Long‐term administration of theophylline and glucose recovery after hypoglycaemia in patients with Type 1 diabetes mellitus

Abstract

The methylxanthine theophylline increases intrahepatic c-AMP and c-AMP mediates the hepatic glucose response to adrenaline and glucagon. Intravenous theophylline increases glucose recovery during acute insulin-induced hypoglycaemia and caffeine increases hypoglycaemia awareness and glucoregulatory hormone secretion. In this study we tested the hypothesis that long-term administration of theophylline might augment glucose recovery after insulin-induced hypoglycaemia. Eleven healthy subjects and 8 patients with Type 1 diabetes mellitus were made hypoglycaemic by 60 min insulin infusion (40 mU m−2) after 2 weeks’ oral therapy with Euphyllin Retard (theophylline) or placebo. Plasma glucose nadir was 2.54 (2.31–2.77) mmol l−1 after Euphyllin Retard and 2.27 (2.05–2.48) mmol l−1 after placebo (mean difference 0.26 (0.05–0.58) mmol l−1, p = 0.09) for healthy control subjects and 2.56 (2.07–3.04) mmol l−1 and 2.19 (1.37–2.65) mmol l−1 (mean difference 0.38 (0.12–0.63) mmol l−1, p = 0.01), respectively, for diabetic patients. The area under the glucose curve was greater after theophylline treatment for healthy control subjects (p = 0.0292) and for diabetic patients (p = 0.0241) but there were no concomitant significant increases in plasma c-AMP or in endogenous glucose production rate. Whether the increase in glucose recovery is large enough to suggest that chronic theophylline administration will protect against insulin-induced hypoglycaemia remains unsettled. © 1998 John Wiley & Sons, Ltd.