Characterization of data-driven clusters in diabetes-free adults and their utility for risk stratification of type 2 diabetes.

BACKGROUND: The prevention of type 2 diabetes is challenging due to the variable effects of risk factors at an individual level. Data-driven methods could be useful to detect more homogeneous groups based on risk factor variability. The aim of this study was to derive characteristic phenotypes using cluster analysis of common risk factors and to assess their utility to stratify the risk of type 2 diabetes. METHODS: Data on 7317 diabetes-free adults from Sweden were used in the main analysis and on 2332 diabetes-free adults from Mexico for external validation. Clusters were based on sex, family history of diabetes, educational attainment, fasting blood glucose and insulin levels, estimated insulin resistance and ß-cell function, systolic and diastolic blood pressure, and BMI. The risk of type 2 diabetes was assessed using Cox proportional hazards models. The predictive accuracy and long-term stability of the clusters were then compared to different definitions of prediabetes. RESULTS: Six risk phenotypes were identified independently in both cohorts: very low-risk (VLR), low-risk low ß-cell function (LRLB), low-risk high ß-cell function (LRHB), high-risk high blood pressure (HRHBP), high-risk ß-cell failure (HRBF), and high-risk insulin-resistant (HRIR). Compared to the LRHB cluster, the VLR and LRLB clusters showed a lower risk, while the HRHBP, HRBF, and HRIR clusters showed a higher risk of developing type 2 diabetes. The high-risk clusters, as a group, had a better predictive accuracy than prediabetes and adequate stability after 20 years. CONCLUSIONS: Phenotypes derived using cluster analysis were useful in stratifying the risk of type 2 diabetes among diabetes-free adults in two independent cohorts. These results could be used to develop more precise public health interventions.

Elevated serum uric acid is a facilitating mechanism for insulin resistance mediated accumulation of visceral adipose tissue.

OBJECTIVE: Serum uric acid (SUA) has been associated with cardiometabolic conditions such as insulin resistance (IR) and visceral adipose tissue (VAT) accumulation. Here, we aimed to clarify a unifying mechanism linking elevated SUA to IR and VAT. METHODS: We conducted analyses in 226 subjects from the UIEM cohort with both euglycemic hyperinsulinemic clamp (EHC) and dual X-ray absorptiometry (DXA) measurements for IR and VAT accumulation and explored the role of SUA and adiponectin by developing a network of causal mediation analyses to assess their impact on IR and VAT. These models were then translated to two population-based cohorts comprising 6337 subjects from NHANES 2003-2004 and 2011-2012 cycles in the US and ENSANUT Medio Camino 2016 in Mexico, using HOMA2IR and adipoIR as indicators of peripheral and adipose tissue IR, and METS-VF as a surrogate for VAT accumulation. RESULTS: SUA has a mediating role inside a bidirectional relationship between IR and visceral obesity, which was similar using either gold standard measurements or surrogate measures for IR and VAT. Furthermore, adiponectin acts as a linking mediator between elevated SUA and both peripheral IR and VAT accumulation. The proportion of the mechanism for IR-mediated (in either peripheral or adipose tissue) VAT accumulation was greater, compared to VAT-mediated IR accumulation (10.53% [9.23%-12.00%] to 5.44% [3.78%-7.00%]). Normal-range SUA levels can be used to rule-out underlying cardio-metabolic abnormalities in both men and women. CONCLUSIONS: Elevated SUA acts as a mediator inside the bidirectional relationship between IR and VAT accumulation and these observations could be applicable at a phenotype scale.

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.

Natural course of metabolically healthy phenotype and risk of developing Cardiometabolic diseases: a three years follow-up study.

