J M Gómez-Zumaquero

Hospital Regional Universitario Carlos Haya Málaga, Málaga, Andalusia, Spain

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Publications (40)146.29 Total impact

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    ABSTRACT: The serum fatty acid (FA) composition is influenced by dietary fat and the endogenous production of FAs. Stearoyl CoA desaturase 1 (SCD1) is the rate-limiting enzyme catalyzing the synthesis of MUFAs from saturated FAs. Variations in SCD1 activity have been associated with obesity, diabetes, or inflammation. We evaluated the associations between genetic variation of the SCD1 gene, SCD1 activity, intake of oil, and obesity in a population-based prospective study in southern Spain. We collected phenotypic, metabolic, nutritional, and genetic information. The type of dietary fat was assessed from samples of cooking oil taken from the participants' kitchens and analyzed by GC. A total of nine single nucleotide polymorphisms (SNPs) of the SCD1 gene were analyzed by SNPlex technology. We found a significant association between SCD1 genetic variation and enzyme activity in four of nine polymorphisms studied. An interaction between rs10883463 and olive oil intake on the [18:1/18:0] desaturase index was found (p = 0.009). We also showed that genetic variations in the SCD1 gene were associated with obesity. Our results show a relationship between genetic variation of the SCD1 gene, enzyme activity, and the risk of obesity, an association that is not independent of the type of oil consumed.
    Molecular Nutrition & Food Research 08/2013; · 4.31 Impact Factor
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    ABSTRACT: BACKGROUND: A recent study using a rat model found significant differences at the time of diabetes onset in the bacterial communities responsible for type 1 diabetes modulation. We hypothesized that type 1 diabetes in humans could also be linked to a specific gut microbiota. Our aim was to quantify and evaluate the difference in the composition of gut microbiota between children with type 1diabetes and healthy children and to determine the possible relationship of the gut microbiota of children with type 1 diabetes with the glycemic level. METHODS: A case-control study was carried out with 16 children with type 1 diabetes and 16 healthy children. The fecal bacteria composition was investigated by polymerase chain reaction-denaturing gradient gel electrophoresis and real-time quantitative polymerase chain reaction. RESULTS: The mean similarity index was 47.39% for the healthy children and 37.56% for the children with diabetes, whereas the intergroup similarity index was 26.69%. In the children with diabetes, the bacterial number of Actinobacteria and Firmicutes, and the Firmicutes to Bacteroidetes ratio were all significantly decreased, with the quantity of Bacteroidetes significantly increased with respect to healthy children. At the genus level, we found a significant increase in the number of Clostridium, Bacteroides and Veillonella and a significant decrease in the number of Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale group and Prevotella in the children with diabetes. We also found that the number of Bifidobacterium and Lactobacillus, and the Firmicutes to Bacteroidetes ratio correlated negatively and significantly with the plasma glucose level while the quantity of Clostridium correlated positively and significantly with the plasma glucose level in the diabetes group. CONCLUSIONS: This is the first study showing that type 1 diabetes is associated with compositional changes in gut microbiota. The significant differences in the number of Bifidobacterium, Lactobacillus and Clostridium and in the Firmicutes to Bacteroidetes ratio observed between the two groups could be related to the glycemic level in the group with diabetes. Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children. These findings could be useful for developing strategies to control the development of type 1 diabetes by modifying the gut microbiota.
