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OBJECTIVE--Antioxidized LDL (anti-oxLDL) antibodies have recently been suggested to be protective against the development of diabetes. We measured the changes in anti-oxLDL antibody levels in the inverse situation of improvement [...]

Background: The intestinal fatty acid-binding protein (FABP2) is involved in the intracellular transport and metabolism of fatty acids and may affect insulin sensitivity and glucose metabolism. Objective: The objective was to study the effect of interaction between the Ala54Thr polymorphism of the FABP2 gene (FABP2) and the type of dietary cooking oil used on peripheral insulin sensitivity in a population from southern Spain. Design: The study was cross-sectional. Anthropometric measurements were obtained for 1226 persons aged 18-65 y selected randomly from the municipal census of Pizarra, Spain. An oral-glucosetolerance test was given to 1020 of these persons. Insulin resistance was measured by homeostasis model assessment. Samples of the cooking oil being used were taken from the kitchens of a random subset of 538 persons. Results: Persons who consumed sunflower oil and who also had the Thr54 variant had higher insulin resistance than did those who consumed olive oil (P = 0.01). We detected an interaction between the Ala54Thr polymorphism and the type of oil consumed that accounted for the variance in insulin resistance (P = 0.02). Conclusions: The effect of dietary fatty acids on the populational pattern of insulin resistance is not independent of the Ala54Thr polymorphism of FABP2. An interaction existed between this polymorphism and the intake of dietary fats in a population with a high intake of monounsaturated fatty acids. KEY WORDS Cross-sectional study, general population, dietary fatty acid, insulin resistance, FABP2, Ala54Thr polymorphism

Glucokinase (GK) is a glycolytic key enzyme that functions as a glucose sensor in the pancreatic β-cell, where it governs glucose-stimulated insulin secretion (GSIS). Heterozygous inactivating mutations in the glucokinase gene (GCK) cause a mild form of diabetes (maturity-onset diabetes of the young [MODY]2), and activating mutations have been associated with a mild form of familial hyperinsulinemic hypoglycemia. We describe the first case of severe persistent hyperinsulinemic hypoglycemia due to a 'de novo' mutation in GCK (Y214C). A baby girl presented with hypoglycemic seizures since the first postnatal day as well as with inappropriate hyperinsulinemia. Severe hypoglycemia persisted even after treatment with diazoxide and subtotal pancreatectomy, leading to irreversible brain damage. Pancreatic histology revealed abnormally large and hyperfunctional islets. The mutation is located in the putative allosteric activator domain of the protein. Functional studies of purified recombinant glutathionyl S-transferase fusion protein of GK-Y214C showed a sixfold increase in its affinity for glucose, a lowered cooperativity, and increased [k.sub.cat]. The relative activity index of GK-Y214C was 130, and the threshold for GSIS predicted by mathematical modeling was 0.8 mmol/l, compared with 5 mmol/l in the wild-type enzyme. In conclusion, we have identified a de novo GCK activating mutation that causes hyperinsulinemic hypoglycemia of exceptional severity. These findings demonstrate that the range of the clinical phenotype caused by GCK mutations varies from complete insulin deficiency to extreme hyperinsulinemia., Failure of the pancreatic β-cell to suppress insulin secretion during hypoglycemia is the pathophysiological basis of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). Mutations in the β-cell sulfonylurea receptor (SUR1) (1), [...]

Background: The family kitchen resembles an uncontrolled laboratory experiment, and some discrepancies in the relation between the risk of hypertension and dietary fat may be partly due to the manipulation to which the fats were subjected. Objective: We investigated whether deterioration in the quality of the cooking oils in the family household contributes to the risk of high blood pressure. Design: The study was cross-sectional. Anthropometric measurements were obtained for 1226 persons aged 18-65 y who were selected randomly from the municipal census of Pizarra, Spain. An oral-glucose-tolerance test was given to 1020 of these persons. Samples of the cooking oil being used were taken from the kitchens of a random subset of 538 persons. The concentrations of polar compounds and polymers were used as markers of the deterioration of the oils. The strength of association between variables was measured by calculating the odds ratio from logistic models. Results: Hypertension was strongly associated with obesity and was influenced by sex, diabetes, and age. The presence of excess polar compounds in the cooking oil and the use of sunflower oil were related to the risk of hypertension, whereas the concentration of monounsaturated fatty acids in the serum phospholipids was negatively related to this risk. These associations remained after inclusion in the models of age, sex, obesity, and the presence of carbohydrate metabolism disorder. Conclusions: The risk of hypertension is positively and independently associated with the intake of cooking oil polar compounds and inversely related to blood concentrations of monounsaturated fatty acids. KEY WORDS Cross-sectional study, general population, hypertension, cooking oils, frying oils, oil polar compounds, monounsaturated fatty acids

