A network perspective on the ecology of gut microbiota and progression of type 2 diabetes: Linkages to keystone taxa in a Mexican cohort.

Introduction: The human gut microbiota (GM) is a dynamic system which ecological interactions among the community members affect the host metabolism. Understanding the principles that rule the bidirectional communication between GM and its host, is one of the most valuable enterprise for uncovering how bacterial ecology influences the clinical variables in the host. Methods: Here, we used SparCC to infer association networks in 16S rRNA gene amplicon data from the GM of a cohort of Mexican patients with type 2 diabetes (T2D) in different stages: NG (normoglycemic), IFG (impaired fasting glucose), IGT (impaired glucose tolerance), IFG + IGT (impaired fasting glucose plus impaired glucose tolerance), T2D and T2D treated (T2D with a 5-year ongoing treatment). Results: By exploring the network topology from the different stages of T2D, we observed that, as the disease progress, the networks lose the association between bacteria. It suggests that the microbial community becomes highly sensitive to perturbations in individuals with T2D. With the purpose to identify those genera that guide this transition, we computationally found keystone taxa (driver nodes) and core genera for a Mexican T2D cohort. Altogether, we suggest a set of genera driving the progress of the T2D in a Mexican cohort, among them Ruminococcaceae NK4A214 group, Ruminococcaceae UCG-010, Ruminococcaceae UCG-002, Ruminococcaceae UCG-005, Alistipes, Anaerostipes, and Terrisporobacter. Discussion: Based on a network approach, this study suggests a set of genera that can serve as a potential biomarker to distinguish the distinct degree of advances in T2D for a Mexican cohort of patients. Beyond limiting our conclusion to one population, we present a computational pipeline to link ecological networks and clinical stages in T2D, and desirable aim to advance in the field of precision medicine.

Diagnostic performance of questionnaires to identify individuals with impaired fasting glucose in Mexican adult population.

AIMS: To evaluate the diagnostic performance of five questionnaires to identify impaired fasting glucose (IFG) in Mexican adult population. METHODS: The study included 23,311 subjects from five cohorts, three composed of individuals who sought medical advice in their first level clinics or participated in research studies and two representative surveys of the Mexican population. The reference standard was IFG which was defined as a fasting glucose ≥ 100 mg/dL. Diagnostic performance was evaluated with specificity, sensitivity, positive and negative predictive values, area under the curve, and the proportion of correctly classified individuals. RESULTS: The prevalence of IFG ranged from 14.4 to 48.1 % across the cohorts. Diagnostic performance of the questionnaires varied in each cohort depending on IFG prevalence. The questionnaires designed by Rojas, American Diabetes Association and International Diabetes Federation had the best performance considering the correct classification (>66.0 %) of subjects in all cohorts. However, Rojas' questionnaire had the best balance between sensitivity and specificity across the cohorts. CONCLUSION: In the Mexican population, considering different scenarios, the Rojas' questionnaire had the best diagnostic performance. The implementation of questionnaires for the identification of prediabetes and undiagnosed diabetes requires further study in specific populations.

Prevalencia de hiperinsulinismo patológico post carga de glucosa y su relación con factores de riesgo cardiovascular, en adultos no diabéticos con insulinemia basal normal / Prevalence of pathologic hyperinsulinism after a glucose load charge: its relation to cardiovascular risk factors

Introducción: 25% de personas con hiperinsulinismo desarrolla diabetes 3-5 años luego del primer diagnóstico y 70% lo hará en el resto de la vida. Intervenir los niveles de glicemia desde que se detecta hiperinsulinemia evita la progresión a diabetes y restaura el metabolismo glicémico. Objetivos: Determinar la prevalencia de hiperinsulinismo patológico post-carga de glucosa (HPPG) y su relación con factores de riesgo cardiovascular en adultos 100 UI/ml a las 2 horas), sexo, hipertensión arterial, dislipidemia, malnutrición por exceso, sedentarismo, tabaquismo, ateromatosis e infarto miocárdico documentado. Con STATA 17 se calculó la prevalencia de variables en población general y según categoría de HPPG y se evaluó la significancia con prueba exacta de Fisher. Se compararon medias con ANOVA y t-test con nivel de significancia <0,05. Se usó regresión binomial para estimar Razón de Prevalencia e intervalos de confianza en variables cuantitativas y cualitativas. Resultados: la prevalencia de HPPG fue 41%. La edad promedio 37,5 años, el sexo masculino 52,9%, la hipertensión-arterial 40,5% y la dislipidemia 74,4%. Al comparar las poblaciones con y sin HPPG existieron diferencia estadísticamente significativa en las variables dislipidemia, hipertensión-arterial, malnutrición por exceso y sexo-masculino. La razón de prevalencia alcanzó a un 62%, 37%, 59% y 20% respectivamente. Conclusión: Se encontró una alta prevalencia de HPPG. Los factores de riesgo asociados a ella fueron dislipidemia, hipertensión arterial, malnutrición por exceso y sexo masculino. Esto sugiere que encontrar HPPG puede ser de utilidad para detectar precozmente a la población con un mayor riesgo de enfermedad cardiovascular.

