C A Aguilar-Salinas

Publications of C A Aguilar-Salinas

• Association of the metabolic syndrome and long-term renal function in kidney donors.

  Authors: D Cuevas-Ramos, P Almeda-Valdés, M Arvizu, J Mata, L E Morales-Buenrostro, B Gabilondo, M Vilatobá, R Correa-Rotter, F Gabilondo-Navarro, R Mehta, C A Aguilar-Salinas, J Alberú, F J Gómez-Pérez

  Transplantation proceedings. 06/2011; 43(5):1601-6.

  Metabolic syndrome (MetS) may represent risk factor for long-term renal function of kidneys from living donors. The aim of this study was to evaluate the impact of MetS on renal function inMetabolic syndrome (MetS) may represent risk factor for long-term renal function of kidneys from living donors. The aim of this study was to evaluate the impact of MetS on renal function in donors. Data regarding the presence or absence of MetS and renal function, as assessed by estimated glomerular filtration rate (eGFR) were obtained from 140 kidney donors before nephrectomy (BN) and at follow-up (AF). Donors were divided into those with (group 1; n =28) versus without MetS (group 2; n = 112). Comparing the groups, we observed a significantly greater reduction in eGFR among the group with MetS BN versus AF 27.5% (19.3-33.0) versus 21.4% (9.6-34.1 P = .02) respectively using a Cox regression model, including age, gender, serum uric acid, body mass index (BMI), and basal eGFR, MetS BN (hazard ratio = 2.2; 95% confidence interval [CI], 1.21-4.01; p = .01) was an independent factor associated with a greater risk of a-eGFR <70 mL/min/1.73 m(2) at follow-up (P < .001). Additionally, age (hazard ratio = 1.03%; 95% CI, 1.01-1.06; P < .001), and female gender (hazard ratio = 1.86; 95% CI, 1.03-3.36; P = .03) were associated with a greater decrease in eGFR. Individuals with MetS BN showed a GFR <70 mL/min/1.73 m(2) at significantly shorter follow-up time (5.6 ± 0.8 years) versus persons without MetS (12.8 ± 1.0 years; P = .001) Kidney donors with MetS BN experiment a significantly greater decrease in eGFR at follow-up.

• High frequency of T130I mutation of HNF4A gene in Mexican patients with early-onset type 2 diabetes.

  Authors: M Menjívar, M A Granados-Silvestre, I Montúfar-Robles, M Herrera, M T Tusié-Luna, S Canizales-Quinteros, C A Aguilar-Salinas, M G Ortiz-López

  Clinical genetics. 03/2008; 73(2):185-7.

• Association of PPARG2 Pro12Ala variant with larger body mass index in Mestizo and Amerindian populations of Mexico.

  Authors: S Canizales-Quinteros, C A Aguilar-Salinas, M G Ortiz-López, M Rodríguez-Cruz, M T Villarreal-Molina, R Coral-Vázquez, A Huertas-Vázquez, A Hernández-Caballero, M López-Alarcón, O R Brito Zurita, A Domínguez-Banda, L R Martinez-Sánchez, T Canto-de Cetina, G Vilchis-Dorantes, H Rosas-Vargas, M A Granados-Silvestre, A Medeiros-Domingo, M. Menjivar, M T Tusié-Luna

  Human biology; an international record of research. 02/2007; 79(1):111-9.

  Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, withPrevious studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, with controversial results. We have determined the Pro12Ala variant frequency in 370 nondiabetic Mexican Mestizo subjects and in five Mexican Amerindian groups and have investigated its possible association with lipid metabolism, insulin serum levels, and obesity in three of these populations. Two independent case-control studies were conducted in 239 nondiabetic individuals: 135 case subjects (BMI > or = 25 kg/m2) and 104 control subjects (BMI < 25 kg/m2). The PPARG2 Ala12 allele frequency was higher in most Amerindian populations (0.17 in Yaquis, 0.16 in Mazahuas, 0.16 in Mayans, and 0.20 in Triquis) than in Asians, African Americans, and Caucasians. The Pro12Ala and Ala12Ala (X12Ala) genotypes were significantly associated with greater BMI in Mexican Mestizos and in two Amerindian groups. X12Ala individuals had a higher risk of overweight or obesity than noncarriers in Mestizos (OR = 3.67; 95% CI, 1.42-9.48; p = 0.007) and in Yaquis plus Mazahuas (OR = 3.21; 95% CI, 1.27-8.11; p = 0.013). Our results provide further support of the association between the PPARG2 Ala12 allele and risk of overweight or obesity in Mestizos and two Amerindian populations from Mexico.

• HNF-1alpha G574S is a functional variant with decreased transactivation activity.

  Authors: K Navalón-García, L Mendoza-Alcantar, M E Díaz-Vargas, M A Martínez-Godínez, H Reyna-Garfias, C A Aguilar-Salinas, L Riba, S Canizales-Quinteros, T Villarreal-Molina, A González-Chávez, V Argueta-Villamar, M T Tusié-Luna, A Miliar-García

  Diabetic medicine : a journal of the British Diabetic Association. 01/2007; 23(12):1295-300.

