BackgroundGrip strength is a key marker for sarcopenia screening, yet the influence of iodine nutritional status on low grip strength (LGS) remains poorly understood.MethodsThis cross-sectional study analyzed 810 community-dwelling adults in Lanzhou, China, randomly assigned to training (n = 568) and validation (n = 242) cohorts. Logistic regression analyses identified factors associated with LGS. A nomogram integrating urinary iodine concentration (UIC), systolic blood pressure (SP), and routine clinical variables was constructed. Model performance was evaluated using ROC curves, Hosmer-Lemeshow test, and Brier scores. Restricted cubic spline (RCS) analysis assessed the dose–response relationship between UIC and LGS, with subgroup analyses by thyroid function.ResultsLGS prevalence was 18.8% in the training cohort. Multivariate analysis showed female sex (OR = 0.34), greater height (OR = 0.94), and excessive iodine (OR = 0.36) were inversely associated with LGS, whereas age (60–74 years: OR = 2.20; ≥75 years: OR = 9.73), smoking (OR = 3.20), and SP (OR = 1.02) correlated with higher LGS odds. The nomogram demonstrated moderate discrimination (AUC: 0.723 training, 0.662 validation) with good calibration (Brier scores: 0.134 training, 0.147 validation; H-L p > 0.05). RCS analysis revealed a U-shaped association between UIC and LGS in unadjusted analyses, with the inverse associations most evident among euthyroid participants.ConclusionThe nomogram provides a practical, objective tool for early identification of individuals at high probability of LGS. Moderate-to-high UIC is associated with LGS odds, particularly in euthyroid adults. This model may guide targeted screening and interventions in community settings. In the cross-sectional design, causal inferences cannot be drawn; Further research is warranted to elucidate these complex relationships.

OBJECTIVES:To investigate the relationship between cholesterol, high-density lipoprotein, and glucose (CHG) index and metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with type 2 diabetes mellitus (T2DM). METHODS:1,789 patients with T2DM aged ≥50 years were divided into MASLD (age: 62.56 ± 7.59) and non-MASLD groups (age: 62.78 ± 7.79). Adjusted regression models, threshold analysis, mediation analysis, and receiver operating characteristic (ROC) curves were used. Based on CHG index levels and various immunoinflammatory markers, patients with T2DM were divided into different groups, and the prevalence of MASLD was compared. RESULTS:The CHG index, neutrophil-to-albumin ratio (NAR), neutrophil-to-lymphocyte ratio (NLR,) systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI) were higher in the MASLD group than in the non-MASLD group (p < 0.05). Multiple logistic regression analysis showed that the CHG index, NAR, NLR, SII, SIRI, and AISI were positively correlated with MASLD risk (all p < 0.05). Threshold analysis showed that when the CHG index was <5.474, it was positively associated with MASLD risk (p < 0.05). MASLD prevalence increased with increasing levels of inflammatory markers and the CHG index (p < 0.05). Mediation analysis of NAR, NLR, and SII between the CHG index and MASLD showed that the total effect estimates were 0.0159, 0.0153, and 0.0157, respectively; the direct effect estimates were 0.0107, 0.0134, and 0.0120; and the mediation effect estimates were 0.0053, 0.0019 and 0.0037, with the mediated proportions accounting for 27.25%, 11.47%, and 27.25% of the total effect, respectively. ROC curve analysis showed that the CHG index combined with SIRI had improved diagnostic performance for MASLD, with an area under the curve of 0.71. CONCLUSION:The CHG index was positively associated with MASLD risk in patients with T2DM aged ≥50 years. NAR, NLR, and SII partially mediated this association, highlighting their potential application in MASLD diagnosis.

