Accuracy of the 13C-glucose breath test to identify insulin resistance in non-diabetic adults.

AIMS: To assess the validity of the 13C-glucose breath test (13C-GBT) to identify insulin resistance (IR) in non-diabetic individuals, using hyperinsulinemic-euglycemic clamps as gold standard. This validity was compared with that of other IR surrogates. METHODOLOGY: Non-diabetic adults were studied in a cross-sectional design. In a first appointment, oral glucose tolerance tests were conducted simultaneously with 13C-GBTs. Oral 75 g glucose dissolved in 150 ml water, followed by 1.5 mg/Kg body weight U-13C-glucose dissolved in 50 ml water, was administered. Breath and blood samples were collected at baseline and at 30-min intervals. The percentages of glucose-oxidized dose at given periods were calculated. Clamps were conducted a week later. A clamp-derived M value ≤ 6.0 mg/kg*min was used as cut-off. ROC curves were constructed for 13C-GBT, fasting insulin, HOMA, and ISI-composite. RESULTS: Thirty-eight subjects completed the study protocol. The correlation coefficient between the 13C-GBT derived glucose-oxidized dose at 180 min and M values was 0.524 (p = 0.001). The optimal value to identify IR with the 13C-GBT was 4.23% (AUC 0.81; 95CI 0.66, 0.96; accuracy 0.82, 95CI 0.66, 0.92). The 13C-GBT sensitivity (0.88) was higher than HOMA and fasting insulin sensitivities (0.83 and 0.75 respectively), while their specificities were comparable (0.71, 0.71, and 0.79, respectively). The sensitivity of ISI-C was higher (0.92) than that of the 13C-GBT, but its specificity was poor (0.36). The accuracy of the 13C-GBT was superior to that of the other studied surrogates. CONCLUSIONS: The 13C-GBT is a valid and accurate method to detect IR in non-diabetic adults. Therefore, it is potentially useful in clinical and community settings.

Optimal Cut-off Points of Fasting and Post-Glucose Stimulus Surrogates of Insulin Resistance as Predictors of Metabolic Syndrome in Adolescents According to Several Definitions

OBJECTIVE: The aim of this study was to determine optimal cut-off points for fasting and post-glucose stimulus surrogates of insulin resistance to predict metabolic syndrome in adolescents according to several definitions. METHODS: One hundred fifty-five adolescents living in Mexico City were enrolled during 2011 and 2012. Waist circumference and blood pressure were recorded. Subjects received an oral glucose load of 1.75 g per kg up to a maximum dose of 75 g. Blood samples were drawn at baseline and 120 minutes. Concentrations of plasma glucose, triglycerides, high-density lipoprotein cholesterol and insulin were determined. RESULTS: The frequency of metabolic syndrome showed a large variability when using a variety of published definitions; in contrast, the optimal cut-off points for fasting insulin, homeostatic model assessment of insulin resistance and two-hour oral glucose tolerance test insulin were very similar in almost all the definitions considered and had adequate diagnostic performance: area under the curve >0.869, sensitivity >0.835 and specificity >0.755. Insulin resistance surrogates had substantial agreements with Ford, Cook and Salas definitions (Kappa~0.62; agreement~82%); moderate agreement was observed for International Diabetes Federation, Cruz and Ferranti definitions (Kappa~0.41­0.59; agreement~77%). CONCLUSION: Insulin resistance surrogates may be a better approach for metabolic syndrome assessment in an adolescent population because of reduced variability and a higher predictive value.

The 13C-Glucose Breath Test for Insulin Resistance Assessment in Adolescents: Comparison with Fasting and Post-Glucose Stimulus Surrogate Markers of Insulin Resistance.

