The Journal of clinical investigation
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No studies are available that have compared early defects in glucose metabolism in the offspring of insulin-deficient and insulin-resistant probands with non-insulin-dependent diabetes mellitus (NIDDM). To investigate this issue, we evaluated insulin secretion capacity with oral and intravenous glucose tolerance tests and with the hyperglycemic clamp, and insulin action with the euglycemic insulin clamp in 20 offspring of NIDDM patients with low fasting C-peptide (+/-450 pmol/liter), reflecting deficient insulin secretion (IS-group), 18 offspring of NIDDM patients with high fasting C-peptide (>/= 880 pmol/liter), reflecting insulin resistance (IR-group), and 14 healthy control subjects without a family history of NIDDM. The frequency of impaired glucose tolerance was 45.0% in the IS-group and 50% in the IR-group. ⋯ Maximal insulin secretion capacity evaluated by C-peptide levels during the hyperglycemic clamp did not differ between the groups. The IR-group had lower rates of whole body glucose uptake (60.1+/-4.6 micromol per lean body mass per minute) than did the control group (84.2+/-5.0 micromol per lean body mass per minute; P < 0.001) or the IS-group (82.6+/-5.9 micromol per lean body mass per minute; P < 0.01) and this was due to reduced glucose nonoxidation. To conclude, both impaired insulin secretion and insulin action seem to be inherited and could represent the primary defects in glucose metabolism in the offspring of NIDDM probands.