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      Homeostatic model assessment of adiponectin (HOMA-Adiponectin) as a surrogate measure of insulin resistance in adolescents: Comparison with the hyperglycaemic clamp and homeostatic model assessment of insulin resistance

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          Abstract

          Background

          Studies on adults have reported inverse association between the homeostatic model assessment (HOMA) of adiponectin (HOMA-Adiponectin) and the insulin resistance assessed by the glucose clamp technique. To our knowledge, in the pediatric population this association has not been previously investigated.

          Objectives

          To evaluate the association between the HOMA-Adiponectin and the insulin resistance assessed by the glucose clamp technique in adolescents, and to compare the accuracy of HOMA-Adiponectin and HOMA-insulin resistance (HOMA-IR) for identifying insulin resistance.

          Methods

          This was a cross-sectional study of 56 adolescents (aged 10–18 years). Insulin resistance was assessed using the HOMA-IR, HOMA-Adiponectin and the hyperglycaemic clamp technique. The clamp-derived insulin sensitivity index, HOMA-Adiponectin, and HOMA-IR were log-transformed to get closer to a normal distribution before analysis.

          Results

          In the multivariable linear regression analysis controlling for sex and Tanner stage, HOMA-Adiponectin was inversely associated with the clamp-derived insulin sensitivity index (unstandardized coefficient [B] = -0.441; P < 0.001). After additional adjustment for waist circumference-to-height ratio, this association remained significant (B = -0.349; P = < 0.001). Similar results were observed when HOMA-IR replaced HOMA-Adiponectin in the model (B = -1.049 and B = -0.968 after additional adjustment for waist circumference-to-height ratio); all P < 0.001. The area under the receiver operating characteristic curve for predicting insulin resistance was 0.712 ( P = 0.02) for HOMA-Adiponectin and 0.859 ( P < 0.0001) HOMA-IR.

          Conclusions

          The HOMA-Adiponectin was independently associated with insulin resistance and exhibited a good discriminatory power for predicting it. However, it did not show superiority over HOMA-IR in the diagnostic accuracy.

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          Most cited references21

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          A novel serum protein similar to C1q, produced exclusively in adipocytes.

          We describe a novel 30-kDa secretory protein, Acrp30 (adipocyte complement-related protein of 30 kDa), that is made exclusively in adipocytes and whose mRNA is induced over 100-fold during adipocyte differentiation. Acrp30 is structurally similar to complement factor C1q and to a hibernation-specific protein isolated from the plasma of Siberian chipmunks; it forms large homo-oligomers that undergo a series of post-translational modifications. Like adipsin, secretion of Acrp30 is enhanced by insulin, and Acrp30 is an abundant serum protein. Acrp30 may be a factor that participates in the delicately balanced system of energy homeostasis involving food intake and carbohydrate and lipid catabolism. Our experiments also further corroborate the existence of an insulin-regulated secretory pathway in adipocytes.
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            Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents.

            To compare insulin sensitivity and pancreatic beta-cell function measured by the euglycemic and the hyperglycemic clamp, with simple estimates of insulin sensitivity and pancreatic beta-cell function in youth. Study design We measured insulin sensitivity with a euglycemic clamp and first- and second-phase insulin secretion with a hyperglycemic clamp in 156 AA and white youths. Estimates of insulin sensitivity (fasting insulin level [I(F)], the ratio of fasting glucose [G(F)] to I(F) [G(F)/I(F)], homeostasis model assessment estimate of insulin sensitivity [HOMA IS], and quantitative insulin sensitivity check index [QUICKI]) and estimates of pancreatic beta-cell function (I(F), the ratio of I(F) to G(F) [I(F)/G(F)], and homeostasis model assessment estimate of pancreatic beta-cell function [HOMA %B]) were derived from fasting measurements. In the total group, IS(Eu) correlated strongly with I(F) (r=-0.92), G(F)/I(F) (r=0.92), HOMA IS (r=0.91), and QUICKI (r=0.91) (P<.01). First-phase and second-phase insulin secretion correlated with I(F), I(F)/G(F), and HOMA %B (first-phase insulin secretion: r=0.76, 0.79, 0.82; second-phase insulin secretion: r=0.83, 0.86, 0.86, respectively; P<.01). Simple estimates of insulin sensitivity and pancreatic beta-cell function using fasting insulin and glucose levels serve as surrogate measures of insulin sensitivity and secretion in nondiabetic youths. The validity of these conclusions in children with impaired glucose tolerance and type 2 diabetes mellitus remains to be determined.
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              Adolescents' self-assessment of sexual maturation.