  AIM: To assess the functional consequence of the hepatocyte nuclear factor 1alpha gene (HNF-1alpha) G574S variant previously proposed as a diabetes susceptibility allele, in a group of Mexican Type 2AIM: To assess the functional consequence of the hepatocyte nuclear factor 1alpha gene (HNF-1alpha) G574S variant previously proposed as a diabetes susceptibility allele, in a group of Mexican Type 2 diabetic patients with end-stage renal disease (ESRD). METHODS: The transcriptional activity of the HNF-1alpha G574S recombinant protein on the human insulin promoter was assessed by transfection assays in RINm5f and HepG2 cell lines. RESULTS: Two unrelated Mexican diabetic patients with no known African ancestry were found to carry the G574S variant. This substitution was not found among unrelated healthy control subjects. Whereas the G574S HNF-1alpha transcription activation of the human insulin promoter was 40% lower than that of the wild-type protein in RINm5f beta cells, no difference was found in a hepatic cell line (HepG2). CONCLUSIONS: G574S affects the transactivation potential of HNF-1alpha on the insulin promoter in pancreatic beta-cells. Although it has been difficult to prove its role in the development of diabetes in case-control association studies, this variant exhibits functional effects consistent with it being a potential diabetes susceptibility allele.

• The body mass index is a less-sensitive tool for detecting cases with obesity-associated co-morbidities in short stature subjects.

  Authors: A Lara-Esqueda, C A Aguilar-Salinas, O Velazquez-Monroy, F J Gómez-Pérez, M Rosas Peralta, R Mehta, R Tapia-Conyer

  International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 12/2004; 28(11):1443-50.

  OBJECTIVE: To assess the ability of the body mass index (BMI) to detect obesity-associated morbidity in subjects with a normal or short stature. METHODS: Information was obtained on 119 975 subjectsOBJECTIVE: To assess the ability of the body mass index (BMI) to detect obesity-associated morbidity in subjects with a normal or short stature. METHODS: Information was obtained on 119 975 subjects from a cardiovascular risk factors detection program. Standardized questionnaires were used. Capillary glucose and cholesterol concentrations were measured. Diabetes, arterial hypertension and hypercholesterolemia were selected as end points. Sensitivity, specificity and the likelihood ratio for several BMI thresholds were calculated. ROC curves were constructed to identify the BMI cutoff points with best diagnostic performance. The area under the curve (AUC) was used to assess the proficiency of BMI. RESULTS: Short stature (height </=150 cm for women or </=160 cm for men) was found in 24 854 subjects (20.7%). These cases had a higher prevalence of type II diabetes and arterial hypertension even after adjusting for confounding variables. In addition, the frequency of the abnormalities was higher even at the lowest BMI values; the prevalence increased in direct proportion with the BMI, but at a lower rate compared to cases with normal stature. The AUC for every co-morbidity was smaller in short stature subjects. The likelihood ratio for detecting co-morbidities increased at the same BMI value in subjects with or without short stature. CONCLUSIONS: The prevalence of obesity-associated co-morbidities is higher in subjects with short stature compared to those without it. The proficiency of BMI as a diagnostic tool is poor in short stature subjects. This problem is not resolved by decreasing BMI thresholds used to define overweight.

• Contribution of chromosome 1q21-q23 to familial combined hyperlipidemia in Mexican families.

  Authors: A Huertas-Vázquez, J P del Rincón, S Canizales-Quinteros, L Riba, G Vega-Hernández, S Ramírez-Jiménez, M Aurón-Gómez, F J Gómez-Pérez, C A Aguilar-Salinas, M T Tusié-Luna

  Annals of human genetics. 10/2004; 68(Pt 5):419-27.

  Familial combined hyperlipidemia (FCHL) is the most common familial dyslipidemia, with a prevalence of 1-2% in the general population. A major locus for FCHL has been mapped to chromosome 1q21-q23 inFamilial combined hyperlipidemia (FCHL) is the most common familial dyslipidemia, with a prevalence of 1-2% in the general population. A major locus for FCHL has been mapped to chromosome 1q21-q23 in Finnish, Chinese, German and US families. We studied seven extended Mexican families with 153 members, including 64 affected subjects. A total of 11 markers were genotyped, including D1S104 which has been linked to FCHL in other studies. Two point linkage analysis for the FCHL phenotype, and for the elevated triglyceride (TG) trait, allowing for heterogeneity, gave a maximum HLOD of 1.67 (alpha = 0.49) and 1.93 (alpha = 0.43) at D1S2768 (2.69 cM proximal to D1S104) respectively. Heterogeneity and non-parametric (NPL) multipoint analyses for the FCHL phenotype and the TG trait showed maximum HLODs of 1.27 (alpha = 0.46) and 1.64 (alpha = 0.38), and NPLs of 4.00 (P = 0.0001) and 3.68 (P = 0.0003) near D1S2768, respectively. In addition, analysis of four candidate genes putatively involved in the expression of FCHL showed no evidence of linkage for the LCAT gene or the APOA1/C3/A4/A5 gene cluster. However, we cannot exclude the participation of these genes, or the LIPC and LPL genes, as minor susceptibility loci in the expression of FCHL, or the TG or elevated total cholesterol (TC) traits in our families. In conclusion, our data confirm the involvement of a major susceptibility locus on chromosome 1q21-q23 in FCHL Mexican families, consistent with findings in other populations.

