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Objective: Evaluate the effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on cardiovascular and cerebrovascular diseases. Methods: Articles of SGLT2i on cardiovascular and cerebrovascular diseases were searched. Two authors independently screened the literature, extracted the data, assessed the quality of the study and performed statistical analyses using Review Manager 5.4. Results: Random-effect model was used to merge the OR values, and the pooled effect showed that SGLT2i had significant preventive effects on cardiovascular death (OR=0.76, 95%CI 0.64 to 0.89), myocardial infarction (OR=0.90, 95%CI 0.84 to 0.96), heart failure (OR=0.69, 95%CI 0.64 to 0.74) and all-cause mortality (OR=0.65, 95%CI 0.58 to 0.73). Empagliflozin, dapagliflozin and canagliflozin all reduced the incidence of heart failure (OR=0.72, 95%CI 0.64 to 0.82; OR=0.56, 95%CI 0.39 to 0.80; OR=0.62, 95%CI 0.53 to 0.73), but only dapagliflozin displayed a favorable effect on inhibiting stroke (OR=0.78, 95%CI 0.63 to 0.98). SGLT2i could prevent stroke (OR=0.86, 95%CI 0.75 to 0.99), heart failure (OR=0.63, 95%CI 0.56 to 0.70) and all-cause mortality (OR=0.64, 95%CI 0.57 to 0.72) compared to DPP-4i. Furthermore, SGLT2i could reduce the incidence of heart failure (OR=0.72, 95%CI 0.67 to 0.77) and cardiovascular death (OR=0.72, 95%CI 0.54 to 0.95) in patients with high-risk factors. Conclusions: SGLT2i affects cardiovascular death, myocardial infarction, heart failure and all-cause mortality. Only dapagliflozin displayed a favorable effect on inhibiting stroke. SGLT2i could prevent stroke, heart failure and all-cause mortality compared to DPP-4i. In addition, SGLT2i significantly reduced the development of heart failure and cardiovascular death in patients with high-risk factors. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024532783.

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Early detection of diabetic retinopathy (DR) is an urgent ophthalmological problem in Russia and globally. PURPOSE: This study assesses the prevalence of asymptomatic retinopathy and attempts to identify risk groups for its development in patients with type 1 and 2 diabetes mellitus (T1DM and T2DM). MATERIAL AND METHODS: The study involved clinics from 5 cities in the Russian Federation and it included 367 patients with DM, 34.88% men and 65.12% women, aged 50.88±20.55 years. 34.88% of patients suffered from T1DM, 65.12% suffered from T2DM, the average duration of the disease was 9.02±7.22 years. 58.31% of patients had a history of arterial hypertension, 13.08% had a history of smoking. The primary endpoint was the frequency of detection of diabetic changes in the eye fundus of patients with T1DM and T2DM in general; the secondary endpoint - same but separately, and for T2DM patients depending on the duration of the disease. The exploratory endpoint was the assessment of the influence of various factors on the development of DR. The patients underwent visometry (modified ETDRS table), biomicroscopy, mydriatic fundus photography according to the «2 fields¼ protocol. RESULTS: The average detection rate of DR was 12.26%, primarily observed in patients with T2DM (13.81%), women (9.26%), in both eyes (8.17%). Among patients with DR, 26 (19.55%) had glycated hemoglobin (HbA1c) level exceeding 7.5% (p=0.002), indicating a direct relationship between this indicator and the incidence of DR. Logistic regression analysis showed that the duration of diabetes of more than 10 years has a statistically significant effect on the development of DR. In the modified model for odds estimation, the likelihood of developing DR is increased by the duration of DM for more than 10 years; increased blood pressure; HbA1c level >7.5%. CONCLUSION: The obtained results, some of which will be presented in subsequent publications, highlight the effectiveness of using two-field mydriatic fundus photography as a screening for DR.