BACKGROUND: Whether the metabolically healthy obese (MHO) phenotype is a single, stable or a transitional, fluctuating state is currently unknown. The Mexican-Mestizo population has a genetic predisposition for the development of type 2 diabetes (T2D) and other cardiometabolic complications. Little is known about the natural history of metabolic health in this population. The aim of this study was to analyze the transitions over time among individuals with different degrees of metabolic health and body mass index, and evaluate the incidence of cardiometabolic outcomes according to phenotype. METHODS: The study population consisted of a metabolic syndrome cohort with at least 3 years of follow up. Participants were apparently-healthy urban Mexican adults ≥20 years with a body mass index (BMI) ≥20 kg/m2. Metabolically healthy phenotype was defined using the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) metabolic syndrome criteria and the subjects were stratified into 4 groups according to their BMI and metabolic health. For cardiometabolic outcomes we estimated the incidence of cardiometabolic outcomes and standardized them per 1, 000 person-years of follow-up. Finally, to evaluate the risk for transition and development of cardiometabolic outcomes, we fitted Cox Proportional Hazard regression models. RESULTS: Amongst the 5541 subjects, 54.2% were classified as metabolically healthy and 45.8% as unhealthy. The MHO prevalence was 39.3%. Up to a third of the population changed from their initial category to another and the higher transition rate was observed in MHO (42.9%). We also found several novel factors associated to transition to metabolically unhealthy phenotype; socioeconomic status, number of pregnancies, a high carbohydrate intake, history of obesity and consumption of sweetened beverages. Similarly, visceral adipose tissue (VAT) was a main predictor of transition; loss of VAT ≥5% was associated with reversion from metabolically unhealthy to metabolically healthy phenotype (hazard ratio (HR) 1.545, 95%CI 1.266-1.886). Finally, we observed higher incidence rates and risk of incident T2D and hypertension in the metabolically unhealthy obesity (MUHO) and metabolically unhealthy lean (MUHL) phenotypes compared to MHO. CONCLUSIONS: Metabolic health is a dynamic and continuous process, at high risk of transition to metabolically unhealthy phenotypes over time. It is imperative to establish effective processes in primary care to prevent such transitions.

Familial hypertriglyceridemia: an entity with distinguishable features from other causes of hypertriglyceridemia.

BACKGROUND: Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease. METHODS: This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups. RESULTS: Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901-0.970, 98.5% sensitivity, 92.2% specificity, P < 0.001). The polygenic set of SNPs, accounted for 1.78% of the variance in triglyceride levels in FHTG and 6.73% in CHTG. CONCLUSIONS: The clinical and genetic differences observed between FHTG and CHTG supports the notion that FHTG is a unique entity, distinguishable from other causes of hypertriglyceridemia by the higher concentrations of insulin, FGF-21, ANGPTL3, apo A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia.

Trends in the prevalence of metabolic syndrome and its components in Mexican adults, 2006-2018.

OBJECTIVE: To examine trends in the prevalence of metabolic syndrome (MS) and its components. MATERIALS AND METHODS: Data from 27 800 Mexican adults who participated in Ensanut 2006, 2012, 2016 and 2018 were analyzed. Linear regression was used across each Ensanut period to assess temporal linear trends in the prevalence of MS. Logistic regression models were obtained to calculate the percentage change, p-value for the trend and the association between the presence of MS and the risk of developing type 2 diabetes mellitus (T2DM) over 10 years using the Finnish Diabetes Risk Score (FINDRISC) and cardiovascular disease (CVD) using Globorisk. RESULTS: The prevalence of MS in Mexican adults according to the harmonized definition was: 40.2, 57.3, 59.99 and 56.31%, in 2006, 2012, 2016 and 2018 respectively (p for trend <0.0001). In 2018, 7.62% of metabolic syndrome cases had a significant risk for incident DM2 and 11.6% for CVD. CONCLUSION: It is estimated that there are 36.5 million Mexican adults living with metabolic syndrome, of which 2 million and 2.5 million have a high risk of developing T2DM or cardiovascular disease respectively, over the next 10 years.

Association between insulin resistance and arterial stiffness in Mexican patients without type 2 diabetes.

