Expert Review of Endocrinology & Metabolism最新文献

Introduction: Diabetic foot infections (DFIs) and diabetic foot osteomyelitis (DFO) are common and serious complications in patients with diabetes, often leading to severe morbidity (including amputation) and even mortality. Professional footcare, prompt diagnosis and appropriate treatment are crucial to preventing limb loss and improving outcomes in infections.

Areas covered: This narrative review addresses the management of all DFIs, including the approach to clinical evaluation, appropriate diagnostic methods, and optimal therapeutic strategies. We specifically address key areas in antibiotic therapy, and surgical interventions and techniques. Based on our literature review and extensive, multidisciplinary experience, we developed a novel treatment flowchart specifically for the management of DFO.

Expert opinion: Managing DFIs, including DFO, requires a multidisciplinary approach tailored to each patient's clinical presentation. While antibiotics, surgery, and wound care each play a crucial role, the decision-making process should always consider the infection's severity and chronicity. Our proposed flowchart for DFO management emphasizes the importance of logically-sequenced, easy to apply and tailored interventions to prevent unnecessary amputations and improve outcomes. Further research is needed to further refine this flowchart in clinical practice and demonstrate its effectiveness.

Background: Skeletal muscle is the key target of insulin action. Therefore, a reduction in skeletal muscle mass may trigger insulin resistance, a mechanism of diabetes. Creatinine is the only metabolite of creatine phosphate in the skeletal muscle. Exploring the association between serum creatinine level and T2DM is helpful for the early identification and prevention of T2DM.

Research design and methods: Five electronic databases, PubMed, Scopus, Web of Science, Embase, and Epistemonikos, were searched for relevant articles published up to June 2024. Cohort studies and case-control studies were evaluated using the Joanna Briggs Institute (JBI) checklist. The random-effects model calculated the pooled risk ratio and 95% confidence intervals (CIs) based on a heterogeneity test (I² statistics). Egger's test was used to evaluate publication bias.

Results: The pooled RR of diabetes type 2 for the lowest versus the highest serum creatinine was 1.39 (95% CI: 1.17-1.64); I² = 90.1%; p = 0.002. We found a non-linear association between low serum creatinine level and T2DM risk (p_Nonlinearity = 0.02), and a decrease of each 0.1 mg/dL serum creatinine increases 1% risk of T2DM [RR = 1.49 (95% CI: 1.17-2.82), I² = 0%, p = 0.999].

Conclusions: This meta-analysis offers evidence of the negative relationship between serum creatinine levels and the risk of developing T2DM in a linear dose-response pattern.

Background: Interest has grown in glucagon-like peptide-1 receptor-agonist (GLP-1 RA) semaglutide long-term outcomes. This retrospective cohort study compared effectiveness of oral and subcutaneous semaglutide for weight loss outcomes in adults with type 2 diabetes (T2D) over a 2-year treatment period.

Research design and methods: Weight loss was evaluated through mean percentage change from baseline, proportion achieving at least 5% weight loss and at least 10% weight loss comparing subcutaneous (n = 310) versus oral users (n = 57) and by age group.

Results: Subcutaneous users experienced a mean percentage weight loss of 7.5% (16.7 pounds) with 58.7% and 32.9% achieving ≥5% and ≥10% loss, respectively. Oral users lost 4.4% (8.7 pounds) with 50.9% and 17.5% achieving ≥5% and ≥10% loss, respectively. Significant differences existed between formulations in mean percentage weight change (p-value <0.01) and proportion achieving ≥10% loss (p-value = 0.03), but not in proportion achieving ≥5% loss (p-value = 0.34). Outcomes differed by age within oral semaglutide (p-value = 0.02). Regression analyses adjusted for confounders yielded similar findings.

Conclusion: Subcutaneous users achieved superior weight loss compared to oral users. Older oral users experienced better weight loss compared to younger users. However, no differences were observed between subcutaneous users.

Background: Glucagon-like peptide-1 (GLP-1) agonists are commonly prescribed for type 2 diabetes mellitus (T2DM). Concerns have emerged regarding their potential link to diabetic retinopathy (DR).

Methods: To evaluate the association between GLP-1 agonists and DR, a disproportionality analysis was conducted using FDA Adverse Event Reporting System (FAERS) data from Q4/2003 to Q2/2024 via OpenVigil 2.1 software. We focused on GLP-1 agonists and glucose-dependent insulinotropic polypeptide (GIP) agonist: Semaglutide, liraglutide, dulaglutide, lixisenatide, and tirzepatide, as primary suspect drugs. 'Diabetic retinopathy' was the key search term mapped to Medical Dictionary for Regulatory Activities (MedDRA) Lower-Level Terms (LLTs). We calculated Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), with 95% confidence intervals (CI) and the Evans' criteria were applied to check the significant associations.

