Lack of C-peptide suppression by exogenous hyperinsulinemia in subjects with symptoms suggesting reactive hypoglycemia.

The C-peptide suppression test employing the euglycemic hyperinsulinemic clamp technique has been proposed as a useful diagnostic measure for insulinoma. To examine the specificity of the C-peptide suppression, we applied this test to subjects with symptoms suggesting reactive hypoglycemia. Five subjects studied had never experienced fasting hypoglycemia, and were negative in ultrasound, CT and MRI of the pancreas. Plasma C-peptide was not suppressed by physiological (50-100 microU/ml) and supraphysiological (200-500 microU/ml) hyperinsulinemia (% of baseline: 97.3 +/- 8.6% and 90.6 +/- 10.4%, +/- SEM, respectively, both NS). Three subjects were re-examined one year later, when their hypoglycemic episodes were noticeably attenuated. No significant suppression was found. Significant suppression was observed when plasma glucose was clamped at 50-60 mg/dl in four of five subjects (61.7 +/- 11.5%, P < 0.05), but one subject responded to neither higher plasma insulin nor low-normal glucose. In contrast, normal glucose tolerance (n = 13), IGT (n = 12) and obese NIDDM (n = 31) subjects showed highly significant suppression during euglycemic and physiological hyperinsulinemia (37.1 +/- 3.8%, 46.3 +/- 5.6%, 39.9 +/- 2.6%, respectively, all P < 0.001). In conclusion, the results of the present study indicate that a failure of hyperinsulinemic suppression of C-peptide in euglycemia is not specific for insulinoma, and that suppression of C-peptide by insulin at lower plasma glucose levels (50-60 mg/dl) would be a better diagnostic test.