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• Effect of malnutrition during the first year of life on adult plasma insulin and glucose tolerance.

  Authors: J González-Barranco, J M Ríos-Torres, L Castillo-Martínez, J C López-Alvarenga, C A Aguilar-Salinas, C Bouchard, J P Deprès, A Tremblay

  Metabolism: clinical and experimental. 09/2003; 52(8):1005-11.

  There is evidence linking intrauterine growth retardation with increased cardiovascular risk and diabetes mellitus (DM) later in life. However, little is known about the association betweenThere is evidence linking intrauterine growth retardation with increased cardiovascular risk and diabetes mellitus (DM) later in life. However, little is known about the association between malnutrition during the first year of life and metabolic abnormalities in adulthood. The objective of this study was to assess the effect of documented malnutrition during the first year of life on glucose tolerance, plasma insulin, lipid profile, and blood pressure in early adulthood, as well as to assess the interaction between body mass index (BMI) and malnutrition on these variables. A study group of young men with a documented history of malnutrition during their first year of life was recruited from 4 pediatric hospitals in Mexico City and compared with a control group. Subjects included were 52 men, aged 20.2 +/- 3.6 years, with a mean birth weight of 3.0 +/- 0.7 kg and documented malnutrition in their first year of life; controls were 50 men, aged 23.3 +/- 1.8 years, with a mean birth weight of 3.2 +/- 0.5 kg. Insulin and glucose concentrations, fasting and in response to an oral glucose load, plasma lipids, blood pressure, and an insulin sensitivity index (ISI) were measured. The areas under the curves of glucose (AUCG) and insulin (AUCI) were significantly higher in cases (P =.012 and <.002, respectively), independent of birth weight, BMI, or age. BMI was significantly associated with fasting plasma insulin (FPI), AUCI, ISI, triglyceride, and high-density lipoprotein (HDL)-cholesterol concentrations in cases, but not in controls. These data suggest that early malnutrition in extrauterine life, independently of birth weight, has an adverse effect on insulin metabolism and glucose tolerance in young men, and it worsens as body mass increases even within the normal range of BMI. Therefore, it is advisable to prevent obesity in individuals exposed to early malnutrition.

• Insulin resistance and abdominal adiposity in young men with documented malnutrition during the first year of life.

  Authors: N G Boulé, A Tremblay, J Gonzalez-Barranco, C A Aguilar-Salinas, J C Lopez-Alvarenga, J P Després, C Bouchard, F J Gomez-Perez, L Castillo-Martinez, J M Rios-Torres

  International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 05/2003; 27(5):598-604.

  OBJECTIVE: The main objective of the study was to examine the effect of early life malnutrition on the relation between insulin sensitivity and abdominal adiposity in adulthood. It was hypothesisedOBJECTIVE: The main objective of the study was to examine the effect of early life malnutrition on the relation between insulin sensitivity and abdominal adiposity in adulthood. It was hypothesised that participants with early life malnutrition would display a more pronounced deterioration of insulin sensitivity in association with a gain in abdominal fat. DESIGN: As a first attempt to investigate this issue, we studied the effect of body fat gains in a cross-sectional context. SUBJECTS: A total of 26 young adult men with evidence of malnutrition during the first year of life and 27 control subjects were recruited for this study. Malnutrition status was determined from medical files of paediatric hospitals in the Mexico City metropolitan area. MEASUREMENTS: Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp, and body composition was measured by anthropometrics, bioelectrical impedance and computed tomography. RESULTS: There was a negative correlation between total abdominal adipose tissue area and insulin sensitivity in the previously malnourished and control groups (r(2)=0.65 and 0.35, P<0.01, respectively). When matched for low amounts of abdominal fat (114 cm(2)), participants with and without early life malnutrition had similar insulin sensitivity (9.03 vs 8.88 mg kg(-1) x min(-1)). However, when matched for high amounts of abdominal fat (310 cm(2)) participants who were malnourished during the first year of life had lower insulin sensitivity (4.74 vs 6.85 mg kg(-1) x min(-1), P<0.05). CONCLUSION: Higher levels of abdominal adipose tissue are more detrimental to insulin sensitivity in previously malnourished individuals.

• High prevalence of low HDL cholesterol concentrations and mixed hyperlipidemia in a Mexican nationwide survey.

  Authors: C A Aguilar-Salinas, G Olaiz, V Valles, J M Torres, F J Gómez-Pérez, J A Rull, R Rojas, A Franco, J Sepulveda

  Journal of lipid research. 09/2001; 42(8):1298-307.

