Associated factors to the consumption of non-nutritive sweeteners in the Mexican adult population.

OBJECTIVE: To identify the associated factors to the consumption of non-nutritive sweeteners (NNS) in the Mexican adult population since its consumption has increased exponentially worldwide. MATERIALS AND METHODS: An online survey was applied to 5 038 Mexican adults to evaluate the frequency of NNS consumption and classify the population in tertiles. The sociodemographic, lifestyle and health status characteristics of the participants were compared by gradient of NNS consumption, and a multiple linear regression analysis was performed to determine the associated factors to the NNS consumption. RESULTS: The variables that showed a positive association (p≤0.01) with the consumption of NNS were economic income, BMI, smoking, physical activity, diet quality, the presence of chronic diseases (diabetes, hypertension, or dyslipidemias), and the consumption of fruit. The age and the consumption of confectionery and sugar-sweetened beverages were negatively associated (p<0.01) with the consumption of NNS. CONCLUSION: The results of this study help to characterize the target population that is a consumer of NNS since it is recommended not encourage the preference for sweet taste and to promote a decrease in the consumption of both caloric and NNS, preferring the natural flavor of food.

Chronic kidney disease acquired knowledge in a diabetic and hypertensive population using a translated and validated questionnaire.

Chronic kidney disease (CKD) is the progressive and irreversible functional and/or structural impairment of the kidney; its main etiologies include hypertension and diabetes. Mexico has the second highest prevalence of CKD worldwide with a high economic burden affecting public and private health systems. Patients with higher knowledge about CKD increase their adherence to preventive treatment. In this study we aim to describe the knowledge of CKD in a sample of Mexican high-risk population, comparing it with general Mexican population, medical students and nephrologists. A cross-sectional, observational study was performed divided in two phases: translation and validation of the knowledge questionnaire to Spanish, and cross-sectional survey to evaluate the knowledge of CKD in patients with diagnosis of diabetes and/or hypertension. We interviewed medical students, general population, and nephrologists to attain validation of the questionnaire in Spanish. The questionnaire was answered by 1,061 participants within the high-risk population. The results of the questionnaire were: 22/24, 18/24, 13.8/24, and 13.4/24 in nephrologists, medical students, normal subjects, and high-risk population, respectively. The questions with least correct answers were related to kidney functions and CKD risk factors. To our knowledge this is the first time a questionnaire for CKD knowledge is applied in Mexican population. These findings suggest poor understanding of kidney functions, risk factors, and symptoms of CKD. It is important not only to provide medical treatment to chronic illness but also awareness of the consequences of not achieving goals of treatment.

Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus.

PURPOSE OF REVIEW: Diabetes mellitus is a complex, chronic illness characterized by elevated blood glucose levels that occurs when there is cellular resistance to insulin action, pancreatic ß-cells do not produce sufficient insulin, or both. Diabetes prevalence has greatly increased in recent decades; consequently, it is considered one of the fastest-growing public health emergencies globally. Poor blood glucose control can result in long-term micro- and macrovascular complications such as nephropathy, retinopathy, neuropathy, and cardiovascular disease. Individuals with diabetes require continuous medical care, including pharmacological intervention as well as lifestyle and dietary changes. RECENT FINDINGS: The most common form of diabetes mellitus, type 2 diabetes (T2DM), represents approximately 90% of all cases worldwide. T2DM occurs more often in middle-aged and elderly adults, and its cause is multifactorial. However, its incidence has increased in children and young adults due to obesity, sedentary lifestyle, and inadequate nutrition. This high incidence is also accompanied by an estimated underdiagnosis prevalence of more than 50% worldwide. Implementing successful and cost-effective strategies for systematic screening of diabetes mellitus is imperative to ensure early detection, lowering patients' risk of developing life-threatening disease complications. Therefore, identifying new biomarkers and assay methods for diabetes mellitus to develop robust, non-invasive, painless, highly-sensitive, and precise screening techniques is essential. This review focuses on the recent development of new clinically validated and novel biomarkers as well as the methods for their determination that represent cost-effective alternatives for screening and early diagnosis of T2DM.