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Type 2 diabetes mellitus (T2DM) is globally recognized as a significant health concern, with diabetic foot (DF) identified as a severe long-term complication that can lead to tissue death or amputation. The discovery of the impact of mycobiota, a diverse group of multicellular eukaryotes in the gut microbiome, on the onset of endocrine disorders holds great significance. Therefore, this research aimed to examine variations in fungal mycobiome and identify potential biomarkers for T2DM and T2DM-DF. Fecal and blood samples were collected from 33 individuals with T2DM, 32 individuals with T2DM-DF, and 32 healthy individuals without any health conditions (HC). Blood samples were used for laboratory parameters analysis, while total DNA was extracted from fecal samples and sequenced using Illumina 18s rRNA. Bioinformatics tools were employed to analyze fungal abundance and diversity, revealing differentially expressed fungal species and signature fungi that distinguished between T2DM, T2DM-DF, and HC groups. Firstly, significant alterations in some laboratory parameters were observed among the three groups, which also differed between T2DM and T2DM-DF. The diversity of gut fungi in T2DM and T2DM-DF significantly differed from that of the HC group; however, more pronounced changes were observed in T2DM-DF. Additionally, two significantly altered phyla, Ascomycota and Basidiomycota, were identified with higher Ascomycota abundance but lower Basidiomycota abundance in both the T2DM and T2DM-DF compared to the HC group. Furthermore, the top 15 fungi showing significant changes at the species level included a notable decrease in Rhodotorula_mucilaginosa abundance in patients with T2DM compared to HC and a substantial increase in unclassified_g_Candida abundance specifically seen only among patients with T2DM-DF, but not among those diagnosed with T2DM or HC. Thirdly, KEGG was employed to analyze enzyme expression across the three groups, revealing a more pronounced alteration in gut fungal function within T2DM-DF compared to T2DM. Subsequently, to accurately identify signature fungi in each group, a random forest was utilized to rank the top 15 significant fungi. Notably, 11 fungi were identified as potential biomarkers for distinguishing T2DM or T2DM-DF from HC, while eight fungi could discriminate between T2DM and T2DM-DF. Furthermore, receiver operating characteristic curve (ROC) analysis demonstrated enhanced accuracy of predicted outcomes. These findings suggest that changes in fungal mycobiome are closely associated with the progression and complications of T2DM and DF, offering promising prospects for diagnosis and treatment.

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This meta-analysis investigated efficacy of dapagliflozin as adjunctive therapy for patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) stages 2-5. A systematic search was conducted of selected databases for randomised controlled trials that reported the mean change in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) from baseline. Out of 1,682 identified studies, 9 trials comprising 13,057 patients were included. A pooled estimate of 5 studies indicated that dapagliflozin did not affect eGFR; however, in 2 studies, it significantly reduced chronic eGFR decline compared to placebo (mean difference [MD] ± 2.74; 95% confidence interval [CI]: 1.55, 3.92; P <0.00001). Additionally, a pooled estimate of 4 studies showed that dapagliflozin significantly reduced UACR (MD -23.99%; 95% CI: -34.82--13.15; P <0.0001; I2 = 0%). Therefore, long-term use of dapagliflozin significantly attenuates eGFR decline and reduces albuminuria in patients with T2DM and CKD.

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Background: Sodium‒glucose cotransporter-2 (SGLT2) inhibitors offer glycaemic and cardiorenal benefits in the early stage of chronic kidney disease (CKD). However, the use of SGLT2 inhibitors may increase the risk of genitourinary tract infection (GUTI). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may also cause deterioration of kidney function. The long-term follow-up of cardiorenal outcomes and GUTI incidence in patients with advanced CKD receiving SGLT2 inhibitors combined with ACEIs/ARBs should be further investigated. Methods: We analysed data from 5,503 patients in Taiwan's Taipei Medical University Research Database (2016-2020) who were part of a pre-end-stage renal disease (ESRD) program (CKD stages 3-5) and received ACEIs/ARBs. SGLT2 inhibitor users were matched 1:4 with nonusers on the basis of sex, CKD, and program entry duration. Results: The final cohort included 205 SGLT2 inhibitor users and 820 nonusers. SGLT2 inhibitor users experienced a significant reduction in ESRD/dialysis risk (aHR = 0.35, 95% CI = 0.190.67), and SGLT2 inhibitor use was not significantly associated with acute kidney injury or acute kidney disease risk. Among SGLT2 inhibitor users, those with a history of cardiovascular disease (CVD) had greater CVD rates. Conversely, those without a CVD history had lower rates of congestive heart failure, arrhythmia, acute pulmonary oedema, and acute myocardial infarction, although the differences were not statistically significant. Notably, SGLT2 inhibitor usage was associated with a greater GUTI incidence (aHR = 1.78, 95% CI = 1.122.84) shortly after initiation, irrespective of prior GUTI history status. Conclusion: Among patients with CKD stages 3-5, SGLT2 inhibitor use was linked to increased GUTI incidence, but it also significantly reduced the ESRD/dialysis risk without an episodic AKI or AKD risk. Clinical physicians should consider a personalized medicine approach by balancing GUTI episodes and cardiorenal outcomes for advanced CKD patients receiving SGLT2 inhibitors.

