Carlos A Aguilar-Salinas

Publications of Carlos A Aguilar-Salinas

• Association between carotid intima-media thickness, buccodental status, and glycemic control in pediatric type 1 diabetes.

  Authors: Rita A Gómez-Díaz, Eleazar Ramírez-Soriano, Janet Tanus Hajj, Elia Bautista Cruz, Cesar Jiménez Galicia, Miguel Angel Villasis-Keever, Carlos A Aguilar-Salinas, Niels H Wacher

  Pediatric diabetes. 05/2012;

  OBJECTIVE: To evaluate the association between carotid intima-media thickness, buccodental status, and glycemic control in patients with type 1 diabetes. METHODS: Cross-sectional study withOBJECTIVE: To evaluate the association between carotid intima-media thickness, buccodental status, and glycemic control in patients with type 1 diabetes. METHODS: Cross-sectional study with consecutive cases attended in an outpatient clinic (n = 69). Medical and clinical dental history, HbA1c, lipid profile, treatment period, and daily insulin dosage were recorded. Sociodemographic data and anthropometrical measurements were obtained by standardized questionnaire. Doppler real-time ultrasound was performed by a single experienced vascular radiologist blinded to the study. Assessment of buccodental status was done by the Maxillofacial Unit of the Pediatrics Hospital, and an oral scrape culture was collected. RESULTS: The mean age was 11.7 ± 3.0 years, with diabetes 5.1 ± 3.3 years. Mean HbA1c was 8.5 ± 1.7%. Primary teeth were present in 52.2% and bacterial plaque in 94.2%. Buccodental conditions featured caries (63.8%), gingivitis (84%), and enamel demineralization (26.1%): white spot lesions (18.8%) and cavitated lesions (7.3%). Bacteria associated with caries were found in 44.1%. Patients in the highest HbA1c tertile (>8.5%) had greater frequency of buccodental conditions and were positive for Streptococcus mutans and Candida albicans; also, cIMT increased and vessel compliance decreased compared to those in the lowest tertile (<7.0%) (p < 0.05). CONCLUSIONS: More buccodental conditions and carotid intima-media thickness increase appeared in the patients with HbA1c level > 8.5%, suggesting onset of atherosclerosis. The correlation between buccodental status and HbA1c values may indicate the connection between inflammatory states of atherosclerosis and type 1 diabetes.

• Evidence-Based Medicine and the Selection of Lipid-Lowering Therapy in Type 2 Diabetes.

  Authors: Carlos A Aguilar-Salinas, Roopa Mehta, Rita A Gomez-Diaz

  Current diabetes reports. 03/2012;

• A dietary pattern including nopal, chia seed, soy protein, and oat reduces serum triglycerides and glucose intolerance in patients with metabolic syndrome.

  Authors: Martha Guevara-Cruz, Armando R Tovar, Carlos A Aguilar-Salinas, Isabel Medina-Vera, Lidia Gil-Zenteno, Isaac Hernández-Viveros, Patricia López-Romero, Guillermo Ordaz-Nava, Samuel Canizales-Quinteros, Luz E Guillen Pineda, Nimbe Torres

  The Journal of nutrition. 11/2011; 142(1):64-9.

  Metabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of aMetabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of a dietary pattern (DP; soy protein, nopal, chia seed, and oat) on the biochemical variables of MetS, the AUC for glucose and insulin, glucose intolerance (GI), the relationship of the presence of certain polymorphisms related to MetS, and the response to the DP. In this randomized trial, the participants consumed their habitual diet but reduced by 500 kcal for 2 wk. They were then assigned to the placebo (P; n = 35) or DP (n = 32) group and consumed the reduced energy diet plus the P or DP beverage (235 kcal) minus the energy provided by these for 2 mo. All participants had decreases in body weight (BW), BMI, and waist circumference during the 2-mo treatment (P < 0.0001); however, only the DP group had decreases in serum TG, C-reactive protein (CRP), and AUC for insulin and GI after a glucose tolerance test. Interestingly, participants in the DP group with MetS and the ABCA1 R230C variant had a greater decrease in BW and an increase in serum adiponectin concentration after 2 mo of dietary treatment than those with the ABCA1 R230R variant. The results from this study suggest that lifestyle interventions involving specific DP for the treatment of MetS could be more effective if local foods and genetic variations of the population are considered.

• The N342S MYLIP polymorphism is associated with high total cholesterol and increased LDL receptor degradation in humans.

