Association of GLP-1 secretion with parameters of glycemic control in women after gestational diabetes mellitus.

INTRODUCTION: Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes, while the exact mechanisms underlying its pathophysiology are still unclear. We investigated the association of glucagon-like peptide-1 (GLP-1) response to oral glucose with parameters of glycemic control in women with previous GDM in the prospective PPSDiab (Prediction, Prevention, and Subclassification of Type 2 Diabetes) study. RESEARCH DESIGN AND METHODS: Glucose metabolism parameters and GLP-1 secretion were analyzed during oral glucose tolerance test (OGTT) in women with previous GDM (n=129) and women with a history of normal glucose tolerance (n=67) during pregnancy (controls). First- and second-phase insulin and GLP-1 secretion in relation to plasma glucose (PG) levels were assessed, and development of pre-diabetes was analyzed after 5-year follow-up among women with previous GDM and a normal glycemic state at baseline (n=58). RESULTS: The area under the curve (AUC during the OGTT 0-120 min) of PG and insulin but not GLP-1 differed significantly between post-GDM women and controls. However, women with previous GDM had a significantly decreased GLP-1 response in relation to PG and plasma insulin during the second phase of the OGTT. After a follow-up of 5 years, 19.0% post-GDM women with a normal glycemic state at the baseline visit developed abnormal glucose metabolism. The total, first- and second-phase AUC GLP-1/PG and GLP-1/insulin ratios were not associated with development of abnormal glucose tolerance. CONCLUSIONS: Women with previous GDM showed a reduced GLP-1 response in relation to PG and insulin concentrations indicating early abnormalities in glucose metabolism. However, the altered GLP-1 response to oral glucose did not predict progression to pre-diabetes and type 2 diabetes in the first 5 years after GDM.

Age- and sex-adjusted reference intervals for steroid hormones measured by liquid chromatography-tandem mass spectrometry using a widely available kit.

Objective: Measurements utilizing commercially available sets of reagents for determination of steroid hormone profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS) have become increasingly important for routine laboratories. However, method-specific publications of reference intervals obtained from sufficiently large studies are often missing. Methods: After validation of performance characteristics, a widely available kit for steroid analysis by LC-MS/MS was used to measure concentrations of 15 endogenous steroids (aldosterone, cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, estradiol, testosterone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, 11-deoxycorticosterone, progesterone) in more than 500 blood samples from a population-based study. While randomly selected from a larger cohort, the samples equally represented both sexes and covered a wide range of adult age groups. Age- and sex-specific reference intervals were calculated, and correlation with BMI was assessed. Results: Performance characteristics of the assay matched expectations for 9 of 15 steroids. For most of them, reference intervals obtained from our study population were comparable to those reported by others, with age and sex being the major determinants. A sex-specific correlation with BMI was found for seven steroids. We identified limitations regarding sensitivity of the method for quantification of progesterone in males and postmenopausal females. Concentrations of aldosterone, 21-deoxycortisol, estradiol, 11-deoxycorticosterone, and dihydrotestosterone could not be quantified in a large percentage of samples. Conclusions: The reference intervals for nine steroids will support meaningful interpretation for steroid profiles as measured by a widely used kit for LC-MS/MS-based quantification. Laboratories using such kits must be aware of potential limitations in sensitivity for some steroids included in the profile. Significance Statement: Quantification of steroid hormones is a cornerstone for diagnosis of several diseases. Commonly used immunoassays have limitations in specificity. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a promising alternative, particularly if methods are harmonized across laboratories. The use of kits from commercial suppliers might support this. Clinical interpretation of steroid concentrations requires availability of appropriate reference intervals (RIs), but studies on RIs reported in the literature differ in preanalytical and analytical procedures. Here, we provide RIs for steroids measured by a widely available kit under preanalytical conditions mirroring common clinical practice. Such RIs might facilitate interpretation for those using the same method and comparable conditions in clinical routine.

Sarcopenia: investigation of metabolic changes and its associated mechanisms.

