The Divisions main research activities are currently in clinical and translational research. Recruitment of bench researchers is a top priority for the Division. Current areas of investigation include: pathogenesis of type 2 diabetes; developing innovative treatment strategies for type 2 diabetes; insulin action and b-cell function in gestational diabetes; clinical and community approaches to diabetes prevention; and the role of magnesium in osteoporosis, and management of thyroid neoplasms.

Special Basic Research Activities

Robert Rude, M.D.
Magnesium Depletion as a Pathogenic Factor in the Causation of Osteoporosis. Dr. Rude has been awarded an NIH grant to pursue the role of magnesium depletion in producing osteoporosis employing a new rat model recently developed in his laboratory. As magnesium depletion commonly occurs in the American population and is a critically important micro-nutrient required for bone formation, magnesium depletion is very likely to play an important role in the pathogenesis of this very common disorder. In further pursuit of this hypothesis, Dr. Rude received a Wright Foundation grant to assess the influence of dietary magnesium intake on bone mass in women.

Carole A. Spencer, Ph.D., M.T.
The clinical utility of serum thyroglobulin (Tg) and Tg autoantibody (TgAb) measurements in patients with differentiated thyroid carcinomas (DTC) remains one of Dr. Spencer’s primary research interests. The pioneering work of Dr. Spencer and her clinical colleagues maintains USC on the cutting edge of clinical research on thyroid cancer prognosis and management. Dr. Spencer’s current research suggests that the use of a serum Tg assay with 100-fold more sensitivity than current clinical assays would greatly reduce or obviate the need for expensive recombinant human TSH (rhTSH)-stimulated Tg testing of DTC patients.

Special Clinical Research Activities

Thomas A. Buchanan, M.D.
Pathogenesis of Type 2 Diabetes in Latino Women. This is a 10-year cohort study designed to: 1) identify early metabolic defects that predict the development of type 2 diabetes after gestational diabetes, and 2) identify the metabolic changes that occur as young Latino women develop early diabetes. The study has defined the interaction between insulin resistance and insulin secretion during the development of type 2 diabetes. Basically, insulin resistance requires increased insulin secretion from the pancreas. In a subset of people, the increased secretion cannot be maintained over long periods of time. Their insulin secretion falls and, when it reaches a critical level, glucose rises rapidly and to diabetic levels.

Prevention of Type 2 Diabetes: Drs. Thomas Buchanan, Anny Xiang (Department of Preventive Medicine) and Siri Kjos (Department of Ob/Gyn) have continued their diabetes prevention work using clinically approved insulin-sensitizing drugs. The current study, referred to as PIPOD (for pioglitazone in prevention of diabetes), continues to show a reduction in the risk of diabetes in women who initially entered a troglitazone-based program in 1996-1998.

Genetics of Pancreatic b-cell Failure in Mexican-Americans (the BetaGene Study). The diabetes prevention work conducted by Dr. Buchanan and colleagues revealed a specific b-cell defect that leads to type 2 diabetes in Hispanic women who have had gestational diabetes. Dr. Buchanan and two colleagues from the USC Department of Preventive Medicine, Richard Watanabe and Anny Xiang, conducted a pilot study in 54 Mexican American families that demonstrated the b-cell defect to be highly heritable, suggesting important genetic regulation. Drs. Buchanan, Watanabe and Xiang, along with Dr. Jean Lawrence from Kaiser Permanente and Dr. Francis Collins from the National Human Genome Research Institute, have been awarded a five-year, $7M grant to recruit and phenotype ~3,000 individuals to try to identify the causal gene(s).

GCRC Highlights. The USC General Clinical Research Center (GCRC) program, directed by Dr. Thomas Buchanan with assistance from Drs. Fred Sattler and Richard Watanabe, continues as one of the largest GCRC programs in the U.S., with sites on the USC Health Sciences Campus, Children’s Hospital Los Angeles, and City of Hope National Medical Center. During 2003- 2004, the Parent GCRC supported ~4,000 outpatient visits and ~700 inpatient visits for research studies in diabetes, obesity, cancer, AIDS, multiple sclerosis, aging, hepatitis, and several other diseases. All told, there were 66 active protocols being conducted by 47 principal investigators.

Adina Zeidler, M.D.
Prediction of cardiomyopathy in type 1 diabetes by 31P Magnetic Resonance Spectroscopy (MRS). This is a six-year study of patients who have had type 1 diabetes for at least ten years prior to enrollment. Sixty patients will be studied, mostly of Latino ancestry, and 60 control subjects, age and sex matched. The recruitment of the diabetic patients is conducted from an ongoing type 1 diabetic registry of Latino ancestry, which has over 3,000 patients currently listed. This registry was established by Dr. Zeidler in 1989. There are three parts of the protocol: Potential patients and controls are screened by Dr. Zeidler’s research team, who enroll qualified subjects. Dr. Rohit Varma (Department of Ophthalmology) evaluates the participants for diabetic eye disease. Dr. Gerald Pohost (Chief of the Division of Cardiovascular Medicine and Principal Investigator for the project) and his research team perform 31P-NMR spectroscopy baseline and annually during the study to evaluate cardiac biochemistry and energetics. These results of this project will provide a better understanding of the etiology of diabetic cardiomyopathy and a basis for improved management of diabetic patients with cardiac diseases as well as the development of novel therapeutic intervention.