  Authors: Daphna Weissglas-Volkov, Anna C Calkin, Teresa Tusie-Luna, Janet S Sinsheimer, Noam Zelcer, Laura Riba, Ana Maria Vargas Tino, Maria Luisa Ordoñez-Sánchez, Ivette Cruz-Bautista, Carlos A Aguilar-Salinas, Peter Tontonoz, Päivi Pajukanta

  The Journal of clinical investigation. 08/2011; 121(8):3062-71.

  Atherosclerotic cardiovascular disease (ASCVD) affects more than 1 in 3 American adults. Hypercholesterolemia is a major treatable risk factor for ASCVD, yet many individuals fail to reach targetAtherosclerotic cardiovascular disease (ASCVD) affects more than 1 in 3 American adults. Hypercholesterolemia is a major treatable risk factor for ASCVD, yet many individuals fail to reach target levels of LDL-cholesterol (LDL-C) through the use of statins and lifestyle changes. The E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP; also known as IDOL) is a recently identified regulator of the LDL receptor (LDLR) pathway. Genome-wide association studies (GWASs) in populations of mixed European descent have identified noncoding variants in the MYLIP region as being associated with LDL-C levels, but no underlying functional variants were pinpointed. In order to fine-map actual susceptibility variants, we studied a population demographically distinct from the discovery population to ensure a different pattern of linkage disequilibrium. Our analysis revealed that in a Mexican population, the nonsynonymous SNP rs9370867, which encodes the N342S amino acid substitution, is an underlying functional variant that was associated with high total cholesterol and accounted for one of the previous significant GWAS signals. Functional characterization showed that the Asn-encoding allele was associated with more potent LDLR degradation and decreased LDL uptake. Mutagenesis of residue 342 failed to affect intrinsic MYLIP E3 ligase activity, but it was critical for LDLR targeting. Our findings suggest that modulation of MYLIP activity can affect LDL-C levels and that pharmacologic inhibition of MYLIP activity might be a useful strategy in the treatment of dyslipidemia and ASCVD.

• The role of natural killer T (NKT) cells in the pathogenesis of type 1 diabetes.

  Authors: Rita A Gómez-Díaz, Mayra V Aguilar, Elisa N Meguro, Rocío H Márquez, Eulalia G Magaña, M Carmen Martinez-García, Niels W Rodarte, Carlos A Aguilar-Salinas, Elsy Canché-Pool, Vianney Ortiz-Navarrete

  Current diabetes reviews. 06/2011; 7(4):278-83.

  In type 1 diabetes, a failure in the regulation of either innate or acquired immunity may be the cause of autoimmune response. A cell population that may have a regulatory role of the immune responseIn type 1 diabetes, a failure in the regulation of either innate or acquired immunity may be the cause of autoimmune response. A cell population that may have a regulatory role of the immune response are the Natural Killer T (NKT) cells, which are a population expressing T lymphocyte antigen receptor (TCR), and are a common marker for NK cells. A distinctive characteristic in NKT cells is their capacity to produce large amounts of immune-modulating cytokines. A decrease in the number and/or functional incapability of NKT cells is associated with progression of type 1 diabetes and with other self-immune diseases. However, the relevance of such findings is not completely understood. Limitations of the current studies include the existing methods to measure NKT activation and the lack of assessment of the expression of genes affected by NKT action. Nevertheless, the study of NKT cells may be a new clinical approach to detect individuals at risk for having type 1 diabetes. Additional studies are needed to evaluate the clinical value of this new predictive tool.

• Evidence of how rs7575840 influences apolipoprotein B-containing lipid particles.

  Authors: Blake E Haas, Daphna Weissglas-Volkov, Carlos A Aguilar-Salinas, Elina Nikkola, Laurent Vergnes, Ivette Cruz-Bautista, Laura Riba, Alena Stancakova, Johanna Kuusisto, Pasi Soininen, Antti J Kangas, Mika Ala-Korpela, Teresa Tusie-Luna, Markku Laakso, Päivi Pajukanta

  Arteriosclerosis, thrombosis, and vascular biology. 03/2011; 31(5):1201-7.