BACKGROUND: Sarcopenia is one of the most predominant musculoskeletal diseases of the elderly, defined as age-related progressive and generalized loss of muscle mass with a simultaneous reduction in muscle strength and/or function. Using metabolomics, we aimed to examine the association between sarcopenia and the plasma metabolic profile of sarcopenic patients, measured using a targeted HPLC-MS/MS platform. METHODS: Plasma samples from 22 (17 men) hip fracture patients undergoing surgery (8 sarcopenic, age 81.4+6.3, and 14 non-sarcopenic, age 78.4±8.1) were analyzed. T test, fold change, orthogonal partial least squares discriminant analysis, and sparse partial least squares discriminant analysis were used for mining significant features. Metabolite set enrichment analysis and mediation analysis by PLSSEM were thereafter performed. RESULTS: Using a univariate analysis for sarcopenia z score, the amino acid citrulline was the only metabolite with a significant group difference after FDR correction. Positive trends were observed between the sarcopenia z score and very long-chain fatty acids as well as dicarboxylic acid carnitines. Multivariate analysis showed citrulline, non-esterified fatty acid 26:2, and decanedioyl carnitine as the top three metabolites according to the variable importance in projection using oPLS-DA and loadings weight by sPLS-DA. Metabolite set enrichment analysis showed carnitine palmitoyltransferase deficiency (II) as the highest condition related to the metabolome. CONCLUSIONS: We observed a difference in the plasma metabolic profile in association with different measures of sarcopenia, which identifies very long-chain fatty acids, Carn.DC and citrulline as key variables associated with the disease severity. These findings point to a potential link between sarcopenia and mitochondrial dysfunction and portraits a number of possible biochemical pathways which might be involved in the disease pathogenesis.

Associations of gestational diabetes and proton density fat fraction of vertebral bone marrow and paraspinal musculature in premenopausal women.

Background and objective: Fat content in bones and muscles, quantified by magnetic resonance imaging (MRI) as a proton density fat fraction (PDFF) value, is an emerging non-invasive biomarker. PDFF has been proposed to indicate bone and metabolic health among postmenopausal women. Premenopausal women with a history of gestational diabetes (GDM) carry an increased risk of developing type 2 diabetes and an increased risk of fractures. However, no studies have investigated the associations between a history of GDM and PDFF of bone or of paraspinal musculature (PSM), composed of autochthonous muscle (AM) and psoas muscle, which are responsible for moving and stabilizing the spine. This study aims to investigate whether PDFF of vertebral bone marrow and of PSM are associated with a history of GDM in premenopausal women. Methods: A total of 37 women (mean age 36.3 ± 3.8 years) who were 6 to 15 months postpartum with (n=19) and without (n=18) a history of GDM underwent whole-body 3T MRI, including a chemical shift encoding-based water-fat separation. The PDFF maps were calculated for the vertebral bodies and PSM. The cross-sectional area (CSA) of PSM was obtained. Associations between a history of GDM and PDFF were assessed using multivariable linear and logistic regression models. Results: The PDFF of the vertebral bodies was significantly higher in women with a history of GDM (GDM group) than in women without (thoracic: median 41.55 (interquartile range 32.21-49.48)% vs. 31.75 (30.03-34.97)%; p=0.02, lumbar: 47.84 (39.19-57.58)% vs. 36.93 (33.36-41.31)%; p=0.02). The results remained significant after adjustment for age and body mass index (BMI) (p=0.01-0.02). The receiver operating characteristic curves showed optimal thoracic and lumbar vertebral PDFF cutoffs at 38.10% and 44.18%, respectively, to differentiate GDM (AUC 0.72 and 0.73, respectively, sensitivity 0.58, specificity 0.89). The PDFF of the AM was significantly higher in the GDM group (12.99 (12.18-15.90)% vs. 10.83 (9.39-14.71)%; p=0.04) without adjustments, while the CSA was similar between the groups (p=0.34). Conclusion: A history of GDM is significantly associated with a higher PDFF of the vertebral bone marrow, independent of age and BMI. This statistical association between GDM and increased PDFF highlights vertebral bone marrow PDFF as a potential biomarker for the assessment of bone health in premenopausal women at risk of diabetes.

