The metabolic profile in early rheumatoid arthritis: a high prevalence of metabolic obesity.

The aim of the study was to compare the prevalence of metabolic syndrome (MetS) in early RA patients with age-gender-matched population controls focusing on the presence of MetS in different weight categories. The study group consisted of 91 consecutive patients with early RA and 273 age- and gender-matched controls subjects. MetS was diagnosed according to the National Cholesterol Education Program (NCEP-ATP III) criteria. Mean age in both groups was 52 years, and 72.5 % were female. The prevalence of MetS did not differ between the two groups (35.2 % in RA, 34.1 % in control group). Mean systolic blood pressure in the RA group was 137 mmHg, in control group 131 mmHg, P = 0.01, and diastolic blood pressure 85 versus 81 mmHg, respectively (P < 0.01). We found that 20 of 65 (30.8 %) of RA patients compared to 80 of 152 (52.6 %) of the control subjects with elevated blood pressure received antihypertensive treatment (P < 0.01). When comparing subgroups with normal BMI, the odds of having MetS (being metabolically obese) were higher among early RA subjects (OR 5.6, CI 1.3-23.8). Of the individual components of metabolic syndrome, we found increased prevalence of hypertension (OR 2.8, CI 1.3-6.0) and hyperglycemia (OR 2.9, CI 1.0-8.0) in the RA group. Recognition of abnormal metabolic status among normal-weight RA patients who have not yet developed CVD could provide a valuable opportunity for preventative intervention.

Epigenetic profiling in CD4+ and CD8+ T cells from Graves' disease patients reveals changes in genes associated with T cell receptor signaling.

In Graves' disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. To identify the epigenetic changes involved in GD, we performed a genome-wide analysis of DNA methylation and enrichment of H3K4me3 and H3K27ac histone marks in sorted CD4+ and CD8+ T cells. We found 365 and 3322 differentially methylated CpG sites in CD4+ and CD8+ T cells, respectively. Among the hypermethylated CpG sites, we specifically found enrichment of genes involved in T cell signaling (CD247, LCK, ZAP70, CD3D, CD3E, CD3G, CTLA4 and CD8A) and decreased expression of CD3 gene family members. The hypermethylation was accompanied with decreased levels of H3K4me3 and H3K27ac marks at several T cell signaling genes in ChIP-seq analysis. In addition, we found hypermethylation of the TSHR gene first intron, where several GD-associated polymorphisms are located. Our results demonstrate an involvement of dysregulated DNA methylation and histone modifications at T cell signaling genes in GD patients.

Comparison of the metabolic syndrome risk in valproate-treated patients with epilepsy and the general population in Estonia.

BACKGROUND: No study has explored the risk of metabolic syndrome (MS) in patients with epilepsy treated with valproate (VPA) at the population level. The aim of this study was to compare the risk of MS in VPA-treated patients in Estonia to the risk in the general population. METHODS: This study involved 118 patients with epilepsy (63 men, 55 women) who received VPA monotherapy. MS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Data were compared with the results of a population-based study of the prevalence of MS in the same geographic region (N = 493; 213 men, 280 women). RESULTS: In the multiple logistic regression analysis, after adjustment for age and sex, the risk of MS in VPA-treated patients was not increased compared to the control subjects (odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.59-1.68). VPA-treated patients had higher serum insulin concentrations than control subjects, independent of body mass index (BMI). A positive association was found between MS development and BMI (OR = 1.47; 95% CI, 1.25-1.73) in VPA-treated patients, but there were no associations with the VPA dosage or the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. In control subjects, BMI and HOMA-IR had similar predictive abilities for MS occurrence. In VPA-treated patients, the predictive ability of the HOMA-IR index was significantly lower than that of BMI, with areas under the receiver operating characteristic curves of 0.808 and 0.897 (P = 0.05), respectively. CONCLUSIONS: The risk of MS is not increased among VPA-treated patients with epilepsy in Estonia compared to the general population. The HOMA-IR index likely has a lower predictive ability for MS in VPA-treated patients compared to its predictive ability in the general population.

Obesity, high-molecular-weight (HMW) adiponectin, and metabolic risk factors: prevalence and gender-specific associations in Estonia.

