Issue 167 Item 8 Theophylline Improves Hypoglycemic Unawareness In Type 1’s

In diabetic patients with hypoglycemic unawareness who took theophylline for two weeks, the drug’s effects on glucose counterregulation were sustained over the course of treatment.

In the July issue of Clinical Pharmacology and Therapeutics, Dr. Paul Smits and colleagues at the University Medical Center Nijmegen, The Netherlands, explain that a single dose of theophylline is known to improve hypoglycemic unawareness in patients with type I diabetes. Because tolerance to many of theophylline’s pharmacologic effects emerges with prolonged use, the researchers sought to determine whether improvements in hypoglycemic unawareness would also disappear with extended administration.

Twelve patients with type I diabetes and hypoglycemic unawareness participated in a crossover study in which they took 250 mg of theophylline twice daily for 15 days, or matching placebo for 15 days. On the final day of each period, hyperinsulinemic, hypoglycemic clamp studies were performed.

The authors report, "Under hyperglycemic conditions, theophylline enhanced responses of growth hormone, symptoms, heart rate, and pulse pressure (all p < 0.05), induced sweating at higher plasma glucose levels (p = 0.039) and reduced exogenous glucose requirements (p = 0.018)."

The drug did not improve responses of epinephrine, norepinephrine, or cortisol, however.

In summary, the authors write, "Two weeks of theophylline treatment increased cardiovascular, thermoregulatory, symptomatic and composite metabolic responses, but not individual hormone responses, to hypoglycemia."

They conclude that the results "suggest that theophylline retains efficacy in supporting glucose counterregulatory responses to hypoglycemia, despite long-term use." Clin Pharmacol Ther 2003;74:77-84.

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FACT: More than 61 percent of adults and 13 percent of children nationwide are overweight or obese, making them susceptible to such diseases as hypertension, diabetes and certain cancers, according to U.S. Surgeon General Richard H. Carmona.