Exploration of mitochondrial defects in sarcopenic hip fracture patients.

Severe cases of age-related loss of muscle function and mass are clinically unique to sarcopenia. Mitochondrial dysfunction has been associated with aging and sarcopenia, but the causal connection in this context is not well eluded. Here we investigated different aspects of mitochondrial respiration in sarcopenia. Open muscle biopsies were taken from a total of 31 hip fracture patients, older than 70 years. Patients were assigned a sarcopenia Z-score based on EWGSOP2 criteria. Primary myoblast cultures were generated from the muscle tissue samples and used for real time metabolic measurement. Muscle and serum samples showed correlation of high Z-scores with reduced mitochondrial complex I activity, increased tricarboxylic acid cycle (TCA) metabolites, reduced vitamin D3 levels, and signs of an altered iron metabolism. Primary myoblast cultures gained from the same muscle biopsies did not show significant mitochondrial defects. We hypothesize that a sum of external consequences, including vitamin D3 deficiency and iron deficiency caused by disturbances in the iron metabolism, result in complex I deficiency, which in turn affects the TCA and contributes to muscle weakness and loss.

Pre-diabetes, diabetes and fluctuations of glucose tolerance after gestational diabetes mellitus: 5-year follow-up of a contemporary, prospective study in Germany.

INTRODUCTION: Ten years ago, Germany started offering screening for gestational diabetes mellitus (GDM) to all pregnant women. This approach revealed more but also, on average, less severe cases of GDM than the risk-based screening practiced previously. We now examined the incidence of pre-diabetes and diabetes following a GDM diagnosis in the era of universal screening in Germany and compared our results with studies in the previous period. Additionally, we examined the year-to-year fluctuations of glucose tolerance after a pregnancy complicated by GDM. RESEARCH DESIGN AND METHODS: We report 5-year follow-up data from 202 women in the prospective, monocenter, postpartum study PPSDiab. Consecutive recruitment took place in Munich, Germany between 2011 and 2016. In the study, we conducted yearly examinations that included anthropometrics, laboratory chemistry and oral glucose tolerance testing. RESULTS: During the first 5 years post partum, 111 (55%) and 12 (6%) of the women developed pre-diabetes and type 2 diabetes, respectively, while 2 (1%) developed type 1 diabetes. Impaired fasting glucose (IFG) was the most common first manifestation of disturbed glucose tolerance, followed by impaired glucose tolerance (IGT), the combination of IFG and IGT, and diabetes. Glucose tolerance did not deteriorate steadily in most women but fluctuated from year to year. CONCLUSIONS: In our analysis, the incidence of diabetes, both type 1 and type 2, after GDM diagnosed in universal screening was substantially lower than in studies from the previous period of risk-based screening. Nevertheless, the high incidence of pre-diabetes we observed after GDM still confirms the importance of this diagnosis as a risk marker. Additionally, we documented frequent fluctuations of glucose tolerance from 1 year to the next. Therefore, a single postpartum glucose tolerance test, as currently practiced in routine care, may be insufficient for reliable risk stratification after GDM.

Association of serum uromodulin with adipokines in dependence of type 2 diabetes.

