Cardiovascular diabetology. Endocrinology reports最新文献

{"title":"Diagnostic accuracy of the COMPASS-31 orthostatic intolerance domain for detecting cardiovascular autonomic neuropathy in resource-limited settings.","authors":"Hassan Thabit Haji, Ramla Muhidin Ali, Ahmed Gharib Khamis, Marina Njelekela, Kaushik Ramaiya, Fredirick L Mashili","doi":"10.1186/s40842-026-00313-4","DOIUrl":"10.1186/s40842-026-00313-4","url":null,"abstract":"<p><strong>Background: </strong>Cardiac autonomic neuropathy (CAN) is a frequent but under-recognized complication of type 2 diabetes mellitus (T2DM) that is strongly associated with arrhythmia, silent myocardial ischemia, and cardiovascular mortality. The use of cardiovascular autonomic reflex tests (CARTs) to assess CAN is often limited in resource-constrained clinical settings. Therefore, symptom-based tools such as the Composite Autonomic Symptom Score-31 (COMPASS-31) have been proposed as screening approaches, but evidence on their feasibility remains scarce. This study assessed the feasibility, diagnostic accuracy, and agreement of the COMPASS-31 for identifying cardiovascular autonomic dysfunction assessed using standardized CARTs among adults with T2DM in Zanzibar.</p><p><strong>Methods: </strong>A cross-sectional study was conducted among adults with T2DM attending the diabetes clinic at Mnazi Mmoja Hospital, Zanzibar. Participants were recruited using a systematic random sampling technique. Orthostatic symptoms were assessed using the COMPASS-31 questionnaire. Objective autonomic function was assessed using an automated CAN analyser implementing standardized CARTs, including resting heart rate variability, deep breathing test, Valsalva maneuver, heart rate response to standing, postural hypotension, and sustained handgrip test. Agreement between the COMPASS-31 orthostatic intolerance domain and CARTs findings was assessed using Cohen's kappa. Diagnostic performance measures included sensitivity, specificity, predictive values, likelihood ratios, and accuracy.</p><p><strong>Results: </strong>Among 364 participants, the COMPASS-31 orthostatic intolerance domains classified 260 (71.4%) as abnormal, while 291 (79.9%) demonstrated abnormal autonomic findings on CARTs assessment. Overall agreement was 86.0%, with substantial agreement beyond chance (κ = 0.62). Sensitivity and specificity of the COMPASS-31 domain were 85.9% and 86.3%, respectively, with positive and negative likelihood ratios of 6.27 and 0.16. Internal consistency of the orthostatic intolerance domain was good (Cronbach's alpha = 0.82). However, correlations between the orthostatic intolerance domain and CAN analyser findings were weak, and ROC analyses demonstrated poor discrimination (AUC 0.51-0.56).</p><p><strong>Conclusion: </strong>The COMPASS-31 orthostatic intolerance domain showed substantial agreement and moderate screening performance for detecting CAN in adults with T2DM. These findings support its use as a practical symptom-based screening adjunct to identify individuals who may benefit from further objective autonomic testing, particularly in resource-limited settings.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body mass index, sedentary lifestyle, and HbA1c predict cardiac autonomic neuropathy in type 2 diabetes.","authors":"Hassan Thabit Haji, Ramla Muhidin Ali, Ahmed Gharib Khamis, Ashabilan Ebrahim, Mwajuma Ramadhani Muya, Kaushik Ramaiya, Fredirick L Mashili","doi":"10.1186/s40842-026-00308-1","DOIUrl":"10.1186/s40842-026-00308-1","url":null,"abstract":"<p><strong>Background: </strong>Cardiac autonomic neuropathy (CAN) is a serious but often underdiagnosed complication among type 2 diabetes mellitus (T2DM) patients that increases the risk of morbidity and mortality. Evidence on the burden of CAN and its associated factors in Zanzibar is very limited. Therefore, this study aimed to determine the prevalence and predictors of CAN in patients with T2DM attending a tertiary diabetes clinic in Zanzibar.