    BMC Medicine 02/2013; 11(1):46. · 6.68 Impact Factor
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    ABSTRACT: Objective:Thyroid hormone receptor-beta resistance has been associated with metabolic traits. THRA gene sequencing of an obese woman (index case) who presented as empirical thyroid hormone receptor-α (THRA) resistance, disclosed a polymorphism (rs12939700) in a critical region involved in TRα alternative processing.Design and subjects:THRA gene variants were evaluated in three independent europid populations (i) in two population cohorts at baseline (n=3417 and n=2265), 6 years later (n=2139) and (ii) in 4734 high cardiovascular risk subjects (HCVR, PREDIMED trial).Results:The minor allele of the index case polymorphism (rs12939700), despite having a very low frequency (4%), was significantly associated with higher body mass index (BMI) (P=0.042) in HCVR subjects. A more frequent THRA polymorphism (rs1568400) was associated with higher BMI in subjects from the population (P=0.00008 and P=0.05) after adjusting for several confounders. Rs1568400 was also strongly associated with fasting triglycerides (P dominant=3.99 × 10(-5)). In the same sample, 6 years later, age and sex-adjusted risk of developing obesity was significantly increased in GG homozygotes (odds ratio 2.93 (95% confidence interval, 1.05-6.95)). In contrast, no association between rs1568400 and BMI was observed in HCVR subjects, in whom obesity was highly prevalent. This might be explained by the presence of an interaction (P <0.001) among the rs1568400 variant, BMI and saturated fat intake. Only when saturated fat intake was high (>24.5 g d(-1)), GG carriers showed a significantly higher BMI than A carriers after controlling for energy intake and physical activity.Conclusions:THRA gene polymorphisms are associated with obesity development. This is a novel observation linking the THRA locus to metabolic phenotypes.International Journal of Obesity advance online publication, 12 February 2013; doi:10.1038/ijo.2013.11.
    International journal of obesity (2005) 02/2013; · 5.22 Impact Factor
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    ABSTRACT: Several evidences indicate that gut microbiota is involved in the control of host energy metabolism. To evaluate the differences in the composition of gut microbiota in rat models under different nutritional status and physical activity and to identify their associations with serum leptin and ghrelin levels. IN A CASE CONTROL STUDY, FORTY MALE RATS WERE RANDOMLY ASSIGNED TO ONE OF THESE FOUR EXPERIMENTAL GROUPS: ABA group with food restriction and free access to exercise; control ABA group with food restriction and no access to exercise; exercise group with free access to exercise and feed ad libitum and ad libitum group without access to exercise and feed ad libitum. The fecal bacteria composition was investigated by PCR-denaturing gradient gel electrophoresis and real-time qPCR. In restricted eaters, we have found a significant increase in the number of Proteobacteria, Bacteroides, Clostridium, Enterococcus, Prevotella and M. smithii and a significant decrease in the quantities of Actinobacteria, Firmicutes, Bacteroidetes, B. coccoides-E. rectale group, Lactobacillus and Bifidobacterium with respect to unrestricted eaters. Moreover, a significant increase in the number of Lactobacillus, Bifidobacterium and B. coccoides-E. rectale group was observed in exercise group with respect to the rest of groups. We also found a significant positive correlation between the quantity of Bifidobacterium and Lactobacillus and serum leptin levels, and a significant and negative correlation among the number of Clostridium, Bacteroides and Prevotella and serum leptin levels in all experimental groups. Furthermore, serum ghrelin levels were negatively correlated with the quantity of Bifidobacterium, Lactobacillus and B. coccoides-Eubacterium rectale group and positively correlated with the number of Bacteroides and Prevotella. Nutritional status and physical activity alter gut microbiota composition affecting the diversity and similarity. This study highlights the associations between gut microbiota and appetite-regulating hormones that may be important in terms of satiety and host metabolism.
    PLoS ONE 01/2013; 8(5):e65465. · 3.73 Impact Factor
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    ABSTRACT: Childhood obesity has grown very fast over recent decades and now it represents a serious public health problem. The number of adipocytes is set in childhood and adolescence and then, an effective understanding of the development of adipose tissue during these periods will help in the prevention of this pathology. The current study aimed to determine which adipose tissue characteristics are related to a high weight Z-score in childhood. The current study included 82 children aged 5-130 months who underwent inguinal hernia surgery. Anthropometric variables were measured, and a nutritional and physical activity questionnaire was completed. Subcutaneous adipose tissue samples, taken during the operation, were analyzed for preadipocyte number, adipocyte volume, fatty acid composition (gas chromatography of FAME), and relative gene expression of various genes (real time PCR). The results showed that children with a higher weight Z-score spend more time in sedentary activities and less time running or involved in active games. SCD-1 activity index, arachidonic/linoleic index, and adipocyte volume were significantly higher in children with a weight Z-score greater than 0. The preadipocyte number and the genetic expression of the studied genes did not differ between the groups. A multiple regression analysis was done to determine which variables were related to the weight Z-score. R2 values indicated that the model which included adipocyte volume, SREBP-1c, SCD-1 expression, and activity index, predicted 59% of the variability in the weight Z-score among the children. The main variables associated with adipocyte volume were PPARγ, Adiponectin, CB1R expressions, as well as the SCD-1 activity and normalized weight. It was concluded that in childhood, the weight Z-score is related to adipocyte volume and adipose tissue gene expression.
