Diferencias de género en la mortalidad de personas con diabetes tipo 2: Estudio Asturias 2018 / Gender differences in the mortality of people with type 2 diabetes: Asturias Study 2018

OBJETIVO: Investigar la influencia del sexo en la mortalidad según la presencia o ausencia de diabetes mellitus tipo 2 (DM2) y otros factores de riesgo cardiovascular en la cohorte del Estudio Asturias. MÉTODO: El Estudio Asturias (iniciado en 1998) es un estudio de cohortes observacional, prospectivo, de una muestra representativa de la población asturiana de entre 30 y 75 años. Se dividió la población en grupos según la presencia o ausencia de DM2 y el sexo para valorar el control de los factores de riesgo cardiovascular. Además, conociendo el estatus vital de la cohorte 18 años después del inicio del estudio, se analizaron las diferencias en causas de mortalidad según las categorías anteriores. RESULTADOS: En 1998 iniciaron el estudio 1034 personas, de las cuales 561 eran mujeres (54,25%) y 473 eran hombres (45,75%). Padecían diabetes 131 (12,66%; 75 varones y 56 mujeres). Las mujeres con DM2 presentaron una hazard ratio (HR) para mortalidad total de 1,64 (intervalo de confianza del 95% [IC95%]: 0,97-2,77), y los hombres de 1,63 (IC95%: 1,07-2,50); para mortalidad cardiovascular, la HR fue de 3,06 (IC95%: 1,44-6,47) en las mujeres y de 1,49 (IC95%: 0,64-3,46) en los hombres. La tasa de mortalidad para las personas con DM2 en ambos sexos fue más alta que para las personas sin DM2. CONCLUSIONES: Las mujeres con DM2 tienen un riesgo de fallecer por causas cardiovasculares tres veces mayor que las mujeres sin DM2. Deberían implementarse estrategias de tratamiento en las mujeres con esta condición

OBJECTIVE: To investigate the influence of gender on mortality according to the presence or absence of type 2 diabetes mellitus (DM2) and other cardiovascular risk factors in the Asturias Study cohort. METHOD: The Asturias Study (started in 1998) is an observational, prospective cohort study of a representative sample of a population of Asturias aged 30-75 years. The population was divided into groups according to the presence or absence of DM2 and according to gender to assess control of cardiovascular risk factors. In addition, aware of the vital status of the cohort 18 years after the beginning of the study, we analyzed differences in causes of mortality according to the previous categories. RESULTS: In 1998, 1034 people started the study, 561 women (54.25%) and 473 men (45.75%). Of these, 131 (12.66%) had diabetes (75 men and 56 women). The women with T2D presented a hazard ratio (HR) for total mortality of 1.64 (95% confidence interval [95%CI]: .97-2.77), which was 1.63 (95%CI: 1.07-2.50) for the men and, for cardiovascular mortality, 3.06 (95%CI: 1.44-6.47) for the females, versus 1.49 (95%CI: 0.64-3.46) for the males. The mortality rate for people with T2D of both sexes was higher than for people without T2D. CONCLUSIONS: Women with T2D have a risk more than three times higher than women without diabetes of dying from cardiovascular causes. We should implement treatment strategies in women with this condition

[Gender differences in the mortality of people with type 2 diabetes: Asturias Study 2018]. / Diferencias de género en la mortalidad de personas con diabetes tipo 2: Estudio Asturias 2018.

OBJECTIVE: To investigate the influence of gender on mortality according to the presence or absence of type 2 diabetes mellitus (DM2) and other cardiovascular risk factors in the Asturias Study cohort. METHOD: The Asturias Study (started in 1998) is an observational, prospective cohort study of a representative sample of a population of Asturias aged 30-75 years. The population was divided into groups according to the presence or absence of DM2 and according to gender to assess control of cardiovascular risk factors. In addition, aware of the vital status of the cohort 18 years after the beginning of the study, we analyzed differences in causes of mortality according to the previous categories. RESULTS: In 1998, 1034 people started the study, 561 women (54.25%) and 473 men (45.75%). Of these, 131 (12.66%) had diabetes (75 men and 56 women). The women with T2D presented a hazard ratio (HR) for total mortality of 1.64 (95% confidence interval [95%CI]: .97-2.77), which was 1.63 (95%CI: 1.07-2.50) for the men and, for cardiovascular mortality, 3.06 (95%CI: 1.44-6.47) for the females, versus 1.49 (95%CI: 0.64-3.46) for the males. The mortality rate for people with T2D of both sexes was higher than for people without T2D. CONCLUSIONS: Women with T2D have a risk more than three times higher than women without diabetes of dying from cardiovascular causes. We should implement treatment strategies in women with this condition.