AimsTo clarify the relationship between serum ferritin (SF) levels and diabetic retinopathy (DR) and to analyze the mediating role of the neutrophil-to-albumin ratio (NAR).MethodsA total of 1,884 middle-aged and elderly patients (aged ≥ 45 years) with type 2 diabetes mellitus (T2DM) were included in this study. Participants were divided into non-DR and DR groups. Adjusted regression models, receiver operating characteristic (ROC) curve analysis, threshold effect analysis, and mediation effect analysis were performed. T2DM patients were divided into three groups, and differences in the prevalence of DR were compared.ResultsSF and NAR levels were higher in the DR group than in the non-DR group (P < 0.05). Logistic regression analysis showed a significant positive correlation between SF levels and the risk of DR. Restricted cubic spline (RCS) and threshold effect analyses revealed a nonlinear relationship between SF and the risk of DR, with an optimal inflection point at a SF value of 27.9556. Additionally, NAR was positively correlated with the risk of DR. The prevalence of DR increased with increasing levels of NAR markers and SF (P < 0.05). Mediation analysis of the association between NAR and the risk of DR showed that the total effect estimate was 0.0003, the direct effect estimate was 0.0003, and the mediation effect estimate was 0.0001, with the mediation proportion accounting for 20.99% of the total effect. The combination of SF and NAR demonstrated potential as an indicator for DR, with an area under the ROC curve (AUC) of 0.69.ConclusionsSF levels in middle-aged and elderly patients with T2DM are associated with an increased risk of DR. NAR, an inflammatory marker, plays an important mediating role in the association between ferritin and the risk of DR. The combined use of SF and NAR may serve as a more sensitive indicator for the early diagnosis of DR.

Background Atherosclerotic cardiovascular disease (ASCVD) is one of the common complications in patients with type 2 diabetes mellitus (T2DM). Thyroid hormones affect cardiovascular function through multiple pathways. Purpose To explore the relationships between impaired thyroid hormone sensitivity and the 10-year risk of ASCVD in euthyroid patients with T2DM. Methods 899 patients with T2DM were divided into three groups according to the different ASCVD risk levels, the difference of thyroid hormone sensitivity indices [Parametric Thyroid Feedback Quantile-based Index (PTFQI), Thyroid Feedback Quantile-based Index (TFQI), Thyroid Stimulating Hormone Index (TSHI), Serum-Free triiodothyronine to Free thyroxine (FT3/FT4) ratio, and Thyrotropin Thyroxine Resistance Index (TT4RI)] between three groups were compared. Results As the 10-year ASCVD risk grade increased, TT4RI level showed a gradually rising trend, while FT3/FT4 ratio exhibited a decreasing trend ( P < 0.05). PTFQI, TFQI, TSHI, and TT4RI were positively, and FT3/FT4 was negatively correlated with ASCVD risk (all P < 0.05). Thyroid hormone sensitivity indicators had a linear dose-response relationships with ASCVD risk. As the levels of PTFQI, TFQI, TSHI, and TT4RI increase and the level of FT3/FT4 decreases, the ASCVD risk showed an upward trend. Conclusion To patients with T2DM, impaired thyroid hormone sensitivity is associated with ASCVD risk.

