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Irisin is a myokine, which is mainly inversely associated with the risk for non-communicable diseases. Irisin improves cellular energy metabolism by uncoupling the mitochondrial respiratory chain resulting in increased energy expenditure using lipids. To date potential associations between irisin concentration and lipid profile are poorly understood. Therefore, this investigation aimed to evaluate potential associations between irisin and lipid levels in the general population. Data of 430 men and 537 women from the population-based Study of Health in Pomerania (SHIP-TREND) with available irisin and lipid concentrations were used. Analyses of variance, linear and logistic regression models adjusted for age, HBA1c, waist circumference, physical activity, smoking, alcohol consumption, systolic blood pressure, ALAT were calculated. We detected significantly inverse associations between irisin and circulating levels of total [beta coefficient 0.21 (standard error 0.08), p = 0.01], low-density cholesterol [-0.16 (0.07), p = 0.03] and triglycerides [-0.17 (0.08), p = 0.02] for men. Females without lipid lowering medication had an inverse association between irisin and total cholesterol [-0.12 (0.06), p = 0.05]. Further, male subjects with irisin concentrations in the third tertile had an increased odds for elevated low-density cholesterol [odds ratio 1.96 (95% confidence interval 1.07-3.48), p = 0.03) and triglyceride [1.95 (1.09-3.47), p = 0.02] levels, even after exclusion of subjects with lipid lowering medication. In addition, our data revealed an annual rhythm of serum irisin levels with peak levels arise in winter and summer months. This is the first investigation to report a significant association between circulating irisin and a favourable lipid profile in the general population. This may infer that higher irisin concentrations are associated with a reduced risk for non-communicable diseases.

To analyze the association between cardiorespiratory fitness (CRF) and global and local brain volumes. We studied 2103 adults (21-84 years old) from 2 independent population-based cohorts (Study of Health in Pomerania, examinations from June 25, 2008, through September 30, 2012). Cardiorespiratory fitness was measured using peak oxygen uptake (VO2peak), oxygen uptake at the anaerobic threshold (VO2@AT), and maximal power output from cardiopulmonary exercise testing on a bicycle ergometer. Magnetic resonance imaging brain data were analyzed by voxel-based morphometry using regression models with adjustment for age, sex, education, smoking, body weight, systolic blood pressure, glycated hemoglobin level, and intracranial volume. Volumetric analyses revealed associations of CRF with gray matter (GM) volume and total brain volume. After multivariable adjustment, a 1–standard deviation increase in VO2peak was related to a 5.31 cm³ (95% CI, 3.27 to 7.35 cm³) higher GM volume. Whole-brain voxel-based morphometry analyses revealed significant positive relations between CRF and local GM volumes. The VO2peak was strongly associated with GM volume of the left middle temporal gyrus (228 voxels), the right hippocampal gyrus (146 voxels), the left orbitofrontal cortex (348 voxels), and the bilateral cingulate cortex (68 and 43 voxels). Cardiorespiratory fitness was positively associated with GM volume, total brain volume, and specific GM and white matter clusters in brain areas not primarily involved in movement processing. These results, from a representative population sample, suggest that CRF might contribute to improved brain health and might, therefore, decelerate pathology-specific GM decrease.

Chronic kidney disease (CKD) is characterized by a gradual and irreversible decline in renal function. Arginine derivatives like symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) have been associated with the progression of renal disease in cross-sectional studies. This study aimed to investigate the longitudinal associations between arginine derivatives and renal function over time in a population-based cohort. Data were derived from the Study of Health in Pomerania-START (SHIP-START-0, n = 3100, mean age 49 years, women 51.3%). The 5-year follow-up included 2174 and the 10-year follow-up 1657 individuals. At baseline, serum concentrations of Arg, ADMA, SDMA and homoarginine were measured using liquid chromatography–tandem mass spectrometry, while renal parameters (creatinine and cystatin C) were quantified at baseline, 5- and 10-year follow-up. Three different statistical analyses (linear regression, logistic regression, analyses of covariance (ANCOVA)), were performed to investigate the longitudinal associations between baseline levels of Arg, ADMA, SMDA and homoarginine as exposure and renal function parameters as outcome. The results showed a significantly inverse longitudinal association between SDMA and renal function. Specifically, a one μmol/l greater SDMA was related to an odds ratio of 1.77 (95% confidence interval (CI) 1.41; 2.21) at 5-year follow-up and 1.43 (95% CI 1.11; 1.84) at 10-year follow-up for kidney dysfunction defined as estimated glomerular filtration rate less than 60 ml/min/1.73 m 2 . These findings suggest that SDMA might predict future deterioration of renal function. This supports previous findings which suggested that SDMA may be a biomarker for renal function.

