World Journal of Diabetes最新文献

Background: Obesity and diabetes are well-established risk factors for cardiovascular disease (CVD), and their coexistence is particularly detrimental in chronic kidney disease (CKD). However, the interactions between various adiposity patterns and glycemic status in influencing CVD outcomes in CKD remain inadequately defined.

Aim: To evaluate the combined effects of diabetes, body mass index (BMI), and waist circumference (WC) on CVD risk.

Methods: We analyzed data from 1714859 adults with CKD sourced from the Korean National Health Insurance database. Participants were classified into three glycemic groups: Normoglycemia, impaired fasting glucose (IFG), and diabetes mellitus (DM). BMI and WC were further categorized into five and six levels, respectively. Incident CVD events and all-cause mortality were assessed across the combined categories of glycemic status and adiposity. Incidence rates and adjusted hazard ratios were computed using Cox proportional hazards models.

Results: A significant interaction was identified between glycemic status and adiposity indices concerning CVD risk (P for interaction < 0.001). Among normoglycemic individuals, both underweight (BMI < 18.5 kg/m²) and central obesity (WC ≥ 100/95 cm in men/women) were associated with increased CVD risk and mortality. In individuals with IFG, underweight remained a consistent risk factor, while WC displayed a linear relationship with CVD but not with mortality. In those with DM, the highest CVD risk was observed in individuals who were underweight (BMI < 18.5 kg/m²) and had low WC (< 80 cm in men/< 75 cm in women).

Conclusion: Cardiovascular risk is jointly influenced by glycemic status and adiposity, with diabetes consistently elevating risk across all BMI and WC categories, underscoring the importance of their assessment in CKD.

Background: Diabetic osteoporosis (DOP), a serious complication of type 2 diabetes mellitus (T2DM), involves ferroptosis-mediated disruption of bone metabolism. While endothelial cell-derived exosomes (EC-Exos) demonstrate inherent bone-targeting properties, their role in counteracting high glucose (HG)-induced osteoblast ferroptosis remains unexplored.

Aim: To investigate whether EC-Exos protect against HG-induced osteoblast ferroptosis through microRNA (miR)-335-3p-mediated regulation of prostaglandin endoperoxide synthase 2 (PTGS2) and evaluate clinical relevance in DOP.

Methods: Mouse vascular endothelial cells (bEND.3) and osteoblasts (MC3T3E1) were used. Exosomes were isolated and subsequently characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting for CD63 and CD81. miR expression profiles were compared between HG-treated osteoblasts and exosome-cocultured groups using high-throughput sequencing and quantitative reverse transcription polymerase chain reaction. Targeting of PTGS2 mRNA by miR-335-3p was validated by dual-luciferase reporter assay. Ferroptosis markers, reactive oxygen species, malondialdehyde, glutathione (GSH), PTGS2, GSH peroxidase 4, solute carrier family 7 member 11, and solute carrier family 3 member 2, were quantified following miR-335-3p inhibition. Serum samples from 30 T2DM patients and 32 DOP patients were analyzed. miR-335-3p levels were measured by quantitative reverse transcription polymerase chain reaction, and PTGS2 concentrations were determined via enzyme-linked immunosorbent assay. Diagnostic performance was assessed using receiver operating characteristic curves and logistic regression.

Results: EC-Exos significantly reduced reactive oxygen species levels and malondialdehyde, while increasing GSH in HG-treated osteoblasts. miR-335-3p expression increased 3.7-fold in exosome-treated cells vs HG controls. miR-335-3p directly bound the PTGS2 3' untranslated region. Inhibition of miR-335-3p abolished exosomal protection against ferroptosis, as demonstrated by increased PTGS2 expression and reduced levels of GSH peroxidase 4, solute carrier family 7 member 11, and solute carrier family 3 member 2. DOP patients exhibited lower serum miR-335-3p and higher PTGS2 compared with T2DM controls, showing a strong inverse correlation. miR-335-3p demonstrated diagnostic potential for DOP.

Conclusion: EC-Exos affect ferroptosis in osteoblasts induced by HG by activating miR-335-3p/PTGS2. Serum miR-335-3p may be a novel diagnostic biomarker.

Background: The incidence of diabetic cardiomyopathy (DCM) is increasing significantly as the population ages. DCM is one of the main causes of heart failure and mortality among patients with diabetes. Impaired mitophagy leads to mitochondrial dysfunction, which in turn aggravates DCM progression. Microtubule affinity-regulating kinase 4 (MARK4) is a key regulator of autophagy in adipocytes.

Aim: To investigate the role of MARK4 in mitophagy in DCM.

Methods: A mouse model of type 2 DCM was developed by administration of low-dose streptozotocin (50 mg/kg) combined with a high-fat diet. After 12 weeks MARK4 expression was knocked down in the mice by injection of the adeno-associated virus AAV9 into the tail vein. Four weeks later, cardiac function and structure were evaluated by echocardiography, and blood glucose levels and body weights were recorded. Mitochondrial ultrastructure and autophagosomes were assessed using electron microscopy. Mitochondrial membrane potentials were examined using fluorescence microscopy while the MARK4 and mitophagy-associated protein levels were investigated using western blotting. The downstream factors of MARK4 were identified using RNA-seq sequencing and bioinformatics with empirical confirmation.