</p><p><strong>Methods: </strong>This was a hospital-based cross-sectional study among patients with T2DM attending Mnazi Mmoja Hospital, Zanzibar. All participants were selected by systematic random sampling. CAN was measured using the CAN 504 analyzer with Ewing's cardiovascular reflex tests. Sociodemographic, clinical, anthropometric, and biochemical data were collected using standardized procedures. A modified Poisson regression model with robust variance was used to identify factors associated with CAN.</p><p><strong>Results: </strong>A total of 364 patients were analyzed, with a mean (SD) age of 56 (10.9) years, and the majority were female (n = 243, 66.8%). The prevalence of CAN was found in 291 (79.9%) patients. Of those with CAN, 220 (60.4%) had early CAN, 65 (17.9%) had definite CAN, and only 6 (1.6%) had severe CAN. Patients with normal body mass index (BMI) had lower risk of CAN (aPR 0.86, 95% CI 0.76-0.99, p = 0.036), while patients with sedentary lifestyle (aPR 1.00, 95% CI 1.00-1.00, p = 0.002) and elevated HbA1c levels (aPR 1.01, 95% CI 1.00-1.03, p = 0.013) had higher risk.</p><p><strong>Conclusion: </strong>This study revealed a high prevalence of CAN among adults with T2DM attending a tertiary diabetes clinic in Zanzibar. Normal BMI was associated with lower CAN prevalence, whereas greater sedentary behavior and higher HbA1c were associated with higher prevalence. These findings support earlier screening and targeted risk factor modification in high-risk patients.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The adipomyokine paradox and sex-specific metabolic divergence in subclinical hypothyroidism: a systematic review and meta-analysis.","authors":"Sarang Barbind, Alaka Chandak","doi":"10.1186/s40842-026-00314-3","DOIUrl":"10.1186/s40842-026-00314-3","url":null,"abstract":"<p><strong>Background: </strong>Subclinical hypothyroidism (SCH) increases CVD risk but the threshold for treatment remains controversial. Sex-based metabolic profiles, novel adipocytokines (Irisin/Apelin), and reversibility of vascular remodeling were examined.</p><p><strong>Methods: </strong>A PRISMA 2020-compliant systematic review of PubMed/MEDLINE, Scopus, and Web of Science was conducted using the PROSPERO-aligned search window from 1 January 2010 to 31 December 2023. Ten studies met the final eligibility criteria and were synthesized according to outcome comparability. Study quality was assessed using RoB 2 and the Newcastle-Ottawa Scale, and certainty of evidence was considered using GRADE principles.</p><p><strong>Results: </strong>SCH was associated with a pro-atherogenic phenotype, including higher Atherogenic Index of Plasma (AIP) in observational evidence. Sex-specific patterns were observed: cohort evidence suggested increased incident metabolic syndrome among younger men with SCH (HR 1.87; 95% CI: 1.21-2.90), whereas studies in perimenopausal women showed a more lipid-dominant atherogenic profile. Narrative synthesis suggested divergent adipomyokine behavior, with persistent irisin abnormalities despite biochemical euthyroidism and more rapid apelin change in limited interventional evidence. Levothyroxine therapy was associated with modest improvement in selected lipid parameters and CIMT in some interventional studies; however, these findings should not be extrapolated to hard cardiovascular outcomes.</p><p><strong>Conclusion: </strong>SCH appears to be associated with heterogeneous cardiometabolic risk patterns across sex, age, adiposity, lipid phenotype, and baseline TSH. The available evidence supports individualized risk assessment but remains insufficient to mandate phenotype-specific treatment thresholds or to infer long-term cardiovascular-risk reduction without further prospective validation.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of continuous glucose monitoring (CGM) in diabetes management in Africa: opportunities, challenges, and future prospects.","authors":"M A Olamoyegun, O D Olamoyegun, A T Akinlade, O O Saliu, T A Adeyemi","doi":"10.1186/s40842-026-00310-7","DOIUrl":"10.1186/s40842-026-00310-7","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus represents a growing public health crisis across Africa, with prevalence rates increasing due to urbanization, lifestyle transitions, and epidemiological transition. Despite numerous technological advances in diabetes management, including continuous glucose monitoring (CGM), access to these innovations remains limited across the continent.