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.

Austerity Policies and Mortality in Spain After the Financial Crisis of 2008.

OBJECTIVES: To analyze mortality in Spain and the United States before and after these countries implemented divergent policies in response to the financial crisis of 2008. METHODS: We examined mortality statistics in both countries in the years 2000 to 2015. Spain started austerity policies in 2010. We compared differences in mortality ratios, on the basis of trends and effect size analysis. RESULTS: During 2000 to 2010, overall mortality rates (r = 0.98; P < .001; Cohen's d = -0.228) decreased in both countries. In 2011, this trend changed abruptly in Spain, where observed mortality surpassed expected mortality by 29% in 2011 and by 41% in 2015. By contrast, observed mortality surpassed expected mortality in the United States by only 8% in 2015. As the mortality statistics diverged, the effect size greatly increased (d = 7.531). During this 5-year period, there were 505 559 more deaths in Spain than the expected number, while in the United States the difference was 431 501 more deaths despite the 7-fold larger population in the United States compared with Spain. CONCLUSIONS: The marked excess mortality in 2011 to 2015 in Spain is attributable to austerity policies.

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.

On the problem of type 2 diabetes-related mortality in the Canary Islands, Spain. The DARIOS Study.

AIMS: To compare diabetes-related mortality rates and factors associated with this disease in the Canary Islands compared with other 10 Spanish regions. METHODS: In a cross-sectional study of 28,887 participants aged 35-74 years in Spain, data were obtained for diabetes, hypertension, dyslipidemia, obesity, insulin resistance (IR), and metabolic syndrome. Healthcare was measured as awareness, treatment and control of diabetes, dyslipidemia, and hypertension. Standardized mortality rate ratios (SRR) were calculated for the years 1981 to 2011 in the same regions. RESULTS: Diabetes, obesity, and hypertension were more prevalent in people under the age of 64 in the Canary Islands than in Spain. For all ages, metabolic syndrome and insulin resistance (IR) were also more prevalent in those from the Canary Islands. Healthcare parameters were similar in those from the Canary Islands and the rest of Spain. Diabetes-related mortality in the Canary Islands was the highest in Spain since 1981; the maximum SRR was reached in 2011 in men (6.3 versus the region of Madrid; p<0.001) and women (9.5 versus Madrid; p<0.001). Excess mortality was prevalent from the age of 45 years and above. CONCLUSIONS: Diabetes-related mortality is higher in the Canary Islands population than in any other Spanish region. The high mortality and prevalence of IR warrants investigation of the genetic background associated with a higher incidence and poor prognosis for diabetes in this population. The rise in SRR calls for a rapid public health policy response.

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.

Leptin and altitude in the cardiovascular diseases.

OBJECTIVE: The lower mortality from coronary ischemic disease in populations living at high altitude has been related to an increase of high-density lipoprotein (HDL)-cholesterol at altitude. Leptin has been proposed as a cardiovascular risk factor. We investigated whether leptin varies according to the altitude at which people live. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional study of the first 889 people enrolled in a cohort study in the Canary Islands, Spain. The relationship among serum leptin, altitude, obesity, and other cardiovascular risk factors was analyzed by bivariate and multivariate tests. RESULTS: Leptin levels showed an inverse correlation to altitude expressed in meters (r = -0.10). Obese subjects had this leptin-altitude association (r = -0.19), but they also had a direct correlation of leptin to HDL-cholesterol (r = 0.27) and an inverse correlation of leptin to the total cholesterol-to-HDL-cholesterol ratio (r = -0.34), triglycerides (r = -0.29), apolipoprotein B (r = -0.21), and glycemia (r = -0.19). Nonobese subjects had only the leptin-altitude association (r = -0.11). The final regression model included altitude as predictor. Other associated variables were gender, physical activity, BMI, age, smoking (reducing leptin independently of BMI), alcohol, heart rate, and income. DISCUSSION: Serum leptin level decreases when altitude increases, and this association could help to explain the lower cardiovascular mortality rate at high altitude. However, because in obese subjects there is a direct association of leptin with HDL-cholesterol and an inverse association with the lipid atherogenic fractions, we suggest the hypothesis of different roles for bound and free leptin, with free leptin being a cardiovascular protective factor in obese people.

Arthritis in mice: allogeneic pregnancy protects more than syngeneic by attenuating cellular immune response.

OBJECTIVE: We tested the hypothesis that collagen induced arthritis benefits more from allogeneic pregnancy than syngeneic pregnancy. METHODS: Arthritis was induced in female B10.RIII (H-2r) mice by injecting bovine type II collagen. Female mice were subsequently paired, one group with q-haplotype males (B10.Q) and the other with r-haplotype males (B10.RIII). The effect of q- and r-haplotype was measured by determining the acute phase reactant serum amyloid A (m-SAA), bovine anti-collagen type II antibodies (a-CBII), and the ratio of CD4/CD8 T lymphocytes during pregnancy and after delivery. Clinical assessment of arthritis was also performed. RESULTS: The number of mice with maximum severity of clinical arthritis was significantly higher in the syngeneic group (11/20 vs 5/21; p = 0.04). Although we noted that in the allogeneic group the females had had a significantly higher level of a-CBII during pregnancy (p = 0.02), we also found that the ratio of CD4/CD8 was higher in the syngeneic group even if it was measured during (p = 0.04) or after gestation (p = 0.05). Taking into account all the cases of arthritis initiated in the post-gestational period there was no difference in m-SAA or in a-CBII between the 2 groups, but the ratio of CD4/CD8 was higher in the syngeneic group measured during (p = 0.03) or post gestation (p = 0.02). CONCLUSION: Allogeneic pregnancy benefits more than syngeneic pregnancy by attenuating the cellular immune response, and the ratio of CD4/CD8 indicates the attenuation of cellular immunity when measured during gestation or post partum.