              The variability in time on onset and progression of puberty warrants the use of stage of sexual maturation rather than chronologic age in assessing biological and behavioral measures during adolescence. The necessity to undress the teenage has seriously curtailed the application of stage of sexual maturation to behavioral and developmental research. This study demonstrated that adolescents can accurately assess their own developmental stage according to Tanner's standard photographs. Self-ratings by 43 females, aged 9 to 17, and 23 males, 11 to 18, were compared to those based on physical examination by one of the investigators. Agreement with the physician rating occurred for breast stage in 37/43, for female pubic hair stage in 40/43, and for male combined pubic hair and genital stage in 21/23 (kappa coefficients: 0.81, 0.91, 0.88). The excellent agreement between physician and adolescent's assessment compared favorably with the interrater agreement of professionals. This study suggests the value of utilizing adolescent self-staging in research. In addition, this exercise provides teenagers with an objective way to understand the wide range of normal pubertal development and to follow their own sexual maturation.
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                Author and article information

                Contributors
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: Writing – review & editing
                Role: Investigation
                Role: InvestigationRole: Project administration
                Role: ConceptualizationRole: MethodologyRole: Supervision
                Role: InvestigationRole: Supervision
                Role: Investigation
                Role: Investigation
                Role: Investigation
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 March 2019
                2019
                : 14
                : 3
                : e0214081
                Affiliations
                [1 ] Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas - Unicamp, Campinas, São Paulo, Brazil
                [2 ] Postgraduate Program in Child and Adolescent Health, Faculty of Medical Sciences, University of Campinas - Unicamp, Campinas, São Paulo, Brazil
                [3 ] Department of Pediatrics, University of Campinas - Unicamp, Campinas, São Paulo, Brazil
                [4 ] School of Applied Sciences, University of Campinas - Unicamp, Limeira, São Paulo, Brazil
                [5 ] School of Health and Life Sciences, University Center Our Lady of Patronage, Itu, São Paulo, Brazil
                [6 ] Postgraduate Program of Nutrition, Federal University of São Paulo - Unifesp, São Paulo, São Paulo, Brazil
                [7 ] Department of Psychobiology, Federal University of São Paulo - Unifesp, São Paulo, São Paulo, Brazil
                [8 ] School of Physical Education, Physiotherapy and Occupational Therapy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
                [9 ] Department of Physiotherapy, Therapeutic Resources Laboratory, Federal University of São Carlos - UFSCar, São Carlos, São Paulo, Brazil
                Helmholtz Zentrum München, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ¶ Membership of the Brazilian Metabolic Syndrome Study (BRAMS) Investigators is provided in the Acknowledgments.

                Author information
                http://orcid.org/0000-0001-5503-9533
                http://orcid.org/0000-0002-7290-7950
                Article
                PONE-D-18-29792
                10.1371/journal.pone.0214081
                6433366
                30908521
                d3bfb611-9a96-4193-944a-6b7a10df7913
                © 2019 da Silva et al

                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
                : 14 October 2018
                : 6 March 2019
                Page count
                Figures: 2, Tables: 2, Pages: 12
                Funding
                Funded by: National Council for Scientific and Technological Development (CNPq)
                Award ID: 563664/2010-0
                Award Recipient :
                Funded by: São Paulo Research Foundation (FAPESP)
                Award ID: #2013/21476-3
                Award Recipient :
                This study was funded by the National Council for Scientific and Technological Development (CNPq), grant number 563664/2010-0 (BG), and CCS was supported by a doctoral grant from the São Paulo Research Foundation (FAPESP), grant number #2013/21476-3 ( http://www.bv.fapesp.br/pt/pesquisa/?sort=-data_inicio&q2=id_pesquisador_exact%3A671472+AND+bolsa_exact%3A%22Bolsas+no+Brasil%22+AND+situacao_exact%3A%22Conclu%C3%ADdos%22). The funders had no role in the design and implementation of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The opinions, assumptions, and conclusions or recommendations expressed in this material are the responsibility of the authors and do not necessarily reflect the views of the São Paulo Research Foundation (FAPESP) and of the National Council for Scientific and Technological Development (CNPq).
                Categories
                Research Article
                Medicine and Health Sciences
                Endocrinology
                Endocrine Physiology
                Insulin Resistance
                Biology and Life Sciences
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                Endocrine Physiology
                Insulin Resistance
                Medicine and Health Sciences
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                Endocrine Physiology
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