    International journal of endocrinology and metabolism. 01/2013; 11(2):82-7.
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    ABSTRACT: Few studies have investigated the effect of dietary polyphenols on the complex human gut microbiota, and they focused mainly on single polyphenol molecules and select bacterial populations. The objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits. Ten healthy male volunteers underwent a randomized, crossover, controlled intervention study. After a washout period, all of the subjects received red wine, the equivalent amount of de-alcoholized red wine, or gin for 20 d each. Total fecal DNA was submitted to polymerase chain reaction(PCR)-denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota. Several biochemical markers were measured. The dominant bacterial composition did not remain constant over the different intake periods. Compared with baseline, the daily consumption of red wine polyphenol for 4 wk significantly increased the number of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, and Blautia coccoides-Eubacterium rectale groups (P < 0.05). In parallel, systolic and diastolic blood pressures and triglyceride, total cholesterol, HDL cholesterol, and C-reactive protein concentrations decreased significantly (P < 0.05). Moreover, changes in cholesterol and C-reactive protein concentrations were linked to changes in the bifidobacteria number. This study showed that red wine consumption can significantly modulate the growth of select gut microbiota in humans, which suggests possible prebiotic benefits associated with the inclusion of red wine polyphenols in the diet. This trial was registered at controlled-trials.com as ISRCTN88720134.
    American Journal of Clinical Nutrition 05/2012; 95(6):1323-34. · 6.50 Impact Factor
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    ABSTRACT: High resolution melting is a post-PCR-based method for detecting DNA sequence variation by measuring changes in the melting of a DNA duplex. Melting of double-stranded DNA molecules is influenced by several factors. We evaluated the influence of the DNA isolation method in the melting curve analysis to detect genetic variations. We isolated DNA from whole blood of 547 subjects by two different methods: Maxwell 16 Instrument and DNA FlexiGene Kit. A fragment of 159 bp was amplified and analyzed by high resolution melting. Those samples that showed a different melting curve pattern were sequenced. Of the samples extracted with the Maxwell 16 Instrument, 42% showed variation compared with 0.18% of the samples extracted with DNA FlexiGene Kit. After sequencing, we showed that all samples extracted with the Maxwell 16 Instrument were false positive except one, which coincided with the only sample that showed variation in those extracted with the DNA FlexiGene Kit. The method used to extract DNA is an important factor to consider in the analysis of melting curves obtained by high resolution melting, as it may influence the melting behaviour of the samples, giving false positive results in the detection of genetic variants.
    Clinica chimica acta; international journal of clinical chemistry 09/2011; 413(1-2):331-3. · 2.54 Impact Factor
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    ABSTRACT: Insulin has several biological functions besides glycaemic control. We investigated and compared the effects of six different commercial insulins on adipocyte cell differentiation, the lipolytic activity of differentiated cells, and the expression levels of genes involved in adipogenesis and associated with insulin activity. 3T3-L1 cells were induced to differentiate with six commercial insulins: glargine, lispro, aspart, detemir, NPH and regular recombinant human insulin (used as control). Cell differentiation, lipolysis and gene expression were measured at day 7 (D7) and day 10 (D10) after induction of differentiation in these cells. The highest values of cell differentiation and lipolysis were found at D10 for all the insulins used. Preadipocyte differentiation differed at both times depending on the insulin used, with detemir insulin being the least adipogenic. The PPARγ mRNA level varied according to the insulin and was a good genetic marker of adipogenesis at D7. Cells treated with glargine insulin showed the highest lipolysis and HSL expression on both days. Gene expression levels of InsR, SREBP-1c and SCD-1 differed depending on the insulin studied. Detemir insulin was the least adipogenic of the insulins tested, whereas treatment with glargine insulin tended to produce the highest lipolysis levels. Under these experimental conditions, the modifications made in commercial insulins to improve glycaemic control also affect adipocyte differentiation, the lipolysis level of differentiated cells, and the expression of different genes that can modify metabolic pathways independently of glucose metabolism.
