Journal of Diabetes Research最新文献

Background: Inconsistencies exist in the literature regarding the associations among age at menarche (AAM), prepregnancy menstrual characteristics, and the risk of gestational diabetes mellitus (GDM). These discrepancies may be attributable to variations in population demographics. The aim of this study was to investigate the impact of prepregnancy menstrual characteristics and AAM on the likelihood of developing GDM among Chinese women.

Methods: A 1:1 age-matched case-control study was conducted that included 2289 patients with GDM and 2289 normoglycemic pregnant women as controls at Wuhan Union Hospital from September 2020 to August 2022. Fasting blood samples were collected during 24-28 weeks of gestation. AAM and menstrual cycle characteristics were categorized and incorporated into a conditional logistic regression model that was adjusted for potential confounders. Additionally, restricted cubic spline curves were employed to assess the trend in GDM risk associated with AAM.

Results: The final analysis included 4578 participants. The AAM in the GDM group presented significantly earlier than that in the normoglycemic group (p < 0.05). After adjusting for confounding factors, we found that women with an AAM of 12 years (aOR = 1.44, 95% CI: 1.25-1.67) or 14 years (aOR = 1.36, 95% CI: 1.15-1.61) had a significantly higher risk of developing GDM compared with those with an AAM of 13 years. Furthermore, analysis of the data by means of restricted cubic splines revealed an L-shaped association that linked AAM to GDM (p < 0.001). The association between prolonged and irregular menstrual cycles and GDM risk remained statistically significant, albeit attenuated, after multivariable adjustment. Irregular menstrual cycles (classified as "usually irregular" or "always irregular") were significantly associated with an increased risk of GDM, with aORs of 2.36 (95% CI: 1.47-3.79) and 2.40 (95% CI: 1.01-5.71), respectively. Moreover, menstrual cycle durations of 32-39 days or more than 50 days were significantly associated with an increased risk of GDM (aORs: 1.20 and 1.37; 95% CIs: 1.10-1.41 and 1.03-1.83, respectively).

Conclusion: Early AAM, irregular menstrual cycles, and prolonged menstrual cycle length were associated with an increased risk of GDM. Among women with menarche occurring before the age of 13, there was an association with a higher risk of GDM. These indicators may help identify women at high risk and facilitate preconception interventions to prevent GDM.

Trial registration: ClinicalTrials.gov identifier: ChiCTR2200063189.

Background: Yixiao formula (YXF), a traditional Chinese herbal medicine, has demonstrated clinical efficacy in alleviating symptoms of diabetic cardiomyopathy (DCM). The therapeutic mechanism underlying YXF's effects on DCM remains poorly understood. Myocardial fibrosis is a key pathogenic mechanism in DCM, and previous studies have indicated that miR-133a may be involved in its progression. Given that the TGF-β/Smads signaling pathway is a well-established mediator of myocardial fibrosis, investigating the mechanistic role of YXF through miR-133a and the TGF-β/Smads pathway warrants further exploration.

Objective: The main objective of this study is to investigate the potential contribution of the TGF-β/Smads pathway to the effects of YXF, as well as the role of miR133a, through in vivo DCM models and in vitro experiments.

Materials and methods: Spontaneously diabetic KKAy mice were used to establish a DCM model by continuous high-fat feeding, with C57BL/6 mice as controls. Echocardiography, body weight, and blood glucose data were collected every 4 weeks to examine the effects of YXF on blood glucose levels and changes in cardiac function and structure in DCM mice. Immunohistochemistry, RT-qPCR, and western blot were used to detect the expression levels of the TGF-β/Smads pathway. Additionally, the potential molecular mechanism of YXF in mouse cardiac fibroblasts (MCFs) was investigated by knocking down miR-133a.

Results: YXF improved fasting blood glucose levels in DCM mice, promoted cardiac diastolic function, upregulated miR133a, and inhibited the expression of the TGF-β/Smads pathway. Furthermore, when miR133a inhibitors were transfected under YXF intervention, we found that YXF's inhibitory effect on the TGF-β/Smads pathway was weakened.

