World Journal of Diabetes最新文献

Background: Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults, with an increasing prevalence due to the global burden of diabetes.

Aim: To develop a polygenic risk score (PRS) to identify high-risk groups for DR and evaluate its severity in patients with type 2 diabetes (T2D).

Methods: This population-based study included 13335 patients with T2D, comprising 7295 patients with DR and 6040 without DR. Genetic data, duration of DR diagnosis, body mass index, systolic blood pressure, diastolic blood pressure, and glycated hemoglobin A1c levels were obtained from the study population. The PRS was constructed from a genome-wide association study conducted in a Taiwanese Han population. Electronic medical records were used to track patients with T2D and analyze the associations between PRS, timing of DR diagnosis, and therapeutic interventions. The hazard ratio (HR) of PRS for DR development and severity was estimated using multivariate Cox proportional hazards regression.

Results: The results demonstrated that patients with T2D in the top PRS decile had a 1.21-fold greater risk of developing DR [HR = 1.21; 95% confidence interval (CI): 1.01-1.45; P = 0.041] over a 20-year follow-up period. Among patients with DR, those in the highest PRS decile exhibited a 4.81-fold increased risk of requiring more than four laser treatments (HR = 4.81; 95%CI: 1.40-16.5; P = 0.012) and a 1.38-fold increased risk of undergoing vitreoretinal surgery (HR = 1.38; 95%CI: 1.01-1.90; P = 0.044).

Conclusion: Patients with T2D with a higher PRS are at increased risk of developing DR and may experience more severe forms of the disease.

Diabetes mellitus (DM) and its complications continue to impose a substantial burden on healthcare systems worldwide. Diabetic neuropathy (DN) is one of the most common chronic microvascular and neurodegenerative complications of DM. It is clinically characterized by allodynia, hyperalgesia, and abnormal or absent nerve fiber sensation, which collectively contribute to poor quality of life, sleep disturbances, depression, and increased mortality. Although several pharmacological agents are available to alleviate DN-related symptoms, their limited long-term efficacy and adverse side effects underscore the urgent need for novel therapeutic approaches. This limitation may be attributed to an incomplete understanding of the underlying mechanisms of DN. Accumulating evidence has highlighted the contribution of glial cells including astrocytes, microglia, and oligodendrocytes to the pathogenesis of DN. However, the specific role of astrocytes remains insufficiently defined. Therefore, this review provides a comprehensive evaluation of current knowledge regarding astrocyte involvement in DN mechanisms, with the goal of clarifying their contribution to disease progression and identifying potential therapeutic targets.

Background: Diabetes has become a widespread metabolic disease affecting multiple organs. Among diabetic complications, cardiovascular complications are the main cause of patient morbidity and mortality. Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes (T1D) than in type 2 diabetes. Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular (LV) dysfunction, while studies of right ventricular (RV) dysfunction have been sparse but are gaining attention. Although T1D accounts for only 5%-10% of the total diabetic population, diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long, long-term complications.

Aim: To evaluate longitudinal RV and LV functional changes in female transgenic OVE26, T1D mice and wild-type FVB mice over a 30-week period.

Methods: RV and LV structure and function were evaluated by transthoracic echocardiography. RV systolic pressure was measured by a transducer-tipped pressure catheter. Sirius-red staining was used to quantify collagen and fibrosis, wheat germ agglutinin staining was utilized to measure cardiomyocyte size, and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance, respectively.

Results: RV systolic function, measured by tricuspid valve annular plane systolic excursion and RV systolic velocity, was similar between control and T1D mice, but LV systolic function decreased in T1D mice at 30 weeks of age. RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks, while LV diastolic dysfunction trended towards abnormal at 12 weeks, significantly increased by 18 weeks, and continued to progress by 30 weeks. Furthermore, RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice, occurring later than that in the LV. Pulmonary arterial hypertension developed in T1D mice, evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks. These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.

Conclusion: RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice. Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.

Background: Urosepsis is a life-threatening condition frequently associated with renal and ureteral calculi (RUC) and diabetes mellitus (DM), a combination that exacerbates susceptibility to infection due to urinary obstruction and impaired immune response.