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BACKGROUND: Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. METHODS: A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. RESULTS: WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261-1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032-4.371, P for trend < 0.001). CONCLUSIONS: Our study illustrated that higher WHRadjBMI is likely to be associated with an increased risk of CI among patients with T2DM. These findings support the detrimental effects of excess visceral fat accumulation on cognitive function in middle-aged and elderly T2DM patients.

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BACKGROUND: This study aimed to synthesize and quantitatively examine Health State Utility Values (HSUVs) for Type 2 Diabetes Mellitus (T2DM) and its complications, providing a robust meta-regression framework for selecting appropriate HSUV estimates. METHOD: We conducted a systematic review to extract HSUVs for T2DM and its complications, encompassing various influencing factors. Relevant literature was sourced from a review spanning 2000-2020, supplemented by literature from PubMed, Embase, and the Web of Science (up to March 2024). Multivariate meta-regression was performed to evaluate the impact of measurement tools, tariffs, health status, and clinical and demographic variables on HSUVs. RESULTS: Our search yielded 118 studies, contributing 1044 HSUVs. The HSUVs for T2DM with complications varied, from 0.65 for cerebrovascular disease to 0.77 for neuropathy. The EQ-5D-3L emerged as the most frequently employed valuation method. HSUV differences across instruments were observed; 15-D had the highest (0.89), while HUI-3 had the lowest (0.70) values. Regression analysis elucidated the significant effects of instrument and tariff choice on HSUVs. Complication-related utility decrement, especially in diabetic foot, was quantified. Age <70 was linked to increased HSUVs, while longer illness duration, hypertension, overweight and obesity correlated with reduced HSUVs. CONCLUSION: Accurate HSUVs are vital for the optimization of T2DM management strategies. This study provided a comprehensive data pool for HSUVs selection, and quantified the influence of various factors on HSUVs, informing analysts and policymakers in understanding the utility variations associated with T2DM and its complications.

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BACKGROUND: Heart failure with mildly reduced or preserved ejection fraction (hereafter referred to as HFpEF) is the most common type of heart failure and is associated with a high risk of hospitalisation and death, especially in patients with overweight, obesity, or type 2 diabetes. In the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide improved heart failure-related symptoms and physical limitations in participants with HFpEF. Whether semaglutide also reduces clinical heart failure events in this group remains to be established. METHODS: We conducted a post-hoc pooled, participant-level analysis of four randomised, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) to examine the effects of once-weekly subcutaneous semaglutide (2·4 mg in SELECT, STEP-HFpEF, and STEP-HFpEF DM; 1·0 mg in FLOW) on heart failure events. The STEP-HFpEF and STEP-HFpF DM trials enrolled participants with obesity-related HFpEF, the SELECT trial enrolled participants with atherosclerotic cardiovascular disease and overweight or obesity, and the FLOW trial enrolled participants with type 2 diabetes and chronic kidney disease. Hence, for this analysis, we include all participants from the STEP-HFpEF trials and those with an investigator-reported history of HFpEF from SELECT and FLOW. The main outcomes for this analysis were the composite endpoint of time to cardiovascular death or first worsening heart failure event (defined as hospitalisation or urgent visit due to heart failure), time to first worsening heart failure event, and time to cardiovascular death. Efficacy and safety endpoints were analysed with the full analysis set (ie, all participants randomly assigned to treatment, according to the intention-to-treat principle). The SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials are registered at ClinicalTrials.gov, NCT03574597, NCT03819153, NCT04788511, and NCT04916470, respectively, and all are complete. FINDINGS: Across the four trials, 3743 (16·8%) of 22 282 participants had a history of HFpEF (1914 assigned to semaglutide and 1829 assigned to placebo). In this group of participants with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or heart failure events (103 [5·4%] of 1914 in the semaglutide group had events vs 138 [7·5%] of 1829 in the placebo group; hazard ratio [HR] 0·69 [95% CI 0·53-0·89]; p=0·0045). Semaglutide also reduced the risk of worsening heart failure events (54 [2·8%] vs 86 [4·7%]; HR 0·59 [0·41-0·82]; p=0·0019). No significant effect on cardiovascular death alone was seen (59 [3·1%] vs 67 [3·7%]; HR 0·82 [0·57-1·16]; p=0·25). A lower proportion of patients treated with semaglutide had serious adverse events than did those who were treated with placebo (572 [29·9%] vs 708 [38·7%]). INTERPRETATION: In patients with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or worsening heart failure events, and worsening heart failure events alone, whereas its effect on cardiovascular death alone was not significant. These data support the use of semaglutide as an efficacious therapy to reduce the risk of clinical heart failure events in patients with HFpEF, for whom few treatment options are currently available. FUNDING: Novo Nordisk.