Correction: Mortality risk in adults according to categories of impaired glucose metabolism after 18 years of follow-up in the North of Spain: The Asturias Study.

[This corrects the article DOI: 10.1371/journal.pone.0211070.].

Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function.

During adipogenesis, preadipocytes' cytoskeleton reorganizes in parallel with lipid accumulation. Failure to do so may impact the ability of adipose tissue (AT) to shift between lipid storage and mobilization. Here, we identify cytoskeletal transgelin 2 (TAGLN2) as a protein expressed in AT and associated with obesity and inflammation, being normalized upon weight loss. TAGLN2 was primarily found in the adipose stromovascular cell fraction, but inflammation, TGF-ß, and estradiol also prompted increased expression in human adipocytes. Tagln2 knockdown revealed a key functional role, being required for proliferation and differentiation of fat cells, whereas transgenic mice overexpressing Tagln2 using the adipocyte protein 2 promoter disclosed remarkable sex-dependent variations, in which females displayed "healthy" obesity and hypertrophied adipocytes but preserved insulin sensitivity, and males exhibited physiologic changes suggestive of defective AT expandability, including increased number of small adipocytes, activation of immune cells, mitochondrial dysfunction, and impaired metabolism together with decreased insulin sensitivity. The metabolic relevance and sexual dimorphism of TAGLN2 was also outlined by genetic variants that may modulate its expression and are associated with obesity and the risk of ischemic heart disease in men. Collectively, current findings highlight the contribution of cytoskeletal TAGLN2 to the obese phenotype in a gender-dependent manner.-Ortega, F. J., Moreno-Navarrete, J. M., Mercader, J. M., Gómez-Serrano, M., García-Santos, E., Latorre, J., Lluch, A., Sabater, M., Caballano-Infantes, E., Guzmán, R., Macías-González, M., Buxo, M., Gironés, J., Vilallonga, R., Naon, D., Botas, P., Delgado, E., Corella, D., Burcelin, R., Frühbeck, G., Ricart, W., Simó, R., Castrillon-Rodríguez, I., Tinahones, F. J., Bosch, F., Vidal-Puig, A., Malagón, M. M., Peral, B., Zorzano, A., Fernández-Real, J. M. Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function.

Mortality risk in adults according to categories of impaired glucose metabolism after 18 years of follow-up in the North of Spain: The Asturias Study.

People who develop type 2 diabetes (T2D) are known to have a higher mortality risk. We estimated all-cause, cardiovascular, and cancer mortality-risks in our patient cohort according to categories of impaired glucose metabolism. This 18-year retrospective analysis included a region-wide, representative sample of a population aged 30-75 years. Age- and sex-stratified hazard ratios (HRs) were calculated for 48 participants with diagnosed T2D, 83 with undiagnosed T2D (HbA1c ≥6.5%, fasting glycemia ≥126 mg/dL, or glycemia after 75 g glucose load ≥200 mg/dL); 296 with prediabetes (HbA1c 5.7%-6.4%, fasting glycemia 100-125 mg/dL, or glycemia after 75 g glucose load 140-199 mg/dL), and 607 with normoglycemia. Over 18,612 person-years, 32 individuals with undiagnosed T2D, 30 with diagnosed T2D, 62 with prediabetes, and 80 with normoglycemia died. Total sample crude mortality rate (MR) was 10.96 deaths per 1,000 person-years of follow-up. MR of the diagnosed T2D group was more than 3-times higher and that of newly diagnosed T2D was 2-times higher (34.72 and 21.42, respectively) than total sample MR. Adjusted HR for all-cause mortality was 2.02 (95% confidence interval 1.29-3.16) and 1.57 (95% CI 1.00-2.28) in the diagnosed T2D group and the newly diagnosed T2D group, respectively. Adjusted HR for cardiovascular mortality in the T2D group was 2.79 (95% CI 1.35-5.75); this risk was greatly increased in women with T2D: 6.72 (95% CI 2.50-18.07). In Asturias, age- and sex-standardized all-cause mortality is more than 2-times higher for adults with T2D than for adults without T2D. The HR for cardiovascular mortality is considerably higher in T2D women than in normoglycemic women.

Genetic variations of the bitter taste receptor TAS2R38 are associated with obesity and impact on single immune traits.