El Di@bet.es es un estudio nacional diseñado con el objetivo de estimar la prevalencia de diabetes mellitus y otros factores de riesgo cardiovascular en la población adulta española. Se presenta la prevalencia de hipertensión arterial y en qué grado se reconoce, se trata y se controla.

Advantages of continuous subcutaneous insulin infusion (CSII) over multiple daily injections with glargine (MDI/G) are still uncertain. We compared CSII vs. MDI/G therapy in unselected patients with type 1 diabetes using continuous glucose monitoring (CGSM). The primary end-points were glycaemic control and quality of life (QOL).

The dyslipidemia associated with type 2 diabetes mellitus (T2DM) is an important risk factor for atherosclerotic cardiovascular disease. However, until now little attention has been paid to the role that the intestine might have. The aim of this research was to determine the relation between insulin resistance and intestinal de novo lipogenesis/lipoprotein synthesis in morbidly obese subjects and to study the effect of insulin on these processes. Jejunal mRNA expression of the different genes involved in the intestinal de novo lipogenesis/lipoprotein synthesis was analyzed in three groups of morbidly obese subjects: Group 1 with low insulin resistance (MO-low-IR), group 2 with high insulin resistance (MO-high-IR), and group 3 with T2DM and treatment with metformin (MO-metf-T2DM). In addition, intestinal epithelial cells (IECs) from MO-low-IR were incubated with different doses of insulin/glucose. In Group 2 (MO-high-IR), the jejunal mRNA expression levels of apo A-IV, ATP-citrate lyase (ACLY), pyruvate dehydrogenase (lipoamide) beta (PDHB), and sterol regulatory element-binding protein-1c (SREBP-1c) were significantly higher and acetyl-CoA carboxylase alpha (ACC1) and fatty-acid synthase lower than in Group 1 (MO-low-IR). In Group 3 (MO-metf-T2DM), only the ACLY and PDHB mRNA expressions were significantly higher than in Group 1 (MO-low-IR). The mRNA expression of most of the genes studied was significantly linked to insulin and glucose levels. The incubation of IEC with different doses of insulin and glucose produced a higher expression of diacylglycerol acyltransferase 2, microsomal triglyceride transfer protein, apo A-IV, SREBP-1c, and ACC1 when both, glucose and insulin, were at a high concentration. However, with only high insulin levels, there were higher apo A-IV, PDHB and SREBP-1c expressions, and a lower ACLY expression. In conclusion, the jejunum of MO-high-IR has a decreased mRNA expression of genes involved in de novo fatty-acid synthesis and an increase of genes involved in acetyl-CoA and lipoprotein synthesis. This effect is attenuated by metformin. In addition, the expression of most of the genes studied was found to be regulated by insulin.

En España no se dispone de estudios poblacionales de ámbito nacional en los que se haya evaluado el riesgo cardiovascular total. El objetivo del estudio es describir el riesgo cardiovascular y la consecución de los objetivos terapéuticos según lo establecido en la guía europea de 2012 para la estrategia de prevención de la enfermedad cardiovascular. Se investigaron también las características clínicas (factores de riesgo no clásicos) asociadas a un riesgo moderado.

In the last years, epigenetic processes have emerged as a promising area of complex diseases research. DNA methylation measured in Long Interspersed Nucleotide Element 1 (LINE-1) sequences has been considered a surrogate marker for global genome methylation. New findings have suggested the potential involvement of epigenetic mechanisms in Type 2 diabetes (T2DM) as a crucial interface between the effects of genetic predisposition and environmental influences. Our study evaluated whether global DNA methylation predicted increased risk from T2DM or other carbohydrate metabolism disorders in a cohort study. We used a prospective cohort intervention study and a control group. We collected phenotypic, anthropometric, biochemical, and nutritional information from all subjects. Global LINE-1 DNA methylation was quantified by pyrosequencing technology. Subjects that did not improve their carbohydrate metabolism status showed lower levels of global LINE-1 DNA methylation (63.9 ± 1.7 vs. 64.7 ± 2.4) and they practiced less intense physical activity (5.8% vs. 21.5%). Logistic regression analyses showed a significant association between LINE-1 DNA methylation and metabolic status after adjustment for sex, age, BMI, and physical activity. Our study showed that lower LINE-1 DNA methylation levels were associated with a higher risk metabolic status worsening, independent of other classic risk factors. This finding highlights the potential role for epigenetic biomarkers as predictors of T2DM risk or other related metabolic disorders.

