MECHANISMS OF FASTING HYPOGLYCEMIA AND CONCOMITANT INSULIN RESISTANCE IN INSULINOMA PATIENTS

To gain further insight into the pathogenesis of fasting hypoglycemia in patients with insulin-secreting adenoma of the pancreas, we studied seven patients affected by insulinoma (age, 42 ± 7 years; body mass index [BMI], 27 ± 2 kg/m2) and seven normal subjects. In insulinoma patients, hepatic glucose production (HGP) and glucose utilization (Rd) were evaluated by infusion of 3-3H-glucose at spontaneous fasting plasma glucose concentration, after restoration of euglycemia and during euglycemic insulin clamp (40 mU/m2/min). In insulinoma patients, fasting plasma glucose concentration (2.8 ± 0.2 v 4.5 ± 0.1 mmol/L; P < .001), HGP, and glucose Rd (7.8 ± 1.1 v 12.0 ± 0.3 μmol/kg/min; P < .01) were lower than in normal subjects, while plasma insulin level was higher (138 ± 19 v 38 ± 3 pmol/L; P < .001). In insulinoma patients after attainment of euglycemia (4.7 ± 0.2 mmol/L) by exogenous glucose infusion, insulin level increased slightly (174 ± 18 pmol/L; P < .01) and glucose Rd was similar to that of normal individuals (12.8 ± 0.6 v 12.0 ± 0.3 μmol/kg/min). During the clamp studies, glucose Rd was lower in insulinoma patients (18.7 ± 1.2 v 33.8 ± 3.1 μmol/kg/min; P < .01) despite higher plasma insulin concentration (612 ± 48 v 420 ± 12 pmol/L). Therefore, glucose Rd I × 100 ratio (where I is plasma insulin concentration) was much lower in insulinoma patients (3.1 ± 0.9 v 8.0 ± 0.7; P < .01), suggesting a marked degree of insulin resistance. HGP was completely suppressed in both groups. Plasma insulin clearance rate was reduced in insulinoma patients (9.8 ± 0.9 v 14.3 ± 0.4 mL/kg/min; P < .05). In conclusion, our data demonstrate that in insulinoma patients (1) fasting hypoglycemia is mainly due to inhibition of HGP; (2) at euglycemia, glucose Rd is similar to that of normal subjects; and (3) insulin-mediated glucose disposal is markedly impaired. © 1993.