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ZusammenfassungPatienten mit koronarer Herzerkrankung (KHK) und Diabetes mellitus Typ 2 (T2D) weisen ein besonders hohes Risiko für (rezidivierende) kardiovaskuläre Ereignisse (CVE) auf; in der Sekundärprävention wirkt sich eine suffiziente Kontrolle der kardiovaskulären Risikofaktoren prognostisch besonders günstig aus. Für diese Patientengruppe konnte in den letzten Jahren der kardioprotektive Nutzen der SGLT2-Inhibitoren und GLP-1-Rezeptor-Agonisten nachgewiesen werden, sodass diese Substanzgruppen mittlerweile bei der Initiierung einer medikamentösen antidiabetischen Therapie zu bevorzugen sind. Auch lipidmodifizierende Medikamente wie die PCSK9-Inhibitoren oder Icosapent-Ethyl haben sich insbesondere bei Patienten mit KHK und T2D als vorteilhaft erwiesen. Zudem haben sich zuletzt die Empfehlungen zum Management der Koronarrevaskularisation bei Patienten mit stabiler KHK und T2D verändert. So sollte bei Mehrgefäß-KHK und komplexer Koronarmorphologie zwar weiterhin eine chirurgische Koronarrevaskularisation (CABG) bevorzugt empfohlen werden; bei einem niedrigen SYNTAX-Score kann die interventionelle Koronarrevaskularisation jedoch eine gleichwertige Alternative zur CABG darstellen.

Background: Lipoprotein(a) [Lp(a)] has recently been gaining increasing interest, with numerous studies pointing to a causal relationship with cardiovascular disease, coronary heart disease, as well as aortic valve stenosis. However, so far only a few studies have assessed the association between Lp(a) and pulmonary health and there have been some inconsistent findings regarding this topic. This study’s aim is to examine whether high level of serum Lp(a) is associated with better lung function in a dataset of relatively healthy older women and men in a sex-specific manner. Methods: We used the longitudinal data collected at two time points 7.4 ±1.5 years apart from 679 participants (52% females, 68 [65-71] years old) in the Berlin Aging Study II (BASE-II). Several lipid parameters, including Lp(a), and lung function were measured in these subjects as part of a comprehensive medical assessment. The baseline dataset was collected between 2009 to 2014, and the follow-up data were collected between 2018 and 2020. Multiple linear regression models adjusting for covariates (BMI, physical inactivity, smoking status, alcohol intake, and a morbidity index) were applied to strengthen evidence for the relationship observed between Lp(a) and lung function in a sex-specific manner. Results: Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were higher in men and declined with age in both sexes. Men had lower Lp(a) levels than women. Average lung function measurements were higher in both men and women with higher Lp(a) levels. However, this association was statistically apparent in men only. Conclusions: The data suggest that Lp(a) might act as a protective and possibly sex specific factor in pulmonary health, a putative role which has not been anticipated so far. Future studies will be required to further establish the relationship between Lp(a) and lung function also with regard to possible causality and sex differences, as well as to further investigate the exact function Lp(a) plays in lung physiology.

BACKGROUND Adequate total and meal-specific protein intake is considered an important prerequisite to preserve appendicular lean mass (ALM) in older adults and to prevent sarcopenia. OBJECTIVES We analyzed the meal-specific protein intake across the main meals between participants with normal vs. low ALM to BMI ratio (ALMBMI). METHODS 782 participants [59.6% men; median 69 (IQR: 65, 71) y] of the Berlin Aging Study II have been included in this analysis. ALM was assessed by dual X-ray absorptiometry. Low lean mass was defined as ALMBMI using recommended sex-specific cut-offs. A 5-day nutritional protocol was used to assess total and meal-specific protein intake. RESULTS Median total protein intake was 0.89 (IQR: 0.74, 1.05) g/kg/d body weight (BW) in participants with low ALMBMI and 1.02 (IQR: 0.86, 1.21) g/kg BW in participants with normal ALMBMI (P

Aim: To describe the prevalence, incidence, and severity of diabetes mellitus type 2 (T2D) and antidiabetic medication in older people and to assess the prognostic value of diagnostic laboratory parameters. Methods: Baseline data of 1,671 participants of the Berlin Aging Study II (68.8 ±3.7 years) and follow-up data assessed 7.4 ±1.5 years later were analysed. T2D was diagnosed based on self-report, antidiabetic medication use, laboratory parameters. T2D severity was determined by the diabetes complications severity index (DCSI). Prognostic capacity of laboratory parameters was evaluated by Receiver Operating Characteristics (ROC) and Areas Under the Curve (AUCs). Results: The proportion of participants with T2D increased from 12.9% (37.3% women) at baseline to 17.1% (41.1% women) with 74 incident cases and 22.2% not being aware of the disease at follow-up. More than half of the 41 newly identified incident T2D cases were diagnosed solely by the 2h-plasma glucose test (OGTT) and diagnosis based on OGTT as the only criterion among incident cases was found more frequently in women (p=0.028). The OGTT assessed at baseline predicted incident T2D less accurate in men (AUC: 0.671, 95% CI 0.570-0.771) when compared to women (AUC: 0.7893, 95% CI 0.7036-0.8751). No sex differences were detected with respect to antidiabetic medication used and T2D severity. Conclusions: A comprehensive picture of T2D with respect to prevalence, incidence, and severity in older people is provided. Clinically relevant sex differences in the capacity of the commonly used T2D diagnostic laboratory parameters to predict incident T2D on average 7.4 years later were detected.