  Recent genome-wide association studies identified a variant rs7575840 in the apolipoprotein B (APOB) gene region as associated with low-density lipoprotein (LDL) cholesterol. However, the underlyingRecent genome-wide association studies identified a variant rs7575840 in the apolipoprotein B (APOB) gene region as associated with low-density lipoprotein (LDL) cholesterol. However, the underlying functional mechanism of this variant, which resides 6.5 kb upstream of APOB, has remained unknown. Our objective was to investigate rs7575840 for association with refined apoB-containing lipid particles, for replication in a Mexican population, and for its underlying functional mechanism. Our data show that rs7575840 is associated with serum apoB levels (P=4.85×10(-10)) and apoB-containing lipid particles, very small very-low-density lipoprotein, intermediate lipoprotein, and LDL particles (P=2×10(-5) to 9×10(-7)) in the Finnish Metabolic Syndrome in Men study sample (n=7710). Fine mapping of the APOB region using 43 single-nucleotide polymorphisms replicated the association of rs7575840 with apoB in a Mexican study sample (n=2666, P=3.33×10(-5)). Furthermore, our transcript analyses of adipose RNA samples from 175 subjects in the Finnish Metabolic Syndrome in Men study indicate that rs7575840 alters expression of APOB (P=1.13×10(-10)) and a regional noncoding RNA (BU630349) (P=7.86×10(-6)) in adipose tissue. It has been difficult to convert genome-wide association study associations into mechanistic insights. Our data show that rs7575840 is associated with serum apoB levels and apoB-containing lipid particles, as well as influencing expression of APOB and a regional transcript BU630349 in adipose tissue. We thus provide evidence how a common genome-wide significant single-nucleotide polymorphism, rs7575840, may affect serum apoB, LDL cholesterol, and total cholesterol levels.

• Management of type 2 diabetes: more evidence is required to address the clinical and contextual facets.

  Authors: Sergio Hernandez-Jimenez, Carlos A Aguilar-Salinas, Roopa Mehta, Juan A Rull, Francisco J Gómez-Pérez

  Current diabetes reviews. 02/2011; 7(2):99-105.

  Evidence based medicine has changed the manner in which medicine is practiced and learned. Epidemiological studies, meta-analyses and systematic reviews have been used to create algorithms for theEvidence based medicine has changed the manner in which medicine is practiced and learned. Epidemiological studies, meta-analyses and systematic reviews have been used to create algorithms for the treatment of hyperglycemia in patients with type 2 diabetes. Recently, several randomized controlled trials (i.e. ACCORD, ADVANCE, VADT) have generated new and valuable information regarding the benefits and risks of achieving optimal glucose control. As a result, guidelines and algorithms have been updated. However, many aspects remain controversial. In this article, the clinical implications of the existing guidelines are critically analyzed. The limitations of the current guidelines include the lack of applicability to relevant diabetic subgroups, the exclusion of important factors that modify the therapeutic response to glucose-lowering agents and the limited recognition of the importance of the socioeconomic situation on treatment efficacy. Many subgroups of patients have not been included in the studies used to generate recommendations. There is insufficient evidence to support the use of current treatment recommendations in patients with early onset type 2 diabetes, patients with advanced microvascular complications, and the elderly with or without chronic complications. The characteristics of the candidates for conservative or intensive treatment are poorly defined. Interventions are recommended without considering clinical variables (i.e. obesity, time since diagnosis or prolonged exposure to hyperglycemia) that may modify treatment efficacy and the occurrence of side effects. Finally, no consideration is given to the socioeconomic context of the population in which the guidelines are to be applied. In summary, this manuscript highlights the key areas which require further work. If these issues are adequately addressed, the guidelines for the management of type 2 diabetes will be relevant and applicable to all diabetic groups.

• Estimated incidence of cardiovascular complications related to type 2 diabetes in Mexico using the UKPDS outcome model and a population-based survey.

  Authors: Nancy Reynoso-Noverón, Roopa Mehta, Paloma Almeda-Valdes, Rosalba Rojas-Martinez, Salvador Villalpando, Mauricio Hernández-Ávila, Carlos A Aguilar-Salinas

  Cardiovascular diabetology. 01/2011; 10:1.

  To estimate the incidence of complications, life expectancy and diabetes related mortality in the Mexican diabetic population over the next two decades using data from a nation-wide, population basedTo estimate the incidence of complications, life expectancy and diabetes related mortality in the Mexican diabetic population over the next two decades using data from a nation-wide, population based survey and the United Kingdom Prospective Diabetes Study (UKPDS) outcome model. The cohort included all patients with type 2 diabetes evaluated during the National Health and Nutrition Survey (ENSANut) 2006. ENSANut is a probabilistic multistage stratified survey whose aim was to measure the prevalence of chronic diseases. A total of 47,152 households were visited. Results are shown stratified by gender, time since diagnosis (> or ≤ to 10 years) and age at the time of diagnosis (> or ≤ 40 years). The prevalence of diabetes in our cohort was 14.4%. The predicted 20 year-incidence for chronic complications per 1000 individuals are: ischemic heart disease 112, myocardial infarction 260, heart failure 113, stroke 101, and amputation 62. Furthermore, 539 per 1000 patients will have a diabetes-related premature death. The average life expectancy for the diabetic population is 10.9 years (95%CI 10.7-11.2); this decreases to 8.3 years after adjusting for quality of life (CI95% 8.1-8.5). Male sex and cases diagnosed after age 40 have the highest risk for developing at least one major complication during the next 20 years. Based on the current clinical profile of Mexican patients with diabetes, the burden of disease related complications will be tremendous over the next two decades.