SCOPE: Changes in genetic variations affecting the taste receptor, type 2, member 38 (TAS2R38) may identify the interacting mechanism leading to obesity and potential associations with proteins partaking in innate immunity, such as surfactant protein D (SPD) and mannan-binding lectin (MBL). METHODS AND RESULTS: We evaluated haplotypes of the bitter-taste receptor TAS2R38 in an identification sample of 210 women in different weight conditions, including anorexia nervosa and obesity. The association with SPD and MBL was tested in an independent sample picturing general population (n = 534). The relationship with obesity was validated in an extended final sample of 1319 participants. In the sample comprised of women in extreme weight conditions, increased obesity was identified in AVI/AVI subjects (OR = 2.5 [1.06-6.11], p = 0.035). In the sample picturing general population, increased SPD and MBL concentrations were found in nonsmoking AVI carriers. In this cohort, smoking and obesity blunted associations between TAS2R38 haplotypes and SPD and MBL. In the extended sample, the association of AVI/AVI haplotypes with increased obesity was also identified (OR = 1.4 [0.99/1.85], p = 0.049), being more robust in subjects aged <40 years (OR = 1.9 [1.06/3.42], p = 0.031). CONCLUSION: Current data reinforce the impact of TAS2R38 gene on phenotypic and clinical outputs affecting obesity, showing significant associations with extreme weight conditions (i.e., obesity and anorexia nervosa), and changes in both olfactory capacity and immune traits.

Circulating irisin levels are positively associated with metabolic risk factors in sedentary subjects.

INTRODUCTION: A physically active life-style plays an independent role in the protection against type 2 diabetes and cardiovascular diseases. Irisin, a novel exercise-induced myokine, activates thermogenesis in rodents through increasing beige fat cells abundance within white fat. We aimed to investigate circulating irisin levels in association with the degree of physical activity and various metabolic parameters in humans. METHODS: Circulating irisin levels (ELISA) and metabolic parameters were analyzed in 428 subjects (195 men/233 women). Participants were classified according to their self-reported physical activity and to their area of residence. RESULTS: Circulating irisin levels were higher in active than in sedentary subjects (p = 0.006). Rural inhabitants showed higher circulating irisin levels than urban subjects (p < 0.0001). The increase in irisin levels related to an active lifestyle was only observed in rural citizens (p = 0.014). Among sedentary participants, irisin levels were positively associated with metabolic risk factors (BMI, fasting insulin, HOMA and fasting triglycerides). The area of residence (ß = - 0.592, p = < 0.0001) contributed independently to circulating irisin levels variance after controlling for age, gender, BMI, HOMAIR, triglycerides and physical activity. CONCLUSIONS: In sedentary participants, circulating irisin levels were positively associated with parameters related to an increased cardiometabolic risk. The present study confirmed that an active lifestyle increases circulating irisin levels, but only among subjects living in a rural environment. Area of residence might be a determinant of irisin levels.

Common genetic variants of surfactant protein-D (SP-D) are associated with type 2 diabetes.

CONTEXT: Surfactant protein-D (SP-D) is a primordial component of the innate immune system intrinsically linked to metabolic pathways. We aimed to study the association of single nucleotide polymorphisms (SNPs) affecting SP-D with insulin resistance and type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We evaluated a common genetic variant located in the SP-D coding region (rs721917, Met(31)Thr) in a sample of T2D patients and non-diabetic controls (n = 2,711). In a subset of subjects (n = 1,062), this SNP was analyzed in association with circulating SP-D concentrations, insulin resistance, and T2D. This SNP and others were also screened in the publicly available Genome Wide Association (GWA) database of the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). RESULTS: We found the significant association of rs721917 with circulating SP-D, parameters of insulin resistance and T2D. Indeed, G carriers showed decreased circulating SP-D (p = 0.004), decreased fasting glucose (p = 0.0002), glycated hemoglobin (p = 0.0005), and 33% (p = 0.002) lower prevalence of T2D, estimated under a dominant model, especially among women. Interestingly, these differences remained significant after controlling for origin, age, gender, and circulating SP-D. Moreover, this SNP and others within the SP-D genomic region (i.e. rs10887344) were significantly associated with quantitative measures of glucose homeostasis, insulin sensitivity, and T2D, according to GWAS datasets from MAGIC. CONCLUSIONS: SP-D gene polymorphisms are associated with insulin resistance and T2D. These associations are independent of circulating SP-D concentrations.

Targeting the association of calgranulin B (S100A9) with insulin resistance and type 2 diabetes.