    European Journal of Clinical Investigation 03/2011; 41(9):979-86. · 3.37 Impact Factor
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    ABSTRACT: As interleukin-6 (IL-6) has an important role in general metabolism with high circulating levels in obesity and other associated diseases, the factors regulating its synthesis and release have been considered possible therapeutic targets and have recently been studied. We examined the influence of three different diets, each having a different fatty acid composition--saturated, monounsaturated or polyunsaturated (coconut oil, olive oil and sunflower oil diets), on IL-6 release from rat adipocytes, and the interaction between diet and other regulatory factors of IL-6 release, such as epinephrine. A group of rats was assigned to one of the three different diets, each with a significantly different concentration of saturated, monounsaturated and polyunsaturated fatty acids. Samples were taken from the omental adipose tissue for measurement of the triacylglycerol fatty acid composition of the tissues and for adipocyte isolation. IL-6 release from adipocytes was measured in vitro, under nonstimulated conditions and also with two concentrations of epinephrine in the medium. Animals fed with the olive oil diet showed lower values of IL-6 release with and without epinephrine stimulation. IL-6 release from adipocytes varied according to the diet, but not according to epinephrine dose. However, a significant interaction was found between the epinephrine dose and the diet in IL-6 release regulation. IL-6 release from adipocytes was markedly regulated by the dietary fatty acid composition, even under epinephrine stimulation, with lower values of IL-6 release in the olive oil diet. The study also showed that epinephrine regulation of IL-6 release was related to the diet.
    International journal of obesity (2005) 03/2010; 34(8):1328-32. · 5.22 Impact Factor
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    ABSTRACT: To study the role of Trp64Arg polymorphism of the ADRB3 gene in the risk of developing hyperuricemia in 1051 subjects from southern Spain, with a followup of 6 years. The inclusion of plasma levels of uric acid as a diagnostic criterion to define the metabolic syndrome is under discussion. Genes responsible for insulin resistance could contribute to the development of hyperuricemia. Previous cross-sectional studies have suggested ADRB3 as a possible candidate gene in the development of hyperuricemia and insulin resistance. A prospective, population-based, cohort study of 1051 persons examined in 1997-98 and reassessed at a second examination 6 years later. The metabolic phenotype was assessed at baseline and again at the followup. Insulin resistance was measured by homeostasis model assessment. The Trp64Arg polymorphism of ADRB3 was detected by real-time polymerase chain reaction. Subjects were considered normouricemic if their serum uric acid levels were <or=7 mg/dl for men or <or= 6 mg/dl for women. Carriers of the Arg64 allele who were normouricemic at baseline had a higher risk of developing hyperuricemia 6 years later (p = 0.017, OR 2.3, 95% CI 1.1-4.6). Multivariate logistic regression analysis showed that the OR of having hyperuricemia at the 6-year followup was significantly associated with the Arg64 allele, after adjusting for age, weight gain, baseline levels of triglycerides, serum uric acid, and insulin resistance (OR 3.1, 95% CI 1.3-7.1). Trp64Arg polymorphism of the ADRB3 gene predicted the risk of developing hyperuricemia in this adult population.