Introduction: 25% of people with hyperinsulinism develop diabetes 3-5 years after the first diagnosis and 70% will do so in the rest of their lives. To control glycemia levels as soon as hyperinsulinemia is detected, progression to diabetes is prevented and glycemic metabolism is restored. Aim: To determine the prevalence of post-glucose load pathological hyperinsulinism (HPPG) and its relationship with cardiovascular risk factors in adults 100 uIU/ ml at 2 hours), sex, hypertension, dyslipidemia, excess malnutrition due to, sedentary lifestyle, smoking, documented atheromatosis and myocardial infarction. The prevalence of variables in the general population was calculated and, in relation to the HPPG category, significance is evaluated with Fisher's exact test. Finally means are compared with ANOVA and t-test. With significance level <0.05. Binomial regression was used to estimate the prevalence ratio and confidence intervals in quantitative and qualitative variables. Statistical analysis was performed with the STATA 17 software. Results: HPPG prevalence was 41%, mean age 37.5 years, male sex 52.9%, arterial hypertension 40.5% and dyslipidemia 74.4%. Un relation to the presence of HPPG a statistically significant difference in the variables dyslipidemia, arterial hypertension, malnutrition due to excess and male sex was found. The prevalence ratios were 62%, 37%, 59% and 20%, respectively. Conclusion: A high prevalence of HPPG was found. Risk factors associated to HPPG were dyslipidemia, arterial hypertension, malnutrition due to excess and male sex. Thus, HPPG can play a role in the early detection of a higher risk of cardiovascular disease in the general population.

Early vs. Late Gestational Diabetes: Comparison between Two Groups Diagnosed by Abnormal Initial Fasting Plasma Glucose or Mid-Pregnancy Oral Glucose Tolerance Test.

Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancy. It may be diagnosed using a fasting plasma glucose (FPG) early in pregnancy (eGDM) or a 75-g oral glucose tolerance test (OGTT) (late GDM). This retrospective cohort of women with GDM presents data from 1891 patients (1004 in the eGDM and 887 in the late GDM group). Student's t-test, chi-squared or Fisher's exact test and the Bonferroni test for post hoc analysis were used to compare the groups. Women with eGDM had higher pre-pregnancy BMI, more frequent family history of DM, more frequent history of previous GDM, and were more likely to have chronic hypertension. They were more likely to deliver by cesarean section and to present an abnormal puerperal OGTT. Even though they received earlier treatment and required insulin more frequently, there was no difference in neonatal outcomes. Diagnosing and treating GDM is necessary to reduce complications and adverse outcomes, but it is still a challenge. We believe that women with eGDM should be treated and closely monitored, even though this may increase healthcare-related costs.

Association of fat mass and obesity-associated (FTO) gene rs9939609 with obesity-related traits and glucose intolerance in an indigenous population, the Xavante.

BACKGROUND AND AIMS: Common variants in fat mass and obesity-associated (FTO) gene have been implicated as a susceptibility locus for obesity and type 2 diabetes in different populations. Here, in an indigenous population-based study, we examined whether FTO rs9939609 has a role in susceptibility to glucose intolerance and obesity. METHODS: The study population comprised 949 full Xavante indigenous people (465 men) aged 18-99 years. The participants were submitted to clinical examination, anthropometrical measures and basal and 2-h post 75g oral glucose load capillary glucose measurements. FTO rs9939609 was genotyped and logistic regression was carried out to test the additive effect of the risk allele. RESULTS: The frequency of the minor allele of the FTO rs9939609 (0.06) was lower in Xavante than observed in some populations. A significant association between the variant and overweight was observed (OR = 1.56 (95% CI:1.06-2.29, p = 0.02), using an additive model of inheritance, adjusted by age and gender and considering the family structure. We found no associations with obesity or glucose intolerance. CONCLUSIONS: The FTO rs9939609 is associated with overweight, but not with obesity or glucose intolerance. The low frequency of the A allele suggests that it is not an important risk determinant for these conditions in Xavante indigenous people.

The positive association between serum uric acid, impaired fasting glucose, impaired glucose tolerance, and diabetes mellitus in the ELSA-Brasil study.

