Insulin resistance: a new consequence of altered carotid body chemoreflex? : Insulin and carotid body dysfunction

Sleep-disordered breathing is prevalent in the general population and has been linked to chronically elevated blood pressure in cross-sectional epidemiologic studies. We performed a prospective, population-based study of the association between objectively measured sleep-disordered breathing and hypertension (defined as a laboratory-measured blood pressure of at least 140/90 mm Hg or the use of antihypertensive medications). We analyzed data on sleep-disordered breathing, blood pressure, habitus, and health history at base line and after four years of follow-up in 709 participants of the Wisconsin Sleep Cohort Study (and after eight years of follow-up in the case of 184 of these participants). Participants were assessed overnight by 18-channel polysomnography for sleep-disordered breathing, as defined by the apnea-hypopnea index (the number of episodes of apnea and hypopnea per hour of sleep). The odds ratios for the presence of hypertension at the four-year follow-up study according to the apnea-hypopnea index at base line were estimated after adjustment for base-line hypertension status, body-mass index, neck and waist circumference, age, sex, and weekly use of alcohol and cigarettes. Relative to the reference category of an apnea-hypopnea index of 0 events per hour at base line, the odds ratios for the presence of hypertension at follow-up were 1.42 (95 percent confidence interval, 1.13 to 1.78) with an apnea-hypopnea index of 0.1 to 4.9 events per hour at base line as compared with none, 2.03 (95 percent confidence interval, 1.29 to 3.17) with an apnea-hypopnea index of 5.0 to 14.9 events per hour, and 2.89 (95 percent confidence interval, 1.46 to 5.64) with an apnea-hypopnea index of 15.0 or more events per hour. We found a dose-response association between sleep-disordered breathing at base line and the presence of hypertension four years later that was independent of known confounding factors. The findings suggest that sleep-disordered breathing is likely to be a risk factor for hypertension and consequent cardiovascular morbidity in the general population.

The International Diabetes Federation (IDF) has proposed a new definition of the metabolic syndrome that emphasizes central adiposity as determined by ethnic group-specific thresholds of waist circumference. The objective of this study was to estimate the prevalence of this syndrome using the IDF definition among U.S. adults and to compare it with the prevalence estimated using the definition of the National Cholesterol Education Program (NCEP). A total of 3,601 men and women aged > or =20 years from the National Health and Nutrition Examination Survey 1999-2002 were included in the analyses. Based on the NCEP definition, the unadjusted prevalence of the metabolic syndrome was 34.5 +/- 0.9% (percent +/- SE) among all participants, 33.7 +/- 1.6% among men, and 35.4 +/- 1.2% among women. Based on the IDF definition, the unadjusted prevalence of the metabolic syndrome was 39.0 +/- 1.1% among all participants, 39.9 +/- 1.7% among men, and 38.1 +/- 1.2% among women. The IDF definition led to higher estimates of prevalence in all of the demographic groups, especially among Mexican-American men. The two definitions similarly classified approximately 93% of the participants as having or not having the metabolic syndrome. In the U.S., the use of the IDF definition of the metabolic syndrome leads to a higher prevalence estimate of the metabolic syndrome than the estimate based on the NCEP definition.

To describe the role of free fatty acid (FFA) as a cause for insulin resistance in obese people. Elevated plasma FFA levels can account for a large part of insulin resistance in obese patients with type 2 diabetes. Insulin resistance is clinically important because it is closely associated with several diseases including type 2 diabetes, hypertension, dyslipidemia and abnormalities in blood coagulation and fibrinolysis. These disorders are all independent risk factors for cardiovascular disease (heart attacks, strokes and peripheral arterial disease). The mechanisms by which FFA can cause insulin resistance, although not completely known, include generation of lipid metabolites (diacylglycerol), proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP1) and cellular stress including oxidative and endoplasmic reticulum stress. Increased plasma FFA levels are an important cause of obesity-associated insulin resistance and cardiovascular disease. Therapeutic application of this knowledge is hampered by the lack of readily accessible methods to measure FFA and by the lack of medications to lower plasma FFA levels.