Diabetes is a chronic metabolic disease that is endemic worldwide and is characterized by persistent hyperglycemia accompanied by multiple severe complications, including cardiovascular disease, kidney dysfunction, neuropathy, and retinopathy. The pathogenesis of diabetes mellitus and its complications is multifactorial, involving various molecular and cellular pathways. In recent years, research has indicated that mechanisms of cell death play a significant role in the advancement of diabetes and its complications. PANoptosis is a complex phenomenon caused by three cell death pathways: programmed apoptosis, necroptosis and pyroptosis. The contribution of PANoptosis to diabetes and its complications remains incompletely understood. Non-coding RNA, an important molecule in gene expression regulation, has shown significant regulatory functions in a variety of diseases. This paper reviews the underlying mechanisms of diverse types of non-coding RNAs (including lncRNA, miRNA and circRNA) in regulating PANoptosis and their specific contributions in diabetes, aiming to explore how non-coding RNAs influence PANoptosis and their effects in diabetes.

Sarcopenia and diabetes are prevalent diseases among middle-aged and elderly population. This study aimed to investigate the bidirectional association between sarcopenia and diabetes.

This study comprised two longitudinal analyses. In cohort 1, the association between baseline diabetes and the risk of new-onset sarcopenia was assessed. In cohort 2, the association between baseline sarcopenia and the risk of new-onset diabetes was examined. Multivariate logistic regression models were used to calculate odds ratios (OR) and 95 % confidence intervals (95 % CI). Cross-lagged panel analysis was used to further validate their bidirectional associations.

Significant bidirectional associations were observed between sarcopenia and diabetes in both cross-sectional and longitudinal analyses (P < 0.05). After four years of follow-up, low handgrip strength (OR: 2.31, 95 % CI: 1.74-3.08) and appendicular skeletal muscle mass index (ASM/Ht2) (OR: 1.25, 95 % CI: 1.20-1.30) were associated with an increased risk of diabetes. Conversely, elevated fasting plasma glucose (FPG) (OR: 1.52, 95 % CI: 1.17-1.96) and glycated hemoglobin A1c (HbA1c) (OR: 1.35, 95 % CI: 1.05-1.73) were associated with a higher risk of sarcopenia. Cross-lagged analysis further confirmed their bidirectional longitudinal association.

This study identified significant longitudinal bidirectional association between sarcopenia and diabetes, highlighting that each condition serves as a risk factor for the other. Clinically, early assessments of handgrip strength and ASM/Ht2 may aid in diabetes prevention, while monitoring FPG and HbA1c could help reduce the risk of sarcopenia.

Patients with Type 2 diabetes mellitus (T2DM) have elevated late-night cortisol levels and a flattened circadian rhythm. Cortisol oversecretion mediates muscle breakdown and reduces muscle strength and mass, thus possibly leading to sarcopenia. This study first investigated the association between cortisol circadian rhythm and sarcopenia in patients with T2DM.

Patients with T2DM and adrenal nodules were screened for eligibility. Skeletal muscle index (SMI) and skeletal muscle density (SMD) were obtained by analysing computed tomography images at Lumbar 3 level. Sarcopenia was defined as the presence of both myopenia and myosteatosis. Cortisol and adrenocorticotropic hormone levels at 8 AM, 4 PM and 0 AM were measured. The cumulative logit models and receiver operating characteristic (ROC) curve analyses were performed to evaluate the association between cortisol circadian rhythm and sarcopenia.