Non-enzymatic glycation is an important post-translational modification of proteins, ultimately forming advanced glycation end products (AGEs). In a high-glucose environment, the glycation degree of transferrin (Tf) increases, leading to elevated levels of AGE-modified transferrin (AGE-Tf), which reduces the binding capacity of Tf for iron. However, the role of AGE-Tf-associated iron dysregulation in diabetic nephropathy remains unclear. In this study, human podocytes were treated in vitro with AGE-Tf prepared by incubating Tf with 5.6 or 33.3 mM glucose (hereafter termed 5.6-Glc-AGE-Tf and 33.3-Glc-AGE-Tf, respectively) in combination with iron. Additionally, plasmids encoding Tf with mutations at three glycation sites (K206 A/K296 A/K534A; MT-Tf) or wild-type Tf (WT-Tf) were packaged into adeno-associated viral vectors and administered to diabetic rats. Compared with podocytes treated with 5.6-Glc-AGE-Tf, podocytes treated with 33.3-Glc-AGE-Tf exhibited reduced viability and greater oxidative stress. After ferric-citrate addition, intracellular Fe2+ was also higher in the 33.3-Glc-AGE-Tf group than in the 5.6-Glc-AGE-Tf group. The 33.3-Glc-AGE-Tf group showed decreased GPX4, Nrf-2, and SLC7A11 expression and increased ACSL4 expression. In vivo, diabetic rats receiving an empty vector (DM-empty-vector) or a wild-type Tf vector (DM-WT-Tf-vector) exhibited higher renal AGE-Tf, Fe2+, and oxidative stress levels; lower nephrin and podocin expression; ferroptosis-related alterations; mesangial cell proliferation and matrix expansion; increased interstitial collagen deposition; and focal nodular sclerosis. These alterations were attenuated in diabetic rats receiving the glycation-resistant mutant Tf vector (DM-MT-Tf-vector). Deferoxamine (DFO) or TBHQ (an Nrf-2 activator) ameliorated oxidative stress, iron dysregulation, and ferroptosis in AGE-Tf-treated podocytes and in the kidneys of diabetic rats receiving the WT-Tf vector, whereas LY294002 (a PI3K/AKT pathway inhibitor) primarily alleviated oxidative stress. These findings identify AGE-Tf-associated iron dysregulation as a potential therapeutic target in diabetic kidney disease.

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes. The glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide exerts renoprotective effects beyond glucose control; however, the underlying mechanisms remain incompletely understood. The protective effects and mechanisms of liraglutide were investigated using in vitro (HK-2 cells under glucolipotoxic conditions) and in vivo (DKD rat) models. Key molecular and functional assessments included the evaluation of oxidative stress, apoptosis, mitochondrial function (dynamics (MFN1, MFN2, FIS1, and DRP1), mitophagy (PINK1, PARKIN, LC3II/I, and P62), and ultrastructure), and histone acetylation (H3K9/14/18/27ac). The critical role of the NQO1/SIRT3 pathway was validated using pharmacological inhibition and genetic silencing (shRNA/AAV). Both in vitro and in vivo, a multifaceted injury phenotype, including oxidative stress, apoptosis, mitochondrial dysfunction, and histone hyperacetylation, was induced, accompanied by downregulation of the NQO1/SIRT3 pathway. Disruption of this pathway further exacerbated these injuries. Conversely, liraglutide treatment effectively counteracted this phenotype, improving metabolic parameters (blood glucose, blood insulin, and blood lipids), renal function (blood urea nitrogen, serum creatinine, and urine albumin-to-creatinine ratio) and histopathology. Liraglutide attenuated oxidative stress and apoptosis, restored mitochondrial function and mitophagy, and reduced histone hyperacetylation. These protective effects were consistently associated with the restoration of NQO1/SIRT3 expression. Genetic or pharmacological disruption of the NQO1/SIRT3 axis significantly attenuated the efficacy of liraglutide, and combined inhibition completely abolished its effects. Our findings demonstrate that liraglutide attenuates DKD by activating the NQO1/SIRT3 pathway, which coordinates the enhancement of mitochondrial function and the restoration of epigenetic homeostasis. This study revealed that the NQO1/SIRT3 pathway is a critical mechanistic mediator of the renoprotective effect of liraglutide.

To investigate the relationship between low skeletal muscle mass and specific immunoinflammatory markers in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). 978 hospitalized middle-aged and elderly patients with type 2 diabetes mellitus (T2DM), all with a confirmed diagnosis and disease duration ≥ 1 year, were enrolled in this study from the Department of Endocrinology. Patients were divided into a low and a normal skeletal muscle mass group using the appendicular skeletal muscle mass index (ASMI). Differences in clinical indicators between the two groups were compared. Six inflammatory markers, including the neutrophil-to-albumin ratio (NAR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI) were grouped by quartile levels. The prevalence of low skeletal muscle mass was compared between the quartile groups and logistic regression analyses used to explore the independent association between each marker and risk of low skeletal muscle mass. Levels of all six immunoinflammatory markers were significantly higher in the low skeletal muscle mass group (all P < 0.05) than in the normal group. The prevalence of low skeletal muscle mass increased with increasing quartile levels of each marker. After adjusting for confounding factors (age, gender, body mass index (BMI), and blood lipid levels), all immunoinflammatory markers were independently and positively correlated with the risk of low skeletal muscle mass. NAR×10 (OR = 2.146, 95

