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.

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.

Autoantibody detection with indirect immunofluorescence on HEp-2 cells: starting serum dilutions for systemic rheumatic diseases.

Antinuclear antibodies (ANA) are determined, among other reasons, to identify samples which need a second test to detect the associated specificities. Our aim was to evaluate the clinical and economic impact generated by using an initial dilution for ANA of 1:160. We analyzed all samples for which ANA, anti-ENA and anti-dsDNA were requested over a 1-year period. ANA were detected by indirect immunofluorescence. Anti-ENA were analyzed with a combination of techniques. Anti-dsDNA were detected by radioimmunoassay. Cost analysis was performed by calculating the difference between two cut-offs (ANA 1:40 and 1:160). A total of 13,233 samples were processed for ANA, of which 59.9% were positive with the 1:40 cut-off and 39.2% with the 1:160 cut-off. At ANA titer 1:40, 0.2% of the samples were anti-ENA-positive and 2.2% were anti-dsDNA positive. Only ANA dilutions of 1:160 and higher showed significantly increased positive predictive value for anti-ENA (1.5 versus 0.2, p=0.029) and anti-dsDNA (8.3 versus 2.2, p<0.001) compared to the 1:40 titer. With the 1:160 cut-off, 16.6% fewer ANA tests, 41.8% fewer anti-ENA determinations and 36.4% fewer anti-dsDNA tests would have been needed. The average saving was 0.87 cost-units per sample (1 unit=2.06euro). We conclude that setting the starting dilution for ANA at 1:160 avoids unnecessary studies, increases the positive predictive values of ANA for anti-ENA and anti-dsDNA, and generates clinical and economic benefits.

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.

[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.

A simple clinical score for type 2 diabetes mellitus screening in the Canary Islands.

AIM: To develop a straightforward risk score for type 2 diabetes (DM2) screening to use in clinical practice. METHODS: A sample of 6237 adult inhabitants of the Canary Islands (Spain) was randomly divided into two subgroups: one yielded data used to develop the instrument, and the other yielded data used for validation testing. Performance of the instrument was compared in persons with clinically diagnosed DM2 and undiagnosed diabetes. The risk score, calculated by multivariate logistic regression, included the potential risk variables that yielded the highest odds ratio in the univariate analysis. A cut-off point for screening purposes was established at a 99% negative predictive value. RESULTS: In men, variables included in the risk score were age, waist/height ratio, familial antecedents of diabetes, and systolic blood pressure (ROC curve 0.837, 95% CI: 0.803-0.871). In women, the risk score contained the same variables plus gestational diabetes history (ROC curve 0.874, 95% CI: 0.847-0901). Excluding systolic blood pressure from the score had no significant effect on the area under the curve. This instrument resulted valid only for people aged less than 55 years. CONCLUSIONS: This simple risk score for DM2 would be easy to apply in clinical practice.