Francisco J Gómez-Pérez

Publications of Francisco J Gómez-Pérez

• Sensorineural hearing loss is a common finding in early onset type 2 diabetes.

  Authors: Israel Lerman-Garber, Daniel Cuevas-Ramos, Samantha Valdés, Lorena Enríquez, Marlette Lobato, Melannie Osornio, Ana Rosa Escobedo, Virginia Pascual-Ramos, Roopa Mehta, Jacqueline Ramírez-Anguiano, Francisco J Gómez-Pérez

  Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 03/2012;

  Objective: To evaluate the prevalence and potential associations of hearing impairment in patients aged 30-50 years with diabetes diagnosed before age 40 (early onset type 2 diabetes).Methods:Objective: To evaluate the prevalence and potential associations of hearing impairment in patients aged 30-50 years with diabetes diagnosed before age 40 (early onset type 2 diabetes).Methods: Forty-six consecutive patients with early onset type 2 diabetes (T2DM) and forty-seven age-matched controls with rheumatoid arthritis were included. All subjects completed clinical, serologic and auditory assessments.Results: Patients with T2DM had a mean age of 42±6 years and mean disease duration of 11±6 years. Microalbuminuria was present in 26.1%, symptomatic peripheral neuropathy in 23.9%, and proliferative retinopathy in 26.1%. The prevalence of unilateral or bilateral hearing loss was significantly higher in diabetic rather than in RA patients (21.7% vs. 6.4%, p=0.01). Most cases were mild and involved high or acute tones. After multivariate analysis adjusting for age, there was a significant association between hearing loss and HbA1c (OR=1.3, IC95% 1.02-1.81, p=0.035). In diabetic patients the lengthening of the brainstem response was not significantly increased; however, the wave morphology was abnormal and/or the reproducibility was poor in 28% of the patients.Conclusions: Patients with early onset T2DM and poor glycemic control have an increased prevalence of subclinical hearing loss and impaired auditory brainstem responses. Hearing impairment may be an under-recognized complication of diabetes.

• 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.

• 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.

• 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.

• 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%).

• Prevalence of dyslipidemias in the Mexican National Health and Nutrition Survey 2006.

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

  Salud pública de México. 01/2010; 52 Suppl 1:S44-53.

  To describe the prevalence of lipid abnormalities found in the Mexican National Health and Nutrition Survey 2006 (ENSANut 2006). Information was obtained from 4 040 subjects aged 20 to 69 years,To describe the prevalence of lipid abnormalities found in the Mexican 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-hour fast. Median lipid concentrations were: cholesterol 198.5 mg/dl, triglycerides 139.6 mg/dl, HDL-cholesterol 39.0 mg/dl, non-HDL-cholesterol 159.5 mg/dl and LDL-cholesterol 131.5 mg/dl. The most frequent abnormality was HDL-cholesterol below 40 mg/dl with a prevalence of 60.5% (95%CI 58.2-62.8%). Hypercholesterolemia (> 200 mg/dl) had a frequency of abnormality of 43.6% (95%CI 41.4-46.0%). Only 8.6% of the hypercholesterolemic subjects knew their diagnosis. Hypertriglyceridemia (>or= 150 mg/dl) was observed in 31.5% (IC 95% 29.3-33.9%) of the population. The ENSANUT 2006 data confirm that the prevalence of hypoalphalipoproteinemia and other forms of dyslipidemia in Mexican adults is very high.

• Early-onset type 2 diabetes in a Mexican survey: results from the National Health and Nutrition Survey 2006.

  Authors: Aída Jiménez-Corona, Rosalba Rojas, Francisco J Gómez-Pérez, Carlos A Aguilar-Salinas

  Salud pública de México. 01/2010; 52 Suppl 1:S27-35.

  To describe the characteristics of patients with type 2 diabetes diagnosed before age 40 (early-onset type 2 diabetes) identified in a nation-wide, population-based study. The survey was done inTo describe the characteristics of patients with type 2 diabetes diagnosed before age 40 (early-onset type 2 diabetes) identified in a nation-wide, population-based study. The survey was done in Mexico during 2006. Medical history, anthropometric and biochemical measurements were obtained in every subject. Cases diagnosed before (n=181) and after age 40 (n=659) were included. Early-onset type 2 diabetes was present in 13.1% of the previously diagnosed, 30.3% of the cases identified during the survey and 21.5% of the whole population with diabetes. These individuals had a greater prevalence of obesity and hypertriglyceridemia compared to the cases diagnosed after age 40. Early-onset type 2 diabetes was present in 21.5 % of patients with type 2 diabetes in Mexico. Close to 70% of them were obese or overweight and had the clinical profile of the metabolic syndrome.