BACKGROUND: Central aortic arterial stiffness (CAAS) is an independent cardiovascular risk factor. Insulin resistance (IR) contributes to CAAS-associated risk. OBJECTIVE: To evaluate the association between IR and CAAS in a Mexican population without diabetes. METHODS: IR was estimated with Homeostatic Model Assessment 2-Insulin Resistance (HOMA2-IR) and other surrogate markers (Metabolic score for IR [METS-IR], Quantitative Insulin Sensitivity Check Index [QUICKI], triglycerides/glucose index [TyG], TyG*body mass index [TyG*BMI] and triglycerides/high-density lipoprotein cholesterol ratio [TG/HDL-C]). CAAS was evaluated using carotid-femoral pulse wave velocity analysis (PWVcf) and the standardized augmentation index (AI-75). Bivariate correlations were made between surrogate markers and PWVcf. Increased CAAS was defined as PWVcf above the 90th percentile. Thresholds and area under the curve (AUC) were obtained for each surrogate marker in order to evaluate their performance in estimating increased CAAS. RESULTS: Three hundred and fifty-eight patients were included. A correlation was found between HOMA2-IR and PWVcf; this correlation was replicated with other surrogate markers. METS-IR and TyG*BMI had the highest degree of correlation with PWVcf. When adjustments were made for covariates, the correlations with TyG*BMI, METS-IR, HOMA2-IR and QUICKI maintained significance. HOMA2-IR showed the strongest correlation with AI-75. METS-IR and TyG showed the best AUC. Patients with prediabetes had the highest PWVcf. CONCLUSIONS: The relationship between IR and CAAS is present before the onset of diabetes; this association may entail higher cardiovascular risk.

ANTECEDENTES: La rigidez arterial central aórtica (RACA) es un factor de riesgo cardiovascular independiente. La resistencia a la insulina (RI) contribuye al riesgo asociado a RACA. OBJETIVO: Evaluar la asociación entre RI y RACA en una población mexicana sin diabetes. MÉTODOS: La RI se estimó con HOMA2-IR y (Homeostatic Model Assessment 2-Insulin Resistance) otros subrogados (METS-IR [Metabolic score for IR], QUICKI [Quantitative Insulin Sensitivity Check Index], TyG [ratio triglicéridos/glucosa], TyG*IMC [TyG*índice de masa corporal] y TG/HDL [ratio TG/lipoproteínas de alta densidad]). Se evaluó la RACA mediante el análisis de velocidad de onda del pulso carotídeo-femoral (VOPcf) y el índice de aumentación estandarizado (AI-75). Se realizaron correlaciones bivariante entre los subrogados y la VOPcf. RACA aumentada se definió como VOPcf arriba del percentil 90. Se obtuvieron puntos de corte y área bajo la curva (ABC) para cada subrogado para estimar RACA aumentada. RESULTADOS: Se incluyó 358 pacientes. Se encontró una correlación entre HOMA2-IR y VOPcf; esta correlación se replicó con los subrogados. METS-IR y TyG*IMC tuvieron el mayor grado de correlación con VOPcf. Al ajustar, las correlaciones con TyG*IMC, METS-IR, HOMA2-IR y QUICKI mantuvieron significancia. La correlación con AI-75 fue mayor para HOMA2-IR. METS-IR y TyG mostraron la mejor ABC. Los pacientes con prediabetes tuvieron mayor VOPcf. CONCLUSIONES: La relación entre la RI y la RACA está presente desde etapas no diabéticas; esta asociación puede conllevar mayor riesgo cardiovascular.

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.

Identification of a threshold to discriminate fasting hypertriglyceridemia with postprandial values.

BACKGROUND: Postprandial lipemia is an important cardiovascular risk factor. The assessment of postprandial lipid metabolism is a newly trend that several consortiums and countries have adopted. The aim of the study is to determine a postprandial triglyceride concentration cut-off point that accurately discriminate individuals with fasting normal triglyceride concentrations from those with fasting hypertriglyceridemia. METHODS: Cross sectional population-based study. A total of 212 subjects underwent an eight hours' oral fat tolerance test. Samples were taken fasting, three, four, five, six and eight hours after the meal. The area under the receiver operating characteristic curve (c-statistic) was computed using postprandial triglycerides concentrations as independent predictor, and fasting hypertriglyceridemia as dependent variable. RESULTS: The best threshold of postprandial lipemia to discriminate fasting hypertriglyceridemia was 280 mg/dL at any hour area under the curve 0.816 (95% confidence interval 0.753-0.866), bootstrap-corrected c-statistic = 0.733 (95% confidence interval 0.68-0.86). The same value was compared with apolipoprotein B concentrations (>90th percentile) having a good performance: area under the curve 0.687 95% confidence interval 0.624-0.751). Likewise, subjects with high postprandial lipemia have higher Globo risk scores. CONCLUSION: The 280 mg/dL cut-off point value of postprandial triglycerides concentration any time after a test meal discriminate subjects with fasting hypertriglyceridemia. This threshold has a good performance in a heterogeneous population and has a good concordance with cardiovascular risk surrogates.