In total, 128 patients with T2DM and nonfunctional adrenal adenomas were enrolled in this study, of whom 25 were diagnosed with sarcopenia. The mean age was 54.4 years, and 83 (64.8%) patients were male. Patients with sarcopenia showed higher nighttime cortisol levels at 0 AM (Cor 0 AM) (4.91 [4.05, 9.95] vs. 2.44 [1.55, 4.77] μg/dL, p < 0.001) than those without. The Cor 0 AM was negatively correlated with both SMI and SMD (r = -0.318, p < 0.001 and -0.284, p < 0.001, respectively). As the Cor 0 AM tertiles increased, the odds ratios (ORs) for sarcopenia consistently increased (OR = 4.69 [0.93, 23.53], p = 0.061, for the intermediate group and OR = 11.39 [2.41, 53.84], p = 0.002, for the high group). After adjustment for multiple risk factors, the high Cor 0 AM group still showed a significantly higher risk of sarcopenia than the low group (OR = 7.92 [1.45, 43.29], p = 0.017). ROC curve analyses showed that Cor 0 AM had the highest predictive power for sarcopenia, with an area under the ROC curve (AUC) of 0.760, compared to haemoglobin, age, alanine transaminase and sex (AUC = 0.703, 0.695, 0.679, and 0.633, respectively).

The cortisol circadian rhythm is associated with sarcopenia in patients with T2DM. Patients with higher levels of nighttime cortisol, rather than morning or afternoon cortisol, have a higher risk of sarcopenia. This result offers a new strategy for the further research of sarcopenia.

Sarcopenia, characterized by progressive and generalized loss of skeletal muscle (SkM) mass, strength, and physical performance, is a prevalent complication in type 2 diabetes (T2D). Nitric oxide (NO), a multifunctional gasotransmitter involved in whole-body glucose and insulin homeostasis, plays key roles in normal SkM physiology and function. Here, we highlight the role of NO in SkM mass maintenance and its potential contribution to the development of T2D-related sarcopenia. Physiologic NO level, primarily produced by sarcolemmal neuronal nitric oxide synthase (nNOSμ isoform), is involved in protein synthesis in muscle fibers and maintenance of SkM mass. The observed effect of nNOSμ on SkM mass is muscle-type specific and sex-dependent. Impaired NO homeostasis [due to a diminished nNOSμ-NO availability and excessive NO production through inducible NOS (iNOS) in response to atrophic stimuli, e.g., inflammatory cytokines] in SkM occurred during the development and progression of T2D, may cause sarcopenia. Theoretically, restoration of NO through nNOS overexpression, supplying NOS substrates (e.g., L-arginine and L-citrulline), phosphodiesterase (PDE) inhibition, and supplementation with NO donors (e.g., inorganic nitrate) may be potential therapeutic approaches to preserve SkM mass and prevents sarcopenia in T2D.

Diabetes is one of the most common metabolic diseases worldwide, leading to complications, mortality, and significant healthcare expenditures, which impose a substantial social and financial burden globally. A diabetic environment can induce metabolic changes, negatively affecting tendon homeostasis, leading to alterations in biomechanical properties and histopathology. Numerous studies have investigated the mechanisms through which diabetes exerts pathological effects on tendons, including increased free radical production, oxidative stress, inflammatory responses, deposition of advanced glycation end products (AGEs), and microvascular changes. These metabolic changes damages tendon structure, biomechanics, and tendon repair processes. The proliferation of tendon stem cells decreases, apoptosis increases, and abnormal differentiation, along with abnormal expression of myofibroblasts, ultimately lead to insufficient tendon repair, fibrosis, and remodeling. Although researches unveiling the effects of diabetes on tendinopathy, fibrosis or contracture, and tendon injury healing are growing, systematic understanding is still lacking. Therefore, this review summarizes the current research status and provides a comprehensive overview, offering theoretical guidance for future in-depth exploration of the impact of diabetes on tendons and the development of treatments for diabetes-related tendon diseases.

Diabetes is associated with impairments in muscle mass and quality increasing the risk of sarcopenia. Thus, this study aimed to investigate the odds of sarcopenia and its associated risk factors among Qatari adults (> 18 years), while exploring the modulating effects of health and lifestyle factors.

Using a case-control design, data from 767 participants (481 cases with diabetes and 286 controls without diabetes) was collected from Qatar Biobank (QBB). Sociodemographic, lifestyle factors including dietary intake, anthropometric and biochemical measures were analyzed. Handgrip strength, Dual X-ray absorptiometry (DXA), and Bio-impedance were used to assess muscle strength, muscle mass and muscle quality, respectively. The risk of sarcopenia was estimated using the European consensus on definition and diagnosis of sarcopenia.

