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Nocturnal Hypoglycemia in Type 1 Diabetes: An Assessment of Preventive Bedtime Treatments

Division of Endocrinology, Metabolism, and Lipid Research and the General Clinical Research Center and the Diabetes Research and Training Center, Washington University School of Medicine, St. Louis, Missouri 63110

Address all correspondence and requests for reprints to: Philip E. Cryer, M.D., Campus Box 8127, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110. E-mail: pcryer{at}wustl.edu.

Objective: We assessed four putative bedtime treatments in the prevention of nocturnal hypoglycemia in type 1 diabetes.

Research Design and Methods: Plasma glucose concentrations were measured every 15 min from 2200 h through 0700 h in 21 patients with type 1 diabetes (mean ± SD HbA_1C = 7.1 ± 1.0%) on five occasions with, in random sequence, bedtime (2200 h) administration of 1) no treatment, 2) a snack, 3) the snack plus the -glucosidase inhibitor acarbose, 4) an uncooked cornstarch bar, or 5) the ß₂-adrenergic agonist terbutaline.

Results: In the absence of a bedtime treatment, 27% of the measured nocturnal plasma glucose concentrations were less than 70 mg/dl (3.9 mmol/liter) in 12 patients; 16, 6, and 1% were less than 60, less than 50, and less than 40 mg/dl (3.3, 2.8, and 2.2 mmol/liter), respectively. Neither the snack (without or with acarbose) nor cornstarch raised the mean nadir nocturnal glucose concentration or reduced the number of low glucose levels or the number of patients with low levels. Terbutaline raised the mean nadir nocturnal glucose concentration (mean ± SE, 127 ± 11 vs. 75 ± 9 mg/dl; P < 0.001), eliminated glucose levels less than 50 mg/dl (P = 0.038), reduced levels less than 60 mg/dl (P = 0.005) to one, and reduced levels less than 70 mg/dl (P = 0.001) to five (four at 2215 h, one at 2230 h). However, it also raised glucose levels the following morning.

Conclusions: Nocturnal hypoglycemia is common in aggressively treated type 1 diabetes. Bedtime administration of a conventional snack or of uncooked cornstarch does not prevent it. That of terbutaline prevents nocturnal hypoglycemia but causes hyperglycemia the following morning. The efficacy of a lower dose of terbutaline remains to be determined.

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