Secretion of insulin or connecting peptide: a predictor of insulin dependence of obese "diabetics".

Ninety obese "diabetic" patients, including 55 treated with insulin injection, were characterized by measurement of levels of insulin or connecting peptide of proinsulin (C peptide) induced during oral glucose tolerance testing. After reduction of body weight to ideal values, patients whose peak serum insulin levels were initially 64 microunits/mL or greater had reductions of blood glucose values from 227 +/- 24 to 122 +/- 10 mg/dL (fasting) and from 400 +/- 49 to 160 +/- 11 mg/dL (two hours postprandial); at C-peptide peaks of 6.0 ng/mL or greater, these blood glucose values fell from 244 +/- 30 to 118 +/- 12 mg/mL and from 400 +/- 51 to 160 +/- 16 mg/dL, respectively. Patients with peak values of less than 60 microunits/ml for insulin or less than 6.0 ng/mL for C peptide did not normalize the blood glucose concentration after weight loss. This critical level of insulin secretory reserve separating these groups was similar to that previously reported for avoidance of diabetic retinopathy and neuropathy. These results suggest that levels of insulin or C peptide induced during glucose tolerance testing distinguish between two types of hyperglycemic obesity-insulin-dependent diabetes mellitus and insulin-resistant obesity. Blood glucose levels alone did not identify these groups. Among consecutive hyperglycemic obese patients, 36% achieved normoglycemia by weight loss alone, including 33% of those previously treated with insulin injection.