Cases with diabetes were older (55 vs. 36 years; P < 0.001), had higher BMI (31.6 vs. 28.3 kg/m2; P < 0.001), lower cardiorespiratory fitness (50.0% "Moderate" fitness for cases, 62.9% "High" fitness for controls), and consumed less total (59.0 vs. 64.0; P = 0.004) and animal protein (39.0 vs. 42.0; P = 0.001), compared to controls based on a computed score. Participants with diabetes also had lower appendicular lean mass/BMI, handgrip strength, and higher probability of sarcopenia/probable sarcopenia (P < 0.005). Adjusted multiple logistic regression revealed that elevated cardiorespiratory fitness (β = 0.299, 95%CI:0.12-0.74) and blood triglycerides (β = 1.475, 95% CI: 1.024-2.124), as well as being a female (β = 0.086, 95%CI: 0.026-0.288) and having higher BMI (β = 0.908, 95%CI: 0.852-0.967) and ALM/BMI (β = 0.000, 95% CI: 0.000-0.007) are independent predictors (p < 0.05) of sarcopenia risk.

This study highlights the intricate relationship between diabetes and sarcopenia, revealing modifiable risk factors. Individuals with diabetes were found to have a higher likelihood of sarcopenia, which was associated with lower fitness levels and higher blood triglycerides. Protective factors against sarcopenia included being female and having higher BMI and ALM/BMI ratios.

To investigate the correlation between bone metabolism markers, bone mineral density (BMD), and sarcopenia.

A total of 331 consecutive patients aged ≥ 60 years who were hospitalized between November 2020 and December 2021 were enrolled. Participants were divided into sarcopenia and non-sarcopenia groups according to the Asian Working Group on Sarcopenia criteria (AWGS, 2019). The clinical data, bone metabolism markers (β-CTX, N-MID, and TP1NP), and BMD were compared between the two groups.

Age, β-CTX, and N-MID of the sarcopenia group were higher than those of the non-sarcopenia group (P < 0.05), but the BMD T values were lower than those of the non-sarcopenia group (P < 0.05). Binary logistic regression analysis showed that increased femoral neck BMD (FNBMD) was a protective factor for sarcopenia, while increased β-CTX was a risk factor. Pearson/Spearman correlation analysis showed that the diagnostic indices of sarcopenia were positively correlated with FNBMD and negatively correlated with β-CTX and N-MID. Multiple linear regression analysis revealed that BMI and FNBMD significantly positively affected muscle strength and appendicular skeletal muscle mass (ASM). The FNBMD significantly positively affected physical performance, while β-CTX significantly negatively affected muscle strength, ASM, and physical performance.

Increased FNBMD may be a protective factor against sarcopenia, and increased β-CTX may be a risk factor. The FNBMD significantly positively affected the diagnostic indices of sarcopenia, while β-CTX significantly negatively affected them. BMD and bone metabolism marker levels may be considered in early screening for sarcopenia.

Sarcopenia is a chronic, progressive skeletal muscle disease characterised by low muscle strength and quantity or quality, leading to low physical performance. Patients with type 2 diabetes mellitus (T2DM) are more at risk of sarcopenia than euglycemic individuals. Because of several shared pathways between the two diseases, sarcopenia is also a risk factor for developing T2DM in older patients. Various biomarkers are under investigation as potentially valuable for sarcopenia diagnosis and treatment monitoring. Biomarkers related to sarcopenia can be divided into markers evaluating musculoskeletal status (biomarkers specific to muscle mass, markers of the neuromuscular junction, or myokines) and markers assuming causal factors (adipokines, hormones, and inflammatory markers). This paper reviews the current knowledge about how diabetes and T2DM complications affect potential sarcopenia biomarker concentrations. This review includes markers recently proposed by the expert group of the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) as those that may currently be useful in phase II and III clinical trials of sarcopenia: myostatin (MSTN); follistatin (FST); irisin; brain-derived neurotrophic factor (BDNF); procollagen type III N-terminal peptide (PIIINP; P3NP); sarcopenia index (serum creatinine to serum cystatin C ratio); adiponectin; leptin; insulin-like growth factor-1 (IGF-1); dehydroepiandrosterone sulphate (DHEAS); C-reactive protein (CRP); interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). A better understanding of factors influencing these biomarkers' levels, including diabetes and diabetic complications, may lead to designing future studies and implementing results in clinical practice.