El objetivo de este estudio fue comparar la prevalencia de obesidad, diabetes mellitus y otros factores de riesgo cardiovascular en la región de Andalucía con las prevalencias en el resto de España.

Evaluar el patrón de consumo de ocho grupos de fármacos para el tratamiento de la diabetes mellitus y otros factores de riesgo cardiovascular; identificar en la población española los determinantes sociodemográficos y de salud asociados al consumo de aquellos.

OBJECTIVE: 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. METHODS: 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 ≤7 mg/dl for men or ≤ 6 mg/dl for women. RESULTS: 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). CONCLUSION: Trp64Arg polymorphism of the ADRB3 gene predicted the risk of developing hyperuricemia in this adult population.

The aim of this study was to undertake a prospective study of the changes in certain risk factors for cardiovascular disease occurring during menopause.

Background: Obesity is often associated with hyper-secrection of insulin. Impaired fasting glucose (IFG) has recently been redefined as a fasting plasma glucose of 5.6-6.9 mmol/L. The aim of this study was to determine whether changes in insulin secretion in morbidly obese persons also commence with normal serum glucose levels. Methods: 32 morbidly obese subjects were studied before and after bariatric surgery. Measurements were made of glucose tolerance (KG), insulin sensitivity (SI), first-phase insulin release and the disposition index (DI) from a frequently sampled intravenous glucose tolerance test. Result: In morbidly obese subjects, the SI (P<0.01), DI (P<0.01) and first-phase insulin release (P<0.02) started changing with serum glucose levels considered to be normal (5.00-5.28 mmol/L). KG showed a clear slope according to the baseline glycemia status (P<0.05), and it was significantly related with the DI, both before (r=0.76, P<0.001) and after (r=0.57, P=0.002) surgery. Following surgery, all the variables significantly associated with insulin secretion and insulin sensitivity recovered significantly. The most significant changes occurred in morbidly obese individuals with IFG. Conclusions: Morbidly obese subjects show slopes of insulin sensitivity and insulin secretion in accordance with their baseline serum glucose levels. The fall in first-phase insulin release begins when serum glucose values are considered normal. Morbidly obese persons with the IFG phenotype have a specific pattern of insulin sensitivity and insulin secretion. KG clearly discriminates the clinical phenotypes, depending on baseline serum glucose levels.

OBJECTIVE: The apolipoprotein AI-CIII-AIV cluster has been associated with the response to a urate-lowering diet, and polymorphisms in the apolipoprotein CIII gene have been associated with hyperuricemia and hypertriglyceridemia. We assessed the influence of polymorphisms in the apolipoprotein AI-CIII-AIV cluster on the response to a urate-lowering diet in patients with hyperuricemia. METHODS: A urate-lowering diet was followed for 2 weeks by 64 men with hyperuricemia. Plasma concentrations of triglycerides, cholesterol, glucose, and uric acid, and the uric acid clearance and 24-hour uric acid urinary excretory fraction were measured before and after the diet. The data were analyzed in association with the polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster. RESULTS: After the urate-lowering diet, the plasma levels of triglycerides, cholesterol, glucose, and uric acid and 24-hour uric acid excretion all fell significantly. Paired sample ANOVA showed that the decrease was mainly due to the diet, except for the plasma triglycerides, which were influenced by allele X2 of the XmnI polymorphism of the apolipoprotein AI gene. CONCLUSION: The response of the biological variables to a urate-lowering diet was mainly influenced by diet. Changes in triglycerides were also influenced by the apolipoprotein AI XmnI polymorphism (p = 0.04), suggesting a gene-diet interaction (p = 0.03).

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.

