Familial diabetes mellitus with variable B cell reserve; analysis of a pedigree

Some patients do not fall neatly into the categories of Type 1 (insulin-dependent), Type 2 (non-insulin-dependent) or maturity onset diabetes of young people diabetes. The pedigree and characteristics of the family reported here illustrate this problem. Nine cases of diabetes are known in 4 out of 5 generations, with onset between 17-70 years. Treatment was with insulin in 5 (onset 17-29 years), tablets in 3 (onset 32-70 years), and in one diabetes occurred before the insulin era. Plasma C-peptide was 0.04-0.52 nmol/l (fasting) and 0.35-1.33 nmol/l (peak stimulation with glucagon). HLA typing, available in 7 diabetic patients showed DR2 or DR7 in all, DR4 in 2 and DR3 in none. Pancreatic islet cell antibodies were absent at diagnosis in the most recently diagnosed patient. Diabetic complications remain absent in two insulin-treated patients (duration 28 and 24 years), but have occurred extensively in the remainder. The form of diabetes in this family is therefore characterised by (a) strong family history (possible autosomal dominant with variable penetrance), (b) widely variable age of onset, (c) a variable degree of B cell reserve (d) no association with HLA DR3/4 and the presence of DR2 or DR7 and (e) no protection from complications.