  The prevalence of lipid abnormalities revealed in a survey done in 417 Mexican cities is described. Information was obtained on 15,607 subjects, aged 20 to 69 years. In this report, only samplesThe prevalence of lipid abnormalities revealed in a survey done in 417 Mexican cities is described. Information was obtained on 15,607 subjects, aged 20 to 69 years. In this report, only samples obtained after a 9- to 12-h fast were included (2,256 cases: 953 men and 1,303 women). The population is representative of Mexican urban adults. Mean lipid concentrations were: cholesterol, 4.80 mmol/l; triglycerides, 2.39 mmol/l; HDL cholesterol, 1.00 mmol/l; and LDL cholesterol, 3.06 mmol/l. The most prevalent abnormality was HDL cholesterol below 0.9 mmol/l (46.2% for men and 28.7% for women). Hypertriglyceridemia (>2.26 mmol/l) was the second most prevalent abnormality (24.3%). Severe hypertriglyceridemia (>11.2 mmol/l) was observed in 0.42% of the population. Increased LDL cholesterol (> or =4.21 mmol/l) was observed in 11.2% of the sample. Half of the hypertriglyceridemic subjects had a mixed dyslipidemia or low HDL cholesterol. More than 50% of the low HDL cholesterol cases were not related to hypertriglyceridemia. Insulin resistance was found in 59% of them. In conclusion, the prevalence of hypoalphalipoproteinemia and other forms of dyslipidemia in Mexican adults is very high and it is among the highest previously reported worldwide.

• Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: an open-label, multicenter study.

  Authors: C A Aguilar-Salinas, G Fanghänel-Salmón, E Meza, J Montes, A Gulías-Herrero, L Sánchez, E A Monterrubio-Flores, H González Valdez, F J Gómez-Pérez

  Metabolism: clinical and experimental. 06/2001; 50(6):729-33.

  Mixed hyperlipidemia is a common risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of ciprofibrate versus gemfibrozil for the treatment of patientsMixed hyperlipidemia is a common risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of ciprofibrate versus gemfibrozil for the treatment of patients with mixed hyperlipidemia carefully selected for similar lipid profiles. A total of 68 patients who had mixed hyperlipidemia after following an isocaloric American Heart Association (AHA) phase I diet for 4 weeks were included. The plasma lipid levels at the inclusion were low-density lipoprotein-cholesterol (LDL-C) > or = 130 mg/dL, cholesterol > or = 240 mg/dL, and triglycerides > or = 200 mg/dL. Patients were randomly assigned to receive ciprofibrate 100 mg/d or gemfibrozil 1,200 mg/d. At the end of the 8-week treatment period, efficacy and safety parameters were compared with baseline values. The primary efficacy parameters of the study were percentage changes in triglycerides and LDL-C from baseline. After 8 weeks, plasma triglyceride concentrations were decreased by 43.5% and 54% compared with baseline during ciprofibrate and gemfibrozil therapy, respectively (P <.001). High-density lipoprotein-cholesterol (HDL-C) concentrations were increased 20.8% and 19.3% during ciprofibrate and gemfibrozil, respectively (P <.001). Apoprotein B, cholesterol, and very-low-density lipoprotein-cholesterol (VLDL-C) concentrations were also improved by the study drugs (18.6%, 13.2%, and 30.9%, respectively, during ciprofibrate and 44%, 13.8%, and 14.4%, respectively, during gemfibrozil). Meanwhile, the effect of the drug was minimal on LDL-C. A significant decrease in non-HDL-C resulted from both treatments (19% and 19.5%, respectively, P <.05). The only statistically significant difference observed between treatments was the effects on fibrinogen concentration, a coronary risk factor. Ciprofibrate significantly decreased its concentration by 18.8%, fibrinogen was slightly increased during gemfibrozil treatment. No patient had a significant modification on any of the safety tests. In summary, ciprofibrate and gemfibrozil are well-tolerated and efficacious treatments for mixed hyperlipidemia. Significant reductions in triglycerides, non-HDL-C, and apolipoprotein B were achieved with both drugs. A significant fibrinogen reduction was obtained with ciprofibrate.

• Lipids, apoprotein B, and associated coronary risk factors in urban and rural older Mexican populations.

  Authors: C A Aguilar-Salinas, I Lerman-Garber, J Pérez, A R Villa, C L Martinez, L C Turrubiatez, B Wong, F J Gómez-Pérez, L M Gutierrez Robledo

  Metabolism: clinical and experimental. 04/2001; 50(3):311-8.

