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Effect of 2 weeks of theophylline on glucose counterregulation in patients with type 1 diabetes and unawareness of hypoglycemia . 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 whether prolonged use of theophylline retains efficacy for counterregulatory defects in patients with type 1 diabetes and hypoglycemia unawareness . METHODS Experiments were performed with 12 subjects with type 1 diabetes and hypoglycemia unawareness . All subjects participated in a crossover study of 2 randomly scheduled 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 x m ( -2 ) x min ( -1 ) ) hypoglycemic ( 5.0 , 3.5 , 2.5 mmol x 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 glucose 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 , metabolic , and symptom responses to hypoglycemia in patients with type 1 diabetes and hypoglycemia unawareness . Whether these results translate into clinical benefit remains to be determined .
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Intervention_Pharmacological
250 mg theophylline twice daily
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Intervention_Control
matching placebo
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Intervention_Physical
counterregulatory and cardiovascular responses
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Outcome_Physical
glucose counterregulation
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Outcome_Physical
counterregulatory defects
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Outcome_Physical
counterregulatory and cardiovascular responses
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Outcome_Physical
growth hormone , symptoms , heart rate , and pulse pressure
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Outcome_Physical
induced sweating at higher plasma glucose levels
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Outcome_Physical
reduced exogenous glucose requirements
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Outcome_Physical
cardiovascular , metabolic , and symptom responses
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Participant_Condition
type 1 diabetic patients
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Participant_Condition
type 1 diabetes
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Participant_Condition
hypoglycemia unawareness
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Participant_Sample-size
12 subjects
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Participant_Sample-size
subjects