Adiponectin predicts the antioxidant capacity and size of high-density lipoprotein (HDL) in individuals with diabetes mellitus.

AIMS: The relationship between adiponectin and type 2 diabetes mellitus (T2DM) is established; however the evidence on its role in high-density lipoprotein (HDL) functionality is still scant. The aim of this study was to assess the association of adiponectin with HDL functionality especially on the antioxidant capacity and HDL subfractions in individuals with T2DM. METHODS: This case-control study enrolled 356 individuals who were divided into two groups: diabetics [T2DM (n = 188)] and non-diabetic [nT2DM (n = 168)]. The association of adiponectin level on HDL functionality parameters was done in function of the cut-off point for adiponectin [percentile p < 75 = 12.9 µg/mL versus p ≥ 75 = 12.9 µg/mL] and multiple adjustments applied in the logistic regression models. RESULTS: Body mass index (BMI), waist circumference (WC) and body fat mass (FM) were higher in T2DM. The larger HDL particles (HDLLARGE) were lower in T2DM group in comparison with nT2DM (28.20% versus 30.40%; p = 0.016). Individuals with T2DM and simultaneous highest adiponectin (p ≥ 75) had 2.25 OR (95% CI = 1.03-4.91) and 5.14 OR (95% CI = 2.37-11.15) to present higher HDL-C and HDLLARGE concentrations. After adjustment for multiple confounders, high level of adiponectin was independently related with improvement of the HDL antioxidant capacity (OR = 2.78; 95% CI = 1.16-6.67). CONCLUSIONS: High adiponectin level associates with a lesser negative impact of T2DM on HDL functionality by increase in APO AI, particles size, and cholesterol content. On the same token, higher adiponectin was associated with greater odds to have high antioxidant capacity.

Cardiopulmonary fitness is strongly associated with body cell mass and fat-free mass: The Study of Health in Pomerania (SHIP).

Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to determine cardiopulmonary fitness (CPF). This approach may lead to misinterpretation, particularly in obese subjects. We investigated the normalization of VO2peak by different body composition markers. We analyzed combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-2 and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing. Body cell mass (BCM), fat-free mass (FFM), and fat mass (FM) were determined by bioelectrical impedance analysis. The suitability of the different markers as a normalization variable was evaluated by taking into account correlation coefficients (r) and intercept (α-coefficient) values from linear regression models. A combination of high r and low α values was considered as preferable for normalization purposes. BCM was the best normalization variable for VO2peak (r = .72; P ≤ .001; α-coefficient = 63.3 mL/min; 95% confidence interval [CI]: 3.48-123) followed by FFM (r = .63; P ≤ .001; α-coefficient = 19.6 mL/min; 95% CI: -57.9-97.0). On the other hand, a much weaker correlation and a markedly higher intercept were found for TBW (r = .42; P ≤ .001; α-coefficient = 579 mL/min; 95% CI: 483 to 675). Likewise, FM was also identified as a poor normalization variable (r = .10; P ≤ .001; α-coefficient = 2133; 95% CI: 2074-2191). Sex-stratified analyses confirmed the above order for the different normalization variables. Our results suggest that BCM, followed by FFM, might be the most appropriate marker for the normalization of VO2peak when comparing CPF between subjects with different body shape.

Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study.

BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. CONCLUSION: Our findings suggest that prediabetes might have harmful effects on the kidney.

Hyperthyroxinemia is positively associated with prevalent and incident type 2 diabetes mellitus in two population-based samples from Northeast Germany and Denmark.

BACKGROUND AND AIMS: A potential causal relationship between thyroid function and type 2 diabetes mellitus is currently under debate, but the current state of research is limited. Our aim was to investigate the association of thyroid hormone levels with prevalent and incident type 2 diabetes mellitus (T2DM) in two representative studies. METHODS AND RESULTS: Analyses are based on data from the Study of Health in Pomerania (SHIP), a German population based cohort with 4308 individuals at baseline and 3300 individuals at a five-year follow-up, and from INTER99, a Danish population-based randomized controlled trial with 6784 individuals at baseline and 4516 individuals at the five-year-follow-up. Serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) concentrations were measured in both studies, while free triiodothyronine was measured in SHIP only. T2DM was defined by self report or intake of anti-diabetic medication. Neither in SHIP nor in INTER99 we detected significant associations of serum TSH levels with prevalent or incident T2DM. Serum fT4 levels were significantly positively associated with prevalent T2DM in SHIP and INTER99. In longitudinal analyses baseline levels of fT4 were significantly positively associated with incident T2DM in SHIP (RR per pmol/L = 1.07; 95%-CI = 1.05-1.10), while this association barely missed statistical significance in INTER99 (RR per pmol/L = 1.03; 95%-CI = 0.99-1.06). In SHIP baseline fT3 levels were significantly associated with incident T2DM (RR per pmol/L = 1.21; 95%-CI = 1.16-1.27). CONCLUSION: We demonstrated positive associations of thyroid hormones with prevalent and incident type 2 diabetes mellitus suggesting that hyperthyroxinemia may contribute to the pathogenesis of this condition.