Statine zahlen zu den am haufigsten verordneten Medikamenten deutschlandweit. Ihr Nutzen in der Senkung des kardiovaskularen Risikos ist unbestritten. Dennoch klagen viele Patienten uber Nebenwirkungen unter Statintherapie, wozu insbesondere statinassoziierte Muskelsymptome (SAMS) zahlen. Diese sind trotz ihrer relativen Haufigkeit schwer zu erfassen und objektiv zu diagnostizieren, da der Zeitraum bis zum ersten Auftreten von Symptomen, die Art der Beschwerden und der Schweregrad der Muskelprobleme sehr stark variieren. In diesem narrativen Review werden die Ursachen der SAMS sowie neue Moglichkeiten zur Diagnostik und Therapie zusammengefasst.

Patients with diabetes mellitus are at risk for micro- and macrovascular complications that are responsible for a substantial part of the individual health burden and socio-economic costs. Therefore, implementable risk scores are needed to improve targeted prevention for patients that are particularly susceptible to complications. The “epigenetic clock” estimates an individual’s biological age using DNA methylation profiles and was previously shown to be associated with morbidity and mortality.In this study, we examine older adults of the BASE-II study that were reexamined on average 7.4 years after baseline assessment as part of the GendAge study. For DNA methylation age (DNAmA) estimation we used the 7-CpG clock which was available for two timepoints (n=1,071 at follow-up). In addition, we determined epigenetic age using Horvath’s clock, Hannum’s clock, PhenoAge and GrimAge which were available at follow-up only (n=1,067). The deviation of DNAmA from chronological age, DNA methylation age acceleration (DNAmAA), was calculated as residuals of a leukocyte cell count adjusted linear regression analysis. Diabetes associated complications were assessed with the Diabetes Complications Severity Index (DCSI).Cross-sectionally, a statistically significant association between oral glucose tolerance test results and Hannum (ß=0.8, SE=0.3, p=0.02, n=762) and PhenoAge DNAmAA (ß=0.8, SE=0.3, p=0.003, n=762) was found. PhenoAge was also associated with fasting glucose (ß=0.3, SE=0.1, p=0.013, n=966). In contrast, we observed no cross-sectional association after covariate adjustment between DNAmAA and a diagnosis of diabetes mellitus with any of the five clocks employed. This was true for longitudinal analyses with the 7-CpG clock as well. However, longitudinal analyses showed that every year in the 7-CpG-based DNAmAA estimate at baseline increased the risk for developing of one or more additional complications or worsening of an already existing complication during the follow-up period by 11% in male participants with diabetes mellitus type 2. This association persisted after adjustment for DCSI at baseline, chronological age, smoking, alcohol, diabetes medication, and BMI (OR =1.11, p=0.045, n=56). No statistically significant association was found in the subgroup of women or when the whole dataset was analyzed (p>0.05).Although our findings still need to be independently validated, the 7-CpG clock appears to be a promising biomarker which is informative about the individual risk for diabetic complications independent of age, sex, lifestyle factors, or complications at baseline.

ObjectiveDiabetes is a risk factor for dementia but little is known about the impact of diabetes duration on the risk of dementia. We investigated the effect of type 2 diabetes duration on the risk of dementia.DesignProspective cohort study using health claims data representative for the older German population. The data contain information about diagnoses and medical prescriptions from the in- and outpatient sector.MethodsWe performed piecewise exponential models with a linear and a quadratic term for time since first type 2 diabetes diagnosis to predict the dementia risk in a sample of 13,761 subjects (2,558 dementia cases) older than 65 years. We controlled for severity of diabetes using the Adopted Diabetes Complications Severity Index.ResultsWe found a U-shaped dementia risk over time. After type 2 diabetes diagnosis the dementia risk decreased (26% after 1 year) and reached a minimum at 4.75 years, followed by an increase through the end of follow-up. The pattern was consistent over different treatment groups, with the strongest U-shape for insulin treatment and for those with diabetes complications at the time of diabetes diagnosis.ConclusionsWe identified a non-linear association of type 2 diabetes duration and the risk of dementia. Physicians should closely monitor cognitive function in diabetic patients beyond the first few years after diagnosis, because the later increase in dementia occurred in all treatment groups.

Aim: To describe the prevalence, incidence, and severity of diabetes mellitus type 2 (T2D) and antidiabetic medication in older people and to assess the prognostic value of diagnostic laboratory parameters.Methods: Baseline data of 1,671 participants of the Berlin Aging Study II (68.8 ±3.7 years) and follow-up data assessed 7.4 ±1.5 years later were analysed. T2D was diagnosed based on self-report, antidiabetic medication use, laboratory parameters. T2D severity was determined by the diabetes complications severity index (DCSI). Prognostic capacity of laboratory parameters was evaluated by Receiver Operating Characteristics (ROC) and Areas Under the Curve (AUCs).Results: The proportion of participants with T2D increased from 12.9% (37.3% women) at baseline to 17.1% (41.1% women) with 74 incident cases and 22.2% not being aware of the disease at follow-up. More than half of the 41 newly identified incident T2D cases were diagnosed solely by the 2h-plasma glucose test (OGTT) and diagnosis based on OGTT as the only criterion among incident cases was found more frequently in women (p=0.028). The OGTT assessed at baseline predicted incident T2D less accurate in men (AUC: 0.671, 95% CI 0.570-0.771) when compared to women (AUC: 0.7893, 95% CI 0.7036-0.8751). No sex differences were detected with respect to antidiabetic medication used and T2D severity. Conclusions: A comprehensive picture of T2D with respect to prevalence, incidence, and severity in older people is provided. Clinically relevant sex differences in the capacity of the commonly used T2D diagnostic laboratory parameters to predict incident T2D on average 7.4 years later were detected.

