Obesity represents a significant risk factor in the development of type 2 diabetes (T2D), a chronic metabolic disorder characterized by elevated blood glucose levels, and a previous step for its development. Significant sex differences have been identified in the prevalence, development, and pathophysiology of obesity and T2D; however, the underlying molecular mechanisms remain unclear. This study aims to identify sex-specific signatures in obesity and T2D and enhance our understanding of the underlying mechanisms associated with sex differences by integrating expression data. We performed a systematic review and individual transcriptomic analysis of eight selected studies which included 302 subcutaneous adipose tissue samples. Then, we conducted different gene-level meta-analyses and functional characterizations for obesity and T2D separately, identifying common and sex-specific transcriptional profiles, many of which were previously associated with obesity or T2D. The obesity meta-analysis yielded nineteen differentially-expressed genes from a sex-specific perspective (e.g., SPATA18, KREMEN1, NPY4R, and PRM3), while a comparison of the expression profiles between sexes in T2D prompted the identification and validation of specific transcriptomic signatures in males (SAMD9, NBPF3, LDHD, and EHD3) and females (RETN, HEY1, PLPP2, and PM20D2). At the functional level, we highlighted the fundamental role of the Wnt pathway in the development of obesity and T2D in females, and the roles of mitochondrial damage and free fatty acids in males. Overall, our sex-specific meta-analyses supported the detection of differentially expressed genes in males and females associated with the development of obesity and further T2D development, emphasizing the relevance of sex-based information in biomedical data and opening new avenues for research.

Beyond its established glucose-lowering and weight-reducing benefits, glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as liraglutide may also mitigate sarcopenia. This study investigates the effects of liraglutide on diabetic sarcopenia and its underlying mechanisms.

A type 2 diabetic SD rat model was induced using a high-fat, high-sugar diet supplemented with a low dose of streptozotocin. Comparisons were made among control (Con), diabetic (DM), and liraglutide-treated (Li) groups for gastrocnemius muscle wet weight and length, histology (HE staining), immunofluorescence for muscle fiber typing, and Western blotting for aging-related proteins and YAP/TAZ pathway components. Concurrently, C2C12 myoblasts were differentiated into myotubes, treated with 60 mM glucose to model diabetic conditions, and assessed for morphological changes, senescence (SA-β-gal staining), and protein expression dynamics.

Diabetic rats displayed significant reductions in muscle mass, length, and cross-sectional area, along with disorganized fiber architecture, all of which were improved by liraglutide. In vitro, C2C12 myotubes showed accelerated aging and atrophy under high-glucose conditions, which were significantly reduced by liraglutide. Analysis revealed increased expression of aging markers P53 and P21 and decreased YAP/TAZ/TEAD and Cyclin D1 levels in diabetic conditions, which were reversed following liraglutide treatment. The inhibition of YAP significantly negated the protective effects of liraglutide.

High glucose promotes muscle cell aging and sarcopenia, processes that liraglutide can attenuate by modulating the YAP/TAZ signaling pathway. This study underscores liraglutide's potential to alleviate muscle degeneration in diabetic sarcopenia through its regulatory impact on critical aging pathways.

While glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively reduce body weight, their impact on lean mass remains uncertain. This meta-analysis evaluated the effects of GLP-1RAs and GLP-1/GIP receptor dual agonists (GLP-1/GIP-RAs) on body composition, focusing on total weight, fat mass, and lean mass in adults with diabetes and/or overweight/obesity.

A systematic search of Medline, Embase, and the Cochrane Library was conducted through November 12, 2024. Data were analyzed using random-effects pairwise and network meta-analyses to compare interventions with placebo or active comparators.

Twenty-two randomized controlled trials (2258 participants) were included. GLP-1RAs significantly reduced total body weight (MD -3.55 kg, 95 %-CI [-4.81, -2.29]), fat mass (MD -2.95 kg, 95 %-CI [-4.11, -1.79]), and lean mass (MD -0.86 kg, 95 %-CI [-1.30, -0.42]), with lean mass loss comprising approximately 25 % of the total weight loss. However, the relative lean mass, defined as percentage change from baseline, was unaffected. Liraglutide, at 3.0 mg weekly or 1.8 mg daily, was the only GLP-1RA to achieve significant weight reduction without significantly reducing lean mass. Tirzepatide (15 mg weekly) and semaglutide (2.4 mg weekly) were the most effective for weight and fat mass reduction but were among the least effective in preserving lean mass.

Potent GLP-1 RAs, such as tirzepatide and semaglutide, demonstrate greater overall weight loss but are associated with a significant reduction in lean mass.

The American Heart Association has recently emphasized the significance of the cardiovascular-kidney-metabolic (CKM) syndrome. However, the cumulative impact of these factors on cardiorespiratory fitness remains inadequately characterized. This study aimed to examine the responses observed during cardiopulmonary exercise testing (CPET) of CKM syndrome patients and explore the potential correlation between cardiorespiratory fitness and hemoglobin concentration in this cohort.

Cross-sectional study.