[Development and validation of a screening score for prediabetes and undiagnosed diabetes.] / Diseño y validación de un score para detectar adultos con prediabetes y diabetes no diagnosticada.

OBJECTIVE: To develop and validate an easy-to-use risk score to detect prediabetes and undiagnosed diabetes in Mexican population. MATERIALS AND METHODS: Using information from the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán's cohort study of 10 234 adults, risk factors were identified and included in multiple logistic regression models stratified by sex. The beta coefficients of the final model were multiplied by 10, thus obtaining the weights of each variable in the score. RESULTS: The proposed score correctly classifies 55.4% of women with undiagnosed diabetes and 57.2% of women with prediabetes or diabetes. While for men it correctly classifies them at 68.6% and 69.9%, respectively. CONCLUSIONS: We present the design and validation of a risk score stratified by sex, to determine if an adult could have prediabetes or diabetes, in which case laboratory studies should be performed to confirm or not the diagnosis.

OBJETIVO: Diseñar y validar un score de riesgo de fácil aplicación para detectar prediabetes y diabetes no diagnosticada en población mexicana. MATERIAL Y MÉTODOS: Empleando la información del estudio de cohorte de 10 234 adultos del Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), se identificaron factores de riesgo incluidos en modelos de regresión logística múltiple estratificados por sexo. Los coeficientes beta fueron multiplicados por 10 para obtener el peso de cada variable en el score. Una submuestra de la Encuesta Nacional de Salud y Nutrición (Ensanut) 2012 se usó para validar el score. RESULTADOS: El score propuesto clasificó correctamente 55.4% a las mujeres con diabetes no diagnosticada y 57.2% a las mujeres con prediabetes o diabetes. Por su parte, clasificó correctamente a los hombres en 68.6 y 69.9%, respectivamente. CONCLUSIONES: Presentamos el diseño y validación de un score de riesgo estratificado por sexo para determinar si un adulto podría tener prediabetes o diabetes, en cuyo caso deberán realizarse estudios de laboratorio para confirmar o descartar el diagnóstico.

[Índices para la evaluación de la resistencia a la insulina en individuos mexicanos sin diabetes].

OBJECTIVE: To evaluate the correlation between subrogate index for the evaluation of insulin resistance with the M value obtained with the euglycemic-hyperinsulinemic clamp as well as their sensitivity, specificity, and positive and negative predictive values. METHOD: The euglycemic-hyperinsulinemic clamp was performed in subjects having both normal fasting glucose and glycated hemoglobin concentrations. HOMA-IR, QUICKI, HOMA2%S, TyG, TyG*body mass index (BMI) and triglyceride/HDL indexes were calculated. Correlations coefficients were estimated between indexes results and the M-value adjusted by fat-free mass. Areas under the ROC curve were constructed to evaluate overall performance, sensitivity, specificity and predictive values of the subrogate indexes. RESULTS: 57 subjects, 68.4% women, with a mean age of 32.9 ± 11 years-old were included. The subrogate index with the best correlation with the M value was HOMA2%S (r = 0.428), HOMA-IR had the greatest area under the ROC curve (0.683; 95 % confidence interval: 0.503-0.864) and TyG*BMI the best sensitivity (98.2 %) and specificity (51.1 %). CONCLUSIONS: The surrogated indexes for the evaluation of insulin resistance show a significant correlation with the M value obtained with the gold standard. Additional studies are required to determine cut-off values in Mexican population.