LCAT deficiency: a systematic review with the clinical and genetic description of Mexican kindred.

BACKGROUND: LCAT (lecithin-cholesterol acyltransferase) deficiency is characterized by two distinct phenotypes, familial LCAT deficiency (FLD) and Fish Eye disease (FED). This is the first systematic review evaluating the ethnic distribution of LCAT deficiency, with particular emphasis on Latin America and the discussion of three Mexican-Mestizo probands. METHODS: A systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) Statement in Pubmed and SciELO. Articles which described subjects with LCAT deficiency syndromes and an assessment of the ethnic group to which the subject pertained, were included. RESULTS: The systematic review revealed 215 cases (154 FLD, 41 FED and 20 unclassified) pertaining to 33 ethnic/racial groups. There was no association between genetic alteration and ethnicity. The mean age of diagnosis was 42 ± 16.5 years, with fish eye disease identified later than familial LCAT deficiency (55 ± 13.8 vs. 41 ± 14.7 years respectively). The prevalence of premature coronary heart disease was significantly greater in FED vs. FLD. In Latin America, 48 cases of LCAT deficiency have been published from six countries (Argentina (1 unclassified), Brazil (38 FLD), Chile (1 FLD), Columbia (1 FLD), Ecuador (1 FLD) and Mexico (4 FLD, 1 FED and 1 unclassified). Of the Mexican probands, one showed a novel LCAT mutation. CONCLUSIONS: The systematic review shows that LCAT deficiency syndromes are clinically and genetically heterogeneous. No association was confirmed between ethnicity and LCAT mutation. There was a significantly greater risk of premature coronary artery disease in fish eye disease compared to familial LCAT deficiency. In FLD, the emphasis should be in preventing both cardiovascular disease and the progression of renal disease, while in FED, cardiovascular risk management should be the priority. The LCAT mutations discussed in this article are the only ones reported in the Mexican- Amerindian population.

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.

The panorama of familial hypercholesterolemia in Latin America: a systematic review.

The burden caused by familial hypercholesterolemia (FH) varies among countries and ethnic groups. The prevalence and characteristics of FH in Latin American (LA) countries is largely unknown. We present a systematic review (following the PRISMA statement) of FH in LA countries. The epidemiology, genetics, screening, management, and unique challenges encountered in these countries are discussed. Published reports discussing FH in Hispanic or LA groups was considered for analysis. Thirty studies were included representing 10 countries. The bulk of the data was generated in Brazil and Mexico. Few countries have registries and there was little commonality in FH mutations between LA countries. LDL receptor mutations predominate; APOB and PCSK9 mutations are rare. No mutation was found in an FH gene in nearly 50% of cases. In addition, some country-specific mutations have been reported. Scant information exists regarding models of care, cascade screening, cost, treatment effectiveness, morbidity, and mortality. In conclusion, FH is largely underdiagnosed and undertreated in the LA region. The genetic admixture with indigenous populations, producing mestizo's groups, may influence the mutational findings in Latin America. Potential opportunities to close gaps in knowledge and health care are identified.

A systematic review of biobanks in Latin America: Strengths and limitations for biomedical research.

Biobanks are valuable tools for developing and applying scientific research and international cooperation through the collection of biological materials and their associated data. Systematic research following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines was conducted in late 2022 in PubMed and Scopus, and generated 17 articles to be reviewed in depth and critically assessed using the Critical Appraisal Skills Programme Checklist due to the limited available data; 12 relevant health organizations and government websites outside of peer-reviewed journals were also included. Our research identified 44 biobanks in Latin America. In general, there is a lack of regulation and legislation guaranteeing the stored materials' quality and institutional collaboration. We believe a consensus needs to be reached regarding the terminology and definitions used for biobanks. The design for informed consent should also be agreed upon to ensure the privacy of the data shared among institutions. In conclusion, in Latin America, there is a clear need for government support in creating specific procedures for biobanks and providing further support for existing biobanks.