Results: MARK4 levels were markedly increased in the DCM animal and cardiomyocyte models. Downregulation of MARK4 in DCM mice reduced myocardial tissue injury, increased mitophagy, and mitigated damage to cardiac function. RNA-seq indicated that MARK4 downregulation promoted mitophagy via upregulation of UNC-51-like kinase 1, alleviating myocardial injury in mice. This was confirmed in cell rescue experiments. Bioinformatics predicted interaction between MARK4 and the autophagy marker protein microtubule-associated protein 1 light chain 3B. This was verified using co-immunoprecipitation.

Conclusion: Downregulation of MARK4 in DCM mice can reduce myocardial injury, protect mitochondrial function, and promote mitophagy by upregulating UNC-51-like kinase 1, protecting against cardiac damage.

Background: Proliferative diabetic retinopathy (PDR) is a major cause of vision loss, often requiring pars plana vitrectomy (PPV). Systemic and intraocular metabolic alterations, including dysregulation of homocysteine (Hcy) and uric acid (UA), may influence surgical outcomes. While prior studies suggest associations between these biomarkers and retinal pathology, the role of these biomarkers in postoperative prognosis remains unclear. This study hypothesized that elevated serum and vitreous Hcy and UA levels are associated with visual, structural, and microvascular changes following PPV in patients with PDR.

Aim: To evaluate the associations between serum and vitreous Hcy/UA concentrations with postoperative outcomes in patients with PDR following PPV.

Methods: In this prospective observational study at a tertiary care center, 44 patients with PDR and 46 non-diabetic controls undergoing PPV between June 2021 and December 2022 were enrolled. Serum and vitreous Hcy and UA levels were measured. Best-corrected visual acuity, multimodal retinal imaging, and capillary density metrics were evaluated preoperatively and postoperatively. Correlation analyses assessed the relationships between biomarkers and clinical outcomes.

Results: Patients with PDR showed significantly higher serum and vitreous Hcy and UA concentrations compared to those of controls. Serum Hcy and UA levels correlated with vitreous levels. In patients with PDR, elevated vitreous Hcy correlated with worse best-corrected visual acuity at 1 day and reduced peripapillary retinal nerve fiber layer thickness at 7 days and 90 days. It also correlated with foveal avascular zone enlargement at 90 days and inferior superficial capillary plexus (SCP) width density at 7 days. Vitreous UA had negative correlations at 30 days with nasal SCP length density and temporal/inner ring SCP width density.

Conclusion: Vitreous, but not serum, Hcy predicts post-PPV impairment, underscoring the prognostic value of the local ocular environment over systemic factors in PDR.

This article discusses a recent article by Zha et al, which explores new pathogenic pathways contributing to diabetic nephropathy in a study conducted on male mice. Diabetic kidney disease outcomes remain suboptimal; it is the leading cause of end-stage kidney disease in the developed world. Previous knowledge about diabetic nephropathy focused on glomerular pathology. Advancing knowledge led to the introduction of new pathogenic concepts beyond glomerulopathy. This work by Zha et al explored an important podocyte pathway and its link to the proximal tubular cells. Podocytes are essential for maintaining glomerular health and preserving body proteins. In a state of hyperglycaemic stress, podocytes show features of internalisation of nephrin, an integral surface protein of the podocytes. The novel pathway uncovered in this experimental study involved crosstalk between the podocytes and the proximal tubular cells, more precisely, the secretion of interleukin 6 (IL-6) and Rab5 by the proximal tubular cells. When the podocytes were cultured in the conditioned medium, this resulted in podocyte dysfunction. IL-6 neutralising antibodies ameliorated this effect. Nicotinamide mononucleotide is essential for the integrity of the proximal tubular cells. Interestingly, it has been found that nicotinamide mononucleotide treatment can disrupt the IL-6-Rab signalling between the proximal tubules and podocytes, leading to improved podocyte morphology and function. The clinical applicability of this novel pathway is yet to be explored; however, it is one of the key pathways mediating inflammation and dysfunction in diabetic nephropathy.

Background: The 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.

Aim: To investigate the independent and combined associations of SHR and TIR with 28-day mortality among surgical ICU patients.

Methods: In 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.

Results: Logistic 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).

Conclusion: Combined 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.

While left ventricular (LV) impairment in diabetic cardiomyopathy is well recognized, the contribution of right ventricular (RV) dysfunction has received far less attention. In their longitudinal investigation, Yu et al systematically examined RV and LV performance in a type 1 diabetic mouse model and demonstrated that RV diastolic dysfunction develops later than LV abnormalities, coinciding with structural remodeling marked by fibrosis, hypertrophy, and mild pulmonary hypertension. These observations underscore the progressive yet distinct trajectory of RV pathology in diabetes and point to the importance of incorporating RV assessment into the overall cardiac evaluation of diabetic patients. This letter explores the broader significance of these findings and highlights the urgent need for studies focused on RV-specific mechanisms and targeted therapies aimed at preventing or attenuating biventricular injury in diabetic cardiomyopathy.

Recent real-world evidence suggests that improved regulation of metabolic and inflammatory pathways can substantially lower the risk of periodontal complications in individuals with type 2 diabetes. Periodontitis, a frequent yet often overlooked complication, arises from chronic hyperglycaemia and systemic inflammation, illustrating the bidirectional link between metabolic imbalance and oral health. Recognizing this interplay emphasizes the need for integrative diabetes management strategies that combine glycaemic control with inflammatory modulation to achieve broader health benefits. This letter highlights the clinical and scientific importance of such an approach, calls for interdisciplinary collaboration between endocrinologists and oral health professionals, and advocates for mechanistic and preventive studies addressing oral health as an integral component of comprehensive diabetes care.