Determinants of VLDL composition and apo B-containing particles in familial combined hyperlipidemia.

Background: In familial combined hyperlipidemia (FCHL) the severity of the dyslipidemia is determined by an overproduction of VLDL (very low density lipoprotein) particles and by its abnormal lipid composition. However, few are known regarding the metabolic factors that determine these abnormalities. We investigated the impact of metabolic factors on the number of atherogenic particles (apolipoprotein B level (apoB)) and the triglyceride content of very low-density lipoproteins (VLDLs-TG).

[Caloric restriction: about its positive metabolic effects and cellular impact].

Caloric restriction, as a 30 to 60% decrease of ad libitum balanced caloric intake, without malnutrition, is the non-genetic strategy that has consistently extended the average and maximum lifespan of most living beings, and it has been tested from unicellular organisms like yeast Saccharomyces cerevisiae to Rhesus primates. In addition, various genetic and pharmacological caloric restriction models have shown to protect against cancer, cardiovascular and neurodegenerative diseases. Primate studies suggest that this intervention delays the onset of age-related diseases; in humans, it has physiological, biochemical and metabolic effects decreasing diabetes and cardiovascular disease risk factor.

Prevalence of lipid phenotypes, serum lipid behaviour over follow-up and predictors of serum lipid levels in a cohort of Mexican Mestizo early rheumatoid arthritis patients treated with conventional disease-modifying anti-rheumatic drugs.

Objectives: Our aim was to describe the prevalence of dyslipidaemia, serum lipid behaviour and predictors of serum lipid levels in a cohort of early rheumatoid arthritis (RA) patients.

Methods: Charts from 146 patients who were lipid-lowering therapy (LLT) free at inclusion and had baseline complete serum fasting lipid profile and ≥1 lipid profile/patient/year of follow-up were reviewed. Patient's prevalence of dyslipidemia was compared to matched controls.

Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population.

Importance: Latino populations have one of the highest prevalences of type 2 diabetes worldwide.

Objectives: To investigate the association between rare protein-coding genetic variants and prevalence of type 2 diabetes in a large Latino population and to explore potential molecular and physiological mechanisms for the observed relationships.

Design, Setting, And Participants: Whole-exome sequencing was performed on DNA samples from 3756 Mexican and US Latino individuals (1794 with type 2 diabetes and 1962 without diabetes) recruited from 1993 to 2013.

Amerindian-specific regions under positive selection harbour new lipid variants in Latinos.

Dyslipidemia and obesity are especially prevalent in populations with Amerindian backgrounds, such as Mexican-Americans, which predispose these populations to cardiovascular disease. Here we design an approach, known as the cross-population allele screen (CPAS), which we conduct prior to a genome-wide association study (GWAS) in 19,273 Europeans and Mexicans, in order to identify Amerindian risk genes in Mexicans. Utilizing CPAS to restrict the GWAS input variants to only those differing in frequency between the two populations, we identify novel Amerindian lipid genes, receptor-related orphan receptor alpha (RORA) and salt-inducible kinase 3 (SIK3), and three loci previously unassociated with dyslipidemia or obesity.

Genetic and environmental determinants of the susceptibility of Amerindian derived populations for having hypertriglyceridemia.

Here, we discuss potential explanations for the higher prevalence of hypertriglyceridemia in populations with an Amerindian background. Although environmental factors are the triggers, the search for the ethnic related factors that explain the increased susceptibility of the Amerindians is a promising area for research. The study of the genetics of hypertriglyceridemia in Hispanic populations faces several challenges.

PNPLA3 I148M polymorphism is associated with elevated alanine transaminase levels in Mexican Indigenous and Mestizo populations.

The patatin like phospholipase domain-containing (PNPLA3) I148M variant is the strongest genetic factor associated with elevated alanine transaminase (ALT) levels in different populations, particularly in Hispanics who have the highest 148M risk allele frequency reported to date. It has been suggested that Indigenous ancestry is associated with higher ALT levels in Mexicans. The aim of the present study was to assess the frequency of the PNPLA3 148M risk allele in Mexican indigenous and Mestizo individuals, and to examine its association with serum ALT levels.

Epidemiology of type 1 diabetes in Latin America.

Latin America is among the regions with the highest diabetes-related burden. Research and treatment programs have increased in number and complexity in recent years, but they are focused in type 2 diabetes, because this condition explains a large proportion of the cases. In contrast, the information regarding the epidemiology of type 1 diabetes is scant in this area.

Diabetes in South and Central America: an update.

The estimated population of the South and Central America (SACA) Region is 467.6 million and 64% is in the age range of 20-79 years but the population pyramid and age distribution are changing. The average prevalence of diabetes in the Region is 8.

Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico.

Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls.

Long-term 4-year safety of saxagliptin in drug-naive and metformin-treated patients with Type 2 diabetes.