OBJETIVO: Evaluar la correlación entre índices subrogados de resistencia a la insulina y el valor M obtenido mediante pinza euglucémica-hiperinsulinémica, así como su sensibilidad, especificidad y valores predictivos positivo y negativo, en mexicanos sin diabetes. MÉTODO: Se realizó una pinza euglucémica-hiperinsulinémica en individuos con glucosa en ayuno y hemoglobina glucosilada normales. Se estimaron los índices HOMA-IR, QUICKI, HOMA2%S, TyG, TyG*índice de masa corporal (IMC) y triglicéridos/colesterol ligado a lipoproteínas de alta densidad. Se estimaron coeficientes de correlación de Pearson entre los resultados y el valor M ajustado por masa libre de grasa. Se construyeron curvas ROC para evaluar su desempeño y se estimaron la sensibilidad, la especificidad y los valores predictivos de los índices. RESULTADOS: Se incluyeron 57 individuos, el 68.4 % mujeres, de 32.9 ± 11 años, con IMC de 26.5 ± 3.9 kg/m2. El índice subrogado con mejor correlación con el valor M fue HOMA2%S (r = 0.428), con la mayor área bajo la curva ROC (0.683; intervalo de confianza del 95 %: 0.503-0.864) HOMA-IR, y con mejor sensibilidad (92.8 %) y especificidad (51.1 %) TyG*IMC. CONCLUSIONES: Los índices subrogados para estimar la resistencia a la insulina muestran una correlación significativa con el valor M obtenido con el método de referencia. Se requieren más estudios para determinar puntos de corte en población mexicana.

Non-Nutritive Sweeteners: Evidence on their Association with Metabolic Diseases and Potential Effects on Glucose Metabolism and Appetite.

There is ongoing debate concerning non-nutritive sweeteners, their usage, and their effects on metabolism. The association between non-nutritive sweeteners consumption, development of metabolic diseases, and changes in appetite-regulating hormones is not clear. The aim of this article is to present an overview of non-nutritive sweeteners and to examine the scientific evidence of their effects on glucose metabolism and appetite-regulating hormones. Some observational studies suggest an association between non-nutritive sweeteners consumption and development of metabolic diseases; however, adiposity is a confounder frequently found in these studies. Results of the available clinical trials are heterogeneous and not comparable because of major differences between them. Future controlled studies evaluating specific non-nutritive sweeteners, with an appropriate sample size, including a uniform study group, with sufficient exposure time, and considering adjustment for confounder variables, such as anthropometric characteristics, previous consumption of non-nutritive sweeteners, and coexistence of significant metabolic comorbidities, are needed.

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.

Evaluation of a Web Platform to Record Lifestyle Habits in Subjects at Risk of Developing Type 2 Diabetes in a Middle-Income Population: Prospective Interventional Study.

BACKGROUND: Lifestyle is the focus of type 2 diabetes (T2D) prevention strategies. Prevention strategies using mobile health (mHealth)-based therapy have shown positive results for T2D prevention in high-income settings, but little is known about their effectiveness in low- and middle-income populations where the burden of T2D is substantial. "Vida Sana" is a web platform designed to record lifestyle habits and medication use within a lifestyle change program. OBJECTIVE: We sought to identify the barriers, feasibility, usability, and effectiveness of Vida Sana to record lifestyle habits in subjects at risk of developing T2D in a middle-income setting. METHODS: This was a 3-month prospective interventional study in Mexican individuals. A total of 77 subjects at risk of T2D (with prediabetes and BMI between 24 and 40 kg/m2) were selected. Feasibility was assessed by study retention. Usability was evaluated with the System Usability Scale (SUS). Effectiveness measures included changes in weight, body composition, BMI, glycated hemoglobin A1c (HbA1c), and fasting blood glucose from baseline to 3 months. Linear regression models were used to account for covariates. RESULTS: The feasibility of Vida Sana was 42%, with 33 subjects using the platform, and the usability was 48.7 (SD 14.24). Reported barriers to platform usage were; difficulty in accessing the platform from difficulty of use (12 subjects, 36%), lack of time to record their habits (11 subjects, 34%), lack of interest to record their habits (6 subjects, 18%), and lack of resources (4 subjects, 11%). The platform was effective for lowering glucose in fasting (-3.1 mg/dL vs -0.11 [SD 8.08] mg/dL; P=.038) and at 2 hours (-16.9 mg/dL vs 2.5 [SD 26.1] mg/dL; P=.045), body fat percentage (-1.3 [-2.2 to -0.7] vs -1.02 [-1.9 to -0.3]; P=.02), and waist circumference (-3.2 [SD 5.1] cm vs -1.7 [SD 5.0] cm; P=.02) independent of their age, sex, treatment, and education level. CONCLUSIONS: The use of the web platform was effective for improving glycemic and anthropometric parameters in a population at risk of developing diabetes. Improving accessibility and ease of navigation could improve the acceptance of digital health solutions in a middle-income population.