</p><p><strong>Objective: </strong>This narrative review examines the current state, opportunities, challenges, and prospects of CGM technology in African diabetes care, with emphasis on the socioeconomic, infrastructural, and cultural factors influencing implementation.</p><p><strong>Methods: </strong>A comprehensive review of peer-reviewed literature, clinical trials, and implementation studies from African contexts was conducted, incorporating evidence on CGM technology, diabetes epidemiology, healthcare systems, and policy frameworks across African nations.</p><p><strong>Results: </strong>CGM technology offers substantial benefits for glycaemic control, complication reduction, and patient empowerment. However, widespread adoption in Africa faces significant barriers including prohibitive costs, limited healthcare infrastructure, supply chain challenges, inadequate healthcare workforce training, and sociocultural factors. Emerging clinical trials in South Africa, Kenya, and Malawi demonstrate feasibility and clinical benefits, though large-scale implementation remains constrained.</p><p><strong>Conclusions: </strong>While CGM holds important potential at transforming African diabetes care, successful integration requires multisectoral collaboration, innovative financing mechanisms, capacity building, and feasible implementation strategies. Policy frameworks that support equitable access, regulatory harmonization, and sustainable scale-up models are essential for realizing CGM's full potential across the continent.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the lipid etiology of atherogenic index of plasma and gout: establishing the causal role of triglycerides through NHANES, Mendelian randomization, and network pharmacology.","authors":"Yajing Tian, Xingzheng Zhang, Shaofang Gao, Hefei Wang","doi":"10.1186/s40842-026-00309-0","DOIUrl":"10.1186/s40842-026-00309-0","url":null,"abstract":"<p><strong>Background: </strong>Although a cross-sectional relation between the atherogenic index of plasma (AIP) and gout has been well documented, the causal roles of its principal components, TG and HDL-C, have not yet been clearly established. Therefore, this study sought to explicate the causal relations between AIP, its individual constituents, and the risk of gout, as well as to investigate the potential molecular mechanisms underlying these associations.</p><p><strong>Methods: </strong>We adopted an integrated analytical pipeline. First, mediation and cross-sectional analyses were carried out to quantify the phenotypic associations of TG, HDL-C, and AIP with gout. Second, both multivariable and univariable Mendelian randomization (MR) analyses were applied to assess causal directions. Finally, a network pharmacology approach was applied to construct interaction networks linking lipid-related factors with gout, and subsequent enrichment analyses were done to identify the main biological pathways involved and key genes were identified using the Icelandic database's pQTLs.</p><p><strong>Results: </strong>AIP showed a significant positive link with gout prevalence (OR = 1.700, p = 0.010), with this relationship being mediated mainly by HDL-C (45.19%), rather than TG or LDL-C. Univariable MR analyses indicated that TG exerted a substantial causal effect on gout risk (OR = 1.0058, p < 0.001). Although univariable MR showed a nominally protective association for HDLC (OR = 0.623, 95% CI: 0.399-0.974, p = 0.042), this effect was attenuated and became statistically nonsignificant after multivariable adjustment for other lipid traits (p > 0.05). After adjustment for genetic correlations in multivariable MR analyses, TG remained the sole lipid trait with a robust and independent causal effect on gout (OR = 1.0077, p < 0.001), whereas neither HDL-C nor LDL-C reached statistical significance. The TG-specific gout-associated gene set (Group B) was significantly enriched in T-cell receptor and NF-κB signaling pathways, with hub genes including PTPRC, MYD88, and LCK, supporting a direct lipid-immune axis. By contrast, the combined TG/HDL-C gene set (Group F) showed predominant enrichment in PI3K-Akt and cytokine-cytokine receptor pathways, whereas genes uniquely shared between HDL-C and gout (Group C) were mainly enriched in fundamental cellular processes without marked inflammatory pathway involvement.