hunger, Mood, and Cognition in Youth

Principal Investigator: Mark A. Pereira
Leslie Lytle
Funding Agency: Minnesota Obesity Center
This study is designed to evaluate the effects of eating breakfast and to examine the content of breakfast meals on appetite, mood, and cognitive performance in boys. Many studies have documented high rates of skipping breakfast among youth, but prospective and experimental studies are lacking. We hypothesize that children will be less hungry, less irritable, more energetic, and demonstrate superior memory and analytical skills following a breakfast meal in comparison to skipping breakfast. Due to effects of dietary composition on blood glucose and satiety, we further hypothesize that children may be less hungry and perform better on these parameters following a balanced breakfast meal containing whole grain cereal, fruit, and milk than after a refined carbohydrate breakfast meal including a pastry and fruit juice. The proposed study will include a crossover experimental design in 15 overweight adolescent boys in good health and between the ages of 11 and 14 (middle school). The study findings may provide insight into the role of breakfast habits in modulating energy regulation, behavior, and academic performance.

Effects of Dietary Carbohydrate on Glycemia, Appetite, and Mood

Principal Investigator: Mark A. Pereira
Investigators: Susan Raatz, Alex Rothman, Bruce Redmon
Funding Agency: Minnesota Medical Foundation & General Clinical Research Center, U of MN
This study is aimed at testing the effects of four different breakfast meals, and of a fasting (water only) condition, on postprandial blood concentrations of glucose, insulin, and fatty acids, and on appetite and mood levels. The meals vary in amount and type of carbohydrate and fat. This pilot study will help us to design protocols needed to test other potential effects of dietary composition, such as effects on physiologic and psychologic states during and after exercise, and ultimately adherence to dietary and physical activity interventions.