Background Mortality attributable to heart failure remains high. The prevalence of heart failure in patients with diabetes mellitus ranges from 19 to 26%. It is estimated that up to 21.1 million adults in the United States have diagnosed diabetes mellitus and around 80.8 million have impaired fasting glucose. We investigated the associations of fasting glucose (FG) and fasting insulin (FI), the homeostasis model assessment-insulin resistance index (HOMA-IR) and 2-h postload glucose (2HG) and insulin (2HI) with parameters of left ventricular geometry and function and arterial stiffness determined by magnetic resonance imaging in individuals without diagnosed type 2 diabetes. Methods Cross-sectional analyses of 1001 individuals (453 women, 45.3%), aged 21 to 80 years, from two independent population-based studies, the Study of Health in Pomerania (SHIP-TREND-0) and KORA FF4 Study. FG, FI, HOMA-IR, 2HG and 2HI, as well as glucose tolerance categories, were analyzed for associations with heart and arterial parameters using multivariable-adjusted linear regression models. Results In total, 390 individuals (39%) had prediabetes (isolated impaired fasting glucose, isolated glucose tolerance or both), and 49 (4.9%) were found to have unknown type 2 diabetes. In the multivariable-adjusted analysis, positive linear associations of FG, FI, HOMA-IR, 2HG and 2HI with arterial stiffness index and left ventricular wall-thickness and concentricity and inverse linear associations with left ventricular end-diastolic volume were observed. A 1 mmol/l higher FG was associated with a 1.18 ml/m 2.7 (1.80 to 0.57; p < 0.001) lower left ventricular end-diastolic volume index, a 0.042 mm/m 2.7 (0.014 to 0.070) higher left ventricular wall-thickness index, a 0.12 mmHg m 2.7 /ml (0.06 to 0.17; p < 0.001) greater arterial stiffness index and a 0.037 g/ml (0.018 to 0.056; p < 0.001) higher left ventricular concentricity. Conclusions Our findings suggest that higher glucose levels in the prediabetic range and insulin resistance might lead to higher arterial stiffness and concentric remodeling of the heart.

Background Metabolic Syndrome (MetS) is characterized by risk factors such as abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), hypertension, and hyperglycemia, which contribute to the development of cardiovascular disease and type 2 diabetes. Here, we aim to identify candidate metabolite biomarkers of MetS and its associated risk factors to better understand the complex interplay of underlying signaling pathways. Methods We quantified serum samples of the KORA F4 study participants (N = 2815) and analyzed 121 metabolites. Multiple regression models adjusted for clinical and lifestyle covariates were used to identify metabolites that were Bonferroni significantly associated with MetS. These findings were replicated in the SHIP-TREND-0 study (N = 988) and further analyzed for the association of replicated metabolites with the five components of MetS. Database-driven networks of the identified metabolites and their interacting enzymes were also constructed. Results We identified and replicated 56 MetS-specific metabolites: 13 were positively associated (e.g., Val, Leu/Ile, Phe, and Tyr), and 43 were negatively associated (e.g., Gly, Ser, and 40 lipids). Moreover, the majority (89%) and minority (23%) of MetS-specific metabolites were associated with low HDL-C and hypertension, respectively. One lipid, lysoPC a C18:2, was negatively associated with MetS and all of its five components, indicating that individuals with MetS and each of the risk factors had lower concentrations of lysoPC a C18:2 compared to corresponding controls. Our metabolic networks elucidated these observations by revealing impaired catabolism of branched-chain and aromatic amino acids, as well as accelerated Gly catabolism. Conclusion Our identified candidate metabolite biomarkers are associated with the pathophysiology of MetS and its risk factors. They could facilitate the development of therapeutic strategies to prevent type 2 diabetes and cardiovascular disease. For instance, elevated levels of lysoPC a C18:2 may protect MetS and its five risk components. More in-depth studies are necessary to determine the mechanism of key metabolites in the MetS pathophysiology.

