Journal of Diabetes Research最新文献

[This retracts the article DOI: 10.1155/2021/5445349.].

Background: Hyperuricemia remains a critical risk factor for diabetic kidney disease (DKD) currently. Recent studies have confirmed that allopurinol, an inhibitor of xanthine oxidase (XO), does not have any beneficial effects on DKD. However, it is still unclear how uricosurics, such as benzbromarone (BZ), affect the progression of DKD.

Methods: STZ-induced diabetic and control rats were treated with BZ for 8 weeks. Blood samples were collected to measure fasting blood glucose (FBG), serum uric acid (SUA), serum creatinine (SCr), and blood urea nitrogen (BUN). Simultaneously, urinary samples were tested, and the daily urinary amounts of albumin (UAE), uric acid (UUA), creatinine (UCr), urea nitrogen (UUN), were calculated. Gene expressions of XO, urate transporter 1 (URAT1), and glucose transporter 9 (GLUT9) in the kidney, as well as XO, uricase, and GLUT9 in the liver, were detected.

Results: (1) Compared with normal rats, diabetic rats exhibited significant increases in FBG, BUN, UUN, UAE, UUA, while SUA was significantly decreased. BZ significantly decreased UAE and increased SUA over 8 weeks in diabetic rats. (2) Diabetic rats developed noticeable hyaline degeneration, and a slight decrease in mean glomerular area. BZ treatment significantly attenuated tubular damage in diabetic rats without affecting glomerular morphology. (3) In the kidney, gene expression of XO was increased, while URAT1 and GLUT9 were unchanged in diabetic rats. BZ treatment had no effect on GLUT9 and XO gene expression but significantly inhibited URAT1 expression in diabetic rats. (4) In the liver, gene expression of XO, uricase, and GLUT9 did not differ between diabetic and normal rats. BZ treatment significantly inhibited GLUT9 expression but had no effect on XO and uricase expression in diabetic rats.

Conclusions: BZ treatment significantly protects against renal damage in STZ-induced diabetic rats independent of its uricosuric effects, possibly because of its inhibition of renal URAT1.

The insulin-like growth factor (IGF) axis, an evolutionarily conserved system, is critical in regulating cell growth, proliferation, and survival, affecting nearly all organ systems. This axis comprises two growth factors, IGF-I and IGF-II, and six insulin-like growth factor-binding proteins (IGFBPs), modulating IGF activity. Due to their structural similarity to insulin, IGFs can interact with insulin receptors, facilitating glucose uptake in adipose and muscle tissues, suppressing hepatic glucose production, and modulating blood glucose levels. Pregnancy induces unique metabolic challenges, with the IGF axis adapting to support maternal metabolic changes and fetal growth. In pregnancies complicated by prediabetes or diabetes, disruptions in the IGF axis, including altered levels of IGFs and IGFBPs, have been linked to adverse outcomes such as macrosomia and intrauterine growth restriction. This review discusses the role of the IGF system in pregnancies with diabetes, focusing on how dysregulation of IGFs and IGFBPs contributes to pregnancy complications. We emphasize the dual role of the IGF axis in metabolism and growth and evaluate its potential as a therapeutic target in managing high-risk pregnancies.

Introduction: Waist-triglyceride index (WTI) is a novel indicator of insulin resistance that can effectively identify glucose metabolism abnormalities and metabolic syndrome. No study discussed the predictive ability of WTI for incident Type 2 diabetes (T2D) risk from a longitudinal perspective. We aimed to evaluate the relationship between the baseline WTI level and the risk of T2D during follow-up in an elderly cohort.

Methods: A total of 7578 participants aged over 60 years were enrolled in a follow-up study conducted from January 2018 to December 2023. The Cox proportional hazard models were performed to evaluate the independent effect of WTI level on T2D risk. The Kaplan-Meier method and restricted cubic spline (RCS) analysis were used to visually demonstrate the relationship between WTI and T2D risk. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate the efficacy of WTI and other composite lipid parameters in assessing the risk of T2D.

Results: During a median follow-up of 3.91 years (interquartile range: 2.89-4.86 years), 758 participants (10.0%) developed T2D. Fully adjusted Cox proportional hazard models demonstrated a positive and independent association between WTI and T2D risk (HR = 1.57, 95% CI: 1.37-1.80, p < 0.001). The highest WTI group (Q4) exhibited the greatest cumulative incidence of T2D (log-rank test, p < 0.001). Additionally, the RCS analysis indicated that the relationship between WTI and T2D risk was linear. ROC analysis and DCA suggested that WTI performed better in the diagnosis and prediction of T2D risk. Subgroup analysis further validated the stability of these findings.