  The objective of this comparative cross-sectional study was to determine the prevalence of dyslipidemias and examine its association with food intake and metabolic variables in urban and rural elderThe objective of this comparative cross-sectional study was to determine the prevalence of dyslipidemias and examine its association with food intake and metabolic variables in urban and rural elder Mexican populations. Three different communities (urban areas of medium and low income and a rural area) were studied. A total of 344 subjects aged 60 years and older and 273 aged 35 to 59 years were included. The evaluated parameters were personal medical data, 24-hour diet recall, and fasting plasma lipids, insulin, and glucose levels. Older subjects, especially men, living in the rural area had lower cholesterol levels (5.02 +/- 0.97 v 5.6 +/- 1.07 mmol/L; P <.05) and insulin levels (12 +/- 10 v 42 +/- 68 mU/mL) and higher high-density lipoprotein cholesterol concentrations (1.31 +/- 0.36 v 1.07 +/-0.28 mmol/L) than the elders from the urban medium-income group. Possible explanations for these differences are found in the dietary habits of the groups. Rural elders had higher amounts of fiber (20 +/- 11 v 10 +/- 6 g/d) and carbohydrate (70% +/- 0.08% v 52% +/- 0.11% of calories) and lower fat (18% +/- 0.07% v 33% +/- 0.1% of calories) in their diets. In the urban groups, low-density lipoprotein hypercholesterolemia was present in 17.8% of adult and 39.1% of elderly women (P =.00001). In conclusion, environmental factors still play a prominent role in the pathophysiology of the dyslipidemias in the elderly.

• Effects of estrogen/medrogestone therapy on the apoprotein B-containing lipoproteins in postmenopausal women with type 2 diabetes mellitus under satisfactory and non-satisfactory glycemic control.

  Authors: C A Aguilar-Salinas, O Arita-Melzer, L Sauque Reyna, A Lopez, M L Velasco Perez, L E Guillen, F J Gomez-Perez, J A Rull-Rodrigo

  The Israel Medical Association journal : IMAJ. 02/2001; 3(2):137-43.

  BACKGROUND: Information is lacking on the effects of hormone replacement therapy in women with diabetes, especially during moderate chronic hyperglycemia. OBJECTIVES: To study the effects of HRT onBACKGROUND: Information is lacking on the effects of hormone replacement therapy in women with diabetes, especially during moderate chronic hyperglycemia. OBJECTIVES: To study the effects of HRT on the lipid profile and the low density lipoprotein subclass distribution in women with type 2 diabetes under satisfactory and non-satisfactory glycemic control. METHODS: Fifty-four postmenopausal women after a 6 week run-in diet were randomized to receive either placebo (HbA1c < 8%, n = 13; HbA1c > 8%, n = 17) or HRT (HbA1c < 8%, n = 11; HbA1c > 8%, n = 13) for 12 weeks. HRT consisted of cyclical conjugated estrogens 0.625 mg/day plus medrogestone 5 mg/day. At the beginning and at the end of each treatment period the LDL subclass distribution was estimated by density gradient ultracentrifugation. RESULTS: At the baseline and during the study, the HbA1c level was significantly higher in hyperglycemic patients than in the near-normoglycemic controls (baseline 10.2 +/- 2.9 vs. 6.5 +/- 0.7%, P < 0.01). They showed a trend for higher total and LDL cholesterol, triglycerides and lower high density lipoprotein-cholesterol compared to near-normoglycemic controls, as well as significantly higher triglyceride concentrations in very low density lipoprotein, intermediate density lipoprotein and LDL-1 particles and cholesterol content in LDL-1 and -2 particles. HRT decreased LDL-cholesterol in both groups. In the normoglycemic patients a small increase in HbA1c was observed (6.5 +/- 0.7 vs. 7.4 +/- 1%, P = 0.04). In all cases, HRT did not modify the proportion of LDL represented by denser LDLs. CONCLUSIONS: HRT did not modify the LDL subclass distribution, even in the presence of moderate chronic hyperglycemia in women with type 2 diabetes.

• Early-onset type 2 diabetes: metabolic and genetic characterization in the mexican population.

  Authors: C A Aguilar-Salinas, E Reyes-Rodríguez, M L Ordóñez-Sánchez, M A Torres, S Ramírez-Jiménez, A Domínguez-López, J R Martínez-Francois, M L Velasco-Pérez, M Alpizar, E García García, F Gómez-Pérez, J Rull, M T Tusié-Luna

  The Journal of clinical endocrinology and metabolism. 02/2001; 86(1):220-6.

  The objective of this study was to investigate possible defects in the insulin sensitivity and/or the acute insulin response in a group of Mexican patients displaying early-onset type 2 diabetes andThe objective of this study was to investigate possible defects in the insulin sensitivity and/or the acute insulin response in a group of Mexican patients displaying early-onset type 2 diabetes and to evaluate the contribution of mutations in three of the genes linked to maturity-onset diabetes of the young. We studied 40 Mexican patients with an age of diagnosis between 20 and 40 yr in which the insulin sensitivity as well as the insulin secretory response were measured using the minimal model approach. A partial screening for possible mutations in 3 of the 5 genes linked to maturity-onset diabetes of the young was carried out by PCR-single strand conformation polymorphism analysis. A low insulin secretory capacity (AIRg = 68.5 +/- 5 muU/mL.min) and a near-normal insulin sensitivity (3.43 +/- 0.2 min/muU.mL x 10(4)) were found in these patients. Among this group we found two individuals carrying missense mutations in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-->His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive titers for glutamic acid decarboxylase antibodies. Thirty-five percent of cases had insulin resistance; these subjects had the lipid abnormalities seen in the metabolic syndrome. A defect in insulin secretion is the hallmark in Mexican diabetic patients diagnosed between 20 and 40 yr of age. Mutations in either the HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop early-onset diabetes in our population. These particular sequence changes have not been previously reported and therefore represent putative new mutations. Even in the absence of endogenous hyperinsulinemia, insulin resistance is associated with an adverse lipid profile.

