Metabolic surgery has emerged as an important therapeutic option for the management of type 2 diabetes mellitus (T2DM) and obesity and has gained increasing clinical attention in recent years. Ongoing research has expanded the understanding of various surgical techniques and their therapeutic efficacy. Nevertheless, concerns related to postoperative diabetes recurrence and the prevention and management of procedure-related complications continue to constrain the routine application of metabolic surgery in T2DM care. This review provides a systematic overview of the principal metabolic surgical procedures primarily used in the management of T2DM, compares their efficacy, and examines the incidence and management of associated complications. In addition, preoperative predictors of surgical outcomes are evaluated, and long-term postoperative effectiveness is reviewed. By synthesizing recent evidence, this review aims to offer clinicians and researchers a coherent theoretical framework and practical insights to support the incorporation of metabolic surgery into comprehensive multimodal strategies for diabetes management.

Diabetic foot (DF)-related amputation remains a major cause of morbidity in patients with type 2 diabetes, yet biomarkers associated with amputation risk remain limited. We aimed to assess the independent association between a deep learning (DL)-derived retinal biomarker using coronary artery calcification (Dr. Noon CVD) and DF-related amputation in patients with type 2 diabetes. This retrospective observational study conducted in a university hospital in South Korea included 392 individuals with type 2 diabetes receiving ophthalmic care (79 with DF-related amputation and 313 without). Participants were randomly split into training (70%) and validation (30%) sets. Model performance in relation to DF-related amputation was assessed using area under the receiver operating characteristic curve (AUC), continuous net reclassification index (cNRI), and integrated discrimination improvement (IDI). Prespecified rule-out (sensitivity ≥0.85) and rule-in (specificity ≥0.90) thresholds were also applied. Adding the retinal biomarker to a basic clinical model showed incremental association with DF-related amputation in the validation set (AUC 0.146, 95% CI: 0.046-0.249; cNRI 0.629, 95% CI: 0.184-1.027; IDI 0.062, 95% CI: 0.012-0.110). The full model achieved an AUC of 0.791, and the association remained consistent across sensitivity analyses using DF risk score derived from the external dataset. Under a 27% amputation prevalence (based on the reported prevalence of amputation among patients with diabetic foot), sensitivity was 87.5% with a negative predictive value of 92.6% at the rule-out cutoff; specificity was 90.4% with a positive predictive value of 56.3% at the rule-in cutoff. A DL-derived retinal biomarker shows meaningful association with DF-related amputation beyond conventional diabetes variables.

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used in patients with type 2 diabetes and obesity. Although tirzepatide improves metabolic and cardiovascular risk factors, its association with venous thromboembolism, including pulmonary embolism and deep vein thrombosis, remains insufficiently characterized in real-world populations.

We conducted a population-based retrospective cohort study using the TriNetX US Collaborative Network. Adults with type 2 diabetes and overweight or obesity who initiated tirzepatide were propensity score matched to patients receiving lifestyle intervention alone with no exposure to weight-loss medications. Outcomes included incident pulmonary embolism, deep vein thrombosis, and superficial vein thrombosis occurring between 30 days and 12 months after index. Additional analyses included a 90-day landmark sensitivity analysis and an active comparator analysis comparing tirzepatide with semaglutide.

After propensity score matching for demographic, metabolic, and clinical covariates, 235, 200 patients were included in the primary analysis (117, 600 per cohort). Tirzepatide use was associated with a significantly lower 12-month risk of pulmonary embolism compared with lifestyle intervention alone (RR, 0.215; 95% CI, 0.185-0.250; HR, 0.258; 95% CI, 0.222-0.299; log-rank P < 0.001). Similar reductions were observed for deep vein thrombosis (RR, 0.303; 95% CI, 0.270-0.340; HR, 0.361; 95% CI, 0.322-0.406; log-rank P < 0.001). No statistically significant difference was observed for superficial vein thrombosis (RR, 0.716; 95% CI, 0.484-1.060; HR, 0.868; 95% CI, 0.586-1.286; log-rank P = 0.480). Findings for pulmonary embolism and deep vein thrombosis remained significant in the 90-day landmark analysis. In the semaglutide comparator analysis, tirzepatide was associated with a significantly lower risk of deep vein thrombosis, while the pulmonary embolism association was significant by risk-ratio analysis but not by Cox regression.