For more than a decade the pedicled island neurovascular flap of the glans penis has been the standard procedure for clitoroplasty in intersex anomalies and in male-to-female genital sex reassignment surgery. Most authors focusing on genitoperineal reconstructions have used the island neurovascular flap of the dorsal shaft of the penis, including a variable-sized dorsal chip of the glans penis as the distal and functional portion of the flap. Although this dorsal glans clitoroplasty technique for neoclitoral reconstruction is well known, it nevertheless deserves scientific revision, with a view to improving several neglected aesthetic and functional points. The authors describe a new method for reconstruction of the neoclitoris in male-to-female transsexuals, the corona glans clitoroplasty. It is based on a modification of the original pedicled island neurovascular flap of the glans penis. The main difference compared with the dorsal glans clitoroplasty is that, distally, this method includes a bifid dorsolateral coronal flap designed in the shape of an open lotus flower or a bull’s horns. Furthermore, a semicircular preputial flap is retained, attached to the bifid coronal flap of the glans, to improve the cosmetic appearance of the vestibulum and avoid growth of hair around the neoclitoris. Finally, a small dorsal flap of the spongiomucosa urethra designed in the shape of a pencil tip is added to improve the cosmetic appearance of the vestibulum between the neoclitoris and the urethral neomeatus. Since October of 1999, the authors have performed more than 30 genital sex reassignment surgeries in male-to-female transsexuals, of whom 16 underwent their technique of corona glans clitoroplasty. The authors describe and discuss the anatomic basis and clinical implications of this technique and its cosmetic and potential functional advantages. They also consider the anatomic differences among four distal designs of the pedicled island neurovascular flap of the glans penis: dorsal, lateral, ventral, and corona glans clitoroplasty in male-to-female transsexuals.

We undertook a systematic evaluation of the lipid, protein, calorie, and fatty acid composition in 35 species of fish, shellfish and molluscs commonly consumed throughout the four seasons of the year in Andalusia, Spain. Using a portion of muscle tissue the following were measured in each study unit: total lipids (extraction using Folch's method and gravimetry), protein concentration (Kjehldal's method), total calories (direct calorimetry), and composition of fatty acids (gas chromatography). The lipid, protein, and different fatty acid concentrations found are presented in table form. There was a high degree of inter-species variability in the concentration of lipids and the various fatty acids. There was also a high degree of intra-species seasonal variability in some cases. The relative proportion of fatty acids was not independent of the total concentration of lipids, independently of the season studied. This systematic study of a large group of species shows that the cataloguing of fish as ‘white’ or ‘blue’ depends especially on the time of year they are captured. For example, in spring the mackerel (Scomber scombrus), a fish considered traditionally to be ‘blue’ (fatty), has the same lipid concentration as the dover sole (Solea vulgaris), commonly considered to be ‘white’ (little fat), and the sea pike (Merluccius merluccius) has a higher lipid concentration in autumn than the jack mackerel (Trachurus trachurus). Even greater differences existed when the fish were classified according to their richness in n-3 fatty acids. These differences in the total lipid concentration and the composition of fatty acids, as well as the inter-relations between them, may, under certain circumstances, be important for the calculation of dietary calories and nutritional values, and may explain the differences found between the various tables of food composition, as well as the divergent results in epidemiological studies on the association between fish in diets and various diseases, such as diabetes or ischaemic cardiopathy.

La miocardiopatía inducida por catecolaminas esuna complicación infrecuente del feocromocitoma.Presentamos un caso de feocromocitoma que cursócon insuficiencia cardíaca preoperatoria. Se comprobódilatación e hipocinesia grave y difusa delventrículo izquierdo por ecocardiografía. La situacióncardiológica del paciente fue estabilizada condigital, diuréticos y captopril. No hubo complicacionesperioperatorias y la evolución postintervenciónha sido satisfactoria, con franca mejoría de lafunción sistólica a 3 y 6 meses, valorada por ecocardiografíay ventriculografía isotópica. Revisamosla fisiopatología y evolución de la miocardiopatíadilatada inducida por catecolaminas.Sugerimos que uno de los mecanismos de adaptaciónempleados en esta entidad puede ser la reservade precarga. La terapéutica convencional de lahipertensión arterial y de la insuficiencia cardíacapuede ser eficaz en el control de los síntomas defallo cardíaco en la miocardiopatía asociada a feocromocitoma.