Monozygotic triplets with discordance for diabetes mellitus and diabetic microangiopathy

A set of monozygotic triplets (PE.K., P.K., S.K.) has been studied. There is no diabetes in first-degree relatives. PE.K. developed insulin-requiring (60 U. NPH) diabetes at the age of 13 years. Over a period of 11 years since that time, numerous studies of insulin and growth-hormone secretion were performed on P.K. and S.K., including multiple oral glucose tolerance tests (OGTTs), cortisone-primed oral glucose tolerance tests (C-OGTTs), intravenous glucose tolerance tests (IVGTTs), and intravenous tolbutamide tests (IVTTs). The results of each test were compared with age- and sex-matched control subjects. P. K. developed insulin-requiring (56 U. NPH) diabetes after remaining discordant for eight years. Glucose, insilin, and growth-hormone responses during all tests were normal except during the IVGTT performed four months prior to the onset of diabetes. This last IVGTT revealed a glucose disappearance rate of 0.98 per cent per minute, and the slope of the regression line of serum-insulin response (IRI) on blood glucose (BG) was markedly decreased to 0.005 micronU./ml. IRI/mg./dl. BG (controls 0.340 +/- 0.04; mean +/- S.E.M.). The insulin responses in P.K. and S.K. were similar during all OGTTs, C-OGTTs, and IVTTs. S.K. has continued to maintain normal glucose tolerance and normal insulin and growth-hormone responses during all tests. The histocompability antigen studies have revealed HLA-A2, AW24, BW15, and BW40 phenotype in these monozygotic triplets. Muscle capillary basement membranes of the nondiabetic triplet were normal, whereas both diabetic triplets manifested evidence of capillary basement membrane thickening. The clinical and biochemical profiles in these triplets and the capillary basement membrane data lend strong credence to the role of "nongenetic" determinants in the development of "genetic" diabetes as well as diabetic microangiopathy in juvenile-onset-type diabetes.