Reduced Sleep Duration or Quality: Relationships With Insulin Resistance and Type 2 Diabetes Esra Tasali, Rachel Leproult and Karine Spiegel T ype 2 diabetes mellitus is a chronic condition that is increasing at alarming rates worldwide. 1 Type 2 diabetes mellitus occurs when insulin resistance (ie, reduced insulin action) is accompa- nied by impaired insulin secretion. 2,3 Insulin resistance and type 2 diabetes mellitus are both associated with an increased risk of cardiovascular disease. 4,5 Obesity, family history of diabetes, decreased physical activity, and aging are among the most common factors known to contribute to the development of diabetes. An improved under- standing of the pathogenesis could lead to better preventive and therapeutic strategies. Rapidly accumulating evidence suggests that sleep loss resulting from either behavioral sleep curtailment or sleep disorders may be a novel risk factor for the development of insulin resistance and type 2 diabetes mellitus. In this article, we will first review the current epidemiologic evidence that links reduced sleep duration and/or quality to diabetes. We will then summarize the laboratory studies on the effects of manipulations of sleep duration and quality on glucose metabolism in healthy subjects with a brief discussion of potential mechanisms. In the last section, we will review the studies examining the association between insulin resis- tance, diabetes, and obstructive sleep apnea (OSA), an increasingly common sleep disorder associated with both sleep loss and poor sleep quality. Epidemiologic Studies Linking Sleep Loss to Diabetes Several population studies, originating from different geographical locations and involving diverse subject populations, investigated the association between sleep and type 2 diabetes mellitus. In all of these studies, the information on sleep duration and/or quality was obtained from self-reported measures; thus, an important limita- tion is the lack of objective assessments of sleep. Multivariate statistical models were used in nearly all these studies in an attempt to control for a variety of potential confounders such as age, body mass index, waist circumference, physical activity, smoking, caffeine or alcohol use, hypertension, depressive symptoms, and so on. A number of studies have examined the cross- sectional association between sleep and markers of diabetes or glucose control. Sleep durations of 6 hours or less or 9 hours or more were found to be associated with increased prevalence of diabetes and impaired glucose tolerance among participants in the Sleep Heart Health Study (n = 1486), after adjustments for known diabetes risk factors and the presence of insomnia symptoms. 6 A multicenter study in Finland reported independent associations between both short ( ≤6 hours) and long (≥8 hours) sleep durations and type 2 diabetes mellitus in middle-aged women, but these associa- tions did not reach statistical significance in men. 7 Another study among adults in Canada showed an increased risk of impaired glucose tolerance or type 2 diabetes mellitus for those who reported sleeping between 5 and 6 hours or 9 and 10 hours after adjustment for potential confounding variables. 8 Three independent studies examined the cross- sectional association between diabetes and sleep quality using the Pittsburgh Sleep Quality Index, 9 a validated survey. 10-12 In one study involving 161 From the Department of Medicine, University of Chicago, Chicago, IL, and INSERM / UCBL - U628, Integrated Physiology of Brain Arousal Systems, Lyon, France. Address reprint requests to Esra Tasali, MD, Department of Medicine, MC 6026, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637. E-mail: etasali@medicine.bsd.uchicago.edu 0033-0620/$ - see front matter © 2009 Published by Elsevier Inc. doi:10.1016/j.pcad.2008.10.002 Progress in Cardiovascular Diseases, Vol. 51, No. 5 (March/April), 2009: pp 381-391 381