Lipid accumulation product index (LAPI) is a new indicator for evaluating visceral obesity and has been used in the assessment of risk of diabetes and diabetic kidney disease, however the association with the risk of osteoporosis (OP) in patients with type 2 diabetes mellitus (T2DM) remains unclear. We aimed to determine the association between the lipid accumulation product index (LAPI) and osteoporosis (OP) risk in elderly patients with type 2 diabetes mellitus (T2DM). A total of 1280 patients with T2DM aged over 60 years were divided into OP and non-OP groups, and the LAPI levels were compared, patients were categorized into Q1, Q2, Q3, and Q4 groups based on quartiles of LAPI, and the prevalence of OP was compared. Correlation between the LAPI and risk of OP in male or female was analyzed by multivariate logistic regression and subgroup analyses. LAPI levels were significantly higher in OP group (50.80 ± 16.95) than in the non-OP group (45.64 ± 14.38, p < 0.05), the prevalence of OP was significantly higher in the Q4 group than in the Q1, Q2, and Q3 groups. Multivariate regression analyses showed that compared with the Q1 group, people in the Q4 group had a higher risk of OP, the OR was 2.748 (95

Previous studies have found the increased levels of transferrin (Tf) modified by advanced-glycation-end-products (AGE-Tf) in the serum of patients with type 2 diabetes mellitus and the kidneys of diabetic rats. The study aimed to investigate the effects of AGE-Tf on human podocytes in vitro. AGE-Tf was prepared by incubating Tf with different concentrations of glucose (0 mM, 5.6 mM, 11.1 mM, and 33.3 mM) in vitro. Podocytes were treated with AGE-Tf produced at different concentrations of glucose, and rescue experiments include AGE-Tf + deferoxamine mesylate (DFO), AGE-Tf + Ferrostatin-1 (Fer-1, inhibitors of ferroptosis), and AGE-Tf + advanced glycation end-product receptor (RAGE) antagonist peptide (RAP) groups. The total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), lipid peroxidation (LPO), and malonic dialdehyde (MDA) were measured, and the expression levels of glutathione peroxidase 4 (GPX4), acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4), and nuclear factor erythroid 2-related factor 2 (NRF2) were analyzed. In vitro, with increasing glucose levels, the degree of glycation of Tf increased gradually, and the total iron binding capacity decreased gradually. When podocytes were treated by AGE-Tf, podocyte activity decreased, and apoptosis increased. Antioxidant capacity decreased, and LPO and ROS levels increased. The expression of GPX4, NRF2, and SLC7A11 was down-regulated; the expression of ACSL4 was up-regulated. Whereas the addition of Fer-1 or RAP reduced the effects of AGE-Tf on podocytes, including oxidative stress and ferroptosis, which were inhibited, and cell viability and apoptosis rate were partially improved. AGE-Tf may mediate oxidative stress and ferroptosis in podocytes via AGE/RAGE.

