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      Reduced atherogenic indices in prepubertal girls with precocious adrenarche born appropriate for gestational age in relation to the conundrum of DHEAS

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          Abstract

          Context

          An association between low birth weight, insulin resistance (IR), dyslipidemia, and atherogenesis has been shown in girls with precocious adrenarche (PA).

          Objective

          To evaluate whether girls with PA born appropriate for gestational age (AGA) have increased risk for metabolic complications at initial evaluation.

          Design/methods

          We conducted a cross-sectional study on 69 AGA born girls with PA (mean (± s.d.) age 7.1±1 years) and 45 body mass index (BMI)- and waist circumference (WC)-matched prepubertal peers born AGA (mean (± s.d.) 7.5±1.9 years). A standard 2-h oral glucose tolerance test with insulin sampling was performed. Fasting plasma lipids and high-sensitivity C-reactive protein were analyzed, and blood pressure was recorded. Insulin sensitivity (IS) index (ISI comp), homeostasis model assessment of IR, and atherogenic index (AI) (triglycerides/high-density lipoprotein cholesterol) were calculated.

          Setting

          The study was performed at University Hospital.

          Results

          AI was significantly lower in girls with PA than in controls ( P<0.001), and it was correlated with BMI SDS ( r=0.44, P=0.001) and WC ( r=0.39, P=0.001). The significant correlation of AI with ISI comp ( r=−0.38, P=0.001) disappeared after correcting for BMI ( r=−0.185, P=0.16). Multivariate regression analysis revealed that DHEAS was the only significant parameter influencing AI in girls with born AGA ( R 2=0.475 β=−0.018, P=0.0001).

          Conclusions

          Metabolic screening in prepubertal AGA born girls with PA may yield favorable lipid profiles. AI in girls with PA is increased in relation to decreasing IS and increasing BMI and WC. DHEAS seems to have the most significant effect on AI.

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          Most cited references39

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          Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.

          Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test (OGTT). However, the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique. In this study, we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique. In this study, 153 subjects (66 men and 87 women, aged 18-71 years, BMI 20-65 kg/m2) with varying degrees of glucose tolerance (62 subjects with normal glucose tolerance, 31 subjects with impaired glucose tolerance, and 60 subjects with type 2 diabetes) were studied. After a 10-h overnight fast, all subjects underwent, in random order, a 75-g OGTT and a euglycemic insulin clamp, which was performed with the infusion of [3-3H]glucose. The indices of insulin sensitivity derived from OGTT data and the euglycemic insulin clamp were compared by correlation analysis. The mean plasma glucose concentration divided by the mean plasma insulin concentration during the OGTT displayed no correlation with the rate of whole-body glucose disposal during the euglycemic insulin clamp (r = -0.02, NS). From the OGTT, we developed an index of whole-body insulin sensitivity (10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]), which is highly correlated (r = 0.73, P < 0.0001) with the rate of whole-body glucose disposal during the euglycemic insulin clamp. Previous methods used to derive an index of insulin sensitivity from the OGTT have relied on the ratio of plasma glucose to insulin concentration during the OGTT. Our results demonstrate the limitations of such an approach. We have derived a novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT.
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            Insulin resistance in children: consensus, perspective, and future directions.

            Emerging data indicate that insulin resistance is common among children and adolescents and is related to cardiometabolic risk, therefore requiring consideration early in life. However, there is still confusion on how to define insulin resistance, how to measure it, what its risk factors are, and whether there are effective strategies to prevent and treat it. A consensus conference was organized in order to clarify these points. The consensus was internationally supported by all the major scientific societies in pediatric endocrinology and 37 participants. An independent and systematic search of the literature was conducted to identify key articles relating to insulin resistance in children. The conference was divided into five themes and working groups: background and definition; methods of measurement and screening; risk factors and consequences; prevention; and treatment. Each group selected key issues, searched the literature, and developed a draft document. During a 3-d meeting, these papers were debated and finalized by each group before presenting them to the full forum for further discussion and agreement. Given the current childhood obesity epidemic, insulin resistance in children is an important issue confronting health care professionals. There are no clear criteria to define insulin resistance in children, and surrogate markers such as fasting insulin are poor measures of insulin sensitivity. Based on current screening criteria and methodology, there is no justification for screening children for insulin resistance. Lifestyle interventions including diet and exercise can improve insulin sensitivity, whereas drugs should be implemented only in selected cases.
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              Applicability of body composition techniques and constants for children and youths.

              This review has focused on the chemical immaturity of children and the implications for body composition estimates. Prepubescent and pubescent children deviate considerably in fat-free body composition from the adult reference male, and this has lead investigators to overestimate body fatness in this population using conventional body composition formulas. The use of multicomponent approaches to body composition to obtain more accurate estimates of body fatness in children has provided new information on the body composition of this population. Sex- and age-specific constants, to replace those derived from the reference male, are suggested for further testing and verification as well as for use in the clinical setting. The chemical immaturity in children has its greatest effect on estimating the extent of obesity in children 6 to 11 years of age and in estimating body fatness in the lean, athletic, prepubescent population. Previous estimates of the growth rate of fat and fat-free body are also affected by chemical immaturity. Further research is needed to study the impact of physical activity and inactivity on the composition of the fat-free body during growth, to develop constants for more accurate estimates of fatness in physically active samples of all ages and to validate the constants presented in the less active populations. Future research with multicomponent body composition systems in all populations of children and youth is essential for progress in this area. Results will have an important contribution to the estimation of childhood obesity, prediction of minimal weight in the athletic population and estimates of growth rate of fat and fat-free body mass. The development of body composition methodologies which more accurately measure the growth of muscle and bone as well as fat is a major challenge ahead.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                BioScientifica (Bristol )
                2049-3614
                19 November 2012
                01 March 2013
                : 2
                : 1
                : 1-10
                Affiliations
                [1]Pediatric Endocrine Unit, Istanbul Medical Faculty Istanbul University 34093, Fatih, IstanbulTurkey
                [1 ]Pediatric Endocrine Unit, Erciyes Medical Faculty Erciyes University KayseriTurkey
                Author notes
                Correspondence should be addressed to A Uçar Email aucar76@ 123456yahoo.com
                Article
                EC120059
                10.1530/EC-12-0059
                3680958
                23781312
                ff78cdd8-5471-4a52-9037-f7c07bd9d87c
                © 2012 The Authors. Published by BioScientifica Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 September 2012
                : 4 October 2012
                Categories
                Research

                precocious adrenarche,dheas,insulin sensitivity,body mass index,waist circumference,atherogenic index

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