BACKGROUND: The renal tubular glycoprotein uromodulin is associated with obesity and type 2 diabetes, but the underlying mechanisms are elusive. We investigated the association of serum uromodulin with adipokines and tested the effect modification by diabetes status. METHODS: The associations of serum uromodulin with eight adipokines were assessed in 795-1080 participants of the KORA F4 study aged 62-81 years using linear regression models adjusted for sex, age, BMI, estimated glomerular filtration rate and diabetes. Significant associations were assessed for effect modification by diabetes status. We further tested using logistic regression whether adjustment for the significant adipokines affected the association of uromodulin with type 2 diabetes. RESULTS: Serum uromodulin was inversely associated with chemerin and retinol-binding protein-4 after multivariable adjustment (p < 0.001) and Bonferroni correction for multiple testing. No significant association was observed between uromodulin and the other adipokines (leptin, adiponectin, secreted frizzled-related protein 5, progranulin, omentin-1 and vaspin) after correcting for multiple testing. The association of uromodulin with chemerin and retinol-binding protein-4 was stronger in participants with type 2 diabetes than in participants without diabetes (p for interaction < 0.05). However, inclusion of chemerin and retinol-binding protein-4 in logistic regression models did not attenuate the association of serum uromodulin with diabetes. CONCLUSIONS: Serum uromodulin was inversely associated with the predominantly pro-inflammatory adipokines chemerin and retinol-binding protein-4. The associations were stronger in participants with type 2 diabetes compared to participants without diabetes. However, the association of serum uromodulin with type 2 diabetes was independent of chemerin and retinol-binding protein-4.

Peripheral Quantitative Computed Tomography Derived Muscle Density Is Associated With Physical Performance in Older Adults.

PURPOSE: The assessment of body composition is an integral part in diagnosing sarcopenia. The purpose of this study was to determine the relationships between peripheral quantitative computed tomography (pQCT)-derived measures of body composition and measures of physical performance in older adults. METHODS: Muscle density, muscle area, and fat area of 168 patients aged 65 years and older (76.3±6.5) were measured with pQCT at the distal forearm additionally to clinical assessment consisting of medical history, physical examination and physical assessment including hand grip strength, gait speed and chair rise tests. Regression analyses assessed associations between patients' physical performance and pQCT derived data. RESULTS: Among the three pQCT parameters, especially muscle density was significantly correlated with all of the three measures of physical performance even after adjusting for sex, age, BMI, vitamin D serum level and the level of physical activity. The same analysis for muscle area achieved significance level only for handgrip strength but not for gait speed nor for chair rise time. Fat area was significantly correlated only with gait speed after adjusting for sex and age. The association of muscle density with physical performance held up in an additional subanalysis stratified by body mass index. CONCLUSION: Muscle density, a proxy for muscle fat infiltration, seems to be better than muscle area or fat area at assessing muscle quality and physical performance in older adults. This association seems to be independent of the body mass index.

Influence of IGF-I serum concentration on muscular regeneration capacity in patients with sarcopenia.

BACKGROUND: Previous research has described a neuroprotective effect of IGF-I, supporting neuronal survival, axon growth and proliferation of muscle cells. Therefore, the association between IGF-I concentration, muscle histology and electrophysiological markers in a cohort of patients with sarcopenia dares investigation. METHODS: Measurement of serum concentrations of IGF-I and binding partners, electromyographic measurements with the MUNIX (Motor Unit Number Index) method and muscle biopsies were performed in 31 patients with acute hip fracture older age 60 years. Molecular markers for denervation (neural cell adhesion molecule NCAM) and proliferation markers (Ki67) were assessed by immunofluorescence staining of muscle biopsy tissue. Skeletal muscle mass by bioelectrical impedance analysis and hand-grip strength were measured to assess sarcopenia status according to EWGSOP2 criteria. RESULTS: Thirty-one patients (20 women) with a mean age of 80.6 ± 7.4 years were included. Concentrations of IGF-I and its binding partners were significantly associated with sarcopenia (ß = - 0.360; p = 0.047) and MUNIX (ß = 0.512; p = 0.005). Further, expression of NCAM (ß = 0.380; p = 0.039) and Ki67 (ß = 0.424; p = 0.022) showed significant associations to IGF-I concentrations. CONCLUSIONS: The findings suggest a pathogenetic role of IGF-I in sarcopenia based on muscle denervation.

Late-onset neuromuscular disorders in the differential diagnosis of sarcopenia.