Agreement Between Bioelectrical Impedance Analysis and Dual-Energy X-ray Absorptiometry to Estimate Fat Mass in Hispanic Adults With Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background: Adipose tissue excess is associated with adverse health outcomes, including type 2 diabetes. Body mass index (BMI) is used to evaluate obesity but is inaccurate as it does not account for muscle mass, bone density, and fat distribution. Accurate measurement of adipose tissue through dual-energy X-ray absorptiometry (DXA) and computed axial tomography (CT) is crucial for managing and monitoring adiposity-related diseases. Still, these are not easily accessible in most hospitals in Mexico. Bioelectrical impedance analysis (BIA) is non-invasive and low-cost but may not be reliable in conditions affecting the body's hydration status, like diabetes. Objectives: To assess fat mass concordance between BIA and DXA in Hispanic-American adults with type 2 diabetes mellitus (T2DM). Methods: Cross-sectional study of a non-probabilistic sample of subjects over 18 years with type 2 diabetes. We used DXA as the reference method. Results: We evaluated the accuracy of FM estimation through BIA and DXA in 309 subjects with type 2 diabetes. Results showed a trend of overestimating the diagnosis of obesity using BIA, especially in individuals with a higher fat mass index (FMI). At the group level, we found BIA accurate; however, at the individual level, it is not. The bias between the 2 methods showed a statistically significant overestimation of body fat by BIA (P ⩽ .01) in both sexes. BIA demonstrated high precision in estimating fat mass. We were able to provide a correction factor of 0.55 kg in men. Conclusion: BIA is inaccurate compared to DXA for body composition assessment in patients with diabetes. Inaccurate measurements can result in misclassification. However, BIA is precise for body composition assessment in patients with diabetes, so it is reliable for tracking patient progress over time.

Agreement between bioelectrical impedance analysis and dual-energy X-ray absorptiometry to estimate fat mass in adults with type 2 Diabetes Mellitus This study compares 2 methods for measuring body composition in patients with diabetes in Mexico. The first method is Bioelectrical Impedance Analysis (BIA), which is non-invasive, low-cost, and easy to use but may not be reliable in conditions that affect the body's hydration status, like diabetes. The second method is Dual-energy X-ray Absorptiometry (DXA), which is more accurate but less easily accessible. The study was a cross-sectional evaluation of 309 participants over 18 years with type 2 diabetes mellitus (T2DM) by HbA1C levels. The present study found BIA to be precise for body composition assessment but not accurate compared to DXA as the reference method. The study showed a trend of overestimating the diagnosis of obesity using BIA, especially in individuals with a higher fat mass index. This study found BIA is accurate at the group level but not at the individual level. The bias between the 2 methods showed a statistically significant overestimation of body fat by BIA. We provided a correction factor of 0.55 kg in men but not women. BIA is not ideal for diagnosing obesity but is reliable for tracking patient progress over time.

Phase Angle as a Potential Screening Tool in Adults with Metabolic Diseases in Clinical Practice: A Systematic Review.

BACKGROUND: Phase angle (PhA) has been used as mortality prognostic, but there are no studies about its possible use as a screening tool. Therefore, an assessment of the possible utility of PhA in clinical practice is required. The aim of this systematic review was to explore all recent available evidence of PhA, and its possible utility as a screening tool in clinical practice in subjects with chronic metabolic diseases. MATERIALS AND METHODS: This systematic review was performed and written as stated in the PRISMA 2020 guidelines. The search was conducted in PubMed, ScienceDirect and SciElo. In order to be considered eligible, within the entire search, only articles involving PhA and their utility in metabolic diseases were included. RESULTS: PhA was associated with hyperuricemia and vitamin D deficiency in obese subjects, and decreased cardiovascular risk and malnutrition in hospitalized patients. CONCLUSION: PhA may be a potential screening tool in clinical practice to evaluate different biomarkers, cardiovascular risk, and nutritional diagnosis in metabolic diseases in adults.

HDL abnormalities in type 2 diabetes: Clinical implications.

