Muscle Mass and Inflammation in Older Adults: Impact of the Metabolic Syndrome.

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)-1ß, 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-1ß 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.

Association of thyroid function with insulin resistance: data from two population-based studies.

OBJECTIVE: Thyroid dysfunction is associated with relevant disturbances in glucose metabolism. Moreover, thyroid function undergoes important changes with ageing. The objective of this study was to investigate the association of thyroid function with insulin resistance with particular consideration of possible age-related effect modifications. DESIGN: A sample of 4193 participants from two independent epidemiological studies, the Study of Health in Pomerania-TREND-0 and the Berlin Aging Study II, was included in this cross-sectional analysis. METHODS: Insulin resistance was estimated by homeostasis model of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI). Associations of thyroid biomarkers (thyroid-stimulating hormone, free thyroxine, and free triiodothyronine (fT3)) with parameters of glucose metabolism were analysed by regression models adjusted for age, sex, smoking status, and study site. RESULTS: A higher fT3 was significantly associated with higher fasting glucose and higher fasting and 2-h postload insulin levels, a higher HOMA-IR, and lower ISI. A higher fT3 was also associated with a higher risk for impaired fasting glucose (RR 1.09, 95 CI 1.02; 1.18; P = 0.017). Many of these associations between thyroid markers and parameters of glucose metabolism were significant in young and middle-aged participants but not in older individuals. CONCLUSIONS: The main finding of this study was a consistent association of fT3 with almost all markers of insulin resistance. However, this effect seems to be wearing off in higher age highlighting a potential age-related modification of the interaction between thyroid function and glucose metabolism. Further studies are needed to clarify causal relationships.

Sex Differences in Characteristics Associated with Potentially Inappropriate Medication Use and Associations with Functional Capacity in Older Participants of the Berlin Aging Study II.

INTRODUCTION: Medication safety is a vital aim in older adults' pharmacotherapy. Increased morbidity and vulnerability require particularly careful prescribing. Beneath avoiding unnecessary polypharmacy and prescribing omissions, physicians have to be aware of potentially inappropriate medications (PIMs) and related outcomes to optimize older adults' drug therapy, and to reduce adverse drug events. OBJECTIVE: The aim of this study was to identify participants characteristics associated with PIM use and associations of PIM use with functional capacity with a focus on sex differences. METHODS: Multivariable logistic regression analyses of cross-sectional Berlin Aging Study II (BASE-II) data (N = 1,382, median age 69 years, interquartile range 67-71, 51.3% women) were performed with PIM classification according to the EU(7)-PIM list. RESULTS: In the overall study population, higher education was associated with lower odds of PIM use (odds ratio [OR] 0.93, confidence interval [CI] 95% 0.87-0.99, p = 0.017). Falls (OR 1.53, CI 95% 1.08-2.17, p = 0.016), frailty/prefrailty (OR 1.68, 1.17-2.41, p = 0.005), and depression (OR 2.12, CI 95% 1.32-3.41, p = 0.002) were associated with increased odds of PIM use. A better nutritional status was associated with lower odds of PIM use (OR 0.88, CI 95% 0.81-0.97, p = 0.008). In the sex-stratified analysis, higher education was associated with lower odds of PIM use in men (OR 0.90, CI 95% 0.82-0.99, p = 0.032). Frailty/prefrailty was associated with increased odds of PIM use in men (OR 2.04, CI 95% 1.18-3.54, p = 0.011) and a better nutritional status was associated with lower odds of PIM use in men (OR 0.83, CI 95% 0.72-0.96, p = 0.011). Falls in the past 12 months were related to an increased prevalence of PIM use in women (OR 1.74, CI 95% 1.10-2.75, p = 0.019). Depression was associated with a higher prevalence of PIM use in both men (OR 2.74, CI 95% 1.20-6.24, p = 0.016) and women (OR 2.06, CI 95% 1.14-3.71, p = 0.017). We did not detect sex differences regarding the overall use of drugs with anticholinergic effects, but more men than women used PIMs referring to the cardiovascular system (p = 0.036), while more women than men used PIMs referring to the genitourinary system and sex hormones (p < 0.001). CONCLUSION: We found similarities, but also differences between men and women as to the associations between PIM use and participants' characteristics and functional capacity assessments. The association of lower education with PIM use may suggest that physicians' prescribing behavior is modified by patient education, a relationship that could evolve from more critical attitudes of educated patients towards medication use. We conclude that sex differences in associations of PIM use with functional capacities might be partly attributable to sex differences in drug classes used, but not with regard to anticholinergics, as these are used to a similar extent in men and women in the cohort studied here.

Low muscle strength and increased arterial stiffness go hand in hand.