Conclusion: According to our study, the elderly with an elevated WTI level were at a higher risk of incident T2D. WTI may serve as a promising novel biomarker for T2D in large-scale epidemiological studies.

Aim: This study utilized db/db mice and MPC5 cells induced by high glucose as experimental models to examine the protective mechanisms of the traditional Chinese medicine formula TangNaikang (TNK) in mitigating podocyte injury in diabetic nephropathy (DN).

Methods: The chemical constituents of TNK and TNK-containing serum were identified through UPLC-Q-TOF/MS. The underlying mechanism of TNK in treating DN was analyzed using network pharmacology. In vivo, following an 8-week intervention, db/db mice's serum biomarkers (TC, TG, HDL, LDL, AGEs, BUN, Scr, and β2-MG) were compared. H&E, PAS staining, and electron microscopy were used to perform a histopathological investigation on kidney sections. High glucose-induced MPC5 cells were treated with TNK-containing serum. Cellular viability was measured through a CCK-8 assay. The expression levels of podocyte-associated and PI3K/AKT pathway proteins in kidney tissues and MPC5 cells were determined by immunofluorescence, western blotting, and RT-qPCR analysis.

Results: The UPLC-Q-TOF/MS results showed that the TNK formula consisted of 69 compounds, including flavonoids, triterpenoids, and lignans. TNK-containing serum was identified with 34 compounds including 9 TNK prototype components and 25 metabolites. TNK was found to be substantially linked with the PI3K/AKT pathway using network pharmacology. When compared to the model group, the TNK-H group mice had significantly improved serum lipid profiles as well as renal structural and functional profiles. Immunofluorescence and western blotting analyses indicated that TNK regulated the expression levels of the podocyte-associated (SYNPO, nephrin, CD2AP, and podocin) as well as PI3K/AKT pathway proteins (PI3K, AKT, SHIP2, IRS2, and GLUT4). These data were confirmed by RT-qPCR results. TNK-containing serum enhanced MPC5 cell viability via modulating the PI3K/AKT pathway and inhibiting SHIP2.

Conclusion: TNK ameliorates podocyte injury in DN and high glucose-induced MPC5 cells by modulating the SHIP2/PI3K/AKT pathway.

Aims: We aimed to explore the relationship of noise exposure in the workplace, genetic risk, and lifestyle with Type 2 diabetes (T2D).

Methods: A total of 154,708 participants without T2D in UK Biobank were included. A lifestyle score was determined using smoking, alcohol intake, physical activity, television viewing time, sleep duration, and diet.

Results: During a median follow-up of 11.83 years (1,776,919.62 person-years), 5921 T2D cases were observed. Compared to no noise exposure, the hazard ratios (HRs) and 95% confidence intervals (CIs) were 1.06 (0.95-1.18) in less than a year, 1.01 (0.91-1.12) in around 1-5 years, and 1.11 (1.04-1.20) in more than 5 years, respectively. Compared to participants with low genetic risk and no noise exposure, individuals with high genetic risk and noise exposure for more than 5 years did not show the highest risk of T2D (HR = 1.16, 95%CI = 0.98-1.36). However, participants with the least healthy lifestyle and noise exposure for more than 5 years revealed a higher risk of T2D (HR = 1.72, 95%CI = 1.27-2.33).

Conclusions: Prolonged noise exposure in the workplace is related to a higher risk of T2D.

Aim: Acute ischemic stroke (AIS) patients with diabetes mellitus (DM) have significantly lower brain-derived neurotrophic factor (BDNF) levels compared to nondiabetic patients. However, the impact of BDNF on thrombus characteristics is unclear. The relationship between the plasma BDNF and fibrin ultrastructure of thrombi was investigated.

Methods: This study analyzed 72 AIS patients (35 with T2DM) with first-ever stroke and 10 healthy controls. All patients were assessed for severity and type of stroke, risk factors, and levels of plasma BDNF in the acute stroke. Retrieved arterial thrombi from AIS patients underwent histopathological (immunohistochemical, Martius scarlet blue staining, and immunofluorescence), ultrastructural (scanning/transmission electron microscopy), and permeability (CT/CTA) analyses. In vitro effects of recombinant BDNF (rHu-BDNF) on fibrin polymerization (turbidity assay), clot firmness (thromboelastography), and lysis were assessed in plasma pools.

