ANTIINSULIN ANTIBODIES ARE A CAUSE OF HYPOGLYCEMIA FOLLOWING PANCREASTRANSPLANTATION

OBJECTIVE- Hypoglycemic symptoms have been reported by more than half of pancreas transplantation (PTX) recipients. To better understand the mechanism for the hypoglycemia documented in some of these patients, we studied the glucose and pancreatic hormone response to Sustacal in patients with and without hypoglycemia following PTX. RESEARCH DESIGN AND METHODS- Twelve patients with established, repeated episodes of hy poglycemia following PTX (hypo) were case-matched to PTX recipients wi thout hypoglycemic symptoms (control; n = 7). On the day of the study, fasting glucose, free and total immunoreactive insulin (IRI), C-pepti de, proinsulin, and glucagon were drawn (time 0); Sustacal was adminis tered; and glucose, free and total IRI, and C-peptide were assayed at 15, 30, 45, 75, 120, 150, 180, and 240 min. Based on the glucose respo nse to Sustacal, the hypo group was further divided into those whose g lucose rose after Sustacal (hypo-high; n = 7) and those with no increa se in glucose from baseline concentration (hypo-flat; n = 5). RESULTS- Before the administration of Sustacal, the hypo-high group had a lowe r fasting free/total IRI (0.26 +/- 0.06, mean +/- SE) than the hypo-fl at(0.51 +/- 0.02) or control (0.52 +/- 0.04) groups (both P < 0.05 com pared with hypo-high). The glucose response to Sustacal was greatest i n the hypo-high group as defined. Area under the curve (AUC) for total IRI following Sustacal was also greatest in the hypo-high group (P < 0.05 compared with both control and hypo-flat groups), but there was n o significant difference in free IRI AUC following Sustacal between th e three groups. Two individuals developed hypoglycemia during the Sust acal challenge, both in the hypo-high group. CONCLUSIONS- The lower fa sting free/total IRI ratio and greater increase in glucose and total I RI in response to Sustacal in the hypo-high group compared with either the hypo-flat or control groups are consistent with the presence of s ignificant quantities of anti-insulin antibodies in the hypo-high grou p. Because anti-insulin antibodies are, in turn, an established cause of episodic hypoglycemia, this study provides the first data to suppor t the hypothesis that significant quantities of anti-insulin antibodie s are a cause of symptomatic hypoglycemia following PTX in some recipi ents.