BACKGROUND: Sarcopenia is the age-related loss of muscle mass and strength. Undiagnosed late-onset neuromuscular disorders need to be considered in the differential diagnosis of sarcopenia. AIM: Based on emblematic case reports and current neuromuscular diagnostic guidelines for three common late-onset neuromuscular disorders, a differential diagnostic approach for geriatric patients presenting with a sarcopenic phenotype is given. METHODS: Patients over 65 years of age with sarcopenia, amyotrophic lateral sclerosis, inclusion body myositis and myotonic dystrophy type 2 were recruited. All patients were assessed for sarcopenia based on the revised European consensus definition. Patients with neuromuscular diseases were diagnosed according to the revised El Escorial criteria and the European neuromuscular centre criteria. Phenotypes and diagnostic criteria for all patients were summarized including their specific histopathological findings. RESULTS: All patients with neuromuscular diseases were positively screened for sarcopenia and classified as severe sarcopenic by means of assessment. The clinical phenotype, the evolution pattern of weakness and muscle atrophy combined with laboratory finding including electromyography could unquestionably distinguish the diseases. DISCUSSION: Neuromuscular disorders can manifest beyond the age of 65 years and misdiagnosed as sarcopenia. The most common diseases are inclusion body myositis, amyotrophic lateral sclerosis and myotonic dystrophy type 2. A diagnostic work-up for neuromuscular diseases ensures their correct diagnosis by clinical-, electrophysiological, histopathological, and genetic work-up. CONCLUSIONS: In geriatric patients with a focal or asymmetrical muscular weakness and atrophy, sarcopenia assessment should be extended with patient's history of disease course. Furthermore, concomitant diseases, analysis of serum creatine kinase, electrophysiological examination, and in selected patients muscle biopsy and gene analysis is needed to rule out a late-onset neuromuscular disorder.

IGF-I/IGFBP3/ALS Deficiency in Sarcopenia: Low GHBP Suggests GH Resistance in a Subgroup of Geriatric Patients.

CONTEXT: Definition of etiological subgroups of sarcopenia may help to develop targeted treatments. insulin like growth factor-I (IGF-I), Insulinlike growth factor binding protein 3 (IGFBP3), and acid labile subunit (ALS) build a ternary complex that mediates growth hormone (GH) effects on peripheral organs, such as muscle. Low GH binding protein (GHBP) as a marker of GH receptor number would hint toward GH resistance. OBJECTIVE: We aimed to analyze the association of IGF-I, IGFBP3, and ALS with sarcopenia. STUDY PARTICIPANTS AND SETTING: A total of 131 consecutively recruited patients of a geriatric ward were included in a single-center cross-sectional analysis; the nonsarcopenic patients served as controls. METHODS: Measures included sarcopenia status by hand-grip strength measurement and Skeletal Muscle Index (SMI); IGF-I, IGFBP3, ALS, GH, GHBP; body mass index (BMI); Activity of Daily Living (ADL); Mini-Mental State Examination (MMSE); routine laboratory parameters; and statistical regression modeling. RESULTS: Compared with controls, sarcopenic patients did not differ regarding age, sex, ADL, MMSE, C-reactive protein, glomerular filtration rate, and albumin serum concentrations. However, sarcopenic patients had significantly lower IGF-I, IGFBP3, and ALS. IGF-I and ALS associated significantly with sarcopenia and low hand-grip strength, even after adjustment for age, sex, BMI, and albumin, but not with low SMI. GHBP serum was low in sarcopenic patients, but normal in geriatric patients without sarcopenia. Over 60% of patients with IGF-I/ALS deficiency patients showed GH resistance. CONCLUSIONS: Our data suggest that in geriatric patients, low IGF-I/IGFBP3/ALS could be evaluated for causative connection of the sarcopenia spectrum. Low GHBP points toward potential GH resistance as one possible explanation of this deficiency.

Type-2 muscle fiber atrophy is associated with sarcopenia in elderly men with hip fracture.

