To assess the predictive value of serum lipoprotein(a) [Lp(a)] for contrast-induced nephropathy in patients with type 2 diabetes mellitus (T2DM).

Consecutive T2DM patients who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI) between January 2019 and December 2021 were enrolled. Baseline Lp(a) was measured before the operation. CIN was defined as an increase in serum creatinine of more than 25% or 44 μmol within 72 h of contrast administration. The relationship between Lp(a) and CIN risk was analyzed.

A total of 928 T2DM patients were included. CIN developed in 11.1% (103/928) of patients. The Lp(a) level was significantly higher in patients with CIN than in non-CIN patients (311.12 ± 278.66 vs. 254.19 ± 274.56 mg/L, P = 0.048). Patients were divided into three groups based on Lp(a) levels: <150 mg/L (n = 428), 150 mg/L-300 mg/L (n = 266), and ≥300 mg/L (n = 234). Each group stratified by increasing Lp(a) concentrations had incrementally greater risks of CIN (7.2% vs. 12% vs. 17.1%, P < 0.001). Multivariate logistic regression analysis showed that patients with Lp(a) ≥300 mg/L had a 2.41-fold higher risk of CIN than those with Lp(a)< 150 mg/L (OR = 2.41, 95% CI: 1.38-4.21, P = 0.002). Additionally, for each increase of 1 logarithmic unit in Lp(a), the risk of CIN increased by 1.27 times (OR = 1.27, 95% CI: 1.01-1.64, P = 0.045).

A higher serum Lp(a) level indicates an increased risk of CIN in T2DM patients undergoing CAG or PCI and can serve as an independent predictor of CIN in this population. This study's findings will aid in the clinical prevention and treatment of contrast agent-induced kidney disease.

Surgical site infection (SSI) is a major complication in patients with open hand injuries. However, current clinical risk assessment largely relies on subjective judgment or traditional scoring systems, which often lack predictive precision and generalizability. This study aimed to develop, compare, and externally validate multiple machine learning (ML) models for predicting SSI in open hand injuries using routinely collected clinical indicators.

A total of 800 patients with open hand injuries were retrospectively enrolled. The primary cohort (n=500) was randomly divided into training (70%, n=350) and internal testing (30%, n=150) sets, while an independent cohort (n=300) was used for external validation. Eight ML algorithms were constructed and compared, including logistic regression, decision tree, random forest, support vector machine, k-nearest neighbor, naive Bayes, extreme gradient boosting, and light gradient boosting machine. Model performance was evaluated using area under the curve (AUC), accuracy, sensitivity, specificity, and other metrics in internal cross-validation and external validation. SHapley Additive exPlanations (SHAP) were applied for feature interpretability.

The random forest model demonstrated the best performance, with an AUC of 0.903 (95% CI 0.863 to 0.943) in training, 0.870 (95% CI 0.822 to 0.918) in internal testing, and 0.849 (95% CI 0.802 to 0.896) in external validation. Six key variables (age, smoking, diabetes mellitus, time from injury to surgery, wound contamination, and negative pressure drainage) were identified as the most influential predictors. SHAP analysis provided interpretable insights into their contributions to infection risk.

The random forest model showed robust predictive performance and generalizability for SSI in open hand injuries. These findings highlight the model's potential as a clinical decision-support tool to assist surgeons in early risk stratification and personalized interventions, potentially reducing morbidity and improving outcomes. Future prospective studies are needed for further validation.

The Platelet-to-HDL-cholesterol ratio (PHR), an emerging inflammatory biomarker, shows promise as a predictor in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). However, the association between PHR and glycemic metabolism status and their combined effects on the prognosis of CAD patients undergoing percutaneous coronary intervention (PCI) remains unclear.

A total of 31,761 CAD patients hospitalized for PCI were included. The primary endpoint was defined as major adverse cardiovascular events (MACEs). According to the median PHR levels, patients were grouped into higher levels of PHR (PHR-H) and lower levels of PHR (PHR-L) and further divided by glycemic status into four groups: PHR-H/T2DM, PHR-H/Non-T2DM, PHR-L/T2DM, PHR-L/Non-T2DM.

During the 1-year follow-up, 2258 (7.1%) MACEs occurred. Elevated PHR conferred 17% excess risk for MACEs. A 1-unit increase in LnPHR was associated with a 26% increased risk of MACEs in the T2DM cohort, and a 27% increase of MACEs risks in the non-T2DM cohort. Compared to those in PHR-H/T2DM group, patients in PHR-L/T2DM, PHR-H/Non-T2DM, PHR-L/Non-T2DM had significantly decreased risk of MACEs [adjusted hazard ratio (aHR): 0.83, 95% confidence interval (CI): 0.73-0.96, P =0.009; aHR: 0.81, 95% CI: 0.69-0.95, P =0.009; aHR: 0.70, 95% CI: 0.60-0.83, P <0.001; respectively]. Cox regression analysis also indicated the highest risk of MACEs among patients in PHR-H/T2DM group than in other groups (P for trend <0.001). Restricted cubic spline analyses revealed positive linear associations of PHR with MACEs, all-cause death, and unplanned target vessel revascularization, while a significant non-linear relationship between PHR and myocardial infarction. Additionally, subgroup analysis indicated consistent effects on MACEs within diverse subsets.

