World Journal of Diabetes最新文献

Background: China has the highest incidence of diabetes among all Asian countries, and environmental factors have a significant impact on the onset of diabetes. Lead is one of the important legacy environmental pollutants that disrupts endocrine function. Both lead and diabetes have damaging effects on the nervous system, while the gut microbiota is considered an important mediator of brain damage.

Aim: To determine the effects and underlying mechanisms of environmental lead exposure and diabetes on neural function.

Methods: A mouse model of lead exposure and diabetes was used. Lead levels were measured using inductively coupled plasma mass spectrometry, and blood glucose levels were assessed. Immunofluorescence was used to analyze brain damage in mice. The Morris water maze was used for evaluating neural function. Neurotransmitters including vanillylmandelic acid, 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were quantified with high performance liquid chromatography. Proteomics analysis was conducted on hippocampal brain tissue, and gut microbiota analysis was performed on colonic fecal samples. PI3K and COX2 proteins were detected by Western blotting, and then glutathione (GSH) levels in brain tissue were measured.

Results: Mice in the lead-exposure diabetic model exhibited significantly elevated lead and blood glucose levels, with the most severe neural damage observed. The neurotransmitters DOPAC and HVA were markedly increased. Proteomics revealed that differential proteins were primarily involved in neural and metabolic pathways. Correlation analysis between the top 20 gut microbiota and differential proteins identified Sutterella as the most associated gut microbe with proteins. The levels of COX2, PI3K, and GSH in the mouse brain provided preliminary validation of these findings.

Conclusion: The coexistence of lead exposure and diabetes has an interactive effect on neural damage. This interaction appears to affect the abundance of the gut microbe Sutterella, which, through inflammation, influences the expression of related differential proteins in the brain, ultimately resulting in neural damage.

This letter comments on the study by Ge et al. Serum α1-microglobulin (α1-MG) was reported to be associated with diabetic nephropathy, retinopathy, peripheral neuropathy, and left ventricular hypertrophy. The letter further highlights the need for multicenter validation and evaluation of clinical applicability to clarify the role of α1-MG in diabetes management.

Glucose homeostasis is crucial for metabolic health, with disruptions leading to hyperglycemia (e.g., diabetes affecting over 589 million adults worldwide in 2025) or hypoglycemia, both associated with severe complications like nephropathy, neuropathy, and cardiovascular disease. The peripheral nervous system (PNS) is a less studied regulator of glucose balance through neural circuits involving the sympathetic, parasympathetic, sensory, and somatic nerves, which interact with organs like the liver, pancreas, and gut. This review aims to synthesize recent advances in PNS-mediated glucose lowering, covering mechanistic foundations, organ-specific pathways, translational interventions (e.g., device-based neuromodulation, pharmacological approaches, closed-loop systems, and regenerative strategies), preclinical/clinical evidence, translational challenges, and future perspectives to provide a roadmap for developing novel, drug-free therapies for dysglycemia.

Background: Fasting glucose and glycated hemoglobin (HbA1c) were used to diagnose gestational diabetes during the coronavirus disease 2019 (COVID-19) pandemic.

Aim: To determine whether the diagnostic criteria used during the COVID-19 pandemic may play a role outside the pandemic.

Methods: From 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.

Results: Sensitivity 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.

Conclusion: Despite 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.