</p><p><strong>Conclusions: </strong>AIP exhibits a non-linear positive association with gout, but this association is primarily mediated by HDL‑C, which itself has no independent causal protective effect. TG may play an independent causal role in gout, potentially involving T‑cell receptor/NF‑κB signaling pathways. However, these findings are exploratory and require further validation.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13362044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between obesity and telomere shortening is mediated through total bilirubin.","authors":"Bin Zhou, Lei Ding, Xuerong Sun, Wei Hua, Daoliang Zhang, Zhiyong Liao","doi":"10.1186/s40842-026-00307-2","DOIUrl":"10.1186/s40842-026-00307-2","url":null,"abstract":"<p><strong>Background: </strong>Both obesity and oxidative stress are closely linked to leukocyte telomere length (LTL) shortening, yet the specific mediating role of total bilirubin in this association remains insufficiently explored. This study aimed to quantify the extent to which total bilirubin, a potent endogenous antioxidant, mediates the association between obesity and LTL.</p><p><strong>Methods: </strong>We analyzed data from 6,717 adults participating in the National Health and Nutrition Examination Survey 1999-2002. Causal mediation analysis with 1,000 bootstrap iterations was employed to investigate the mediating effect of serum total bilirubin on the association between body mass index (BMI) and LTL.</p><p><strong>Results: </strong>In the fully adjusted model, BMI was significantly and inversely associated with LTL, with a total effect of -3.532 base pairs (bp) per 1-unit increase in BMI (95% confidence interval [CI]: -6.225 to -1.178; P = 0.002). Serum total bilirubin significantly mediated this association (average causal mediation effect = -0.446 bp; 95% CI: -0.726 to -0.237; P < 0.001). The estimated proportion of the association explained by bilirubin was 13.2% (95% CI: 5.5% to 41.2%; P = 0.002). A series of sensitivity analyses confirmed the robustness and stability of these mediation findings.</p><p><strong>Conclusions: </strong>Total bilirubin serves as a significant statistical mediator in the relationship between obesity and LTL shortening. However, given the cross-sectional design of this study, further longitudinal investigations are required to confirm these associations and establish causality.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk stratification in diabetic ankle fractures: a systematic review of reviews and proposal of the MADRAS scoring system.","authors":"Ahmed Bakr, Maher Nassor, Usman Muhammad, Marwan Tahoun, Anand Pillai","doi":"10.1186/s40842-026-00292-6","DOIUrl":"10.1186/s40842-026-00292-6","url":null,"abstract":"<p><strong>Background: </strong>Diabetic ankle fractures present significant clinical challenges, with higher rates of complications including infection, non-union, Charcot neuroarthropathy, and amputation compared to non-diabetic patients. Despite this burden, no universally accepted guidelines exist for risk stratification and management. The Adelaide Fracture in the Diabetic Ankle (AFDA) score was proposed in 2014 but has limitations including uniform weighting of risk factors and exclusion of local injury characteristics. This systematic review of reviews aimed to synthesise current evidence and develop an updated, evidence-based risk stratification tool.</p><p><strong>Methods: </strong>A comprehensive search of Embase, PubMed, and Web of Science was conducted. Eligible studies included systematic and narrative reviews examining outcomes, risk factors, or interventions for diabetic ankle fractures. Risk of bias was assessed using the ROBIS tool. Data were synthesised narratively, and an evidence-informed, consensus-based scoring system was developed by translating observed effect sizes from the included reviews into weighted risk scores.