Sarcopenia is a common geriatric syndrome and can lead to falls and fragility fractures. It is associated with a decline of muscle fiber numbers and size. Muscle biopsies of the vastus lateralis muscle were taken from thirty-two patients with hip fracture (18 women and 14 men; mean age: 82.2 ± 6.2 years). Serial cross sections of skeletal muscle were labeled with myosin heavy chain slow (fiber type-1) and fast (fiber type-2) antibodies in order to measure the size, ratio and percentage of mixed fiber types. The presence of sarcopenia was defined according to the EWGSOP2 criteria by using BIA and handgrip strength measurement. Sarcopenia was identified in 5 patients (3 women and 2 men), probable-sarcopenia in 11 patients (4 women and 7 men). Significant differences in fiber diameter were found for fiber type-2 in men but not in women. Only 1-3% mixed fiber types were found in sarcopenic patients, indicating a final stage where reinnervation is not possible to occur anymore. Muscle fiber type-2 atrophy seems to be a histological marker for sarcopenia in men.

[The Actual Sarcopenia Definition 2019]. / Die aktuelle Sarkopenie-Definition.

Sarcopenia is characterized by a generalized loss of muscle function, strength and mass and is codable in Germany since 2018 in the ICD-10-GM (M62.50). For screening in primary care, it is possible to determine muscle function and strength by means of a sarcopenia questionnaire (SARC-F) as a self-filler with 5 questions of restrictions. With an increased score of 4 and higher, an examination of the musculature and a determination of the skeletal muscle mass index should be performed via dual energy X-ray absorption measurement (DXA) or bioelectric impedance analysis (BIA).If hand and/or leg strength is limited, the patient has probable sarcopenia and, according to the current revised version of the European consensus on sarcopenia, therapy can already be started and the cause clarified. A DXA or BIA examination confirms the diagnosis of sarcopenia by a lowered skeletal muscle index. A follow-up examination is recommended to differentiate between acute or chronic sarcopenia and to assess the progression of the disease. The severity of the disease is defined by additional examinations such as gait speed, timed up and go test (TUG) and/or short physical performance battery (SPPB). Patients with sarcopenia suffer from increasing immobility and disability and have an increased risk of falls, fractures and mortality. Frequently, co-morbidities should be clarified in all affected patients.

No Independent Association of Circulating Fetuin-A with Insulin Sensitivity in Young Women.

Animal data link high circulating fetuin-A to low insulin sensitivity and observational studies identify the hepatokine as a marker of future incident type 2 diabetes mellitus in humans. However, a recent, well-powered Mendelian randomization study finds no causal role. We therefore tested in a deeply-phenotyped human cohort if circulating fetuin-A correlates independently with insulin sensitivity and how it relates to the metabolic syndrome and ectopic fat deposition. We analyzed data from 290 young women with and without recent gestational diabetes mellitus. We found that circulating fetuin-A correlates inversely with insulin sensitivity in univariate analyses, but that this correlation is lost after adjustment for markers of the metabolic syndrome and of fatty liver. Additionally, we investigated which fat compartment associates most strongly with circulating fetuin-A. In whole body MRI data from a subcohort of 152 women, this was liver fat content. We conclude that high circulating fetuin-A occurs as part of the metabolic syndrome in young women and associates most strongly with liver fat content. Its close link to the metabolic syndrome may also cause the inverse correlation of circulating fetuin-A with insulin sensitivity as we found no independent association.

Longitudinal association of type 2 diabetes and insulin therapy with muscle parameters in the KORA-Age study.