Diabetic kidney disease (DKD) represents a significant challenge for diabetes management and public health as it affects the quality of life and metabolic control of millions of people around the world. Characterized by persistent albuminuria and impaired renal function, DKD is an insidious consequence of chronic hyperglycemia and has far-reaching implications for cardiovascular health and mortality. More and more researchers in this field are focusing on the identification of reliable urinary biomarkers that can serve as early indicators of kidney disease progression and enable timely intervention through tailored therapeutic strategies. These biomarkers offer a potential way to improve the diagnosis, monitoring and understanding of kidney disease associated with diabetes, a persistent global health problem. Different types of urinary biomarkers provide insight into the pathophysiological processes involved in DKD. Albumin, for instance, is a crucial biomarker that signals microalbuminuria even before kidney function declines. Other promising candidates include several proteins, such as kidney injury molecule-1, which clearly indicates tubular damage to the kidneys, and neutrophil gelatinase-associated lipocalin, a marker of severe acute kidney injury. In addition, innovations in metabolomics have led to the discovery of certain specific metabolic signatures. These signatures can help distinguish DKD from other forms of kidney disease and show a certain complexity and interconnectivity in overall renal pathology. Finally, the role of many genetic and epigenetic factors is being investigated, highlighting how urinary biomarkers may reflect not only extreme injury but also an individual's genetic predisposition to renal complications. As they become better understood, urinary biomarkers have the potential to significantly improve outcomes and risk stratification for people with DKD. Incorporating biomarker data into routine clinical practice could improve the ability to detect the disease earlier, monitor disease progression more effectively and personalize treatment methods. Moreover, elucidating the mechanisms behind these biomarkers could inspire new treatment approaches that focus on the underlying causes of DKD rather than just treating the symptoms. This will lead to better patient care and improved outcomes for this at-risk group.

Background: Rabson-Mendenhall syndrome (RMS) is an extremely rare monogenic form of diabetes caused by mutations in the insulin receptor (INSR) gene, with only about 50 cases reported worldwide to date. Here, we report a case of RMS caused by a previously unreported c.1123+2 T>C splice mutation.

Case summary: The patient was diagnosed with acanthosis nigricans and hypertrichosis at birth, and the growth rate was slower than that of normal children. At age 5, the patient had severe hyperinsulinemia, congenital heart abnormalities, and pineal cysts. At age 13, he was diagnosed with diabetes and exhibited symptoms of hyperinsulinemia, low body weight, growth retardation, acanthosis nigricans, dental anomalies, an oversized penis, and a pineal cyst. Sequencing results indicated an INSR c.1123+2 T>C mutation, and bioinformatic analysis suggested that this mutation led to splicing abnormalities, thereby affecting INSR function. Both parents carried the mutated gene, whereas his brother had a normal genotype.

Conclusion: Genetic diagnosis is vital in RMS; c.1123+2 T>C mutation of INSR causes pancreatic decline; current treatments show limited effectiveness.

Background: Gestational diabetes mellitus (GDM) is characterized by glucose intolerance first identified during pregnancy. Adipokines are adipose-derived hormones regulating insulin sensitivity, while body composition describes the body's fat and non-fat components, which change dynamically in gestation.

Aim: To explore the associations between body composition, adipokines, and GDM risk, identifying early predictive markers to enhance prenatal risk assessment.

Methods: A retrospective analysis included 1656 singleton pregnant women (276 with GDM, 1380 with normal glucose tolerance) from 2020-2024. Early pregnancy (6-16 weeks) body composition was assessed via bioelectrical impedance analysis. Adipokines (leptin, adiponectin, fatty acid-binding protein 4) and metabolic indices were measured during 24-28 weeks oral glucose tolerance test. Group comparisons, logistic regression, correlation analysis, and receiver operating characteristic curves were used to evaluate relationships and diagnostic performance.

Results: GDM women had higher pre-pregnancy body mass index (BMI), glucose/insulin, homeostasis model assessment of insulin resistance, lower insulin sensitivity index (all P < 0.05). GDM showed higher fat mass percentage (FMP) (36.23% ± 7.54% vs 33.12% ± 9.87%), fat mass index (FMI) (9.87 ± 3.32 kg/m² vs 8.34 ± 4.11 kg/m²), extracellular-to-intracellular water ratio (ECW/ICW) (0.63 ± 0.03 vs 0.61 ± 0.02), lower lean mass indices (all P < 0.001 except ECW/ICW P = 0.012). GDM had higher leptin (P = 0.014), lower adiponectin (P = 0.021). FMP elevation was independent risk factor (odds ratio = 1.412, P = 0.030). Pre-pregnancy BMI (area under the curve = 0.662), FMP (0.651), FMI (0.650) had better diagnostic value than ECW/ICW (0.606).