Results: Semaglutide (PRR: 19.43, 95% CI: 15.17-24.88; ROR: 19.48, 95% CI: 15.20-24.96; Chi-square: 1078.08) and dulaglutide (PRR: 9.01, 95% CI: 7.11-11.42; ROR: 9.02, 95% CI: 7.11-11.44; Chi-square: 478.31) showed a strong association with DR. Tirzepatide and liraglutide showed a weaker but significant association while lixisenatide showed no significant association.

Conclusion: GLP-1 agonists (except lixisenatide) were found to be associated with DR. These findings emphasize the need for close monitoring and further research to clarify these associations.

Introduction: Many patients struggle to control glucose without side effects. Due to their immunomodulatory and regenerative properties, mesenchymal stem cells (MSCs) might treat Diabetes Mellitus (DM). The authors employed this meta-analysis to evaluate the efficacy and safety of umbilical cord MSCs (UCMSCs) for DM management.

Methods: The PubMed, Cochrane, WOS, Embase, and Scopus databases were searched for randomized controlled trials (RCTs) investigating the effects of UCMSCs on DM (Types 1, 2) till January 2024. Patient demographics, interventions, and outcomes, including glycated hemoglobin (HbA1c%), C-peptide levels, and insulin requirements, were extracted. A comprehensive meta-analysis software was used.

Results: Eight CTs of 334 patients (172 experimental and 162 controls) were included. UMSCs treatment substantially lowered HbA1c levels (MD = -1.06, 95% CI [-1.27, -0.85], p < 0.00001) with consistent outcomes (i² = 0%, p = 0.43). Fasting C-peptide levels were heterogeneous but favored placebo (MD = 0.35, 95% CI [0.15, 0.56], p = 0.0007). In T1D patients, daily insulin requirements decreased considerably (MD = -0.24, 95% CI [-0.29, -0.18], p < 0.00001), with heterogeneity addressed by sensitivity analysis.

Conclusion: UMSCs therapy reduced HbA1c and insulin requirements, and increased C-peptide levels. Multicenter clinical trials are required to confirm the long-term efficacy and safety of UMSC therapy.

Objective: Anaplastic thyroid carcinoma (ATC) is a rare and aggressive thyroid neoplasm. This study is the largest to date and aims to provide the most up-to-date analysis of demographics and clinicopathological factors of ATC.

Methods: Data for this study were extracted from the Surveillance, Epidemiology, and End Results (SEER) database.

Results: A total of 1,769 cases of ATC were included with a median age at diagnosis was 71 years, and 59% were females. The most common site of metastasis was the lung (40.7%). The majority of patients underwent combination therapy (surgery with adjuvant chemoradiation) (19.2%). The 5-year OS was 7.3% (95% C.I. 6.6-8.0). The 5-year CSS was 11.8% (95% C.I. 10.8-12.8). The highest 5-year survival was observed with combination therapy (surgery with adjuvant chemoradiation) at 20.9%. Multivariable analysis revealed that age >60 years, Asian/Pacific Islander, >2 cm tumor size, and metastatic disease were independent risk factors.

Conclusions: ATC is an uncommon tumor that mainly affects Caucasian females in their 70s. Older age, Asian/Pacific Islander race, and larger tumor size (>2 cm) were also associated with a worse prognosis. For better comprehension of pathogenesis, prospective clinical trials should include patients from all ethnicities, gender, and genomic analysis of ATC.

Background: Hypothyroidism (HT) is associated with different comorbidities comprising increased arterial stiffness and decreased flow-mediated dilatation. The exact pathological mechanism of endothelial activation and dysfunction (ED) in HT remains unknown. We conducted a systematic review and meta-analyses to provide an overview of the pathogenesis of ED in HT.

Methods: The literature search was done in February 2024 for studies analyzing traditional and novel circulating biomarkers of ED in patients with HT, including cytokines and chemokines. Random-effect models were used except when no heterogeneity was found. Protocol was registered under the number PROSPERO CRD42024540560.