There is a conflict in the literature regarding the association between serum uric acid (SUA) levels and glycemic status. Therefore, we evaluated the association between SUA level and glycemic status - impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus - and insulin resistance, in a large Brazilian study. This is a cross-sectional, observational study with 13,207 participants aged 35-74 years, at baseline (2008-2010) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). A multinomial regression analysis was performed to test the association between SUA and glycemic status (IFG, IGT, and newly diagnosed type 2 diabetes at the cohort baseline) after adjustments by age, sex, skin color, body mass index, physical activity, smoking, alcohol consumption, comorbidities, and medicines use. Logistic regression model was used to evaluate the association between SUA and insulin resistance by HOMA-IR. Stratified analyses by sex were performed. The mean age (standard deviation) was 51.4 (8.9) years, 55.2% of participants were women. There were 1,439 newly diagnosed diabetes. After all adjustments, higher SUA was associated with IFG, IGT, and diabetes, with odds ratio (OR) = 1.15 (95%CI: 1.06; 1.25), 1.23 (95%CI: 1.14; 1.33), and 1.37 (95%CI: 1.24; 1.51), respectively. There was association between SUA levels and insulin resistance with OR = 1.24 (95%CI: 1.13; 1.36). In analysis stratified by sex, higher SUA persisted independently associated with impaired glycemic status. Our results suggest that a higher SUA levels were significantly associated with glycemic status in a large Latin American population, mainly among women.

Association between anthropometric measures and insulin resistance in Brazilian adolescents: data from the national study of cardiovascular risk factors in adolescents - ERICA.

OBJECTIVES: To evaluate anthropometric measures (AM) and insulin resistance (IR) association in adolescents aged 12-17 years and investigates how body mass index (BMI) interrelates with specific indicators of fat distribution in this association. METHODS: This analysis is from the Study of Cardiovascular Risks in Adolescents (ERICA) study, a national, cross-sectional study. AM was categorized by quartiles, and their means and 95% confidence intervals (95% CI) were estimated. The prevalence of IR was estimated for each AM according to the quartiles. The associations between AM and homeostatic model assessment of insulin resistance (HOMA-IR) levels were analyzed using Poisson models. RESULTS: 37,892 adolescents were included. IR prevalence tended to increase as quartiles increased for each AM. The association of BMI with IR persisted with the adjustment for others AM. The greatest reduction in the association's strength was achieved with the adjustment by the waist circumference (WC) and the waist-to-height ratio (WHtR). Most other AM were also associated with IR. CONCLUSION: AM has a positive association with the prevalence of IR, and the joint effect of BMI and central adiposity measures should be considered in cardiometabolic risk evaluation in adolescents.

Clinical and metabolomic predictors of regression to normoglycemia in a population at intermediate cardiometabolic risk.

BACKGROUND: Impaired fasting glucose (IFG) is a prevalent and potentially reversible intermediate stage leading to type 2 diabetes that increases risk for cardiometabolic complications. The identification of clinical and molecular factors associated with the reversal, or regression, from IFG to a normoglycemia state would enable more efficient cardiovascular risk reduction strategies. The aim of this study was to identify clinical and biological predictors of regression to normoglycemia in a non-European population characterized by high rates of type 2 diabetes. METHODS: We conducted a prospective, population-based study among 9637 Mexican individuals using clinical features and plasma metabolites. Among them, 491 subjects were classified as IFG, defined as fasting glucose between 100 and 125 mg/dL at baseline. Regression to normoglycemia was defined by fasting glucose less than 100 mg/dL in the follow-up visit. Plasma metabolites were profiled by Nuclear Magnetic Resonance. Multivariable cox regression models were used to examine the associations of clinical and metabolomic factors with regression to normoglycemia. We assessed the predictive capability of models that included clinical factors alone and models that included clinical factors and prioritized metabolites. RESULTS: During a median follow-up period of 2.5 years, 22.6% of participants (n = 111) regressed to normoglycemia, and 29.5% progressed to type 2 diabetes (n = 145). The multivariate adjusted relative risk of regression to normoglycemia was 1.10 (95% confidence interval [CI] 1.25 to 1.32) per 10 years of age increase, 0.94 (95% CI 0.91-0.98) per 1 SD increase in BMI, and 0.91 (95% CI 0.88-0.95) per 1 SD increase in fasting glucose. A model including information from age, fasting glucose, and BMI showed a good prediction of regression to normoglycemia (AUC = 0.73 (95% CI 0.66-0.78). The improvement after adding information from prioritized metabolites (TG in large HDL, albumin, and citrate) was non-significant (AUC = 0.74 (95% CI 0.68-0.80), p value = 0.485). CONCLUSION: In individuals with IFG, information from three clinical variables easily obtained in the clinical setting showed a good prediction of regression to normoglycemia beyond metabolomic features. Our findings can serve to inform and design future cardiovascular prevention strategies.

