SURGICAL REMOVAL OF INSULINOMA RESTORES GLUCOSE RECOVERY FROM HYPOGLYCEMIA BUT DOES NOT NORMALIZE INSULIN ACTION

In the present study we have evaluated the effects of chronic hyperinsulinaemia secondary to insulinoma, on insulin sensitivity and on counterregulatory responses to hypoglycaemia. We studied six patients (M/F = 3/3; age = 40 +/- years), before and 6-9 months after surgical ablation of the neoplasia, by means of an euglycaemic-hyperinsulinaemic clamp (1 mU kg(-1) min(-1)). Seven normal subjects (M/F = 4/3; age = 38 +/- 6 years) underwent the same experimental study as the control subjects. In insulinoma patients after 100 min of the euglycaemic-hyperinsulinaemic clamp, glycaemia was allowed to drop to a minimum value of 1.9 mmol L(-1), and recovery evaluated after interrupting insulin infusion. During the entire study, 3-H-3-glucose was infused to determine hepatic glucose production and glucose utilization. Surgical removal of the pancreatic adenoma was followed by a reduction in body weight (BMI = 25.7 +/- 1.9 vs. 23.0 +/- 1.6 kg m(-2) P < 0.05), normalization of fasting plasma levels of glucose (2.94 +/- 0.16 vs. 4.83 +/- 0.11 mmol L(-1)), insulin (162 +/- 24 vs. 48 +/- 12 pmol L(-1)) and of basal hepatic glucose production (7.6 +/- 0.7 vs. 12.2 +/- 1.11 mu mol kg(-1) min(-1)). Before the operation, insulin-mediated glucose disposal was significantly lower than in the controls (30.8 +/- 3.1 vs. 49.1 +/- 3.1 mu mol kg(-1) min(-1)). Six to nine months after surgical removal of the adenoma, glucose utilization was unchanged (30.5 +/- 3.3 mu mol kg(-1) min(-1)) and still significantly lower than in controls (P < 0.01). After the euglycaemic phase, the plasma glucose level dropped to the same hypoglycaemic nadir (2.0 +/- 0.1 vs. 2.2 +/- 0.2 mmol L(-1)) in both studies. Upon withdrawal of insulin infusion, recovery from hypoglycaemia was much slower before than after removal of the insulinoma (0.66 +/- 0.16 vs. 2.50 +/- 0.38 mu mol min(-1); P < 0.01). The impaired recovery from hypoglycaemia was associated with a sluggish rise in plasma glucagon concentration (+ 49 +/- 15 vs. + 95 +/- 27 ng L(-1)), growth hormone (+ 16 +/- 6 vs. + 30 +/- 3 mu g L(-1)), and cortisol (+ 156 +/- 41 vs. + 361 +/- 62 nmol L(-1) all P < 0.05-0.005). In contrast to that found after adenoma removal, hepatic glucose production in insulinoma patients remained suppressed even after induction of hypoglycaemia. Our data suggest that in hyperinsulinaemic insulinoma patients restoration of normal insulin levels (a) ameliorates the response of some parameters of the counter-regulation to acute hypoglycaemia; but (b) is not able to restore normal insulin sensitivity.