Aim: To identify the risk factors for urosepsis in patients with RUC complicated by DM to enhance early detection and intervention strategies.

Methods: This retrospective observational study included 298 patients with RUC and DM admitted between January 2020 and June 2024. Patients were divided into an observation group (n = 32) with urosepsis and a control group (n = 266) without urosepsis. Comprehensive clinical, laboratory, and imaging data were collected and analyzed using univariate and multivariate logistic regression models to identify factors associated with urosepsis. The study adhered to the STROBE guidelines and received ethical approval.

Results: Multivariate analysis identified several independent risk factors for urosepsis. Female sex (OR = 2.237, 95%CI: 1.086-4.605, P = 0.03), advanced age (OR = 1.05, 95%CI: 1.018-1.084, P = 0.002), and fever (OR = 2.999, 95%CI: 1.283-7.015, P = 0.015) significantly increased the risk. Laboratory findings such as elevated urine leukocyte (U-LEU) (+++, OR = 66.0, 95%CI: 7.031-580.125, P < 0.001) and glucose (U-GLU) (+++, OR = 7.248, 95%CI: 1.862-28.211, P = 0.005) levels were strongly associated with urosepsis. Severe hydronephrosis also emerged as a significant predictor (OR = 6.129, 95%CI: 3.027-9.623, P = 0.011). Other factors, such as gross hematuria, stone laterality, and mild to moderate hydronephrosis, were not significantly associated with urosepsis.

Conclusion: This study identifies key demographic, clinical, laboratory, and imaging factors associated with urosepsis risk in patients with RUC and DM. Early identification of female patients, elderly individuals, those presenting with fever, severe hydronephrosis, and elevated U-LEU and U-GLU levels may facilitate timely intervention. These findings highlight the importance of comprehensive assessment and targeted management in the care of high-risk patients.

Type 2 diabetes mellitus (T2DM) promotes a risk of the development of atherosclerosis and potentiates atherosclerotic cardiovascular events. Among these patients, chronic hyperglycemia, dyslipidemia, oxidative stress and systemic inflammation has been found as triggers for accelerating plaque formation. Additionally, conventionally used risk factors, such as age, overweight/obesity, hypertension, poor glycemic control, renal dysfunction, and metabolic disturbances frequently underestimate the patients at the risk of asymptomatic carotid atherosclerosis. Further interventions may be required to prevent vascular complications. To note, asymptomatic carotid plaque in T2DM is associated with older age, increased body mass index, biomarkers of poor glycemic control (glycated hemoglobin, fasting glucose), kidney dysfunction [urinary albumin-to-creatinine ratio (UACR)], and metabolic abnormalities [high-density lipoprotein cholesterol, serum uric acid (SUA)]. However, renal (UACR) and metabolic (SUA) biomarkers are likely to be investigated as promising biomarkers for early stage of asymptomatic coronary atherosclerosis, which as expecting could improve diagnostic value of intima-media thickness.

Background: Current evidence suggests that commonly used antidiabetic drugs have varying effects on cancer risk. Some antidiabetics offer protective effects against cancer, whereas others may increase risk in specific populations.

Aim: To comprehensively compare the effects of different antidiabetic drugs on the risk of various cancers in patients with type 2 diabetes mellitus (T2DM) through a systematic review and network meta-analysis.

Methods: Four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched from their inception until April 11, 2025. Published randomized controlled trials that enrolled at least 100 participants and had an intervention duration of at least 1 year were included. The inclusion criteria were studies involving adult patients with T2DM and interventions that compared different classes of antidiabetic drugs with a placebo or another antidiabetic drug. Network meta-analysis was conducted using Stata 17.0 software. Confidence in network meta-analysis was used to assess the quality of evidence regarding the risk of cancer associated with different antidiabetic drugs.

