Serum sclerostin and glucose homeostasis: No association in healthy men. Cross-sectional and prospective data from the EGIR-RISC study.

INTRODUCTION: Sclerostin, an inhibitor of bone formation, has emerged as a potential negative regulator of glucose homeostasis. We aimed to investigate if serum sclerostin associates with insulin sensitivity, beta cell function, prediabetes or metabolic syndrome in healthy men. MATERIALS AND METHODS: Serum sclerostin was measured in basal and insulin-stimulated samples from 526 men without diabetes from the RISC cohort study. An OGTT was performed at baseline and after 3 years. An IVGTT and a hyperinsulinaemic-euglycaemic clamp were performed at baseline. Insulin sensitivity was estimated by the oral glucose sensitivity index (OGIS) and the M-value relative to insulin levels. Beta cell function was assessed by the acute and total insulin secretion (ISRtot) and by beta cell glucose sensitivity. RESULTS: Serum sclerostin levels correlated positively with age but were similar in individuals with (n = 69) and without (n = 457) prediabetes or the metabolic syndrome. Serum sclerostin was associated with measures of neither insulin sensitivity nor beta cell function at baseline in age-adjusted analyses including all participants. However, baseline serum sclerostin correlated inversely with OGIS at follow-up in men without prediabetes (B: -0.29 (-0.57, -0.01) p = 0.045), and inversely with beta cell glucose sensitivity in men with prediabetes (B: -13.3 (-26.3, -0.2) p = 0.046). Associations between serum sclerostin and 3-year changes in measures of glucose homeostasis were not observed. Acute hyperinsulinemia suppressed serum sclerostin (p = 0.02), and this reduction correlated with OGIS and ISRtot. CONCLUSIONS: Overall, serum sclerostin was not associated with prediabetes, insulin sensitivity or insulin secretion in healthy men. The inverse relationship between serum sclerostin and insulin sensitivity at follow-up was weak and likely not of clinical relevance. The ability of insulin to reduce sclerostin, possibly promoting bone formation, needs to be clarified.

High prevalence of cardiovascular risk in patients with toxic oil syndrome: a comparative study using the general Spanish population.

BACKGROUND: The objective of this study was to compare current prevalence of major cardiovascular risk factors (CRF) between a cohort of patients affected by the toxic oil syndrome (TOS) epidemic, which occurred in Spain in 1981, and the unaffected Spanish population. METHODS: This was a case-referent study covering 1276 TOS cases and a referent population of 2843 (aged 35-65 years) using data collected from 1996 to 2003. Study variables were high blood pressure, hyperglycemia, dyslipemia, obesity, and metabolic syndrome. Smoking habit, alcohol intake, family and personal history of ischemic heart disease, as well as a personal history of cerebrovascular disease were also assessed in TOS patients. RESULTS: Compared to the general population, TOS patients registered a threefold rise in prevalence of diabetes, a 2.57-fold increase in hypertension, a 1.38-fold increase in total hypercholesterolemia, a 1.20-fold increase in hyper-LDL-cholesterolemia, and a high prevalence of metabolic syndrome (35% versus 25%). Nevertheless, the prevalence of hypo-HDL-cholesterolemia was significantly lower in those affected by TOS. No differences were found for other CRFs. CONCLUSION: Compared to the general population, cases display a much higher prevalence of all major CRFs. However, an increase in HDL-cholesterol protective factor is in evidence for the first time.

[The EPICARDIAN project, a cohort study on cardiovascular diseases and risk factors among the elderly in Spain: methodological aspects and major demographic findings]. / El proyecto EPICARDIAN: un estudio de cohortes sobre enfermedades y factores de riesgo cardiovascular en ancianos españoles: consideraciones metodológicas y principales hallazgos demográficos.

BACKGROUND: Despite a greater incidence of ischemic heart disease among individuals over age 65, most cardiovascular research has been focused on the middle-aged adult population. To date no cohort study on this population have been made in Spain. This study is aimed as reviewing the role and methodology of cohort studies as an epidemiological tool absolutely essential for researching the prevalence and incidence of angina, AMI, stroke and the major cardiovascular risk factors. METHODS: Cohort study in three areas of Spain (Lista district in Madrid), Arevalo (Avila) and Begonte (Lugo). Age and sex stratified random sample by based on the municipal censuses of each area and municipality (n = 5.079). Two-stage initial cohort assessment: home survey structured for the screening ischemic heart disease and classic risk factors (hypertension, dyslipemia, diabetes and smoking habit) and clinical assessment for case confirmation. In the follow-up phase the MONICA project "cold pursuit" method modified for pinpointing and investigating indicent cases was used, employing all of the hospital and primary care clinical records for confirming the cardiovascular event. Data was also requested from the Spanish National Institute of Statistics as to the cause and date of death of the deceased individuals in the cohort. RESULTS: The overall AMI prevalence was 4% (95% CI: 3.4%, 4.5%); definite plus probable AMI being 6.2% (95% CI: 5.5-6.9). The definite AMI prevalence was higher among the mean 6.7% (95% CI: 5.63-7.79) than among the women, 2% (95% CI: 1.51-2.55) (p < 0.001). Hypertension prevalence according to JNCV1 criteria was 68%, hypercholesterolemia 26.4% according to NCEP criteria, diabetes prevalence 13.4% according to WHO criteria, and 11.3% were smokers. The cumulative incidence for a 3.2-year period for nonfatal definite AMI was 1.4% (95% CI: 1.1-1.8); 1.1% (95% CI: 0.74-1.37) probable AMI: 1.17 (IC95%: 0.824-1.48) for fatal definite AMI or death due to AMI and 1.13% (IC 95%: 0.824-1.48) for sudden death. CONCLUSIONS: The elderly population included in this study shows a high prevalence of cardiovascular risk factors, as well as ischemic heart disease incidence rates three times higher than those of the middle-aged adult population in Spain. The risk profile for women is significantly worse than for men, which may be due to the higher death rate at earlier ages among men.