Insulin-dependent or Type 1 diabetes is a major public health problem resulting in blindness, kidney failure, nerve and vascular damage and life-threatening acute metabolic problems. Currently, successful treatment is directed at the organs involved in these complications and insulin replacement. Understanding the origin of insulin-dependent diabetes could result in specific treatment aimed at correcting endogenous insulin deficiency. Immune abnormalities have been associated with insulin-dependent diabetes, and thus several in vitro quantitative and functional immunologic techniques have been developed. The functional in vitro immunologic assays include: a) immune regulatory studies using mixed lymphocyte-islet cell cultures, allogeneic and autologous mixed lymphocyte reactivity, and the production of and responsiveness to interleukin-2, b) immune islet killing studies using patient effector cells and/or antibody and islet target cells, and c) complement activation studies using islet cell induced C3 and Factor B consumption induced by serum from diabetic subjects and measurement of circulating levels of C3a, C4a, C5a, C5 activation antigen, and Factor B in patient plasma. To more directly characterize the immunological abnormalities, both cross-sectional and longitudinal designs will be used. To evaluate the natural history of immune dysfunction, insulin-dependent diabetic patients will be evaluated during disease onset, remission and thereafter using the longitudinal design. The immunologic in vitro studies will then be correlated with endogenous islet B cell function by measuring basal and stimulated circulating C-peptide levels, so as to relate the immune abnormalities to islet B cell function. Cross-sectional studies will evaluate disease specificity (Type 2 diabetic controls), disease activity (new onset, remission and chronic Type 1 studies) and genetics (HLA matched control groups). These studies may provide initial data to permit a reassessment of the current treatment of Type 1 diabetes. The health care impact of determining a treatable cause of Type 1 diabetes is of major social, medical and economic significance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033167-02
Application #
3231549
Study Section
Metabolism Study Section (MET)
Project Start
1985-09-05
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697