The cardiac muscle has the ability to adapt to different loading conditions. We analyzed the associations of the age-related decreasing handgrip strength (HGS), a marker of muscular fitness, on cardiac structure and function in a community-based sample.We performed cross-sectional analyses of 4646 subjects (2554 women; 55.0%) aged 20 to 93 years from two independent cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analyzed the associations of HGS with structural and functional left and right ventricular (LV and RV) and left atrial (LA) parameters as determined by echocardiography and magnetic resonance imaging (MRI) as well with log-transformed NT-proBNP values using multivariable-adjusted linear regression models.MRI data showed that a 1 kg lower HGS was associated with a 0.40 mL (95% confidence interval: 0.26 to 0.54; p 0.001) lower LV end-diastolic volume, a 0.011 mm (0.005 to 0.018; p = 0.001) lower LV wall-thickness, a 0.59 g (0.43 to 0.75; p 0.001) lower LV mass, a 0.58 mL/beat (0.43 to 0.74; p 0.001) lower LV stroke volume, a 0.03 L/min (0.02 to 0.04; p 0.001) lower LV cardiac output, a 0.48 mL (0.27 to 0.68; p 0.001) lower LA end-diastolic volume, and a 1.02 mL (0.71 to 1.32) lower RV end-diastolic volume. Similar findings were observed for echocardiographic parameters. Moreover, lower HGS was associated with higher echocardiographic LV diastolic stiffness and NT-proBNP levels.In this large population-based sample, lower muscular fitness as assessed by HGS was associated with lower LV wall thickness and mass as well as with smaller chamber size, stroke volume and cardiac output of the LV, LA and RV. Moreover, HGS was inversely related to LV diastolic stiffness and NT-proBNP values. These outcomes might demonstrate the effects of an aging-related decrease in physical activity and lower muscular fitness on the heart - "the sedentary's heart".

Background Although an inverse association between type II diabetes mellitus and Lipoprotein (a) [LP(a)] has already been well researched, there is sparse data on the association between metabolic syndrome (MetS) with Lp(a). MetS is highly prevalent in older people and insulin resistance in MetS might link Lp(a) with MetS. Thus, we analyzed the association between Lp(a) with MetS in two large cohorts the Berlin Aging Study II [BASE-II] and the Study of Health in Pomerania [SHIP-0] Methods Complete cross-sectional data was available for 5,743 BASE-II and SHIP-0 participants (48.7% men; age 58 [20-85] years). MetS was defined according to modified criteria of the AHA/NHLBI 2009 definition. The association between MetS with Lp(a) was examined by median regression adjusted for age, sex and study and models were stratified by gender and menopause. Results MetS was prevalent in 27.6% (n=1,573) participants. We found an inverse association between MetS with Lp(a) in the whole study sample (β=-11.9 [95% confidence interval (95% CI) -21.3 to -2.6]) as well as in men (β=-16.5 [95% CI -28.6 to -4.3]) and in postmenopausal women (β=-25.4 [95% CI -46.0 to -4.8]). In contrast to this, in premenopausal women a positive association between MetS and Lp(a) (β=39.2 [95% CI 12.3 to 65.9]) was evident. Conclusion Postmenopausal changes in hormone metabolism impact both MetS and Lp(a). With respect to the ongoing development of Lp(a)-lowering drugs, their use must be examined, particularly in old age and in subjects with MetS.

BACKGROUND: An inverse association between lipoprotein(a) (Lp[a]) and type 2 diabetes mellitus is well documented. However, data on the association of the metabolic syndrome (MetS) with Lp(a) are sparse. METHODS: Cross-sectional data for MetS and Lp(a) were available for 5743 BASE-II and SHIP-0 participants (48.7% men; age 58 [20–85] years) (BASE, Berlin Aging Study; SHIP, Study of Health in Pomerania). The association of MetS and its components with Lp(a) was analyzed by means of median regression adjusted for age, sex, and study. Associations were evaluated for the total population as well as stratified by sex and menopausal status. RESULTS: Overall, 27.6% (n = 1573) of the participants in the two studies had MetS and 22.5% (n = 1291) were premenopausal women. There was an inverse association between MetS and Lp(a) in the whole study sample (ß = -11.9, 95% confidence interval [-21.3; -2.6]) as well as in men (ß = -16.5 [-28.6; -4.3]). Participants with MetS (whole study sample) had 11.9 mmol/L lower Lp(a). Analogous results were found in postmenopausal women (ß = -25.4 [-46.0; -4.8]). In premenopausal women with MetS, Lp(a) levels were higher by 39.1 mg/L on average [12.3; 65.9]) than in premenopausal women without MetS. CONCLUSION: Hormonal aspects and menopausal alterations seem to affect the association between MetS and Lp(a), as the expected inverse association was not present in premenopausal women.

Statins are among the most frequently prescribed drugs in Germany. Their benefits in lowering cardiovascular risk are beyond dispute. Nevertheless, many patients complain of side effects from statin therapy, including statin-associated muscle symptoms (SAMS) in particular. Despite their relative frequency, it is difficult to objectively diagnose them, as the time until appearance of first symptoms, the nature of the complaints and the severity of muscle problems vary widely. This narrative review summarizes the causes of SAMS as well as new possibilities regarding their diagnosis and therapy.Statine zählen zu den am häufigsten verordneten Medikamenten deutschlandweit. Ihr Nutzen in der Senkung des kardiovaskulären Risikos ist unbestritten. Dennoch klagen viele Patienten über Nebenwirkungen unter Statintherapie, wozu insbesondere statinassoziierte Muskelsymptome (SAMS) zählen. Diese sind trotz ihrer relativen Häufigkeit schwer zu erfassen und objektiv zu diagnostizieren, da der Zeitraum bis zum ersten Auftreten von Symptomen, die Art der Beschwerden und der Schweregrad der Muskelprobleme sehr stark variieren. In diesem narrativen Review werden die Ursachen der SAMS sowie neue Möglichkeiten zur Diagnostik und Therapie zusammengefasst.

