BACKGROUND The combined effects of C-reactive protein (CRP) and fasting C-peptide (FCP) on cardiovascular risk remain unclear. AIM To introduce a novel variable, the CRP-FCP product and to evaluate whether it better reflects the cardiovascular risk burden than either biomarker alone in patients with type 2 diabetes mellitus (T2DM). METHODS Overall, 8486 patients with T2DM were enrolled and stratified into quartiles based on CRP-FCP product to compare their clinical characteristics. The associations of CRP, FCP, and the CRP-FCP product with cardiovascular events (CVEs), cerebrovascular events (CBVEs), and cardio-CBVEs (CCBVEs, defined as the presence of CVEs and/or CBVEs) were analyzed by logistic regression. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the discriminative performance of the CRP-FCP product. RESULTS The adjusted prevalences of CVEs, CBVEs, and CCBVEs increased significantly across the CRP-FCP product quartiles (all P < 0.05 for trend). In fully adjusted models, the CRP levels were positively associated with CBVEs (P = 0.016) and CCBVEs (P = 0.005), but not with CVEs (P = 0.070). Conversely, higher FCP levels were associated with an increased risk of CVEs (P = 0.039) and CCBVEs (P = 0.007), but not with CBVEs (P = 0.290). Notably, the CRP-FCP product was independently associated with all three outcomes (all P < 0.05). ROC analyses showed that the area under the curve values of the CRP-FCP product were 0.550 for CVEs, 0.555 for CBVEs, and 0.558 for CCBVEs. CONCLUSION The CRP-FCP product was linked to an increased risk of CVEs, CBVEs and CCBVEs. The CRP-FCP product may provide a more comprehensive assessment of the cardiovascular risk burden than CRP or FCP alone in patients with T2DM.

BACKGROUND Delayed wound repair is commonly observed among individuals with diabetes. AIM To determine the mechanism of C1q tumor necrosis factor associated protein 3 (CTRP3) in regulation of wound healing. METHODS Wounds were created in wild-type C57BL/6J and db/db diabetic mice. CTRP3 expression was measured in mouse blood on days 0, 4, 8, 12, 16 and in high glucose-treated HaCaT cells. CTRP3’s role was assessed via cell growth and migration assays. Vascular endothelial growth factor (VEGF) levels were detected. A phospho-kinase array identified phosphorylated kinases. Co-immunoprecipitation verified CTRP3 interaction with phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway proteins. RESULTS CTRP3 expression increased significantly with the passage of wound healing time and CTRP3 expression is low in high-glucose-treated HaCaT cells. High glucose treatment significantly suppressed the cell growth and migration of HaCaT cells, while high expression of CTRP3 reversed the effects of high glucose. Meanwhile, the growth factor VEGF down-regulated by high glucose treatment in HaCaT cells significantly elevated in HaCaT cells with highly-expressed CTRP3. CTRP3 promotes wound healing in diabetic mice in vivo . Moreover, CTRP3 activates PI3K/AKT pathway by reducing PTEN protein level. CONCLUSION CTRP3 accelerates diabetic wound healing, potentially by protecting keratinocytes through downregulating PTEN and activating the PI3K/AKT pathway, presenting a novel therapeutic target.

The study by Caturano et al published in the recent issue of the World Journal of Diabetes focused on high-risk type 2 diabetes patients, particularly those with albuminuria and retinopathy. The key finding was that maintaining glycated hemoglobin A1c (HbA1c) levels at or below 7% was significantly associated with a reduced incidence of major adverse cardiovascular events (MACE) only in the standard care group, while this association was not evident in the intensive multifactorial treatment group. Additionally, there was a U-shaped relationship between continuous HbA1c levels and both MACE and all-cause mortality. However, the study had limitations, including the exclusion of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists and a focus on specific high-risk subgroups. These findings align with current guidelines and support a personalized management strategy for type 2 diabetes, emphasizing that comprehensive multifactorial intervention is more beneficial for improving long-term patient outcomes than solely targeting HbA1c levels.