Results: A total of 13535 articles were identified. After applying the inclusion and exclusion criteria, 87 high-quality studies involving 216106 patients and 26 different drugs across seven classes were included in this study. Indirect evidence from network meta-analysis revealed some heterogeneity; however, this did not affect the reliability of the results. The results indicated that antidiabetic drugs did not increase the overall risk of cancer compared with placebo. In contrast, some antidiabetic medications demonstrated a more pronounced advantage in reducing cancer risk, such as dipeptidyl peptidase-4 inhibitors for thyroid and rectal cancers; sodium-glucose co-transporter type 2 inhibitors for lung and bronchial cancers; sulfonylureas for gastric and colon cancers; biguanides for pancreatic cancer; insulin for bladder cancer; glucagon-like peptide-1 receptor agonists for prostate, uterine, hepatocellular, renal, and hematologic cancers; and thiazolidinediones for breast cancer.

Conclusion: Antidiabetic drugs reduce cancer risk in patients with T2DM. However, given the limitations in the number and quality of the included studies, our conclusions should be interpreted with caution. More large-scale, high-quality clinical trials are required to validate our findings towards the optimization of comprehensive cancer management strategies for patients with T2DM.

Background: Diabetic nephropathy (DN) is a leading cause of chronic kidney disease and end-stage renal disease, and is a significant global healthcare burden. Although proximal tubular epithelial cells (PTECs) and podocytes are involved in DN progression, the specific molecular interactions between these cells are not well understood.

Aim: To elucidate the role of interleukin-6 (IL-6)/Rab5 signaling in mediating crosstalk between PTECs and podocytes, and to evaluate the protective effects of nicotinamide mononucleotide (NMN) against DN progression.

Methods: We utilized in vitro and in vivo models to investigate the pathogenesis of DN. In vitro, human PTECs and murine podocytes were cultured under high-glucose conditions, and IL-6 neutralizing antibodies or NMN treatments were applied. Podocyte injury was assessed by measurements of nephrin endocytosis, Rab5 activity, cytoskeletal organization, cell adhesion, and cell-spreading assays. In vivo, DN was induced in mice using streptozotocin, and mice then received NMN, insulin, or both treatments over an 8-week period. Renal tissues were analyzed histologically, ultrastructurally, and immunochemically, and urinary albumin excretion was measured to assess renal function. Statistical analyses were conducted using one-way ANOVA and Tukey's test.

Results: High-glucose conditions induced the epithelial-mesenchymal transition (EMT) in PTECs, increased IL-6 secretion, and activated Rab5 signaling in podocytes, leading to increased nephrin endocytosis and podocyte injury. Blocking IL-6 significantly attenuated these effects. NMN treatment of diabetic mice markedly reduced podocyte injury, glomerular hypertrophy, foot-process effacement, and urinary albumin excretion. Mechanistically, NMN suppressed the EMT and IL-6 secretion by PTECs, inhibited Rab5 activation in podocytes, and prevented nephrin endocytosis, thereby preserving the cytoskeletal integrity and function of podocytes.

Conclusion: Our findings reveal a novel pathogenic mechanism of DN in which IL-6 released from glucose-stressed PTECs activates Rab5 signaling in podocytes, followed by nephrin endocytosis and structural injury of podocytes. Importantly, NMN treatment effectively disrupted this pathological pathway of intercellular communication, and provided significant protection against DN progression. These results suggest that NMN supplementation and targeting the IL-6/Rab5 signaling axis has promise as a therapeutic strategy for managing DN.

Background: Poor glycaemic control in patients with type 2 diabetes mellitus (T2DM) is often accompanied by multiple complications, including diabetic nephropathy (DN), diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), and cardiac structural abnormality left ventricular hypertrophy (LVH). Early identification of high-risk populations for these complications and the implementation of intervention measures are crucial for improving patient outcomes. Serum alpha-1-microglobulin (α1-MG), a multifunctional protein synthesized by the liver and lymphocytes, has been considered a potential biomarker of diabetes-related diseases in recent years.

Aim: To investigate the associations of serum α1-MG with DN, DR, DPN, and LVH in T2DM patients and its predictive value.

Methods: This retrospective study included 5045 T2DM patients. The study participants were stratified into quartiles according to their serum α1-MG levels. Multivariate logistic regression, restricted cubic spline, and explainable machine learning models were employed for risk assessment and feature importance evaluation.

