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Objective: To analyse the correlation between urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR) and the risk factors for reducing eGFR in patients with type 2 diabetes mellitus (T2DM)., Methods: A total of 431 T2DM patients admitted between January 2019 and March 2020 were selected and divided into two groups according to eGFR level. Comparing the differences between baseline data and clinical indicators, multivariate logistic regression was used to analyse the risk factors of eGFR reduction and to analyse the association between UAER and eGFR., Results: In total, 167 patients were included in the study group and 264 patients were included in the conventional group. The study group participants were older, had longer diabetes duration, and had higher fatty liver, peripheral vascular disease (PVD), hypertension prevalence, and mean body mass index (P < 0.05). The levels of various indicators were lower than those of the conventional group (P < 0. 05). Additionally, PVD, nocturnal systolic blood pressure, fatty liver, and beta-2-microglobulin (β 2-MG) were independent risk factors for eGFR decline, with high density lipoprotein (HDL) and fasting C-peptide (CP) as protective factors. There was no obvious correlation between UAER and eGFR., Conclusion: Peripheral vascular disease, systolic blood pressure, fatty liver, and beta-2-microglobulin are risk factors for decreased eGFR levels in patients with T2DM, which should be applied for control DKD. HDL and fasting CP have important effects on maintaining eGFR, and blood pressure and fasting CP can be used as new targets for subsequent diabetic kidney disease treatment., (© 2024. The Author(s).)

Background: A Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes., Methods: The Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006-2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%)., Results: With the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min - 1 ·1.73 m - 2 . The median difference was 4.10 ml·min - 1 ·1.73 m - 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations., Conclusion: Changing from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR < 30 ml·min - 1 ·1.73 m - 2 , but virtually no impact on mortality prediction., Trial Registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008., (© 2024. The Author(s).)

Background: Diabetes mellitus is characterized by insulin resistance (IR) and dysfunctional insulin secretion from pancreatic β-cells. However, little research has been conducted on the relationship between IR and β-cell function in relation to diabetic complications among Korean diabetic patients. This study aimed to examine the differential associations between IR and β-cell function and various diabetic complications among Korean diabetic patients., Methods: The analysis employed a common data model (CDM). IR and β-cell function were quantified using the homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β), respectively. Hazard ratios for diabetic nephropathy, diabetic retinopathy, and cardiovascular disease (CVD) events were calculated., Results: The study cohort consisted of 2,034 diabetic patients aged over 20 years who visited EUMC between January 2001 and December 2019. Among diabetic patients in the highest quartile of HOMA-IR, the adjusted hazard ratio for total CVD events was 1.76 (95% confidence interval [CI], 1.20-2.57) compared with those in the lowest quartile of HOMA-IR (P = 0.004). In contrast, diabetic patients in the lowest quartile of HOMA-β exhibited an adjusted hazard ratio of 3.91 (95% CI, 1.80-8.49) for diabetic retinopathy compared to those in the highest quartile of HOMA-β (P = 0.001)., Conclusion: Insulin resistance and β-cell function exhibited different associations with diabetic complications among Korean diabetic patients. Specifically, lower β-cell function was associated with an increased risk of diabetic retinopathy, whereas higher IR was associated with an increased risk of CVD events. Individuals with pronounced IR should prioritize CVD prevention measures, and those with significant β-cell dysfunction may benefit from early, intensive surveillance for diabetic retinopathy., Competing Interests: We declare that we have no conflict of interests., (Copyright: © 2024 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Microvascular complications, affecting small blood vessels, can lead to serious conditions such as kidney failure, painful nerve damage, and vision loss. Early detection and effective treatment of these issues are vital for improving patient outcomes and reducing healthcare expenses. Thus, this study aimed to assess diabetic microvascular complications among adults with type 2 diabetes in Adama, central Ethiopia. An institutional-based cross-sectional study was conducted among 381 adult type 2 diabetes patients. A computer-generated simple random sampling method was used to select study participants. Data were collected using a structured data extraction checklist. The collected data were entered into Epi info version 7.2 and exported to SPSS version 27 for processing and analysis. Binary logistic regression was employed to model the association between diabetic microvascular complications and explanatory variables. An adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to estimate the strength of association, and statistical significance was proclaimed at a p-value < 0.05. The prevalence of diabetic microvascular complications was 21.8% (95% CI: 17.8-25.6) with diabetic neuropathy being the most common (16.8%), followed by diabetic retinopathy (4.2%), and diabetic nephropathy (2.9%). Poor glycemic control (AOR = 2.00, 95% CI: 1.01-3.98), and a history of hypertension (AOR = 2.36, 95% CI: 1.39-4.00) were positively associated with the development of diabetic microvascular complications. Conversely, being aged 41-60 years (AOR = 0.35, 95% CI: 0.18-0.68) was negatively associated with the development of these complications. About one in five patients developed at least one diabetic microvascular complication. Age, poor glycemic control, and a history of hypertension were associated with the development of these complications. Therefore, intervening to improve glycemic control and manage hypertension is crucial in preventing the onset of diabetic microvascular complications., (© 2024. The Author(s).)