AIMS: The aim of the current study was to investigate the association of type 2 diabetes (T2D) and insulin treatment with changes in muscle mass, muscle strength, and physical performance in older adults. METHODS: In 731 participants of the population-based KORA-Age study aged 74.6 ± 6.2 years (T2D: n = 118; insulin treatment: n = 20), skeletal muscle index (SMI [kg/m2]), hand grip strength (GS [kg]), and a timed up and go test (TUG [s]) were performed at baseline and after a follow-up time of 3 years. The association of T2D and insulin therapy with changes in muscle parameters was analyzed using linear regression models. RESULTS: After adjustment for sex, age, BMI, physical activity, smoking, and multimorbidity, T2D was associated with the change in SMI during follow-up (ß - 0.1 (95% CI - 0.3 to - 0.02) kg/m2; p = 0.02), but not with a change in GS (ß - 0.9 (95% CI - 1.9 to 0.04) kg) or TUG (ß - 0.1 (95% CI - 0.7 to 0.5) s). Insulin therapy was positively associated with change in SMI (ß 0.6 (95% CI 0.3-0.9) kg/m2; p = 0.001), but not in GS (ß - 1.6 (95% CI - 4.1 to 0.8) kg) or TUG (ß 1.6 (95% CI - 0.2-3.4) s) in comparison with treatment with oral anti-diabetic medication alone. CONCLUSIONS: Participants with T2D showed an accelerated decline in muscle mass compared to non-diabetic participants. Insulin therapy was associated with preserved muscle mass, but not muscle function parameters, indicating a discrepancy between muscle mass and function in this high-risk population.

Measurement of total and visceral fat mass in young adult women: a comparison of MRI with anthropometric measurements with and without bioelectrical impedance analysis.

OBJECTIVE: MRI is established for measurement of body fat mass (FM) and abdominal visceral adipose tissue (VAT). Anthropometric measurements and bioelectrical impedance analysis (BIA) have been proposed as surrogates to estimation by MRI. Aim of this work is to assess the predictive value of these methods for FM and VAT measured by MRI. METHODS: Patients were selected from cohort study PPS-Diab (prediction, prevention and subclassification of Type 2 diabetes). Total FM and VAT were quantified by MRI and BIA together with clinical variables like age, waist and hip circumference and height. Least-angle regressions were utilized to select anthropometric and BIA parameters for their use in multivariable linear regression models to predict total FM and VAT. Bland-Altman plots, Pearson correlation coefficients, Wilcoxon signed-rank tests and univariate linear regression models were applied. RESULTS: 116 females with 35 ± 3 years and a body mass index of 25.1 ± 5.3 kg/m2 were included into the analysis. A multivariable model revealed weight (ß = 0.516, p < 0.001), height (ß = -0.223, p < 0.001) and hip circumference (ß = 0.156, p = 0.003) as significantly associated with total FM measured by MRI. A additional multivariable model also showed a significant predictive value of FMBIA (ß = 0.583, p < 0.001) for FM. In addition, waist circumference (ß = 0.054, p < 0.001), weight (ß = 0.016, p = 0.031) in one model and FMBIA (ß = 0.026, p = 0.018) in another model were significantly associated with VAT quantified by MRI. However, deviations reached more than 5 kg for total FM and more than 1 kg for VAT. CONCLUSION: Anthropometric measurements and BIA show significant association with total FM and VAT. ADVANCES IN KNOWLEDGE: As these measurements show significant deviations from the absolute measured values determined by MRI, MRI should be considered the gold-standard for quantification.

Interrelation between Sarcopenia and the Number of Motor Neurons in Patients with Parkinsonian Syndromes.

INTRODUCTION: Pathogenesis in a subgroup of sarcopenic patients seems to be based on a reduced number of motor neurons. This study aimed at investigating the overlap between sarcopenia and neurodegeneration, as reflected by a low number of motor neurons in patients with Parkinsonian syndromes (PS). METHODS: The motor unit number index (MUNIX) of the hypothenar muscle was used to assess the number and size (MUSIX) of motor units (MUs) in patients with idiopathic Parkinson disease (iPD, n = 53), patients with atypical Parkinsonian syndrome (aPS, n = 21), and a control group (n = 30). Mean age of participants was 70.3 years and 54.1% were female. Skeletal muscle mass by bioelectrical impedance analysis, hand-grip strength and gait speed were measured. Based on these assessments, sarcopenia was diagnosed according to the criteria of the European Working Group on Sarcopenia in Older People. RESULTS: Sarcopenia criteria were met by 10 patients with PS (13.5%). The study group had significantly lower MUNIX values than the control group (109 [SD ±39.1] vs. 129 [SD ±45.1]; p = 0.020) even after adjustment for age and sex. Three of the 5 sarcopenic iPD patients (75%) had pathological low MUNIX values (<80). DISCUSSION/CONCLUSION: Sarcopenia is a frequent comorbidity in PS. The pathologically low MUNIX values found in 75% of our sarcopenic iPD patients provides further support for the existence of a neurodegenerative overlap syndrome with a reduced number of MUs potentially leading to sarcopenia. This finding warrants further evaluation.