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This study investigated osteoporosis risk factors among older Asian men with type-2 diabetes mellitus, hypertension, or hyperlipidaemia in primary care. Advanced age, dementia, depression, and polypharmacy were associated with higher risks for osteoporosis. Screening strategies targeting these factors are crucial for improving bone health as part of comprehensive preventive care. PURPOSE: Asian patients with type-2 diabetes mellitus (T2DM), hypertension, or hyperlipidaemia (DHL) are predominantly managed in primary care. They are also at risk of osteoporosis, but men are often under-screened and under-treated for this preventable bone disorder. This study aimed to identify the clinical characteristics and risk factors of osteoporosis among older men with DHL in primary care for early intervention. METHODS: This retrospective study included men aged 65 years and older managed in public primary care clinics for their DHL between 1st July 2017 and 30th June 2018. Demographic, clinical, laboratory, and imaging data were extracted from their electronic medical records based on their International Classification of Diseases-10 (ICD-10) diagnosis codes. Descriptive statistical analyses, with statistical significance set at p < 0.05, were conducted, followed by generalized estimating equation (GEE) modelling. RESULTS: Medical records of 17,644 men (83.1% Chinese, 16.9% minority ethnic groups, median age 71 years) were analysed. 2.3% of them had diagnosis of osteoporosis, 0.15% had fragility fracture, and 26.0% of those diagnosed with osteoporosis were treated with bisphosphonates. Their mean HbA1c was 6.9%; mean systolic and diastolic blood pressure were 133 and 69 mmHg. The GEE model showed that age (OR = 1.07, 95%CI = 1.05-1.09, p < 0.001), dementia (OR = 2.24, 95%CI = 1.33-3.77, p = 0.002), depression (OR = 2.38, 95%CI = 1.03-5.50, p = 0.043), and polypharmacy (OR = 6.85, 95%CI = 3.07-15.26, p < 0.001) were significantly associated with higher risks for osteoporosis. CONCLUSION: Age, dementia, depression, and polypharmacy are associated with osteoporosis risks in men with DHL. Strategies to incorporate osteoporosis screening among older men with these risk factors are needed to improve their bone health.