Background and Objectives: To investigate the correlation between weight-adjusted-waist index (WWI), a novel obesity index, and serum ferritin (SF) level in patients with type 2 diabetes mellitus (T2DM), and the association between WWI and the prevalence of hyperferritinemia. Methods and Study Design: A total of 943 patients with T2DM were divided into three groups based on WWI tertile levels. Disparities in SF levels and the prevalence of hyperferritinemia were compared among these groups. The correlations among WWI, SF levels, and hyperferritinemia were analyzed in patients with T2DM. Results: As WWI tertile levels increased, SF levels tended to increase (p for trend <0.01). A statistically significant positive correlation was observed between the WWI and SF levels (R = 0.263, p < 0.001). After adjusting for confounders by multiple linear regression, a significant positive correlation was maintained between the WWI and SF levels [beta = 0.194, 95% CI (49.914, 112.120)], p < 0.01]. Binary logistic regression analysis revealed a positive association between the WWI and the likelihood of hyperferritinemia, with a notably stronger correlation observed in females compared to males [OR = 3.248, 95% CI (2.027, 5.204), p < 0.01 vs. OR = 2.091, 95% CI (1.432, 3.054), p < 0.01]. Conclusions: Along with increasing WWI, SF levels gradually increased in patients with T2DM. The WWI exhibited a positive correlation with SF levels and hyperferritinemia, more significantly in female patients.

Type 2 diabetes mellitus (T2DM) is a chronic medical condition prevalent worldwide. Currently, probiotic therapy has demonstrated favorable outcomes in T2DM management, albeit with a lingering controversy. In this network meta-analysis (NMA), we aimed to assess and rank the glycemic control efficacy of various probiotic strains or combinations in T2DM patients. A systematic literature review was conducted across 4 major databases (PubMed, Embase, Web of Science, and Cochrane Library) including data published up to November 8, 2023, to identify randomized controlled trials (RCTs) on probiotic therapy in T2DM patients. The quality of the included RCTs was evaluated using the risk-of-bias tool version 2, while Bayesian NMA was used for analysis. The efficacy of different probiotics and their combinations was ranked based on the surface under the cumulative ranking curve (SUCRA) for various outcome indicators. This study included 1861 T2DM patients from 30 RCTs. The combination of LAC (Lactobacillus) + BIF (Bifidobacterium) + PRO (Propionibacterium) + STR (Streptococcus) exhibited the most favorable effect in reducing the fasting plasma glucose concentration and improving the homeostatic model assessment of insulin resistance (SUCRA: 88.8% and 77.3%). For reducing the concentration of glycated hemoglobin A1c, BIF (SUCRA: 93.1%) was the most effective; for improving insulin secretion, LAC + BIF (SUCRA: 84.7%) exhibited the most favorable outcome for improving insulin secretion. Cluster analysis of the 4 outcome indicators showed that the LAC + BIF + STR combination may have superior therapeutic effects. Multistrain probiotic combinations demonstrated greater glycemic control effects than single-strain probiotics. Thus, LAC + BIF + STR may be a promising probiotic combination for the treatment of T2DM. Nevertheless, owing to the inherent limitations of existing studies, further research is warranted to ascertain the long-term efficacy of probiotics.

Most cases of hereditary severe insulin-resistance syndrome (H-SIRS) are linked to mutations in the insulin receptor (INSR) gene. Patients with H-SIRS typically manifest symptoms of hyperinsulinemia, insulin resistance, and diabetes mellitus. Other symptoms include impaired glucose regulation, hyperandrogenism, and the presence of acanthosis nigricans (AN). In this report, we present two cases of H-SIRS in female children exhibiting various symptoms, including hyperinsulinemia, fasting hypoglycemia, postprandial hyperglycemia, overweight, fatty liver, hyperandrogenism, and varying degrees of AN. One patient also presented with mental retardation. Gene sequencing identified specific mutations in the INSR gene for both patients: c.2663A > G (p.Tyr888Cys) in Patient 1 and c.38_61del (p.Pro13_Ala20del) in Patient 2. These mutations both have the potential to disrupt the interaction between the insulin receptor, INSR, and insulin, leading to abnormal insulin signaling, insulin resistance, and various clinical manifestations.