Conclusion: Through this study, we found that YXF can increase miR133a and inhibit the expression of the TGF-β/Smads pathway, thereby inhibiting myocardial fibrosis and exerting a protective effect on DCM.

Background: Diabetic retinopathy (DR) is a common microvascular complication of diabetes, which seriously affected the life quality in diabetic patients. Developing novel therapy to improve DR is essential. Qinggan Mingshi granules (QGMS) have been demonstrated with protective effects on DR clinically. However, the mechanisms of QGMS remain unclear.

Method: In order to more thoroughly investigate the mechanism underlying the positive effects of QGMS on DR, a mouse model of DR was established in this study, and the positive effects of QGMS on the DR mice were observed. Next, the effects of QGMS on ferroptosis and the NRF2/GPX4 axis were investigated. In addition, we used an NRF2 inhibitor to determine whether QGMS inhibits ferroptosis in DR mice via the NRF2/GPX4 axis.

Result: Our results revealed the therapeutic effects of QGMS on DR including improving the permeability of blood-retina barrier (BRB), reducing the pathological changes and ferroptosis in retina. QGMS also induced the expression of NRF2/GPX4 axis in retina. Furthermore, ML385, an NRF2 inhibitor, abolished the effects of QGMS on DR.

Conclusion: This study revealed that QGMS can effectively treat DR by alleviating retinal damage through enhancing the expression of NRF2/GPX4 axis-related proteins and thus scavenging of LPOs, ultimately reducing ferroptosis.

Diabetes substantially increases the risk of ischemic stroke through complex metabolic, inflammatory, and vascular mechanisms, yet early identification of high-risk individuals remains challenging. This narrative review synthesizes emerging circulating and genomic biomarkers that illuminate the pathways linking diabetes and ischemic stroke and evaluates their potential for early detection and precise risk stratification. Systematic searches of PubMed, Scopus, and Web of Science identified 141 relevant studies examining biomarkers, genetic and epigenetic factors, or risk prediction models in adults with diabetes. Evidence highlights several biomarker domains. Inflammatory markers such as high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α indicate immune activation driving atherogenesis and plaque instability. Endothelial markers, including endothelin-1, soluble vascular cell adhesion molecule-1, and asymmetric dimethylarginine, reflect endothelial dysfunction and a prothrombotic state. Metabolic indicators, notably glycated hemoglobin, adipokines, and lipoprotein(a), capture cumulative glycemic burden, adipose signaling, and inherited atherothrombotic risk. Genetic and epigenetic measures, including polygenic risk scores, microRNAs, long noncoding RNAs, and DNA methylation, quantify inherited susceptibility and molecular imprints of the diabetic environment. Renal markers such as albuminuria and reduced eGFR reflect microvascular injury and consistently associate with stroke risk. Multimarker panels and multi-omics integration using machine learning approaches show promise for improving predictive accuracy, though standardization, external validation, and demonstration of clinical utility are needed. Integrating these biomarkers with established clinical risk factors could transform stroke prevention in diabetes from reactive to proactive, enabling personalized, mechanism-informed strategies for early detection and risk stratification.

Background: Solid organ transplant recipients with diabetes mellitus face unique challenges in glycemic control, compounded by the metabolic effects of immunosuppressants. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective in diabetes, evidence for their use in transplant recipients remains limited. We aimed to systematically review the efficacy and safety of SGLT2 inhibitors in transplant recipients with diabetes.

Methods: A systematic review and meta-analysis was conducted by searching the MEDLINE, Embase, and Cochrane CENTRAL databases for studies published before July 2025. Seventeen comparative studies involving 12,892 transplant recipients with diabetes were included. Efficacy and safety data of SGLT2 inhibitors were extracted and analyzed. A random-effects model was used to pool the results.