Calgranulin B (S100A9) was recognized as a candidate type 2 diabetes (T2D) gene in the genomic profiling of muscle from a rodent model of T2D and identifying the human orthologs of genes localized in T2D susceptibility regions. Circulating and S100A9 expressions in muscle and adipose tissue, isolated fat cells, and mouse models were evaluated. A common 5'-upstream single-nucleotide polymorphism (SNP; rs3014866) for S100A9 was analyzed, as well as the effects of weight loss and treatments in vitro with recombinant S100A9. S100a9 expression was increased in muscle of diabetic mice (1.6-fold, p = 0.002), and in muscle from subjects with impaired glucose tolerance (∼4-fold, p = 0.028; n = 34). The rs3014866 SNP was associated with circulating S100A9 and the risk of T2D, having TT carriers at 28 % (p = 0.03) lower risk (n = 1,450). Indeed, increased circulating S100A9 (∼4-fold, p = 0.03; n = 206) and subcutaneous (2-fold, p = 0.01) and omental (1.4-fold, p = 0.04) S100A9 gene expressions (n = 83) in TT carriers run in parallel to decreased fasting glucose and glycated hemoglobin. Accordingly, metformin led to increased S100A9 mRNA in ex vivo-treated adipose tissue explants (n = 5/treatment). Otherwise, obese subjects showed a compensatory increase in circulating and S100A9 expressions in adipose (n = 126), as further demonstrated by decreased levels after diet- (-34 %, p = 0.002; n = 20) and surgery-induced (-58 %, p = 0.02; n = 8) weight loss. Lipopolysaccharide led to increased S100A9 in adipose from mice (n = 5/treatment) while recombinant S100A9 downregulated inflammation in adipocytes (n = 3/treatment). Current findings support the strategy of testing differentially expressed genes in mice and human orthologs associated with T2D. The increased S100A9 reported for obesity and insulin resistance may be envisioned as a compensatory mechanism for inflammation.

Factors determining weight gain in adults and relation with glucose tolerance.

OBJECTIVE: Modifications in lifestyle, diet and certain clinical events are major contributors for the high prevalence of obesity. The aim of this study was to assess factors associated with weight gain in a population of Spanish adults. DESIGN: The study was undertaken in two population-based cohorts from the north and the south of Spain (baseline and after 6 years). The Asturias Study, in the north, included 1034 persons aged 30-75 years, of whom 701 were reassessed. The Pizarra Study, in the south, included 1226 persons aged 18-65 years, of whom 783 were re-evaluated. Both studies involved a nutritional questionnaire, a physical examination and an oral glucose tolerance test (OGTT). RESULTS: During the follow-up, 32.3% of the participants lost weight, 34.5% gained fewer than 4 kg and 33.2% gained more than 4 kg. Weight gain was greater in persons younger than 50 years and in those with an initial body mass index below 30. Weight gain was associated with a greater incidence of type 2 diabetes mellitus (T2DM) and abnormal glucose tolerance, whereas weight loss in persons with these disorders was associated with a normal OGTT 6 years later. Persons who took less exercise and those who reported a higher daily calorie intake experienced greater weight gain. CONCLUSION: The longitudinal changes in weight affect the development of T2DM and abnormal glucose tolerance. The weight is a dynamic phenomenon affected by several social customs.

Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes.

OBJECTIVE: Increased circulating calprotectin has been reported in obese subjects but not in association with measures of insulin resistance and type 2 diabetes (T2D). The main aim of this study was to determine whether calprotectins in plasma and urine are associated with insulin resistance. DESIGN: We performed both cross-sectional and longitudinal (diet-induced weight loss) studies. METHODS: Circulating calprotectin concentrations (ELISA), other inflammatory markers, homeostasis model assessment of insulin resistance (HOMA-IR), and parameters of glucose and lipid metabolism were evaluated in 298 subjects (185 with normal (NGT) and 62 with impaired (IGT) glucose tolerance and 51 T2D subjects). Calprotectin was also evaluated in urine samples from 71 participants (50 NGT and 21 subjects with IGT). Insulin sensitivity (S(I), Minimal Model) was determined in a subset of 156 subjects, and the effects of weight loss were investigated in an independent cohort of obese subjects (n=19). RESULTS: Circulating calprotectin was significantly increased in IGT-T2D (independently of BMI) and positively associated with HOMA-IR, obesity measures, inflammatory markers, and parameters of glucose and lipid metabolism. Similar findings were reported for calprotectin concentrations in urine. In the subset of subjects, the association of calprotectin with S(I) was independent of BMI and age. In fact, S(I) together with C-reactive protein contributed to 27.4% of calprotectin variance after controlling for age and blood neutrophils count. Otherwise, weight loss led to decreased circulating calprotectin in parallel to fasting glucose and HOMA-IR. CONCLUSION: These findings suggest that circulating and urinary concentrations of calprotectin are linked to chronic low-grade inflammation and insulin resistance beyond obesity.