MicroRNAs are small regulatory molecules that control gene expression. An emerging property of muscle miRNAs is the cooperative regulation of transcriptional and epitranscriptional events controlling muscle phenotype. miR-155 has been related to muscular dystrophy and muscle cell atrophy. However, the function of miR-155 and its molecular targets in muscular dystrophies remain poorly understood. Through in silico and in vitro approaches, we identify distinct transcriptional profiles induced by miR-155-5p in muscle cells. The treated myotubes changed the expression of 359 genes (166 upregulated and 193 downregulated). We reanalyzed muscle transcriptomic data from dystrophin-deficient patients and detected overlap with gene expression patterns in miR-155-treated myotubes. Our analysis indicated that miR-155 regulates a set of transcripts, including Aldh1l, Nek2, Bub1b, Ramp3, Slc16a4, Plce1, Dync1i1, and Nr1h3. Enrichment analysis demonstrates 20 targets involved in metabolism, cell cycle regulation, muscle cell maintenance, and the immune system. Moreover, digital cytometry confirmed a significant increase in M2 macrophages, indicating miR-155's effects on immune response in dystrophic muscles. We highlight a critical miR-155 associated with disease-related pathways in skeletal muscle disorders.

This review will try to elucidate the interconnected pathophysiology of sarcopenia and type 2 diabetes (T2D) and will try to identify a common pathway to explain their development. To this end, the PubMed and Scopus databases were searched for articles published about the underlying pathophysiology, diagnosis and treatment of both sarcopenia and T2D. The medical subject heading (MeSH) terms 'sarcopenia' AND 'diabetes mellitus' AND ('physiopathology' OR 'diagnosis' OR 'therapeutics' OR 'aetiology' OR 'causality') were used. After screening, 32 papers were included. It was evident that sarcopenia and T2D share multiple pathophysiological mechanisms. Common changes in muscle architecture consist of a shift in myocyte composition, increased myosteatosis and a decreased capacity for muscle regeneration. Further, both diseases are linked to an imbalance in myokine and sex hormone production. Chronic low-grade inflammation and increased levels of oxidative stress are also known pathophysiological contributors. In the future, research efforts should be directed towards discovering common checkpoints in the development of T2D and sarcopenia as possible shared therapeutic targets for both diseases. Current treatment for T2D with biguanides, incretins and insulin may already convey a protective effect on the development of sarcopenia. Furthermore, attention should be given to early diagnosis of sarcopenia within the population of people with T2D, given the sizeable physical and medical burden it encompasses. A combination of simple diagnostic techniques could be used at regular diabetes check-ups to identify sarcopenia at an early stage and start lifestyle modifications and treatment as soon as possible.

