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      Aspects of Inflammation and Oxidative Stress in Pediatric Obesity and Type 1 Diabetes: An Overview of Ten Years of Studies

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          Abstract

          Obesity and type 1 diabetes (T1DM) are the two most common conditions of altered metabolism in children and adolescents. In both, similar long-term cardiovascular complications are known to occur, mediated in large part by underlying inflammatory and oxidative processes whose biochemical details remain relatively unclear. Through a series of experiments in these patient populations, over the last decade our laboratory has clarified a number of key issues in this field. Interestingly, while obese and type 1 diabetic children often differed in the specific type and magnitude of molecular alterations, in both groups a clear exaggeration of inflammatory and oxidative activation was detected when compared to healthy, age-matched controls. Our main findings include definition of resting and exercise-induced cytokine patterns and leukocyte profiles, patterns of activation of immune cells in vitro, and correlation of the magnitude of observed alterations with severity of obesity and quality of glycemic control. Further, we have identified a series of alterations in growth factor profiles during exercise that parallel inflammatory changes in obese children. This paper offers a concise overview of the salient results from this decade-long research effort.

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          Most cited references29

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          Inflammation: the link between insulin resistance, obesity and diabetes.

          Recent data have revealed that the plasma concentration of inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), is increased in the insulin resistant states of obesity and type 2 diabetes, raising questions about the mechanisms underlying inflammation in these two conditions. It is also intriguing that an increase in inflammatory mediators or indices predicts the future development of obesity and diabetes. Two mechanisms might be involved in the pathogenesis of inflammation. Firstly, glucose and macronutrient intake causes oxidative stress and inflammatory changes. Chronic overnutrition (obesity) might thus be a proinflammatory state with oxidative stress. Secondly, the increased concentrations of TNF-alpha and IL-6, associated with obesity and type 2 diabetes, might interfere with insulin action by suppressing insulin signal transduction. This might interfere with the anti-inflammatory effect of insulin, which in turn might promote inflammation.
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            Inflammation: the link between insulin resistance, obesity and diabetes

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              Association between general and central adiposity in childhood, and change in these, with cardiovascular risk factors in adolescence: prospective cohort study

              Objectives To examine the prospective associations between body mass index (BMI), waist circumference, and fat mass in childhood and cardiovascular risk factors at age 15-16. Design Prospective cohort study. Setting Avon Longitudinal Study of Parents and Children. Participants 5235 children aged 9-12 at start of study. Main exposures BMI, waist circumference, and fat mass determined by dual energy x ray absorptiometry, assessed at age 9-12 and at age 15-16. Main outcome measures Systolic and diastolic blood pressure and concentrations of fasting glucose, insulin, triglycerides, low density lipoprotein cholesterol, and high density lipoprotein cholesterol assessed at age 15-16. Results In girls a 1 SD greater BMI at age 9-12 was associated with cardiovascular risk factors at age 15-16 in fully adjusted models: odds ratio 1.23 (95% confidence interval 1.10 to 1.38) for high systolic blood pressure (≥130 mm Hg); 1.19 (1.03 to 1.38) for high concentration of low density lipoprotein cholesterol (≥2.79 mmol/l); 1.43 (1.06 to 1.92) for high concentration of triglycerides (≥1.7 mmol/l); 1.25 (1.08 to 1.46) for low concentration of high density lipoprotein cholesterol ( 0.2 for heterogeneity). When waist circumference or fat mass or both were added to models including BMI they did not increase the variation in cardiovascular risk factors already explained by BMI and confounders alone. Girls who were overweight/obese at age 9-12 but were normal weight by 15-16 had similar odds of adverse levels of risk factors to those who were normal weight at both ages. In boys odds of high systolic blood pressure, high concentrations of triglycerides and insulin, and low concentrations of high density lipoprotein cholesterol remained higher in this group compared with those who were normal weight at both ages but were lower than in those who remained overweight/obese at both ages. Conclusions Measurements of waist circumference or directly assessed fat mass in childhood do not seem to be associated with cardiovascular risk factors in adolescence any more strongly than BMI. Girls who favourably alter their overweight status between childhood and adolescence have cardiovascular risk profiles broadly similar to those who were normal weight at both time points, but boys who change from overweight to normal show risk factor profiles intermediate between those seen in boys who are normal weight at both ages or overweight at both ages.
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                Author and article information

                Journal
                Exp Diabetes Res
                Exp Diabetes Res
                EDR
                Experimental Diabetes Research
                Hindawi Publishing Corporation
                1687-5214
                1687-5303
                2012
                11 October 2012
                : 2012
                : 683680
                Affiliations
                1Insitute for Clinical and Translational Science, University of California, 843 Health Science Road, Irvine, CA 92697, USA
                2Department of Pediatrics, School of Medicine, University of California, 100 Theory, Irvine, CA 92697, USA
                3Department of Pharmacology, School of Medicine, University of California, 360 Med. Suzge II, Irvine, CA 92697, USA
                Author notes
                *Pietro Galassetti: pgalasse@ 123456uci.edu

                Academic Editor: Dan Nemet

                Article
                10.1155/2012/683680
                3475317
                23093953
                dfb22c21-c381-4458-bfee-1b8f0ed2b2ee
                Copyright © 2012 Brian Tran et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 May 2012
                : 16 August 2012
                Categories
                Review Article

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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