• The non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 is associated with low HDL cholesterol concentrations in Mexican adults: a population based nation wide study.

  Authors: Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros, Rosalba Rojas-Martínez, Roopa Mehta, Rosario Rodriguez-Guillén, María Luisa Ordoñez-Sanchez, Laura Riba, María Teresa Tusié-Luna

  Atherosclerosis. 01/2011; 216(1):146-50.

  To search for an association between the non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 and low HDL cholesterol levels in a Mexican, population-based nation wideTo search for an association between the non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 and low HDL cholesterol levels in a Mexican, population-based nation wide survey. The 2000 National Health Survey is a cross sectional study that included individuals from 400 cities. All individuals who had a 9-12-h fasted blood sample and a DNA sample were selected (n = 1729). These cases were randomly distributed; no bias was detected for sex, education, region or socioeconomic status. The R230C variant was genotyped using TaqMan assays. In individuals with the R230C/C230C genotypes (39.03 mg/dl (36.63-41.43)) lower HDL-C levels (p < 0.001) were observed compared to those with the R230R genotype (44.7 mg/dl (43.31-46.24)). The difference remained significant after adjusting for gender, body mass index and waist circumference; the mean difference in HDL cholesterol levels between alleles was 5.73 ± 1.4 mg/dl. The magnitude of the effect was significantly greater in males. The C230 allele of ABCA1 was associated with an increased risk for hypoalphalipoproteinemia (OR 1.66 (95%CI 1.08-2.54), p < 0.05). The population attributable risk (PAR) for having hypoalphalipoproteinemia of the C230 allele of the ABCA1, after considering the confounding effect of waist circumference and gender, was 12.2% (95%CI 1.4-24.2%). The non-synonymous Arg230Cys variant of ABCA1 is associated with low levels of HDL cholesterol levels in Mexican adults. The HDL cholesterol lowering effect of the variant is greater in males. The size of the effect is greater compared to that reported for other ABCA1 variants.

• Awareness of Abdominal Adiposity as a Cardiometabolic Risk Factor (The 5A Study): Mexico.

  Authors: Daniel Cuevas Ramos, Roopa Mehta, Julieta De La Luz Castro, Rutila Castañeda Limones, Ernesto García Rubí, Carlos A Aguilar-Salinas

  Diabetes, metabolic syndrome and obesity : targets and therapy. 01/2011; 4:107-17.

  The Awareness of Abdominal Adiposity as a Cardiometabolic Risk Factor Study assesses the prevalence of cardiometabolic risk factors in adults with abdominal obesity (waist circumference ≥90 cm in menThe Awareness of Abdominal Adiposity as a Cardiometabolic Risk Factor Study assesses the prevalence of cardiometabolic risk factors in adults with abdominal obesity (waist circumference ≥90 cm in men and ≥80 cm in women) and evaluates how physicians manage these patients. This is an observational cross-sectional study. Internists, cardiologists, and endocrinologists contributed patients to the study. A standardized questionnaire was completed and registered demographics, anthropometric measurements, lab results from the medical files, and any treatment utilized to manage dyslipidemia, arterial hypertension, diabetes, and cardiovascular disease. A total of 1312 patients was included. The mean age was 49.3 ± 14.6 years and 834 (63.6%) were female. The primary reason for the physician consultation was treatment of obesity (47.5%), followed by management of arterial hypertension (27.7%), diabetes (18.3%), dyslipidemia (14.2%), and cardiovascular disease (7.1%). The majority of patients identified excess body weight as a health problem (81.4%). However, patients had lost a mean of 4.3 ± 3.5 kg. Only 63.4% of patients with arterial hypertension were on drug therapy. Few of them had reached target values for diastolic (24.1%) and systolic/diastolic (13.3%) pressure. Less than half of the patients with dyslipidemia were receiving lipid-lowering medication. Only 32.2% were at their target low-density lipoprotein cholesterol levels. In patients with type 2 diabetes, mean fasting plasma glucose level (8.9 ± 3.4 mmol/L) was above the threshold recommended by current guidelines. The study describes the medical care given to individuals with abdominal obesity during daily clinical practice by general practitioners, cardiologists, and endocrinologists in urban Mexico. Our data confirm that a large proportion of patients are undertreated. Only a small percentage of patients with obesity-related comorbidities reach treatment targets. Interventions proven to be effective in the prevention of chronic complications have in general not been implemented.