    The Journal of Rheumatology 12/2009; 37(2):417-21. · 3.26 Impact Factor
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    ABSTRACT: Anti-oxidized low-density lipoprotein (LDL) antibodies are associated with the oxidative capacity of plasma, but whether they protect or promote diabetes is unknown. We undertook a prospective study to determine the predictive capacity of anti-oxidized LDL antibodies for the onset of type 2 diabetes mellitus (T2DM). We selected 391 non-diabetic women aged 18-65 years. The subjects were classified as being normal (oral glucose test tolerance normal, OGTT-N), or having impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or T2DM according to their baseline glucose levels and after an OGTT. The same subjects were studied six years later. The levels of anti-oxidized LDL antibodies were classified as above or below the 50th percentile. Of the women who were OGTT-N at the start of the study and who had anti-oxidized LDL antibody levels below the 50th percentile, only 65.1% were still OGTT-N after 6 years versus 79.5% of those who had anti-oxidized LDL antibody levels above the 50th percentile (P = 0.015). Women who had IGT or IFG at the start of the study whose anti-oxidized LDL antibody levels were below the 50th percentile had a relative risk of 9.79 (95% confidence interval, 1.40-68.45) of developing diabetes (P < 0.001). Logistic regression analysis showed that the variables predicting the development of a carbohydrate metabolism disorder in the women after 6 years were body mass index (P < 0.001) and the levels of anti-oxidized LDL antibodies (P = 0.042). Levels of anti-oxidized LDL antibodies are independent predictors for the development of T2DM in women.
    European Journal of Clinical Investigation 09/2008; 38(9):615-21. · 3.37 Impact Factor
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    ABSTRACT: Transsexual persons afford a very suitable model to study the effect of sex steroids on uric acid metabolism. This was a prospective study to evaluate the uric acid levels and fractional excretion of uric acid (FEUA) in a cohort of 69 healthy transsexual persons, 22 male-to-female transsexuals (MFTs) and 47 female-to-male transsexuals (FMTs). The subjects were studied at baseline and 1 and 2 yr after starting cross-sex hormone treatment. The baseline levels of uric acid were higher in the MFT group. Compared with baseline, uric acid levels had fallen significantly after 1 yr of hormone therapy in the MFT group and had risen significantly in the FMT group. The baseline FEUA was greater in the FMT group. After 2 yr of cross-sex hormone therapy, the FEUA had increased in MFTs (P = 0.001) and fallen in FMTs (P = 0.004). In MFTs, the levels of uric acid at 2 yr were lower in those who had received higher doses of estrogens (P = 0.03), and the FEUA was higher (P = 0.04). The FEUA at 2 yr was associated with both the estrogen dose (P = 0.02) and the serum levels of estradiol-17beta (P =0.03). In MFTs, a correlation was found after 2 yr of therapy between the homeostasis model assessment of insulin resistance and the serum uric acid (r = 0.59; P = 0.01). Serum levels of uric acid and the FEUA are altered in transsexuals as a result of cross-sex hormone therapy. The results concerning the MFT group support the hypothesis that the lower levels of uric acid in women are due to estrogen-induced increases in FEUA.
    Journal of Clinical Endocrinology &amp Metabolism 07/2008; 93(6):2230-3. · 6.43 Impact Factor
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    ABSTRACT: The aim of this study was to test the hypothesis of an association between the -30G>A polymorphism of the promoter of the glucokinase gene and the prevalence and incidence of obesity. We studied the -30G>A polymorphism of the glucokinase gene promoter in 981 persons, of whom 866 were seen again 6 years later. All the persons underwent an oral glucose-tolerance test and the BMI (weight/height(2)) was recorded. The -30G>A polymorphism of the glucokinase gene promoter was studied using RFLP-PCR. At the initial study, the probability of having a BMI > or =25 in carriers of the A allele was significantly lower than expected by chance (odds ratio (OR) = 0.63; 95% confidence interval (CI) = 0.456-0.885). In those persons with a BMI > or =30 at the first study, the probability at 6 years of losing weight (reaching a BMI < 30) was greater in carriers of the A allele (OR = 0.22; 95% CI = 0.087-0.576). The increase in weight over these 6 years, taken as a continuous variable, was significantly less only in those persons who were originally obese (P = 0.018). In conclusion, in a population from southern Spain, carriers of the A allele of the -30G>A polymorphism in the promoter of the glucokinase gene had a lower risk for obesity and the likelihood of losing weight was greater in those obese persons who had the A allele (GA or AA).
