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[IP] theophylline on glucose counterregulation ..& unawareness of hypoglycemia

Clin Pharmacol Ther. 2003 Jul;74(1):77-84.
Effect of 2 weeks of theophylline on glucose counterregulation in patients
with type 1 diabetes and unawareness of hypoglycemia.

De Galan BE, Tack CJ, Lenders JW, Lutterman JA, Smits P.

Background and objective A single dose of theophylline improves hypoglycemia
unawareness in type 1 diabetic patients. Prolonged theophylline use is,
however, associated with emergence of tolerance. This study investigated
prolonged use of theophylline retains efficacy for counterregulatory defects
patients with type 1 diabetes and hypoglycemia unawareness. METHODS:
Experiments were performed with 12 subjects with type 1 diabetes and
unawareness. All subjects participated in a crossover study of 2 randomly
15-day study periods during which 250 mg theophylline twice daily or matching
placebo was used. On the final day of each period, hyperinsulinemic (360 pmol.
m(-2). min(-1)) hypoglycemic (5.0, 3.5, 2.5 mmol. L(-1)) glucose clamps were
used to assess counterregulatory and cardiovascular responses. RESULTS: Under
normoglycemic conditions, there were no differences between theophylline and
placebo. Under hypoglycemic conditions, theophylline enhanced responses of
growth hormone, symptoms, heart rate, and pulse pressure (all P <.05), induced
sweating at higher plasma glucose levels (P =.039), and reduced exogenous
requirements (P =.018). Hypoglycemia-induced responses of epinephrine,
norepinephrine, and cortisol were not enhanced by theophylline. CONCLUSIONS:
Prolonged use of theophylline has a sustained effect on cardiovascular,
and symptom responses to hypoglycemia in patients with type 1 diabetes and
hypoglycemia unawareness. Whether these results translate into clinical
remains to be determined.

PMID: 12844138 [PubMed - in process]

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