BACKGROUND Diabetic retinopathy (DR) is a leading cause of adult blindness and involves Müller cell dysfunction, which contributes to neurovascular damage in the retina. PRDX2, a member of the thioredoxin family, possesses antioxidant properties and plays roles in cell survival and vascular remodeling. It also exhibits proinflammatory effects in diabetic nephropathy. However, its specific role in the pathogenesis of DR, particularly in relation to Müller cells, remains poorly understood. AIM To investigate the role of PRDX2 in DR progression and to elucidate its mechanism in regulating high-glucose (HG)-induced reactive hyperplasia of Müller cells. METHODS A case-control study involving 220 participants (47 healthy controls and 173 individuals with diabetes) was conducted to evaluate plasma PRDX2 levels. Ocular PRDX2 expression was analyzed using vitreous humor samples from proliferative DR (PDR) patients, retinal tissues from DR patients (GSE53257), and retinas from streptozotocin (STZ)-induced diabetic mice (GSE178121). In vitro , PRDX2 -knockdown rMC-1 cells (a rat Müller glial cell line) exposed to HG conditions were used to assess the role of PRDX2 in HG-induced gliosis through functional and molecular analyses. RESULTS Plasma PRDX2 levels were positively correlated with DR severity (r = 0.267, P < 0.0001) and independently predicted PDR risk after adjustment for confounding factors, including hypertension, age, serum creatinine, urea, fasting blood glucose, and vascular endothelial growth factor A levels (cut-off > 124.3 pg/mL; adjusted odds ratio = 9.097; 95% confidence interval: 2.819-29.355; P = 0.0002). In alignment with its systemic elevation, PRDX2 was markedly upregulated in vitreous humor of PDR patients, retinas of DR patients (GSE53257), Müller cells from STZ-induced diabetic mice (GSE178121), and HG-treated rMC-1 cells. PRDX2 silencing attenuated HG-induced Müller cell hyperproliferation and reduced nestin expression, a marker of gliosis. Mechanistically, this effect was mediated through upregulation of RhoGDI1 and suppression of the RhoA/ROCK signaling pathway, as demonstrated by quantitative proteomics and western blot analysis. CONCLUSION PRDX2 promotes Müller cell gliosis in DR via the RhoGDI1-RhoA/ROCK axis, making it a potential biomarker and therapeutic target.

BACKGROUND Coffee consumption exhibits significant geographical variation between coffee and diabetes between China and Western countries. Furthermore, existing research on the relationship between coffee consumption and diabetes yields inconsistent results, with limited studies focusing on the Chinese population. AIM To investigate the association among coffee consumption, diabetes, and glucose indices among Chinese adults. METHODS A cross-sectional survey, involving 6876 individuals from the communities, was conducted in Guangdong, China. Participants provided detailed records of their coffee consumption, including any additives such as milk, sugar, or artificial sweeteners. Diabetic indicators measured included glycated hemoglobin (HbA1c), fasting plasma glucose, and 2-hour postprandial glucose (2h-PG). Statistical analyses were performed using multivariable logistic regression, adjusting for three categories of covariates: Demographic and anthropometric characteristics, lifestyle factors, and clinical and family history indicators. RESULTS In the adjusted model, coffee consumption was found to be inversely associated with the prevalence of diabetes, with an odds ratio (OR) of 0.79 and a 95% confidence interval (CI) of 0.64 to 0.98 (P = 0.029). Additionally, higher coffee consumption was inversely associated with elevated 2h-PG levels (OR = 0.83, 95%CI: 0.73-0.95; P = 0.005). Among individuals who consumed coffee with milk, the odds of elevated 2h-PG levels were reduced by 24% (OR = 0.76, 95%CI: 0.66-0.88; P < 0.001), and the odds of elevated HbA1c levels were reduced by 28% (OR = 0.72, 95%CI: 0.63-0.83; P < 0.001). CONCLUSION Coffee consumption, particularly the intake of coffee with milk, is inversely associated with the prevalence of diabetes, elevated 2h-PG, and increased HbA1c levels. The intake of coffee with milk is a factor of interest in the context of diabetes prevention or glycemic control; however, this observation necessitates further validation through additional randomized controlled trials.

Diabetic gastroparesis (DGP) is a common but long-underestimated gastrointestinal complication of diabetes, characterized by complex and heterogeneous clinical manifestations, and shows only a limited correlation between symptom severity and delayed gastric emptying. Traditional pathological paradigms centered on gastric motility disturbances are insufficient to fully account for its multidimensional phenotypes and variable therapeutic responses. In recent years, advances in neuroscience, immunology, and gut microbiota research have increasingly supported the concept that DGP represents a systemic disorder primarily mediated by brain-gut axis dysfunction. Its pathogenesis involves the coordinated disruption of multilevel regulatory networks, encompassing the central nervous system, autonomic nervous system, the enteric nervous system-interstitial cells of Cajal network, pyloric function, inflammatory and immune responses, and the gut microbiota. Under conditions of chronic hyperglycemia and metabolic stress, neurodegenerative alterations, immune-neural coupling imbalance, and gut microbiota dysbiosis interact to impair gastrointestinal sensorimotor integration. This review systematically summarizes the key pathological mechanisms and cross-system regulatory features of DGP in an integrated brain-gut axis framework. Furthermore, based on recent advances, it discusses pharmacological, neuromodulatory, and metabolic intervention strategies that target the brain-gut axis. Future research should prioritize brain-gut axis-based phenotypic stratification, biomarker system development, and multitarget precision interventions to facilitate the transition of DGP management from a single-function motility-centered approach to mechanism-guided personalized therapy.

