Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health

Sex differences in the association of social network satisfaction and the risk for type 2 diabetes

Abstract Background The role of an individual’s social network satisfaction (SNS) in the association of social isolation or living alone and incident type 2 diabetes (T2D) is unclear. We assessed the association of SNS with incident T2D and analysed potential modifications of the SNS-T2D association by social isolation or living alone. Methods The study population (N = 6839 aged 25–74 years without diabetes at baseline) derived from the prospective population-based MONICA/KORA study (1989–2009). Social network satisfaction was assessed by a single item. Cox regression was used to estimate hazard ratios (HR) for SNS separately in men and women. Results In men with low SNS, risk for incident T2D increased significantly (HR: 2.15, 95% CI: 1.33–3.48, p value 0.002). After additional adjustments for social isolation or living alone, the risk for incident T2D was still significant, albeit less pronounced (HRs 1.85 or 2.05, p values 0.001 or 0.004). The interaction analysis showed an increased T2D risk effect for low SNS compared to high SNS in women living in a partnership (HR: 2.11, 95% CI: 1.00–4.44, p value for interaction: 0.047) and for moderate SNS compared to high SNS in socially connected women (1.56, 1.01–2.39, 0.010). Conclusions Further research is needed to address the complexities of the perception of social relationships and social interactions, or interdependence, especially when another major public health issue such as T2D is concerned

Dysregulated diurnal cortisol patterns are associated with cardiovascular mortality: Findings from the KORA-F3 study.

Psychosocial stress has been associated with an increased risk for cardiovascular disease and death. Dysregulated diurnal cortisol slopes, which have also been associated with stress, might mediate this association. However, existing evidence on the cardiovascular health consequences of dysregulated cortisol slopes remains limited and inconclusive. To elucidate whether dysregulated diurnal cortisol slopes are related to cardiovascular mortality, we assessed salivary cortisol and cardiovascular morbidity and mortality in 1090 participants from the KORA-F3 study, a prospective, observational cohort study of a random representative sample from the general population. Eighty-seven deaths were registered during the mean follow-up period of approximately 11 years, 31 of which were classified as cardiovascular deaths. A more pronounced cortisol awakening response was associated with a lower risk of cardiovascular mortality in the adjusted Cox proportional hazards analysis (HR 0.59 [95-%-CI 0.36–0.96], p = 0.03). A greater diurnal cortisol peak-to-bedtime ratio at baseline also predicted a decreased risk of cardiovascular mortality (HR 0.50 [95-%-CI 0.34–0.73], p 0.01) and a decreased risk of stroke (HR 0.71 [95-%-CI 0.55–0.92], p 0.01). Increased levels of late night salivary cortisol predicted a higher risk of cardiovascular mortality (HR 1.49 [95-%-CI 1.13–1.97], p 0.01) and an increased risk of stroke (HR 1.24 [95-%-CI 1.01–1.52], p = 0.04). There was no association between measures of cortisol and non-cardiovascular related mortality. In conclusion, dysregulated diurnal cortisol patterns are associated with cardiovascular mortality, while greater diurnal cortisol variation seems to have a protective effect. This adds evidence to suggest a pathophysiological role of diurnal cortisol secretion patterns in cardiovascular health

The association of social connectivity and body weight with the onset of type 2 diabetes: Findings from the population-based prospective MONICA/KORA cohort.

OBJECTIVE: Low levels of social connectivity are related to the onset of type 2 diabetes mellitus (T2D), and this study investigates the role of body weight in this association. METHODS: In a sample of 9448 participants followed for a mean of 15.3 years (186,158.5 person-years) from the Monitoring of Trends and Determinants in Cardiovascular Disease Augsburg/Cooperative Health Research in the Region of Augsburg population-based cohort conducted in Germany, we investigated the association of social connectivity, measured by the Social Network Index, and body mass index (BMI) with the risk of clinically validated T2D incidence using stratified Cox proportional hazards regression models adjusted for sociodemographic, life-style, cardiometabolic, and psychosocial risk factors. RESULTS: During a mean follow-up of 14.1 years (186,158.5 person-years), 975 (10.3%) participants developed T2D. Participants with low social connectivity developed T2D at a higher rate than socially connected participants (10.0 versus 8.0 cases/10,000 person-years); however, BMI played a significant role in the association of social connectivity with T2D ( p < .001). In comparison to their socially connected counterparts, low social connectivity was associated with a higher rate of T2D incidence in normal-weight (6.0 versus 2.0 cases/10,000 person-years), but not overweight (13.0 versus 13.0 cases/10,000 person-years) or obese participants (32.0 versus 30.0 cases/10,000 person-years). Correspondingly, Cox regression analysis showed that 5-unit increments in BMI increased the risk of T2D in socially connected participants (hazard ratio = 3.03, 95% confidence interval = 2.48-3.79, p < .001) at a substantially higher rate than in low socially connected participants (hazard ratio = 1.77, 95% confidence interval = 1.45-2.16, p < .001). CONCLUSION: The detrimental link between low social connectivity and increased risk of T2D is substantially stronger in participants with a lower BMI