Background: Inflammatory processes are a cause of accelerated loss of muscle mass. Metabolic syndrome (MetS) is a highly prevalent age-related condition, which may promote and be promoted by inflammation. However, whether inflammation in MetS (metaflammation) is associated with lower muscle mass is still unclear. Methods: Complete cross-sectional data on body composition, MetS, and the inflammatory markers interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF), and C-reactive protein (CRP) were available for 1,377 BASE-II participants (51.1% women; 68 ± 4 years old). Appendicular lean mass (ALM) was assessed by dual-energy X-ray absorptiometry. Low muscle mass (low ALM-to-BMI ratio [ALMBMI]) was defined according to the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project. Regression models, adjusted for an increasing number of confounders (sex, age, physical activity, morbidities, diabetes mellitus type II, TSH, albumin, HbA1c, smoking habits, alcohol intake, education, and energy intake/day), were used to calculate the association between low ALMBMI and high inflammation (tertile 3) according to MetS. Results: MetS was present in 36.2% of the study population, and 9% had low ALMBMI. In the whole study population, high CRP (odds ratio [OR]: 2.7 [95% CI: 1.6–4.7; p = 0.001]) and high IL-6 (OR: 2.1 [95% CI: 1.2–1.9; p = 0.005]) were associated with low ALMBMI. In contrast, no significant association was found between TNF, IL-10, or IL-1β with low ALMBMI. When participants were stratified by MetS, results for IL-6 remained significant only in participants with MetS. Conclusions: Among BASE-II participants, low ALMBMI was associated with inflammation. Low-grade inflammation triggered by disease state, especially in the context of MetS, might favor loss of muscle mass, so a better control of MetS might help to prevent sarcopenia. Intervention studies to test whether strategies to prevent MetS might also prevent loss of muscle mass seem to be promising.

Contains fulltext : 228447.pdf (Publisher’s version ) (Open Access) We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults. 17 p.

Purpose: Age-related changes affect vitamin D absorption and metabolism. Low 25-hydroxyvitamin D concentrations have been reported as risk factor for the development of metabolic syndrome (MetS). However, recent evaluations suggest this association might be explained by obesity or insulin resistance (IR) in subjects with MetS. Our aim was to analyze associations between vitamin D insufficiency and MetS in a young cohort without diabetes and two senior cohorts with and without diabetes. Methods: Four hundred sixteen young and 1357 older BASE-II participants were analyzed. Type 2 diabetes (T2D) was defined according to European Society of Cardiology (ESC) guidelines, MetS as suggested by International Diabetes Federation/American Heart Association/National Heart, Lung and Blood Institute (IDF/AHA/NHLBI 2009). Vitamin D insufficiency was defined as 25-hydroxyvitamin D concentrations

BackgroundObesity is associated with chronic low-grade inflammation leading to metabolic and cardiovascular diseases, but a subset of obese individuals is considered metabolically healthy. The underlying pathophysiologic mechanisms remain elusive and clinical studies on the relationship between inflammatory markers and metabolically healthy obesity (MHO) are scarce.MethodsIn this cross-sectional analysis, we included a sample of 437 older participants (60–84 years) from the Berlin Aging Study II (BASE-II). Peripheral blood mononuclear cells were isolated, immune cell subsets were analyzed with multiparameter flow cytometry and systemic cytokine levels were measured. Immune cell parameters were correlated with metabolic measures and multiple linear regression analysis was conducted and adjusted for various demographic and clinical factors.ResultsWe found that frequencies of naïve and memory CD4+ and CD8+ T cells inversely correlated with measures for insulin sensitivity in the older population. Moreover, the percentages of naïve CD4+ and CD8+ T cells were significantly higher, whereas activated T cells and IL-6 levels were lower in metabolically healthy compared to metabolically unhealthy obese individuals. The percentages of naïve CD4+ and CD8+ T cells were predictive for impaired insulin sensitivity (ß=0.16, p = 0.01 and ß=0.11, p = 0.04), and the association of naïve CD4+ T cells with insulin sensitivity persisted after multivariate adjustment (ß=0.14, p = 0.02).ConclusionsThese findings support the hypothesis that parameters of systemic inflammation can differentiate metabolically healthy from metabolically unhealthy obese individuals that are at higher risk for cardiometabolic diseases and may have clinical implications with regard to obesity treatment stratification.Trial registrationDRKS00009277. Registered 31 August 2015 - Retrospectively registered, https://www.base2.mpg.de/de

BACKGROUND: Walking ability is an important prerequisite for activity, social participation and independent living. While in most healthy adults, this ability can be assumed as given, limitations in walking ability occur with increasing age. Furthermore, slow walking speed is linked to several chronic conditions and overall morbidity. Measurements of gait parameters can be used as a proxy to detect functional decline and onset of chronic conditions. Up to now, gait characteristics used for this purpose are measured in standardized laboratory settings. There is some evidence, however, that long-term measurements of gait parameters in the living environment have some advantages over short-term laboratory measurements. METHODS: We evaluated cross-sectional data from an accelerometric sensor worn in a subgroup of 554 participants of the Berlin Aging Study II (BASE-II). Data from the two BASE-II age groups (age between 22-36 years and 60-79 years) were used for the current analysis of accelerometric data for a minimum of two days and a maximum of ten days were available. Real world walking speed, number of steps, maximum coherent distance and total distance were derived as average data per day. Linear regression analyses were performed on the different gait parameters in order to identify significant determinants. Additionally, Mann-Whitney-U-tests were performed to detect sex-specific differences. RESULTS: Age showed to be significantly associated with real world walking speed and with the total distance covered per day, while BMI contributed negatively to the number of walking steps, maximum coherent distance and total distance walked. Additionally, sex was associated with walking steps. However, R2-values for all models were low. Overall, women had significantly more walking steps and a larger coherent distance per day when compared to men. When separated by age group, this difference was significant only in the older participants. Additionally, walking speed was significantly higher in women compared to men in the subgroup of older people. CONCLUSIONS: Age- and sex-specific differences have to be considered when objective gait parameters are measured, e.g. in the context of clinical risk assessment. For this purpose normative data, differentiating for age and sex would have to be established to allow reliable classification of long-term measurements of gait.