Arterial Stiffness and HbA1c: Association Mediated by Insulin Resistance in Hispanic Adults.

Arterial stiffness may be associated with glucose metabolism parameters, such as HbA1c, mainly via insulin resistance. We aimed to investigate the association between arterial stiffness and HbA1c and explore the mediator effect of insulin resistance. In this cross-sectional study, arterial stiffness (pulse-wave velocity; PWV), HbA1c, and insulin resistance (METS-IR) were determined in Hispanic adults. In addition to sex and age, various biochemical measurements (glucose, lipid profile, etc.) and adipose tissue (fat mass and visceral fat mass) were considered as potential confounding variables. A multivariate regression analysis shows that HbA1c is associated with PWV, even after adjusting for several confounding variables. Importantly, the results show that insulin resistance mediated 17.9% of the effect of HbA1c over PWV. In conclusion, HbA1c may be a potential resource for predicting arterial stiffness due to the influence of insulin resistance in Hispanic subjects.

Primary Barriers of Adherence to a Structured Nutritional Intervention in Patients with Dyslipidemia.

PURPOSE: To describe the primary barriers to adequately adhering to a structured nutritional intervention. PATIENTS AND METHODS: A total of 106 participants diagnosed with dyslipidemia and without a medical nutrition therapeutic plan were included in this two-year study conducted at the INCMNSZ dyslipidemia clinic in Mexico City. All patients were treated with the same structured strategies, including three face-to-face visits and two telephone follow-up visits. Diet plan adherence was evaluated at each site visit through a 3-day or 24-h food recall. RESULTS: Barriers to adhere to the nutritional intervention were: lack of time to prepare their meals (23%), eating outside the home (19%), unwillingness to change dietary patterns (14%), and lack of information about a correct diet for dyslipidemias (14%). All barriers decreased significantly at the end of the intervention. Female gender, current smoking, and following a plan of more than 1500 kcal (R2 = 0.18 and p-value = 0.004) were associated with good diet adherence. Participants showed good levels of adherence to total caloric intake at visit 2 and 3, reporting 104.7% and 95.4%, respectively. Adherence to macronutrient intake varied from 65.1% to 126%, with difficulties in adhering to recommended carbohydrate and fat consumption being more notable. CONCLUSION: The study findings confirm that a structured nutritional intervention is effective in reducing barriers and improving dietary adherence and metabolic control in patients with dyslipidemias. Health providers must identify barriers to adherence early on to design interventions that reduce these barriers and improve adherence.

Two novel variants in DYRK1B causative of AOMS3: expanding the clinical spectrum.

BACKGROUND: We investigated pathogenic DYRK1B variants causative of abdominal obesity-metabolic syndrome 3 (AOMS3) in a group of patients originally diagnosed with type 2 diabetes. All DYRK1B exons were analyzed in a sample of 509 unrelated adults with type 2 diabetes and 459 controls, all belonging to the DMS1 SIGMA-cohort (ExAC). We performed in silico analysis on missense variants using Variant Effect Predictor software. To evaluate co-segregation, predicted pathogenic variants were genotyped in other family members. We performed molecular dynamics analysis for the co-segregating variants. RESULTS: After filtering, Mendelian genotypes were confirmed in two probands bearing two novel variants, p.Arg252His and p.Lys68Gln. Both variants co-segregated with the AOMS3 phenotype in classic dominant autosomal inheritance with full penetrance. In silico analysis revealed impairment of the DYRK1B protein function by both variants. For the first time, we describe age-dependent variable expressivity of this entity, with central obesity and insulin resistance apparent in childhood; morbid obesity, severe hypertriglyceridemia, and labile type 2 diabetes appearing before 40 years of age; and hypertension emerging in the fifth decade of life. We also report the two youngest individuals suffering from AOMS3. CONCLUSIONS: Monogenic forms of metabolic diseases could be misdiagnosed and should be suspected in families with several affected members and early-onset metabolic phenotypes that are difficult to control. Early diagnostic strategies and medical interventions, even before symptoms or complications appear, could be useful.

