Empagliflozin is a potent, highly selective antihyperglycemic agent indicated for the treatment of adults with type 2 diabetes mellitus. This review aims to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of empagliflozin in healthy and diseased subjects. Google Scholar, PubMed, and Cochrane Library databases were systematically searched for PK and PD studies on empagliflozin. Of the 1,340 articles identified, 28 studies met the eligibility criteria and were involved in this systematic review. PK analysis showed dose-proportional increases in area under the curve for empagliflozin from 0 to infinity (AUC_0-∞), similar bioavailability across formulations, and reduced absorption under fed conditions. In healthy subjects, urinary glucose excretion (UGE) after an evening dose of empagliflozin was approximately 1.7-fold higher compared with morning administration. The AUC_0-∞ for empagliflozin in patients with severe renal impairment was significantly higher than in subjects with normal renal function, i.e. 7485.1 ng.hr/mL vs. 4779.646 ng.hr/mL. The maximum plasma concentration (C_max) of empagliflozin was 1.4-fold greater in patients with severe liver impairment. The AUC_0-∞ in the fasting condition was significantly greater than that of the fed state. Furthermore, empagliflozin exhibited a C_max that was 1.1-fold greater when administered alone but decreased in the presence of linagliptin. This systematic review consolidates all available PK and PD parameters of empagliflozin from accessible studies to assist clinicians in dose adjustment for patients with renal or hepatic impairment and type 2 diabetes, as well as in minimizing the risk of adverse reactions and drug-drug interactions.

Prior studies often examine single telehealth encounter types or aggregate all digital care, overlooking how patients combine multiple digital and in-person modalities in hybrid care. To address this gap, we derived hybrid care engagement phenotypes and assessed sociodemographic differences and associations with glycemic control among adults with type 2 diabetes (T2DM).

We conducted a retrospective cohort study of 10 671 adults with T2DM receiving primary care at an academic (UCSF) or safety-net system (SFHN) from April 2021 to March 2023. K-medoids clustering was applied to five encounter modalities (in-person, video, telephone visits; portal messages; unscheduled telephone calls) to derive four engagement phenotypes. We assessed sociodemographic differences using chi-square and Kruskal-Wallis tests and evaluated associations between phenotype and follow-up HbA1c control using logistic regression. We tested interactions with baseline HbA1c and estimated predicted probabilities using Tukey-adjusted contrasts.

Four phenotypes emerged per system: Digitally Engaged Multimodal, Traditional High Utilizers, Digitally Leaning (UCSF), Telephone Reliant (SFHN), and Low Digital. UCSF patients belonged to digitally forward phenotypes, whereas SFHN patients concentrated in traditional, lower-tech phenotypes. Among patients with uncontrolled diabetes, digitally forward phenotypes had 13-20 percentage points higher predicted probability of achieving control (UCSF: 56% Digitally Leaning vs 36% Traditional; SFHN: 53% Multimodal vs 40% Telephone).

Phenotypes varied by health system and sociodemographic factors, with modest, system-specific associations between digitally forward phenotypes and glycemic control among patients with uncontrolled diabetes. Findings underscore structural and sociodemographic inequities in hybrid care engagement and the need for proactive, tailored strategies to promote equitable hybrid care.

BackgroundDiabetic foot infections are difficult to eradicate and could lead to serious complications such as multiple surgeries, amputation and mortality. Culture-based IV antibiotics and particularly amputation are usually the available options. Only few studies articles reported the use of cement impregnated with antibiotics to fill temporarily or permanently a bone defect, but with no evidence synthesis yet. Therefore, this study aims at assessing the outcomes of the use of antibiotic-impregnated cement for infection or mechanical support in diabetic foot osteomyelitis.MethodsA systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We searched multiple electronic databases using the terms "osteomyelitis AND cement AND diabetic AND foot." The quality of the included studies was evaluated using the Joanna Briggs Institute Appraisal Tool.ResultsSix studies met the inclusion criteria combining 82 patients with 85 procedures. With a mean follow-up period of 22 ±14.6 months, the meta-analytical results were as follows: (1) the weighted healing rate was 85.2%, (2) 63.6% of cement were kept in place, (3) 8.2% of cement had to be exchanged, (4) 24.4% of placed cement had to be removed, (5) minor amputation following cement placement was 13.4%, and (6) the rate of secondary surgery was 18.7%, with arthrodesis being the most common (94%).ConclusionThere are limited studies available detailing the outcomes of cement use in diabetic foot osteomyelitis. In the case of the difficult-to-heal osteomyelitis of the diabetic foot and whenever a peripheral bone rim could be preserved, filling the void within to deliver local infection control and to assure mechanical resistance for ambulation could be a non-radical limb preserving option.Level of EvidenceLevel IV.

