The purpose of this study is to determine whether a low-fat or low-glycemic load diet is more effective for controlling weight and blood glucose in persons with type 2 diabetes.

This study focuses on the validation of the Adaptation Index instrument as a measurement of adaptive behaviors used to reduce symptoms of FI and to describe the use of adaptive behaviors among women with FI.

Women diagnosed with gestational diabetes mellitus (GDM) are at substantially increased risk of developing type 2 diabetes and obesity, currently at epidemic rates in the United States. GDM, therefore, identifies a population of women at high risk of developing type 2 diabetes and thus provides an excellent opportunity to intervene years before the development of this disorder. It is well recognized that acute as well as chronic physical activity reduce fasting plasma glucose as well as improve glucose tolerance in type 2 diabetes. Recent studies have suggested that women with higher levels of physical activity have reduced risk of GDM. Therefore, we will test the hypothesis that an exercise intervention is an effective tool for preventing GDM among women with a history of GDM.

Prevention and treatment strategies for diabetes use exercise as the cornerstone. Even though endurance training and strength training both improve insulin resistance, strength training may be better suited for persons at risk for type 2 diabetes. We will expand our pilot studies of muscle adaptation induced by resistance exercise training to determine the biochemical mechanisms that will cause people with the Metabolic Syndrome to secure major benefit from intense strength training.

African-American (AA) individuals are less sensitive to insulin than Caucasian (C ) individuals, a difference that may bear upon the greater prevalence of type 2 diabetes among AA. Lower insulin sensitivity (Si) among AA is independent of body composition, body fat distribution, diet, and physical activity. To date, no explanation has been uncovered for lower Si among AA. The PI's recent research has indicated that intramyocellular (IM) lipid, as estimated using attenuation values from a single-slice computed tomography scan of the quadriceps muscle, is higher among AA vs C postmenopausal women. Accumulation of IM lipid has been associated with impaired Si. The Specific Aims of this proposal are to:

1. Verify, using magnetic resonance spectra, that IM lipid is higher in AA vs C;
2. Determine how IM lipid relates to Si among AA and C subjects.
3. Determine if manipulation of ML via dietary intervention alters Si in healthy AA and C subjects.

A. Quantify ML and Si before and after treatment with a low- vs moderate-fat diet. Preliminary data from the investigative team have shown that a low-fat diet will deplete IMCL. B. Quantify ML and Si before and after treatment with a low- vs moderate-carbohydrate (CHO) diet. Preliminary data from the investigative team have shown that a low CHO diet reduces AIRg. The specific hypotheses to be tested are that:

1. IM lipid will be higher in AA vs C;
2. Greater IM lipid will be associated with lower Si;
3. Greater IM lipid will explain lower Si among AA vs C.
4. A low-fat diet will deplete ML and increase Si among both AA and C.
5. A low-CHO diet will decrease glucose-stimulated insulin secretion, which will result in an increase in adiponectin. The increased adiponectin will lead to an increase in ML oxidation, and a decrease in measured ML; as a result, Si will increase. These effects will be apparent primarily among AA, who have greater first-phase insulin secretion than C.

We have observed that vitamin D deficiency, as evidenced by low serum 25(OH)D concentrations, is common in children and adolescents with HIV infection. To determine whether vitamin D and calcium supplementation improve bone mineral content (BMC) and bone mineral density (BMD) in HIV-infected children and adolescents, we propose a double-blind, randomized, placebo-controlled trial comparing supplementation with oral vitamin D and calcium to placebo. The specific aims of this project are to:

1. Determine the effect of vitamin D and calcium supplementation on bone mineral accrual in HIV-infected children. We hypothesize that BMC and BMD will increase to a greater extent in HIV-infected children who receive supplementation with vitamin D and calcium. This hypothesis will be tested by comparing changes in BMC and BMD, measured by dual energy x-ray absorptiometry (DXA), after one and two years of treatment in HIV-infected children and adolescents receiving vitamin D and calcium supplementation compared to those receiving placebo.
2. Determine the effect of HIV infection and vitamin D and calcium supplementation on indices of mineral metabolism and markers of bone turnover. We hypothesize that indices of mineral metabolism and markers of bone formation and resorption will return toward normal in HIV-infected children and adolescents who are randomized to receive vitamin D and calcium supplementation. We will test these hypotheses by comparing longitudinal changes in indices of mineral metabolism and bone turnover markers in HIV-infected children and adolescents receiving vitamin D and calcium supplement versus those receiving placebo
3. Evaluate if vitamin D stores are a determinant of bone mass in HIV infected children and adolescents receiving HAART.