The relationship between thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and diabetic kidney disease (DKD) is still controversial, and this study analyzed the correlation between TSH, FT3, FT4 and DKD in patients with type 2 diabetes mellitus (T2DM). T2DM patients (1216) were divided into five groups based on serum TSH, FT3, and FT4 levels, differences in urinary albumin excretion rate (UACR), estimated glomerular filtration rate (eGFR) were compared. Binary logistic regression verified independent correlations among TSH, FT3, FT4 and UACR, eGFR. TSH and FT3 predictive values for DKD were analyzed using receiver operating characteristic (ROC) curves. The prevalence of albuminuria with decreased eGFR was higher in T2DM patients with subclinical hypothyroidism and overt hypothyroidism than that in patients with normal thyroid function. TSH positively correlated with UACR (r = 0.133, p < 0.001) and positively correlated with eGFR (r = -0.218, p < 0.001), FT3 negatively correlated with UACR (r = -0.260, p < 0.001) and positively correlated with eGFR (r = 0.324, p < 0.001). With the change from the lower normal level to the increased level of TSH and the change from the higher normal level to the reduced level of FT3, the prevalence of albuminuria gradually increased, the prevalence of decreased eGFR gradually increased in TSH groups and FT3 groups. After adjusting for age, BMI, duration of diabetes, TPOAb, TGAb, smoking, drinking, hypertension, the use of anti-diabetic medications (metformin, sodium–glucose cotransporter 2 inhibitors), HbA1c, CRP, TC, TG, LDL-C, and HDL-C, both TSH and FT3 correlated with increased UACR (TSH: OR 1.253, p = 0.001; FT3: OR 0.166, p < 0.001) and decreased eGFR (TSH: OR 1.245, p < 0.001, FT3: OR 0.579, p < 0.001), but this correlation of TSH with eGFR < 60 mL/min/1.73 m2 was not found in male. The area under the ROC curve (AUC) for FT3 was greater than that for TSH (FT3: 0.64; TSH: 0.61). Increased TSH and reduced FT3 levels were associated with DKD in T2DM patients, but in a sex-dependent manner. FT3 had a higher predictive value for DKD.

Nephrogenic diabetes insipidus (NDI) is a rare genetic disorder primarily associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin 2 (AQP2) gene, resulting in impaired water reabsorption in the renal tubules. This report describes a case of a young male patient with NDI from China with a history of polydipsia and polyuria for over 15 years. Laboratory examinations of the proband indicated low urine-specific gravity and osmolality. Urologic ultrasound revealed severe bilateral hydronephrosis in both kidneys, bilateral dilatation of the ureters, roughness of the bladder wall, and the formation of muscle trabeculae. The diagnosis of diabetes insipidus was confirmed by water deprivation tests. The administration of posterior pituitary hormone did not alter urine-specific gravity, and osmolality remained at a low level (<300 mOsm/kg). Based on these findings, and the genetic tests of the proband and his parents were performed. A missense mutation (c.616 G>C) in exon 3 of the AVPR2 gene of the proband was found, caused by the substitution of amino acid valine to leucine at position 206 [p.Val206Leu], which was a hemizygous mutation and consistent with X-chromosome recessive inheritance. The administration of oral hydrochlorothiazide improves the symptoms of polydipsia and polyuria in the proband. This novel AVPR2 gene mutation may be the main cause of NDI in this family, which induces a functional defect in AVPR2, and leads to reduced tubular reabsorption of water.