Serum 25-hydroxyvitamin D concentration and its association with glucose intolerance in an indigenous population.

BACKGROUND AND AIMS: Type 2 diabetes is a multifactorial disease resulting from diverse genetic and environmental factors as well as the interaction between them. Low levels of 25-hydroxyvitamin D [25(OH)D], an indicator of vitamin D status, have been associated with an increased risk of type 2 diabetes, but not consistently. Also, it remains to be determined if this association differs among ethnic groups. Therefore, we aimed to evaluate vitamin D status and its association with glucose intolerance in a Brazilian indigenous population, the Xavante Indians. METHODS: The study population consisted of 819 full Xavante Indians (410 women), aged ≥18 years and living in two indigenous reserves located in Mato Grosso State, central region of Brazil. Clinical examination and anthropometrical measurements were made, blood samples were obtained for total cholesterol, HDL-cholesterol, triglycerides and 25(OH)D measurement. Fasting and 2-h post 75 g oral glucose load capillary glucose was measured. Vitamin D status was defined by serum 25(OH)D levels: vitamin D sufficiency (25(OH)D: 30-100 ng/mL), vitamin D insufficiency (25(OH)D: 20- <30 ng/mL) and vitamin D deficiency (25(OH)D: < 20 ng/mL). Multiple logistic regression was performed to identify independent associations between 25(OH)D levels and impaired glucose tolerance or diabetes mellitus. RESULTS: Analyses stratified by 25(OH)D levels shows that 65.5% of the population had vitamin D deficiency/insufficiency (25(OH)D < 30 ng/mL). 25(OH)D concentrations were lower in individuals with impaired glucose tolerance or diabetes mellitus than in normal glucose tolerant individuals. Multiple logistic regression analysis showed an inverse association between increments of 25(OH)D and presence of diabetes mellitus (OR per 1 ng/mL increase in 25(OH)D: 0.97; 95% confidence interval: 0.95-0.99), or impaired glucose tolerance (OR per 1 ng/mL increase in 25(OH)D: 0.87; 95% confidence interval: 0.85-0.89), in an age, sex, BMI and season of sampling-adjusted model. CONCLUSIONS: The present population-based study found a high prevalence of hypovitaminosis D among Xavante Indians. In this at-risk population of type 2 diabetes, a significant association of higher serum 25(OH)D with a decreased prevalence of diabetes mellitus and impaired glucose tolerance was observed.

Insulin resistance may be misdiagnosed by HOMA-IR in adults with greater fat-free mass: the ELSA-Brasil Study.

AIMS: Conflicting results have been reported on the association of fat-free mass (FFM) and insulin resistance (IR). This study sought to test the association of FFM and IR by indexing FFM to avoid collinearity with fat mass. METHODS: This cross-sectional study comprised 11,284 volunteers, aged 38-79 years. Body composition was assessed by multi-frequency bioelectrical impedance. FFM indexed to body surface area (FFMbsa) was calculated. IR and impaired glucose tolerance (IGT) were estimated with homeostatic model assessment of insulin resistance index (HOMA-IR) and 2-h oral glucose tolerance test (2h-OGTT), respectively. RESULTS: Percent body fat decreased from the 1st to the 5th quintile of FFMbsa in both women (Eta2 = 0.166) and men (Eta2 = 0.133). In women, fasting insulin (Eta2 = 0.002), glucose (Eta2 = 0.006), and HOMA-IR (Eta2 = 0.007) increased slightly, but 2-h plasma glucose (2-h PG) was similar across the quintiles of FFMbsa. In men, fasting insulin and HOMA-IR were similar across the quintiles of FFMbsa, whereas fasting glucose increased slightly (Eta2 = 0.002) and 2-h PG decreased (Eta2 = 0.005) toward the highest quintile of FFMbsa. The higher the odds ratio for IR, the greater the FFMbsa in both sexes. Differently, FFMbsa did not affect the odds of IGT in women, while in men the odds ratio for IGT was lower in the 5th quintile compared with the 1st quintile of FFMbsa. CONCLUSIONS: Higher odds of IR associated with greater FFMbsa contrasted with lower odds of IGT associated with greater FFMbsa. IR may be misdiagnosed by HOMA-IR in adults with greater fat-free mass.