BackgroundOlder persons with poor sleep are more likely to develop neurodegenerative disease, but the causality underlying this association is unclear. To move towards explanation, we examine whether sleep quality and quantity are similarly associated with brain changes across the adult lifespan.MethodsAssociations between self-reported sleep parameters (Pittsburgh Sleep Quality Index;PSQI) and longitudinal cortical change were tested using five samples from theLifebrainconsortium (n=2205, 4363 MRIs, 18-92 years). Analyses were augmented by considering episodic memory change, gene expression from the Allen Human Brain Atlas, and amyloid-beta (Aβ) accumulation (n=1980).ResultsPSQI components sleep problems and low sleep quality were related to thinning of the right lateral temporal cortex. The association with sleep problems emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. BMI and symptoms of depression had negligible effects. Sleep problems were neither related to longitudinal change in episodic memory function nor to Aβ accumulation, suggesting that sleep-related cortical changes were independent of AD neuropathology and cognitive decline.ConclusionWorse self-reported sleep in later adulthood was associated with more cortical thinning in regions of high expression of genes related to oligodendrocytes and S1 pyramidal neurons, but not to Aβ accumulation or memory decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes, except for a few restricted regions, indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

Zusammenfassung Hintergrund Diabetes mellitus Typ 2 (T2DM) und Sarkopenie nehmen mit steigendem Alter in ihrer Prävalenz zu und können langfristig betrachtet jeweils zu erheblichen gesundheitlichen und funktionellen Einschränkungen führen. Während eine zunehmende Insulinresistenz bei abnehmender Muskelmasse plausibel erscheint, sind umgekehrt auch glukotoxische negative Effekte auf die Skelettmuskulatur im Sinne einer sekundären Sarkopenie denkbar. Ziel dieser Arbeit war es, den Zusammenhang zwischen Sarkopenie, Insulinresistenz und T2DM bei älteren Menschen zu untersuchen. Methoden Untersucht wurden 1555 Probanden der Berliner Altersstudie II (BASE-II) mit einem durchschnittlichen Alter von 68 ± 4 Jahren. Die Diagnose T2DM wurde basierend auf der Anamnese sowie oralem Glukosetoleranztest und HbA1c-Wert nach ADA-Kriterien gestellt und die Insulinresistenz wurde via Homeostatic Model Assessment for Insulin resistance (HOMA-IR) und Insulinsensitivitätsindex nach Matsuda (ISI) eingeschätzt. Die appendikuläre Skelettmuskelmasse (ALM) wurde mittels Dual-Röntgen-Absorptiometrie (DXA) und eine Sarkopenie mithilfe der anhand des Body-Mass-Index (BMI) korrigierten Muskelmasse (ALM/BMI) nach den Cut-off-Werten des FNIH Sarcopenia Project bestimmt. Gruppenvergleiche wurden mittels Kruskal-Wallis-Test berechnet, und der Zusammenhang zwischen Diabetes mellitus und Sarkopenie bzw. ALM und Insulinresistenz wurde mittels geeigneter Regressionsmodelle überprüft. Ergebnisse 25,2 % der insgesamt 160 Probanden mit T2DM hatten bereits eine Sarkopenie. Sarkopenisch-adipöse Probanden wiesen im Vergleich zu nur adipösen, nur sarkopenen oder weder adipösen noch sarkopenen Probanden im Median einen niedrigeren ISI und einen höheren HOMA-IR auf (jeweils p Diskussion Sarkopenie ist sowohl mit Insulinresistenz als auch T2DM assoziiert. Die Frage bzgl. der Kausalität ist aufgrund des querschnittlichen Designs der Studie nicht zu beantworten, jedoch sollte eine mögliche Rolle des T2DM als sekundäre Sarkopenieursache berücksichtigt und weiter untersucht werden. Im Hinblick auf mögliche Folgen erscheinen die Identifizierung von Risikopatienten mit kombiniertem Auftreten von Sarkopenie und Insulinresistenz und die Evaluation basaler präventiver Maßnahmen wie gezieltes körperliches Training und angepasste Ernährung ein weiterführendes sinnvolles Ziel.

