Uric acid is more strongly associated with impaired glucose regulation in women than in men from the general population: the KORA F4-Study.

High serum uric acid (UA) levels are associated with the metabolic syndrome, type 2 diabetes and cardiovascular disease. It is largely unknown whether there are gender-specific differences regarding the association between UA and prediabetic states. We examined the possible association between UA levels and known as well as newly diagnosed diabetes (NDD), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined IFG/IGT in a population-based sample of 32-to-81-year-old men and women. An oral glucose tolerance test was carried out in all 2,740 participants without known diabetes of the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study conducted between 2006 and 2008 in Southern Germany. Serum UA was analysed by the uricase method. In women after multivariable adjustment the associations between UA and i-IFG (OR 1.57, 95% CI 1.15-2.14), IFG/IGT (OR 1.52, 1.07-2.16), NDD (OR 1.67, 95% CI 1.28-2.17), and known diabetes (OR 1.47, 95% CI 1.18-1.82) remained significant, but the association with i-IGT (OR 1.14, 95% CI 0.95-1.36) lost significance. In contrast in men, after multivariable adjustment there was only a significant association between UA levels and i-IFG (OR 1.49, 95% CI 1.21-1.84), all other associations were non-significant (i-IGT: OR 1.09, IFG/IGT: OR 1.06, NDD: OR 0.91, known diabetes: OR 1.04; all p-values>0.05). Serum UA concentrations were associated with different categories of impaired glucose regulation in individuals from the general population, particularly in women. Further studies investigating the role of UA in the development of derangements in glucose metabolism are needed

Age at menarche and its association with the metabolic syndrome and its components

The metabolic syndrome is a major public health challenge and identifies persons at risk for diabetes and cardiovascular disease. The aim of this study was to examine the association between age at menarche and the metabolic syndrome (IDF and NCEP ATP III classification) and its components. 1536 women aged 32 to 81 years of the German population based KORA F4 study were investigated. Data was collected by standardized interviews, physical examinations, and whole blood and serum measurements. Young age at menarche was significantly associated with elevated body mass index (BMI), greater waist circumference, higher fasting glucose levels, and 2 hour glucose (oral glucose tolerance test), even after adjusting for the difference between current BMI and BMI at age 25. The significant effect on elevated triglycerides and systolic blood pressure was attenuated after adjustment for the BMI change. Age at menarche was inversely associated with the metabolic syndrome adjusting for age (p-values: <0.001 IDF, 0.003 NCEP classification) and additional potential confounders including lifestyle and reproductive history factors (p-values: 0.001, 0.005). Associations remain significant when additionally controlling for recollected BMI at age 25 (p-values: 0.008, 0.033) or the BMI change since age 25 (p-values: 0.005, 0.022). Young age at menarche might play a role in the development of the metabolic syndrome. This association is only partially mediated by weight gain and increased BMI. A history of early menarche may help to identify women at risk for the metabolic syndrome

Serum levels of interleukin-22, cardiometabolic risk factors and incident type 2 diabetes: KORA F4/FF4 study

AIMS: Interleukin-22 (IL-22) has beneficial effects on body weight, insulin resistance and inflammation in different mouse models, but its relevance for the development of type 2 diabetes in humans is unknown. We aimed to identify correlates of serum IL-22 levels and to test the hypothesis that higher IL-22 levels are associated with lower diabetes incidence. METHODS: Cross-sectional associations between serum IL-22, cardiometabolic risk factors and glucose tolerance status were investigated in 1107 persons of the population-based KORA F4 study. The prospective association between serum IL-22 and incident type 2 diabetes was assessed in 504 initially non-diabetic study participants in both the KORA F4 study and its 7-year follow-up examination KORA FF4, 76 of whom developed diabetes. RESULTS: Male sex, current smoking, lower HDL cholesterol, lower estimated glomerular filtration rate and higher serum interleukin-1 receptor antagonist were associated with higher IL-22 levels after adjustment for confounders (all P &lt; 0.05). Serum IL-22 showed no associations with glucose tolerance status, prediabetes or type 2 diabetes. Baseline serum IL-22 levels (median, 25th/75th percentiles) for incident type 2 diabetes cases and non-cases were 6.28 (1.95; 12.35) and 6.45 (1.95; 11.80) pg/ml, respectively (age and sex-adjusted P = 0.744). The age and sex-adjusted OR (95% CI) per doubling of IL-22 for incident type 2 diabetes of 1.02 (0.85; 1.23) was almost unchanged after consideration of further confounders. CONCLUSIONS: High serum levels of IL-22 were positively rather than inversely associated with several cardiometabolic risk factors. However, these associations did not translate into an increased risk for type 2 diabetes. Thus, our data argue against the utility of IL-22 as biomarker for prevalent or incident type 2 diabetes in humans, but identify potential determinants of IL-22 levels which merits further research in the context of cardiovascular diseases

Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism

The mechanism of antihypertensive and lipid-lowering drugs on the human organism is still not fully understood. New insights on the drugs&#39; action can be provided by a metabolomics-driven approach, which offers a detailed view of the physiological state of an organism. Here, we report a metabolome-wide association study with 295 metabolites in human serum from 1,762 participants of the KORA F4 (Cooperative Health Research in the Region of Augsburg) study population. Our intent was to find variations of metabolite concentrations related to the intake of various drug classes and-based on the associations found-to generate new hypotheses about on-target as well as off-target effects of these drugs. In total, we found 41 significant associations for the drug classes investigated: For beta-blockers (11 associations), angiotensin-converting enzyme (ACE) inhibitors (four assoc.), diuretics (seven assoc.), statins (ten assoc.), and fibrates (nine assoc.) the top hits were pyroglutamine, phenylalanylphenylalanine, pseudouridine, 1-arachidonoylglycerophosphocholine, and 2-hydroxyisobutyrate, respectively. For beta-blockers we observed significant associations with metabolite concentrations that are indicative of drug side-effects, such as increased serotonin and decreased free fatty acid levels. Intake of ACE inhibitors and statins associated with metabolites that provide insight into the action of the drug itself on its target, such as an association of ACE inhibitors with des-Arg(9)-bradykinin and aspartylphenylalanine, a substrate and a product of the drug-inhibited ACE. The intake of statins which reduce blood cholesterol levels, resulted in changes in the concentration of metabolites of the biosynthesis as well as of the degradation of cholesterol. Fibrates showed the strongest association with 2-hydroxyisobutyrate which might be a breakdown product of fenofibrate and, thus, a possible marker for the degradation of this drug in the human organism. The analysis of diuretics showed a heterogeneous picture that is difficult to interpret. Taken together, our results provide a basis for a deeper functional understanding of the action and side-effects of antihypertensive and lipid-lowering drugs in the general population

Characterization of the metabolic profile associated with serum 25-hydroxyvitamin D : a cross-sectional analysis in population-based data

Background: Numerous observational studies have observed associations between vitamin D deficiency and cardiometabolic diseases, but these findings might be confounded by obesity. A characterization of the metabolic profile associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in general and stratified by abdominal obesity, may help to untangle the relationship between vitamin D, obesity and cardiometabolic health. Methods: Serum metabolomics measurements were obtained from a nuclear magnetic resonance spectroscopy (NMR)- and a mass spectrometry (MS)-based platform. The discovery was conducted in 1726 participants of the population-based KORA-F4 study, in which the associations of the concentrations of 415 metabolites with 25(OH)D levels were assessed in linear models. The results were replicated in 6759 participants (NMR) and 609 (MS) participants, respectively, of the population-based FINRISK 1997 study. Results: Mean [standard deviation (SD)] 25(OH)D levels were 15.2 (7.5) ng/ml in KORA F4 and 13.8 (5.9) ng/ml in FINRISK 1997; 37 metabolites were associated with 25(OH) D in KORA F4 at P <0.05/415. Of these, 30 associations were replicated in FINRISK 1997 at P <0.05/37. Among these were constituents of (very) large very-low-density lipoprotein and small low-density lipoprotein subclasses and related measures like serum triglycerides as well as fatty acids and measures reflecting the degree of fatty acid saturation. The observed associations were independent of waist circumference and generally similar in abdominally obese and non-obese participants. Conclusions: Independently of abdominal obesity, higher 25(OH)D levels were associated with a metabolite profile characterized by lower concentrations of atherogenic lipids and a higher degree of fatty acid polyunsaturation. These results indicate that the relationship between vitamin D deficiency and cardiometabolic diseases is unlikely to merely reflect obesity-related pathomechanisms.Peer reviewe

BiomarCaRE: rationale and design of the European BiomarCaRE project including 300,000 participants from 13 European countries