Results: SGLT2 inhibitors led to a significantly greater reduction in HbA1c (mean difference [MD]: -0.59% and 95% confidence interval [CI]: -0.91 to -0.26) and body mass index (MD: -0.82 kg/m² and 95% CI: -1.54 to -0.10) compared to controls. The risks of dialysis (odds ratio [OR]: 0.50 and 95% CI: 0.31-0.79), major adverse cardiovascular events (OR: 0.29 and 95% CI: 0.22-0.38), heart failure (OR: 0.66 and 95% CI: 0.52-0.83), urinary tract infection (OR: 0.45 and 95% CI: 0.22-0.92), graft rejection (OR: 0.73, 95% and CI: 0.64-0.83), and all-cause mortality (OR: 0.40 and 95% CI: 0.27-0.59) were significantly lower in the SGLT2 inhibitor group.

Conclusions: SGLT2 inhibitors were associated with improved glycemic control, weight reduction, and favorable trends in cardiovascular outcomes among solid organ transplant recipients. Most safety outcomes, including urinary tract infection and graft rejection, were comparable between groups or more favorable in the SGLT2 inhibitor group, particularly among kidney transplant recipients. These findings support the use of SGLT2 inhibitors in this population. However, further large-scale studies are warranted to validate these results and assess the long-term effects across different transplant types.

Purpose: This study investigated the association of different serum vitamin D levels on macular microvascular structure in Type 2 diabetes mellitus (T2DM) patients without diabetic retinopathy (DR), utilizing optical coherence tomography angiography (OCTA).

Methods: A cross-sectional observational study was designed that includes 83 patients (83 eyes) with T2DM but without DR. Three groups were defined based on vitamin D levels, including vitamin D deficiency (serum vitamin D < 20 ng/mL), vitamin D insufficiency (20 ng/mL ≤ serum vitamin D < 30 ng/mL), and normal vitamin D (≥ 30 ng/mL) groups. All patients underwent OCTA with a 6 × 6-mm scan centered on the fovea. Assessment was conducted on the perfusion density (PD) of the retinal full layer (FL) and the superficial capillary plexus (SCP). In addition, evaluation of the foveal avascular zone (FAZ) included its area, perimeter, and acircularity index (AI).

Results: The PD of the SCP was significantly lower in the vitamin D deficiency group, especially in the temporal regions (42.04 ± 3.8 vs. 44.94 ± 4.5 vs. 47.24 ± 3.9, p < 0.001). The PD of the retinal FL was also significantly lower in the vitamin D deficiency group perifoveal area (32.94 ± 4.5 vs. 35.75 ± 4.2 vs. 35.57 ± 4.4, p < 0.05).

Conclusions: Changes in PD were found to be particularly sensitive to changes in the temporal-perifoveal region in individuals with vitamin D deficiency. Thus, vitamin D deficiency may be associated with DR.

Objective: The objective of this study is to explore the effect of bedside normobaric saturated oxygen inhalation combined with upper and lower limb rehabilitation training on diabetic lower extremity arterial disease (LEAD).

Methods: From January 2022 to December 2023, 60 DM-LEAD patients from the Second Hospital of Hebei Medical University were randomly divided into control (30 cases) and study (30 cases) groups. Both received standard treatment; the control group added MOTOmed-based limb rehabilitation training, and the study group further received atmospheric saturated oxygen therapy. Pre- and posttreatment indices (VAS, Barthel index, blood glucose, blood lipid, inflammatory factors, ABI, TcPO₂, and DPA flow velocity) were compared.

Results: Both groups improved posttreatment (all p < 0.05), with the study group showing greater benefits (all p < 0.05): VAS decreased more (3.82 ± 0.75 vs. 2.15 ± 0.62 points), Barthel index increased more (28.67 ± 4.21 vs. 15.33 ± 3.85 points), FBG (2.35 ± 0.52 vs. 1.21 ± 0.45 mmol/L) and 2hPBG (3.12 ± 0.68 vs. 1.78 ± 0.59 mmol/L) decreased more, IL-6 (8.76 ± 1.52 vs. 4.23 ± 1.18 pg/mL) and CRP (12.35 ± 2.18 vs. 6.12 ± 1.85 mg/L) decreased more, and ABI (0.38 ± 0.07 vs. 0.20 ± 0.06), TcPO₂ (18.67 ± 3.25 vs. 9.35 ± 2.78 mmHg), and DPA flow velocity (0.18 ± 0.04 vs. 0.09 ± 0.03 m/s) increased more.