• Effects of omapatrilat on blood pressure and insulin sensitivity in an animal model of insulin resistance.

  Authors: C A Aguilar-Salinas, S A Arellano, O Villanueva-Sanchez, G A Magos, L E Guillén-Pineda, R Rodriguez, F J Gómez-Pérez

  Blood pressure. 01/2001; 10(3):164-9.

  OBJECTIVE: To assess the effects of omapatrilat, fosinopril and placebo on blood pressure, plasma insulin, glucose and triglycerides concentrations in Zucker rats, a model for insulin resistance.OBJECTIVE: To assess the effects of omapatrilat, fosinopril and placebo on blood pressure, plasma insulin, glucose and triglycerides concentrations in Zucker rats, a model for insulin resistance. DESIGN: Double blind, parallel, prospective trial. METHODS: Forty-two male obese Zucker (falfa) rats (aged 13-18 week) initially weighing 400-600 g were used for the experiments. Omapatrilat (n = 14), placebo (n = 14) or fosinopril (n = 14) were administrated once daily at 10 micromol/kg oral for 15 days. At baseline and at the end of the study, a tail-cuff blood pressure measurement was performed; an oral glucose tolerance test was done at the end of the study. RESULTS: Omapatrilat and fosinopril resulted in significant lower systolic blood pressure compared to the placebo group (p < 0.001). This parameter was significantly lower in the omapatrilat group compared with fosinopril-treated rats (116+/-9 vs 125+/-4 mmHg, p < 0.05). After an overnight fast, there was no difference in the fasting glucose concentrations among treatment groups. The basal and post-glucose challenge insulin concentrations were lower in the omapatrilat group compared to the placebo group. No difference was observed in the fasting triglycerides concentrations between the treatment groups. CONCLUSIONS: Compared to placebo and fosinopril treatment, omapatrilat results in lower arterial blood pressure in an animal model of insulin resistance. The results suggest that omapatrilat may have a positive effect on insulin sensitivity.

• Efficacy and safety of atorvastatin in hyperlipidemic, type 2 diabetic patients. A 34-week, multicenter, open-label study.

  Authors: C A Aguilar-Salinas, F J Gómez-Pérez, C Posadas-Romero, C Vázquez-Chávez, E Meaney, A Gulías-Herrero, L E Guillén, A Alvarado Vega, E Mendoza Pérez, L Eduardo Romero-Nava, R Angélica Gómez-Díaz, S Salinas-Orozco, R Moguel, G Novoa

  Atherosclerosis. 10/2000; 152(2):489-96.

  Hyperlipidemia is common in type 2 diabetic patients and is an independent risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of once-dailyHyperlipidemia is common in type 2 diabetic patients and is an independent risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of once-daily atorvastatin 10-80 mg for the treatment of hyperlipidemia in type 2 diabetics with plasma low-density lipoprotein cholesterol (LDL-C) levels exceeding 3.4 mmol/l (130 mg/dl). One hundred and two patients met the study criteria and received 10 mg/day atorvastatin. Patients who reached the target LDL-C level of </=2.6 mmol/l (100 mg/dl) maintained the same dosage regimen until they had completed 16 weeks of treatment. Patients not reaching the target LDL-C underwent dose titration to atorvastatin 20, 40 and 80 mg/day at Weeks 4, 8 and 12, respectively. All 88 patients who completed the study attained target LDL-C levels and 52 (59%) of patients achieved the target goal at the starting dose of atorvastatin 10 mg/day. In this group the differences between baseline and post-treatment values for LDL-C were 4.3+/-0.7 mmol/l (166+/-26 mg/dl) versus 2. 2+/-0.4 mmol/l (87+/-14 mg/dl) (P<0.0001), respectively, a decrease of 47%. Similar trends were observed for total cholesterol, triglycerides, very low-density lipoprotein cholesterol and apolipoprotein B levels. The safety profile of atorvastatin in these patients was highly favorable and similar to those reported with other statins. Only one patient withdrew due to a possible drug-related adverse event. These data confirm the marked efficacy and safety of atorvastatin in type 2 diabetic patients with hyperlipidemia and the efficacy of atorvastatin 10 mg in helping patients attain their LDL-C goal.

• The prevalence of obesity and its determinants in urban and rural aging Mexican populations.

  Authors: I Lerman-Garber, A R Villa, C L Martinez, L C Turrubiatez, C A Aguilar-Salinas, V Lucy, B Wong, J C López-Alvarenga, F Gómez-Pérez, L M Gutierrez Robledo

  Obesity research. 08/1999; 7(4):402-6.

