ERRATIC OSCILLATORY CHARACTERISTICS OF PLASMA-INSULIN CONCENTRATIONS IN PATIENTS WITH INSULINOMA - MECHANISM FOR UNPREDICTABLE HYPOGLYCEMIA

Patients with insulin-producing tumors may have hypoglycemic symptoms at unpredictable times. This study evaluated whether plasma insulin os cillations, known to occur in normal individuals but not explored in p atients with insulinomas, could be an underlying mechanism for such ev ents. Nine normal subjects and five patients with proven insulinomas w ere studied in the fasting state. Serial sampling of arterialized bloo d over 80-100 min, at 2- or 3-min intervals was performed. In normal s ubjects, mean plasma glucose and insulin concentrations were 5.3 +/- 0 .1 mmol/L and 58 +/- 9 pmol/L, respectively. Regular, low-amplitude pl asma insulin oscillations were observed, with a period of 10-17 min. T he subjects with insulinomas had lower mean plasma glucose and higher insulin concentrations than controls, 3.6 +/- 0.3 mmol/L (P = 0.01) an d 150 +/- 42 pmol/L, (P = 0.01), respectively. They also had insulin o scillations that appeared unstable as a result of variability in durat ion and amplitude compared with controls. The insulin pulses were irre gular, and interpeak intervals varied between 4-54 min in different su bjects; in some subjects, the amplitude was also variable, with sudden spontaneous pulses as high as 565 pmol/L, with an associated glucose decrement. We conclude that large spontaneous bursts of insulin secret ion occur in patients with insulinomas as part of an erratic pattern o f oscillatory insulin secretion, and these can account for unpredictab le occurrences of hypoglycemia.