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      Métodos diagnósticos de la resistencia a la insulina en la población pediátrica Translated title: Diagnostic methods of insulin resistance in a pediatric population

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          Abstract

          La obesidad es el principal factor de riesgo para el desarrollo de la resistencia a la insulina (RI) en la población pediátrica. Esto es trascendente porque la RI se asocia con un mayor riesgo de desarrollar diabetes mellitus tipo 2 (DM2) y enfermedad cardiovascular (ECV) en la edad adulta. El diagnóstico temprano de RI junto con una intervención oportuna pueden prevenir la aparición de DM2 y ECV en sujetos de riesgo. En este artículo describimos las alternativas diagnósticas de RI en niños y sus implicaciones en la práctica clínica. Se describen a detalle tres métodos diagnósticos: la técnica del clamp, que representa el estándar de oro para medir la sensibilidad tisular a la insulina y la secreción de insulina; los índices derivados de mediciones en ayuno, HOMA y QUICKI, que son los métodos más sencillos, y los más utilizados en la clínica; y el ISI-Compuesto, que se calcula a partir de las mediciones de glucosa e insulina obtenidas en una curva de tolerancia a la glucosa oral (CTGO), de la cual se desprende información adicional sobre el metabolismo de la glucosa. En conclusión, el estándar de oro para el diagnóstico de RI es muy complejo e invasivo por lo que no tiene aplicación clínica. El ISI-Compuesto es prometedor pero hacen falta estudios enfocados a identificar puntos de corte en niños. Finalmente, los índices de HOMA y QUICKI, a pesar de la falta de precisión, siguen siendo los más utilizados en la clínica para la población pediátrica.

          Translated abstract

          Obesity is the main risk factor for insulin resistance (IR) in the pediatric population. IR represents a link between obesity and other metabolic complications such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Therefore, accurate diagnosis and early intervention may reduce the incidence of T2DM and CVD in at-risk individuals. In this study we describe the techniques used to assess insulin sensitivity in pediatric populations. We also describe in detail three diagnostic tests: the glucose clamp technique, which represents the gold standard to determine tissue insulin sensitivity and insulin secretion; HOMA and QUICKI, which are indexes obtained from fasting glucose and insulin concentrations; and ISI-Composite, obtained from an oral glucose tolerance test, which provides additional information on glucose metabolism after an oral glucose load. In conclusion, the glucose clamp technique is an invasive procedure that is diffcult to use in routine clinical settings. Because the cut-off points to diagnose IR with values derived from ISI-Composite have not been established for pediatric populations, HOMA and QUICKI, despite their lack of precision, remain the most used in clinical practice.

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          Most cited references63

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          Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.

          Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes. We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
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            Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.

            Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.
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              Use and abuse of HOMA modeling.

              Homeostatic model assessment (HOMA) is a method for assessing beta-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. It has been reported in >500 publications, 20 times more frequently for the estimation of IR than beta-cell function. This article summarizes the physiological basis of HOMA, a structural model of steady-state insulin and glucose domains, constructed from physiological dose responses of glucose uptake and insulin production. Hepatic and peripheral glucose efflux and uptake were modeled to be dependent on plasma glucose and insulin concentrations. Decreases in beta-cell function were modeled by changing the beta-cell response to plasma glucose concentrations. The original HOMA model was described in 1985 with a formula for approximate estimation. The computer model is available but has not been as widely used as the approximation formulae. HOMA has been validated against a variety of physiological methods. We review the use and reporting of HOMA in the literature and give guidance on its appropriate use (e.g., cohort and epidemiological studies) and inappropriate use (e.g., measuring beta-cell function in isolation). The HOMA model compares favorably with other models and has the advantage of requiring only a single plasma sample assayed for insulin and glucose. In conclusion, the HOMA model has become a widely used clinical and epidemiological tool and, when used appropriately, it can yield valuable data. However, as with all models, the primary input data need to be robust, and the data need to be interpreted carefully.
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                Author and article information

                Journal
                bmim
                Boletín médico del Hospital Infantil de México
                Bol. Med. Hosp. Infant. Mex.
                Instituto Nacional de Salud, Hospital Infantil de México Federico Gómez (México, DF, Mexico )
                1665-1146
                October 2011
                : 68
                : 5
                : 397-404
                Affiliations
                [01] México D.F. orgnameInstituto Mexicano del Seguro Social orgdiv1Centro Médico Nacional SXXI orgdiv2Hospital de Pediatría México
                Article
                S1665-11462011000500010 S1665-1146(11)06800500010
                a1886e0e-07a1-4b2b-8a98-0d9931b10566

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 11 August 2011
                : 31 May 2011
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 38, Pages: 8
                Product

                SciELO Mexico

                Categories
                Tema pediátrico

                resistencia a insulina,diabetes mellitus,glucosa,insulin resistance,glucose

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