• Hypoalphalipoproteinemia in populations of Native American ancestry: an opportunity to assess the interaction of genes and the environment.

  Authors: Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros, Rosalba Rojas-Martínez, Roopa Mehta, Ma Teresa Villarreal-Molina, Olimpia Arellano-Campos, Laura Riba, Francisco J Gómez-Pérez, Ma Teresa Tusié-Luna

  Current opinion in lipidology. 05/2009; 20(2):92-7.

  PURPOSE OF THIS REVIEW: Our aim is to review the environmental and genetic factors associated with hypoalphalipoproteinemia in populations of Native American ancestry. We examine the strength of thePURPOSE OF THIS REVIEW: Our aim is to review the environmental and genetic factors associated with hypoalphalipoproteinemia in populations of Native American ancestry. We examine the strength of the association and outline the population-specific genetic factors that lead to a higher susceptibilty for this condition. RECENT FINDINGS: Low HDL is the most common lipid abnormality in populations of Native American ancestry. Population-based surveys carried out in Latin America and in Mexican Americans shows that 40-60% of adults have hypoalphalipoproteinemia. The contribution of this trait to the metabolic syndrome is greater in individuals with Native American ancestry than in other ethnic groups. Several environmental factors have contributed to this phenomenon (i.e. high dietary content of carbohydrates and fat due to cultural factors and a growing incidence of obesity). In addition, results from recent genetic studies show that certain hypoalphalipoproteinemia susceptibility alleles are ethnic specific for Native Americans. The variant R230C of the ATP-binding cassette transporter subfamily A member 1 gene (ABC-A1) is common among mestizos (10.9% in Mexican mestizos) and its presence has a significant negative effect on HDL cholesterol levels (-4.2%). An additional noteworthy finding is that the R230C variant appears to be specific for the Amerindian populations. Its allele frequency is 0.28 in Mayans, 0.214 in Purepechas, 0.203 in Yaquis and 0.179 among Teenek. In contrast, the C230 allele has not been found in African, European, Chinese or South Asian populations. SUMMARY: The assessment of the genetic and environmental determinants of hypoalphalipoproteinemia in populations of Native American origin provides an opportunity to assess the population-specific interactions between genes and the environment

• High adiponectin concentrations are associated with the metabolically healthy obese phenotype.

  Authors: Carlos A Aguilar-Salinas, Eduardo García-García, Lorena Robles, Daniela Riaño, Doris Georgina Ruiz-Gomez, Ana Cristina García-Ulloa, Marco A Melgarejo, Margarita Zamora, Luz E Guillen Pineda, Roopa Mehta, Samuel Canizales-Quinteros, Ma Teresa Tusie Luna, Francisco J Gómez-Pérez

  The Journal of clinical endocrinology and metabolism. 09/2008;

  Context: In the ob/ob mice, keeping adiponectin concentrations in the physiological range (through overexpression of this gene in the adipose tissue) results in expansion of fat mass and protectionContext: In the ob/ob mice, keeping adiponectin concentrations in the physiological range (through overexpression of this gene in the adipose tissue) results in expansion of fat mass and protection against metabolic co-morbidities. Objective: To test in humans whether plasma adiponectin levels, similar to those found in lean subjects, are associated with the metabolically healthy obese phenotype. Design and Setting: A cross-sectional analysis of a cohort of obese and non-obese subjects aged 18-70 years. A medical history was taken and glucose, plasma lipids and total adiponectin were measured. Participants: We studied 189 men and 527 women. The majority were obese (n=470, 65.6%). The metabolically healthy obese phenotype was found in 38 men and 133 women. This is defined as a body mass index (BMI) above 30 kg/m(2) plus HDL cholesterol >/= 40 mg/dl in the absence of type 2 diabetes and arterial hypertension. Results: Twenty percent of the cases with a BMI above 40 kg/m(2) had adiponectin concentrations above the median value of normal BMI subjects. Adiponectin levels above 12.49 mg/l in obese women (OR 3.02 (95% CI 1.95-4.67, p<0.001) and above 8.07 mg/l in obese men (OR 2.14 (95%CI 1.1-4.06, p=0.01) increased the probability of being metabolically healthy. The association remained significant (beta 0.673 +/- 0.205, p<0.001) in a logistic regression model (r(2)=0.25, p<0.001) after controlling for the confounding effect of age, insulin and waist circumference. Conclusions: Certain obese individuals have adiponectin levels similar to those found in normal BMI subjects; this is associated with the metabolically healthy obese phenotype.