[Glucose tolerance and plasma testosterone concentrations in men. Results of the Asturias Study]. / Tolerancia a la glucosa y concentraciones plasmáticas de testosterona en varones. Resultados del Estudio Asturias.

BACKGROUND AND OBJECTIVE: Studies in men have demonstrated a correlation between serum concentrations of androgens and sex hormone binding globulin (SHBG) with the presence of impaired glucose tolerance, diabetes and metabolic syndrome. The aim of this study was to evaluate circulating levels of total testosterone, SHBG, and bioavailable testosterone in the cohort of the Asturias Study and their association with the degree of glucose tolerance and metabolic syndrome. PATIENTS AND METHODS: The study population consisted of 282 men aged 36 to 85 years old with normal concentrations of total testosterone. The degree of glucose tolerance and the presence of metabolic syndrome were evaluated. RESULTS: Serum concentrations of testosterone and bioavailable testosterone were negatively correlated with age, body mass index, waist circumference, blood glucose, glycated hemoglobin levels and insulin. Serum concentrations of total testosterone, bioavailable testosterone and SHBG were lower in men with glucose intolerance or diabetes than in those with normal glucose tolerance. After multivariate analysis, age and total testosterone levels were independent predictors of the presence of diabetes or glucose intolerance. The risk of glucose intolerance or diabetes mellitus was over 2.5 times higher in men with total testosterone levels in the lowest quartile than in those with total testosterone in the top quartile. CONCLUSIONS: In this general population sample from Asturias, men with lower plasma concentrations of total testosterone--even when within the normal range--have an increased risk of glucose intolerance or diabetes, regardless of age and body mass index.

Tolerancia a la glucosa y concentraciones plasmáticas de testosterona en varones. Resultados del Estudio Asturias / Glucose tolerance and plasma testosterone concentrations in men. Results of the Asturias Study

Antecedentes y objetivo Diversos estudios realizados en varones han demostrado la existencia de una correlación entre las concentraciones séricas de andrógenos así como de proteína transportadora de hormonas sexuales (sex hormone binding globulin o SHBG), y la presencia de alteraciones de la tolerancia a la glucosa, diabetes y síndrome metabólico. El objetivo de este estudio fue evaluar las concentraciones séricas de testosterona total, SHBG y testosterona biodisponible en la cohorte del Estudio Asturias, y su asociación con el grado de tolerancia a la glucosa y el síndrome metabólico. Pacientes y métodos Se estudiaron 282 varones adultos de 36 a 85 años de edad con concentraciones séricas normales de testosterona total, evaluándose tanto su grado de tolerancia a la glucosa como la presencia o no de síndrome metabólico. Resultados Las concentraciones en suero de testosterona y testosterona biodisponible se correlacionaron negativamente con la edad, el índice de masa corporal, el perímetro de cintura, la glucemia, las concentraciones de hemoglobina glucosilada y la insulinemia. Los hombres con intolerancia a la glucosa o diabetes mellitus tenían concentraciones en suero de testosterona total, SHBG y testosterona biodisponible inferiores a las de los que tenían tolerancia normal a la glucosa. Tras el análisis multivariable, la edad y las concentraciones de testosterona (..) (AU)

Background and objective Studies in men have demonstrated a correlation between serum concentrations of androgens and sex hormone binding globulin (SHBG) with the presence of impaired glucose tolerance, diabetes and metabolic syndrome. The aim of this study was to evaluate circulating levels of total testosterone, SHBG, and bioavailable testosterone in the cohort of the Asturias Study and their association with the degree of glucose tolerance and metabolic syndrome. Patients and methods The study population consisted of 282 men aged 36 to 85 years old with normal concentrations of total testosterone. The degree of glucose tolerance and the presence of metabolic syndrome were evaluated. Results Serum concentrations of testosterone and bioavailable testosterone were negatively correlated with age, body mass index, waist circumference, blood glucose, glycated hemoglobin levels and insulin. Serum concentrations of total testosterone, bioavailable testosterone and SHBG were lower in men with glucose intolerance or diabetes than in those with normal glucose tolerance. After multivariate analysis, age and total testosterone levels were independent predictors of the presence of diabetes or glucose intolerance. The risk of glucose intolerance or diabetes mellitus was over 2.5 times higher in men with total testosterone levels in the lowest quartile than in those with total testosterone in the top quartile. Conclusions In this general population sample from Asturias, men with lower plasma concentrations of total testosterone – even when within the normal range – have an increased risk of glucose intolerance or diabetes, regardless of age and body mass index (AU)

Surfactant protein d, a marker of lung innate immunity, is positively associated with insulin sensitivity.