Conclusion: The combined therapy improves pain and daily living abilities, delays DM-LEAD progression, may reduce amputation risk, and improves outcomes. Long-term effects need further study. Trial Registration: The UK's Clinical Study Registry: ISRCTN11014449.

Background: There is insufficient evidence to determine whether the risk factors and pregnancy outcomes associated with gestational diabetes mellitus (GDM) in twin pregnancies vary by chorionicity.

Materials: A retrospective cohort study was conducted among twin pregnancies. GDM was diagnosed using the IADPSG diagnostic criteria. Logistic regression and generalized estimation equation (GEE) models were used to identify the risk factors of GDM and its impact on pregnancy outcomes, stratified by monochorionic (MC) and dichorionic (DC) pregnancies.

Results: Advanced maternal age (MC: aOR 2.18, 95% CI 1.25-3.81 and DC: aOR 1.32, 95% CI 1.06-1.67) and preexisting hypertension (MC: aOR 2.69, 95% CI 1.04-9.36 and DC: aOR 1.70, 95% CI 1.12-2.59) were risk factors for GDM regardless of chorionicity. Overweight (aOR 1.65, 95% CI 1.26-1.98), obesity (aOR 2.31, 95% CI 1.43-3.74), multiparity (aOR 1.43, 95% CI 1.10-1.88), assisted reproductive technology (ART) use (aOR 1.75, 95% CI 1.36-2.26), and polycystic ovary syndrome (PCOS) (aOR 1.98, 95% CI 1.37-4.12) were risk factors for GDM only in DC pregnancies. GDM was only associated with an increased risk of preeclampsia in MC pregnancies (aOR 1.29, 95% CI 1.04-2.26). GDM was associated with an increased risk of preterm delivery (PTD) at < 37 (aOR 1.13, 95% CI 1.05-1.34) and < 34 gestational weeks (aOR 1.15, 95% CI 1.07-1.75) in DC pregnancies.

Conclusion: The risk factors and pregnancy outcomes associated with GDM in twin pregnancies vary by chorionicity.

Background: Recent studies have demonstrated an association between amino acids (AAs) and the occurrence of Type 2 diabetes mellitus (T2DM). However, whether there is an underlying causal relationship between AAs and T2DM, as well as their potential links to T2DM progression, complications, and treatment selection, still lacks sufficient clinical evidence.

Methods: This study included 205,208 participants from the UKB database, with 14,066 diagnosed with T2DM. We used LASSO regression, supplemented by Mendelian randomization (MR), to explore the causal relationship between AA levels and T2DM. Additionally, restricted cubic splines, receiver operating characteristic (ROC) curves, and multivariable-adjusted regression models were applied to analyze the association between AA levels, insulin resistance, secondary complications, and treatment options for T2DM.

Results: Alanine and valine were positively associated with T2DM, while glutamine, glycine, and histidine were negatively associated with T2DM. In particular, the MR results indicated a causal relationship between T2DM and plasma glutamine and glycine, which were identified as protective factors. Other branched-chain AAs, such as leucine and isoleucine, did not show significant positive associations in the regression analysis. Additionally, we integrated various AAs to develop a predictive model for secondary complications of T2DM. The model demonstrated high predictive accuracy for a range of T2DM-related complications (all areas under the ROC curve > 0.730). In addition, specific AA profiles were related to insulin resistance and demand for insulin or oral hypoglycemic drug treatment.

Conclusion: Our study results demonstrate a close relationship between AA levels and the occurrence, development, and treatment demand for T2DM, offering potential biomarkers for predicting complications and guiding personalized treatment.