Resistin as a risk factor for all-cause (and cardiovascular) death in the general population.

Serum resistin is a pro-inflammatory cytokine that has been described as a risk factor associated with mortality in several clinical sets including type 2 diabetes. Mortality studies in the general population are needed to find out the risk of death associated to this cytokine. In a follow-up study of a cohort of adult population (n = 6636) in Spain over a period of fifteen years (447 deaths/102,255 person-years), serum resistin measurements and death records were obtained. The risks of all-cause deaths, and deaths from cardiovascular and oncological diseases were estimated. Hazard ratios (HR) and its confidence intervals (CI) were calculated using multivariable Cox models, adjusting the effect of 11 traditional risk factors. The risk of all-cause mortality among participants exposed to the highest quintile of resistin was always higher than among those in the lowest quintile (HR varied between 1.55 when smoking was the adjusted factor [95% CI 1.17-2.05], and 1.68 when the adjusted factor was physical activity [95% CI 1.27-2.21]). The maximally adjusted model, accounting for the effect of all traditional factors, corroborated this higher risk of all-cause mortality among people in the highest resistin quintile (HR = 1.52; 95% CI 1.13-2.05). The effect of resistin was even higher for cardiovascular deaths (HR = 2.14; 95% CI 1.13-4.06), being exceeded only by suffering diabetes (HR = 3.04; 95% CI 1.98-4.69) or previous acute coronary syndrome (HR = 3.67; 95% CI 2.18-6.18). This findings corroborate the role of resistin as a risk factor for all-cause (and cardiovascular) death in the general population.

Myokines, physical activity, insulin resistance and autoimmune diseases.

Myokines are peptides produced and released by myocytes of muscle fibers that influence physiology of muscle and other organs and tissues. They are involved in mediating the beneficial effects that exercise has on health. More than one hundred have been identified and among them are IL6, myostatin, irisin, mionectin and decorin. Physical inactivity leads to an altered response of the secretion of myokines and resistance to them; this leads to a pro-inflammatory state that favors sarcopenia and fat accumulation, promoting the development of cardiovascular diseases, insulin resistance, and diabetes mellitus type 2. Some myokines, including irisin, are responsible for the improvement that exercise produces in many chronic diseases such as type 2 diabetes and cardiovascular diseases, some types of cancer and many autoimmune diseases such as idiopathic inflammatory myopathy, rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease.

Strategies to improve the efficiency of celiac disease diagnosis in the laboratory.

The demand for testing to detect celiac disease (CD) autoantibodies has increased, together with the cost per case diagnosed, resulting in the adoption of measures to restrict laboratory testing. We designed this study to determine whether opportunistic screening to detect CD-associated autoantibodies had advantages compared to efforts to restrict testing, and to identify the most cost-effective diagnostic strategy. We compared a group of 1678 patients in which autoantibody testing was restricted to cases in which the test referral was considered appropriate (G1) to a group of 2140 patients in which test referrals were not reviewed or restricted (G2). Two algorithms A (quantifying IgA and Tissue transglutaminase IgA [TG-IgA] in all patients), and B (quantifying only TG-IgA in all patients) were used in each group, and the cost-effectiveness of each strategy was calculated. TG-IgA autoantibodies were positive in 62 G1 patients and 69 G2 patients. Among those positive for tissue transglutaminase IgA and endomysial IgA autoantibodies, the proportion of patients with de novo autoantibodies was lower (p=0.028) in G1 (11/62) than in G2 (24/69). Algorithm B required fewer determinations than algorithm A in both G1 (2310 vs 3493; p<0.001) and G2 (2196 vs 4435; p<0.001). With algorithm B the proportion of patients in whom IgA was tested was lower (p<0.001) in G2 (29/2140) than in G1 (617/1678). The lowest cost per case diagnosed (4.63 euros/patient) was found with algorithm B in G2. We conclude that opportunistic screening has advantages compared to efforts in the laboratory to restrict CD diagnostic testing. The most cost-effective strategy was based on the use of an appropriate algorithm.

Hemodynamics and metabolism at low versus moderate altitudes.

Despite the higher prevalence of diabetes and hypertension in populations residing at moderate altitudes, mortality in these populations is lower than in populations residing at low altitudes. To examine whether metabolic and hemodynamic differences can explain this apparent paradox, we performed a cross-sectional study of a general population sample recruited in the Canary Islands, Spain (n=6729). We recorded altitude of residence, age, heart rate, blood pressure, body mass index, social class, physical activity, energy intake, alcohol intake, smoking habit, prevalence of type 2 diabetes mellitus and hypertension. In a subsample (n=903), we recorded serum concentration of cholesterol, triglycerides, glucose, C peptide, leptin, soluble leptin receptor (sObR), C-reactive protein, resistin, soluble CD40 ligand (sCD40L), and paraoxonase activity (PON), and we estimated insulin resistance and free leptin index. We found an inverse association between altitude and heart rate (p<0.001), leptin (p<0.001), free leptin index (p<0.001), resistin (p<0.001), and sCD40L (p<0.05) and a direct association between altitude and hypertension (odds ratio=1.29 for altitude >600 m; 95% confidence interval=1.03-1.62), glycemia (p<0.05), C peptide (p<0.001), insulin resistance (p<0.001), sObR (p<0.05), and PON (p<0.05). When social class was included in the multivariate model, the association with PON was no longer significant. In conclusion, individuals residing at moderate altitudes have a lower heart rate and lower serum concentration of total leptin, free leptin, and sCD40L. These differences may partially explain the lower mortality in these populations.