Preclinical heart failure (HF) (stages A and B) is common but easily overlooked in asymptomatic patients with type 2 diabetes (T2D). There is a paucity of evidence regarding how coexisting risk factors contribute to the development of HF in asymptomatic Asian patients with T2D, and there is a lack of guidance on the early identification of asymptomatic patients to help cost-effectively allocate preventive therapies. The Diabetes Mellitus Heart Failure Events Analysis and Risk Tracking (DM-HEART) trial, a prospective, multicenter, longitudinal cohort study, recruited asymptomatic patients with T2D and no prior HF between January 2021 and June 2024, with a minimum follow-up period of 12 months. The primary outcome was incident HF, defined as new-onset HF (requiring either hospitalization or an urgent care visit). Secondary outcomes are measured as 3-point major adverse cardiovascular events, comprised of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. DM-HEART will provide epidemiological data on the incidence of HF and assess the prognostic utility of clinical parameters, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), for predicting incident HF events among asymptomatic patients with T2D in preclinical stages of HF. Furthermore, we aim to determine the optimal NT-proBNP cut-off value for predicting incident HF events in East Asian patients with diabetes.

The global rise in obesity, a major driver of metabolic diseases, has prompted scrutiny of distinct obesity phenotypes. While overall obesity is concerning, abdominal obesity demonstrates a stronger association with metabolic dysfunction, type 2 diabetes (DM2), and cardiovascular disease (CVD). This review examines the risk of DM2, CVD, and mortality in adults with a metabolically healthy abdominal obese phenotype.

A systematic search of PubMed/MEDLINE, Web of Science, Cochrane Library, and ProQuest was conducted on April 7, 2025, to identify prospective cohort studies in adults. Eligible studies compared MHAO individuals to metabolically healthy, non-abdominally obese (MHNAO) controls, focusing on outcomes including incident T2DM, fatal and non-fatal CVD events, and all-cause mortality. Pooled estimates were calculated using random-effects meta-analysis, and heterogeneity was assessed using the I² statistic.

Six prospective cohort studies (n = 98,329) were included. Metabolically unhealthy individuals, regardless of abdominal obesity status, had significantly increased risks of T2DM (RR 9.00, 95% CI 7.51-10.50 for MUHAO; RR 5.03, 95% CI 4.11-5.94 for MUHNAO), CVD, and all-cause mortality (HR 1.67, 95% CI 1.42-1.93 for MUHAO; HR 1.58, 95% CI 1.36-1.79 for MUHNAO). In contrast, MHAO individuals did not show significantly elevated risks of T2DM (RR 2.44, 95% CI 0.95-3.94), CVD, or all-cause mortality (HR 1.07, 95% CI 0.88-1.27) compared to MHNAO controls. Substantial heterogeneity (I² > 50%) was observed, partly explained by differences in outcome definitions and metabolic classifications.

While metabolically unhealthy phenotypes are strongly associated with adverse health outcomes, individuals with MHAO appear to have risk profiles comparable to their metabolically healthy, non-abdominally obese counterparts. Nevertheless, abdominal adiposity and metabolic status remain critical determinants of long-term health, and the MHAO phenotype may not be entirely benign. Trial Registration: PROSPERO (CRD42019111056).

Infertility is defined as the inability to conceive after 12 months or longer of regular unprotected sexual intercourse. Azoospermia affects approximately 1% of men, with non-obstructive azoospermia (NOA) accounting for nearly 60% of cases. The role of hormonal treatment before microdissection testicular sperm extraction (Micro-TESE) in stimulating spermatogenesis in patients with NOA is controversial. From this standpoint, our study aimed to investigate the effect of preoperative hormonal treatment on sperm retrieval rates (SRRs) during Micro-TESE in NOA patients.