  OBJECTIVE: To determine the prevalence of obesity and its association to different variables in urban and rural older Mexican populations. METHODS AND PROCEDURES: A cross-sectional study of threeOBJECTIVE: To determine the prevalence of obesity and its association to different variables in urban and rural older Mexican populations. METHODS AND PROCEDURES: A cross-sectional study of three different Mexican communities. A total of 121 men and 223 women 60 years and older and 93 men and 180 women aged 35 to 59 years old were selected randomly for inclusion in the survey. A personal interview assessed demographic information, personal medical history and functional status and a 24-hour diet recall was obtained. The physical examination included anthropometric and blood pressure measurements. A fasting blood sample was obtained for measurements of lipids, insulin and glucose. RESULTS: Obesity was highly prevalent in women, in individuals from the urban communities and diminished with advancing age. A BMI > or =30 kg/m2 was observed in 23.6% younger vs. 15.6% older adult men (p=0.21) and 28.4% younger vs. 19.7% older adult women (p = 0.06). The association of obesity with other variables was estimated using a stepwise multivariate logistic regression, increased insulin levels [Odds Ratio (OR) 1.68, p=0.006] and living in an urban area (OR 5.90, p<0.007) were variables independently associated to obesity in adult older individuals. In the younger adults, obesity was associated with hypertension (OR 2.74, p<0.0009), higher insulin levels (OR 1.31, p<0.03) and central adiposity (OR 2.97, p = 0.05), these relationship were not observed with gender, distribution of food or alcohol intake or other coronary risk factors. CONCLUSIONS: The present survey confirms the high prevalence of obesity in the Mexican urban population that declines with advanced age. Studies in elderly population must consider the bias produced by increased early mortality in those individuals with a more unfavorable risk profile.

• Acarbose vs. bedtime NPH insulin in the treatment of secondary failures to sulphonylurea-metformin therapy in type 2 diabetes mellitus.

  Authors: J C López-Alvarenga, C A Aguilar-Salinas, M L Velasco Perez, O Arita-Melzer, L E Guillen, B Wong, G Brito, V Mercado, F J Gómez-Pérez, J A Rull-Rodrigo

  Diabetes, obesity & metabolism. 02/1999; 1(1):29-35.

  OBJECTIVE: To evaluate the efficacy of acarbose in the treatment of secondary failures to sulphonylurea-metformin therapy, its comparison against bedtime NPH insulin, and to measure the changes inOBJECTIVE: To evaluate the efficacy of acarbose in the treatment of secondary failures to sulphonylurea-metformin therapy, its comparison against bedtime NPH insulin, and to measure the changes in postprandial metabolism resulting from both treatments. METHODS: One hundred type 2 diabetic patients in a secondary failure were included. The study begun with a run-in diet period of 6 weeks, in which an isocaloric diet was prescribed. Only subjects who continued hyperglycaemic were randomly assigned to placebo and acarbose (n = 17) or bedtime NPH insulin (n = 12). Acarbose (300 mg/day) or placebo were administered using a randomized, double blind, crossover design. Treatment periods of 3 months were separated by a 3-week washout period. Insulin was administered during 3 months. At the beginning and the end of each treatment period, an i.v. glucose tolerance test and a meal test were performed. Safety tests were done every 4 weeks. RESULTS: Acarbose resulted in a small but significant improvement in fasting plasma glucose (13.5 +/- 2.4 vs. 11.3 +/- 3.9 mmol/l, p = 0.05), HbA1c (11.1 +/- 3.4 vs. 10.3 +/- 2.5%, P = 0.3) and in a decreased plasma glucose during the meal test. Bedtime insulin significantly decreased fasting plasma glucose (13.1 +/- 2.9 vs. 8.2 +/- 2.3 mmol/l, p < 0.01), HbA1c (11.7 +/- 2.9 vs. 9.4 +/- 2.7%, p < 0.01) and plasma cholesterol. No change in insulin secretion resulted from insulin and acarbose treatment. CONCLUSIONS: Acarbose decreases blood glucose in secondary failure to sulphonylurea-metformin therapy; however, the decrease is not enough to reach the desired metabolic control. Bedtime NPH insulin is, by far, a more effective alternative.

• Metabolic modes of action of the statins in the hyperlipoproteinemias.

  Authors: C A Aguilar-Salinas, H Barrett, G Schonfeld

  Atherosclerosis. 01/1999; 141(2):203-7.

  Conflicting results have been published during the past few years regarding the physiologic modes of action of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, generally referred to asConflicting results have been published during the past few years regarding the physiologic modes of action of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, generally referred to as statins, using standard doses. Three mechanisms have been described: increased LDL catabolic rate, increased removal of LDL precursors resulting in decreased LDL production and decreased VLDL production. The physiologic effects of statins seem to depend on the underlying pathology of the disorders under therapy. More recent data using either the more potent atorvastatin or larger doses of previously available statins (e.g. simvastatin 80-160 mg/day), suggest that both the potency of the statins and the underlying pathopHysiology are important in determining the predominant physiologic responses of patients. To understand physiologic responses more completely, drug-dose-physiologic response curves of apo B kinetics in various groups of patients are needed. Simultaneous studies of apo B, triglycerides and cholesterol metabolism are also needed and are currently feasible.