We retrospectively collected medical data of 8206 patients who underwent CPET from 2012-2022. Among the 878 individuals enrolled, 12 were healthy controls, 809 had isolated CVD, and 57 were in CKM stage 4. After propensity score matching, 112 patients were included in the matched cohort analysis, with 56 each in the CVD and CKM groups. CPET responses were compared between the groups using propensity matched analysis. Additionally, simple mediation models were employed to investigate the potential mediating role of hemoglobin concentration in the association between CKM syndrome and peak VO2.

After propensity score-matching, CKM stage 4 was associated with diminished cardiorespiratory fitness compared to the other two groups. This included diminished exercise capacity, reflected by shorter exercise time, lower maximum workload (and its percent predicted value), and reduced peak VO2 (including its percent predicted value and peak VO2/kg). Additionally, cardiac autonomic function was impaired, as evidenced by decreased heart rate recovery (HRR) and a reduced slope of HR recovery (all p<0.05). Mediation model regression analysis indicated a significant and direct detrimental effect of CKM syndrome on peak VO2 (β = -228.502; P = 0.003), and a significant indirect partial effect of hemoglobin concentration on the direct effect (β = -335.718; P < 0.001), with the percentage mediated through hemoglobin concentration of 46.9%.

Individuals with CKM syndrome demonstrate compromised responses to CPET manifested by diminished exercise capacity and cardiac autonomic function. While diminished peak oxygen uptake can be partly explained by hemoglobin concentration as we found, further research is necessary to understand other underlying mechanisms.

Diabetes is an independent risk factor for muscle mass loss, with possible mechanisms including impaired insulin signalling and chronic inflammation. The use of a glucagon-like peptide 1 (GLP-1) receptor-based agonist could lead to weight reduction, which might result from the loss of both fat and skeletal muscle. However, the body composition-modifying effects of GLP-1 receptor-based agonists have not been systematically characterized.

PubMed, EMBASE, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from inception to October 2023. Randomized controlled trials of GLP-1 receptor agonist or glucose-dependent insulinotropic polypeptide/GLP-1 receptor dual agonist, which reported the changes of body composition, were included. The results were computed as weighted mean differences (WMDs) and 95% confidence intervals (CIs) in a random-effects model.

In all, 19 randomized controlled trials were included. When compared with controls, substantial reductions in fat body mass were observed in patients using GLP-1 receptor-based agonist treatment (WMD = -2.25 kg, 95% CI -3.40 to -1.10 kg), with decrease in areas of both subcutaneous fat (WMD = -38.35 cm2, 95% CI, -54.75 to -21.95 cm2) and visceral fat (WMD = -14.61 cm2, 95% CI, -23.77 to -5.44 cm2). Moreover, greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users compared with non-users (WMD = -1.02 kg, 95% CI, -1.46 to -0.57 kg), while the changes in lean mass percentage were comparable between GLP-1 receptor-based agonist users and non-users.

Compared with the controls, GLP-1 receptor-based agonist users experienced greater reductions in fat body mass, with body shaping effects in terms of both subcutaneous fat mass and visceral fat mass. Although greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users, the changes in lean mass percentage were comparable between the users and non-users.

Diabetes mellitus (DM) and sarcopenia are bidirectionally linked and commonly co-occur among middle-aged and elderly individuals. This study aims to examine the combined effect of DM and sarcopenia on depressive symptoms and cognitive function.

This was a nationwide cohort study using data from the China Health and Retirement Longitudinal Study. The definition of DM was self-reported and based on hemoglobin A1c (HbA1c) ≥ 6.5% or fasting blood glucose (FBG) ≥ 126 mg/dL. The diagnosis of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 algorithm. The outcomes included depressive symptoms assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10) and cognitive function. Multi-adjusted linear and logistic regression models were conducted to evaluate the combined effect of DM and sarcopenia on depression and cognitive performance.

9148 participants were included in the longitudinal analysis, with 45.5% being men and an average age of 57.4 years. 6987 (76.4%) participants had neither DM nor sarcopenia, 1076 (11.8%) had DM only, 983 (10.8%) had sarcopenia only, and 102 (1.1%) had both DM and sarcopenia. In the cross-sectional analysis, the DM (+)/Sarcopenia (+) group exhibited the highest CES-D-10 score (β: 2.23, 95% confidence interval (CI): 1.26, 3.19) and the lowest cognitive score (β: - 1.02, 95% CI - 1.79, - 0.26) (P for trend < 0.05). In the longitudinal analysis, individuals in the DM (+)/Sarcopenia ( +) group had higher risks of moderate-to-severe depression (odds ratio (OR): 2.09, 95% CI 1.18, 3.71) and cognitive decline (OR: 1.87, 95% CI 1.19, 2.95) compared to the DM (-)/Sarcopenia (-) group. The population attributable fractions of DM and sarcopenia were 42.2% (95% CI 6.3, 90.4) for moderate-to-severe depression and 23.0% (95% CI 8.6, 39.3) for cognitive decline.

DM and sarcopenia additively increase the risk of moderate-to-severe depression and cognitive impairment, highlighting the importance of vigilant monitoring and management of these conditions to preserve mental health in middle-aged and elderly individuals.