Purpose To investigate the relationship between advanced liver fibrosis and osteoporosis in metabolic-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 1144 T2DM patients were divided into the MAFLD and non-MAFLD groups, 460 T2DM patients with MAFLD (277 males aged ≥50 years and 183 postmenopausal females) were divided into N1 (advanced liver fibrosis excluded), N2 (indeterminate advanced liver fibrosis), and N3 (advanced liver fibrosis) groups according to the non-alcoholic fatty liver fibrosis score (NFS), the differences in bone mineral density (BMD) levels and prevalence of osteoporosis were compared. Based on the tertile levels of BMD of the lumbar spine (L), T2DM patients were divided into three groups (T1, T2, and T3), and the differences in the prevalence of advanced liver fibrosis were compared. Results The BMD levels of the L 4 , and L 1-4 in the MAFLD group were lower than those of the non-MAFLD groups in male and female T2DM patients .The BMD levels of the total hip, L 4 , and L 1-4 in the N3 group were lower than those of the N2 and N1 groups in male and female T2DM patients with MAFLD, and the prevalence of osteoporosis in the N3 group of males was higher than that in the N1 group. The BMD levels of the total hip, L 4 , and L 1-4 were negatively correlated with NFS in both males and females. The BMD levels of the total hip and L 4 in males, and the BMD level of L 4 in females were negatively associated with NFS. The prevalence of advanced liver fibrosis was higher in the T1 group than in the T2 and T3 groups in T2DM patients with MAFLD. Conclusion The BMD levels in male aged ≥50 years or postmenopausal female diabetic patients with MAFLD were negatively correlated with the degree of advanced liver fibrosis, which means an increased risk of liver fibrosis with decreasing BMD.

Aim:To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes mellitus (T2DM).Methods:Relevant studies investigating the influence of TZP therapy on weight, lipid profiles and blood pressure in overweight/obese T2DM patients were selected from the PubMed, Embase, Web of Science and Cochrane databases from establishment until November 2022. A systematic review and meta-analysis were conducted to evaluate the effect of TZP on weight, blood lipids and blood pressure in overweight/obese patients with T2DM.Results:Eight randomized controlled trials (RCTs), comprising 7491 patients with T2DM, were included in the meta-analysis. Results showed that compared with the glucagon-like peptide-1 receptor agonist (GLP-1RA), insulin, and placebo groups, body weight, triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels were significantly decreased in the TZP-treated groups, while high-density lipoprotein cholesterol (HDL-C) levels increased. With the gradual increase of TZP doses, the proportions of T2DM patients with weight loss >5% gradually increased. The 10 mg and 15 mg TZP doses had a stronger effect on the levels of TG, VLDL-C, and HDL-C. Moreover, the reduction in SBP levels in the 15 mg TZP-treated group was more pronounced than those in the 10 mg and 5 mg TZP-treated groups [MD=-2.07, 95% CI (-2.52, -1.63) and MD=-3.14, 95% CI (-4.42, -1.87)]. Compared with GLP-1RA, insulin, and placebo groups, the proportions of patients with HbA1c<7% in 10mg and 15mg TZP-treated groups were significantly higher than in the 5mg TZP-treated group [OR=1.53, 95% CI (1.25, 1.8)], OR=1.7, 95% CI (1.15, 2.50)].There was no significant difference regarding the risk of adverse reactions.

Osteoporosis (OP) is a common age-related disease. OP is mainly a decrease in bone density and mass caused by the destruction of bone microstructure, which leads to an increase in bone fragility. SIRT3 is a mitochondrial deacetylase that plays critical roles in mitochondrial homeostasis, metabolic regulation, gene transcription, stress response, and gene stability. Studies have shown that the higher expression levels of SIRT3 are associated with decreased levels of oxidative stress in the body and may play important roles in the prevention of age-related diseases. SIRTs can enhance the osteogenic potential and osteoblastic activity of bone marrow mesenchymal stromal cells not only by enhancing PGC-1α, FOXO3, SOD2, and oxidative phosphorylation, but also by anti-aging and reducing mitochondrial autophagy. SIRT3 is able to upregulate antioxidant enzymes to exert an inhibitory effect on osteoclasts, however, it has been shown that the inflammatory cascade response can in turn increase SIRT3 and inhibit osteoclast differentiation through the AMPK-PGC-1β pathway. SIRT3 plays an important role in different types of osteoporosis by affecting osteoblasts, osteoclasts, and bone marrow mesenchymal cells. In this review, we discuss the classification and physiological functions of SIRTs, the effects of SIRT3 on OCs osteoblasts, and BMSCs, and the roles and mechanisms of SIRT3 in different types of OP, such as diabetic OP, glucocorticoid-induced OP, postmenopausal OP, and senile OP.