A retrospective analysis was conducted on 152 patients who underwent Micro-TESE for NOA at our center between January 2021 and December 2023. Patients were divided into two groups. The first group included patients who received preoperative hormonal therapy consisting of clomiphene citrate (25 mg daily) and subcutaneous human chorionic gonadotropin injections (2,000 IU three times weekly) for at least 3 months prior to Micro-TESE, while the second group did not. The two groups were compared for the presence of viable sperm, age, smoking status, medical illnesses (diabetes mellitus and hypertension), hormonal profile before operation [follicle-stimulating hormone (FSH), luteinizing hormone, and total testosterone], history of undescended testes, and the presence of Klinefelter syndrome. Statistical significant was defined as p-value < 0.05.

A total of 152 NOA patients were included in this study, with 78 patients undergoing preoperative hormonal therapy and 74 patients not receiving any preoperative hormonal therapy. Results revealed no statistically significant differences in most demographic and clinical parameters between the groups. Hormonal analysis revealed a significantly lower median FSH level in the preoperative hormonal therapy group (p = 0.04). Micro-TESE outcomes were also comparable, with 50% success in the non-hormonal therapy group and 45% in the preoperative hormonal therapy group (p = 0.53).

In this retrospective cohort, preoperative hormonal therapy was not associated with a statistically significant improvement in Micro-TESE sperm retrieval outcomes in NOA patients. Further studies are warranted to identify biomarkers predicting responders to preoperative hormonal stimulation.

Type 1 diabetes mellitus (T1DM) requires lifelong insulin therapy due to autoimmune destruction of pancreatic β-cells, the difficulty of achieving ideal glycemic control despite advancements in conventional care has led to a rise interest in alternative and integrative medicine (CIM) practices like naturopathy, yoga, and Ayurveda.

This systematic review and meta-analysis aimed to evaluate the effects of integrative therapies on glycemic control in individuals with T1DM and to map the global research landscape through bibliometric analysis.

Following PRISMA, a thorough literature search was carried out in PubMed, Scopus, Embase, and Google Scholar. Included were studies evaluating CIM interventions for T1DM, such as yoga, naturopathy, and Ayurvedic treatments. Both qualitative and quantitative methods were used to synthesise the data, and bibliometric studies were conducted to evaluate country-level output, temporal trends, institutional contributions, and keyword network analysis.

Out 612 screened records, 12 studies met inclusion criteria for qualitative and quantitative analysis. Integrative therapies showed adjunctive benefits to insulin therapy, including improved glycemic control, insulin sensitivity, stress reduction and quality of life. After 2023, bibliometric study showed a growing research trend, In the context of citation impact, Italy and Vietnam are leading, whereas India leads in publications. Keyword network analysis revealed strong associations between integrative practices, particularly yoga and lifestyle modification and glycemic outcomes.

Integrative therapies appear to be promising alternative in the management of T1DM, supporting glycemic control and holistic well-being. However, larger multicenter clinical trials are required to strengthen the evidence base and support their integration into standard diabetes care frameworks. Broader clinical integration, rigorous multicentric trials, and greater alignment with national AYUSH policies are recommended to optimize T1DM management in India and potentially enhance outcomes globally.

Erectile dysfunction (ED) is a prevalent condition, with vasculogenic ED being the most common subtype, primarily related to endothelial dysfunction and cardiovascular risk factors. Low-intensity extracorporeal shock wave therapy (Li-ESWT) has emerged as a promising non-invasive treatment option. However, predictors of treatment response remain poorly defined.

To identify clinical and vascular predictors of treatment success following Li-ESWT in patients with vasculogenic ED and to develop a novel, practical, and non-invasive scoring system to predict therapeutic response.

This prospective study included 219 men aged 18-80 years with vasculogenic ED between January 2024 and January 2025. All patients underwent Li-ESWT (18 000 pulses over 3 weeks). Clinical and vascular parameters, including age, ED duration, body mass index, presence of cardiovascular risk factors, diabetes mellitus (DM), carotid intima-media thickness (cIMT), flow-mediated dilation rate (FMD), and prior phosphodiesterase type 5 inhibitor (PDE5i) response, were recorded. Treatment success at 6 months was defined as an increase of ≥1 point in the erection hardness score or ≥5 points in the International Index of Erectile Function-5 EF.

The primary outcome was treatment success at 6 months after Li-ESWT. Secondary outcomes included the development and validation of a predictive scoring system.