In this large multicenter cohort study, tirzepatide use was associated with a lower risk of pulmonary embolism and deep vein thrombosis compared with lifestyle intervention alone. These findings suggest a potential association between tirzepatide use and lower observed rates of thromboembolic events in patients with diabetes and obesity.

Osteoporosis is a prevalent yet underdiagnosed complication in patients with type 2 diabetes mellitus (T2DM), significantly increasing the risk of fractures and mortality. However, current screening tools are limited by low accuracy and lack of generalizability. This multicenter cross-sectional study aimed to develop and validate a multimodal interpretable machine learning (ML) model integrating multimodal data to identify and classify osteoporosis risk in T2DM patients, with a focus on clinical translatability.

We retrospectively enrolled 1,002 T2DM patients from two tertiary hospitals in China. After exclusions, Cohort 1 (n = 852) was used for model development and internal validation, and Cohort 2 (n = 126) served as an independent external validation set. Multimodal data included demographics, laboratory tests, abdominal CT-derived parameters (e.g., skeletal muscle index at L3, SMI-L3), and composite metabolic indices (e.g., lymphocyte-to-HDL ratio [LHR], Metabolic Score for Visceral Fat [METS-VF]). Core predictors were selected using univariate analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and the Boruta algorithm. Seven ML algorithms were compared, with model performance evaluated by area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, F1-score, and area under the precision-recall curve (AUPRC). The SHapley Additive exPlanations (SHAP) method was applied for model interpretability.

Seven predictors were identified: age, hemoglobin, neutrophil count, uric acid, LHR, SMI-L3, and METS-VF. The eXtreme Gradient Boosting (XGBoost) model demonstrated superior performance, achieving an AUC of 0.877 (95% confidence interval [CI]: 0.830-0.923) in the training set and 0.911 (95% CI: 0.879-0.943) in the external validation set. SHAP analysis revealed age, hemoglobin, and uric acid as the top contributors. Calibration and decision curve analyses confirmed the model's clinical utility.

This study presents a robust, multimodal interpretable ML model for osteoporosis risk prediction in T2DM using routinely available clinical data. By integrating multimodal features and providing transparent predictions via SHAP, the model offers a proof-of-concept tool for opportunistic screening to facilitate targeted dual-energy X-ray absorptiometry (DXA) referral, although prospective clinical validation is needed before its clinical utility can be established.

Type 2 diabetes mellitus (T2DM) and thyroid nodules are both prevalent endocrine conditions; the prevalence of comorbidity between the two continues to rise. However, the independent and interactive effects of age and body mass index (BMI) on the development of thyroid nodules in patients with T2DM remain unclear. The objective of this study is to examine the correlation between age, BMI, and their interaction with the risk of developing thyroid nodules in patients with T2DM.

A retrospective study encompassed 720 hospitalised T2DM patients. The patients were divided into two groups based on the findings of thyroid ultrasound scans: a thyroid nodule group (n=599) and a non-thyroid nodule group (n=121). A comparison was made between the baseline clinical characteristics of the two groups. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for thyroid nodules, and stratified analyses and interaction tests were conducted to assess the interaction between age and BMI.

