Nature and Science of Sleep (Jul 2017)
Lack of change in glucose metabolism in eszopiclone-treated primary insomnia patients
Abstract
Orfeu M Buxton,1-4 Milena K Pavlova,1,5 Shawn P O’Connor,1 Wei Wang,1,2 John W Winkelman1,6 1Division of Sleep Medicine, Harvard Medical School, 2Department of Medicine, Brigham and Women’s Hospital, 3Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, 4Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, 5Department of Neurology, Brigham and Women’s Hospital, 6Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Study objectives: Primary insomnia (PI) may increase diabetes risk. We tested the hypothesis that the effects of PI on glucose metabolism could be improved by 2 months of pharmacological treatment.Methods: Adult men and women meeting clinical criteria for PI were studied (n=20, body mass index 25.1±2.7 kg/m2, age 39.7±7.9) in a randomized, double-blind, placebo-controlled clinical trial. The study consisted of two 1-day inpatient admissions to a General Clinical Research Center separated by 2 months of at-home treatment with 3 mg eszopiclone or placebo. During inpatient admissions, each subject underwent two intravenous glucose tolerance tests (IVGTTs) pre- and post-treatment. Diet was controlled for micro- and macro-nutrient content and calories on the day prior to pre- and post-treatment IVGTTs. Subjects were randomized following completion of the initial IVGTT to take either placebo or eszopiclone 30 min prior to bedtime at home for 2 months.Results: Two-month eszopiclone treatment did not change insulin sensitivity, glucose tolerance, or any of the sleep measures significantly, compared with placebo. Changes in glycated hemoglobin (HbA1c, clinical measure of glycemic control) were correlated with changes in diary-reported total sleep time in the eszopiclone group (r=0.66, p=0.0360), and in the combined groups’ data (r=0.55, p=0.0125). Changes in polysomnography-measured wake after sleep onset, a hallmark of PI, were positively related to changes in IVGTT-derived glucose effectiveness, or non-insulin-mediated glucose uptake.Conclusion: Treatment with 3 mg eszopiclone for 2 months, compared with placebo, did not significantly influence either sleep or measures of diabetes risk in this preliminary study. Keywords: primary insomnia, sleep duration, metabolism, IVGTT, insulin sensitivity, diabetes, eszopiclone, wake after sleep onset