OBJECTIVE: Impaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations. RESEARCH DESIGN AND METHODS: Serum SP-D was evaluated in four different cohorts. The cross-sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in two cohorts, the cross-sectional relationship with lung function in one cohort, and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in one prospective cohort. RESULTS: In the cross-sectional studies, serum SP-D concentration was significantly decreased in subjects with obesity and type 2 diabetes (P = 0.005) and was negatively associated with fasting and postload serum glucose. SP-D was also associated with A1C, serum lipids, insulin sensitivity, inflammatory parameters, and plasma insulinase activity. Smoking subjects with normal glucose tolerance, but not smoking patients with type 2 diabetes, showed significantly higher serum SP-D concentration than nonsmokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r = 0.54, P = 0.034). In the longitudinal study, fasting serum SP-D concentration decreased significantly after weight loss (P = 0.02). Moreover, the main components of cortisol and SP-D rhythms became synchronous after weight loss. CONCLUSIONS: These findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity, and insulin resistance.

Environmental and genetic factors influence the relationship between circulating IL-10 and obesity phenotypes.

Interleukin-10 (IL-10) is a centrally operating anti-inflammatory cytokine that plays a crucial role in the regulation of the innate immune system. It has strong inactivating properties on the inflammatory host response and has been related with viral persistence. We aimed to evaluate the association among circulating IL-10, obesity phenotypes, IL-10 and IL-10R1 gene polymorphisms, and the environmental exposure to viral infection. IL-10 -819C/T gene promoter and IL-10 receptor-1 -243A/G gene polymorphisms were studied in 760 subjects, whereas the former was also investigated in a replication study of 676 subjects. The association of circulating IL-10 levels (enzyme-linked immunosorbent assay) with the serum IgG against adenoviruses and enteroviruses was evaluated in a subset of 189 subjects. Circulating levels of IL-10 were increased in obese people and were positively associated with weight, BMI, waist, waist-to-hip ratio, fat mass, systolic pressure, and, interestingly, the titer of adenoviruses and enteroviruses. Obese subjects with adenovirus titer over the median had the highest circulating IL-10 concentration. Both obesity and adenovirus titer were independently associated with IL-10 variance. Nonmorbid obese T carriers for the -819CT IL-10 gene polymorphism had significantly higher BMI and waist circumference, and those with normal fasting glucose had increased fasting triglycerides. G carriers for the -536AG IL-10R1 gene polymorphism had higher systolic and diastolic pressures, and IL-10 levels; and obese G carriers had an increased waist-to-hip ratio. In summary, circulating IL-10 levels were associated not only with obesity status but also with genetic factors and with the exposure to environmental pathogens.

Mortality risk in spanish adults with diagnosed diabetes, undiagnosed diabetes or pre-diabetes. The Asturias study 1998-2004.

INTRODUCTION AND OBJECTIVES: Although type-2 diabetes is a well-known cause of death, the mortality associated with undiagnosed diabetes and early-stage dysglycemia has not been clearly determined. METHODS: This study included 1015 individuals aged 30-75 years who took part in the first phase of the Asturias study (1998-1999). Participants completed a questionnaire and underwent a physical examination and an oral glucose tolerance test (OGTT). All deaths that occurred in the cohort within 6 years of follow-up (i.e. December 1998 to December 2004) were recorded. RESULTS: Participants were divided into four groups according to the condition indicated by their OGTT result in the first phase of the study: normoglycemia, pre-diabetes, undiagnosed diabetes or diagnosed diabetes (World Health Organization 1999 criteria). A total of 42 deaths were recorded during follow-up. With normoglycemic individuals acting as a control group, multivariate analysis showed that the relative risk of mortality was 2.5 (95% CI, 1-6.3) in the group with diagnosed diabetes, 2.7 (95% CI, 1.1-6.7) in the group with undiagnosed diabetes and 1.6 (95% CI, 0.7-4) in the group with pre-diabetes. CONCLUSIONS: Both individuals with diagnosed diabetes and those with undiagnosed diabetes had a risk of mortality around 2.5-3 times greater than individuals with normoglycemia. Those with pre-diabetes also had increased mortality relative to the control group, though the difference was not significant.

