World Journal of Diabetes最新文献

Background: Although numerous single nucleotide polymorphism in multiple genes involve in the risk of type 2 diabetes mellitus (T2D), the single gene defects of T2D with strong family history is not clear yet. SPTLC1 are causative for hereditary sensory and autonomic neuropathy, which is clinical overlapping with diabetic peripheral neuropathy. Mice with adipocyte-specific deletion of SPTLC1 had impaired glucose tolerances and insulin sensitivity. Thus, it is necessary to investigate the SPTLC1 mutations in adult-onset T2D with strong family history.

Aim: To analyze the role of SPTLC1 mutation on adult-onset T2D with strong family history.

Methods: By whole-exome sequence analysis of a patient with T2D and his family members, an uncertain variant in SPTLC1 was identified. Bioinformation analysis was used to evaluate the influence of mutation, rare variant gene-level associations for SPTLC1 in T2D, and the relationship between SPTLC1 mRNA and T2D in human islets from GSE25724. The effect of G371R of SPTLC1 on the characteristics of inflammatory cytokines and apoptosis was also tested on human embryonic kidney (HEK) 293 cells.

Results: A single nucleotide variation in SPTLC1 (c.1111G>A: p.G371R) was identified in a family with T2D. The deleterious variant was predicted by functional analysis through hidden Markov models and mendelian clinically applicable pathogenicity software. This pathogenicity might be derived from the different amino acid properties. In HEK 293T cells, p.G371R of SPTLC1 induced the expression of tumor necrosis factor-α and the percent of apoptosis. Meanwhile, rare variant gene-level associations for SPTLC1 also refer to the high risk of T2D (the overall odds ratio = 2.4968, P = 0.0164). Data from GSE25724 showed that SPTLC1 mRNA was lower in pancreatic islets from T2D human islets (P = 0.046), and was associated with the decreased level of insulin mRNA expression (Spearman r = 0.615, P = 0.025).

Conclusion: The study classified SPTLC1 p.G371R mutation as the likely pathogenic mutation from an adult-onset T2D patients with strong family history T2D.

Background: Diabetic foot ulcers (DFUs) present a significant clinical challenge due to their high prevalence and profound impact on morbidity. Ultrasound-assisted wound debridement (UAWD) has emerged as a potential therapeutic modality to improve healing outcomes in DFU management.

Aim: To evaluate the efficacy of UAWD in treating DFUs on wound closure rates, treatment duration, and quality of life outcomes.

Methods: This systematic review and meta-analysis followed PRISMA guidelines, systematically searching PubMed, Embase, Web of Science, and the Cochrane Library with no date restrictions. Randomized controlled trials (RCTs) that evaluated the efficacy of UAWD in DFU treatment were included. Data were independently extracted by two reviewers, with discrepancies resolved through consensus or third-party consultation. The risk of bias was assessed using the Cochrane tool. χ ² and I ² statistics assessed heterogeneity, informing the use of fixed or random-effects models for meta-analysis, supplemented by sensitivity analysis and publication bias assessment through funnel plots and Egger's test.

Results: From 1255 articles, seven RCTs met the inclusion criteria. The studies demonstrated that UAWD significantly reduced DFU healing time (standardized mean difference = -0.78, 95%CI: -0.97 to -0.60, P < 0.001) and increased healing rates (odds ratio = 9.96, 95%CI: 5.99 to 16.56, P < 0.001) compared to standard care. Sensitivity analysis confirmed the stability of these results, and no significant publication bias was detected.

Conclusion: UAWD is a promising adjunctive treatment for DFUs, significantly reducing healing times and increasing healing rates. These findings advocate for the integration of UAWD into standard DFU care protocols.

Background: The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome may play an important role in diabetic kidney disease (DKD). However, the exact link remains unclear.

Aim: To investigate the role of the NLRP3 inflammasome in DKD.

Methods: Using datasets from the Gene Expression Omnibus database, 30 NLRP3 inflammasome-related genes were identified. Differentially expressed genes were selected using differential expression analysis, whereas intersecting genes were selected based on overlapping differentially expressed genes and NLRP3 inflammasome-related genes. Subsequently, three machine learning algorithms were used to screen genes, and biomarkers were identified by overlapping the genes from the three algorithms. Potential biomarkers were validated by western blotting in a db/db mouse model of diabetes.

Results: Two biomarkers, sirtuin 2 (SIRT2) and caspase 1 (CASP1), involved in the Leishmania infection pathway were identified. Both biomarkers were expressed in endothelial cells. Pseudo-temporal analysis based on endothelial cells showed that DKD mostly occurs during the mid-differentiation stage. Western blotting results showed that CASP1 expression was higher in the DKD group than in the control group (P < 0.05), and SIRT2 content decreased (P < 0.05).

Conclusion: SIRT2 and CASP1 provide a potential theoretical basis for DKD treatment.