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AIMS: Type 2 diabetes mellitus (T2DM) is related to an increased risk of postoperative cognitive dysfunction (POCD), which may be caused by neuronal hyperexcitability. Astrocyte glutamate transporter 1 (GLT-1) plays a crucial role in regulating neuron excitability. We investigated if T2DM would magnify the increased neuronal excitability induced by anesthesia/surgery (A/S) and lead to POCD in young adult mice, and if so, determined whether these effects were associated with GLT-1 expression. METHODS: T2DM model was induced by high fat diet (HFD) and injecting STZ. Then, we evaluated the spatial learning and memory of T2DM mice after A/S with the novel object recognition test (NORT) and object location test (OLT). Western blotting and immunofluorescence were used to analyze the expression levels of GLT-1 and neuronal excitability. Oxidative stress reaction and neuronal apoptosis were detected with SOD2 expression, MMP level, and Tunel staining. Hippocampal functional synaptic plasticity was assessed with long-term potentiation (LTP). In the intervention study, we overexpressed hippocampal astrocyte GLT-1 in GFAP-Cre mice. Besides, AAV-Camkllα-hM4Di-mCherry was injected to inhibit neuronal hyperexcitability in CA1 region. RESULTS: Our study found T2DM but not A/S reduced GLT-1 expression in hippocampal astrocytes. Interestingly, GLT-1 deficiency alone couldn't lead to cognitive decline, but the downregulation of GLT-1 in T2DM mice obviously enhanced increased hippocampal glutamatergic neuron excitability induced by A/S. The hyperexcitability caused neuronal apoptosis and cognitive impairment. Overexpression of GLT-1 rescued postoperative cognitive dysfunction, glutamatergic neuron hyperexcitability, oxidative stress reaction, and apoptosis in hippocampus. Moreover, chemogenetic inhibition of hippocampal glutamatergic neurons reduced oxidative stress and apoptosis and alleviated postoperative cognitive dysfunction. CONCLUSIONS: These findings suggest that the adult mice with type 2 diabetes are at an increased risk of developing POCD, perhaps due to the downregulation of GLT-1 in hippocampal astrocytes, which enhances increased glutamatergic neuron excitability induced by A/S and leads to oxidative stress reaction, and neuronal apoptosis.

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Sodium-glucose cotransporter-2 inhibitors (SGLT2i) inhibit urinary glucose and sodium reabsorption in the proximal tubule of the nephron and result in glucosuria, natriuresis and diuresis. In patients with T2DM who have atherosclerotic cardiovascular (CV) disease or CV risk factors, SGLT2is have been shown to reduce major CV events and heart failure (HF) hospitalization. The greatest and most consistent effect of SGLT2is in these trials was found to be reduction in HF hospitalization, which raised the possibility of clinical benefit of SGLT2i in HF patients. In DAPA-HF and EMPEROR-Reduced trials in HFrEF patients with or without T2DM, SGLT2is, dapagliflozin and empagliflozin treatment on top of standard HF therapy has been shown to have clear clinical benefit in reducing primary endpoint of CV mortality or HF hospitalization and improving quality of life. Recently published EMPEROR-Preserved and DELIVER trials showed that SGLT2is were also very effective in the treatment of HFpEF (EF >40%). Furthermore, SGLT2is have also been shown to have potential in improving clinical outcomes in hospitalized acute HF patients in EMPULSE and DICTATE-AHF trials. All of this evidence has changed guidelines recommended therapies, not only for HFrEF but also for HFpEF treatment. The aim of this article is to provide a comprehensive overview focused on the role of SGLT2i in the treatment of HF based on the recent evidence.

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Background: Deposition of adipose tissue may have a promoting role in the development of diabetic complications. This study is aimed at investigating the relationship between adipose tissue thickness and risk of contrast-induced nephropathy (CIN) in patients with Type 2 diabetes mellitus (T2DM). Methods: A total of 603 T2DM patients undergoing percutaneous coronary angiography or angioplasty with suspicious or confirmed stable coronary artery disease were enrolled in this study. The thicknesses of perirenal fat (PRF), subcutaneous fat (SCF), intraperitoneal fat (IPF), and epicardial fat (ECF) were measured by color Doppler ultrasound, respectively. The association of various adipose tissues with CIN was analyzed. Results: Seventy-seven patients (12.8%) developed CIN in this cohort. Patients who developed CIN had significantly thicker PRF (13.7 ± 4.0 mm vs. 8.9 ± 3.6 mm, p < 0.001), slightly thicker IPF (p = 0.046), and similar thicknesses of SCF (p = 0.782) and ECF (p = 0.749) compared to those who did not develop CIN. Correlation analysis showed that only PRF was positively associated with postoperation maximal serum creatinine (sCr) (r = 0.18, p = 0.012), maximal absolute change in sCr (r = 0.33, p < 0.001), and maximal percentage of change in sCr (r = 0.36, p < 0.001). In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of PRF (0.809) for CIN was significantly higher than those of SCF (0.490), IPF (0.594), and ECF (0.512). Multivariate logistic regression analysis further confirmed that thickness of PRF, rather than other adipose tissues, was independently associated with the development of CIN after adjusted for confounding factors (odds ratio (OR) = 1.53, 95% CI: 1.38-1.71, p < 0.001). Conclusions: PRF is independently associated with the development of CIN in T2DM patients undergoing coronary catheterization.