Treatment success rate was 66.2% (145/219). Independent predictors of treatment success were absence of DM (odds ratio [OR] = 2.67, P = .012), ED duration <36 months (OR = 2.23, P = .026), cIMT <0.8 mm (OR = 2.04, P = .042), prior PDE5i benefit (OR = 2.47, P = .016), FMD ≥5% (OR = 2.57, P = .012), age <65 years (OR = 2.28, P = .032), and presence of cardiovascular risk factors (OR = 2.23, P = .036). A scoring system incorporating these 7 variables achieved an area under the curve of 0.819 (95% confidence interval [CI] 0.762-0.877). Using a cut-off of 4.5 points, the sensitivity was 73% and the specificity was 77% (P < .001).

This scoring system may help clinicians identify patients most likely to benefit from Li-ESWT, optimize patient selection, and improve individualized treatment strategies in vasculogenic ED.

The study is strengthened by its prospective design, relatively large sample size, and inclusion of vascular function parameters (FMD, cIMT). Limitations include the lack of external validation and the absence of penile Doppler ultrasound confirmation in all patients.

This study identified key demographic and vascular predictors of Li-ESWT response and introduces a novel, non-invasive clinical scoring system with strong predictive accuracy. This tool may enhance treatment personalization and support clinical decision-making in the management of ED.

Genetic predisposition and unhealthy lifestyles are well-known contributors to disorders of glucose and lipid metabolism, including type 2 diabetes, obesity, and metabolic dysfunction-associated fatty liver disease. However, these factors alone cannot fully explain the rapidly rising prevalence of these conditions. Emerging evidence highlights the pivotal role of the intrauterine environment in gestational diabetes mellitus (GDM) in shaping epigenetic modifications and metabolic reprogramming, thereby predisposing offspring to long-term metabolic complications. Exosomes have recently been identified as key mediators of maternal-fetal communication. In GDM, both the quantity and cargo (e.g., proteins, miRNAs) of exosomes are altered. These altered exosomes not only contribute to maternal glucose and lipid metabolic abnormalities but also act as a critical vector for transmitting adverse metabolic signals to the offspring. This exosome-mediated communication disrupts placental function and the development of fetal metabolic organs, ultimately programming the offspring for long-term metabolic disorders. In this review, we summarize the characteristic changes of maternal exosomes in GDM and explore the potential mechanism by which exosomes regulate offspring metabolism during maternal-fetal crosstalk. We also propose the possible direction of exosomes in application, providing insights into early-life strategies for the prevention of metabolic diseases.

This study aims to investigate the predictive value of the fibrinogen-to-high-density lipoprotein cholesterol ratio (FHR) in relation to sub-clinical diabetic peripheral neuropathy (sDPN) in individuals diagnosed with type 2 diabetes mellitus (T2DM).

A cohort of 281 patients with T2DM was admitted to the Neurology Department of Jiangxi Provincial People's Hospital between January and December 2023. Within this population, 148 patients were diagnosed with sDPN. The clinical profiles, inflammatory biomarkers, and nerve conduction velocities or current perception thresholds (CPTs) were compared between the two distinct groups. A logistic regression analysis was performed to identify the risk factors for sDPN. The predictive performance of each factor was assessed using a receiver operating characteristic (ROC) curve analysis. The FHR was compared among three groups, which were based on the severity of peripheral neuropathy (PN).

Patients with sDPN exhibited significantly elevated levels of fibrinogen (FIB), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), the monocyte-to-lymphocyte ratio (MLR), and the platelet-to-lymphocyte ratio (PLR), along with diminished high-density lipoprotein cholesterol (HDL-C) levels, compared to patients without sDPN. Univariate and multivariate logistic regression analyses indicated that age, FIB levels, HbA1c, HDL-C, and MLR were significant risk factors that contributed to the onset of sDPN in T2DM patients. The ROC curve analysis indicated that the FHR had an area under the curve (AUC) of 65%. The optimal cutoff value for the FHR was 2.65, exhibiting a specificity of 62.4% and a sensitivity of 63.5%. The composite model incorporating the FHR demonstrated superior reclassification performance (net reclassification improvement (NRI) = 0.416, p = 0.001, 95% CI 0.180-0.650) and integrated discrimination improvement (IDI = 0.053, p < 0.001, 95% CI 0.001-0.015) compared to the basic model (age +HbA1c + MLR). Nonparametric test analysis showed significant differences in the FHR among the three groups. The more severe the PN, the higher the FHR.

The FHR may serve as a valuable early diagnostic marker for sDPN in T2DM.