This letter comments on a study by Jin et al, published recently in the World Journal of Diabetes. Hypoglycemia is a significant complication of diabetes, with primary defense mechanisms involving the stimulation of glucagon secretion in α-cells and the inhibition of insulin secretion in pancreatic β-cells, which are often compromised in type 1 diabetes mellitus (T1DM) and advanced type 2 diabetes mellitus. Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness, a condition underpinned by complex pathophysiological processes, encompassing central nervous system adaptations and several hormonal interactions, including a potential role for glucagon-like peptide-1 (GLP-1) in paracrine and endocrine vias. Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreatic δ-cells, which inhibits glucagon secretion from neighboring α-cells. However, current trials evaluating GLP-1 receptor agonists (GLP-1 RAs) in T1DM patients have shown promising benefits in reducing insulin requirements and body weight, without increasing the risk of hypoglycemia. Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex, and their impact on hypoglycemia unawareness in T1DM patients.

Background: With accumulating evidence showing a benefit in the renal and cardiovascular systems, diabetes guidelines recommend that patients with diabetes and chronic kidney disease (CKD) be treated with sodium-glucose cotransporter-2 inhibitor (SGLT2i) and/or glucagon like peptide-1 receptor agonists (GLP-1RAs) for renal protection. The real-world efficacy of the two medications on the urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) remains to be explored.

Aim: To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.

Methods: A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months. Propensity score matching was performed, and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio. Blood glucose, body weight, UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.

Results: A total of 139 (2.54%) patients started GLP-1RA, and 387 (7.06%) received SGLT2i. After 6 months, the variations in fasting blood glucose, prandial blood glucose, and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different. UACR showed a tendency toward a greater reduction compared with the control group, although this difference was not statistically significant (GLP-1RA vs control, -2.20 vs 30.16 mg/g, P = 0.812; SGLT2i vs control, -20.61 vs 12.01 mg/g, P = 0.327); eGFR alteration also showed no significant differences. Significant weight loss was observed in the GLP-1RA group compared with the control group (GLP-1RA vs control, -0.90 vs 0.27 kg, P < 0.001), as well as in the SGLT2i group (SGLT2i vs control, -0.59 vs -0.03 kg, P = 0.010).

Conclusion: Compared with patients who received other glucose-lowering drugs, patients receiving SGLT2i or GLP-1RAs presented significant weight loss, a decreasing trend in UACR and comparable glucose-lowering effects in real-world settings.

Background: Peripheral neuropathy caused by diabetes is closely related to the vicious cycle of oxidative stress and mitochondrial dysfunction resulting from metabolic abnormalities. The effects mediated by the silent information regulator type 2 homolog-1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) axis present new opportunities for the treatment of type 2 diabetic peripheral neuropathy (T2DPN), potentially breaking this harmful cycle.

Aim: To validate the effectiveness of electroacupuncture (EA) in the treatment of T2DPN and investigate its potential mechanism based on the SIRT1/PGC-1α axis.

Methods: The effects of EA were evaluated through assessments of metabolic changes, morphological observations, and functional examinations of the sciatic nerve, along with measurements of inflammation and oxidative stress. Proteins related to the SIRT1/PGC-1α axis, involved in the regulation of mitochondrial biogenesis and antioxidative stress, were detected in the sciatic nerve using Western blotting to explain the underlying mechanism. A counterevidence group was created by injecting a SIRT1 inhibitor during EA intervention to support the hypothesis.

Results: In addition to diabetes-related metabolic changes, T2DPN rats showed significant reductions in pain threshold after 9 weeks, suggesting abnormal peripheral nerve function. EA treatment partially restored metabolic control and reduced nerve damage in T2DPN rats. The SIRT1/PGC-1α axis, which was downregulated in the model group, was upregulated by EA intervention. The endogenous antioxidant system related to the SIRT1/PGC-1α axis, previously inhibited in diabetic rats, was reactivated. A similar trend was observed in inflammatory markers. When SIRT1 was inhibited in diabetic rats, these beneficial effects were abolished.

Conclusion: EA can alleviate the symptoms of T2DNP in experimental rats, and its effects may be related to the mitochondrial biogenesis and endogenous antioxidant system mediated by the SIRT1/PGC-1α axis.

Background: L-arginine (L-Arg) is one of the most widely used amino acids in dietary and pharmacological products. However, the evidence on its usefulness and dose limitations, especially in diabetics is still controversial.

Aim: To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats.

Methods: Of 96 male rats were divided into 8 groups as follows (n = 12): Control, 0.5 g/kg L-Arg, 1 g/kg L-Arg, 1.5 g/kg L-Arg, diabetic, diabetic + 0.5 g/kg L-Arg, diabetic + 1 g/kg L-Arg, and diabetic + 1.5 g/kg L-Arg; whereas L-Arg was orally administered for 3 months to all treated groups.