Riesgo de mortalidad en diabetes diagnosticada, diabetes no diagnosticada y prediabetes en población adulta española. Estudio Asturias 1998-2004 / Mortality risk in spanish adults with diagnosed diabetes, undiagnosed diabetes or pre-diabetes. The Asturias Study 1998–2004

Introducción y objetivos. Aunque la diabetes mellitus DM tipo 2 es una causa establecida de mortalidad, el riesgo de mortalidad asociado a DM no diagnosticada y a estadios previos de disglucemia no está claramente definido. Métodos. El estudio incluyó a 1.015 individuos de 30-75 años de edad que participaron en la primera fase del Estudio Asturias (1998-1999), realizando encuesta, exploración física y SOG. Se registraron los fallecimientos en la cohorte durante 6 años de seguimiento (diciembre de 1998 a diciembre de 2004). Resultados. Se clasificó a los sujetos en cuatro grupos según el resultado de la SOG en la primera fase del estudio: normoglucemia, prediabetes, DM ignorada y DM conocida (criterios de la OMS 1999). Se registraron 42 muertes durante el seguimiento. Respecto al grupo control con normoglucemia, el riesgo relativo (RR) de mortalidad en el modelo multivariable fue 2,5 (intervalo de confianza [IC] del 95%, 1-6,3) en el grupo con DM conocida, RR = 2,7 (IC del 95%, 1,1-6,7) en el grupo con DM ignorada y RR = 1,6 (IC del 95%, 0,7-4) en el grupo con prediabetes. Conclusiones. Tanto los individuos con DM conocida como los que tenían DM no diagnosticada presentaron un riesgo de mortalidad alrededor de 2,5-3 veces superior al de los individuos con normoglucemia. En individuos con prediabetes también se encontró un incremento de mortalidad frente al grupo control, aunque no estadísticamente significativo (AU)

Introduction and Objectives. Although type-2 diabetes is a well-known cause of death, the mortality associated with undiagnosed diabetes and early-stage dysglycemia has not been clearly determined. Methods. This study included 1015 individuals aged 30-75 years who took part in the first phase of the Asturias study (1998-1999). Participants completed a questionnaire and underwent a physical examination and an oral glucose tolerance test (OGTT). All deaths that occurred in the cohort within 6 years of follow-up (ie December 1998 to December 2004) were recorded. Results. Participants were divided into four groups according to the condition indicated by their OGTT result in the first phase of the study: normoglycemia, pre-diabetes, undiagnosed diabetes, or diagnosed diabetes (World Health Organization 1999 criteria). A total of 42 deaths were recorded during follow-up. With normoglycemic individuals acting as a control group, multivariate analysis showed that the relative risk of mortality was 2.5 (95% CI, 1-6.3) in the group with diagnosed diabetes, 2.7 (95% CI, 1.1-6.7) in the group with undiagnosed diabetes, and 1.6 (95% CI, 0.7-4) in the group with pre-diabetes. Conclusions. Both individuals with diagnosed diabetes and those with undiagnosed diabetes had a risk of mortality around 2.5-3 times greater than individuals with normoglycemia. Those with pre-diabetes also had increased mortality relative to the control group, though the difference was not significant. multivariate analysis showed that the relative risk of mortality was 2.5 (95% CI, 1-6.3) in the group with diagnosed diabetes, 2.7 (95% CI, 1.1-6.7) in the group with undiagnosed diabetes and 1.6 (95% CI, 0.7-4) in the group with pre-diabetes. Conclusions. Both individuals with diagnosed diabetes and those with undiagnosed diabetes had a risk of mortality around 2.5-3 times greater than individuals with normoglycemia. Those with pre-diabetes also had increased mortality relative to the control group, though the difference was not significant (AU)

Val1483Ile in FASN gene is linked to central obesity and insulin sensitivity in adult white men.