Results: 25 macromolecules and 66 studies were entered into analyses. HT was associated with increased levels of E-selectin, soluble intercellular adhesion molecule-1, osteoprotegerin, and oxidized-LDL (p < 0.02). Results were not conclusive for endothelin-1. Interleukin (IL)-6, IL-12 and CXCL10 were higher in HT (p < 0.05). Subjects with overt HT may display a proinflammatory tendency with increased levels of IL-6 and interferon-γ, and decreased levels of TGF-β (p < 0.05).

Conclusions: The data presented and discussed here highlights the association between HT and soluble biomarkers of ED. Inflammatory mediators released by activated T-cells and macrophages may aggravate local and systemic inflammation, which arouses more inflammation, forming a vicious circle leading to ED.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are known for their cardiovascular benefits, but their impact on serum uric acid levels is not well understood. This study evaluates the hypouricemic effects of SGLT2is and their potential cardiovascular implications.

Methods: A network meta-analysis was performed, including 56 studies (16,788 participants) contributing data to the meta-analysis. The effects of SGLT2is on serum uric acid levels were analyzed with weighted mean difference (WMD) as the effect estimate. Bootstrapped meta-analysis, trial sequential analysis, and meta-regression were utilized to validate the findings and assess the influence of covariates. The certainty of the evidence was evaluated.

Results: The analysis revealed that SGLT2is significantly reduced serum uric acid levels (WMD: -40.01 μmol/L). Specific reductions were noted for ertugliflozin (-42.17 μmol/L), dapagliflozin (-40.28 μmol/L), empagliflozin (-46.75 μmol/L), canagliflozin (-35.55 μmol/L), and ipragliflozin (-10.48 μmol/L). Both low and high doses were effective, with empagliflozin showing the highest efficacy. No significant associations were found with covariates. The evidence was of moderate certainty.

Conclusion: SGLT2is significantly lower serum uric acid levels, with empagliflozin being the most effective. These findings suggest a potential role in reducing cardiovascular risk. Further research is needed to explore their effects on hyperuricemic patients, and monitoring serum uric acid levels is recommended.

Background: The role of diabetes mellitus (DM) in hospitalized COVID-19 patients and of HbA1c in hospitalized COVID-19 patients with DM were not studied adequately in the past.

Research design and methods: It was a retrospective cohort study. In this study, data from 305 hospitalized COVID-19 patients was analyzed. The study objective was to determine the association of DM with in-hospital mortality in COVID-19 patients. Another study objective was to determine the association of HbA1c with mortality in COVID-19 patients with DM.

Results: In this retrospective study, DM was present in 41.3% (126/305) of the study population. The multivariate Cox regression analysis showed a significant association between DM and mortality (adjusted hazard ratio (aHR): 2.116, 95% CI: 1.088-4.116, p = 0.027). The median HbA1c in diabetic patients was 8.9% (7.5-11.0). HbA1c was found to be associated with mortality in diabetic patients in the multivariate cox-regression analysis (aHR:1.272, 95% CI: 1.028-1.574, p = 0.027). The multivariate Cox regression analysis also showed the association of HbA1c (10.5%≤HbA1c > 10.5%) as a dichotomous variable with in-hospital mortality (aHR: 2.53, 95% CI: 2.606-194.81, p = 0.005) in diabetic patients.

Conclusions: DM was independently associated with mortality in hospitalized COVID-19 patients in the multivariate analysis. In COVID-19 patients with DM, HbA1c was associated with mortality as a continuous and dichotomous variable in the multivariate analysis.

Background: Diabetes mellitus (DM) is an important cause of morbidity and mortality worldwide. DM patients develop both macrovascular and microvascular complications, erectile dysfunction (ED) being one of them. The risk of developing ED in DM patients as compared to those without DM is 3-4 times. Our study has reported the burden of ED in DM patients.

Methods: Literature search was done by using PubMed and EMBASE databases for studies published from 1 January 2013 to 31 December 2013 by using terms such as diabetes, erectile dysfunction, and their synonyms. Pooled prevalence was calculated by using random effect model and Der Simonian-Laird method. Joanna Briggs Institute (JBI) Critical Appraisal scale for cross-sectional studies was used for assessing the study quality.

Results: Five hundred and sixty-seven studies were identified, out of which 10 studies were selected. The prevalence of ED in Type 2 DM patients in India was estimated 60.57% (95% CI: 48.84-72.30%).

Conclusion: Prevalence of ED in DM patients is high in India. Stigma, stress, and phobia related to ED needs to be addressed. Screening, awareness, early diagnosis, and management for ED and DM will help in improving morbidity and mortality of the nation.