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Insulin Resistance and the Cardiometabolic Syndrome: Adipose Tissue and Skeletal Muscle Factors

Liver fat, visceral adiposity, and sleep disturbances contribute to the development of insulin resistance and glucose intolerance in nondiabetic dialysis patients

Departments of ¹Nephrology, ²Radiology, ³Biochemistry, ⁴Biomathematics, School of Medicine, University of Thessaly, Larissa; ⁵Department of Sport Science, University of Thessaly, Trikala; ⁶Institute for Human Performance and Rehabilitation CE.RE.TE.TH, Trikala, Greece; and ⁷Institute of Biomedical Research and Technology, CE.RE.TE.TH, Larissa, Greece

Submitted 31 December 2007 ; accepted in final form 23 September 2008

Hemodialysis patients exhibit insulin resistance (IR) in target organs such as liver, muscles, and adipose tissue. The aim of this study was to identify contributors to IR and to develop a model for predicting glucose intolerance in nondiabetic hemodialysis patients. After a 2-h, 75-g oral glucose tolerance test (OGTT), 34 hemodialysis patients were divided into groups with normal (NGT) and impaired glucose tolerance (IGT). Indices of insulin sensitivity were derived from OGTT data. Measurements included liver and muscle fat infiltration and central adiposity by computed tomography scans, body composition by dual energy X-ray absorptiometer, sleep quality by full polysomnography, and functional capacity and quality of life (QoL) by a battery of exercise tests and questionnaires. Cut-off points, as well as sensitivity and specificity calculations were based on IR (insulin sensitivity index by Matsuda) using a receiver operator characteristics (ROC) curve analysis. Fifteen patients were assigned to the IGT, and 19 subjects to the NGT group. Intrahepatic fat content and visceral adiposity were significantly higher in the IGT group. IR indices strongly correlated with sleep disturbances, visceral adiposity, functional capacity, and QoL. Visceral adiposity, O₂ desaturation during sleep, intrahepatic fat content, and QoL score fitted into the model for predicting glucose intolerance. A ROC curve analysis identified an intrahepatic fat content of >3.97% (sensitivity, 100; specificity, 35.7) as the best cutoff point for predicting IR. Visceral and intrahepatic fat content, as well as QoL and sleep seemed to be involved at some point in the development of glucose intolerance in hemodialysis patients. Means of reducing fat depots in the liver and splachnic area might prove promising in combating IR and cardiovascular risk in hemodialysis patients.

insulin sensitivity index by Matsuda; homeostasis assessment model of insulin resistance; functional capacity; oral glucose insulin sensitivity; quality of life; quantitative insulin-sensitivity check index