Atherosclerotic cardiovascular disease (ASCVD) represents the primary cause of mortality among patients with Type 2 Diabetes Mellitus (T2DM). In this population, High-Density Lipoprotein (HDL) particles exhibit abnormalities in number, composition, and function, culminating in diminished anti-atherosclerotic capabilities despite normal HDL cholesterol (HDL-C) concentrations. Hyperglycemic conditions contribute to these alterations in HDL kinetics, composition, and function, causing T2DM patients' HDL particles to exhibit decreased concentrations of diverse lipid species and proteins. Treatment of hyperglycemia has the potential to correct abnormal HDL particle attributes in T2DM; however, pharmacological interventions, including metformin and thiazolidinediones, yield inconsistent outcomes with respect to HDL-C concentrations and functionality. Despite numerous attempts with diverse drugs, pharmacologically augmenting HDL-C levels has not resulted in clinical benefits in mitigating ASCVD risk. In contrast, reducing Low Density Lipoprotein cholesterol (LDL-C) via statins and ezetimibe has demonstrated significant efficacy in curtailing CVD risk among T2DM individuals. Promising results have been observed in animal models and early-phase trials utilizing recombinant HDL and Lecitin Cholesterol Acyl Transferase (LCAT) -enhancing agents, but the evaluation of their efficacy and safety in large-scale clinical trials is ongoing. While aberrant HDL metabolism constitutes a prevalent aspect of dyslipidemia in T2DM, HDL cholesterol concentrations and composition no longer offer valuable insights for informing therapeutic decisions. Nevertheless, HDL metabolism remains a critical research area in T2DM, necessitating further investigation to elucidate the role of HDL particles in the development of diabetes-associated complications.

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.

Familial hypercholesterolemia in Mexico: Initial insights from the national registry.

BACKGROUND: Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. OBJECTIVE: Report the results of the first years (2017-2019) of the Mexican FH registry. METHODS: There are 60 investigators, representing 28 federal states, participating in the registry. The variables included are in accordance with the European Atherosclerosis Society (EAS) FH recommendations. RESULTS: To date, 709 patients have been registered, only 336 patients with complete data fields are presented. The mean age is 50 (36-62) years and the average time since diagnosis is 4 (IQR: 2-16) years. Genetic testing is recorded in 26.9%. Tendon xanthomas are present in 43.2%. The prevalence of type 2 diabetes is 11.3% and that of premature CAD is 9.8%. Index cases, male gender, hypertension and smoking were associated with premature CAD. The median lipoprotein (a) level is 30.5 (IQR 10.8-80.7) mg/dl. Statins and co-administration with ezetimibe were recorded in 88.1% and 35.7% respectively. A combined treatment target (50% reduction in LDL-C and an LDL-C <100 mg/dl) was achieved by 13.7%. Associated factors were index case (OR 3.6, 95%CI 1.69-8.73, P = .002), combination therapy (OR 2.4, 95%CI 1.23-4.90, P = .011), type 2 diabetes (OR 2.8, 95%CI 1.03-7.59, P = .036) and age (OR 1.023, 95%CI 1.01-1.05, P = .033). CONCLUSION: The results confirm late diagnosis, a lower than expected prevalence and risk of ASCVD, a higher than expected prevalence of type 2 diabetes and undertreatment, with relatively few patients reaching goals. Recommendations include, the use of combination lipid lowering therapy, control of comorbid conditions and more frequent genetic testing in the future.

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.

Prediction of incident hypertension and arterial stiffness using the non-insulin-based metabolic score for insulin resistance (METS-IR) index.

