Relationship between insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus: β-cell function, islet cell antibody, and haptoglobin in parents of IDDM patients

Abstract

To examine the relationship between non—insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM), we studied β-cell function, HLA type, and serologic markers of IDDM and NIDDM in the parents of IDDM patients. Fifty-two parents of 33 IDDM patients were examined in terms of islet-cell antibody (ICA) status, haptoglobin phenotype, HLA type, and insulin responses during an oral glucose tolerance test (OGTT). Twenty-seven parents were prospectively evaluated for up to 113 months. They were divided into the following three groups based on pattern of ICA positivity during the follow-up period: group 1, persistently positive ICA (n = 4); group 2, fluctuating ICA (n = 7); and group 3, persistently negative ICA (n = 16). Twenty-three percent (12 of 52) of the parents of IDDM patients had NIDDM, and 12% (six of 52) of the matched controls did. The prevalence of ICA in the parents (11 of 52, 21%) was greater than in normal controls (one of 112, P < .01). Diabetic parents tended to show a higher prevalence of ICA (six of 12, 50%) than nondiabetic parents (six of 40, 15%; P = .06). ICA-positive parents showed higher glucose levels and lower insulin responses than ICA-negative parents. Three of four parents in group 1 slowly progressed to an insulin-dependent state during 25 ± 3 months of follow-up evaluation. Parents in group 2 and group 3 did not show any changes in glucose levels or insulin responses during the study. Blood glucose levels at entry and during observation in groups 1 and 2 were higher than in group 3. Insulin responses in group 1 became lower than those in group 3 by the time the study was completed. Diabetic parents had higher frequencies of HLA-Bw54 and 1–2 haptoglobin phenotype. A high proportion of parents of IDDM patients have NIDDM. ICA-positive parents demonstrated low insulin responses. Our prospective study indicated that ICA is a marker of ongoing, slowly progressive β-cell destruction in parents of IDDM patients. It was also shown that ICA positivity in parents of IDDM patients can sometimes fluctuate. The high prevalence of NIDDM among parents of IDDM patients may be explained by persistent or fluctuating immunologic insults.