The positive association between serum uric acid, impaired fasting glucose, impaired glucose tolerance, and diabetes mellitus in the ELSA-Brasil study / Associação positiva entre ácido úrico sérico, glicemia em jejum alterada, tolerância glicêmica alterada e diabetes mellitus no estudo ELSA-Brasil / La asociación positiva entre ácido úrico sérico, glucosa alterada en ayunas, tolerancia a la glucosa alterada y diabetes mellitus en el estudio ELSA-Brasil

Abstract: There is a conflict in the literature regarding the association between serum uric acid (SUA) levels and glycemic status. Therefore, we evaluated the association between SUA level and glycemic status - impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus - and insulin resistance, in a large Brazilian study. This is a cross-sectional, observational study with 13,207 participants aged 35-74 years, at baseline (2008-2010) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). A multinomial regression analysis was performed to test the association between SUA and glycemic status (IFG, IGT, and newly diagnosed type 2 diabetes at the cohort baseline) after adjustments by age, sex, skin color, body mass index, physical activity, smoking, alcohol consumption, comorbidities, and medicines use. Logistic regression model was used to evaluate the association between SUA and insulin resistance by HOMA-IR. Stratified analyses by sex were performed. The mean age (standard deviation) was 51.4 (8.9) years, 55.2% of participants were women. There were 1,439 newly diagnosed diabetes. After all adjustments, higher SUA was associated with IFG, IGT, and diabetes, with odds ratio (OR) = 1.15 (95%CI: 1.06; 1.25), 1.23 (95%CI: 1.14; 1.33), and 1.37 (95%CI: 1.24; 1.51), respectively. There was association between SUA levels and insulin resistance with OR = 1.24 (95%CI: 1.13; 1.36). In analysis stratified by sex, higher SUA persisted independently associated with impaired glycemic status. Our results suggest that a higher SUA levels were significantly associated with glycemic status in a large Latin American population, mainly among women.

Resumo: Há uma controvérsia na literatura a respeito da associação entre níveis de ácido úrico sérico (AUS) e glicemia. Portanto, avaliamos a associação entre AUS e glicemia (glicemia em jejum alterada, intolerância glicêmica e diabetes mellitus), além da resistência insulínica, em uma amostra grande no Brasil. O estudo transversal observacional incluiu 13.207 participantes com idade entre 35 e 74 anos na linha de base (2008-2010) do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Foi realizada análise de regressão multivariada para testar a associação entre AUS e glicemia (glicemia em jejum alterada, intolerância glicêmica e diagnóstico novo de diabetes tipo 2 na linha de base da coorte) depois de ajustar para idade, sexo, cor, índice de massa corporal, atividade física, tabagismo, consumo de álcool, comorbidades e uso de medicação. O modelo de regressão logística foi usado para avaliar a associação entre AUS e resistência insulínica por HOMA-IR. Foram realizadas análises estratificadas por sexo. A média de idade (DP) foi 51,4 (8,9) anos, e 55,2% dos participantes eram mulheres. Houve 1.439 novos diagnósticos de diabetes. Depois de todos os ajustes, o AUS esteve associado à glicemia em jejum alterada, intolerância glicêmica e diabetes, com odds ratio (OR) = 1,15 (IC95%: 1,06; 1,25), 1,23 (IC95%: 1,14; 1,33) e 1,37 (IC95%: 1,24; 1,51), respectivamente. Houve uma associação entre níveis de AUS e resistência insulínica, com OR = 1,24 (IC95%: 1,13; 1,36). Na análise estratificada por sexo, persistiu a associação independente entre AUS elevado e glicemia. Os resultados sugerem que níveis elevados de AUS estão associados de maneira significativa com a glicemia em uma população latino-americana grande, sobretudo entre mulheres.

Resumen: Hay un conflicto en la literatura respecto a la asociación entre los niveles de ácido úrico sérico (AUS) y el estado glucémico. Por eso, evaluamos la asociación entre el nivel AUS y el estatus glucémico: glucosa alterada en ayunas (GAA), tolerancia a la glucosa alterada (TGA) y diabetes mellitus (diabetes), comparados con la resistencia a la insulina en un amplio estudio en Brasil. Se realizó un estudio transversal, observacional con 13.207 participantes, con edades comprendidas entre los 35-74 años, en la base de referencia del Estudio Longitudinal de Salud entre Adultos brasileños (2008-2010) (ELSA-Brasil). Se realizó un análisis de regresión multinomial para probar la asociación entre AUS y el estado glucémico (GAA, TGA y de nuevo la diabetes tipo 2, diagnosticada en la cohorte como base de referencia) tras los ajustes por edad, sexo, color de piel, índice de masa corporal, actividad física, fumar, consumo de alcohol, comorbilidades, uso de medicinas. Se usó el modelo de regresión logística para evaluar la asociación entre AUS y la resistencia a la insulina por el HOMA-IR. Se realizó también un análisis estratificado por sexo. La media de edad (desviación estándar) fue 51,4 (8,9) años, un 55,2% de los participantes eran mujeres. Hubo 1.439 nuevos casos de diabetes diagnosticados. Tras todos los ajustes, una AUS más alta estuvo asociada con GAA, TGA y diabetes, con odds ratio (OR) = 1,15 (IC95%: 1,06; 1,25), 1,23 (IC95%: 1,14; 1,33), y 1,37 (IC95%: 1,24; 1,51), respectivamente. Hubo asociación entre los niveles AUS y la resistencia a la insulina con OR = 1,24 (IC95%: 1,13; 1,36). En el análisis estratificado por sexo, una AUS más alta persistía independientemente asociada con un estado glucémico alterado. Nuestros resultados sugieren que unos niveles más altos de AUS estuvieron significativamente asociados con el estado glucémico en una amplia población latinoamericana, principalmente entre mujeres.