Hypertension is associated with insulin resistance (IR), metabolic syndrome (MS), and arterial stiffness. Non-insulin-based IR indexes were developed as tools for metabolic screening. Here, we aimed to evaluate the novel non-insulin-based Metabolic Score for IR (METS-IR) index for the prediction of incident hypertension and arterial stiffness evaluated using pulse wave velocity (PWV) analysis, compared with other non-insulin-based IR indexes. We evaluated two populations, a cross-sectional evaluation of high-risk individuals (n = 305) with a wide range of metabolic comorbidities and dyslipidemia in whom PWV measurement was performed and a 3-year prospective cohort of normotensive individuals (N = 6850). We observed a positive correlation between METS-IR and PWV in the cross-sectional cohort, which was higher compared with other non-insulin-based fasting IR indexes; furthermore, PWV values >75th percentile were associated with the upper tercile of METS-IR values. In the prospective cohort, we observed an increased risk for incident hypertension for the upper METS-IR tercile (METS-IR ≥ 46.42; HR: 1.81, 95% CI: 1.41-2.34), adjusted for known cardiovascular risk factors, and observed that METS-IR had greater increases in the predictive capacity for hypertension along with SBP and the Framingham Hypertension Risk Prediction Model compared with other non-insulin-based IR indexes. Therefore, METS-IR is a novel non-insulin-based IR index which correlates with arterial stiffness and is a predictor of incident hypertension, complementary to previously validated risk prediction models.

The development of the Mexican Familial Hypercholesterolemia (FH) National Registry.

BACKGROUND AND AIMS: In Mexico, familial hypercholesterolemia (FH) is, as in other parts of the world, largely underdiagnosed and undertreated, and represents a significant burden to the healthcare system. However, there is not enough information to design public policies against the disease. Genetic studies have shown that LDLR mutations are the most common cause, but in a large percentage of the cases, no mutation has been identified in the FH genes. METHODS: In accordance with the procedures of the European Atherosclerosis Society (EAS) FH registries network, the Mexican FH registry (www.fhmexico.org.mx) was launched in December 2017 to address the gaps in knowledge regarding this disease. Reference centres and the main nationwide public health providers have been invited to participate. RESULTS: To date, 142 cases have been registered. The mean age at diagnosis of probands is 36.42 ±â€¯19.9 years (adults and children). Tendon xanthomas or premature corneal arcus were present in 40% and 17.6%, respectively. Molecular analysis was present in 70%, with over 95% of alterations located on the LDL receptor gene. The median untreated LDL-C is 6.5 (5.6-8.4) mmol/l and the median on treatment LDL-C level is 4.3 ±â€¯1.7 mmol/l. CONCLUSIONS: The Mexican FH registry aims to obtain real world information regarding the management of patients in this country. By participating in this global call to action, we hope to improve both short and long term outcomes for all FH patients in Mexico.

METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes.

OBJECTIVE: We developed a novel non-insulin-based fasting score to evaluate insulin sensitivity validated against the euglycemic-hyperinsulinemic clamp (EHC). We also evaluated its correlation with ectopic fact accumulation and its capacity to predict incident type 2 diabetes mellitus (T2D). DESIGN AND METHODS: The discovery sample was composed by 125 subjects (57 without and 68 with T2D) that underwent an EHC. We defined METS-IR as Ln((2*G0)+TG0)*BMI)/(Ln(HDL-c)) (G0: fasting glucose, TG0: fasting triglycerides, BMI: body mass index, HDL-c: high-density lipoprotein cholesterol), and compared its diagnostic performance against the M-value adjusted by fat-free mass (MFFM) obtained by an EHC. METS-IR was validated in a sample with EHC data, a sample with modified frequently sampled intravenous glucose tolerance test (FSIVGTT) data and a large cohort against HOMA-IR. We evaluated the correlation of the score with intrahepatic and intrapancreatic fat measured using magnetic resonance spectroscopy. Subsequently, we evaluated its ability to predict incident T2D cases in a prospective validation cohort of 6144 subjects. RESULTS: METS-IR demonstrated the better correlation with the MFFM (ρ = -0.622, P < 0.001) and diagnostic performance to detect impaired insulin sensitivity compared to both EHC (AUC: 0.84, 95% CI: 0.78-0.90) and the SI index obtained from the FSIVGTT (AUC: 0.67, 95% CI: 0.53-0.81). METS-IR significantly correlated with intravisceral, intrahepatic and intrapancreatic fat and fasting insulin levels (P < 0.001). After a two-year follow-up, subjects with METS-IR in the highest quartile (>50.39) had the highest adjusted risk to develop T2D (HR: 3.91, 95% CI: 2.25-6.81). Furthermore, subjects with incident T2D had higher baseline METS-IR compared to healthy controls (50.2 ± 10.2 vs 44.7 ± 9.2, P < 0.001). CONCLUSION: METS-IR is a novel score to evaluate cardiometabolic risk in healthy and at-risk subjects and a promising tool for screening of insulin sensitivity.