The impact of the Type D Personality pattern on prehospital delay in patients suffering from acute myocardial infarction.

Background: The Type D Personality (TDP) has been specifically linked to acute myocardial infarction (AMI). However, the impact on prehospital delay of AMI patients is unclear. The aim of this study was to assess the relationship between TDP and pre-hospital delay time (PHT) in a Chinese population.Methods: A total of 256 AMI patients (47 women and 209 men) were taken from the Multicenter Delay in Patients Experiencing AMI in Shanghai (MEDEA FAR-EAST) study. Sociodemographic and psychobehavioral characteristics were assessed by bedside interviews and questionnaires. TDP was evaluated according to the Type D Personality Scale (DS14) subdivided in social inhibition (SI) and negative affectivity (NA). Based on a significant interaction analysis of TDP and sex on PHT, all analyses were stratified by sex.Results: PHT of female patients with TDP were substantially shorter compared to non-TDP female patients (108 vs. 281 min, P=0.029). In male patients, no effect of TDT on PHT was found. Spearman correlation analysis suggests that NA was negatively correlated with PHT (r=-0.358, P=0.014). Further age-adjusted logistic regression analyses showed that female patients with TDP were generally less likely to prehospital delay compared with non-TDP patients (OR =0.28; 95% CI, 0.08-0.98) and had a lower risk of PHT >360 minutes (OR =0.10; 95% CI, 0.01-0.91). However, statistical significance disappeared after adjustment for psychological factors (anxiety, depression, suboptimal wellbeing, cardiac denial and stress event).Conclusions: TDP is associated with less prehospital delay in female patients during AMI-an effect which may be particularly mediated by NA

Handgrip strength is inversely and independently associated with multimorbidity among older women: results from the KORA-age study

BACKGROUND: Data on the association between handgrip strength and multimorbidity (MMB) are missing. AIM: The purpose of this study was to examine if handgrip strength is related to MMB in a large population-based sample of older persons. METHODS: The cross-sectional analysis was based on 1079 older people (aged 65-94years), who participated in the KORA-Age study in the Augsburg region, southern Germany. Participants underwent an interview and extensive examinations, including anthropometric measurements, registration of chronic diseases, determination of health-related behaviors (smoking, alcohol intake and physical activity), collection of blood samples, and muscle strength measurement using hand-grip dynamometry. RESULTS: In men, handgrip strength correlated strongly with the number of co-existing diseases (r=-0.176, p<0.001), and the same pattern was observed for women (r=-0.287, p<0.001). Among women, handgrip strength in the lower tertile compared to the upper tertile was significantly associated with an increased odds of having MMB (OR: 2.57, 95% CI: 1.30-5.07, p=0.007) after controlling for age, BMI, education, alcohol intake, smoking habits, medications number, inflammatory markers, telomere length and levels of physical activity. Contrary, no significant association between handgrip strength and MMB was found among men (OR: 1.32, 95% CI: 0.73-2.40, p=0.362) after multivariable adjustment. CONCLUSION: Lower levels of handgrip strength are associated with a higher odd of MMB among older women even after adjusting for traditional and novel confounders. Increasing the levels of muscular strength in older women seems to be important in order to reduce the risk for the co-occurrence of multiple chronic diseases

Author Correction: Gender specific somatic symptom burden and mortality risk in the general population.

The original version of this Article contained an error in the spelling of the author Hamimatunnisa Johar, which was incorrectly given as Hamimatunissa Johar. The original Article has been corrected