Low handgrip strength and increased arterial stiffness are both associated with poor health outcomes, but evidence on the relationship between handgrip strength and arterial stiffness is limited. In this cross-sectional analysis of combined baseline datasets from the LipidCardio and Berlin Aging Study II cohorts we aimed to examine whether handgrip strength (HGS) is associated with arterial stiffness. 1511 participants with a median age of 68.56 (IQR 63.13-73.08) years were included. Arterial stiffness was assessed by aortal pulse wave velocity (PWV) with the Mobil-O-Graph device. Handgrip strength was assessed with a handheld dynamometer.The mean HGS was 39.05 ± 9.07 kg in men and 26.20 ± 7.47 kg in women. According to multivariable linear regression analysis per 5 kg decrease in handgrip strength there was a mean increase in PWV of 0.08 m/s after adjustment for the confounders age, sex, coronary artery disease, systolic blood pressure, body mass index, cohort, and smoking. Thus, there was evidence that low handgrip strength and increased arterial stiffness go hand in hand. Arterial stiffness can possibly create the missing link between low handgrip strength and increased cardiovascular morbidity and mortality. Causality and direction of causality remain to be determined.

Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10-17), arthritis (GDF5 p = 4 × 10-13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.

Problematic drinking in the old and its association with muscle mass and muscle function in type II diabetes.

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 (ß-3.7, SE: 1.3, R2 0.481, partial eta square 0.166, observed power 0.816, p-value 0.005) and grip strength (ß-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.

Clinical outcome of a patient with lysosomal acid lipase deficiency and first results after initiation of treatment with Sebelipase alfa: A case report.

We report on a case of very rare autosomal recessive cholesteryl ester storage disease due to lysosomal acid lipase deficiency (LALD). LALD is caused by mutations in the lysosomal acid lipase A (LIPA) gene resulting in cholesteryl ester accumulation in liver, spleen, and macrophages. It can lead to liver failure, accelerated atherosclerosis and premature death. Until recently, treatment options were limited to lipid-lowering medications to control dyslipidemia. Presently, a long-term enzyme replacement therapy with Sebelipase alfa, a recombinant human lysosomal acid lipase, is available for patients with LALD. Our patient's condition became conspicuous at the age of two due to a xanthogranuloma of the chin together with increased lipid levels, elevated liver enzymes and hepatomegaly. It took another five years until our patient was diagnosed with LALD after genetic testing. A bi-weekly therapy with intravenous Sebelipase alfa was started at the age of 26 years. It led to normalization of lipid levels, reduction of liver enzymes and beginning regression of hepatomegaly in the absence of adverse drug reactions after 46 infusions. Since LALD can take a fatal course even in patients with a long-term stable condition, it is essential to identify affected patients early and to treat them appropriately by enzyme replacement therapy. LALD should be suspected in patients with low high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) in conjunction with elevated liver enzymes or hepatomegaly. A registry for LALD patients shall help to advance our understanding of the disease as well as improve patient care (NCT01633489).

Antihypertensive Treatment Patterns and Blood Pressure Control in Older Adults: Results from the Berlin Aging Study II.

BACKGROUND: Hypertension is highly prevalent in older adults and represents a major public health issue since recognition, awareness, treatment and control are insufficient. Analyses of prescription patterns in conjunction with clinical parameters can provide novel insights into the current practice of hypertension management and help to identify barriers to sufficient hypertension control. METHODS: A cross-sectional analysis was conducted. Prevalence of hypertension, patterns of antihypertensive therapy, and determinants of blood pressure (BP) control were examined in the Berlin Aging Study II cohort, including 1654 community-dwelling older adults (60-85 years of age). RESULTS: Of the participants, 75.9% had hypertension; 40.6% of these were not prescribed BP medications. Lack of hypertension awareness, younger age, absence of comorbidities, not being on a statin, and not having visited a physician in the past 3 months were associated with lack of treatment. Forty-two percent of treated hypertensive individuals received monotherapy and 58.0% received combination therapy. Renin-angiotensin-aldosterone system (RAAS) inhibitors, and ß-blockers were most commonly prescribed, while calcium channel blockers were least prescribed. Only 38.5% of treated hypertensive individuals had their BP controlled to < 140/90 mmHg. Number and choice of BP medications were not predictive of BP control; neither were age, glycated hemoglobin (HbA1c), kidney function, or number of healthcare visits. However, female sex, lower low-density lipoprotein cholesterol (LDL-C) levels and current smoking, amongst others, were positively associated with BP control. There was evidence of significant effect modification by statins in the association of LDL-C and BP. CONCLUSION: The majority of older adults do not reach BP goals. Antihypertensive prescription patterns do not conform to current guidelines. Using more BP medications was not associated with higher odds of BP control. Lowering LDL-C might be favorable in terms of BP control.

Historical trends in modifiable indicators of cardiovascular health and self-rated health among older adults: Cohort differences over 20 years between the Berlin Aging Study (BASE) and the Berlin Aging Study II (BASE-II).

