UCSF DIABETES, ENDOCRINOLOGY & METABOLISM TRAINING PROGRAM FACULTY RESEARCH SUMMARIES

I have a number of multidisciplinary collaborations that are ongoing.

(1) The UCSF Diabetes Center has a major interest in the development of effective therapies for type 1 diabetes. Dr. Jeffrey Bluestone of the Diabetes Center has created a humanized monoclonal anti-CD3 antibody which in experimental animals prevents the development of type 1 diabetes. I served as the Principal Investigator for the site for two multicenter phase 1, 2 clinical trials with this drug. These trials showed that the monoclonal antibody delayed the beta cell loss that occurs after the onset of type 1 diabetes mellitus. I have continuing clinical collaborations with Drs. Bluestone and Gitelman (Pediatric Endocrinology) with this and other immunomodulatory agents in the treatment of type 1 diabetes.

(2)The goal of the Islet Transplant Group (a collaboration between the Departments of Surgery and Medicine) is to develop protocols for establishment of long term insulin independence in patients with type 1 diabetes. As a member of the group, I participate in the recruitment, management of diabetes mellitus pre-and posttransplantation and tests of beta cell function pre- and post transplantation. I am also interested in examining the psychosocial impact of pancreas and islet transplantation and am setting up a protocol in collaboration with Dr. Lawrence Fisher in the Department of Family Medicine to do this.

(3) Insulin resistance is an important component of the pathophysiology of type 2 diabetes and the metabolic syndrome. I have established the euglycemic hyperinsulinemic clamp protocol at the UCSF General Clinical Research Center for the study of insulin resistance. Drs. Goldfine, Youngren and I are currently using this clamp protocol to study the effects of exercise training in insulin-resistant nonobese nondiabetic subjects. We are starting a study examining the effect of chromium therapy on a similar cohort.

(4) I am collaborating with Dr. Lawrence Fisher and colleagues (Departments of Family Medicine and Psychiatry) to examine the relationships between glycemic control, co-morbidities, depression and psychosocial stress in two prospective cohorts. It has been hypothesized that psychosocial stress, through changes in cortisol secretory patterns, can lead to visceral obesity and insulin resistance, and he has just established a protocol for collection of salivary cortisol levels in these 2 cohorts to test this idea.

Selected References

Steele C, Hagopian WA, Gitelman S, Masharani U, Cavaghan M, Rother K, Donaldson D, Harlan DM, Bluestone J, Herold KC (2004) Insulin secretion in type 1 diabetes. Diabetes 53:426-433

Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. (2005) A Single Course of Anti-CD3 Monoclonal Antibody hOKT3{gamma}1(Ala-Ala) Results in Improvement in C-Peptide Responses and Clinical Parameters for at Least 2 Years after Onset of Type 1 Diabetes. Diabetes. 54:1763-1769.

Masharani U, Shiboski S, Eisner MD, Katz PP, Janson SL, Granger DA, Blanc PD (2005) Impact of exogenous glucocorticoid use on salivary cortisol measurements among adults with asthma and rhinitis. Psychoneuroendocrinology 30 : 744-752.

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