Prediabetes is associated with lower brain gray matter volume in the general population. The Study of Health in Pomerania (SHIP).

BACKGROUND AND AIMS: We investigated the associations of fasting (FG) and 2-h postload (2HG) plasma glucose from oral glucose tolerance test (OGTT) with gray (GMV) and white (WMV) matter volume. METHODS AND RESULTS: We analyzed data from 1330 subjects without known diabetes mellitus, aged 21 to 81, from the second cohort (SHIP-Trend-0) of the population-based Study of Health in Pomerania (SHIP). Following the OGTT, individuals were classified in five groups (according to the American Diabetes Association criteria): normal glucose tolerance (NGT), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) and unknown type 2 diabetes mellitus (UDM). GMV and WMV were determined by magnetic resonance imaging. FG, 2HG and OGTT groups were associated with GMV and WMV by linear regression models adjusted for confounders. FG and 2HG were inversely associated with GMV. The adjusted mean GMV, when compared with the NGT group (584 ml [95% CI: 581 to 587]), was significantly lower in the groups i-IFG (578 ml [95% CI: 573 to 582]; p = 0.035) and UDM (562 ml [95% CI: 551 to 573]; p < 0.001), but not different in the i-IGT (586 ml [95% CI: 576 to 596]; p = 0.688) and IFG + IGT (579 ml [95% CI: 571 to 586]; p = 0.209) groups. There were no associations of FG, 2HG and OGTT parameters with WMV. CONCLUSION: Our findings suggest that elevated FG levels, even within the prediabetic range, might already have some harmful effects on GMV.

Serum metabolomic profiling highlights pathways associated with liver fat content in a general population sample.

BACKGROUND/OBJECTIVES: Fatty liver disease (FLD) is an important intermediate trait along the cardiometabolic disease spectrum and strongly associates with type 2 diabetes. Knowledge of biological pathways implicated in FLD is limited. An untargeted metabolomic approach might unravel novel pathways related to FLD. SUBJECTS/METHODS: In a population-based sample (n=555) from Northern Germany, liver fat content was quantified as liver signal intensity using magnetic resonance imaging. Serum metabolites were determined using a non-targeted approach. Partial least squares regression was applied to derive a metabolomic score, explaining variation in serum metabolites and liver signal intensity. Associations of the metabolomic score with liver signal intensity and FLD were investigated in multivariable-adjusted robust linear and logistic regression models, respectively. Metabolites with a variable importance in the projection >1 were entered in in silico overrepresentation and pathway analyses. RESULTS: In univariate analysis, the metabolomics score explained 23.9% variation in liver signal intensity. A 1-unit increment in the metabolomic score was positively associated with FLD (n=219; odds ratio: 1.36; 95% confidence interval: 1.27-1.45) adjusting for age, sex, education, smoking and physical activity. A simplified score based on the 15 metabolites with highest variable importance in the projection statistic showed similar associations. Overrepresentation and pathway analyses highlighted branched-chain amino acids and derived gamma-glutamyl dipeptides as significant correlates of FLD. CONCLUSIONS: A serum metabolomic profile was associated with FLD and liver fat content. We identified a simplified metabolomics score, which should be evaluated in prospective studies.

[Lung Health Data of the Study of Health in Pomerania - a Review of Samples, Methods and First Results]. / Pneumologisch relevante Daten aus der "Study of Health in Pomerania" (SHIP) ­ eine Übersicht zu den Kohorten, Methoden und ersten Ergebnissen.