</p><p><strong>Results: </strong>Thirteen reviews were included. Complicated diabetes, particularly peripheral neuropathy, peripheral arterial disease, and prior Charcot neuroarthropathy, emerged as the strongest predictors of adverse outcomes. Non-operative management of unstable fractures was associated with significantly higher complication rates. Based on these findings, we propose the Manchester Ankle Fracture Diabetic Risk Assessment Score (MADRAS), incorporating weighted systemic host factors, local injury characteristics, and modifiable patient factors across a 17-point scale stratifying patients into four management tiers: low risk (0-2), moderate risk (3-5), high risk (6), and very high risk (≥ 7).</p><p><strong>Conclusion: </strong>MADRAS addresses limitations of existing frameworks by incorporating evidence-based weightings and local injury factors. Prospective external validation is required before widespread clinical adoption; until then, MADRAS should be regarded as a decision-support tool. This tool may assist clinicians in systematic risk stratification and surgical decision-making for diabetic ankle fractures.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond blood pressure: carotid intima-media thickness uncovers subclinical atherosclerosis in normotensive adults with type 2 diabetes in Sub-Saharan Africa.","authors":"Mark Kirabo Iga, Faith Ameda, Joyce Nayiga, Denise Apolot, Fatuma OmarAhmed, Ivan Bwire, Rebecca Kyomuhangi, Isaac Ssinabulya","doi":"10.1186/s40842-026-00303-6","DOIUrl":"10.1186/s40842-026-00303-6","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus is strongly linked to a heightened risk of cardiovascular disease. Carotid intima-media thickness (CIMT) is increasingly utilized as a surrogate marker of atherosclerosis and cardiovascular disease risk. This study aimed to evaluate CIMT through high-resolution ultrasonography in adults with Type 2 diabetes and assess its potential association with selected clinical factors within a native Black African population.</p><p><strong>Methodology: </strong>An analytical cross-sectional study was conducted between November 2022 and February 2023 at the Diabetic Clinic of Mulago National Referral Hospital, Kampala, Uganda. One hundred normotensive adults with Type 2 diabetes were enrolled by consecutive sampling. CIMT was measured bilaterally at the common carotid artery using high-resolution Doppler ultrasonography. Clinical variables collected included age, sex, body mass index (BMI), glycated haemoglobin (HbA1c), fasting lipid profile, and diabetes duration. Multivariable Poisson regression with robust standard errors was used to estimate adjusted prevalence ratios (aPR).</p><p><strong>Results: </strong>The mean age was 52.4 years (SD 11.2) and 62% of participants were female. The median diabetes duration was 10.0 years and the median HbA1c was 9.9% (IQR 7.8-10.9). Abnormal CIMT (> 0.9 mm) was found in 61% (61/100) of participants. On multivariable analysis, independent predictors of abnormal CIMT included age > 45 years (aPR 1.17, 95% CI 1.08-1.28), high LDL cholesterol (aPR 1.20, 95% CI 1.07-1.36), poor or very poor glycemic control (HbA1c > 8%; aPR 1.16, 95% CI 1.01-1.32), and diabetes treatment duration > 9 years (aPR 1.11, 95% CI 1.01-1.21).</p><p><strong>Conclusions: </strong>Among normotensive Ugandan adults with Type 2 diabetes, 61% had increased CIMT. Independent predictors were older age, poor glycemic control, high LDL cholesterol, and longer disease duration. CIMT assessment offers a simple, non-invasive adjunct for identifying subclinical atherosclerosis and may improve cardiovascular risk stratification in this population.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of SGLT2 inhibitors versus DPP-4 inhibitors in super-elderly patients (≥ 80 years) with type 2 diabetes: a propensity score-matched cohort study.","authors":"Shankar Biswas, Yashasvi Srivastava, Ahmed Wahba, Bushra Amer, Ayman Hamadttu","doi":"10.1186/s40842-026-00305-4","DOIUrl":"10.1186/s40842-026-00305-4","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter-2 inhibitors (SGLT2i) provide cardiovascular and renal benefits in type 2 diabetes, yet safety data in super-elderly patients (≥ 80 years) remain limited. We compared the safety of SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in this vulnerable population.