OBJECTIVE: To evaluate the use of the 13C-glucose breath test (13C-GBT) for insulin resistance (IR) detection in adolescents through comparison with fasting and post-glucose stimulus surrogates. METHODS: One hundred thirty-three adolescents aged between 10 and 16 years received an oral glucose load of 1.75 g per kg of body weight dissolved in 150 mL of water followed by an oral dose of 1.5 mg/kg of U-13C-Glucose, without a specific maximum dose. Blood samples were drawn at baseline and 120 minutes, while breath samples were obtained at baseline and at 30, 60, 90, 120, 150, and 180 minutes. The 13C-GBT was compared to homeostasis model assessment (HOMA) IR (≥p95 adjusted by gender and age), fasting plasma insulin (≥p90 adjusted by gender and Tanner stage), results of 2-h oral glucose tolerance test (OGTT), insulin levels (≥65 µU/mL) in order to determine the optimal cut-off point for IR diagnosis. RESULTS: 13C-GBT data, expressed as adjusted cumulative percentage of oxidized dose (A% OD), correlated inversely with fasting and post-load IR surrogates. Sexual development alters A% OD results, therefore individuals were stratified into pubescent and post-pubescent. The optimal cut-off point for the 13C-GBT in pubescent individuals was 16.3% (sensitivity=82.8% & specificity=60.6%) and 13.0% in post-pubescents (sensitivity=87.5% & specificity=63.6%), when compared to fasting plasma insulin. Similar results were observed against HOMA and 2-h OGTT insulin. CONCLUSION: The 13C-GBT is a practical and non-invasive method to screen for IR in adolescents with reasonable sensitivity and specificity.

The 13C-glucose breath test is a valid non-invasive screening tool to identify metabolic syndrome in adolescents.

BACKGROUND: Metabolic syndrome (MS) is an important risk factor in pediatric population for the early onset of type 2 diabetes mellitus and cardiovascular disease. New non-invasive tools are required to identify MS in at risk populations; the aim of this study was to determine an optimal cut-off point for the 13C-glucose breath test (13C-GBT) for the diagnosis of MS in adolescents. METHODS: A total of 136 adolescents between 10 and 16 years old were recruited. MS was defined as: waist circumference >90th percentile and at least two of the following; high density lipoprotein-cholesterol (HDL-C) <50 mg/dL, triglycerides >110 mg/dL, diastolic and/or systolic blood pressure >90th percentile adjusted by age, gender and height, and/or fasting glucose >100 mg/dL. After the ingestion of a glucose load of 1.75 g/kg of body weight (up to 75 g) and an oral dose of 1.5 mg of universally labeled 13C-glucose/kg dissolved in water, breath samples were taken at baseline, 30, 60, 90, 120, 150 and 180 min. Exhaled 13CO2 in breath samples was measured by isotope ratio mass spectrometry. RESULTS: 13C-GBT data, expressed as adjusted cumulative percentage of oxidized dose (A% OD) at 180 min, was significantly higher in the healthy subjects group (17.72%±4.9%) in comparison with subjects with ≥3, 2 or 1 components of the MS (9.95%±4.73%, 14.3%±4.47% and 14.62%±4.62%, respectively). The optimal cut-off point for the A% OD was 16.09, with a sensitivity of 81.5% and a specificity of 66.7%. CONCLUSIONS: Our results demonstrate that the 13C-glucose breath test could be a valid screening method to identify MS in adolescents.

The [(13)c]glucose breath test is a reliable method to identify insulin resistance in Mexican adults without diabetes: comparison with other insulin resistance surrogates.

BACKGROUND: Insulin resistance (IR) precedes type 2 diabetes, but tests used to detect it in clinical settings reported poor reproducibility. We assessed the reliability of the [(13)C]glucose breath test ((13)C-GBT) in a sample of subjects without diabetes. Repeatability of the test was compared with that of other IR surrogates derived from the fasting or oral glucose tolerance test (OGTT). SUBJECTS AND METHODS: Eighty-six healthy volunteers received an oral load of 75 g of glucose in 150 mL of water followed by 1.5 mg/kg of [U-(13)C]glucose in 50 mL of water. Breath and blood samples were collected at baseline and at 10, 20, 30, 60, 90, 120, 150, and 180 min following the glucose load; the same procedure was repeated within 1 week. The enrichment of breath (13)CO2 was measured by ratio mass spectrometry and expressed as percentage oxidized dose at a given time period. Intrasubject variability was assessed with Bland-Altman plots and coefficients of variation (CVs). RESULTS: The overall CV of the (13)C-GBT was 12.99±11.61%, compared with 18.42% of fasting insulin, 19.44% for homeostasis model assessment, 17.06% of the composite insulin sensitivity index, and 29.99% for insulin in the 2-h oral glucose tolerance test. The variability of the (13)C-GBT tended to be higher in lean (17.40%) than in overweight (10.17%) and obese (12.61%) individuals. CONCLUSIONS: The variability of the (13)C-GBT is lower than that of other IR surrogates, making it a reproducible method to estimate insulin sensitivity in overweight and obese adults without diabetes. Because the individuals did not have diabetes but were within a high range of insulin sensitivity, the test should have application in clinical and population-based studies, given the evidence for the utility and limitations of this surrogate.

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

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.

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.