Multivariate logistic regression analysis showed that age was an independent risk factor for thyroid nodules in patients with T2DM (P<0.001), and the risk of thyroid nodules in patients aged 45-60 years and ≥60 years was 5.12 times and 9.07 times that of patients aged <45 years, respectively. BMI was an independent protective factor (P<0.05), and the risk of thyroid nodules in patients with BMI 24-28 kg/m² and ≥28 kg/m² was 0.52 times and 0.46 times that of patients with BMI <24 kg/m², respectively. There was a significant interaction between age and BMI (OR = 1.26, 95% CI: 1.08-1.47, P = 0.003). Stratified analysis showed that in the subgroup with BMI ≥24 kg/m², the promoting effect of age on thyroid nodules was more obvious; in the subgroup aged <45 years, the protective effect of BMI was more prominent; in the subgroup aged 45-60 years, BMI ≥28 kg/m² became a risk factor (OR = 8.30, 95% CI: 1.42-48.56, P = 0.019).

Age and BMI have independent and interactive effects on the risk of thyroid nodules in hospitalised T2DM patients. However, the findings may not be generalizable to community-dwelling or outpatient T2DM patients without further validation.

Maturity Onset Diabetes of the Young (MODY) remains an underdiagnosed condition with remarkable genetic variability across populations. While diagnostic tools are based on Caucasian cohorts, Whole Exome Sequencing (WES) studies are needed to identify new genes in non-Caucasians, as up to 77% of patients do not harbor variants of significance in MODY-known genes. No WES studies have addressed the genomic landscape of MODY beyond its canonical genes in Latino populations. We aimed to characterize the genomic landscape of MODY through WES in a Mexican cohort, comparing cases with type 2 diabetes mellitus (T2DM) patients and healthy controls (HC).

WES was performed in 17 patients with MODY, 17 with T2DM and 17 HC. We compared the single nucleotide variant landscape across groups in MODY-known genes and searched for genetic variants with differential enrichment across groups.

MODY genes used for routine diagnosis showed low discrimination utility, as patients with MODY, T2DM and HC harbored genetic variants in MODY-known genes at similar frequencies in most cases. We found 14 genes with variants capable of distinguishing MODY from T2DM and HC. Variants in genes such as MAP2K3, SYT15, KCNJ12, PEX5, and TPTE were found in 75-100% of MODY cases while absent in T2DM and HC. Enrichment analysis revealed involvement in synaptic vesicle trafficking, insulin/IGF pathway-mitogen activated protein kinase kinase/MAPK, and insulin/IGF pathway-protein kinase B/AKT signaling.

MODY presents a complex genetic architecture in the Mexican population. Besides improving our understanding of glycemic regulation pathways, identified genes may serve as diagnostic biomarkers.

Acute limb ischemia is a vascular emergency that requires prompt diagnosis and treatment to avoid permanent tissue loss and possible amputation. Recurrent arterial thrombosis in a relatively young patient, especially while on anticoagulation, should raise concern for an underlying hypercoagulable state. We present the case of a 40-year-old woman with type 2 diabetes mellitus, hyperlipidemia, and heavy tobacco use who developed acute right lower extremity ischemia after sitting with her legs crossed for several hours during an episode of severe vomiting and diarrhea. She underwent emergent thromboembolectomy and was discharged on apixaban and aspirin. About two weeks later, she returned with recurrent right lower extremity ischemia despite reported compliance with anticoagulation and was found to have multifocal arterial thrombosis requiring repeat thromboembolectomy and pedal arch angioplasty. Her postoperative leukocytosis was felt to be reactive and related to ischemia-reperfusion injury rather than infection. Because of recurrent arterial thrombosis despite apixaban therapy, further workup for antiphospholipid syndrome was initiated, and she was transitioned to heparin with recommendation for long-term warfarin therapy. This case highlights that mechanical compression may have contributed to the initial lower extremity ischemic event; however, the subsequent recurrent arterial thromboses, particularly at anatomically distinct sites despite direct oral anticoagulant (DOAC) therapy, were more concerning for an underlying systemic hypercoagulable state such as antiphospholipid syndrome in the setting of additional vascular risk factors.

