New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

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Främjande faktorer för egenvård hos personer med typ 2-diabetes

SAMMANFATTNING Typ 2-diabetes ökar i nästan hela världen med ohälsa och höga samhällskostnader som följd. Stora delar av diabetesvården utförs i form av egenvård, det vill säga medvetna självständiga handlingar utförda av individen själv för att reglera och förbättra den egna hälsan, bidra till ökat välbefinnande och bibehålla integritet. Syftet med litteraturstudien var att undersöka vad vuxna personer med typ 2-diabetes beskriver som främjande för egenvård. Metoden som användes var en allmän litteraturstudie med inriktning mot studier utförda i Norden. Datainsamlingen har skett via databaserna PubMed och Cinahl och vid dataanalysen ingick resultatet av 12 artiklar med kvalitativa metoder där meningsbärande enheter i resultaten tolkades och kondenserades till teman och subteman. Resultatet som framträdde vid analysen gav 4 teman och 3 subteman som beskriver hur kunskap ger kontroll och trygghet samt beskriver socialt stöd, professionellt stöd och balans mellan krav och förutsättningar som främjande för egenvård. Slutsatsen visar att överensstämmelse finns mellan det som förordas avseende patientutbildning och egenvård i riktlinjer för diabetesvård, annan forskning, diabeteslitteratur och resultatet av föreliggande litteraturstudie

Främjande faktorer för egenvård hos personer med typ 2-diabetes

SAMMANFATTNING Typ 2-diabetes ökar i nästan hela världen med ohälsa och höga samhällskostnader som följd. Stora delar av diabetesvården utförs i form av egenvård, det vill säga medvetna självständiga handlingar utförda av individen själv för att reglera och förbättra den egna hälsan, bidra till ökat välbefinnande och bibehålla integritet. Syftet med litteraturstudien var att undersöka vad vuxna personer med typ 2-diabetes beskriver som främjande för egenvård. Metoden som användes var en allmän litteraturstudie med inriktning mot studier utförda i Norden. Datainsamlingen har skett via databaserna PubMed och Cinahl och vid dataanalysen ingick resultatet av 12 artiklar med kvalitativa metoder där meningsbärande enheter i resultaten tolkades och kondenserades till teman och subteman. Resultatet som framträdde vid analysen gav 4 teman och 3 subteman som beskriver hur kunskap ger kontroll och trygghet samt beskriver socialt stöd, professionellt stöd och balans mellan krav och förutsättningar som främjande för egenvård. Slutsatsen visar att överensstämmelse finns mellan det som förordas avseende patientutbildning och egenvård i riktlinjer för diabetesvård, annan forskning, diabeteslitteratur och resultatet av föreliggande litteraturstudie

A five-year prospective study of spinal radiographic progression and its predictors in men and women with ankylosing spondylitis

Background: Knowledge about predictors of new spinal bone formation in patients with ankylosing spondylitis (AS) is limited. AS-related spinal alterations are more common in men; however, knowledge of whether predictors differ between sexes is lacking. Our objectives were to study spinal radiographic progression in patients with AS and investigate predictors of progression overall and by sex. Methods: Swedish patients with AS, age (mean +/- SD) 50 +/- 13 years, were included in a longitudinal study. At baseline and at 5-year follow up, spinal radiographs were graded according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Predictors were assessed by questionnaires, spinal mobility tests and blood samples. Results: Of 204 patients included, 166 (81%) were re-examined and 54% were men. Men had significantly higher mean mSASSS at baseline and higher mean increase in mSASSS than women (1.9 +/- 2.8 vs. 1.2 +/- 3.3; p = 0.005) More men than women developed new syndesmophytes (30% vs. 12%; p = 0.007). Multivariate logistic regression analyses with progression &gt;= 2 mSASSS units over 5 years or development of new syndesmophytes as the dependent variable showed that presence of baseline AS-related spinal radiographic alterations and obesity (OR 3.78, 95% CI 1.3 to 11.2) were independent predictors of spinal radiographic progression in both sexes. High C-reactive protein (CRP) was a significant predictor in men, with only a trend seen in women. Smoking predicted progression in men whereas high Bath Ankylosing Spondylitis Metrology Index (BASMI) and exposure to bisphosphonates during follow up (OR 4.78, 95% CI 1.1 to 20.1) predicted progression in women. Conclusion: This first report on sex-specific predictors of spinal radiographic progression shows that predictors may partly differ between the sexes. New predictors identified were obesity in both sexes and exposure to bisphosphonates in women. Among previously known predictors, baseline AS-related spinal radiographic alterations predicted radiographic progression in both sexes, high CRP was a predictor in men (with a trend in women) and smoking was a predictor only in men

Which measuring site in ankylosing spondylitis is best to detect bone loss and what predicts the decline : results from a 5-year prospective study

Background: Studies have shown increased prevalence of osteoporosis and increased risk for vertebral fractures in patients with ankylosing spondylitis (AS). Measurements of bone mineral density (BMD) in the lumbar spine anterior-posterior (AP) projection may be difficult to interpret due to the ligamentous calcifications, and the lateral projection might be a better measuring site. Our objectives were to investigate BMD changes after 5 years at different measuring sites in patients with AS and to evaluate disease-related variables and medications as predictors for BMD changes. Methods: In a longitudinal study, BMD in Swedish AS patients, 50 +/- 13 years old, was measured with dual-energy x-ray absorptiometry (DXA) at the hip, the lumbar spine AP and lateral projections, and the total radius at baseline and after 5 years. Patients were assessed with questionnaires, blood samples, and spinal radiographs for grading of AS-related alterations in the spine with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and assessment of vertebral fractures by the Genant score. Multiple linear regression analyses were used to investigate predictors for BMD changes. Results: Of 204 patients included at baseline, 168 (82%) were re-examined after 5 years (92 men and 76 women). BMD decreased significantly at the femoral neck and radius and increased significantly at the lumbar spine, both for AP and lateral projections. Mean C-reactive protein during follow-up predicted a decrease in the femoral neck BMD (change in %, beta = -0.15, p = 0.046). Use of bisphosphonates predicted an increase in BMD at all measuring sites (p &lt; 0.001 to 0.013), except for the total radius. Use of tumor necrosis factor inhibitors (TNFi) predicted an increase in AP spinal BMD (beta = 3.15, p = 0.012). Conclusion: The current study (which has a long follow-up, many measuring sites, and is the first to longitudinally assess the lateral projection of the spine in AS patients) surprisingly showed that lateral projection spinal BMD increased. This study suggests that the best site to assess bone loss in AS patients is the femoral neck and that inflammation has an adverse effect, and the use of bisphosphonates and TNFi has a positive effect, on BMD in AS patients

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 x 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-kappaB signaling and mitochondrial dysfunction as biological processes related to timing of menopause