Mexican Carriers of the HNF1A p.E508K Variant Do Not Experience an Enhanced Response to Sulfonylureas.

OBJECTIVE: To assess whether an ethnic-specific variant (p.E508K) in the maturity-onset diabetes of the young (MODY) gene hepatocyte nuclear factor-1α (HNF1A) found in Mexicans is associated with higher sensitivity to sulfonylureas, as documented in patients with MODY3. RESEARCH DESIGN AND METHODS: We recruited 96 participants (46 variant carriers and 50 age- and sex-matched noncarriers). Response to glipizide (one 2.5-5.0-mg dose), metformin (four 500-mg doses), and an oral glucose challenge was evaluated using a previously validated protocol. Glucose and insulin levels and their areas under the curve (AUCs) were compared between groups. RESULTS: Carriers of the p.E508K variant had a lower maximum insulin peak during the glipizide challenge as compared with noncarriers with diabetes (P < 0.05). Also, carriers had a lower insulin response after the oral glucose challenge. Following an oral glucose tolerance test in the presence of metformin, carriers of the p.E508K variant with diabetes had a lower maximum insulin peak and total and incremental insulin AUC value as compared with noncarriers with diabetes (P < 0.05). A similar but nonsignificant trend was seen in participants without type 2 diabetes. CONCLUSIONS: Carriers of variant p.E508K in HNF1A have a reduced insulin response rather than the increased sensitivity to sulfonylureas seen in patients with MODY3.

The amelioration of hepatic steatosis by thyroid hormone receptor agonists is insufficient to restore insulin sensitivity in ob/ob mice.

Thyroid hormone receptor (TR) agonists have been proposed as therapeutic agents to treat non-alcoholic fatty liver disease (NAFLD) and insulin resistance. We investigated the ability of the TR agonists GC-1 and KB2115 to reduce hepatic steatosis in ob/ob mice. Both compounds markedly reduced hepatic triglyceride levels and ameliorated hepatic steatosis. However, the amelioration of fatty liver was not sufficient to improve insulin sensitivity in these mice and reductions in hepatic triglycerides did not correlate with improvements in insulin sensitivity or glycemic control. Instead, the effects of TR activation on glycemia varied widely and were found to depend upon the time of treatment as well as the compound and dosage used. Lower doses of GC-1 were found to further impair glycemic control, while a higher dose of the same compound resulted in substantially improved glucose tolerance and insulin sensitivity, despite all doses being equally effective at reducing hepatic triglyceride levels. Improvements in glycemic control and insulin sensitivity were observed only in treatments that also increased body temperature, suggesting that the induction of thermogenesis may play a role in mediating these beneficial effects. These data illustrate that the relationship between TR activation and insulin sensitivity is complex and suggests that although TR agonists may have value in treating NAFLD, their effect on insulin sensitivity must also be considered.

Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat.

The functional conversion of white adipose tissue (WAT) into a tissue with brown adipose tissue (BAT)-like activity, often referred to as "browning," represents an intriguing strategy for combating obesity and metabolic disease. We demonstrate that thyroid hormone receptor (TR) activation by a synthetic agonist markedly induces a program of adaptive thermogenesis in subcutaneous WAT that coincides with a restoration of cold tolerance to cold-intolerant mice. Distinct from most other browning agents, pharmacological TR activation dissociates the browning of WAT from activation of classical BAT. TR agonism also induces the browning of white adipocytes in vitro, indicating that TR-mediated browning is cell autonomous. These data establish TR agonists as a class of browning agents, implicate the TRs in the browning of WAT, and suggest a profound pharmacological potential of this action.