Conclusion: Body composition parameters (FMP, FMI) and adipokines (leptin, adiponectin) are closely linked to GDM risk. Integrating these assessments into prenatal care facilitates early risk identification and targeted interventions to improve maternal-fetal outcomes.

Background: Prediabetes increases the risk of cardiovascular and cerebrovascular mortality. This study examines the relationship between prediabetes and mortality in post-stroke patients.

Aim: To determine whether prediabetes is associated with increased post-stroke mortality in adults with acute ischemic stroke (IS).

Methods: A systematic search was conducted in PubMed/MEDLINE, Scopus, and Google Scholar databases until May 2023 to identify relevant articles reporting on the association of prediabetes with IS mortality. A random-effects model was used to calculate odds ratio (OR), heterogeneity was assessed using I ² statistics, and sensitivity analysis was performed using the leave-one-out method.

Results: Our analysis of 11 studies included 84833 prediabetic patients with a mean follow-up time of 20.9 months. The prediabetes cohort comprised patients of an average age of 67 years from various countries, including Korea, Italy, Japan, China, Spain, and the Netherlands. Although, the unadjusted analysis showed no significant association between prediabetes and post-stroke mortality (OR = 1.06, 95%CI: 0.51-2.19) with high heterogeneity (I ² = 94.7%, P < 0.01). Post-adjustment for baseline characteristics and comorbidities, the prediabetes cohort exhibited a significantly higher risk of post-stroke mortality (adjusted OR = 1.68, 95%CI: 1.29-2.19) with moderate heterogeneity (I ² = 49.45%, P = 0.03). Subgroup analysis by country revealed non-significant higher odds of mortality in Korea, Italy, Spain, Japan, and the Netherlands, indicating the need for more extensive studies.

Conclusion: Our findings suggest that prediabetes is associated with a nearly 68% higher mortality risk following a stroke. Thereby warranting more prospective studies with prediabetes to validate these findings.

Type 2 diabetes mellitus is a complex metabolic disorder characterized by impaired insulin secretion, insulin resistance, and dysregulated inter-organ communication. Beyond classical endocrine signaling, exosomes have recently emerged as critical mediators of crosstalk between pancreatic β cells and peripheral metabolic tissue. In a recent study, Xu et al demonstrated that hepatocytes can receive exosomal miR-375-3p derived from pancreatic β-cells, which suppresses the Rbpj region and consequently impairing hepatic glycogenesis. These findings provide novel mechanistic insights into how glucotoxic β cells influence hepatic glucose metabolism independently of insulin secretion. Notably, this study highlights exosomal miR-375-3p as a potential biomarker and therapeutic target for metabolic diseases. However, clinical validation in human cohorts and assessment of long-term metabolic outcomes are still required. A deeper understanding of exosome-mediated communication between the pancreas and liver may ultimately pave the way for new strategies to restore metabolic homeostasis and mitigate disease-related complications.

A notable number of patients with diabetes suffer from painful diabetic neuropathy (PDN), which is a debilitating complication of diabetes mellitus. Prolonged hyperglycaemia and metabolic dysregulation lead to PDN, a condition characterised by chronic pain, sensory dysfunction, and reduced quality of life. Although various treatment options are available, clinical management is challenging due to the complex and multifactorial nature of PDN pathophysiology. N-methyl-D-aspartate receptors (NMDARs), particularly the NR2B subtype (NMDAR-2B), have emerged as a key player in the pathophysiology of chronic pain states, including PDN. This review highlights the mechanistic NMDAR-2B involvement in the pathophysiology of PDN, focusing on its upregulation role in pain-processing regions, interaction with inflammatory mediators, glia-derived mediators, and oxidative stress mechanisms. Advancements in targeting NMDAR-2B as a mechanistically driven approach to PDN management also offer potential in enhancing the therapeutic efficacy of NMDAR-2B. Consequently, this review provides a novel perspective on understanding the role of NMDAR-2B in PDN for the future development of effective treatment strategies for managing the condition.