Alterations in Glucose Disposal in Sleep-disordered Breathing.
BACKGROUND
It is well established that sleep-disordered breathing (SDB) is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. However, data on whether SDB alters in vivo kinetics of glucose and insulin are lacking.


OBJECTIVE
The primary goal of this study was to use the frequently sampled intravenous glucose tolerance test (FSIVGTT) in subjects with and without SDB to model the in vivo kinetics of glucose and insulin. Minimal model analysis of the FSIVGTT data was used to derive parameters of insulin sensitivity, glucose effectiveness (a measure of the ability of glucose to mediate its own disposal), and pancreatic beta-cell function.


RESULTS
A total of 118 nondiabetic subjects underwent polysomnography, the FSIVGTT, and body composition measurements including determination of percent body fat. Compared with normal subjects (apnea-hypopnea index < 5 events/h), those with mild, moderate, and severe SDB displayed a 26.7, 36.5 and 43.7% reduction in insulin sensitivity, respectively, independent of age, sex, race, and percent body fat. The disposition index, an integrated measure of pancreatic beta-cell function, was also reduced in patients with moderate to severe SDB. The decrease in insulin sensitivity and the disposition index were correlated with the average degree of oxyhemoglobin desaturation. In contrast, glucose effectiveness was negatively correlated with the frequency of respiratory event-related arousals.


CONCLUSIONS
The results of this study suggest that, independent of adiposity, SDB is associated with impairments in insulin sensitivity, glucose effectiveness, and pancreatic beta-cell function. Collectively, these defects may increase the risk of glucose intolerance and type 2 diabetes mellitus in SDB.
Punjabi
Naresh M
NM
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. npunjabi@jhmi.edu
Beamer
Brock A
BA
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D017286:Polysomnography; D012307:Risk Factors; D012891:Sleep Apnea Syndromes / Q000097:blood* / Q000503:physiopathology
D001786:Blood Glucose; D007328:Insulin