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The objective of this study is to investigate the association between diabetic kidney disease (DKD) and various adiposity indexes, including the visceral adiposity index (VAI), lipid accumulation product index (LAPI), visceral fat area (VFA), and subcutaneous fat area (SFA) in type 2 diabetes mellitus (T2DM) patients. 1176 T2DM patients was stratified into normoalbuminuria (NO), microalbuminuria (MI), and macroalbuminuria (MA) groups based on their urinary albumin-creatinine ratio (UACR) levels. To analyse the correlation between DKD and VAI, LAPI, VFA, and SFA. Multiple linear, restricted cubic spline (RCS), subgroup analyses, and multinomial logistic regression were employed. After adjusting for confounding variables, UACR levels were positively associated with VAI, LAPI, and VFA. RCS curves demonstrated a J-shaped dose-response relationship between VAI and LAPI levels with UACR levels, while a linear correlation was observed between UACR levels and VFA. Using the NO and MI as reference groups, the MA group was analysed as the observational group. DKD severity was positively associated with VAI, LAPI and VFA. When evaluating DKD prognostic risk, with the low-risk and medium-risk groups serving as reference categories, a significant positive correlation was identified with prognostic risk and VAI, LAPI, and VFA in the high-risk or very high-risk groups. In patients with T2DM, DKD severity and prognostic risk were positively correlated with VAI, LAPI, and VFA levels.

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INTRODUCTION: The four variable kidney failure (KF) risk equation (KFRE) is recommended to estimate KF risk (ie, need for dialysis or kidney transplantation). Earlier referral to clinical kidney services for people with high-risk of kidney failure can ensure appropriate care, education and support are in place pre-emptively. There are limited data on investigating the performance of KFRE in estimating risk of end-stage kidney disease (ESKD) in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). The primary ESKD endpoint event was defined as estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m2 and secondary endpoint eGFR <15 mL/min/1.73 m2. RESEARCH DESIGN AND METHODS: We studied 7296 people (30% women, 41% African-Caribbean, 45% Caucasian) with T2DM and CKD (eGFR median (range) 48 (15-59) mL/min/1.73 m2) were included at two hospitals in London (median follow-up 10.2 years). Time to ESKD event was the endpoint and Concordance index (C-index) was used to assess KFRE's discrimination of those experiencing ESKD from those who did not. Mean (integrated calibration index (ICI)) and 90th percentile (E90) of the difference between observed and predicted risks were used as calibration metrics. RESULTS: Of the cohort 746 (10.2%) reached ESKD primary event (135 (1.9%) and 339 (4.5%) over 2 and 5 years, respectively). Similarly, 1130 (15.5%) reached the secondary endpoint (270 (3.7%) and 547 (7.5%) over 2 and 5 years, respectively). The C-index for the primary endpoint was 0.842 (95% CI 0.836 to 0.848) and 0.816 (95% CI 0.812 to 0.820) for 2 and 5 years, respectively. KFRE 'under-predicted' ESKD risk overall and by ethnic group. Likewise, the C-index for secondary endpoint was 0.843 (0.839-0.847) and 0.801 (0.798-0.804) for 2 and 5 years, respectively. KFRE performance analysis performed more optimally with the primary endpoint with 50% enhancement of the calibration metrics than with the secondary endpoint. KFRE recalibration improved ICI by 50% and E90 by more than 78%. CONCLUSIONS: Although derived for predicting KF, KFRE also demonstrated good discrimination for ESKD outcome. Further studies are needed to identify variables/biomarkers that may improve KFRE's performance/calibration and to aid the development of other predictive models to enable early identification of people at risk of advanced stages of CKD prior to onset of KF.

