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Jan 23, 2009

Sleep Disorders May Increase Risk of Developing Insulin Resistance Independent of Obesity

  • A group of scientists from Johns Hopkins report an association between sleep disordered breathing (SDB) and prediabetic changes in insulin production and glucose metabolism. Separately, another Johns Hopkins research team found that obstructive sleep apnea (OSA), a common form of SDB, is connected to the progression of liver disease independent of obesity.

    Taken together the findings suggest that obesity and obstructive sleep apnea exert separate and perhaps additive negative effects on insulin resistance and the liver.

    To investigate the link between SDB and insulin resistance, the group from Johns Hopkins Bayview Medical Center Bariatric Surgery Clinic used dual-energy x-ray absorptiometry (DEXA) and frequently sampled intravenous glucose tolerance test (FSIVGTT). DEXA assesses body fat and FSIVGTT provides a picture of the subject's insulin sensitivity over time rather than at a specific moment.

    They recruited 118 subjects: 39 had no SDB, and 79 were newly diagnosed with SDB but had not been treated. Each subject underwent a sleep study to assess their level of SDB and then underwent a FSIVGGT to determine their glucose metabolism and insulin sensitivity/production the following day.

    “Our major finding was that, as we suspected, SDB was strongly associated with a decrease in the three major metabolic pathways that the body uses to metabolize glucose insulin sensitivity, glucose effectiveness, and pancreatic cell function independent of adiposity,” reports Naresh Punjabi, M.D., Ph.D. “What our research tells us is that SDB is characterized by multiple physiological deficits that increase the predisposition for type 2 diabetes mellitus.”

    A separate team found that the chronic intermittent hypoxia that often characterizes OSA is also independently linked to the progression of liver disease.

    In this study, researchers recruited 90 severely obese patients presenting for bariatric surgery without known diagnoses of obstructive sleep apnea. Each patient underwent a sleep study and blood tests for markers of liver function, insulin resistance, and systemic inflammation. The investigators were also able to analyze liver tissue through a biopsie.

    “We demonstrated that the severity of nocturnal oxyhemoglobin desaturation predicted the severity of insulin resistance and might be implicated in the development of liver disease,” says lead researcher, Vsevolod Y. Polotsky, M.D., Ph.D., of Johns Hopkins' Asthma and Allergy Center. Of the patients whose liver tissue was analyzed, those who were observed to have severe nocturnal hypoxemia also exhibited ballooning of their hepatocytes and a pericellular fibrosis of the liver, indicating liver injury.

    “In contrast, severe obesity was associated with high levels of serum c-reactive protein (CRP), indicating systemic inflammation,” Dr. Polotsky adds. “Interestingly, there was no relationship between the severity of nocturnal hypoxemia and serum CRP. This suggests that that obesity and OSA have distinct metabolic, inflammatory, and hepatic profiles, which act in different detrimental ways on the liver.

    “We hypothesize that severe obesity per se acts as a first hit in the progression of liver disease inducing hepatic steatosis, whereas the presence of the chronic intermittent hypoxemia that often characterizes OSA acts as a second hit. The hypoxic stress of OSA may induce oxidative stress in the livers of patients with severe obesity, leading to further inflammation.”

    Both papers will be published in the first issue in February of the American Journal of Respiratory and Critical Care Medicine.

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