• Association of R230C ABCA1 gene variant with low HDL-C levels and abnormal HDL subclass distribution in Mexican school-aged children.

  Authors: Teresa Flores-Dorantes, Olimpia Arellano-Campos, Rosalinda Posadas-Sánchez, Teresa Villarreal-Molina, Aida Medina-Urrutia, Sandra Romero-Hidalgo, Petra Yescas-Gómez, Oscar Pérez-Méndez, Esteban Jorge-Galarza, Teresa Tusié-Luna, Marisela Villalobos-Comparán, Leonor Jacobo-Albavera, Hugo Villamil-Ramírez, Blanca E López-Contreras, Carlos A Aguilar-Salinas, Carlos Posadas-Romero, Samuel Canizales-Quinteros

  Clinica chimica acta; international journal of clinical chemistry. 09/2010; 411(17-18):1214-7.

  The effect of ABCA1 genetic variation on HDL-C levels has been widely documented, although studies in children are scarce. We recently found a frequent non-synonymous ABCA1 variant (R230C) exclusiveThe effect of ABCA1 genetic variation on HDL-C levels has been widely documented, although studies in children are scarce. We recently found a frequent non-synonymous ABCA1 variant (R230C) exclusive to populations with Native American ancestry, associated with low HDL-C levels and other metabolic traits in adults. We genotyped R230C variant in 1253 healthy unrelated Mexican school-aged children aged 6-15 years (595 boys and 658 girls) to seek associations with HDL-C levels and other metabolic traits. HDL subclass distribution was analyzed in a subgroup of 81 age, gender and BMI-matched children. Individuals carrying the C230 allele showed a significantly lower HDL-C levels (P=2.9x10(-8)), and higher TC/HDL-C ratio, BMI, BMI z-score and percent fat mass (P=0.001, 0.049, 0.032 and 0.039, respectively). HDL size was smaller in R230C heterozygotes as compared to R230R homozygotes (P<0.05). Moreover, the proportion of HDL(2b) was lower, while the proportion of HDL(3a) and HDL(3b) particles was higher in R230C heterozygous and/or C230C homozygous individuals as compared to R230R homozygotes (P<0.05). Our data suggest that the R230C ABCA1 gene variant plays an important role in HDL-C level regulation and HDL subclass distribution in healthy Mexican school-aged children.

• Daily physical activity, fasting glucose, uric acid, and body mass index are independent factors associated with serum fibroblast growth factor 21 levels.

  Authors: Daniel Cuevas-Ramos, Paloma Almeda-Valdes, Francisco J Gómez-Pérez, Clara Elena Meza-Arana, Ivette Cruz-Bautista, Olimpia Arellano-Campos, Mariana Navarrete-López, Carlos A Aguilar-Salinas

  European journal of endocrinology / European Federation of Endocrine Societies. 09/2010; 163(3):469-77.

  Fibroblast growth factor 21 (FGF21) levels have been linked with beneficial effects on glucose and lipid metabolism in animals. It is elevated in humans with the metabolic syndrome. This studyFibroblast growth factor 21 (FGF21) levels have been linked with beneficial effects on glucose and lipid metabolism in animals. It is elevated in humans with the metabolic syndrome. This study investigates independent factors associated with serum FGF21 levels. Cross-sectional study done in healthy blue-collar workers. A medical history was taken, and FGF21 (measured using an ELISA commercial kit), glucose, uric acid, plasma lipids, total/high-molecular weight (HMW) adiponectin, and retinal-binding protein 4 (RBP4) were measured in 210 individuals with (n=81) and without (n=129) metabolic syndrome. The median of serum FGF21 levels were higher in subjects with metabolic syndrome (339.5 vs 276.4 ng/l, P=0.01). Serum FGF21 levels correlated positively with body mass index (BMI; r=0.23, P=0.001) and age (r=0.17, P=0.01). After adjusting for age and BMI, a significant positive correlation persisted for fasting glucose, uric acid, and physical activity in both males (r=0.21, r=0.11, and r=0.19, all P<0.05) and females (r=0.20, r=0.19, and r=0.14, all P<0.05). In addition, FGF21 also correlates negatively with RBP4 (r=-0.27, P=0.02), total (r=-0.26, P=0.03), and HMW adiponectin (r=-0.30, P=0.01) in women. A multiple linear regression model analysis identified that BMI (standardized beta (SB)=0.247; P=0.008), glucose (SB=0.226; P=0.003), uric acid (SB=0.191; P=0.04), and physical activity (SB=0.223; P=0.004) are independent factors influencing serum FGF21 levels (F=10.05, r(2)=0.19, P<0.001). In addition, fasting hyperglycemia > or =100 mg/dl, excess body weight with BMI > or =25 kg/m(2), and uric acid > or =5.5 mg/dl predicted higher serum FGF21 levels. Serum FGF21 levels are influenced by BMI, fasting glycemia, uric acid, and physical activity.

• TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects.

  Authors: Jose de Jesus Garduño-Garcia, Ulices Alvirde-Garcia, Guadalupe López-Carrasco, Ma Elena Padilla Mendoza, Roopa Mehta, Olimpia Arellano-Campos, Ricardo Choza, Leobardo Sauque, Maria Eugenia Garay-Sevilla, Juan Manuel Malacara, Francisco J Gomez-Perez, Carlos A Aguilar-Salinas

  European journal of endocrinology / European Federation of Endocrine Societies. 08/2010; 163(2):273-8.

  To examine the association between thyroid function and the components of the metabolic syndrome and insulin resistance in an Hispanic population. Cross-sectional study. Subjects with no history ofTo examine the association between thyroid function and the components of the metabolic syndrome and insulin resistance in an Hispanic population. Cross-sectional study. Subjects with no history of thyroid disease or diabetes were included. Thyroid function was stratified as euthyroid or subclinical hypothyroidism (SCH) status and subsequently by free thyroxine (FT(4)) and TSH tertiles. The association of the metabolic syndrome components (defined by 2004 Adult Treatment Panel III criteria) and insulin resistance with thyroid status, TSH, and FT(4) were examined. A total of 3148 subjects were analyzed. The prevalence of SCH was 8.3%. The prevalence of the metabolic syndrome was similar in euthyroid and SCH patients (31.6 vs 32.06%, P=0.89). Total cholesterol was higher in patients with SCH (5.51+/-1.19 vs 5.34+/-1.05 mmol/l, P<0.032). Serum TSH values showed a positive correlation (adjusted for age and sex) with total cholesterol, triglycerides, and waist circumference. In contrast, FT(4) showed a positive correlation with high-density lipoprotein cholesterol, and an inverse correlation with waist circumference, insulin, and HOMA-IR. SCH is not associated with an increased risk for the metabolic syndrome (as conceived as a diagnostic category defined by the National Cholesterol, Education Program, Adult Treatment Panel III criteria). Despite this, low thyroid function (even in the euthyroid state) predisposes to higher cholesterol, glucose, insulin, and HOMA-IR levels. The combined use of TSH and FT(4), compared with the assessment based on only FT(4), is a more convenient approach to evaluate the association between thyroid function and metabolic variables.

• Beta-cell adenomas without hyperinsulinemia with use of highly specific insulin radioimmunoassays: case report and review of literature.

  Authors: Francisco J Gómez-Pérez, Daniel Cuevas-Ramos, Paloma Almeda Valdés, Carlos A Aguilar-Salinas, Roopa Mehta, Juan A Rull

  Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 05/2010; 16(4):660-3.

  To report a case of a proinsulin-secreting islet cell adenoma in which the diagnosis was obscured by an ultraspecific insulin assay. We describe the case of a 46-year-old woman, who presented withTo report a case of a proinsulin-secreting islet cell adenoma in which the diagnosis was obscured by an ultraspecific insulin assay. We describe the case of a 46-year-old woman, who presented with fasting hypoglycemia and appropriately low insulin values. A prolonged supervised fast produced symptomatic hypoglycemia (20 mg/dL) after only 7 hours. During the entire fasting test, highly specific insulin remained at <3 mIU/L, with a median value (and interquartile range) of 0.9 (0.8 to 2.3) mIU/L, when the glucose concentration was <50 mg/dL. The serum C-peptide level remained high normal (mean +/- SD, 2.7 +/- 0.6 ng/mL; normal fasting levels, 0.8 to 3.9), and no evidence of sulfonylurea use was detected in the patient's urine. Circulating proinsulin levels were persistently high (>200 pmol/L in all determinations when hypoglycemia was present; expected value, <5 pmol/L). Magnetic resonance imaging and endoscopic ultrasonography confirmed the presence of a 2.5-cm tumor in the head of the pancreas. A proinsulin-secreting islet cell tumor was diagnosed. Surgical resection of the tumor was successfully accomplished, but diabetes mellitus developed 4 months postoperatively. The diagnosis of a hypoglycemia-producing pancreatic adenoma can be missed when an ultraspecific insulin assay is used. The direct measurement of proinsulin established the diagnosis in this case.

• HbA1c for the diagnosis of diabetes mellitus in a developing country. A position article.