• The FTO Gene Is Associated With Adulthood Obesity in the Mexican Population.

  Authors: Marisela Villalobos-Comparán, M Teresa Flores-Dorantes, M Teresa Villarreal-Molina, Maricela Rodríguez-Cruz, Ana C García-Ulloa, Lorena Robles, Adriana Huertas-Vázquez, Nubia Saucedo-Villarreal, Mardia López-Alarcón, Fausto Sánchez-Muñoz [......] Sandra Romero-Hidalgo, Doris G Ruiz-Gómez, Daniela Riaño-Barros, Miguel F Herrera, Francisco J Gómez-Pérez, Philippe Froguel, Eduardo García-García, M Teresa Tusié-Luna, Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros

  Obesity (Silver Spring, Md.). 08/2008;

  Common polymorphisms in the fat mass and obesity-associated gene (FTO) have shown strong association with obesity in several populations. In the present study, we explored the association of FTO geneCommon polymorphisms in the fat mass and obesity-associated gene (FTO) have shown strong association with obesity in several populations. In the present study, we explored the association of FTO gene polymorphisms with obesity and other biochemical parameters in the Mexican population. We also assessed FTO gene expression levels in adipose tissue of obese and nonobese individuals. The study comprised 788 unrelated Mexican-Mestizo individuals and 31 subcutaneous fat tissue biopsies from lean and obese women. FTO single-nucleotide polymorphisms (SNPs) rs9939609, rs1421085, and rs17817449 were associated with obesity, particularly with class III obesity, under both additive and dominant models (P = 0.0000004 and 0.000008, respectively). These associations remained significant after adjusting for admixture (P = 0.000003 and 0.00009, respectively). Moreover, risk alleles showed a nominal association with lower insulin levels and homeostasis model assessment of B-cell function (HOMA-B), and with higher homeostasis model assessment of insulin sensitivity (HOMA-S) only in nonobese individuals (P (dom) = 0.031, 0.023, and 0.049, respectively). FTO mRNA levels were significantly higher in subcutaneous fat tissue of class III obese individuals than in lean individuals (P = 0.043). Risk alleles were significantly associated with higher FTO expression in the class III obesity group (P = 0.047). In conclusion, FTO is a major risk factor for obesity (particularly class III) in the Mexican-Mestizo population, and is upregulated in subcutaneous fat tissue of obese individuals.Obesity (2008) doi:10.1038/oby.2008.367.

• Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides.

  Authors: Jaspal S Kooner, John C Chambers, Carlos A Aguilar-Salinas, David A Hinds, Craig L Hyde, Gregory R Warnes, Francisco J Gómez-Pérez, Kelly A Frazer, Paul Elliott, James Scott, Patrice M Milos, David R Cox, John F Thompson

  Nature genetics. 03/2008; 40(2):149-51.

  We tested over 267,000 SNPs in 1,005 Northern Europeans and 248,000 in 1,006 Indian Asians for association with triglycerides and HDL cholesterol, with replication in 10,536 subjects. We foundWe tested over 267,000 SNPs in 1,005 Northern Europeans and 248,000 in 1,006 Indian Asians for association with triglycerides and HDL cholesterol, with replication in 10,536 subjects. We found association of a nonsynonymous SNP (rs3812316, G771C, Gln241His) in MLXIPL with plasma triglyceride levels (combined P = 1.4 x 10(-10)). MLXIPL coordinates transcriptional regulation of enzymes that channel glycolytic end-products into lipogenesis and energy storage, making MLXIPL a plausible 'thrifty gene'.