Glucose regulation is a key aspect of healthy aging and has been linked to brain functioning and cognition. Here we examined the role of glucose regulation for within-person longitudinal trajectories of well-being. We applied growth models to data from the Berlin Aging Study II (N = 955), using insulin resistance as an index of glucoregulatory capacity. We found that poor glucose regulation (higher insulin resistance) was consistently associated with lower levels of well-being among older men but not women. Our study provides novel evidence for the relevance of glucose regulation for well-being among older men. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Sex-specific differences in factors associated with aging and lifespan, such as sarcopenia and disease development, are increasingly recognized. The study aims to assess sex-specific aspects of the association between vitamin D insufficiency and low lean mass as well as between vitamin D insufficiency and the frailty phenotype.A total of 1102 participants (51% women) from the Berlin Aging Study II were included in this cross-sectional study. Vitamin D insufficiency was defined as a 25(OH)D level50 nmol/L. Lean mass was assessed with dual-energy x-ray absorptiometry and corrected by body mass index. Low lean mass was defined according to the Foundations for the National Institutes of Health Sarcopenia Project criteria (appendicular lean mass/body mass index0.789 in men and0.512 in women) and frailty defined according to the Fried criteria.In a risk factor-adjusted analysis, the association of vitamin D insufficiency was significantly influenced by sex (P for interaction0.001). Men with vitamin D insufficiency had 1.8 times higher odds of having low lean mass, with no association between vitamin D insufficiency and low lean mass in women. Participants with vitamin D insufficiency had 1.5 higher odds of being prefrail/frail with no significant effect modification by sex.We found notable sex-specific differences in the association of vitamin D insufficiency with low lean mass but not of vitamin D insufficiency with frailty. Vitamin D might play a relevant role in the loss of lean mass in men but not women and might be a biological marker of an unfavorable aging process associated with early development of frailty regardless of sex.

Background: Untreated overt hypo- and hyperthyroidism can lead to detrimental effects on muscle tissue and physical performance, but it is still unclear whether subclinical hypo- or hyperthyroidism...

Background: Frailty and the metabolic Syndrome (MetS) are frequently found in old subjects and have been associated with increased risk of functional decline and dependency. Moreover, central characteristics of the MetS like inflammation, obesity and insulin resistance have been associated with the frailty syndrome. However, the relationship between MetS and frailty has not yet been studied in detail. Aim of the current analysis within the Berlin Aging Study II (BASE-II) was to explore associations between MetS and frailty taking important co-variables such as nutrition (total energy intake, dietary vitamin D intake), physical activity and vitamin D-status into account. Methods: Complete cross-sectional data of 1,486 old participants (50.2% women, 68.7 (65.8-71.3) years) of BASE-II were analyzed. MetS was defined following the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity in 2009. Frailty was defined according to the Fried criteria. Limitations in physical performance were assessed via questionnaire, muscle mass was measured using dual energy X-ray absorptiometry (DXA) and grip strength using a Smedley dynamometer. Adjusted regression models were calculated to assess the association between MetS and Frailty. Results: MetS was prevalent in 37.6% of the study population and 31.9% were frail or prefrail according to the here calculated frailty index. In adjusted models the odds of being frail/prefrail were increased about 50% with presence of the MetS (OR1.5; 95% CI 1.2,1.9; p= 0.002). Moreover the odds of being prefrail/frail were significantly increased with low HDL-C (OR: 1.5 (95%CI: 1.0-2.3); p = 0.037); and elevated waist circumference (OR: 1.65 (95%CI: 1.1-2.3); p = 0.008). Conclusion: The current analysis supports an association between MetS and frailty. There are various metabolic, immune and endocrine alterations in MetS that also play a role in mechanisms underlying the frailty syndrome. To what extent cytokine alterations, inflammatory processes, vitamin D supply and hormonal changes in age and in special metabolic states as MetS influence the development of frailty should be subject of further research.

Zusammenfassung Hintergrund: Als metabolisches Syndrom (MetS) wird ein Symptomkomplex metabolischer Veränderungen bezeichnet, der eng mit Insulinresistenz (IR) assoziiert ist. Cutoff Werte für HOMA-IR, einem Surrogatparameter für IR, zur Identifikation von Probanden mit MetS sind nicht etabliert. Methoden: Insgesamt lagen Querschnittsdaten von 446 Studienteilnehmern im jüngeren Lebensalter (53% Frauen, 28±3 Jahre alt) und 1271 im höheren Lebensalter (52% Frauen, 68±4 Jahre alt) ohne Diabetes vor. MetS wurde nach den IDF/AHA/NHLBI (International Diabetes Foundation/American Heart Association/National Health, Lung and Blood Institute) Kriterien von 2009 definiert. Mittels ROC-Analyse wurden Cutoff-Werte für HOMA-IR berechnet, oberhalb derer Probanden mit MetS mit höchster Sensitivität und Spezifität erkannt werden konnten. Zuletzt wurden binär logistische Regressionsmodelle berechnet. Ergebnisse: Die Prävalenz von MetS betrug 6,7% bei den jungen und 28,3% bei den älteren Probanden. Cutoff-Werte für HOMA-IR, oberhalb derer MetS identifiziert werden konnte, waren HOMA-IR >1,88 (bei jungen Studienteilnehmern; Sensitivität 80%, Spezifität 85,3%, positiv prädiktiver Wert 80%, negativ prädiktiver Wert 15%) und HOMA-IR >1,98 (bei den älteren Studienteilnehmern; Sensitivität 73,6%, Spezifität 72,9%, positiv prädiktiver Wert 74%, negativ prädiktiver Wert 27%). Patienten oberhalb dieser Cutoff-Werte hatten im höchst adjustierten (Alter, BMI, Geschlecht, körperliche Aktivität und getrennt nach Altersgruppen) binären Regressionsmodell Odds von 5,7 (95% CI: 4,1–7,9) bei älteren und 22,2 (95% CI: 7,0–70,5) bei jüngeren Studienteilnehmern, MetS aufzuweisen. Schlussfolgerungen: Cutoff-Werte für HOMA-IR sind im Klinikalltag nicht etabliert, könnten aber herangezogen werden, um Personen mit MetS zu identifizieren und gegebenenfalls frühzeitig eine Therapie einzuleiten, auch wenn aufgrund der negativen prädiktiven Werte eine Diagnostik des MetS durch HOMA-IR allein nicht erfolgen kann.