Results: AIS/DM patients exhibited significantly lower plasma BDNF versus AIS/non-DM patients (6.83 ± 0.81 vs. 8.70 ± 0.73 ng/mL, p < 0.001) and controls (9.81 ± 0.59 ng/mL). Meanwhile, AIS/DM patients had higher baseline NIHSS scores than AIS/non-DM patients (17.09 ± 8.29 vs. 13.22 ± 6.15, p = 0.027). AIS/DM thrombi histopathological showed lower BDNF staining intensity, higher fibrin density, and reduced permeability. Moreover, BDNF levels positively correlated with thrombus permeability (r = 0.862, p < 0.001). We showed that rHu-BDNF reduced the density of fibrin fiber (p < 0.001), turbidity (p < 0.05), and maximum clot firmness (p < 0.05), while increasing the diameter of fibrin (p < 0.05), prolonging thrombin time (p < 0.001), and accelerating lysis (p < 0.001) in a concentration-dependent manner in plasma from AIS/DM patients.

Conclusion: This study demonstrates that low BDNF levels in AIS/DM patients promote fibrin-rich, dense clot formation, partly via altered fibrin fiber structure and fibrin polymerization. BDNF may serve as a novel biomarker for thrombus heterogeneity and a potential target to improve thrombolysis in diabetic stroke.

Background: Type 2 diabetes mellitus (T2DM) refers to a chronic metabolic disorder that results from insulin resistance, leading to impaired insulin action and uncontrolled plasma glucose levels. Acalypha wilkesiana is among medicinal plants that are ethnobotanically used in the management of T2DM. However, there is a paucity of information on its antidiabetic potential. This review is aimed at providing a current understanding of the mechanism of action, potency, and safety of Acalypha wilkesiana in T2DM therapy.

Methods: A narrative review was thoroughly conducted by searching Google Scholar and PubMed databases using a predefined combination of keywords. All gathered articles were reviewed for the content regarding T2DM, Acalypha wilkesiana, mechanism of action, and safety. A total of 44 articles were considered in this review.

Results: Several experimental studies revealed that extracts of Acalypha wilkesiana inhibit α-glucosidase and α-amylase, which normally break down carbohydrates postprandially. Notably, the ethanolic root bark extracts of Acalypha wilkesiana have shown lower inhibitory concentrations compared to those of both the plant extracts in other solvents and the acarbose drug, emphasizing its greater potency. Additionally, the leaves of Acalypha wilkesiana have been reported to have no harmful effects on the red blood cells of diabetic rabbits and can even restore the alloxan-induced impairment of pancreas and spleen cells.

Conclusion: Acalypha wilkesiana demonstrates antihyperglycemic activity and can reverse the dysfunction of critical organs. It promises advances in the development of antihyperglycemic agents which are more efficacious and safer than synthetic agents. However, clinical trials should be conducted to establish human-tailored doses, ensuring an improved safety profile of the plant in the treatment of T2DM.

Introduction: Declined renal function is closely linked to diabetes. However, it remains unclear whether the intraindividual difference between cystatin C- and creatinine-based estimated glomerular filtration rates (eGFRdiff) is associated with diabetes. This study was aimed at examining the association between eGFRdiff and prevalent diabetes in a nationally representative cohort of Chinese adults.

Methods: We analyzed data from 11,869 adults aged ≥ 45 years participating in the China Health and Retirement Longitudinal Study (CHARLS), including 2279 individuals with diabetes. We calculated eGFRdiff as the absolute difference between cystatin C- and creatinine-based eGFR levels. Multivariable logistic regression and restricted cubic spline models were used to assess the association between eGFRdiff and prevalent diabetes. Subgroup analyses were conducted on sex, body mass index, hypertension status, and creatinine-based eGFR status.

Results: The mean participant age was 60.3 (±9.6) years, and 53.5% were female. Participants were categorized into three groups based on eGFRdiff: midrange (-15 to 15 mL/min/1.73 m², 67.9%), negative (<-15, 22.7%), and positive (> 15, 9.4%). Compared to the midrange group, individuals in the negative eGFRdiff group had a significantly higher odds of diabetes, even after adjusting for the creatinine-based eGFR (OR: 1.21, 95% CI: 1.08-1.36) and cystatin C-based eGFR (OR: 1.32, 95% CI: 1.16-1.50).

Conclusion: In this large, community-based population, a negative eGFRdiff-where cystatin C-based eGFR is substantially lower than creatinine-based eGFR-is associated with a higher prevalence of diabetes, independent of overall kidney function. These findings suggest that eGFRdiff may serve as a novel marker for metabolic status.

[This retracts the article DOI: 10.1155/2014/678123.].