• Analysis of fasting plasma glucose values for optimal detection of abnormal responses on the oral glucose tolerance test in at-risk study subjects.

  Authors: Ludivina Robles-Osorio, Carlos A Aguilar-Salinas, Roopa Mehta, Francisco J Gómez-Pérez, Juan A Rull

  Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 10/2007; 13(6):583-9.

  OBJECTIVE: To identify the fasting plasma glucose (FPG) value with the best performance for detecting an abnormal response on the oral glucose tolerance test (OGTT) in patients at risk for havingOBJECTIVE: To identify the fasting plasma glucose (FPG) value with the best performance for detecting an abnormal response on the oral glucose tolerance test (OGTT) in patients at risk for having type 2 diabetes. METHODS: All patients who underwent a 2-hour OGTT during an 18-month period were included in this study. Pretest and posttest odds, likelihood ratios, and receiver operating characteristic curves were used to identify the FPG value most strongly associated with an abnormal result on the OGTT (either diabetes or impaired glucose tolerance [IGT]). RESULTS: Of the 1,371 patients who underwent an OGTT during the designated study period, 1,239 fulfilled the inclusion criteria. The prevalence of IGT was 25.34% (314 patients). Diabetes was diagnosed in 141 patients (11.38%). IGT was more commonly found in the FPG strata below 115 mg/dL; above this value, diabetes was more frequently diagnosed. In general, the percentage of cases of IGT increased progressively throughout the "normal" FPG range. The prevalence varied from 11.4% (in patients with FPG values <80 mg/dL) to 32% (in those with FPG levels from 95 to 99.9 mg/dL). FPG values between 95 and 99.9 mg/dL had a likelihood ratio of 2.1 for detecting an abnormal OGTT response, of 1.8 for detecting diabetes, and of 1.66 for detecting IGT. The odds ratio for detecting either IGT or diabetes was increased 2-fold by performing an OGTT. The FPG threshold with the best ability for detecting an abnormal response on the OGTT was 95 mg/dL (sensitivity of 0.72 and specificity of 0.65). CONCLUSION: In patients at risk for type 2 diabetes, the FPG cut point (95 mg/dL) most useful for detecting an abnormal OGTT response is included in the normal range of the FPG.

• Design and validation of a population-based definition of the metabolic syndrome.

  Authors: Carlos A Aguilar-Salinas, Rosalba Rojas, Clicerio Gonzalez-Villalpando, Francisco J Gómez-Pérez, Roopa Mehta, Gustavo Olaiz, Juan A Rull, David R Cox

  Diabetes care. 11/2006; 29(11):2420-6.

  OBJECTIVE: The National Cholesterol Education Program (NCEP) definition of the metabolic syndrome was modified to be described as a continuous variable and adapted to the characteristics of aOBJECTIVE: The National Cholesterol Education Program (NCEP) definition of the metabolic syndrome was modified to be described as a continuous variable and adapted to the characteristics of a Hispanic population. RESEARCH DESIGN AND METHODS: Age/sex population percentiles for every component of the NCEP criteria were included in this approach using population-based data from a Mexican nationwide survey (2,158 subjects). One point was given per decile for every component. The total number of points accumulated was used to classify subjects. The predictive power for incident diabetes was evaluated using the 7-year follow-up results of the Mexico City Diabetes Study. RESULTS: Our population-based method had a significantly better prognostic power compared with the original and the updated NCEP definitions (area under the receiver operating characteristic curve 0.746 vs. 0.697 and 0.723, respectively, P < 0.05). Using individuals with </=1 component of the NCEP definition as reference, the odds ratio was greater in the upper quartile of the points scale (>/=39 points) (12.71 [95% CI 5.67-28.49]) compared with that calculated for the original (9.52 [4.69-19.31]) and the updated (11.14 [5.33-23.30]) NCEP criteria. The major advantage of our approach is the detection of subjects at the extremes of the range of diabetes risk and the ability to estimate this risk as a continuum. CONCLUSIONS: Our method adapts the NCEP criteria to the characteristics of a Hispanic population. It improves the predictive power of the NCEP criteria for future diabetes.

• Genetic heterogeneity of autosomal dominant hypercholesterolemia in Mexico.

