Preliminary evidence for obesity-associated insulin resistance in adolescents without elevations of inflammatory cytokines.
ABSTRACT BACKGROUND: To ascertain whether the associations between obesity, inflammation, and insulin resistance established in human adult studies are found among adolescents. METHODS: We contrasted 36 obese and 24 lean youth on fasting glucose, insulin levels, lipid profile, hemoglobin A1C, markers of hepatic function, white blood cell count, C-reactive protein (CRP) and fibrinogen levels. The cytokines IL-6, TNF-alpha, IFN-gamma, IL-10 and IL-4 and the adipokines leptin, resistin, and adiponectin were also compared between the two groups. The fasting glucose and insulin values were used to estimate the degree of insulin resistance with the homeostatic model assessment of insulin resistance (HOMA-IR). T-tests and correlations were run to examine group differences and associations between groups. In addition, regression analyses were used to ascertain whether the markers of inflammation were predictive of the degree of insulin resistance. RESULTS: Although obese adolescents had clear evidence of insulin resistance, only CRP, fibrinogen and leptin were elevated; there were no group differences in pro- or anti-inflammatory cytokines nor adiponectin and resistin. Anthropometric measures of obesity and level of insulin resistance were highly correlated to the acute phase reactants CRP and fibrinogen; however, the degree of insulin resistance was not predicted by the pro- or anti-inflammatory cytokine markers. Obese adolescents had higher white blood cell counts. In addition they had higher circulating alanine aminotransferase concentrations and lower circulating albumin and total protein than lean adolescents, possibly as a result of hepatocyte damage from fatty liver. CONCLUSION: Unlike rodent or adult studies, we found that wide-spread systemic inflammation is not necessarily associated with insulin resistance among adolescents. This finding does not support the current paradigm that the associations between obesity and insulin resistance are, to a significant degree, mediated by low grade systemic inflammation. These data support the need for further adolescent studies to explore these associations.
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ABSTRACT: Obesity, which is assuming alarming proportions, has been attributed to genetic factors, hypothalamic dysfunction, and intestinal gut bacteria and an increase in the consumption of energy-dense food. Obesity predisposes to the development of type 2 diabetes mellitus, hypertension, coronary heart disease, and certain forms of cancer. Recent studies have shown that the intestinal bacteria in obese humans and mice differ from those in lean that could trigger a low-grade systemic inflammation. Consumption of a calorie-dense diet that initiates and perpetuates obesity could be due to failure of homeostatic mechanisms that regulate appetite, food consumption, and energy balance. Hypothalamic factors that regulate energy needs of the body, control appetite and satiety, and gut bacteria that participate in food digestion play a critical role in the onset of obesity. Incretins, cholecystokinin, brain-derived neurotrophic factor, leptin, long-chain fatty acid coenzyme A, endocannabinoids and vagal neurotransmitter acetylcholine play a role in the regulation of energy intake, glucose homeostasis, insulin secretion, and pathobiology of obesity and type 2 diabetes mellitus. Thus, there is a cross-talk among the gut, liver, pancreas, adipose tissue, and hypothalamus. Based on these evidences, it is clear that management of obesity needs a multifactorial approach.Nutrition 12/2009; 26(5):459-73. · 3.03 Impact Factor