Elevated PHR levels combined with T2DM were associated with worse clinical outcomes after PCI at 1-year follow-up. The PHR may serve as a valuable predictor for identifying high-risk patients post-PCI, particularly in diabetic cohorts.

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2Dm) are increasingly recognized as interrelated metabolic disorders, each contributing to the other's progression. NAFLD, a leading cause of chronic liver disease globally, is often underdiagnosed due to its asymptomatic nature. The startlingly high frequency of NAFLD, especially in those with T2Dm, emphasizes the need of thorough screening in high-risk groups. In the setting of T2Dm, the pathophysiology of NAFLD comprises intricate metabolic pathways that exacerbate the disease's progression. These pathways include insulin resistance, lipotoxicity, and chronic inflammation. Early diagnosis and timely intervention are crucial to prevent the advancement of NAFLD to more severe stages, such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Current guidelines advocate for routine NAFLD screening in patients with T2Dm, emphasizing the importance of early detection. Therapeutic approaches have evolved that are pivotal in managing these intertwined conditions. Each of these treatments offers unique benefits, from improving glycemic control to mitigating liver fat accumulation and reducing cardiovascular risks. This review highlights the pathophysiological linkages, clinical implications, and therapeutic advancements in managing these conditions. By exploring global prevalence, emerging diagnostic tools, and novel therapies, we propose an integrative framework for improved patient outcomes.

Periodontitis is a prevalent chronic infectious and inflammatory disease worldwide, which imposes harms extending far beyond the oral cavity. A large body of research has demonstrated that periodontitis is closely associated with various systemic diseases, such as diabetes mellitus, cardiovascular diseases, inflammatory bowel disease, and rheumatoid arthritis. Serving as a crucial pathway connecting the oral cavity to the entire body, the oral-gut axis becomes the core mechanism through which periodontitis affects systemic health, primarily via the ectopic colonization of salivary microbiota, intestinal dysbiosis, intestinal barrier disruption, and systemic inflammation. This review summarizes recent studies focusing on how periodontitis influences systemic comorbidities via the oral-gut axis, encompassing clinical studies, animal experimental and in vitro research. We summarize the research progress regarding how periodontitis perturbs intestinal homeostasis through ectopic colonization of oral pathogenic bacteria, immunoinflammation, host factor regulation, and metabolic disorders, and eventually affects systemic diseases via the oral-gut axis. This review aims to provide a new perspective for the prevention and treatment of periodontitis-related systemic comorbidities.

Among the side effects of diabetes mellitus is diabetic nephropathy, the main reason for end-stage kidney disease linked to increased mortality and morbidity. Early diagnostic biomarkers for diabetic nephropathy are required to stop or even slow down the progression of the disease and to administer the most appropriate protective treatments on time. Therefore, it is essential to study additional potential biomarkers for the early diagnosis of diabetic nephropathy. This study aims to evaluate elabela, FABP1, and FABP2 levels synergistically as a new diagnostic tool for the early detection of diabetic nephropathy in type 2 diabetic patients. This study was conducted on 95 subjects (75 patients with type 2 diabetes and 20 healthy controls). Type 2 diabetic patients were divided based on their urinary ACR into three groups: normal albuminuria, microalbuminuria (early nephropathy), and macroalbuminuria (overt nephropathy), and compared to healthy controls. Serum elabela, FABP1, and FABP2 levels and some biochemical parameters were evaluated. The level of serum elabela significantly decreased (P < 0.05), while FABP1 and FABP2 levels significantly increased (P < 0.05) with the increase in the severity of diabetic nephropathy compared to the control group. There were significant negative correlations between elabela and FABP1, FABP2, and urinary ACR and significant positive correlations with eGFR in all patient groups. FABP1 and FABP2 levels showed significant negative correlations with eGFR and significant positive correlations with urinary ACR. Multiple linear regression analysis illustrated a significant effect of urinary ACR on the three biomarkers in all studied groups. ROC curve analysis demonstrated that the combination of elabela, FABP1, and FABP2 had the highest diagnostic performance with an AUC of 1.0 (P = 0.001), and the sensitivity and specificity reached 100% in all patient groups compared to the control group. In conclusion, elabela, FABP1, and FABP2 may be potential new biomarkers of diabetic nephropathy. Combining these three biomarkers can be used synergistically as a diagnostic tool for the early diagnosis of diabetic nephropathy in type 2 diabetic patients.