  Authors: Ludivina Robles-Osorio, Alejandra Huerta-Zepeda, Ma Luisa Ordóñez, Samuel Canizales-Quinteros, Andrea Díaz-Villaseñor, Ruth Gutiérrez-Aguilar, Laura Riba, Adriana Huertas-Vázquez, Maribel Rodríguez-Torres, Rita A Gómez-Díaz [......] Laura Ongay-Larios, Guadalupe Codiz-Huerta, Minerva Mora-Cabrera, Roopa Mehta, Francisco J Gómez-Pérez, Juan A Rull, Jean-Pierre Rabès, Ma Teresa Tusié-Luna, Socorro Durán-Vargas, Carlos A Aguilar-Salinas

  Archives of medical research. 02/2006; 37(1):102-8.

  BACKGROUND: Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are relatively common lipid disorders caused by mutations of the low-density lipoprotein receptorBACKGROUND: Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are relatively common lipid disorders caused by mutations of the low-density lipoprotein receptor (LDLR) and apolipoprotein B (apoB) genes, respectively. A third locus on chromosome 1p34.1-p32 was recently linked to FH and the responsible gene has been identified [protein convertase subtilisin/kexin type 9 (PCSK9)]. METHODS: We assessed the contribution of the LDLR, apoB, and PCSK9 genes as cause of FH in Mexico. Forty six unrelated probands, as well as 68 affected and 60 healthy relatives, were included. RESULTS: All index cases were diagnosed as having heterozygous autosomal dominant FH. Seventeen of the 46 index cases had LDLR gene mutations, four of which were novel (Fs92ter108, C268R, Q718X, and Fs736ter743); and only one patient had an apoB mutation (R3500Q). We sequenced the PCSK9 gene in the remainder of the 28 probands with no identified LDLR or APOB gene defects; however, no PCSK9 mutations were found, including one large kindred with positive linkage to the 1p34.1-32 locus (multipoint LOD score of 3.3) and two small pedigrees. Linkage was excluded from these three loci in at least four kindreds suggesting that other yet uncharacterized genes are involved. CONCLUSIONS: Our results underline substantial genetic heterogeneity for FH in the Mexican population.

• Management of the metabolic syndrome as a strategy for preventing the macrovascular complications of type 2 diabetes: controversial issues.

  Authors: Carlos A Aguilar-Salinas, Roopa Mehta, Rosalba Rojas, Francisco J Gómez-Pérez, Gustavo Olaiz, Juan A Rull

  Current diabetes reviews. 06/2005; 1(2):145-58.

  The metabolic syndrome is known to increase cardiovascular morbidity and precede the development of type 2 diabetes. Even before the appearance of hyperglycemia, the components of the metabolicThe metabolic syndrome is known to increase cardiovascular morbidity and precede the development of type 2 diabetes. Even before the appearance of hyperglycemia, the components of the metabolic syndrome play a crucial role in the pathogenesis of the macrovascular complications. Thus, the recognition and treatment of the metabolic syndrome may be a strategy to prevent the most likely cause of death (i.e. cardiovascular events) in cases that eventually develop type 2 diabetes. In this review, controversial issues regarding the treatment of the two main components of the metabolic syndrome (i.e dyslipidemia and arterial hypertension) are discussed. Several disparities in the current NCEP-ATPIII recommendations, when applied to patients with the metabolic syndrome, are pointed out. In population-based studies, the number of individuals with the metabolic syndrome who would need LDL cholesterol lowering treatment following these guidelines is remarkably low compared to subjects belonging to the same risk strata (10 year risk 10-20%). Subjects with the metabolic syndrome do not fall into the same risk category, resulting in differing LDL-C targets. Also, the Framingham tables underestimate the cardiovascular risk associated with the metabolic syndrome; hence fewer cases qualify for drug therapy. In addition, LDL-C underestimates the number of atherogenic particles and is therefore not the ideal target for these patients. The selection of antihypertensive medication in the metabolic syndrome is also controversial. Thus, there is sufficient evidence for a review of the current management of the metabolic syndrome as part of a strategy to prevent the macrovascular complications in type 2 diabetes.

• A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia.