Prevalence of metabolic disturbances among women with polycystic ovary syndrome in different regions of Brazil.

OBJECTIVE: To describe the prevalence of metabolic disturbances in a large cohort of women with polycystic ovary syndrome (PCOS) in southeastern Brazil and to compare the findings with other cohorts of Brazilian women with PCOS. METHODS: A retrospective study analyzing clinical and laboratory data of 462 women with PCOS treated at an outpatient clinic in a tertiary hospital in southeastern Brazil. Prevalence of insulin resistance, glucose intolerance, type 2 diabetes, dyslipidemia, central obesity, hypertension, and metabolic syndrome was compared to that of other cohorts of age and body mass index-matched Brazilian women with PCOS. RESULTS: Women with PCOS had a median age of 25.0 (21.0-29.0) years and BMI of 28.7 (23.9-34.0) kg/m2 . Prevalence of insulin resistance, glucose intolerance, and type 2 diabetes varied from 39.6% to 55.0%, 7.2% to 28.1%, and 2.0% to 4.1%, respectively. Prevalence of central obesity, dyslipidemia due to decreased high-density lipoprotein cholesterol, hypertriglyceridemia, and metabolic syndrome ranged from 57.8% to 66.4%, 54.1% to 70.4%, 22.9% to 35.1%, and 27.4% to 38.3%, respectively, which did not differ among regions in Brazil. CONCLUSION: Prevalence of metabolic disturbances was high among Brazilian women with PCOS. This study suggests that, from a public health perspective, authorities in Brazil should be aware of and encourage screening for metabolic dysfunction in women with PCOS in all regions of the country.

Insulin Sensitivity and Pancreatic ß-Cell Function in Ecuadorian Women With Turner Syndrome.

Objective: To assess insulin sensitivity and pancreatic ß-cell function in an adult population of Ecuadorian individuals with Turner syndrome (TS). Design and Methods: This was a cross-sectional correlational study conducted in TS subjects (>20 years old; n = 38). A standard 2-h oral glucose tolerance test was performed in both women with TS and the reference group. Glucose, lipids, insulin, and C-peptide concentrations were measured. Homeostasis Model Assessment (HOMA) of Insulin Resistance, Quantitative Insulin Sensitivity Check Index, McAuley, Matsuda, and Belfiore indices were calculated to evaluate the degree of insulin resistance (IR). The pancreatic ß-cell function was assessed using HOMA-ß, basal C-Peptide Index (CPI), and CPII at 120'. Results: A higher prevalence of impaired glucose tolerance was found in TS subjects compared with the reference group. Although significant differences were found for glucose concentrations at 60' and 120' (but not at 0'), only the baseline insulin concentrations differed significantly between the two groups. The values of the IR indices were statistically different between study and reference groups. A significant number of TS subjects diagnosed with IR were differently classified according to the index applied. The concentrations of C-peptide at 0' and 120' of TS subjects were similar to those of the control group. In contrast, the CPI and CPII values in the study group were significantly lower than those in the control group. Conclusion: It is impossible to select the best surrogate method for the assessment of IR in women with TS. The CPI and CPII values could be preferable to other indices to assess the pancreatic ß-cell function in TS subjects. Our findings suggest that IR and pancreatic ß-cell dysfunction could be independent events in women with TS, and both conditions seem to be caused by the disease per se. Our results imply that early screening and intervention for TS would be therapeutic for TS women.

High glucose level as a modifier factor in CMT1A patients.

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common type of hereditary neuropathy worldwide and diabetes mellitus (DM) is the most frequent cause of peripheral neuropathy in the Western world. CMT1A typically manifest as a predominant motor neuropathy, while, DM-related neuropathy often manifests as a predominant sensory disorder. There are some evidences that CMT1A patients that also had DM had a more severe neuropathy. Although the real frequency and the underlying mechanisms related to this association has not yet been addressed in the literature. We sought to characterize the phenotypic variability of CMT1A patients with persistent high glucose levels (DM or impaired glucose tolerance [IGT]). Nineteen patients with CMT1A and DM (CMTdiab), seven with CMT1A and IGT (CMTintol) and 27 with CMT1A without comorbidities were analyzed. They were evaluated through clinical assessment, application of the following scales: visual analogue scale, McGill, CMTNS, SF-36 and COMPASS 31 and electrophysiological studies. Patients CMTdiab had a more severe motor and sensory neuropathy, more intense autonomic symptoms and worse quality of life. Surprisingly, proximal weakness and temporal dispersion on nerve conduction studies are frequently observed in this group. Patients CMTintol also had a more severe neuropathy. Curiously, we observed that the association of CMT1A and glucose metabolism disorders (CMTglic) clustered in some families. Patients CMTglic develop a more severe neuropathy. As there is yet no cure to CMT1A, a strict blood sugar control may be a useful measure.

