Long-term administration of theophylline and glucose recovery after hypoglycaemia in patients with type 1 diabetes mellitus.
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.
Department of Internal Medicine and Endocrinology, Hvidovre University Hospital, Copenhagen, Denmark.
A
A
Hvidberg
A
A
Rosenfalck
N J
NJ
Christensen
J
J
Hilsted
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D000242:Cyclic AMP / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000188:drug therapy*; D007328:Insulin / Q000009:adverse effects; D007700:Kinetics; D008297:Male; D010726:Phosphodiesterase Inhibitors; D010919:Placebos; D013806:Theophylline / Q000008:administration & dosage / Q000627:therapeutic use*
D001786:Blood Glucose; D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D010919:Placebos; D013806:Theophylline; D000242:Cyclic AMP