Ferroptosis, characterized by iron accumulation and lipid peroxidation, leads to cell death. Growing evidence suggests the involvement of ferroptosis in sarcopenia. However, the fundamental ferroptosis-related genes (FRGs) for sarcopenia diagnosis, prognosis, and therapy remain elusive. This study aimed to identify molecular biomarkers of ferroptosis in sarcopenia patients. Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between normal and sarcopenia samples were identified using the 'limma' package in R software. FRGs were extracted from GeneCards and FerrDB databases. Functional enrichment analysis determined the roles of DEGs using the 'clusterProfiler' package. A protein-protein network was constructed using Cytoscape software. Immune infiltration analysis and receiver operating characteristic (ROC) analysis were performed. mRNA-miRNA, mRNA-TF, and mRNA-drug interactions were predicted using ENCORI, hTFtarget, and CHIPBase databases. The network was visualized using Cytoscape. We identified 46 FRGs in sarcopenia. Functional enrichment analysis revealed their involvement in critical biological processes, including responses to steroid hormones and glucocorticoids. KEGG enrichment analysis implicated pathways such as carbon metabolism, ferroptosis, and glyoxylate in sarcopenia. Totally, 11 hub genes were identified, and ROC analysis demonstrated their potential as sensitive and specific markers for sarcopenia in both datasets. Additionally, differences in immune cell infiltration were observed between normal and sarcopenia samples. The hub genes identified in this study are closely associated with ferroptosis in sarcopenia and can effectively differentiate sarcopenia from controls. CDKN1A, CS, DLD, FOXO1, HSPB1, LDHA, MDH2, and YWHAZ show high sensitivity and specificity for sarcopenia diagnosis.

Imbalance in glucose metabolism and insulin resistance are two primary features of type 2 diabetes/diabetes mellitus. Its etiology is linked to mitochondrial dysfunction in skeletal muscle tissue. The mitochondria are vital organelles involved in ATP synthesis and metabolism. The underlying biological pathways leading to mitochondrial dysfunction in type 2 diabetes can help us understand the pathophysiology of the disease. In this study, the mitochondrial gene expression dataset were retrieved from the GSE22309, GSE25462, and GSE18732 using Mitocarta 3.0, focusing specifically on genes that are associated with mitochondrial function in type 2 disease. Feature selection on the expression dataset of skeletal muscle tissue from 107 control patients and 70 type 2 diabetes patients using the XGBoost algorithm having the highest accuracy. For interpretation and analysis of results linked to the disease by examining the feature importance deduced from the model was done using SHAP (SHapley Additive exPlanations). Next, to comprehend the biological connections, study of protein-protien and mRNA-miRNA networks was conducted using String and Mienturnet respectively. The analysis revealed BDH1, YARS2, AKAP10, RARS2, MRPS31, were potential mitochondrial target genes among the other twenty genes. These genes are mainly involved in the transport and organization of mitochondria, regulation of its membrane potential, and intrinsic apoptotic signaling etc. mRNA-miRNA interaction network revealed a significant role of miR-375; miR-30a-5p; miR-16-5p; miR-129-5p; miR-1229-3p; and miR-1224-3p; in the regulation of mitochondrial function exhibited strong associations with type 2 diabetes. These results might aid in the creation of novel targets for therapy and type 2 diabetes biomarkers.

Type 2 diabetes mellitus (T2DM) is a lifelong condition and a threat to human health. Thorough understanding of its pathogenesis is acutely needed in order to devise innovative, preventative, and potentially curative pharmacological interventions. MicroRNAs (miRNA), are small, non-coding, one-stranded RNA molecules, that can target and silence around 60% of all human genes through translational repression. MiR-155 is an ancient, evolutionarily well-conserved miRNA, with distinct expression profiles and multifunctionality, and a target repertoire of over 241 genes involved in numerous physiological and pathological processes including hematopoietic lineage differentiation, immunity, inflammation, viral infections, cancer, cardiovascular conditions, and particularly diabetes mellitus. MiR-155 Levels are progressively reduced in aging, obesity, sarcopenia, and T2DM. Thus, the loss of coordinated repression of multiple miR-155 targets acting as negative regulators, such as C/EBPβ, HDAC4, and SOCS1 impacts insulin signaling, deteriorating glucose homeostasis, and causing insulin resistance (IR). Moreover, deranged regulation of the renin angiotensin aldo-sterone system (RAAS) through loss of Angiotensin II Type 1 receptor downregulation, and negated repression of ETS-1, results in unopposed detrimental Angiotensin II effects, further promoting IR. Finally, loss of BACH1 and SOCS1 repression abolishes cytoprotective, anti-oxidant, anti-apoptotic, and anti-inflammatory cellular pathways, and promotes β-cell loss. In contrast to RAAS inhibitor treatments that further decrease already reduced miR-155 Levels, strategies to increase an ailing miR-155 production in T2DM, e.g., the use of metformin, mineralocorticoid receptor blockers (spironolactone, eplerenone, finerenone), and verapamil, alone or in various combinations, represent current treatment options. In the future, direct tissue delivery of miRNA analogs is likely.