Vitamin D status and its relation to insulin resistance in a Mexican pediatric population.

Background Obesity in children and adolescents has increased alarmingly, placing them at a higher risk for impaired glucose tolerance and type 2 diabetes. The prevalence of vitamin D deficiency has increased as well. Vitamin D is critical for glucose homeostasis and insulin secretion. Studies on adults have reported an inverse association between vitamin D levels and insulin resistance (IR), but the results in children are inconsistent. The aim of our study was to determine the association between IR and serum vitamin D levels in obese Mexican children and adolescents. Methods A cross-sectional study was performed on 227 children and adolescents between 6 and 19 years of age. Obesity was diagnosed through body mass index (BMI) for age, according to the World Health Organization (WHO) criteria (2007). 25-Hydroxyvitamin D (25[OH]D) was measured using an immunoassay technique and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated using the Matthews equation. Student's t-test was carried out. Results The mean serum 25(OH)D level was 35.80 ng/mL, and 55.1% of the subjects had levels classified as sufficient, 33.5% as insufficient, and 11.5% as deficient. The mean level of HOMA-IR was 3.16, and 70% of the subjects were diagnosed with IR. Fasting insulin levels and HOMA-IR were significantly different in adolescents with hypovitaminosis, compared with adolescents in the vitamin D sufficiency group (p = 0.01 and p = 0.03, respectively). Conclusions The insulin levels and HOMA-IR were higher in adolescents with hypovitaminosis. The girls presented higher levels of insulin and HOMA-IR than the boys.

Chronic kidney disease in patients with non-alcoholic fatty liver disease: What the Hepatologist should know?

The association of non-alcoholic fatty liver disease (NAFLD) with several other diseases has gained increased interest during the recent years. Among them, the association with chronic kidney disease (CKD) has emerged as an important one regarding both its prevalence and significance. The early recognition of this association is important for the prognosis of patients with NAFLD and CKD. Apart from early diagnosis, the accurate assessment of renal function is also crucial in the clinical practice of hepatologists. Several methods have been used in the literature for the evaluation of kidney function in patients with NAFLD up to now. In this respect, calculators (or formulas) for the estimation of Glomerular Filtration Rate (eGFR) and Albumin to Creatinine Ratio (ACR) are simple, practical and easily available methods for this purpose. The aim of this review is to report on the epidemiology and pathophysiology of the relationship between NAFLD and CKD and to describe the different methods of kidney function assessment in patients with NAFLD. The collection of all relevant data regarding this association will provide hepatologists with pertinent knowledge on this topic and allow them to use the most accurate methods for the assessment of kidney function in these patients in their clinical practice.

Triglyceride/glucose index is a reliable alternative marker for insulin resistance in South American overweight and obese children and adolescents.

Background The aim of the present study was to investigate the correlation between the triglyceride/glucose index (TyG index) and homeostasis model assessment of insulin resistance (HOMA-IR). Additionally, we compared the ability of the TyG index and triglycerides/high-density lipoprotein cholesterol (TG/HDL-c) index and the combination of these two indices (TyG index plus TG/HDL-c) to predict insulin resistance (IR) in South American overweight and obese children and adolescents. Methods A cross-sectional study was carried out in 345 overweight adolescents aged 10-18 years, from both the sexes. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL])/2, while the TG/HDL-c index was calculated by the division of TG (mg/dL) by HDL-c (mg/dL). HOMA-IR was calculated with the formula: fasting insulin (FI) (U/mL) × fasting glucose (mmol/L)/22.5. The cut-off point used to determine the presence of IR was HOMA-IR ≥ 3.16. Results The TyG index showed a positive correlation with HOMA-IR. The area under the receiver operating characteristic (ROC) curve of the TyG index was 0.74, indicating good sensitivity (75.7%) and specificity (67.4%). Furthermore, the TyG index cut-off point of >4.44 was established for IR prediction in this population. Conclusions The TyG index is a simple and cost-effective surrogate marker of IR in South American overweight children and adolescents. Moreover, due to its good accessibility, it can be used in large epidemiological studies.