  Authors: Francisco J Gomez-Perez, Carlos A Aguilar-Salinas, Paloma Almeda-Valdes, Daniel Cuevas-Ramos, Israel Lerman Garber, Juan A Rull

  Archives of medical research. 05/2010; 41(4):302-8.

  An Expert Committee of the American Diabetes Association and the European Association for the Study of Diabetes recommended a move to the use of HbA1c level to diagnose diabetes mellitus. DiagnosisAn Expert Committee of the American Diabetes Association and the European Association for the Study of Diabetes recommended a move to the use of HbA1c level to diagnose diabetes mellitus. Diagnosis should be made if the A1c level is > or = 6.5%. HbA1c provides a reliable measure of chronic glycemia, correlates well with the risk of long-term diabetes complications and technical limitations for standardization have been overcome in laboratories of the U.S. and Europe. The objective of this paper is to analyze critically the advantages and disadvantages of the use of HbA1c as a diagnostic method of diabetes in a developing country. The lack of a universal threshold for the diagnosis of diabetes, the cost of the test and the absence of the standardization network in the majority of the countries are major arguments for not including HbA1c as diagnostic criteria of diabetes. HbA1c diagnostic criteria has a low sensitivity. As a result, there is a lack of agreement between the HbA1c criteria with the other diagnostic methods that lead into significant variations in the number of affected cases. In addition, sensitivity and specificity vary among ethnic groups. No study has compared the diagnostic properties of the HbA1c in Latin America. In conclusion, the logistic limitations that exist in a large proportion of developing countries and the unsolved uncertainties that exist for the definition of the A1c criterion are strong arguments against the inclusion of HbA1c among the diagnostic criteria of diabetes.

• A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans.

  Authors: Víctor Acuña-Alonzo, Teresa Flores-Dorantes, Janine K Kruit, Teresa Villarreal-Molina, Olimpia Arellano-Campos, Tábita Hünemeier, Andrés Moreno-Estrada, Ma Guadalupe Ortiz-López, Hugo Villamil-Ramírez, Paola León-Mimila [......] Carlos A Aguilar-Salinas, Ruben Lisker, Regina S Moises, Marta Menjivar, Francisco M Salzano, William C Knowler, M Cátira Bortolini, Michael R Hayden, Leslie J Baier, Samuel Canizales-Quinteros

  Human molecular genetics. 04/2010; 19(14):2877-85.

  It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassetteIt has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 x 10(-11)) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations.

• Investigation of variants identified in caucasian genome-wide association studies for plasma high-density lipoprotein cholesterol and triglycerides levels in Mexican dyslipidemic study samples.

  Authors: Daphna Weissglas-Volkov, Carlos A Aguilar-Salinas, Janet S Sinsheimer, Laura Riba, Adriana Huertas-Vazquez, Maria L Ordoñez-Sánchez, Rosario Rodriguez-Guillen, Rita M Cantor, Teresa Tusie-Luna, Päivi Pajukanta

  Circulation. Cardiovascular genetics. 02/2010; 3(1):31-8.

  Although epidemiological studies have demonstrated an increased predisposition to low high-density lipoprotein cholesterol and high triglyceride levels in the Mexican population, Mexicans have notAlthough epidemiological studies have demonstrated an increased predisposition to low high-density lipoprotein cholesterol and high triglyceride levels in the Mexican population, Mexicans have not been included in any of the previously reported genome-wide association studies for lipids. We investigated 6 single-nucleotide polymorphisms associated with triglycerides, 7 with high-density lipoprotein cholesterol, and 1 with both triglycerides and high-density lipoprotein cholesterol in recent Caucasian genome-wide association studies in Mexican familial combined hyperlipidemia families and hypertriglyceridemia case-control study samples. These variants were within or near the genes ABCA1, ANGPTL3, APOA5, APOB, CETP, GALNT2, GCKR, LCAT, LIPC, LPL (2), MMAB-MVK, TRIB1, and XKR6-AMAC1L2. We performed a combined analysis of the family-based and case-control studies (n=2298) using the Z method to combine statistics. Ten of the single-nucleotide polymorphisms were nominally significant and 5 were significant after Bonferroni correction (P=2.20 x 10(-3) to 2.6 x 10(-11)) for the number of tests performed (APOA5, CETP, GCKR, and GALNT2). Interestingly, our strongest signal was obtained for triglycerides with the minor allele of rs964184 (P=2.6 x 10(-11)) in the APOA1/C3/A4/A5 gene cluster region that is significantly more common in Mexicans (27%) than in whites (12%). It is important to confirm whether known loci have a consistent effect across ethnic groups. We show replication of 5 Caucasian genome-wide association studies lipid associations in Mexicans. The remaining loci will require a comprehensive investigation to exclude or verify their significance in Mexicans. We also demonstrate that rs964184 has a large effect (odds ratio, 1.74) and is more frequent in the Mexican population, and thus it may contribute to the high predisposition to dyslipidemias in Mexicans.