Previous studies have reported an association between sarcopenia and type 2 diabetes mellitus (T2DM), but causation was prone to confounding factors. A more robust research approach is urgently required to investigate the causal relationship between sarcopenia and T2DM.

The bi-directional two-sample MR study was carried out in two stages: Sarcopenia-related traits were investigated as exposure while T2DM was investigated as an outcome in the first step, whereas the second step was reversed. The GWAS summary data for hand-grip strength (n = 256,523), appendicular lean mass (ALM, n = 450,243), and walking pace (n = 459,915) were obtained from the UK Biobank. T2DM data were obtained from one of the biggest case-control studies on diabetes (DIAGRAM; n = 180,834 cases and 492,191 controls), which was published in 2022. The inverse-variance weighted (IVW) approach was used to obtain MR estimates, and various sensitivity analysis was also performed.

Low hand-grip strength had a potential causal relationship with an increased incidence of T2DM (OR = 1.109; 95% CI, 1.008-1.222; p = 0.0350). T2DM risk was reduced by increasing ALM and walking pace: A 1 kg/m² increase in ALM decreased the risk of T2DM by 10.2% (OR = 0.898; 95% CI, 0.830-0.952; p < 0.001). A 1 m/s increase in walking pace decreased the risk of T2DM by 90.0% (OR = 0.100; 95% CI, 0.053-0.186; p < 0.001). The relationship was bidirectional, with T2DM as a causative factor of sarcopenia-related traits (p < 0.05) except for ALM (β = 0.018; 95% CI, -0.008 to -0.044; p = 0.168).

Hand-grip strength and T2DM had a potential bidirectional causal relationship, as did walking pace and T2DM. We suggest that sarcopenia and T2DM may mutually have a significant causal effect on each other.

Semaphorins are a large family of secreted and/or transmembrane proteins, originally identified as proteins that function in axon guidance during neuronal development. However, semaphorins play crucial roles in other physiological and pathological processes, including immune responses, angiogenesis, maintenance of tissue homeostasis, and cancer progression. Class IV semaphorins may be present as transmembrane and soluble forms and are implicated in the pathogenesis of various diseases. This review discusses recent progress on the roles of class IV semaphorins determined by clinical and experimental pathology studies.

To investigate the value of CT imaging features of paravertebral muscles in predicting abnormal bone mass in patients with type 2 diabetes mellitus.

The clinical and QCT data of 149 patients with type 2 diabetes mellitus were collected retrospectively. Patients were randomly divided into the training group (n = 90) and the validation group (n = 49). The radiologic model and Nomogram model were established by multivariate Logistic regression analysis. Predictive performance was evaluated using receiver operating characteristic (ROC) curves.

A total of 829 features were extracted from CT images of paravertebral muscles, and 12 optimal predictive features were obtained by the mRMR and Lasso feature selection methods. The radiomics model can better predict bone abnormality in type 2 diabetes mellitus, and the (Area Under Curve) AUC values of the training group and the validation group were 0.94(95% CI, 0.90-0.99) and 0.90(95% CI, 0.82-0.98). The combined Nomogram model, based on radiomics and clinical characteristics (vertebral CT values), showed better predictive efficacy with an AUC values of 0.97(95% CI, 0.94-1.00) in the training group and 0.95(95% CI, 0.90-1.00) in the validation group, compared with the clinical model.

The combination of Nomogram model and radiomics-clinical features of paravertebral muscles has a good predictive value for abnormal bone mass in patients with type 2 diabetes mellitus.