Background Low relative fat free mass (FFM) is associated with a greater risk of chronic diseases and mortality. Unfortunately, FFM is currently not being measured regularly to allow for individuals therapy. Objective One reason why FFM is not being used may be related to additional equipment and resources, thus we aimed to identify easily accessible anthropometric markers related with FFM. Materials and methods We analyzed data of 1,593 individuals (784 women; 49.2%, age range 28–88 years) enrolled in the population-based Study of Health in Pomerania (SHIP-TREND 1). Forty-seven anthropometric markers were derived from a 3D optical body-scanner. FFM was assessed by bioelectrical impedance analysis (FFM BIA ) or air displacement plethysmography (FFM ADP ). In sex-stratified linear regression models, FFM was regressed on anthropometric measurements adjusted for body height and age. Anthropometric markers were ranked according to the coefficient of determination (R 2 ) derived from these regression models. Results Circumferences of high hip, belly, middle hip, waist and high waist showed the strongest inverse associations with FFM. These relations were stronger in females than in males. Associations of anthropometric markers with FFM APD were greater compared to FFM BIA . Conclusion Anthropometric measures were more strongly associated with FFM ADP compared to FFM BIA . Anthropometric markers like circumferences of the high or middle hip, belly or waist may be appropriate surrogates for FFM to aid in individualized therapy. Given that the identified markers are representative of visceral adipose tissue, the connection between whole body strength as surrogate for FFM and fat mass should be explored in more detail.

Background Currently total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are used in clinical practice to estimate future cardiovascular risk. We assessed whether other lipoprotein subclasses also contribute to cause-specific and all-cause mortality in the general population. Methods Two independent cohorts of the Study of Health in Pomerania (SHIP-START and SHIP-TREND) were used. Participants were selected from population registration offices. The primary outcomes were all-cause, cardiovascular and cancer mortality. TC, total triglycerides (TG), phospholipids as well as the fractional concentrations of cholesterol, TG, phospholipids, and apolipoproteins of all lipoprotein subclasses were measured using nuclear magnetic resonance spectroscopy. Cox proportional hazard regression models were applied to assess the association between lipoprotein subclasses and mortality. Additionally, cause-specific hazards for cardiovascular disease (CVD) and cancer mortality were modelled considering competing events. Results Data from 3,579 SHIP-START and 4,267 SHIP-TREND individuals were included. During follow-up, 946 (26.4%) SHIP-START and 387 (9.1%) SHIP-TREND participants died. In both cohorts, total LDL-TG and LDL1-TG to LDL6-TG but not total TG were positively or U-shaped related with all-cause mortality. In SHIP-START, total TG, VLDL-TG, IDL-TG and LDL-TG (including subclasses) were associated with CVD mortality. HDL4-C as well as small and dense LDL-C (e.g. LDL6-C) represented risk factors for mortality with mutually enhancing effects. Conclusions The findings suggest that lipoprotein subclasses, especially LDL-TGs or HDL4-C/LDL6-C, provide information beyond the established TC and LDL-C levels and therefore might be of use for an early identification of subjects at risk.