Investigating reasons for differing life expectancy and prevalence of cardiovascular risk factors between old and new states of the Federal Republic of Germany an epidemiological study in Western Pomerania - the population-based project Study of Health in Pomerania (SHIP) - was planned.Prevalence and incidence of common risk factors, subclinical disorders and clinical diseases have been assessed since 1997 in five-year intervals. The third follow up (SHIP-3) was assessed between 2014 and 2016. In addition, an independent representative population sample was investigated between 2008 - 2012 (SHIP-TREND). Recently, the first follow up of this cohort has been started (SHIP-TREND-1). This paper reports the methodological approaches for detecting pneumological relevant morbidities in this population-based study. It aims to offer insights for potential cooperation with interested research groups.

Reduced Bone Stiffness in Women Is Associated with Clinical Attachment and Tooth Loss: The Study of Health in Pomerania.

The authors evaluated the association of reduced bone stiffness of the calcaneus with clinical attachment loss (CAL) and tooth loss. The authors analyzed data from 4,678 subjects (2,384 women), aged 20 to 88 y, from the second follow-up of the population-based Study of Health in Pomerania (SHIP-2) and the baseline examination of the SHIP-Trend cohort. Bone stiffness, characterized by the stiffness index (SI) and the osteoporotic fracture risk (OFR), was assessed by quantitative ultrasound of the heel. SI and OFR were significantly associated with the mean CAL in women. While 1) the SI showed a significant association with the mean CAL and 2) the OFR with the median number of teeth in just the postmenopausal women, the OFR showed a significant association with mean CAL for both pre- and postmenopausal women. In postmenopausal women, a 10-unit increase in the SI was associated with a decrease in the mean CAL of 0.05 mm (95% confidence interval [CI]: -0.10 to 0.00; P = 0.046). Moreover, the adjusted median number of teeth was 21.4 (95% CI: 20.9 to 21.9) among the postmenopausal women with a low OFR, while it was 19.1 (95% CI: 17.8 to 20.3; P = 0.001) among the postmenopausal women with a high OFR. For the premenopausal women with a low OFR, the mean CAL was 1.60 mm (95% CI: 1.53 to 1.66), while for the premenopausal women with a high OFR, it was 2.24 mm (95% CI: 1.78 to 2.69; P = 0.006). Reduced bone stiffness was associated with clinical attachment and tooth loss in women but not in men.

Trends of barriers to eye care among adults with diagnosed diabetes in Germany, 1997-2012.

BACKGROUND AND AIMS: To study trends of barriers to receiving recommended eye care among subjects with diabetes aged 20-81 years in northeast Germany. METHODS AND RESULTS: We analyzed population-based data from two repeated cross-sectional surveys conducted in 1997-2001 and 2008-2012 (Ns of 4308 and 4402). Andersen's Behavioral Model of Health Services Utilization was used to identify individual-level demographic, financial and health-related barriers to annual eye-care utilization in subjects with a self-reported physician's diabetes and to examine population trends in these barriers. The prevalence of diabetes increased from 6.5% to 11.4%. The prevalence of annual eye-care utilization among persons with diabetes decreased from 69.4% to 56.0% (adjusted relative risk = 0.77, p < 0.001). The decline of eye care utilization over the past decade in eye-care use was more pronounced in groups at risk for diabetes-related complications (i.e., lower socio-economic status, >5 years since diagnosis of diabetes, poor glycemic control, obesity, smoking, lack of physical activity, co-existing diseases). We identified relevant predictors of missed annual eye-care use among diabetics. CONCLUSION: The increase of diabetes prevalence and downward trend of eye-care visits at the recommended level call for development, implementation and evaluation of continued efforts to improve access to eye specialists, particularly among those with poor diabetic control, co-existing diabetic complications, and comorbidities.

Positive Association Between Adipose Tissue and Bone Stiffness.

Obesity is often considered to have a protective effect against osteoporosis. On the other hand, several recent studies suggest that adipose tissue may have detrimental effects on bone quality. We therefore aimed to investigate the associations between body mass index (BMI), waist circumference (WC), visceral adipose tissue (VAT) or abdominal subcutaneous adipose tissue (SAT), and bone stiffness. The study involved 2685 German adults aged 20-79 years, who participated in either the second follow-up of the population-based Study of Health in Pomerania (SHIP-2) or the baseline examination of the SHIP-Trend cohort. VAT and abdominal SAT were quantified by magnetic resonance imaging. Bone stiffness was assessed by quantitative ultrasound (QUS) at the heel (Achilles InSight, GE Healthcare). The individual risk for osteoporotic fractures was determined based on the QUS-derived stiffness index and classified in low, medium, and high risk. Linear regression models, adjusted for sex, age, physical activity, smoking status, risky alcohol consumption, diabetes, and height (in models with VAT or abdominal SAT as exposure), revealed positive associations between BMI, WC, VAT or abdominal SAT, and the QUS variables broadband-ultrasound attenuation or stiffness index. Moreover, BMI was positively associated with speed of sound. Our study shows that all anthropometric measures including BMI and, WC as well as abdominal fat volume are positively associated with bone stiffness in the general population. As potential predictors of bone stiffness, VAT and abdominal SAT are not superior to easily available measures like BMI or WC.