Similar to bariatric surgery, incretin receptor agonists have revolutionized the treatment of obesity, achieving up to 15-25 % weight loss in many patients, i.e., at a rate approaching that achieved with bariatric surgery. However, over 25 % of total weight lost from both surgery and pharmacotherapy typically comes from fat-free mass, including skeletal muscle mass, which is often overlooked and can impair metabolic health and increase the risk of subsequent sarcopenic obesity. Loss of muscle and bone as well as anemia can compromise physical function, metabolic rate, and overall health, especially in older adults. The myostatin-activin-follistatin-inhibin system, originally implicated in reproductive function and subsequently muscle regulation, appears to be crucial for muscle and bone maintenance during weight loss. Activins and myostatin promote muscle degradation, while follistatins inhibit their activity in states of negative energy balance, thereby preserving lean mass. Novel compounds in the pipeline, such as Bimagrumab, Trevogrumab, and Garetosmab-which inhibit activin and myostatin signaling-have demonstrated promise in preventing muscle loss while promoting fat loss. Either alone or combined with incretin receptor agonists, these medications may enhance fat loss while preserving or even increasing muscle and bone mass, offering a potential solution for improving body composition and metabolic health during significant weight loss. Since this dual therapeutic approach could help address the challenges of muscle and bone loss during weight loss, well-designed studies are needed to optimize these strategies and assess long-term benefits. For the time being, considerations like advanced age and prefrailty may affect the choice of suitable candidates in clinical practice for current and emerging anti-obesity medications due to the associated risk of sarcopenia.

Recent studies have indicated that coffee consumption is inversely correlated with sarcopenia in the elderly population. Data regarding the association between caffeine intake and muscle mass in young adults are scarce.

We aimed to investigate how dietary caffeine correlates with muscle mass and sarcopenia in the young and middle-aged people.

We performed a cross-sectional study utilizing data from NHANES. Muscle mass was evaluated using DXA and caffeine intake was derived from 24-h dietary recalls. Multivariable regression analysis was adopted to explore association between caffeine and sarcopenia. Restricted cubic spline analysis was conducted to investigate dose-response effect of dietary caffeine on muscle mass. Mediation effect of high-sensitivity C reactive protein was examined by mediation analysis.

A total of 9116 adults aged from 20 to 59 years old were included. Higher ingestion of caffeine was not associated with sarcopenia. Association between dietary caffeine and muscle mass was found to be W-shaped in males and U-shaped in young females, wherein mediation effect of hs-CRP was not discovered.

Caffeine consumption is associated with muscle mass in a nonlinear pattern. ASMI peaks at a daily caffeine intake of 1.23 mg/kg in young adults, while 0.64-1.49 mg/kg is recommended for middle-aged men.

Metabolic syndrome (MetS) and sarcopenia (SP) have emerged as significant public health concerns in contemporary societies, characterized by shared pathophysiological mechanisms and interrelatedness, leading to profound health implications. In this prospective cohort study conducted within a US population, we aimed to examine the influence of MetS and SP on all-cause and cardiovascular mortality.

This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) III for the years 1999-2006 and 2011-2018, and death outcomes were ascertained by linkage to National Death Index (NDI) records through December 31, 2019. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cardiovascular mortality. In addition, subgroup and sensitivity analyses were conducted to test the robustness of the results.

Over a median follow-up period of 13.3 years (95% CI: 12.8-13.8), 1714 deaths were observed. The groups characterized by MetS-/SP+, MetS+/SP-, and MetS+/SP+ exhibited higher all-cause mortality rates in comparison to the MetS-/SP- group, with the MetS+/SP+ group (HR 1.76, 95% CI: 1.37-2.25) displaying the highest all-cause mortality. Increased cardiovascular mortality was observed in the MetS+/SP- (HR 1.84, 95% CI: 1.24-2.72), and MetS+/SP+ groups (HR 2.39, 95% CI: 1.32-4.35) compared to the MetS-/SP- group, whereas it was not statistically significant in the MetS-/SP+ group. However, among males and individuals aged < 60, the presence of both MetS and SP (MetS+/SP+ group) was found to be significantly associated with a higher risk of all-cause and cardiovascular mortality.

The coexistence of MetS and SP increased the risk of all-cause and cardiovascular mortality, particularly in males and in nonelderly populations. Individuals with either MetS or SP may require more careful management to prevent the development of other diseases and thereby reduce mortality.

The prevalence of metabolic-associated fatty liver disease (MAFLD) has increased substantially in recent years because of the global obesity pandemic. MAFLD, now recognized as the number one cause of chronic liver disease in the world, not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease, type 2 diabetes mellitus, obstructive sleep apnoea, lipid disorders and sarcopenia. Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies. Sarcopenia can be either part of the disease process that results in MAFLD (e.g., obesity or adiposity) or a consequence of MAFLD, especially in the advanced stages such as fibrosis and cirrhosis. Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors. Therefore, it is crucial to thoroughly understand how we deal with these diseases, especially when they coexist. We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.