Biomarkers are considered as tools to enhance cardiovascular risk estimation. However, the value of biomarkers on risk estimation beyond European risk scores, their comparative impact among different European regions and their role towards personalised medicine remains uncertain. Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) is an European collaborative research project with the primary objective to assess the value of established and emerging biomarkers for cardiovascular risk prediction. BiomarCaRE integrates clinical and epidemiological biomarker research and commercial enterprises throughout Europe to combine innovation in biomarker discovery for cardiovascular disease prediction with consecutive validation of biomarker effectiveness in large, well-defined primary and secondary prevention cohorts including over 300,000 participants from 13 European countries. Results from this study will contribute to improved cardiovascular risk prediction across different European populations. The present publication describes the rationale and design of the BiomarCaRE project. Electronic supplementary material The online version of this article (doi:10.1007/s10654-014-9952-x) contains supplementary material, which is available to authorized users

Body fat distribution and risk of incident ischemic stroke in men and women aged 50 to 74 years from the general population: the KORA Augsburg cohort study

It remains controversial whether measures of general or abdominal adiposity are better risk predictors for ischemic stroke. Furthermore, so far it is unclear whether body fat mass index (BFMI) and fat free mass index (FFMI) are risk predictors for ischemic stroke. This study examined the sex-specific relevance of body mass index (BMI), BROCA Index, waist circumference (WC), waist-height ratio (WHtR), BFMI and FFMI for the development of ischemic stroke in a Caucasian population.The prospective population-based cohort study was based on 1917 men and 1832 women (aged 50 to 74 years) who participated in the third (1994/95) or fourth (1999/2001) MONICA/KORA Augsburg survey. Subjects were free of stroke at baseline. Standardized anthropometric and bioelectric impedance measurements were obtained at baseline. Hazard ratios (HR) were estimated from Cox proportional hazard models.During a median follow-up of 9.3 years 128 ischemic strokes occurred in men and 81 in women, respectively. Coded as quartiles WC and WHtR were significantly associated with incident stroke in multivariable analyses in women (comparing the 4th vs. the bottom quartile), but none of the adiposity measures was significantly associated with incident stroke in multivariable adjusted analyses in men. When anthropometric measures were used as continuous variables, these findings were confirmed. After multivariable adjustment the associations between obesity measures and incident ischemic stroke were statistically significant only for WC (HR 1.39, 95%CI 1.12-1.72) and WHtR in women (HR 1.39, 95%CI 1.12-1.73) per increase of 1 standard deviation. In both sexes the measures BFMI and FFMI were no independent predictors for incident ischemic stroke.Abdominal obesity measures are independent predictors of incident ischemic stroke in women but not in men from the general adult population. Thus, it may be of particular importance for women to prevent central obesity in order to reduce their risk of ischemic stroke

Multimorbidity and health-related quality of life in the older population: results from the German KORA-Age study

<p>Abstract</p> <p>Background</p> <p>Multimorbidity in the older population is well acknowledged to negatively affect health-related quality of life (HRQL). Several studies have examined the independent effects of single diseases; however, little research has focused on interaction between diseases. The purpose of this study was to assess the impact of six self-reported major conditions and their combinations on HRQL measured by the EQ-5D.</p> <p>Methods</p> <p>The EQ-5D was administered in the population-based KORA-Age study of 4,565 Germans aged 65 years or older. A generalised additive regression model was used to assess the effects of chronic conditions on HRQL and to account for the nonlinear associations with age and body mass index (BMI). Disease interactions were identified by a forward variable selection method.</p> <p>Results</p> <p>The conditions with the greatest negative impact on the EQ-5D index were the history of a stroke (regression coefficient -11.3, p < 0.0001) and chronic bronchitis (regression coefficient -8.1, p < 0.0001). Patients with both diabetes and coronary disorders showed more impaired HRQL than could be expected from their separate effects (coefficient of interaction term -8.1, p < 0.0001). A synergistic effect on HRQL was also found for the combination of coronary disorders and stroke. The effect of BMI on the mean EQ-5D index was inverse U-shaped with a maximum at around 24.8 kg/m².</p> <p>Conclusions</p> <p>There are important interactions between coronary problems, diabetes mellitus, and the history of a stroke that negatively affect HRQL in the older German population. Not only high but also low BMI is associated with impairments in health status.</p