BACKGROUNDDiabetic kidney disease (DKD) continues to pose a substantial public health challenge, in which cellular senescence is recognized as a pivotal driver of disease progression. While formononetin (FN) has been documented to exhibit anti-senescence properties, its potential as a therapeutic agent for DKD and the molecular mechanisms involved remain unexplored.AIMTo evaluate the efficacy of FN using an in vitro model of high glucose (HG)-induced injury in MPC-5 podocytes. Transcriptomic profiling was employed to assess the influence of FN on global gene expression and to identify key signaling pathways affected by FN treatment. Furthermore, we sought to investigate the anti-senescence effects of FN and its regulatory role in the p53 signaling pathway in vitro.METHODSTo elucidate the functional role of MDM2 in the anti-senescence mechanism of FN, MDM2 expression was silenced in MPC-5 cells using gene-specific knockdown. Finally, a mouse model of DKD was generated by combining a high-fat diet with intraperitoneal streptozotocin injections, and the therapeutic as well as anti-senescence effects of FN were evaluated in vivo.RESULTSIn the HG-induced MPC-5 cell model, FN treatment significantly enhanced cell viability and reduced the secretion of senescence-associated secretory phenotype (SASP) factors in the supernatant. Transcriptomic analysis revealed the p53 signaling pathway as a central target of FN under HG conditions. FN treatment markedly suppressed β-galactosidase (β-GAL) activity, upregulated the expression of MDM2 and CCND1, downregulated the expression of p53 and p21, and inhibited p53 transcriptional activity in MPC-5 cells. These protective effects were abrogated upon MDM2 silencing. In DKD mice, FN administration improved renal function, alleviated histopathological damage, reduced renal SASP levels and β-GAL activity, and normalized the expression of key proteins in the p53 pathway.CONCLUSIONOur findings demonstrate that FN confers significant therapeutic benefits against DKD in both cellular and animal models. The mechanism underlying these benefits involves the delay of cellular senescence through suppression of the p53 signaling pathway.

BACKGROUNDDiabetic foot ulcers (DFUs), a common and severe long-term complication of diabetes, are associated with high rates of amputation and mortality. Transverse tibial bone transport (TTT) has recently been applied in DFU management to accelerate wound healing.AIMTo explore the potential mechanism through which TTT aids in the treatment of DF, with a special focus on the role of postoperative distraction osteogenesis and angiogenesis in the affected limb.METHODSFifteen patients with DFUs (Wagner grades 2-5) treated with TTT were enrolled. Pain intensity was assessed using the Visual Analog Scale (VAS), and skin temperature and Ankle-brachial index (ABI) were measured at 1 week, 1 month, and 6 months postoperatively. Wound healing was assessed by tracking the duration and rate of healing. Computed tomography (CT) scans of both lower limbs were conducted before and 1 month after surgery to evaluate distraction osteogenesis, and CT values of the corresponding medullary cavities of the bone blocks were recorded. High-frequency color Doppler ultrasonography was used to assess popliteal artery (POA) blood flow, inner diameters, and velocities of the three middle arteries of the lower leg and dorsalis pedis artery, and the number of collateral vessels of the three middle arteries. Plantar microcirculation was measured before and 1 month after surgery using the laser Doppler flowmetry system PeriScan PIM3.RESULTSComplete wound healing occurred in all patients, with a mean healing duration of 10.1 ± 3.7 weeks. The regenerated skin showed no clear boundary with the surrounding tissue and revealed a visible dermatoglyphic pattern. CT imaging 1 month postoperatively revealed substantial bone formation beneath the distracted bone block, with alignment consistent with the direction of distraction; showing a transverse arrangement, no obvious bone aggregation was observed in the corresponding part of the medullary cavity before surgery. Postoperative assessments revealed significantly increased foot skin temperature and ABI values, accompanied by significant reductions in VAS scores (P < 0.05). CT values of the distracted bone block increased significantly compared to the baseline. POA blood flow was significantly greater at 1 month postoperatively than before surgery. B-ultrasound examinations revealed that collateral branches around the three middle arteries of the lower leg were sparse preoperatively. One month after surgery, the number of collateral vessels increased significantly, although their inner diameters showed no significant change, while blood flow velocity increased significantly. Laser Doppler analysis further revealed that the plantar skin blood flow signals were sparse, indicating poor microcirculatory perfusion before surgery.CONCLUSIONIn patients with DR, TTT appears to promote ulcer healing by enhancing limb blood circulation. This effect is associated with distraction osteogenesis at the surgical site, which supports collateral angiogenesis. These findings suggest a relationship among distraction osteogenesis, local angiogenesis, and improved tissue perfusion that may contribute to ulcer healing; however, the causal mechanisms underlying this relationship remain unclear.