Contribution of Known Genetic Risk Variants to Dyslipidemias and Type 2 Diabetes in Mexico: A Population-Based Nationwide Study.

Dyslipidemias are common risk factors for the development of chronic disorders including type 2 diabetes (T2D). Over 100 associated loci have been identified but few reports have evaluated the population attributable fraction captured by them in population-based nationwide surveys. Therefore, we determined the population contribution of a set of known genetic risk variants to the development of dyslipidemias and T2D in Mexico. This study included 1665 participants from a Mexican National Health Survey carried out in the year 2000. It is a probabilistic complex sample survey of households, which comprises representative data at a national level. 103 previously reported SNPs associated with different dyslipidemias or T2D were genotyped and used to compute polygenic risk scores. We found that the previously known variants associated with dyslipidemias explain at most 7% of the total risk variance of lipid levels. In contrast, the known genetic risk component for T2D explained a negligible amount of variance (0.1%). Notably, variants derived from the Native-American ancestry have the strongest effect and contribute with a high proportion of the variance. These results support the need for additional studies aimed to identify specific genetic risk variants for Mexican population.

Metabolic Score for Visceral Fat (METS-VF), a novel estimator of intra-abdominal fat content and cardio-metabolic health.

BACKGROUND & AIMS: Intra-abdominal and visceral fat (VAT) are risk factors for the development of cardio-metabolic comorbidities; however its clinical assessment is limited by technology and required expertise for its assessment. We aimed to develop a novel score (METS-VF) to estimate VAT by combining the non-insulin-based METS-IR index, waist-height ratio (WHtr), age and sex. METHODS: We developed METS-VF in a sample of 366 individuals with Dual X-ray absorptiometry (DXA). METS-VF was modeled using non-linear regression and validated in two replication cohorts with DXA (n = 184, with n = 118 who also had MRI) and bio-electrical impedance (n = 991). We also assessed METS-VF to predict incident type 2 diabetes (T2D) and arterial hypertension independent of body-mass index (BMI) in our Metabolic Syndrome Cohort (n = 6144). RESULTS: We defined METS-VF as: 4.466 + 0.011*(Ln(METS-IR))3 + 3.239*(Ln(WHtr))3 + 0.319*(Sex) + 0.594*(Ln(Age)). METS-VF showed better performance compared to other VAT surrogates using either DXA (AUC 0.896 95% CI 0.847-0.945) or MRI (AUC 0.842 95% CI 0.771-0.913) as gold standards. We identified a METS-VF cut-off point >7.18 in healthy patients which has 100% sensitivity (95% CI 76.8-100) and 87.2% specificity (95% CI 79.1-93.0) to identify increased VAT (>100 cm2). METS-VF also had adequate performance in subjects with metabolically-healthy obesity. Finally, in our metabolic syndrome cohort, subjects in the upper quintiles of METS-VF (>7.2) had 3.8 and 2.0-fold higher risk of incident T2D and hypertension, respectively (p < 0.001). This effect was independent of BMI for both outcomes. CONCLUSION: METS-VF is a novel surrogate to estimate VAT, which has better performance compared to other surrogate VAT indexes and is predictive of incident T2D and hypertension. METS-VF could be a useful tool to assess cardio-metabolic risk in primary care practice and research settings.

Empowerment of patients with type 2 diabetes: current perspectives.

Patient empowerment is a continuous process in which knowledge, motivation, and capacity to take control of their disease are built within a person. This concept is not always well understood and applied. This review describes the strategies to induce empowerment in patients with diabetes. In addition, the most common scales used to evaluate empowerment in diabetes is described. Furthermore, the effectiveness of the empowerment-based interventions for improving metabolic control and diabetes knowledge are described. Finally, we discuss opportunities for empowerment implementation in clinical practice and current needs on research that can be translated into public policies.