</p><p><strong>Methods: </strong>We conducted a retrospective, new-user, active-comparator cohort study using the TriNetX Global Collaborative Network (176 healthcare organizations). Patients aged ≥ 80 years at treatment initiation with type 2 diabetes newly prescribed SGLT2i or DPP-4i were matched 1:1 using propensity scores incorporating demographics, comorbidities, frailty proxies, and concomitant medications. Primary safety outcomes included falls, hip fracture, acute kidney injury, urinary tract infection, genital candidiasis, hypoglycemia, volume depletion, hypotension, and syncope. Secondary outcomes included stroke, myocardial infarction, heart failure hospitalization, and all-cause mortality. Subgroup analyses assessed falls risk among insulin, benzodiazepine, and loop diuretic users.</p><p><strong>Results: </strong>After matching, 65,119 patients remained in each cohort (mean age 82.2 ± 2.3 years; 48.7% female). Over a mean follow-up of 269 days, SGLT2i was associated with significantly lower risks of falls (HR 0.90; 95% CI 0.85-0.95), hip fracture (HR 0.78; 0.69-0.89), acute kidney injury (HR 0.82; 0.78-0.85), urinary tract infection (HR 0.79; 0.75-0.83), hypoglycemia (HR 0.74; 0.67-0.82), volume depletion (HR 0.91; 0.86-0.97), stroke (HR 0.88; 0.82-0.95), and all-cause mortality (HR 0.73; 0.70-0.76; all p < 0.05). Genital candidiasis risk was higher with SGLT2i (HR 1.70; 1.50-1.93; p < 0.001), as was heart failure hospitalization (HR 1.07; 1.02-1.12; p = 0.007). Hypotension, syncope, and myocardial infarction did not differ significantly. The falls reduction was consistent across subgroups using insulin, benzodiazepines, and loop diuretics. Sensitivity analysis with fixed 250-day follow-up confirmed all primary findings.</p><p><strong>Conclusions: </strong>In super-elderly patients with type 2 diabetes, SGLT2i demonstrated a favorable safety profile compared to DPP-4i, with significantly lower risks of falls (10%), hip fracture (22%), acute kidney injury (18%), hypoglycemia (26%), and mortality (27%). Safety concerns included increased genital candidiasis (70%) and modestly higher heart failure hospitalization (7%). These findings support SGLT2i use in appropriately selected super-elderly patients.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From dual to quintuple agonism for next-generation pharmacology to treat obesity and type 2 diabetes: synergistic incretin and nuclear receptor signaling.","authors":"Gaetano Santulli","doi":"10.1186/s40842-026-00321-4","DOIUrl":"10.1186/s40842-026-00321-4","url":null,"abstract":"<p><p>Receptor-targeted polypharmacology is emerging as a promising strategy for the treatment of obesity, type 2 diabetes, and metabolic dysfunction-associated steatohepatitis. GLP-1-GIP-lanifibranor, a unimolecular conjugate combining GLP-1R/GIPR co-agonism with pan-PPAR activation, enables receptor-guided intracellular delivery of lanifibranor to incretin receptor-expressing cells while limiting systemic off-target exposure. In obese mouse models, the conjugate produced greater reductions in body weight, adiposity, food intake, and hyperglycemia than semaglutide, GLP-1-GIP co-agonism, or lanifibranor alone, while significantly improving insulin sensitivity. Mechanistic analyses demonstrated receptor-dependent delivery and identified PPARδ signaling as a principal mediator of glycemic improvement independent of weight loss. Unlike unconjugated lanifibranor, the conjugate did not induce anemia, fluid retention, renal dysfunction, or adipocyte differentiation, supporting the concept that tissue-restricted PPAR activation may mitigate classical adverse effects of systemic PPAR agonism. These findings establish peptide-directed nuclear receptor targeting as a potentially important platform for next-generation metabolic therapeutics, although substantial translational uncertainties remain regarding clinical efficacy, safety, and long-term applicability.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13308489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}