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To explore the association between serum calcium levels within normal ranges and Diabetic Kidney Disease (DKD) in type 2 diabetes patients. In this cross-sectional study, we analyzed clinical data from type 2 diabetes patients admitted to the Endocrinology Department of the Affiliated Hospital of Qingdao University from January 1, 2021, to December 1, 2022. We measured serum calcium levels, corrected for albumin, and screened for diabetes-related complications, including DKD. The association between corrected serum calcium levels and DKD was evaluated using logistic regression, with adjustments made for potential confounders and a generalized additive model (GAM) to explore non-linear relationships, supplemented by subgroup analyses. Among the 3016 patients (52.55% male, 47.45% female), the mean corrected serum calcium was 2.29 ± 0.08 mmol/L. DKD was present in 38.73% of patients. A 0.1 mmol/L increase in corrected serum calcium was associated with a 44% increased risk of DKD (OR = 1.44, 95% CI 1.28-1.61, p < 0.0001). The GAM indicated a linear relationship between corrected serum calcium and DKD risk, consistent across subgroups. Corrected serum calcium levels were linearly associated with DKD risk in type 2 diabetes patients, underlining its potential role in risk assessment. These findings emphasize the clinical importance of monitoring serum calcium levels. However, the need for further prospective studies to confirm these findings is underscored by the study's cross-sectional design.

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Objective: To determine the prevalence of non-alcoholic fatty liver disease, and the effect of oral hypoglycaemic drugs and lifestyle modifications in reducing fatty liver changes and liver enzymes in these patients. METHODS: The comparative, observational study was conducted at the Department of Pharmacology, Sohail University, Karachi, from October 2022 to October 2023, and comprised patients of either gender having elevated liver enzymes and ultrasound finding of fatty liver changes along with raised glycated haemoglobin, transaminases, total cholesterol and triglycerides. The participants were prescribed oral hypoglycaemic agents by endocrinologists. Those given empaglifazolin + metformin were in group A, empaglifazolin + linglaptin in group B, sitaglaptin + metformin in group C, metformin alone in group D and sitaglaptin alone in group E. Lifestyle modifications were advised in all the treatment groups, while control group F was only advised lifestyle modifications. The intervention lasted 3 months. Investigations included B-mode ultrasound liver, liver enzymes and glycated haemoglobin, which were done at baseline and after the intervention. Data was analysed using SPSS 25. RESULTS: Of 200 patients, 40 were males and 160 were females in ratio of 1:4. The overall mean age was 48±16 years. There were 154(77%) patients who had non-alcoholic fatty liver disease with type 2 diabetes mellitus, while 46(23%) had only fatty liver changes. There were 50(25%) patients in group A, 30(15%) in group B, 30(15%) in group C, 40(20%) in group D, 10(5%) in group E and 40(20%) in group F. Post-intervention improvement was noted in 48(24%) patients, with 20(41.7%) of them being in group A. Conclusion: The prevalence of non-alcoholic fatty liver disease with type 2 diabetes was high. Combination of empagliflozin + metformin along with lifestyle modifications was highly effective in reducing fatty changes and the level of liver enzymes.

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Objective: This study explored the utility of NLR (neutrophil-to-lymphocyte ratio) as a marker to predict Lower Extremity Peripheral Artery Disease (PAD) in the Chinese population, as well as to assess its consistency and diagnostic value with digital subtraction angiography. Methods: Patients were distributed into three groups according to the angiography in lower limb arterial: group L1, plaque with no stenosis; group L2, plaque with luminal stenosis and group L3, total vascular occlusion. Changes in the neutrophil-to-lymphocyte ratio were documented and compared among groups. Results: Compared to group L1, NLR was significantly increased in L2 (1.76 vs 2.35, p=0.037) and L3 (1.76 vs 3.60, p<0.001), with a gradual decrease in ABI (Ankle-Brachial Index, 1.11 vs 1.02 vs 0.94, p<0.001). Those older patients with higher prevalence of hypertension (p=0.002), obesity (p=0.032), or reduced high-density lipoprotein cholesterol (p=0.020) were more likely to develop PAD; higher glycosylated hemoglobin (p=0.045), low-density lipoprotein cholesterol (p=0.006), and systolic blood pressure (p<0.001) levels led to a greater tendency to suffer stenosis or even occlusion; the probability of severe stenosis (>70%) increased to 2.075 times for every 1 increase in NLR, while it was 46.8% for every 0.1 increase in ABI. The optimal NLR cut-off value to predict severe stenosis in PAD was 2.73. Receiver operating characteristic curve analysis of the inflammatory biomarkers and severe stenosis prediction displayed an area under the curve of 0.81. Conclusion: NLR could serve as a new noninvasive and accurate marker in predicting PAD.