Background: The length of the chromosome ends, telomeres, is widely accepted as a biomarker of aging. However, the dynamic of the relationship between telomere length and hematopoietic parameters in the normal aging process, which is of particular interest with respect to age-related anemia, is not well understood. Objective: We have analyzed the relationship between relative leukocyte telomere length (rLTL) and several hematological parameters in the older group of the Berlin Aging Study II (BASE-II) participants. This paper also compares rLTL between both BASE-II age groups (22-37 and 60-83 years). Methods: Genomic DNA was extracted from peripheral blood leukocytes of BASE-II participants and used to determine rLTL by a quantitative PCR protocol. Standard methods were used to determine blood parameters, and the WHO criteria were used to identify anemic participants. Results: Telomere length data were available for 444 younger participants (28.4 ± 3.1 years old; 52% women) and 1,460 older participants (68.2 ± 3.7 years old; 49.4% women). rLTL was significantly shorter in BASE-II participants of the older group (p = 3.7 × 10-12) and in women (p = 4.2 × 10-31). rLTL of older men exhibited a statistically significant, positive partial correlation with mean corpuscular hemoglobin (MCH; p = 0.012) and MCH concentration (p = 0.002). While these correlations were only observed in men, the rLTL of older women was negatively correlated with the number of thrombocytes (p = 0.015) in the same type of analysis. Among all older participants, 6% met the criteria to be categorized as ‘anemic'; however, there was no association between anemia and rLTL. Conclusion: In the present study, we have detected isolated correlations between rLTL and hematological parameters; however, in all cases, rLTL explained only a small part of the variation of the analyzed parameters. In disagreement with some other studies showing similar data, we interpret the association between rLTL and some of the hematological parameters studied here to be at most marginal. This applies also to the role of rLTL in anemia, at least in the age group investigated here. Since BASE-II is yet another large cohort in which women have on average shorter telomeres than men, this finding will be addressed in the discussion with respect to the ongoing debate on gender differences in telomere length.

Problematic drinking behavior is common in the old and negative consequences of hypoglycemic episodes in type 2 diabetes (T2D) as a result of alcohol consumption have been described previously. Although, associations between such hypoglycemic episodes with reduced muscle mass are discussed, it is uncertain if problematic drinking behavior drives decline of muscle mass and/or muscle function. In the current study, we analyzed data of the Berlin Aging Study II (BASE-II) to examine the association of problematic drinking behavior with muscle mass and grip strength in T2D. Cross-sectional data of 1451 old BASE-II participants (51.6% women; 60–84 years old) were analyzed. Problematic drinking behavior was assessed using the Alcohol Use Identification Test (AUDIT). Muscle mass was measured using dual energy X-ray absorptiometry (DXA), grip strength using a Smedley dynamometer. Adjusted regression models were calculated to assess the association of problematic drinking with muscle mass and grip strength. Problematic drinking was evident in 11.2% of BASE-II participants and in 12.5% of BASE-II participants diabetes was evident. In the fully adjusted model (adjusted for age, trunk fat mass, HbA1c, antidiabetic medication, TSH, CRP, testosterone, physical inactivity, depression (GDS-score), morbidities, smoking status and total energy intake/day, we found a statistically significant association between problematic drinking and muscle mass (β-3.7, SE: 1.3, R2 0.481, partial eta square 0.166, observed power 0.816, p-value 0.005) and grip strength (β-8.1, SE: 3.3, R2 0.222, partial eta square 0.134, observed power 0.670, p-value 0.018) in old diabetic men. These associations were not evident in women and subjects without T2D. Problematic drinking behavior was associated with lower muscle mass and grip strength in old men with diabetes. This topic should be addressed in these subjects as they could be at increased risk for early functional decline, sarcopenia or frailty.

Background: Mild-to-moderate chronic kidney disease (CKD G3a) is prevalent in older adults. Substantial evidence suggests that individuals with advanced CKD face a high risk for common geriatric conditions, like functional impairment and cognitive decline, whereas the relationships between mild-to-moderate CKD and functional impairment and cognitive decline, but also poor nutritional status and mood disorders, are still unclear. Objective: The aim of this study was to explore associations between mild-to-moderate CKD and impairments in the core domains of geriatric assessment (GA) in a large cohort of community-dwelling older adults. Methods: This was a cross-sectional analysis of 1,476 participants of the Berlin Aging Study II. Study participants were stratified as to presence or absence of CKD G3a (estimated glomerular filtration rate [eGFR] 45-59 mL/min/1.73 m2 vs. eGFR ≥60 mL/min/1.73 m2). GA comprised the following instruments: the Activities of Daily Living Scale (ADL), the Timed up and Go (TUG), the Tinetti test (Tinetti), the Mini-Mental-State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Mini Nutritional Assessment (MNA). We used logistic regression models to estimate multivariable-adjusted associations between CKD G3a and impairments in the respective domains. Results: A total of 282 subjects with mild-to-moderate CKD (CKD G3a) were identified (19.1%). Overall, the prevalence of impairments identified was higher among subjects with compared to without CKD G3a (21 vs. 15.9%, p = 0.043). In multivariable-adjusted models, CKD G3a was consistently associated with increased odds of an impaired gait performance as to the TUG (adjusted odds ratio 2.06, 95% CI 1.04-4.09). In contrast, on average, individuals with and without CKD G3a did not differ as to their results in the MMSE, the ADL, the MNA, and the GDS. Conclusion: GA identified impairments in 21 versus 15.9% of older adults with and without mild-to-moderate CKD, respectively. However, except for an increased likelihood of impaired gait performance (TUG) with mild-to-moderate CKD, we did not find independent associations between mild-to-moderate CKD and geriatric conditions.

