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Winkelman, John

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Winkelman

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Winkelman, John
Author's Publications: search.filters.isAuthorOfPublication.8b003ae9-7fb1-411e-926a-73442f7a0774

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    Lack of change in glucose metabolism in eszopiclone-treated primary insomnia patients
    (Dove Medical Press, 2017) Buxton, Orfeu; Pavlova, Milena; O’Connor, Shawn P; Wang, Wei; Winkelman, John
    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.
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    Sleep disordered breathing and cardiovascular risk in older patients initiating dialysis in the United States: a retrospective observational study using medicare data
    (BioMed Central, 2016) Tuohy, C. Vaughan; Montez-Rath, Maria E.; Turakhia, Mintu; Chang, Tara I.; Winkelman, John; Winkelmayer, Wolfgang C.
    Background: Sleep disordered breathing (SDB) such as sleep apnea is associated with cardiovascular disease in the general population. However, little is known about the cardiovascular risks of SDB in patients with end-stage renal disease (ESRD). Methods: We identified Medicare fee-for-service beneficiaries aged ≥67 years initiating dialysis between 2004 and 2009. Outcomes of interest included all-cause mortality, incident myocardial infarction, ischemic stroke, and atrial fibrillation. We compared patients with and without diagnosed SDB using Cox proportional hazards regression. Results: Between 2004 and 2009, 184,217 older patients developed ESRD, of whom 15,121 (8.2 %) were previously diagnosed with SDB. Patients diagnosed with SDB were younger, more likely to be male and Caucasian, less Medicaid eligible, had more non-Nephrology clinic visits, higher body mass index, and more comorbidity. In analyses adjusting for demographics and BMI, diagnosed SDB was associated with higher risk of death and atrial fibrillation, but not associated with myocardial infarction or ischemic stroke risk. After further adjustment for all baseline characteristics, diagnosed SDB was associated with slightly lower risks of death (hazard ratio [HR]: 0.93, 95 % confidence interval [CI]: 0.91–0.96), myocardial infarction (HR: 0.92, CI: 0.87–0.98), and ischemic stroke (HR: 0.90, 95 % CI: 0.82–0.98), and not associated with atrial fibrillation (HR: 1.02, CI: 0.98–1.07). Conclusions: In older patients initiating dialysis in the U.S., diagnosed SDB was weakly associated with lower risks of death and important cardiovascular outcomes, thus adding to the list of established risk factors that are paradoxically associated with cardiovascular outcomes in the ESRD population.
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    Nocturnal leg cramps: Prevalence and associations with demographics, sleep disturbance symptoms, medical conditions, and cardiometabolic risk factors
    (Public Library of Science, 2017) Grandner, Michael A.; Winkelman, John
    Background: Nocturnal leg cramps (NLC) are common and poorly understood. Objective: To determine the prevalence of NLC and associations with cardiometabolic, sleep, and behavioral risk factors in the US population. Design: Cross-sectional epidemiology. Participants: National Health and Nutrition Examination Survey, 2005–2006 and 2007–2008 waves. Main outcome(s) and measure(s) NLC were assessed with, “In the past month, how often did you have leg cramps while trying to sleep?” Responses were categorized as None, Mild, or Moderate-Severe. Demographics, medical history, sleep disturbances, and cardiometabolic risk factors were evaluated using the 2005–2006 dataset. Variables that demonstrated significant relationships to NLC after adjusting for age, sex, education, and BMI were assessed in the 2007–2008 dataset. Variables that were still significant were entered into a forward stepwise regression model combining both waves, to determine which variables best explained the variance in NLC. Results: Prevalence was 24–25% reporting mild and 6% reporting moderate-severe NLC. NLC increased with age, lower education, unemployment, shorter sleep duration, all assessed sleep symptoms (nocturnal "leg jerks", snoring, snorting/gasping, difficulty falling asleep, difficulty maintaining sleep, non-restorative sleep, sleepiness, use of sleep medications), higher BMI, smoking, medical history (hypertension, heart failure, angina, stroke, arthritis, respiratory disease, and cancer), depression symptoms, and biomarkers (CRP, HbA1c, calcium, cadmium, red blood cells). Stepwise analysis showed that moderate-severe nocturnal leg cramps were associated with (in decreasing order of partial R2): leg jerks, poor overall health, arthritis, difficulty falling asleep, age, nonrestorative sleep, red blood cell count, lower education, angina, and difficulty maintaining sleep. Conclusions and relevance Based on this first large, representative study, NLC occurring >5x per month are reported by 6% of the adult US population. Sleep disturbance symptoms and health conditions are associated with higher frequency of NLC, suggesting that NLC is a marker, and possibly contributor, to poor sleep and general health.