This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There are approximately 16.9 million adults with diabetes in the United States. Approximately 90-95% of people diagnosed with diabetes have type 2 diabetes, and the vast majority of these are overweight or obese. Using a fasting blood glucose level of 125mg/dL and National Health and Nutrition Examination Survey (NHANES) data, the prevalence of diabetes has increased from 8.9% of the US population in 1976-1980 to 12.3% in 1988-1994.1 Data from the Behavioral Risk Surveillance System (BRFSS) indicate that the proportion of survey participants who reported they had diabetes rose by 49% during the 1990s. The increase in the prevalence of diabetes is largely attributable to the dramatic rise in obesity. Changes in demographic factors such as ethnicity and age, and a lower fasting blood glucose to diagnose diabetes (from 140 mg/dL to 126 mg/dL) may also be contributing factors. As the global rate of obesity increases over the next two decades, the worldwide population with diabetes is expected to more than double from an estimated 135 million people in 1995 to 300 million by 2025. Carefully collected weight data from NHANES III, which was completed in 1994, indicate that overall proportion of overweight adults with a BMI 25 kg/m2 was 54.9% and 22.5% were obese with a BMI 30 kg/m2. During the 1990s, self-reported data from the BRFSS telephone surveys indicate that prevalence of obesity rose by 61% and the overall prevalence of overweight rose by 25%. The risk for developing diabetes increases by six-fold among lean individuals who gain more than 20 pounds in adulthood. Upper body obesity and a large waist circumference are associated with insulin resistance and dyslipidemia characterized by elevation of triglycerides and reduced HDL cholesterol levels. These are linked to an increased risk of developing diabetes and a high rate of cardiovascular morbidity and mortality. The American Diabetes Association has indicated that diabetes annually accounts for 160,000 deaths in the United States and is associated with a premature loss of 2 million years of life. When diabetes is included as a secondary cause of death, the mortality rate doubles. In fact, diabetes accounts for most of the excess morbidity and mortality associated with obesity, which is only second to smoking as a cause of preventable death in the United States. Cardiovascular disease (CVD) is the cause of death in approximately 50% of people with type 2 diabetes. The risk of death from both stroke and heart disease are estimated to be two to four fold greater in people with diabetes than in the nondiabetic population. The American Diabetes Association has estimated that 3.28 million in-patient days and 1.66 million outpatient physician visits were attributable to CVD among individuals with diabetes. Treatment advances have resulted in an overall decline in CVD death, but the diabetes-related CVD mortality has not been substantially lowered. In an effort to reduce this excess risk, the target ranges for glycemic control, lipid levels and blood pressure have recently been substantially reduced with increasing use of multiple medications in an effort to achieve an LDL cholesterol of 100 mg/dL, a blood pressure of 135/85 mmHg, and a HbA1c of 7%. Pharmacological treatment of diabetes often includes insulin therapy to improve HbA1c levels in an effort to reduce the risk of diabetes complications. However, intensifying diabetes management with insulin therapy can further increase body weight and therefore presents a major challenge. A ketogenic weight loss approach appears to increase at least initial weight loss and may reduce the need for medications. This follow-up sub-study is designed to obtain pilot data on the effect of two dietary weight loss approaches in overweight subjects with type 2 diabetes. The weight loss approaches studied will be a low-fat diet versus a ketogenic low-carbohydrate diet. Since a low fat dietary approach plus exercise was recently shown to be highly effective in reducing the incidence of diabetes in a high-risk population, we propose to compare both approaches in a sample of adults with type 2 diabetes who treatment includes insulin therapy or sulfonylureas that enhance endogenouos insulin secretion. The purpose of this comparison is twofold: 1) To compare the efficacy and safety of both dietary approaches in the treatment of type 2 diabetes and 2) Determine whether different phenotypes based on anthropometrics, lipid subfractions, and neuroactive/ orexogenic peptides, may require very different dietary approaches (low carbohydrate versus low fat) to achieve optimal metabolic and glycemic control of their type 2 diabetes.
The specific aims are to: 1. Randomize 126 overweight/obese adults with type 2 diabetes who are stable on insulin or sulfonylurea therapy, to either a low-carbohydrate or low-fat diet for 24 weeks, and then follow the participants for an additional 24 weeks to evaluate the effects of the study intervention on: Glycemic control (HbA1c) as the primary endpoint, and The following secondary endpoints: Pattern of blood glucose control (based on blood glucose monitoring) Weight changes: BMI, percent body fat and distribution of body fat. Cardiovascular and metabolic parameters e.g., blood pressure, lipid measures, CRP, leptin Type and dose of medications for diabetes, lipids and blood pressure. Adverse events such as hypoglycemia, constipation and nausea. Lifestyle (dietary intake, appetite, and physical activity) Quality of life (self-reported questionnaires). Insulin sensitivity (meal tolerance test) 2. Disseminate our study findings in peer-reviewed presentations and publications. 3. Apply for NIH funds to extend our research of the metabolic effects of controlling carbohydrate
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