The Val1483Ile polymorphism in the human fatty acid synthase (FASN) gene is located within the interdomain region of the FASN close to the two dynamic active centers of the FASN enzyme and putatively affects FASN action. We aimed to evaluate the association of this polymorphism with obesity phenotypes, insulin sensitivity, and adipose tissue FASN activity in adult white subjects. The polymorphism was evaluated in association with metabolic variables in two independent studies: in a case-control study of 457 men (229 with normal glucose tolerance (NGT) and 228 with altered glucose tolerance (AGT)); and in 600 population-based NGT subjects (274 men and 326 women). Adipose tissue FASN activity was analyzed using the method of Nepokroeff. The Ile variant was associated with a lower waist-to-hip ratio (WHR) and a lower increase in weight over a 7-year period in NGT men. In a subset of 147 men, carriers of the Ile variant showed significantly increased insulin sensitivity. BMI (P < 0.001), WHR (P = 0.03), and Val1483Ile (P = 0.03), contributed independently to 37% of insulin sensitivity variance. In men from the population-based study, the Ile variant was associated with a lower BMI, WHR, fasting glucose, and systolic blood pressure compared with carriers of the Val variant. In agreement with these results, the adipose tissue FASN activity was significantly lower in subjects with the Ile variant (P = 0.01). In summary, adult white men with the Ile 1483 variant of the FASN gene seem protected from developing central obesity through decreased adipose tissue FASN activity.

Does the new American Diabetes Association definition for impaired fasting glucose improve its ability to predict type 2 diabetes mellitus in Spanish persons? The Asturias Study.

In 2003, the American Diabetes Association reduced the lower limit defining impaired fasting glucose (IFG) to 100 mg/dL. The aim of this study was to analyze the impact of this change in the definition of IFG in a low-risk white population from northern Spain. The Asturias Study is a prospective, population-based survey of diabetes and cardiovascular risk factors. The baseline examination was carried out between 1998 and 1999 when 1034 individuals (age range, 30-75 years) were randomly selected to determine the prevalence of type 2 diabetes mellitus and prediabetes in the Principality of Asturias (northern Spain). In 2004 to 2005, these same subjects were invited for a follow-up examination. All participants without known diabetes underwent an oral glucose tolerance test both at baseline and follow-up. Application of the new American Diabetes Association definition resulted in 3 times more persons having IFG. The incidence rates of diabetes were 3.8, 19.5, and 58.0 per 1000 person-years in subjects with initial FPG values <100, 100 to 109, and 110 to 125 mg/dL, respectively. Inclusion of persons with an intermediate risk in the 100- to 109-mg/dL zone to the definition of IFG changed its positive predictive value, specificity, and sensitivity to predict diabetes from 36.5%, 94.5%, and 43.2% to 19.9%, 77.3%, and 75%, respectively. Receiver operating characteristics curve analysis including all the baseline fasting plasma glucose levels from 64 to 125 mg/dL depending on their ability to predict diabetes showed that the point closest to the ideal of 100% sensitivity and 100% specificity was 100 mg/dL. In conclusion, this study indicated that lowering the cutoff point for IFG optimizes its ability to predict diabetes in this Spanish population. The addition of other risk factors such as impaired glucose tolerance, hypertriglyceridemia, and overweight to IFG can stratify diabetes risk better.

Population-based incidence of type 2 diabetes in northern Spain: the Asturias Study.

OBJECTIVE: The aim of this study was to define the incidence of type 2 diabetes in a low-risk Caucasian population in northern Spain and its association with various risk factors. RESEARCH DESIGN AND METHODS: The Asturias Study is a prospective, population-based survey of diabetes and cardiovascular risk factors. The baseline examination was carried out during 1998-1999 when 1,034 individuals, aged 30-75 years, were randomly selected to determine the prevalence of type 2 diabetes and pre-diabetes in the Principality of Asturias (northern Spain). In 2004-2005, these same subjects were invited for a follow-up examination; 700 participated. This study includes only those individuals who did not have diabetes at baseline. We used the World Health Organization 1999 criteria to classify glucose metabolism at both baseline and follow-up. RESULTS: The incidence of diabetes adjusted for the age and sex structure of Asturias was 10.8 cases/1,000 person-years (95% CI 8.1-14.8). The incidence rates were 5 cases/1,000 person-years in individuals with normoglycemia, 21 cases/1,000 person-years in individuals with isolated impaired glucose tolerance (IGT), 34.7 cases/1,000 person-years in individuals with isolated impaired fasting glucose (IFG), and 95.2 cases/1,000 person-years in individuals with combined IFG-IGT. Stepwise multiple logistic regression analysis showed that, together with fasting plasma glucose (FPG) and 2-h plasma glucose, which were the strongest predictors of diabetes, triglycerides and BMI were also independently associated with progression to diabetes. CONCLUSIONS: In this 6-year prospective population-based study, we found an incidence of type 2 diabetes of 10.8 cases/1,000 person-years. Both FPG and 2-h plasma glucose were strongly predictive of diabetes, and their effect was additive.