German Version of SARC-F: Translation, Adaption, and Validation.

OBJECTIVES: Translation, adaptation, and validation of the German version of the SARC-F for community-dwelling older adults in Germany. DESIGN: Cross-sectional. SETTING AND PARTICIPANTS: 117 community-dwelling outpatients with a mean age of 79.1 ± 5.2 years were included in the study; 94 (80.4%) of them were female. Sixty-three (53.8%) had a positive SARC-F score of ≥4 points. According to the definition of sarcopenia from the European Working Group on Sarcopenia in Older People (EWGSOP2), 8 patients (6.8%) were identified as sarcopenic and 57 (48.7%) as probable sarcopenic. METHODS: According to EWGSOP2, probable sarcopenia was defined for patients with reduced hand grip strength (women: <16.0 kg; men: <27.0 kg) and/or impaired chair-rise time (both genders: >15 seconds). Patients with additional low skeletal muscle index were classified as sarcopenic (women: <5.5 kg/m2; men: <7.0 kg/m2). Translation and cultural adaption was composed of 7 different steps that were in general based on the guidelines put forward by the World Health Organization. Validation include test-retest and the inter-rater reliability (intraclass correlation coefficient) as well as internal consistency (Cronbach alpha). Furthermore, sensitivity, specificity, positive predictive value, and negative predictive value of the SARC-F were calculated. Receiver-operating characteristic analysis was performed to calculate the area under the curve. RESULTS: The translated and culturally adapted version of the SARC-F for the German language has shown excellent inter-rater reliability and good test-retest reliability. The internal consistency is acceptable. Sensitivity (63%) and specificity (47%) for sarcopenia is low. For detecting patients with probable sarcopenia, the SARC-F in the German version has shown 75% sensitivity and 67% specificity. CONCLUSIONS AND IMPLICATIONS: Because of a low sensitivity for detecting sarcopenia but an acceptable sensitivity for identifying probable sarcopenia, the German version of the SARC-F is a suitable tool for case finding of probable sarcopenia.

Vitamin D in Relation to Incident Sarcopenia and Changes in Muscle Parameters Among Older Adults: The KORA-Age Study.

Effects of low serum 25OHD on age-related changes in muscle mass and function remain unclear. Our aims were to explore associations of baseline 25OHD levels with prevalent and incident sarcopenia and changes in muscle parameters, and to examine the role of parathyroid hormone (PTH) therein. Cross-sectional (n = 975) and prospective analyses (n = 702) of older adults aged 65-93 years participating in the KORA-Age study. Sarcopenia was defined using the 2010 European Working Group on Sarcopenia in Older People (EWGSOP) criteria as low muscle mass combined with low grip strength or low physical performance. Associations with baseline 25OHD were examined in multiple regression analyses. Low vitamin D status was linked to increased odds of prevalent sarcopenia. Over three years, low baseline 25OHD < 25 vs. ≥ 50 nmol/L were associated with greater loss of muscle mass and increased time for the Timed Up and Go test. The risk for developing incident sarcopenia was not significantly elevated in individuals with low baseline 25OHD but when including death as combined outcome alongside incident sarcopenia, there was a strong positive association in multivariable analysis [OR (95% CI) 3.19 (1.54-6.57) for 25OHD < 25 vs. ≥ 50 nmol/L]. There was no evidence for a PTH-mediating effect. Low baseline 25OHD levels were associated with unfavorable changes in muscle mass and physical performance, but not with incident sarcopenia. Future randomized trials are needed to assess causality and to address the issue of competing risks such as mortality in older cohorts.