    Obesity 05/2008; 16(8):1973-5. · 3.92 Impact Factor
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    ABSTRACT: Although various studies have noted fatty-acid-mediated regulation of adipocyte lipolysis, determining the isolated effect of a single fatty acid is more difficult. We examined the influence of dietary oleic acid on adipose cell lipolytic activity and the tissue fat content independently of the variation in other dietary fatty acids. We fed 48 rats with six diets designed so that the oleic acid content was not correlated with the content of any other fatty acid and studied the lipolytic activity and fatty acid content of the tissues. There were no differences in the weight of the animals after the diet. The muscle fat content and the epinephrine-stimulated lipolytic activity varied significantly according to the dietary levels of oleic acid and the tissues, showing a dose-dependent behavior of the dietary oleic acid concentration. The results of this study show that diets rich in oleic acid have a beneficial effect on the regulation of lipid metabolism and body weight homeostasis.
    The Journal of Nutritional Biochemistry 04/2008; 19(11):727-31. · 4.55 Impact Factor
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    ABSTRACT: Few European studies have used an oral glucose tolerance test (OGTT) to examine the incidence of type 2 diabetes. We determined the incidence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes in a population from southern Spain. A population-based cohort study was undertaken in Pizarra, Spain. Baseline data were recorded on age, sex, weight, height, waist and hip circumferences, and diabetes status for 1051 persons, of whom 910 were free of type 2 diabetes (at-risk sample). Of these, 714 completed the 6-year follow-up study. Body mass index, waist-to-hip ratio and weight increase since baseline were calculated. The homeostasis model assessment equations were used to estimate the indices of insulin resistance and beta-cell function. Each person received an OGTT at baseline and after 6 years. Type 2 diabetes developed in 81 people for a total of 4253 person-years, representing an incidence of 19.1 cases per 1000 person-years (95% confidence interval, 15.3-23.6). Age and the presence of obesity, central obesity and carbohydrate metabolism disorders [IFG (cut off = 100 mg dL(-1), capillary blood glucose level), IGT or both] at baseline were significant markers for the onset of type 2 diabetes during follow-up. After adjusting for these variables, multivariate analysis showed weight increase, waist-to-hip ratio and the indices of insulin resistance and beta-cell function were significantly associated with the risk for type 2 diabetes. The incidence of type 2 diabetes in a population from southern Spain is high. It is probably associated with the high prevalence of obesity and weight increase in this population.
    European Journal of Clinical Investigation 03/2008; 38(2):126-33. · 3.37 Impact Factor
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    ABSTRACT: Numerous genes have been associated with the risk for type 2 diabetes mellitus (DM2). In an attempt to understand how specific variants of different genes interact and intervene in the molecular and physiological mechanisms of disorders such as diabetes or insulin resistance, the search for gene-gene interactions is constantly growing. We searched for a possible interaction between two polymorphisms (Trp64Arg of ADRB3 gene and -75G/A of APOA1gene) and the risk for DM2 in a population from southern Spain. A cross-sectional study in southern Spain of 1020 people, aged 18-65 years. All persons underwent a clinical, anthropometrical and biochemical evaluation, including an oral glucose tolerance test (OGTT). Insulin resistance was measured by homeostasis model of assessment (HOMA). The polymorphisms -75G/A of APOA1 and Trp64Arg of ADRB3 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR, respectively. The genotype frequencies of the -75G/A polymorphism of the APOA1 gene were 62.7% GG, 25.7% GA and 11.6% AA, whereas for the Trp64Arg polymorphism of the ADRB3 gene, they were 87.5% Trp/Trp, 11.7% Trp/Arg and 0.8% Arg/Arg. Subjects with both gene variants had a greater odds ratio (OR) of having DM2 [OR = 5.5; 95% confidence interval (CI) = 1.2-23.5] than persons with one or none of the variants, after adjusting for age, sex, body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA-IR). Joint association of allele -75A (APOA1) and allele Arg64 (ADRB3) increase the risk of DM2 in a population from southern Spain.
    Clinical Endocrinology 02/2008; 68(1):102-7. · 3.40 Impact Factor
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    ABSTRACT: It was recently described that the alpha5 and the alpha13 helices of human pancreatic glucokinase play a major role in the allosteric regulation of the enzyme. In order to understand the structural importance of these helices, we have performed site-directed mutagenesis to generate glucokinase derivatives with altered residues. We have analyzed the kinetic parameters of these mutated forms and compared them with wild-type and previously defined activating mutations in these helices (A456V and Y214C). We found two new activating mutations, A460R and Y215A, which increase the affinity of the enzyme for glucose. Our results suggest that substitutions in the alpha5 or the alpha13 helices that favor the closed, active conformation of the enzyme, either by improving the interaction with surrounding residues or by improving the flexibility of the region defined by these two helices, enhance the affinity of the enzyme for glucose, and therefore its performance as a glucose phosphorylating enzyme.