  Authors: Samuel Canizales-Quinteros, Carlos A Aguilar-Salinas, Adriana Huertas-Vázquez, María L Ordóñez-Sánchez, Maribel Rodríguez-Torres, José L Venturas-Gallegos, Laura Riba, Salvador Ramírez-Jimenez, Rocío Salas-Montiel, Giovani Medina-Palacios, Ludivina Robles-Osorio, Angel Miliar-García, Luis Rosales-León, Blanca H Ruiz-Ordaz, Alejandro Zentella-Dehesa, Adrian Ferré-D'Amare, Francisco J Gómez-Pérez, Ma Teresa Tusié-Luna

  Human genetics. 01/2005; 116(1-2):114-20.

  Autosomal recessive hypercholesterolemia (ARH) is characterized by elevated LDL serum levels, xanthomatosis, and premature coronary artery disease. Three loci have been described for this conditionAutosomal recessive hypercholesterolemia (ARH) is characterized by elevated LDL serum levels, xanthomatosis, and premature coronary artery disease. Three loci have been described for this condition (1p35, 15q25-q26 and 13q). Recently, the responsible gene at the 1p35 locus, encoding an LDL receptor adaptor protein (ARH) has been identified. We studied a Mexican ARH family with two affected siblings. Sequence analysis of the ARH gene (1p35 locus) revealed that the affected siblings are homozygous for a novel mutation (IVS4+2T>G) affecting the donor splice site in intron 4, whereas both the parents and an unaffected sister are heterozygous for this mutation. The IVS4+2T>G mutation results in a major alternative transcript derived from a cryptic splice site, which carries an in-frame deletion of 78 nucleotides in the mature mRNA. The translation of this mRNA yields a mutant protein product (ARH-26) lacking 26 amino acids, resulting in the loss of beta-strands beta6 and beta7 from the PTB domain. This is the first case where a naturally occurring mutant with an altered PTB domain has been identified.

• Ciprofibrate therapy in patients with hypertriglyceridemia and low high density lipoprotein (HDL)-cholesterol: greater reduction of non-HDL cholesterol in subjects with excess body weight (The CIPROAMLAT study).

  Authors: Carlos A Aguilar-Salinas, Andréia Assis-Luores-Vale, Benjamín Stockins, Hector Mario Rengifo, José Dondici Filho, Abrahão Afiune Neto, Lísia Marcílio Rabelo, Kerginaldo Paulo Torres, José Egídio Paulo de Oliveira, Carlos Alberto Machado [......] Cuauhtémoc Vazquez, Saul Salinas, Ismael Hernández, Octavio Medel, Ricardo Moreno, Paula Lugo, Ricardo Alvarado, Roopa Mehta, Victor Gutierrez, Francisco J Gómez-Pérez

  Cardiovascular diabetology. 08/2004; 3:8.

  BACKGROUND: Hypertriglyceridemia in combination with low HDL cholesterol levels is a risk factor for cardiovascular disease. Our objective was to evaluate the efficacy of ciprofibrate for theBACKGROUND: Hypertriglyceridemia in combination with low HDL cholesterol levels is a risk factor for cardiovascular disease. Our objective was to evaluate the efficacy of ciprofibrate for the treatment of this form of dyslipidemia and to identify factors associated with better treatment response. METHODS: Multicenter, international, open-label study. Four hundred and thirty seven patients were included. The plasma lipid levels at inclusion were fasting triglyceride concentrations between 1.6-3.9 mM/l and HDL cholesterol < or = 1.05 mM/l for women and < or = 0.9 mM/l for men. The LDL cholesterol was below 4.2 mM/l. All patients received ciprofibrate 100 mg/d. Efficacy and safety parameters were assessed at baseline and at the end of the treatment. The primary efficacy parameter of the study was percentage change in triglycerides from baseline. RESULTS: After 4 months, plasma triglyceride concentrations were decreased by 44% (p < 0.001). HDL cholesterol concentrations were increased by 10% (p < 0.001). Non-HDL cholesterol was decreased by 19%. A greater HDL cholesterol response was observed in lean patients (body mass index < 25 kg/m2) compared to the rest of the population (8.2 vs 19.7%, p < 0.001). In contrast, cases with excess body weight had a larger decrease in non-HDL cholesterol levels (-20.8 vs -10.8%, p < 0.001). There were no significant complications resulting from treatment with ciprofibrate. CONCLUSIONS: Ciprofibrate is efficacious for the correction of hypertriglyceridemia / low HDL cholesterol. A greater decrease in non-HDL cholesterol was found among cases with excess body weight. The mechanism of action of ciprofibrate may be influenced by the pathophysiology of the disorder being treated.