Aims: To evaluate the safety of saxagliptin ± metformin over 4 years in patients with Type 2 diabetes mellitus.

Methods: Drug-naive (n = 401; study 11) or metformin-treated (n = 743; study 14) adults with HbA(1c) of 53-86 mmol/mol (7.0-10%) were enrolled in two randomized, placebo-controlled, double-blind trials of saxagliptin 2.

Association of the I148M/PNPLA3 variant with elevated alanine transaminase levels in normal-weight and overweight/obese Mexican children.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) and elevated alanine transaminase (ALT) levels are common in obese Hispanic adults and children. Recently, a PNPLA3 gene variant (I148M) was strongly associated with NAFLD and higher ALT levels in obese adults, including Hispanics. The aims of this study were to estimate the frequency of elevated ALT levels, and to address the influence of obesity and PNPLA3/I148M on ALT levels in a general population sample of Mexican school-aged children.

Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci.

Background: The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations.

Methods And Findings: We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4361), and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TGs) near the Niemann-Pick type C1 protein gene (p=2.

Diabetes in Mexico: cost and management of diabetes and its complications and challenges for health policy.

Background: Mexico has been experiencing some of the most rapid shifts ever recorded in dietary and physical activity patterns leading to obesity. Diabetes mellitus has played a crucial role causing nearly 14% of all deaths. We wanted to make a comprehensive study of the role of diabetes in terms of burden of disease, prevalence, cost of diabetes, cost of complications and health policy.

[Results of a community-based life style intervention program for children].

Objective: Describe the three-year results of a program designed for the adoption of a healthy life style in primary school students on the body mass index (BMI) and the consumption of food.

Materials And Methods: Community randomized and controlled trial. Two communities in the State of Mexico with similar socio-demographic characteristics were randomized to implement the intervention (n=816) or serve as a control (n=408).

[Type 2 diabetes and frecuency of prevention and control measures].

Objective: To determine the frequency of application of prevention and control measures for type 2 diabetes in Mexican population.

Materials And Methods: ENSANUT 2012 is a nationally and by-state representative survey. Sample design was probabilistic, multistage, stratified and clustered.

The R230C variant of the ATP binding cassette protein A1 (ABCA1) gene is associated with a decreased response to glyburide therapy in patients with type 2 diabetes mellitus.

Objective: To test the hypothesis that persons with the R230C allele of ABCA1 show a decreased glycemic response to glyburide. This polymorphism is exclusively found in Ameri-indian populations and is associated with type 2 diabetes.

Research Design And Methods: This is a single blind controlled study including participants with type 2 diabetes (fasting glucose levels 126-250 mg/dl and HbA1c 7%-10%) managed with metformin and a lifestyle program.

Adipose co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes.

Background: High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation.

VNN1 gene expression levels and the G-137T polymorphism are associated with HDL-C levels in Mexican prepubertal children.

Background: VNN1 gene expression levels and the G-137T polymorphism have been associated with high density lipoprotein cholesterol (HDL-C) levels in Mexican American adults. We aim to evaluate the contribution of VNN1 gene expression and the G-137T variant to HDL-C levels and other metabolic traits in Mexican prepubertal children.

Methodology/principal Findings: VNN1 mRNA expression levels were quantified in peripheral blood leukocytes from 224 unrelated Mexican-Mestizo children aged 6-8 years (107 boys and 117 girls) and were genotyped for the G-137T variant (rs4897612).

Normal HDL-apo AI turnover and cholesterol enrichment of HDL subclasses in New Zealand rabbits with partial nephrectomy.

Objective: The kidney has been proposed to play a central role in apo AI catabolism, suggesting that HDL structure is determined, at least in part, by this organ. Here, we aimed at determining the effects of a renal mass reduction on HDL size distribution, lipid content, and apo AI turnover.

Methods: We characterized HDL subclasses in rabbits with a 75% reduction of functional renal mass (Nptx group), using enzymatic staining of samples separated on polyacrylamide electrophoresis gels, and also performed kinetic studies using radiolabeled HDL-apo AI in this animal model.

Contribution of common genetic variation to the risk of type 2 diabetes in the Mexican Mestizo population.

Several studies have identified nearly 40 different type 2 diabetes susceptibility loci, mainly in European populations, but few of them have been evaluated in the Mexican population. The aim of this study was to examine the extent to which 24 common genetic variants previously associated with type 2 diabetes are associated in Mexican Mestizos. Twenty-four single nucleotide polymorphisms (SNPs) in or near genes (KCNJ11, PPARG, TCF7L2, SLC30A8, HHEX, CDKN2A/2B, CDKAL1, IGF2BP2, ARHGEF11, JAZF1, CDC123/CAMK1D, FTO, TSPAN8/LGR5, KCNQ1, THADA, ADAMTS9, NOTCH2, NXPH1, RORA, UBQLNL, and RALGPS2) were genotyped in Mexican Mestizos.