Long-term changes in body weight are associated with changes in blood pressure levels.

BACKGROUND AND AIMS: Hypertension and obesity are highly prevalent in Western societies. We investigated the associations of changes in body weight with changes in blood pressure and with incident hypertension, incident cardiovascular events, or incident normalization of blood pressure in patients who were hypertensive at baseline, over a 5-year period. METHODS AND RESULTS: Data of men and women aged 20-81 years of the Study of Health in Pomerania were used. Changes in body weight were related to changes in blood pressure by linear regression (n = 1875) adjusted for cofounders. Incident hypertension, incident cardiovascular events, or incident blood pressure normalization in patients who were hypertensive at baseline were investigated using Poisson regression (n = 3280) models. A change of 1 kg in body weight was positively associated with a change of 0.45 mm Hg (95% confidence interval (CI): 0.34-0.55 mm Hg) in systolic blood pressure, 0.32 mm Hg (95% CI: 0.25-0.38 mm Hg) in diastolic blood pressure, and 0.36 mm Hg (95% CI: 0.29-0.43 mm Hg) in mean arterial pressure (all p-values <0.001). A 5% weight loss reduced the relative risk (RR) of incident hypertension (RRs 0.84 (95% CI: 0.79-0.89)) and incident cardiovascular events (RRs 0.81 (95% CI: 0.68-0.98)) and increased the chance of incident blood pressure normalization in patients who were hypertensive at baseline by 15% (95% CI: 7-23%). CONCLUSIONS: Absolute and relative changes in body weight are positively associated with changes in blood pressure levels and also affect the risk of cardiovascular events.

Plasma aldosterone levels and aldosterone-to-renin ratios are associated with endothelial dysfunction in young to middle-aged subjects.

OBJECTIVE: Small clinical studies suggested a role for aldosterone in the development of endothelial dysfunction. We investigated whether the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) were associated with decreased endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in the general population. METHODS: Our study population comprised 972 participants from the Study of Health in Pomerania, who were not treated with antihypertensive medication. We performed age-stratified (<50 and ≥ 50 years) ordinal logistic regression analyses. FMD was categorised as decreased (1st quintile), moderate (2nd-4th quintile), or increased (5th quintile). PAC and ARR were divided into low, moderate, and high values according to age- and sex-specific tertiles. All models were re-calculated for 871 subjects with PAC and ARR within the study-specific reference ranges. Odds ratios (OR) and 95% confidence intervals (CI) are presented. RESULTS: Subjects <50 years with high PAC (OR 1.60; 95% CI 1.07-2.38) or ARR (OR 1.81; 95% CI 1.21-2.73) had higher odds for decreased FMD than subjects with low PAC or ARR, respectively. Similar results were obtained in analyses restricted to subjects with PAC and ARR within the reference range. High-normal PAC (OR 1.62; 95% CI 1.07-2.47) or ARR (OR 1.62; 95% CI 1.05-2.50) was associated with higher odds for decreased FMD when compared with low-normal PAC or ARR, respectively. These associations were not observed in subjects ≥ 50 years. CONCLUSIONS: High and high-normal PAC or ARR contribute to an impaired FMD and subsequently the progression of subclinical atherosclerosis in young to middle-aged subjects.

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: the MONICA/KORA Augsburg cohort study.

BACKGROUND AND AIM: It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. METHODS AND RESULTS: We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n=833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n=36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n=21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). CONCLUSIONS: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes.

Postoperative subphrenic abscess after heart-valve replacement.

A 35 year-old male patient developed a subphrenic abscess in the immediate postoperative period after replacement of a calcified mitral bovine pericardium bioprosthesis. He was successfully treated with abdominal percutaneous drainage and antimicrobial therapy.