BACKGROUND: The metabolic consequences of obesity are associated with an imbalance of adipocytokines, e.g. adiponectin. However, some obese subjects remain metabolically healthy and have adiponectin levels similar to normal body weight subjects. Current estimates of the prevalence of obesity in Estonia have relied only on self-report data. OBJECTIVES: To estimate the prevalence of obesity in Estonia, to test for associations between HMW adiponectin and metabolic risk factors and to test if HMW adiponectin levels differentiate metabolically healthy and metabolically unhealthy subjects. METHODS: We conducted a population-based cross-sectional multicentre study to gather history, examination and blood test results for 495 subjects aged 20-74. Metabolically healthy subjects were free from hypertension, dyslipidaemia, impaired glucose regulation and insulin resistance. Metabolically unhealthy subjects had at least one of these four metabolic abnormalities. RESULTS: The prevalence of obesity was 29% in men and 34% in women. HMW adiponectin was positively correlated with HDL cholesterol and negatively correlated with triglycerides, obesity, insulin resistance and blood glucose. This effect was driven by metabolically unhealthy subjects in men, but by both metabolically healthy and metabolically unhealthy subjects in women. Metabolically healthy women had higher HMW adiponectin levels than metabolically unhealthy women. 12% of all obese subjects were metabolically healthy, and their HMW adiponectin levels were similar to normal weight subjects. CONCLUSIONS: Obesity is more prevalent in Estonian adults than previously thought. HMW adiponectin levels were associated with various metabolic risk factors in metabolically healthy women but not in metabolically healthy men. For both genders, HMW adiponectin differentiates metabolically healthy obese subjects from metabolically unhealthy obese subjects.

Gender differences in serum high-molecular-weight adiponectin levels in metabolic syndrome.

OBJECTIVE: The objective of this study was to estimate gender-specific associations between metabolic syndrome (MS) and high-molecular-weight (HMW) adiponectin in an Estonian adult population. METHODS: Plasma HMW adiponectin was measured in 458 subjects (191 men) who participated in a population-based cross-sectional multicenter study (n=495) on the prevalence of metabolic disorders in Estonia. MS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: Median HMW adiponectin levels (µg/ml) were significantly lower among all subjects with MS compared with subjects without MS: 2.1 vs 2.8 in men (P=0.002) and 3.1 vs 5.1 in women (P<0.001). In a fully adjusted, logistic regression model containing HMW adiponectin, homeostasis model assessment of insulin resistance (HOMA-IR), BMI, and age, HMW adiponectin was significantly associated with MS only in women. Comparison of HMW adiponectin and HOMA-IR as markers for MS indicated that HOMA-IR predicted MS better than did HMW adiponectin in both genders. However, after adjusting for age and BMI, HOMA-IR was a significantly better predictor only in men. HMW adiponectin and HOMA-IR predicted the presence of MS at the same level in women. Areas under the receiver operating characteristic curves for HMW adiponectin and HOMA-IR were 0.833 vs 0.88 in men (P=0.02) and 0.897 vs 0.907 in women (P=0.5). CONCLUSIONS: These data suggest that the association between low HMW adiponectin levels and presence of MS might be stronger in women compared with men.

Metabolic syndrome in estonia: prevalence and associations with insulin resistance.

Recently, it has been suggested that metabolic syndrome should be considered a premorbid condition in younger individuals. We evaluated the prevalence of metabolic syndrome in Estonia and compared the characteristic profiles between morbid metabolic syndrome (previously established diabetes, hypertension, or dyslipidaemia) and premorbid metabolic syndrome subgroups. Our study was a cross-sectional, population-based sample of the general population in Estonia aged 20-74 years (n = 495). Metabolic syndrome was diagnosed by National Cholesterol Education Program Adult Treatment Panel III criteria. Insulin resistance was estimated using the homeostasis model assessment (HOMA-IR). The crude and weighted prevalence of metabolic syndrome was 27.9% and 25.9%, respectively. Despite being significantly younger, the premorbid subgroup showed similar levels of insulin resistance as the morbid subgroup (mean HOMA-IR ± SD 2.73 ± 1.8 versus 2.97 ± 2.1, P = 0.5). The most important attribute of metabolic syndrome is insulin resistance, which already characterises metabolic syndrome in the early stages of its metabolic abnormalities.