SYMPTOMS, HORMONES, AND GLUCOSE FLUXES DURING A GRADUAL HYPOGLYCEMIA-INDUCED BY INTRAPERITONEAL VS VENOUS INSULIN INFUSION IN TYPE-I DIABETES

Intraperitoneal (IP) insulin infusion with programmable implantable pu mps is associated with a reduction in hypoglycaemic events when compar ed to intensive diabetes management with subcutaneous insulin in patie nts with Type 1 diabetes mellitus. The mechanism may involve more phys iological insulin kinetics, lower peripheral insulin levels or a speci fic hepatic action of portal insulin on hypoglycaemic counter regulati on. To investigate the latter two hypotheses, we performed two hypogly caemic clamps (controlled blood glucose decrement to 2.2 mmol I-1) in random order in 12 Type 1 diabetic patients. Insulin was infused eithe r IP or IV for 150 min, at rates chosen to generate similar peripheral insulin levels (1 mU/kg(-1) min(-1) IV or 2 mU/k(-1) min(-1) IP, n = 6) to evaluate direct hepatic action, or at similar rates (1 mU/kg(-1) min(-1) IV and IP, n = 6) to evaluate IP indirect effects via lower p eripheral insulinaemia. Hepatic glucose production and glucose utiliza tion were measured by [6,6 H-2] glucose dilution technique. Glucose pr oduction was lower (1.7 +/- 0.4 vs 0.5 +/- 0.4 mg kg(-1) min(-1), p < 0.05), and utilization was similar at the end of the matched-insulinae mia IV and IP clamps, respectively. By contrast, glucose production wa s higher (1.7 +/- 0.5 IV vs 2.7 +/- 0.3 IP mg kg(-1) min(-1), p < 0.01 ) and glucose utilization lower (4.4 +/- 1.0 IV vs 3.3 +/- 0.2 IP mg k g(-1) min(-1), p < 0.05) with IP delivery at the end of the matched-do se clamps. Counterregulatory hormones and hypoglycaemic symptoms incre ased similarly in all clamps. In summary, IP insulin, when compared to IV insulin at similar delivery rates, but not at similar insulinaemia , is associated with a less negative glucose balance (glucose producti on-glucose utilization) during hypoglycaemia. Such a mechanism may pla y a role in the reduced hypoglycaemic risk seen with IP implantable pu mps.