All-cause mortality is a population health indicator of the combined impact of biological, behavioral, social, and healthcare-related factors. We used data from 3,803 participants (1,947 women, 51.2%; aged 20 to 81 years) of the population-based Study of Health in Pomerania (SHIP-START-0, 1997–2001), with a median follow-up duration of 20.2 years. Sex-stratified cox proportional hazard models were used to estimate associations between socioeconomic, lifestyle, anthropometric, and cardiovascular risk factors with all-cause mortality. During the 70,982 person-years, 1,029 deaths (641 men and 388 women) were determined as all-cause mortality. In men, type 2 diabetes (hazard ratio [HR] = 1.83 [95% confidence interval {CI}: 1.48 to 2.25; p  < 0.001]), living without a partner (HR = 1.78 [95% CI: 1.41 to 2.24; p  < 0.001]), being a current smoker (HR = 1.76 [95% CI: 1.41 to 2.20; p  < 0.001]), older age (HR per year = 1.10 [95% CI: 1.10 to 1.11; p  < 0.001]) and elevated hs-CRP (HR per mmol/l = 1.07 [95% CI: 1.03 to 1.11; p  < 0.001]) where significantly associated with increased all-cause mortality. In women, just type 2 diabetes (HR = 1.70 [95% CI: 1.28 to 2.15; p  < 0.001]) and elevated hs-CRP (HR per mmol/l = 1.07 [95% CI: 1.03 to 1.12; p  < 0.001]) where significantly associated with increased all-cause mortality. Type 2 diabetes and inflammation were linked to higher all-cause mortality in both sexes, whereas being without a partner, current smoking, and older age were significant risk factors specifically for men.

Handgrip strength (HGS), cardiorespiratory fitness (CRF) and body size, shape, and composition are all related to cardiometabolic health and are associated in cross-sectional settings. Their longitudinal relationship is less clear. We used observational data from the Study of Health in Pomerania at baseline (SHIP-TREND-0; 2008–2012) and follow-up (SHIP-TREND-1; 2016–2019) with 1,214 men and 1,293 women. HGS was measured with a hand dynamometer. CRF was assessed using cardiopulmonary exercise testing. Linear regression models were adjusted appropriately. Several sensitivity analyses were performed. From baseline to follow-up (7 years) HGS decreased in men (3.5 kg) and women (0.8 kg). VO 2 peak lessened in men (36 ml/min) and increased in women (53 ml/min). We only found significant relations in men where a 1 l decline in VO 2 peak was associated with a 0.87 kg larger decrease in fat free mass and with a 1.15 kg stronger decline in body weight. All other analysis revealed non-significant findings. This longitudinal analysis suggests that age related changes in strength and CRF are not related to body size and shape but only composition (in men). A novelty of our findings are the sex-specific aspects given that strength decreased much stronger in men compared to women.

Malnutrition is a common complication of chronic pancreatitis (CP) and liver cirrhosis (LC). Inadequate food intake is considered a relevant driver of malnutrition in both entities. However, the contribution of habitual diet to impaired nutritional status is unclear. In a prospective, multicenter cross-sectional study, we recruited patients with confirmed CP or LC and healthy volunteers as a control group. Malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition criteria. We comprehensively investigated habitual dietary intake on nutrient, food group, and dietary pattern level applying two validated food frequency questionnaires. We included 144 patients (CP: n = 66; LC: n = 78) and 94 control subjects. Malnutrition was prevalent in 64% and 62% of patients with CP or LC, respectively. In both CP and LC, despite slightly altered food group consumption in malnourished and non-malnourished patients there were no differences in energy or nutrient intake as well as dietary quality. Compared to controls patients showed distinct dietary food group habits. Patients consumed less alcohol but also lower quantities of fruits and vegetables as well as whole grain products ( p  < 0.001, respectively). Nevertheless, overall dietary quality was comparable between patients and healthy controls. Nutritional status in CP and LC patients is rather related to disease than habitual dietary intake supporting the relevance of other etiologic factors for malnutrition such as malassimilation or chronic inflammation. Despite distinct disease-related differences, overall dietary quality in patients with CP or LC was comparable to healthy subjects, which suggests susceptibility to dietary counselling and the benefits of nutrition therapy in these entities.