Results: Increased α1-MG levels were observed in patients with DN, DR, DPN, and LVH (all P < 0.001). Multivariate logistic regression revealed that each standard deviation increase in α1-MG was associated with an 84% increase in DN risk (OR: 1.84, 95%CI: 1.62-2.10, P < 0.001), a 17% increase in DR risk (OR: 1.17, 95%CI: 1.07-1.28, P < 0.001), a 14% increase in DPN risk (OR: 1.14, 95%CI: 1.03-1.27, P = 0.014), and a 28% increase in LVH risk (OR: 1.28, 95%CI: 1.18-1.38, P < 0.001). Subgroup analyses and machine learning confirmed the associations of elevated α1-MG with these complications in T2DM patients.

Conclusion: Elevated serum α1-MG levels were independently associated with increased risks of DN, DR, DPN, and LVH in T2DM patients, suggesting its potential as a predictive biomarker.

Background: Dental implants are widely used to replace missing teeth. Currently, clinicians assess osseointegration success by measuring the implant's stability within the bone and monitoring the marginal tissue height. Diabetes, especially type 2 diabetes mellitus (T2DM), has been reported to impair implant healing, drastically reducing implant success rates.

Aim: To analyze the high-risk factors for inflammatory response and prognosis after dental implantation in patients with T2DM, and provide strong evidence for reducing the incidence of postimplant peri-implantitis (PI).

Methods: We performed a retrospective review of 146 patients with T2DM who had dental implants placed at Tianjin Fifth Central Hospital, between September 2021 and September 2023, which was regarded as the observation group. Moreover, 60 age- and gender-matched individuals with normal blood glucose levels served as the control group. The general information, postoperative periodontal indices, and levels of inflammatory factors were comprehensively analyzed and compared. Furthermore, the incidence of postimplant PI was counted, and multivariate logistic regression was used to identify the determinants of postimplant PI.

Results: In terms of the periodontal indices, the probing depth, modified sulcus bleeding index, and marginal bone loss in the observation cohorts began to increase significantly at 6 months and 3 months, respectively, after the completion of dental implant restoration. The T2DM cases demonstrated significantly elevated counts of leukocytes, lymphocytes, and neutrophils compared to the controls at 24 hours postoperatively. Moreover, the TNF-α, IL-1β, and IL-6 concentrations started to increase significantly in the gingival crevicular fluid 3 months after the completion of dental implant restoration in both cohorts, with the observation group exhibiting higher levels than the controls at each time point. 63 out of the 146 cases developed PI. Multivariate logistic regression analysis indicated that high glycosylated hemoglobin levels, smoking, daily tooth-brushing frequency of less than once, and the anterior tooth as the implant site independently contributed to postimplant PI in T2DM cases, while a tooth-brushing duration of ≥ 3 minutes was a protective factor.

Conclusion: Patients with T2DM are at risk of developing PI following dental implantation. Clinically, it is necessary to enhance the identification of risk factors for postimplant PI, improve risk prediction, prevention, and control, and formulate targeted intervention countermeasures to reduce the occurrence of postimplant PI.

Background: Acute and extreme insulin resistance with persistent hyperglycemia requiring excessively high doses of insulin before rapidly resolving is rare and has been referred to as transient and extreme insulin resistance (TEIR). The underlying pathophysiology and optimal management of TEIR are poorly understood, and previous reports of TEIR in the literature are sparse. This report is the first description of TEIR in a patient requiring mechanical circulatory support (MCS).

Case summary: A 62-year-old male developed cardiogenic shock and was placed on veno-arterial extracorporeal membrane oxygenation following percutaneous coronary intervention and successful revascularization. Over the next 24 hours, glucose levels rose and remained markedly elevated despite increasing insulin infusion rates and repeated boluses. The insulin infusion rate peaked at 450 units/hour, and the patient received 4300 units (33 units/kg) of insulin over the 24-hour period of peak insulin resistance. Insulin resistance resolved rapidly, necessitating an abrupt decrease in the insulin infusion rate and development of rebound hypoglycemia.

Conclusion: Onset of TEIR did not seem to correlate with end-organ hypoperfusion or vasoactive drug dosing.