We hypothesize that vitamin D stores, as assessed by serum 25-hydroxyvitamin D levels, are an important determinant of bone mass in HIV-infected children and adolescents receiving HAART. We will test this hypothesis by evaluating whether measurements of bone mass are associated with vitamin D stores, as measured by serum 25-hydroxyvitamin D levels and other indices of mineral metabolism, in treated HAART-treated HIV-infected children and adolescents.

This study will determine the best location to biopsy the gastrointestinal (GI) tract for early and accurate diagnosis of GI graft-versus-host-disease (GVHD). (A biopsy is the surgical removal of a small piece of tissue for examination under the microscope.) GVHD is a life-threatening complication of stem cell transplantation in which the donor's immune cells destroy the patient's healthy tissues. It most commonly affects the skin, liver and GI tract. This study will establish where to best biopsy tissue from the GI tract and study the tissue to try to explore how GI GVD occurs and how it may be possible to better diagnose and treat it. Patients 18 years of age and older who have undergone or are who will undergo stem cell transplantation and who are at high risk for developing GI GVHD may be eligible for this study. Participants may enter the study before the transplant procedure or later if they develop GVHD symptoms. Participants undergo the following tests and procedures: I. Before starting conditioning chemotherapy or radiation therapy for the transplantation

• Medical history and physical examination
• Sigmoidoscopy (endoscopy of the lower part of the large intestine) and biopsies
• Blood draw
• Stool sample collection

II. Two to 3 weeks after conditioning regimen

• Sigmoidoscopy with biopsies
• Blood draw
• Stool sample collection

III. 30, 45, 60 and 90 days after transplantation

• Blood draw

IV. After completing the tests in part II and at the appearance of GI symptoms suspected to be due to GVHD

• Updated medical history and physical examination
• Esophagogastroduodenoscopy (endoscopy of the esophagus, stomach and upper small intestine)
• Colonoscopy (endoscopy of the entire part of the large intestine) with biopsies
• Blood draw
• Stool collection

V. Two weeks after starting therapy in patients diagnosed with GVHD

• Sigmoidoscopy with biopsies
• Blood draw
• Stool sample collection
• PET/CT scan in selected patients (nuclear medicine and x-ray imaging of the GI tract

The TODAY study group has prepared a protocol with the primary objective of collecting blood and phenotypic information to be used to explore relationships between candidate genes and type 2 diabetes (T2D), as well as obesity, insulin resistance, and cardiovascular complications of insulin resistance. Participation in the genetics study includes a blood draw for analysis of diabetes type and DNA extraction, as well as collection of basic family and medical history. Appropriate informed consent and assent are obtained from all participants to extract DNA and send blood, genetic material, and medical history to the Central Repository of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). The data are kept indefinitely by the Central Repository. The NIDDK will issue requests for proposals (RFP) throughout the scientific community for research that may help in the development of new diagnostic tests, new treatments, and new ways to prevent diabetes and other related comorbidities.

to study the dietary intake and eating behaviors of adolescents who undergo bariatric surgery

This study will test the use of a new device called a segmental stiffening wire (SSW) in colonoscopy to correct a problem called looping. Colonoscopy is the best test for detecting early colon cancer and removing growths called polyps, which can become colon cancer. Sometimes the flexible tube (colonoscope) used in the procedure loops at a certain point as it advances through the colon, making it difficult to move further and causing the patient pain from excessive stretching of the colon. The SSW is designed to prevent this by stiffening the part of the tube that would otherwise form the loop. Healthy subjects between 50 and 80 years of age and healthy subjects 40 years and older who have a family history of colon cancer may be eligible for this study. Participants undergo colonoscopy a day after self-administering a bowel cleansing preparation. The first part of the procedure is done similarly to that of a flexible sigmoidoscopy, and no sedation or pain medication is used. The colonoscope is inserted into the rectum and advanced about one-third the length of the colon. Pain or discomfort should be mild to moderate cramping and a feeling of having to move the bowels. The subject is asked to score his or her pain level at this point using a standard pain scale. If there is pain, the procedure is stopped and an x-ray is taken to determine if the colonoscope has looped. If it has, the loop is undone and the SSW is used. Another x-ray is then taken to document that the loop has been prevented with the SSW, and the procedure is completed as per standard medical practice. Subjects are taken to the recovery area, informed of the test results and then discharged home in the care of an accompanying adult.