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Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder strongly linked to type 2 diabetes mellitus (T2DM). Understanding the predictive value of lipid parameters in identifying abnormal glucose metabolism in NAFLD patients is crucial for early intervention. Methods: This study analyzed data from the National Health and Nutrition Examination Survey(NHANES) database (2017-2020) involving 1066 NAFLD patients. Participants were categorized into three groups: T2DM (n=414), prediabetes mellitus (pre-DM) (n=507), and normoglycemia (NG) (n=145). Traditional lipid parameters [triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)] and nontraditional lipid parameters [atherogenic index of plasma (AIP), residual cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C)] were evaluated for their association with T2DM and pre-DM. Results: Elevated TG levels were significantly associated with an increased risk of T2DM and pre-DM, whereas high HDL-C demonstrated a protective effect. Among nontraditional lipid parameters, increased AIP and RC were most strongly associated with T2DM risk, while high non-HDL-C was best associated with the development of pre-DM. Stratified analyses revealed that these associations were stronger in younger, non-obese, smoking, and female NAFLD patients. Conclusion: Nontraditional lipid parameters, particularly AIP and RC, show superior predictive value over traditional lipid parameters in identifying abnormal glucose metabolism in NAFLD patients. Incorporating these novel biomarkers into clinical practice could enhance early detection and prevention strategies for T2DM and pre-DM in this high-risk population.

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Background: Mitochondrial dysfunction plays a crucial role in Type 2 Diabetes Mellitus (T2DM) and its complications. However, the genetic pathophysiology remains under investigation. Through multi-omics Mendelian Randomization (MR) and colocalization analyses, we identified mitochondrial-related genes causally linked with T2DM and its complications. Methods: Summary-level quantitative trait loci data at methylation, RNA, and protein levels were retrieved from European cohort studies. GWAS summary statistics for T2DM and its complications were collected from the DIAGRAM and FinnGen consortiums, respectively. Summary-data-based MR was utilized to estimate the causal effects. The heterogeneity in dependent instrument test assessed horizontal pleiotropy, while colocalization analysis determined whether genes and diseases share the same causal variant. Enrichment analysis, drug target analysis, and phenome-wide MR were conducted to further explore the biological functions, potential drugs, and causal associations with other diseases. Results: Integrating evidence from multi-omics, we identified 18 causal mitochondrial-related genes. Enrichment analysis revealed they were not only related to nutrient metabolisms but also to the processes like mitophagy, autophagy, and apoptosis. Among these genes, Tu translation elongation factor mitochondrial (TUFM), 3-hydroxyisobutyryl-CoA hydrolase (HIBCH), and iron-sulfur cluster assembly 2 (ISCA2) were identified as Tier 1 genes, showing causal links with T2DM and strong colocalization evidence. TUFM and ISCA2 were causally associated with an increased risk of T2DM, while HIBCH showed an inverse causal relationship. The causal associations and colocalization effects for TUFM and HIBCH were validated in specific tissues. TUFM was also found to be a risk factor for microvascular complications in T2DM patients including retinopathy, nephropathy, and neuropathy. Furthermore, drug target analysis and phenome-wide MR underscored their significance as potential therapeutic targets. Conclusions: This study identified 18 mitochondrial-related genes causally associated with T2DM at multi-omics levels, enhancing the understanding of mitochondrial dysfunction in T2DM and its complications. TUFM, HIBCH, and ISCA2 emerge as potential therapeutic targets for T2DM and its complications.

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