We aim to delve into the characteristics of endogenous endophthalmitis caused by Klebsiella pneumoniae, focusing on the clinical manifestations, systemic risk factors, sources of the microorganism, and treatment outcomes among patients in our clinical series. All patients exhibited the classic symptoms of eye pain, redness, and reduced vision, with discernible risk factors of diabetes mellitus. In all cases, there were identifiable sources of bacteremia, most prominently liver abscess, followed by pneumonia and hand abscess. From the vitreous, positive cultures were obtained in all five cases, and all patients demonstrated bacteremia with positive Klebsiella growth. Late-stage unsalvageable presentations were observed in three cases, necessitating evisceration of the eye. One patient succumbed to sepsis with multiorgan failure. Despite prompt management of Klebsiella endophthalmitis, all patients in this clinical series had unfavorable visual or survival outcomes. Prevention in the form of good systemic control in patients with diabetes is crucial to prevent this life and sight-threatening complication.

 Diabetes mellitus is an independent risk factor for complications following orthopedic shoulder procedures. Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are effective agents that manage type 2 diabetes, but their differential effects on perioperative and long-term shoulder outcomes remain unclear.

 We conducted a retrospective cohort study using the TriNetX Research Network, identifying adults (≥18 years) with type 2 diabetes who underwent orthopedic shoulder procedures and were prescribed either a DPP-4 inhibitor or a GLP-1 receptor agonist. Propensity score matching was performed (1:1), adjusting for demographics, comorbidities, and procedure type, yielding 632 patients per cohort. Outcomes included rates of reoperation at one and two years postoperatively and postoperative opioid use.

 At one- and two-year follow-up, rates of reoperation were similar between cohorts. DPP-4 users had significantly higher early postoperative opioid use compared with GLP-1 users (RR: 1.754; 95% CI: 1.440-2.137; p < 0.001), whereas prolonged and chronic postoperative opioid use were similar between cohorts.

 In patients with type 2 diabetes undergoing orthopedic shoulder procedures, DPP-4 inhibitors and GLP-1 receptor agonists demonstrated comparable long-term surgical outcomes, including reoperation rates at one and two years postoperatively. However, early postoperative opioid use was significantly higher among DPP-4 users, while prolonged and chronic opioid utilization were similar between cohorts. These findings support the perioperative safety of both incretin-based therapies and suggest that GLP-1 receptor agonists may confer additional benefit through potential central pain-modulating effects that reduce early postoperative opioid requirements.

Background Diabetes mellitus increases the risk of postoperative complications following orthopedic shoulder surgery. Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely prescribed for glycemic control in type 2 diabetes mellitus, yet their influence on perioperative and long-term postoperative outcomes remains unclear.  Methods A retrospective cohort study was conducted using the TriNetX Research Network to identify adults (≥18 years) with type 2 diabetes who underwent orthopedic shoulder procedures and were either prescribed or not prescribed a DPP-4 inhibitor. After 1:1 propensity score matching for demographics, comorbidities, and procedure type, 834 patients were included in each cohort. Outcomes included 30-day emergency department (ED) visits, one- and two-year reoperation rates, and postoperative opioid use.  Results ED visits and reoperation rates at one and two years were similar between cohorts. DPP-4 inhibitor users demonstrated significantly lower rates of early postoperative opioid use compared with non-users (33.6% vs. 45.3%; RR: 0.741; 95% CI: 0.656-0.836; p < 0.001). No significant difference was observed in prolonged opioid use (21.5% vs. 21.2%; RR: 1.011; 95% CI: 0.841-1.216; p = 0.952). However, DPP-4 users had significantly higher rates of chronic postoperative opioid use (21.2% vs. 13.7%; RR: 1.553; 95% CI: 1.252-1.925; p < 0.001). Conclusion DPP-4 inhibitor exposure within six months prior to shoulder surgery was not associated with differences in long-term surgical outcomes or early emergency medical utilization among patients with type 2 diabetes. However, DPP-4 users demonstrated lower early but higher chronic postoperative opioid use, suggesting that incretin pathway modulation may have time-dependent effects on postoperative pain physiology. These findings suggest a potential link between metabolic therapy and postoperative pain adaptation and warrant further investigation into the underlying mechanisms.