Diagnostic accuracy of triglyceride/glucose and triglyceride/HDL index as predictors for insulin resistance in children with and without obesity.

OBJECTIVE: To investigate which of two indexes (TyG or TG/HDL) are the best predictors for insulin resistance (IR) and to evaluate the magnitude of each cardiometabolic risk factor in Mexican schoolchildren of 5-9 years with overweight-obesity and normal weight. MATERIAL AND METHODS: We realized a comparative cross-sectional prospective study in accordance of STARD guidelines. Setting was Family Medicine Unit (FMU) No. 80 of Mexican Institute of Social Security(IMSS) of Morelia, Michoacán, Mexico. Children between 5 and 9 years, both genders, 104 with normal weight(NW), 97 with Overweight-Obesity(OO Group) were included. Once the informed consent was signed we obtained the BMI, waist circumference, blood pressure(BP) and 5 mL of blood collected for glucose, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, uric acid and insulin. As main outcome measures TyG or TG/HDL, HOMA-IR, and Receiving Operating Curves(ROC), sensitivity, specificity by ROC were obtained. RESULTS: Cutoff point TyG: 8.5 by ROC had an area under curve (AUC):0.802 IC95% 0.77to0.893, P = 0.0001; diagnostic accuracy of 73%. TG/HDL: 2.22; AUC:0.729 IC95% 0.622to0.837, P = 0.014; diagnostic accuracy of 52%. TyG can identify cardiometabolic alterations more than HOMA and TG/HDL. Cardiometabolic alterations in the OO group were hypertriglyceridemia:49.5%, low HDL:63.9%, IR:39.2% and in NW group were hypertriglyceridemia:30.8%, low HDL:60.6%, IR:9.6%. CONCLUSIONS: We reported high frequency of hypertriglyceridemia and low HDL in Mexican children. TyG and TG/HDL are good predictors for IR. TyG has a better diagnostic accuracy. We need implementing TyG for identifying alterations and intervening in a timely manner to delay the onset of chronic diseases in children.

Optimized fasting and OGTT-based simple surrogate methods for assessing insulin sensitivity.

AIMS: Simple surrogate indices of insulin sensitivity have been conceived to deal with costly and complicated approaches, such as the hyperinsulinemic-euglycemic clamp; however, their use has not been widespread given their variabilities in different populations. In this paper, we present two simple surrogate indices, one that uses fasting glucose and insulin values and the other based on the values from the oral glucose tolerance test. MATERIALS AND METHODS: The proposed methods integrate easy-to-obtain anthropometric measures. Evolutionary algorithms were used to optimize the proposed methods by maximizing its correlation with the Stumvoll MCR method. RESULTS AND CONCLUSION: When the proposed indices were applied to three study groups (control subjects, metabolic syndrome, marathon runners), a reduction in the intergroup variability of the insulin sensitivity was obtained. Moreover, the proposed index based on the oral glucose tolerance test (OGTT), which considers the glucose metabolism process and the hepatic and peripheral insulin sensitivity, showed stronger correlations with the Stumvoll method and lower intergroup variability than the fasting one.

Development and validation of a predictive model for incident type 2 diabetes in middle-aged Mexican adults: the metabolic syndrome cohort.

BACKGROUND: Type 2 diabetes mellitus (T2D) is a leading cause of morbidity and mortality in Mexico. Here, we aimed to report incidence rates (IR) of type 2 diabetes in middle-aged apparently-healthy Mexican adults, identify risk factors associated to ID and develop a predictive model for ID in a high-risk population. METHODS: Prospective 3-year observational cohort, comprised of apparently-healthy adults from urban settings of central Mexico in whom demographic, anthropometric and biochemical data was collected. We evaluated risk factors for ID using Cox proportional hazard regression and developed predictive models for ID. RESULTS: We included 7636 participants of whom 6144 completed follow-up. We observed 331 ID cases (IR: 21.9 per 1000 person-years, 95%CI 21.37-22.47). Risk factors for ID included family history of diabetes, age, abdominal obesity, waist-height ratio, impaired fasting glucose (IFG), HOMA2-IR and metabolic syndrome. Early-onset ID was also high (IR 14.77 per 1000 person-years, 95%CI 14.21-15.35), and risk factors included HOMA-IR and IFG. Our ID predictive model included age, hypertriglyceridemia, IFG, hypertension and abdominal obesity as predictors (Dxy = 0.487, c-statistic = 0.741) and had higher predictive accuracy compared to FINDRISC and Cambridge risk scores. CONCLUSIONS: ID in apparently healthy middle-aged Mexican adults is currently at an alarming rate. The constructed models can be implemented to predict diabetes risk and represent the largest prospective effort for the study metabolic diseases in Latin-American population.