    Protein Science 09/2005; 14(8):2080-6. · 2.74 Impact Factor
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    ABSTRACT: Genes of the Apo AI/CIII/AIV cluster on chromosome 11 have been related to plasma lipid patterns. The close relationship between carbohydrate metabolism and lipid metabolism warrants investigation of the association between this cluster and Type 2 diabetes mellitus. We therefore examined the possible association between polymorphisms of this cluster and Type 2 diabetes mellitus as part of a study of the prevalence of diabetes and the metabolic syndrome in southern Spain. A total of 1224 persons were selected randomly from the town of Pizarra in the province of Malaga, southern Spain. The sample errors for the prevalence of Type 2 diabetes mellitus and the three polymorphisms studied were all < or = 4%. All subjects underwent phenotyping after an oral glucose tolerance test (75 g) (WHO 1998 criteria) and the XmnI and MspI polymorphisms of Apo AI and the SstI polymorphism of Apo CIII were genotyped. Those subjects with the mutated AA genotype of the MspI polymorphism (-75 G-->A) of Apo AI had a greater risk of impaired glucose tolerance [odds ratio (OR) = 1.95, CI = 1.02-3.8, P = 0.05], Type 2 diabetes mellitus, both known (OR = 7.38, CI = 1.3-39.7, P = 0.02) and unknown (OR = 3.7, CI = 1.4-9.9, P = 0.009). This risk was independent of age, sex, obesity, triglyceride level, HDL cholesterol and pattern of insulin resistance. Pending confirmation in prospective studies, the AA genotype of the MspI polymorphism of the Apo AI gene, within the Apo A-I/C-III/A-IV cluster, seems to be a risk factor for Type 2 diabetes mellitus.
    Diabetic Medicine 07/2005; 22(6):782-8. · 3.24 Impact Factor
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    ABSTRACT: Most studies of antibodies to oxidized LDL have been undertaken in patients with different diseases and cardiovascular risk factors. However, very few studies have researched the distribution and determining factors of antibodies to oxidized LDL in the general population. A total of 1,354 persons (817 females and 537 males) aged 5-65 years were included in this study. They were selected randomly from the population census of Málaga, in southern Spain. The females had lower levels of total cholesterol and triglycerides and higher levels of HDL-cholesterol and a very significant increase (P < 0.0001) in levels of anti-oxidized LDL [low density lipoprotein modified by malondialdehyde (MDA-LDL)] antibodies but no difference in levels of immune complexes consisting of LDL and IgG antibodies (anti-LDL immune complex). Younger persons (16-35 years) had higher levels of anti-oxidized LDL (MDA-LDL) antibodies than persons older than 35 years (P = 0.05). Levels of immune complexes were significantly higher (P = 0.05) in persons aged 5-15 years than in persons older than 40 years. A very weak association was found between levels of anti-oxidized LDL (MDA-LDL) antibodies and anti-LDL immune complexes. The higher prevalence of anti-oxidized LDL (MDA-LDL) antibodies in females and young persons is in agreement with studies that found an inverse association between atherosclerosis and the level of these antibodies.
    The Journal of Lipid Research 04/2005; 46(3):452-7. · 4.39 Impact Factor
  • Atherosclerosis Supplements - ATHEROSCLER SUPPL. 01/2005; 6(1):66-66.

Publication Stats

591 Citations
146.29 Total Impact Points

Institutions

  • 1998–2013
    • Hospital Regional Universitario Carlos Haya Málaga
      • Departamento de Endocrinología y Nutrición
      Málaga, Andalusia, Spain
    • Hospital Universitario Reina Sofía
      Cordoue, Andalusia, Spain
  • 2008
    • Hospital Universitario Virgen de la Victoria de Málaga
      Málaga, Andalusia, Spain