Results: L-Arg produced a moderate upregulation of blood glucose levels to normal rats, but when given to diabetics a significant upregulation was observed, associated with increased nitric oxide, inflammatory cytokines, and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg. A substantial decrease in the antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione concentrations, and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups, associated with myocardial injury, fibrosis, α-smooth muscle actin upregulation, and disruption of desmin cardiac myofilaments, and these effects were not noticeable at normal treated groups. On the other hand, L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights.

Conclusion: L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium, while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.

Background: Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM), significantly affecting patients' quality of life and imposing a substantial economic burden. Recent studies have highlighted the role of thyroid hormones in diabetes complications, particularly in elderly patients with T2DM. However, the relationship between thyroid hormone sensitivity and DPN remains unclear.

Aim: To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.

Methods: In a cohort of 256 elderly patients with T2DM, propensity score matching was used to balance age, sex, and diabetes duration. Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN. A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine (FT₃/FT₄) for DPN.

Results: Patients with DPN had a lower FT₃/FT₄ ratio [ (0.302 ± 0.053) vs (0.316 ± 0.049), P = 0.040]. Quartile stratification showed decreasing DPN prevalence with higher FT₃/FT₄ ratios. Spearman's correlation analysis showed that a lower FT₃/FT₄ ratio was associated with higher glycated hemoglobin, fasting blood glucose, reduced nerve conduction velocity, and electrical skin conductance. Logistic regression indicated a positive relationship between the median FT₃/FT₄ ratio and bilateral foot electrochemical skin conductance [odds ratio (OR): 1.019; 95%CI: 1.005-1.034; P = 0.007] and sural nerve sensory amplitude (OR: 1.310; 95%CI: 1.008-1.703; P = 0.043). Receiver operating characteristic analysis using a random forest model showed that incorporating FT₃/FT₄ improved predictive performance for DPN, with an area under the curve of 0.74, sensitivity of 0.79, specificity of 0.64, and accuracy of 0.77.

Conclusion: In elderly patients with T2DM with euthyroidism, a lower FT₃/FT₄ ratio is correlated with increased DPN incidence, affecting both large and small nerve fibers. FT₃/FT₄ is an effective predictor of DPN.

Background: Type 2 diabetes (T2D), as well as obesity, are risk factors for chronic kidney disease (CKD) and end-stage renal disease. The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefits in preventing CKD often guide clinicians in choosing them appropriately. Only limited data based on randomized controlled trials (RCTs) is currently available on the renal effects and safety profile of tirzepatide.

Aim: To explore the renal benefits and safety of tirzepatide vs controls.

Methods: RCTs involving patients receiving tirzepatide for any indication in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases. The co-primary outcomes were percent change from baseline (CFB) in urine albumin-to-creatinine ratio (UACR) and absolute CFB in estimated glomerular filtration rate (eGFR; in mL/min/1.73 m²); the secondary outcome was tirzepatide's renal safety profile. RevMan web was used to conduct meta-analysis using random-effects models. Outcomes were presented as mean differences (MD) or risk ratios with 95% confidence intervals.

Results: Fifteen RCTs (n = 14471) with mostly low risk of bias (RoB) were included. Over 26-72 weeks, tirzepatide 10 mg [MD -26.95% (-40.13, -13.76), P < 0.0001] and 15 mg [MD -18.03% (-28.58, -7.47), P = 0.0008] were superior to placebo in percent reductions of UACR. Tirzepatide, at all doses, outperformed insulin in percent reductions of UACR. Compared to the placebo, the percent UACR reduction was greater in subjects with T2D than those with obesity but without T2D (MD -33.25% vs -7.93%; P = 0.001). The CFB in eGFR with all doses of tirzepatide was comparable [5 mg: MD 0.36 (-1.41, 2.14); 10 mg: MD 1.17 (-0.22, 2.56); 15 mg: MD 1.42 (-0.04, 2.88)]; P > 0.05 for all] vs insulin. Tirzepatide (pooled and separate doses) did not increase the risks of adverse renal events, urinary tract infection, nephrolithiasis, acute kidney injury, and renal cancer compared to the placebo, insulin, and glucagon-like peptide-1 receptor agonists.

Conclusion: Short-term data from RCTs with low RoB suggests that tirzepatide positively impacts UACR without detrimental effects on eGFR in subjects with T2D and obesity without T2D, with a reassuring renal safety profile. Larger RCTs are warranted to prove the longer-term renal benefits of tirzepatide, which might also prevent eGFR decline and worsening of CKD.

The risk factors for type 2 diabetes mellitus (T2DM) have been increasingly researched, but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors, which are categorized in this paper into five categories: Social determinants, lifestyle, checkable/testable risk factors, history of illness and medication, and other factors, which are discussed in a narrative review. Meanwhile, this paper points out the problems of the current research, helps to improve the systematic categorisation and practicality of T2DM risk factors, and provides a professional research basis for clinical practice and industry decision-making.