BACKGROUNDFasting glucose and glycated hemoglobin (HbA1c) were used to diagnose gestational diabetes during the coronavirus disease 2019 (COVID-19) pandemic.AIMTo determine whether the diagnostic criteria used during the COVID-19 pandemic may play a role outside the pandemic.METHODSFrom May 2022 to July 2024, 354 females with an altered 50-g oral glucose tolerance test (OGTT), the usual diagnostic test (100-g OGTT), and the alternative diagnostic (A) criteria (fasting glucose ≥ 95 mg/dL and/or HbA1c ≥ 5.7%) were tested simultaneously, resulting in four different groups: OGTT+/A+ (n = 20); OGTT+/A- (n = 60); OGTT-/A+ (n = 24); and OGTT-/A- (n = 250). Groups were compared for clinical characteristics and obstetric and perinatal outcomes.RESULTSSensitivity of the alternative criteria was 25% and specificity was 91.2%. Body mass index (BMI) was similar from the OGTT-/A+ and OGTT+/A+ groups (30.1 ± 6.3 kg/m2 and 32.7 ± 5.3 kg/m2, respectively) and significantly higher from the OGTT+/A- and OGTT-/A- groups (26.8 ± 5.1 kg/m2 and 25.6 ± 5.0 kg/m2, respectively). The between-group differences were similar for the respective rates of large for gestational age (LGA) infants (OGTT+/A+: 38.9%, OGTT+/A-: 11.8%, OGTT-/A+: 29.4%, OGTT-/A-: 12.4%; P = 0.028). In the regression analysis a history of macrosomia [odds ratio (OR) = 7.948, 95% confidence interval (95%CI): 2.269-27.842; P = 0.001] and higher pregestational BMI (OR = 1.069, 95%CI: 1.002-1.140; P = 0.042) independently increased the risk of LGA.CONCLUSIONDespite insufficient validity to replace the OGTT, alternative criteria identify a group of patients with a higher risk profile and adverse perinatal outcomes who could benefit for health interventions.

BACKGROUNDThe stress hyperglycemia ratio (SHR) reflects patients’ acute hyperglycemia status, and the time in range (TIR) captures glucose control dynamics during their intensive care unit (ICU) stays.AIMTo investigate the independent and combined associations of SHR and TIR with 28-day mortality among surgical ICU patients.METHODSIn total, 706 adult patients with available glucose data were included. SHR was calculated as the ratio of admission glucose levels to glycosylated hemoglobin-derived estimated average glucose. TIR was calculated as percentages of glucose readings within the 3.9-10.0 mmol/L range during the ICU stay. SHR and TIR were divided into quartiles, and patients were allocated to four groups according to combinations of high/low values. The associations of the SHR, TIR, and both combined with mortality were assessed using logistic regression.RESULTSLogistic regression analysis demonstrated that patients in the highest SHR quartile had a significantly increased risk of 28-day mortality compared with the reference quartile [adjusted odds ratio (OR) = 2.24; 95% confidence interval (CI): 1.06-4.71; P = 0.033]. In contrast, higher TIR were associated with a reduced risk of 28-day mortality. Compared with the lowest TIR quartile (Q1), adjusted ORs in Q2, Q3, and Q4 were 0.43 (95%CI: 0.23-0.93; P = 0.030), 0.43 (95%CI: 0.19-0.99; P = 0.046), and 0.41 (95%CI: 0.17-0.98; P = 0.045), respectively. When the SHR and TIR were analyzed in combination, patients with high SHR and low TIR had the highest risk of 28-day mortality (adjusted OR = 2.19; 95%CI: 1.05-4.58; P = 0.038).CONCLUSIONCombined SHR and TIR assessment offers prognostic value in surgical ICU patients. Maintaining glucose within the target range may be important to improve short-term outcomes in patients with stress hyperglycemia.