Sex hormones and autoimmunity.

Autoimmune diseases occur more in women than in men, and this may be attributable to the role of estrogens. Androgens promote autoimmune diseases with a profile of type 1 cytokines, such as rheumatoid arthritis, whereas estrogens promote autoimmune diseases with a type 2 cytokine profile, like systemic lupus erythematosus. Both androgens and estrogens regulate the Th1/Th2 balance. Type 1 autoimmune diseases are improved when decrease type 1 cytokines (i.e. during fasting), or when there is a rise in type 2 cytokines (increased estrogens, as in pregnancy). Type 2 autoimmune diseases improve when type 2 cytokines are diminished (decreased estrogen, as in post-partum period) or when type 1 response is stimulated.

Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy.

PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer.

TYMS, MTHFR, p53 and MDR1 gene polymorphisms in breast cancer patients treated with adjuvant therapy.

PURPOSE: The distribution of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms was investigated in 80 consecutive breast cancer patients treated with adjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.55 and (3) 0.45; MTHFR C677T, (C) 0.65 and (T) 0.35; p53 Arg72Pro, (Arg) 0.76 and (Pro) 0.24; MDR1 C3435T, (C) 0.51 and (T) 0.49. MTHFR C677T was found to be a strong predictor of the presence of multifocal tumour (odds ratio, 4.1; 95% CI, 1.1-15.7; P=0.035). CONCLUSION: Our data indicate that breast cancer patients with the C/C variant may present multifocal tumour most frequently.

[Lifestyle and treatment adherence of type 2 diabetes mellitus people in the Canary Islands]. / Estilo de vida y adherencia al tratamiento de la población canaria con diabetes mellitus tipo 2.

BACKGROUND: The Canary Islands population experiences the highest type 2 diabetes (DM2) mortality in Spain. We studied lifestyle, unknown DM2 and treatment adherence in diabetics of these islands. METHODS: Cross-sectional study of 6729 subjects from the general population (age 18-75) that participate in the cohort study "CDC of the Canary Islands". We found out their medical problems, diet, physical activity, medications, smoking, etc. RESULTS: Prevalence of DM2 was 12% in men and 10% in women (p=0.005). The disease was unknown in 22% of men and 9% of women (p < 0.001). Considering unknown DM2, lack of treatment and lack of adherence, 48% of men and 28% of women did not follow a regular treatment. Diabetics' men prevalences of smoking (28%; CI(95%)=23-33) and sedentariness (62%; CI(95%)=56-68) were similar to non diabetic men, but obesity was more frequent in diabetics (45 versus 25%; p < 0.001). Diabetics women showed a higher obesity (54 versus 27%; p < 0.001) and a lower smoking prevalence (11 versus 22%; p < 0,001) than non diabetics, but they presented a similar sedentariness (75%; CI(95%)=70-79). In both sexes, energy intake was lower in diabetics (p < 0.001), but 93% of them (CI(95%)=91-95) showed a high consumption of calories from saturated fat and 69% (CI(95%)=65-72) presented metabolic syndrome. CONCLUSIONS: The Canarian diabetics are a sedentary and obese population that show a high consumption of saturated fats and high prevalence of metabolic syndrome. The proportion of them following regular treatment is low, specially in diabetic men that, in addition, still smoke.

Evaluating new candidate SNPs as low penetrance risk factors in sporadic breast cancer: a two-stage Spanish case-control study.

OBJECTIVES: A polygenic model has been proposed in order to explain the genetic susceptibility to sporadic breast cancer. According to this model, common population variants would be responsible for low to modest effects on the risk of developing the disease. We have carried out a high-throughput SNP genotyping project in order to shed some light on the complex genetic aetiology of non-familial breast cancer. METHODS: Ninety-one genes have been selected because of their implications in several candidate cell pathways for breast cancer. A total of 640 SNPs in these genes were genotyped in a series of 450 consecutive cases and 448 controls from mainland Spain. Promising SNPs were then studied in an independent series of 294 cases and 299 controls from the Canary Islands. RESULTS: In the first case-control series we identified 25 SNPs with P-values below 0.05 (under a 1 df Chi-square test), five of them with P-values below 0.01 (best=0.0008). In the stage 2 Canary Islands series, odd ratios (OR) for two SNPs in HUS1 were in a consistent direction. CONCLUSIONS: SNPs located at the gene HUS1 are good candidates for further investigation in independent association studies and functional assays.