BACKGROUND: The last decades have seen great advances in the understanding, treatment, and prevention of cardiovascular disease (CVD). Although mortality rates due to CVD have declined significantly in the last decades, the burden of CVD is still high, particularly in older adults. This raises the question whether contemporary populations of older adults are experiencing better or worse objective as well as subjective health than earlier-born cohorts. The aim of this study was to examine differences in modifiable indicators of cardiovascular health (CVH), comparing data obtained 20 years apart in the Berlin Aging Study (BASE, 1990-93) and the Berlin Aging Study II (BASE-II, 2009-2014). METHODS: Serial cross-sectional analysis of 242 propensity-score-matched participants of BASE (born 1907-1922) and BASE-II (born 1925-1942). Body mass index (BMI), blood pressure, total cholesterol, glycated hemoglobin (HbA1c), diet, smoking and physical activity were operationalized according to the "Life's simple 7"(LS7) criteria of the American Heart Association. RESULTS: 121 matched pairs were identified based on age, sex, and education. In the later-born BASE-II sample, the mean LS7 score was significantly higher than in the earlier-born sample (7.8±1.8 vs. 6.4±2.1, p<0.001), indicating better CVH. In detail, diet, physical activity, smoking, cholesterol, and HbA1c were more favorable, whereas blood pressure was significantly higher in individuals from the later-born cohort. BMI did not differ significantly between the two matched samples. Notably, despite better CVH, later-born individuals (BASE-II) reported lower self-rated health, presumably because of higher health expectations. CONCLUSIONS: Overall, cardiovascular health was significantly better in the later-born cohort, but several notable exceptions exist.

Polypharmacy as a Risk Factor for Clinically Relevant Sarcopenia: Results From the Berlin Aging Study II.

BACKGROUND: Sarcopenia affects more than 10% of older adults. Next to age-associated physiologic changes, diseases like diabetes or inflammatory, neurological, malignant and endocrine disorders may contribute to the development of sarcopenia. Likewise, polypharmacy, i.e., multiple drug use, is common among older adults. Although the two conditions frequently co-occur, the association of polypharmacy with sarcopenia has not yet been examined. We investigated the association of polypharmacy and sarcopenia in a large cohort of community-dwelling older adults (60-84 years). METHODS: Thousand five hundred and two participants from the Berlin Aging Study II were included. Polypharmacy was defined as concurrent use of 5 or more drugs (prescription and nonprescription). Body composition was assessed with dual-energy X-ray absorptiometry, and appendicular lean mass (ALM) was calculated as sum of the four limbs' lean mass. Sarcopenia was defined as low ALM-to-body mass index (BMI)-ratio using validated sex-specific cutoffs. RESULTS: Mean age was 68.7 ± 3.7 years, 50.7% were female. The median (interquartile range) number of drugs was 2 (1-4); 21.1% of subjects reported regular use of ≥5 drugs. Subjects with polypharmacy were more often sarcopenic according to the applied ALM/BMI-cutoffs (16.3% vs 6.9%, p < 0.001), with a higher BMI (p < 0.001) and lower ALM/BMI (p < 0.001), but no significant difference in mean ALM. Notably, polypharmacy was also associated with higher rates of reduced gait speed and exhaustion. Even after multivariable adjustment (sex, age, comorbid conditions and physical activity) polypharmacy was consistently associated with a significantly increased likelihood of sarcopenia (odds ratio = 2.24, 95% confidence interval [CI] = 1.33-3.75). CONCLUSION: Polypharmacy is associated with clinically relevant sarcopenia, as assessed by a low ALM/BMI.

Adherence to a Mediterranean-Style Diet and Appendicular Lean Mass in Community-Dwelling Older People: Results From the Berlin Aging Study II.

BACKGROUND: Selected nutrients or food groups have often been studied with regard to long-term mortality and cardiovascular disease, whereas the relation between diet quality and appendicular lean mass (ALM) has rarely been researched. OBJECTIVE: The aim of this study was to explore the association between a Mediterranean-style diet and ALM in community-dwelling older people. METHODS: Cross-sectional data from the Berlin Aging Study II were available for 1,509 participants (51% women, 68.2±3.7 years). Nutrient intake was assessed using the European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire. Adherence to a Mediterranean-style diet was evaluated with the modified Mediterranean-type diet score (mMedTypeDiet). ALM was determined by dual-energy X-ray absorptiometry and related to body mass index (ALM/BMI). A general linear regression model was carried out to assess the association between mMedTypeDiet score groups and ALM/BMI. RESULTS: ALM/BMI was higher in women with a higher adherence to the mMedTypeDiet (0.64±0.1 vs 0.62±0.1 and 0.61±0.1 in low and medium adherence, retrospectively, p = .004). In the risk factor-adjusted general linear regression analysis, a higher adherence to the mMedTypeDiet was associated with higher ALM/BMI in women and better ALM/fat mass ratio when compared to a medium and a low diet quality. No significant associations were seen in men. CONCLUSIONS: Higher adherence to a Mediterranean-style diet was associated with a positive effect on ALM/BMI in women.