LACK OF C-PEPTIDE SUPPRESSION BY EXOGENOUS HYPERINSULINEMIA IN SUBJECTS WITH SYMPTOMS SUGGESTING REACTIVE HYPOGLYCEMIA

The C-peptide suppression test employing the euglycemic hyperinsulinem ic clamp technique has been proposed as a useful diagnostic measure fo r insulinoma. To examine the specificity of the C-peptide suppression, we applied this test to subjects with symptoms suggesting reactive hy poglycemia. Five subjects studied had never experienced fasting hypogl ycemia, and were negative in ultrasound, CT and MRI of the pancreas. P lasma C-peptide was not suppressed by physiological (50-100 mu U/ml) a nd supraphysiological (200-500 mu U/ml) hyperinsulinemia (% of baselin e: 97.3 +/- 8.6% and 90.6 +/- 10.4%, +/- SEM, respectively, both NS). Three subjects were re-examined one year later, when their hypoglycemi c episodes were noticeably attenuated. No significant suppression was found. Significant suppression was observed when plasma glucose was cl amped 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-n ormal glucose. In contrast, normal glucose tolerance (n=13), IGT (n=12 ) and obese NIDDM (n=31) subjects showed highly significant suppressio n during euglycemic and physiological hyperinsulinemia (37.1 +/- 3.8%, 46.3 +/- 5.6%, 39.9 +/- 2.6%, respectively, all P<0.001). In conclusi on, the results of the present study indicate that a failure of hyperi nsulinemic suppression of C-peptide in euglycemia is not specific for insulinoma, and that suppression of C-peptide by insulin at lower plas ma glucose levels (50-60 mg/dl) would be a better diagnostic test.