• Lack of agreement between the World Health Organization Category of impaired glucose tolerance and the American Diabetes Association category of impaired fasting glucose.

  Authors: F J Gómez-Pérez, C A Aguilar-Salinas, J C López-Alvarenga, J Perez-Jauregui, L E Guillen-Pineda, J A Rull

  Diabetes care. 12/1998; 21(11):1886-8.

  OBJECTIVE: To study the concordance between the 1997 American Diabetes Association (ADA) impaired fasting glucose (IFG) category with the World Health Organization (WHO) impaired glucose toleranceOBJECTIVE: To study the concordance between the 1997 American Diabetes Association (ADA) impaired fasting glucose (IFG) category with the World Health Organization (WHO) impaired glucose tolerance (IGT) status in a population with a high prevalence of diabetes. RESEARCH DESIGN AND METHODS: We analyzed the oral glucose tolerance tests (OGTTs) carried out at the Instituto Nacional de la Nutrición Salvador Zubiran (INNSZ) central laboratory from June to December 1997. We included patients with fasting plasma glucose (FPG) between 60 and 160 mg/dl. The results from the glucose tolerance test were selected as the gold standard. RESULTS: Among the 1,802 glucose tolerance test results available for analysis, 1,706 fulfilled the requirements to be included. Diabetes and IGT were remarkably more frequently diagnosed when the WHO criteria were applied. The new ADA criteria failed to diagnose 69% of WHO diabetic patients and the vast majority of WHO glucose-intolerant subjects. Using the new criteria, 82% were considered normal. Of the IFG subjects, 39% were classified as diabetic and 23% were normal according to the 2-h postchallenge glucose values. Only 37% of the IFG patients were, in fact, glucose intolerant according to the WHO criteria. CONCLUSIONS: Our results clearly show that the 1997 ADA criteria are less sensitive for diagnosing diabetes than OGTT-based WHO criteria. Even more important, there is poor agreement between the WHO category of IGT and the ADA category of IFG.

• The prevalence of diabetes and associated coronary risk factors in urban and rural older Mexican populations.

  Authors: I G Lerman, A R Villa, C L Martinez, L Cervantes Turrubiatez, C A Aguilar-Salinas, B Wong, F J Gómez-Pérez, L M Gutierrez Robledo

  Journal of the American Geriatrics Society. 11/1998; 46(11):1387-95.

  OBJECTIVE: To determine the prevalence of diabetes and examine its association with food intake, anthropometric and metabolic variables, and other coronary risk factors in urban and rural olderOBJECTIVE: To determine the prevalence of diabetes and examine its association with food intake, anthropometric and metabolic variables, and other coronary risk factors in urban and rural older Mexican populations. DESIGN: A cross-sectional study. SETTING: Three Mexican communities (urban areas of medium and low income and a rural area). PARTICIPANTS: A total of 121 men and 223 women aged 60 years and older and 93 men and 180 women aged 35 to 59 years were selected randomly for inclusion in the survey, which was derived from the CRONOS study (Cross-Cultural Research on Nutrition in the Older Adult Study Group) promoted by the European Economic Community. MEASUREMENTS: A personal interview assessed demographic information, personal medical history, and functional status, and a 24-hour diet recall was obtained. A physical examination included anthropometric and blood pressure measurements. A fasting blood sample was obtained for measurements of lipids, insulin, and glucose. RESULTS: Diabetes prevalence was higher in men than in women for all age groups: 16.7% versus 9.5% in younger adults and 30.8% versus 22.8% in older adults. For all age groups, diabetes was more highly prevalent in urban communities. Using a multivariate stepwise logistic regression, variables associated independently with diabetes in older individuals were: gender (male sex: OR = 2.1; P < .009); diminished carbohydrate intake in the diet (OR = 0.77; P < .03); central distribution of adiposity (OR = 1.9; P < .03); and functional disability (OR = 2.3; P < .01). This relationship was not observed with living area, income, education, fiber and alcohol intake, body mass index, or age. Individuals 80 years and older had a diminished atherogenic risk profile. Diabetes in older people was associated significantly with hypertriglyceridemia, impaired functional status, and an increased prevalence of ischemic heart disease; in younger adults diabetes was associated with low density lipoprotein (LDL) hypercholesterolemia, hypertriglyceridemia, and a proportionally higher fat intake. CONCLUSION: This survey confirms the high prevalence of diabetes in the older Mexican population - particularly in men and in individuals living in urban areas - associated with an increased prevalence of other coronary risk factors. Diabetes was associated with higher fat, low carbohydrate, low fiber diets and increased prevalence of central distribution of adiposity. In the older subjects, diabetes was associated significantly with hypertriglyceridemia, impaired functional status, and increased prevalence of ischemic heart disease. A bias produced by early mortality and a survivorship effect must be considered in studies of older individuals. The health situation in the older Mexican population presents a complex problem that needs correct diagnosis and better strategies to benefit those segments of the population at increased risk.