• Prevention of cardiovascular disease based on lipid lowering treatment: a challenge for the Mexican health system.

  Authors: Francisco J Gómez-Pérez, Rosalba Rojas, Salvador Villalpando, Simón Barquera, Juan Rull, Carlos A Aguilar-Salinas

  Salud pública de México. 01/2010; 52 Suppl 1:S54-62.

  To estimate the percentage of Mexican adults that may require lipid-lowering treatment according to National Cholesterol Education Program-III guidelines, using data from the National Health andTo estimate the percentage of Mexican adults that may require lipid-lowering treatment according to National Cholesterol Education Program-III guidelines, using data from the National Health and Nutrition Survey 2006 (ENSANut 2006). Information was obtained from 4 040 subjects aged 20 to 69 years, studied after a 9 to 12 hours fast. A cardiovascular risk equivalent was found in 13.8% and >or=2 risk factors were present in 31.5% of the population. LDL-C concentrations were above the treatment goal in 70% of the high-risk group and in 38.6% of subjects with >or=2 risk factors. Nearly 12 million Mexicans should be taught how to change their lifestyles and close to 8 million individuals require drug therapy to decrease their cardiovascular risk. Thirty percent of Mexican adults require some form of lipid-lowering treatment (lifestyle modifications in 36.25%, drug therapy in 24.19%).

• Methodology for the analysis of type 2 diabetes, metabolic syndrome and cardiovascular disease risk indicators in the ENSANUT 2006.

  Authors: Simón Barquera, Ismael Campos-Nonato, Citlali Carrión-Rábago, Salvador Villalpando, Ruy López-Ridaura, Rosalba Rojas, Carlos A Aguilar-Salinas

  Salud pública de México. 01/2010; 52 Suppl 1:S4-10.

  To describe: a) the methods used to quantify biochemical indicators of Type 2 Diabetes (T2D), and other cardiovascular risk indicators in the Mexican National Health and Nutrition Survey 2006To describe: a) the methods used to quantify biochemical indicators of Type 2 Diabetes (T2D), and other cardiovascular risk indicators in the Mexican National Health and Nutrition Survey 2006 (ENSANUT 2006) and b) compare the sub-sample with the non-selected participants in diverse socio-demographic, anthropometric and health characteristics. A sub-sample of 6 021 fasting adult participants was randomly selected from the total fasting participants (n=39 425). We compared diverse socio-demographic, anthropometric and health parameters between this sub-sample and the rest of the participants. No differences were found in sociodemographics characteristics, except age, between the sub-sample and from the rest of the fasting adults. In addition no difference were found between prevalences of overweight and obesity, central obesity, and previously diagnosed high blood pressure, T2D or hypertrigliceridemia. The randomly selected sub-sample was not essentially different from the rest of the fasting subjects. Thus, no bias is expected in the interpretation of cardiovascular risk indicators derived from these data.

• Hypertension in Mexican adults: results from the National Health and Nutrition Survey 2006.

  Authors: Simón Barquera, Ismael Campos-Nonato, Lucía Hernández-Barrera, Salvador Villalpando, César Rodríguez-Gilabert, Ramón Durazo-Arvizú, Carlos A Aguilar-Salinas

  Salud pública de México. 01/2010; 52 Suppl 1:S63-71.

  To describe the prevalence of hypertension among Mexican adults, and to compare to that observed among Mexican-Americans living in the US. The primary data source came from adults (>20 years) sampledTo describe the prevalence of hypertension among Mexican adults, and to compare to that observed among Mexican-Americans living in the US. The primary data source came from adults (>20 years) sampled (n=33366) in the Mexican National Health and Nutrition Survey 2006 (ENSANUT 2006). Hypertension was defined when systolic blood pressure was >or=140 and/or diastolic was >or= 90 or patients previously diagnosed. A total of 43.2% of participants were classified as having hypertension. We found a positive statistically significant association (p<0.05) between hypertension and BMI, abdominal obesity, previous diagnosis of diabetes and hypercholesterolemia. Subjects with hypertension had a significantly higher odd of having a history of diabetes or hypercholesterolemia. Hypertension had a higher prevalence in Mexico than among Mexican-Americans living in the US. Hypertension is one of the most prevalent chronic diseases in Mexico. In the last six years in Mexico, a substantial increase (25%) has been observed in contrast to the reduction seen among Mexican-Americans (-15%).