• Familial combined hyperlipidemia: controversial aspects of its diagnosis and pathogenesis.

  Authors: Carlos A Aguilar-Salinas, Margarita Zamora, Rita A Gómez-Díaz, Roopa Mehta, Francisco J Gómez-Pérez, Juan A Rull

  Seminars in vascular medicine. 06/2004; 4(2):203-9.

  Familial combined hyperlipidemia is the most frequent cause of primary dyslipidemia in Mexico. Its manifestations include hypercholesterolemia, hypertriglyceridemia, or a combination of both. DespiteFamilial combined hyperlipidemia is the most frequent cause of primary dyslipidemia in Mexico. Its manifestations include hypercholesterolemia, hypertriglyceridemia, or a combination of both. Despite its high frequency, a proper diagnosis is rarely made. Assessment of the lipid profiles of at least three first-degree relatives is necessary. The diagnosis of familial combined hyperlipidemia in a family not only leads to the identification of other affected family members but, more important, allows cardiovascular risk stratification of those affected. Prospective studies have confirmed the atherogenicity of the disease. A critical review of the current literature in this field is presented in this article. Although three screenings of the genome have been completed, the genes responsible for this disorder have not been identified. Limitations with respect to the characterization of affected subjects and the heterogeneity of the disease are among possible explanations. However, familial combined hyperlipidemia, because of its high prevalence, must be given greater priority. It represents a great challenge for physicians involved in the treatment of dyslipidemic patients.

• Characteristics of patients with type 2 diabetes in México: Results from a large population-based nationwide survey.

  Authors: Carlos A Aguilar-Salinas, Oscar Velazquez Monroy, Francisco J Gómez-Pérez, Antonio Gonzalez Chávez, Agustin Lara Esqueda, Virginia Molina Cuevas, Juan A Rull-Rodrigo, Roberto Tapia-Conyer

  Diabetes care. 07/2003; 26(7):2021-6.

  OBJECTIVE: To describe the clinical characteristics of the diabetic population that formed part of a population-based survey conducted in México. RESEARCH DESIGN AND METHODS: In 2000, information wasOBJECTIVE: To describe the clinical characteristics of the diabetic population that formed part of a population-based survey conducted in México. RESEARCH DESIGN AND METHODS: In 2000, information was obtained from 42,886 subjects aged > or =20 years using a multistage sampling procedure. Standardized questionnaires were used. Anthropometric measurements, blood pressure, and capillary glucose concentrations were taken. RESULTS: Type 2 diabetes was found in 3,597 subjects (age-adjusted prevalence 8.18%), of which 2,878 (80%) had previously been diagnosed. The average age of the diabetic participants was 55.2 +/- 13.5 years; 13% were <40 years of age. Nine percent had been diagnosed for >10 years. The average BMI was 29.2 +/- 5.7 kg/m(2); three-quarters of the cases had BMI >25 kg/m(2). The average waist circumference was 102 +/- 13.4 cm, and increased waist circumference was more common among women. Arterial hypertension was found in half of the cases and, of those on treatment, only one-third had a blood pressure <140/90 mmHg. Smoking was reported in 34% of the diabetic group, a higher rate than in the nondiabetic subjects. There was at least one modifiable coronary risk factor in 67.6% of the cases. Very few followed an exercise or dietary regimen and a small percentage used insulin. CONCLUSIONS: Diabetes affects a large proportion of Mexican adults (8.18%). This figure may be underestimated. The majority of the subjects had modifiable risk factors for the chronic complications of diabetes. Only a few achieved adequate blood pressure control and other treatment goals.

• Analysis of the agreement between the World Health Organization criteria and the National Cholesterol Education Program-III definition of the metabolic syndrome: results from a population-based survey.

  Authors: Carlos A Aguilar-Salinas, Rosalba Rojas, Francisco J Gómez-Pérez, Victoria Valles, Juan Manuel Ríos-Torres, Aurora Franco, Gustavo Olaiz, Juan A Rull, Jaime Sepulveda

  Diabetes care. 06/2003; 26(5):1635.