Background and Objectives: To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in postmenopausal elderly women with type 2 diabetes mellitus (T2DM). Methods and Study Design: A total of 141 postmenopausal elderly women with T2DM was divided into OP and normal bone mineral density (BMD) groups, the differences in GRNI levels between the two groups were compared. According to the tertile levels of GRNI, T2DM were divided into three groups (T-1, T-2, T-3 groups), and the differences in OP prevalence and levels of BMD among the three groups were compared. Results: Among postmenopausal elderly women with T2DM, GNRI levels were lower in the OP group compared to the normal BMD group [(103 +/- 5.46) vs. (105 +/- 5.46), p<0.05)]. With elevated GNRI levels, the BMD levels of femoral, total hip, total body, and lumbar vertebrae ( L) were gradually increased, which were higher in the T-3 group than in the T-1 group (all p< 0.05). GNRI levels were positively correlated with the BMD levels of femoral, spine, total hip, total body, L-1, L-2, L-3, L-4, and L-1-L-4. GNRI was an independent influencing factor for the occurrence of OP (OR=0.887, 95%CI [0.795,0.988]). The ROC curve showed that the GNRI combined with serum ALP and P levels had a high predictive value for OP, with an area under the curve of 0.725 (p<0.01). Conclusions: In postmenopausal elderly women with T2DM, GNRI was independently and positively correlated with BMD levels. GNRI may be a predictor development of OP.

The interaction and combined effect of the triglyceride-glucose (TyG) index, an alternative parameter of insulin resistance, along with hypertension (HT), on the risk of peripheral arterial disease (PAD), a specific type of atherosclerotic cardiovascular disease, in individuals with type 2 diabetes (T2D) seems straightforward. However, specific research on this topic remains scarce. In this cross-sectional study, 2027 adult participants with T2D were devided into four groups based on the mean values of TyG index and various blood pressure parameters along with its category. Binary logistic regression, interaction analysis, combined effect size, and goodness-of-fit of the constructed models were performed. The TyG index’s individual effect and it’s combined effect with HT, or higher systolic blood pressure (SBP) or higher mean arterial pressure in patients with T2D correlated with a higher PAD risk respectively (odds ratio [OR], 0.50, [95

This study aims to discover the association between serum osteocalcin, the Chinese visceral adiposity index (CVAI), and atherosclerotic cardiovascular disease (ASCVD) risk, and their impact on arterial stiffness in T2DM patients. We included 639 T2DM patients aged 30 and older who received the assessment of ASCVD risk using the China-PAR equation, Osteocalcin and arterial stiffness in this cross-sectional study. We found that osteocalcin and CVAI as independent risk factors for both medium-high-risk ASCVD (osteocalcin: men, OR,0.96, 95% CI 0.92, 1.00; women, OR, 0.93, 95% CI 0.8, 1.08, respectively)(CVAI: men, OR,1.01,95% CI 1.00,1.02; women: OR, 1.08, 95% CI 1.02,1.14, respectively) and arterial stiffness (osteocalcin: men, OR, 0.98, 95% CI 0.94,1.01; women, OR, 0.98, 95% CI 0.90,1.06, respectively)(CVAI: men, OR,1.0, 95% CI 0.99,1.01; women, OR, 1.02, 95% CI 1.00,1.04, respectively) in both men and women patients with T2DM. Combining osteocalcin levels and CVAI improved the prediction accuracy of arterial stiffness in men patients with T2DM (difference of AUC((Model 4 vs. Model 1)):1.5%, NRI: 0.06 [0.0,0.4]). All P-values were < 0.05. The results suggested that osteocalcin levels and CVAI are independent risk factors for ASCVD risk and arterial stiffness in T2DM. Combining osteocalcin and CVAI can enhance the early detection of atherosclerosis through male patients with T2DM.