Inverse relationships have been described between the largely genetically determined levels of serum/plasma lipoprotein(a) [Lp(a)], type 2 diabetes (T2D) and fasting insulin. Here, we aimed to evaluate the nature of these relationships with respect to causality. We tested whether we could replicate the recent negative findings on causality between Lp(a) and T2D by employing the Mendelian randomization (MR) approach using cross-sectional data from three independent cohorts, Berlin Aging Study II (BASE-II; n = 2012), LIFE-Adult (n = 3281) and LIFE-Heart (n = 2816). Next, we explored another frequently discussed hypothesis in this context: Increasing insulin levels during the course of T2D disease development inhibits hepatic Lp(a) synthesis and thereby might explain the inverse Lp(a)–T2D association. We used two fasting insulin-associated variants, rs780094 and rs10195252, as instrumental variables in MR analysis of n = 4937 individuals from BASE-II and LIFE-Adult. We further investigated causality of the association between fasting insulin and Lp(a) by combined MR analysis of 12 additional SNPs in LIFE-Adult. While an Lp(a)–T2D association was observed in the combined analysis (meta-effect of OR [95% CI] = 0.91 [0.87–0.96] per quintile, p = 1.3x10-4), we found no evidence of causality in the Lp(a)–T2D association (p = 0.29, fixed effect model) when using the variant rs10455872 as the instrumental variable in the MR analyses. Likewise, no evidence of a causal effect of insulin on Lp(a) levels was found. While these results await confirmation in larger cohorts, the nature of the inverse Lp(a)–T2D association remains to be elucidated.

Pharmacological options for the treatment of sarcopenia currently do not exist. However, off-label treatment options of some established drugs have been suggested. The aim of this study was to assess differences in various muscle and physical performance parameters in relation to the intake of angiotensin-converting enzyme (ACE) inhibitors in a cohort of community-dwelling older people. Eight hundred and thirty-eight participants from the Berlin Aging Study-II (BASE-II) were included. Appendicular lean mass was assessed with dual-energy X-ray absorptiometry and related to height and body mass index. Muscle strength was measured by grip strength and related to muscle mass (arm muscle quality) and functional status was assessed via the timed “Up and Go” test. Users of ACE inhibitors had higher lean mass related to height but significantly lower lean mass related to body mass index (p = 0.001 for women and p

Background: The metabolic syndrome (MetS) is a cluster of metabolic changes which is associated with insulin resistance (IR). Cutoff values for the homeostasis model of insulin resistance (HOMA-IR) – a surrogate marker of IR-to identify subjects with MetS are not established. Methods: Cross-sectional data of 446 younger (53% women, 28±3 years old) and 1271 elderly study participants (52% women, 68±4 years old) without diabetes were available for the current analysis. MetS was defined according to the IDF/AHA/NHLBI (International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute) criteria of 2009. Using receiving operating characteristics (ROC) analysis cutoff values for HOMA-IR were calculated above which participants with MetS could be identified with highest sensitivity and specificity. Finally, binary logistic regression models were calculated. Results: The prevalence of MetS was 6.7% in young and 28.3% in elderly subjects. HOMA-IR cutoff values for the detection of MetS were HOMA-IR >1.88 (young subjects; sensitivity 80%, specificity 85.3%, positive predictive value 80%, negative predictive value 15%) and HOMAIR >1.98 (elderly subjects; sensitivity 73.6%, specificity 72.9%, positive predictive value 74%, negative predictive value 27%). In adjusted regression models [age, body mass index (BMI), sex, physical activity and age groups] subjects above these cutoff-values had odds of 5.7 [95% confidence interval (CI): 4.1–7.9] in elderly and 22.2 (95% CI: 7.0–70.5) in younger study participants to have MetS. Conclusions: Cutoff values for HOMA-IR are not established in clinical practice; however, they could be used to identify subjects with MetS, even if a diagnosis of MetS cannot made based solely on HOMA-IR considering the negative predictive values.

Background Loss of muscle mass, particularly in old age, can restrict mobility and physical function. Sleep is thought to play a key role in the maintenance of muscle mass; sleep disturbances have a prevalence of 6–30% in Germany. In this study, based on data from the Berlin Aging Study II (BASE-II), we analyze the relationship between sleep efficiency and quality on the one hand, and muscle mass and muscle function on the other.

Background: Decreased bone mineral density (BMD) has been linked to metabolic disorders, such as type 2 diabetes. However, results regarding the metabolic syndrome (MetS), a cluster of at least 3 of 5 cardiovascular risk parameters with potentially contradictory effects on BMD are still inconclusive. Objective: We investigated the effect of MetS and its single parameters on BMD at 3 sites in community-dwelling older subjects. Methods: 1,402 subjects (51.1% female, 68 ± 4 years old) from the Berlin Aging Study II (BASE-II) were included. MetS was defined as suggested by IDF/NHLBI/AHA. Insulin resistance (IR) was assessed by the homeostasis model of IR. BMD (lumbar spine, femur neck, hip) and trunk fat were measured by dual-energy X-ray absorptiometry. Osteoporosis was defined by a T score of ≤-2.5. Results: MetS was present in 29.6% of women and 41.7% of men. In regression models, we observed a positive association of MetS with the BMD of the lumbar spine (p = 0.005) and hip (p = 0.028) in women even after adjustment for risk factors, but no effect of the single parameters apart from IR. In contrast, there was no association between MetS and BMD in men. However, higher trunk fat and higher waist circumference were associated with lower levels of BMD in men with or without MetS (p < 0.05). Conclusion: We obtained different results in men and women. In women, the positive though slight effect of MetS on BMD could not be explained by single MetS components apart from IR. In men, central obesity was negatively associated with BMD, suggesting that the metabolic effects driven by visceral fat have a negative impact.