The online version contains supplementary material available at 10.1007/s12291-024-01231-x.

Type 2 diabetes mellitus (T2DM) is increasingly recognized as a major risk factor for Alzheimer's disease (AD), with mounting evidence highlighting shared pathophysiological mechanisms. This review explores the intricate biological and molecular links between these two chronic disorders. Key overlapping pathways include impaired insulin signaling, chronic inflammation, oxidative stress, mitochondrial dysfunction, amyloid-beta (Aβ) accumulation, tau hyperphosphorylation, and the formation of advanced glycation end-products (AGEs). Disruption of insulin signaling in the brain contributes to synaptic loss and neurodegeneration, while systemic metabolic disturbances aggravate blood-brain barrier dysfunction and neurovascular damage. Emerging studies also underscore the role of antidiabetic treatments, especially newer agents targeting the gut-brain axis, in modulating AD progression. The review further examines preclinical models, clinical observations, and the development of biomarkers to improve early detection and intervention. Despite growing insights, challenges remain in translating mechanistic knowledge into effective therapies. A multidisciplinary approach integrating metabolic control and neuroprotective strategies is essential for addressing the comorbid burden of T2DM and AD. See also the graphical abstract(Fig. 1).

Fructose-1,6-bisphosphatase (FBPase) is a key gluconeogenic enzyme and an attractive target for type 2 diabetes mellitus (T2DM); however, clinical progress has been limited by known inhibitor binding sites. Here, we report the cocrystal structure of human FBPase (HuFBPase) bound to a sulfonylurea-based inhibitor (compound 5, IC₅₀ = 2.93 μM) at a previously unrecognized cryptic allosteric pocket. Compound 5 engages this site via π-π stacking with Y57 and extensive hydrogen-bond interactions, induces conformational rearrangement of K72 and D74, and facilitates the formation of a hydrogen-bond network with S123 that disrupts substrate catalysis. Structure-guided optimization yielded compound 29 with improved potency (IC₅₀ = 0.75 μM). Cellular target engagement was confirmed by thermal stabilization of FBPase in LO2 cells. Notably, compound 29 exhibited hypoglycemic activity in vivo, providing the first evidence that targeting this pocket confers therapeutic benefit. Collectively, our findings establish a novel, druggable allosteric site on HuFBPase for T2DM treatment.

 Type 1 diabetes mellitus is the most common endocrine-metabolic disorder in childhood and adolescence. Some families may find it difficult to administer four daily injections, especially in young children, or to use the newer, expensive insulin analogs and pumps. For this reason, many physicians are still using the classical two-injection schedule, using premixed insulin in certain areas of the world.

 To assess glycemic control and complication indicators in type 1 diabetic children on premixed or basal-bolus insulin.

 One hundred children aged 2-14 years with type 1 diabetes mellitus were studied at multiple diabetes care centers; fifty were receiving premixed insulin, and the other fifty were on a basal-bolus insulin regimen. Evaluations were made based on HbA1c levels, occurrences of hypoglycemia, ketoacidosis, and other complications.

 The study revealed significant improvements in HbA1c levels in the basal-bolus insulin group compared to premixed insulin patients three and six months after treatment (p=0.048 and p=0.005, respectively). Patients using the premixed regimen experienced more frequent hypoglycemia attacks (p=0.001) and injection site complications, such as hypertrophy (p=0.001).

 It has been revealed that a basal-bolus regimen (MDI) improves children's and teenagers' glycemic control with fewer complications.

Non-healing ulcers pose a serious problem for public health due to the high cost of treatment, prolonged disability of patients, and low efficacy of therapy. They are the leading cause of non-traumatic lower limb amputations.The development of innovative bioengineering products is a significant step in the treatment of non-healing diabetic foot ulcers. One such product is a tissue-engineered acellular product made from highly regenerative human umbilical cord biomaterial. It contains growth factors, cytokines, and components of the extracellular matrix of Wharton's jelly, which accelerates wound healing.THE AIM of this clinical study is to evaluate the safety and efficacy of a tissue-engineered acellular product from Wharton's jelly of the umbilical cord for the treatment of chronic non-healing lower limb ulcers in patients with diabetic foot syndrome.RESULTS: a 60-year-old woman diagnosed with type 2 diabetes mellitus had chronic ulcers that had not responded to standard treatment for more than a year and a half. She was observed for 4 weeks in August 2024. As a result of the local application of an acellular product from human umbilical cord, signs of reduction in wound size and their complete healing were noted 4 weeks after the start of observation.CONCLUSION: clinical observation has demonstrated the safety and efficacy of the acellular product from human umbilical cord for the treatment of chronic non-healing ulcers of diabetic origin.