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American Journal of Epidemiology Vol. 120, No. 2: 315-327
Copyright © 1984 by The Johns Hopkins University School of Hygiene and Public Health

research-article

MULTIVARIATE ANALYSES OF THE RISK OF INSULIN-DEPENDENT DIABETES MELLITUS FOR SIBLINGS OF INSULIN-DEPENDENT DIABETIC PATIENTS

DRUIE E. CAVENDER1,2, DIANE K. WAGENER1,3, TREVOR J. ORCHARD1, RONALD E. LAPORTE1,, DOROTHY J. BECKER4 and LEWIS H. KULLER1

1Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh Pittsburgh, PA 15261
2Dr. Cavender is currently with the Department of Internal Medicine, University of Texas Health Science Center at Dallas Dallas, TX
3Department of Psychiatry, Western Psychiatric Institute and Clinic Pittsburgh, PA
4Division of Endocrinology, Department of Pediatrics, Children's Hospital of Pittsburgh Pittsburgh, PA

Reprint requests to Dr. Ronald LaPorte

Muitivarlate models for the risk of insulin-dependent diabetes mellitus for siblings of patients with insulin-dependent diabetes were developed using logistic regression analysis. The individuals studied in this report are full siblings of the insulin-dependent diabetic patients diagnosed at Children's Hospital of Pittsburgh between 1964 and 1982. For all siblings considered together, the sharing of two (but not one) HLA haplotypes, the presence of insulin-dependent diabetes in a parent, and being relatively young at the time the proband in the family was diagnosed were significantly associated with increased risk. On the other hand, B7+ siblings had a significantly decreased risk compared to B7– siblings, indicating the presence of an HLA-linked protective gene for the development of the disease. There was a significant interaction between sharing two HLA haplotypee and maternal age at the time of birth; for non-HLA-identlcal siblings, risk increased with increased maternal age, but maternal age had little or no effect on the risk for HLA-identical siblings. When non-HLA-identical siblings (0 or 1 HLA hapiotypes shared) were analyzed separately, only the presence of insulin-dependent diabetes in one of the parents and increased maternal age at the time of birth of the sibling were found to be significantly associated with increased risk. Both of the totally non-HLA-ldentical diabetic siblings (neither HLA haplotype shared) in this data set had a parent with insulin-dependent diabetes, indicating that at least one HLA haplotype must be inherited in common with an affected family member for diabetes to develop. For HLA-identical siblings, the significant variables were the age of the sibling when the proband was diagnosed, the possession of B7, and maternal age at the time of birth of the sibling, and all three were negatively associated with risk.

diabetes mellitus; HLA antigens; maternal age; regression analysis


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