Background: Observational studies have demonstrated the alterations of gut microbiota composition in diabetic nephropathy (DN), however, the correlation between gut microbiota and DN remains unclear., Methods: A two-sample Mendelian randomization (MR) analysis was designed to estimate the association between gut microbiota and DN. The summary statistics of gut microbiota from phylum level to genus level were obtained from a large-scale, genome-wide association study involving 18,340 individuals, and the data at the species level was derived from the study of TwinsUK Registry, including 1126 twin pairs. The summary statistics of DN were originated from the latest release data of FinnGen (R7, 299623 participants). The MR estimation was calculated using inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was assessed using Cochrane's Q test., Results: Inverse variance weighted results indicated that the order Bacteroidetes and its corresponding class and phylum [odds ratio (OR), 1.58; 95% confidence interval (CI), 1.15-2.17], the family Verrucomicrobiaceae and its corresponding class and order (OR, 1.46; 95% CI, 1.14-1.87), the genera Akkermansia (OR, 1.46; 95% CI, 1.14-1.87) and Catenibacterium (OR, 1.33; 95% CI, 1.07-1.66) might be associated with a higher risk of DN; whereas the genera Coprococcus2 (OR, 0.68; 95% CI, 0.51-0.91) and Eubacterium&#95;coprostanoligenes&#95;group (OR, 0.69; 95% CI, 0.52-0.92) might play protective roles in DN., Conclusions: This MR study suggested that several gut bacteria were potentially associated with DN, further studies are required to validate these findings., (© 2024. The Author(s).)

Objective: To construct a risk prediction model for diabetes kidney disease (DKD). Methods: Patients newly diagnosed with type 2 diabetes mellitus (T2DM) between January 1, 2015, and December 31, 2022, were selected as study subjects from the Yinzhou Regional Health Information Platform in Ningbo City. The Lasso method was used to screen the risk factors, and the DKD risk prediction model was established using Cox proportional hazard regression models. Bootstrap 500 resampling was applied for internal validation. Results: The study included 49 706 subjects, with an median ( Q 1 , Q 3 ) age of 60.00 (50.00, 68.00) years old, and 55% were male. A total of 4 405 subjects eventually developed DKD. Age at first diagnosis of T2DM, BMI, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, past medical history (hyperuricemia, rheumatic diseases), triglycerides, and estimated glomerular filtration rate were included in the final model. The final model's C-index was 0.653, with an average of 0.654 after Bootstrap correction. The final model's area under the receiver operating characteristic curve for predicting 4-year, 5-year, and 6-year was 0.657, 0.659, and 0.664, respectively. The calibration curve was closely aligned with the ideal curve. Conclusions: This study constructed a DKD risk prediction model for newly diagnosed T2DM patients based on real-world data that is simple, easy to use, and highly practical. It provides a reliable basis for screening high-risk groups for DKD.

Background: Most existing risk equations for predicting/stratifying individual diabetic kidney disease (DKD) risks were developed using relatively dated data from selective and homogeneous trial populations comprising predominately Caucasian type 2 diabetes (T2D) patients. We seek to adapt risk equations for prediction of DKD progression (microalbuminuria, macroalbuminuria, and renal failure) using empiric data from a real-world population with T2D in Taiwan., Methods: Risk equations from three well-known simulation models: UKPDS-OM2, RECODe, and CHIME models, were adapted. Discrimination and calibration were determined using the area under the receiver operating characteristic curve (AUROC), a calibration plot (slope and intercept), and the Greenwood-Nam-D'Agostino (GND) test. Recalibration was performed for unsatisfactory calibration (p-value of GND test < 0.05) by adjusting the baseline hazards of risk equations to address risk variations among patients., Results: The RECODe equations for microalbuminuria and macroalbuminuria showed moderate discrimination (AUROC: 0.62 and 0.76) but underestimated the event risks (calibration slope > 1). The CHIME equation had the best discrimination for renal failure (AUROCs from CHIME, UKPDS-OM2 and RECODe: 0.77, 0.60 and 0.64, respectively). All three equations overestimated renal failure risk (calibration slope < 1). After rigorous updating, the calibration slope/intercept of the recalibrated RECODe for predicting microalbuminuria (0.87/0.0459) and macroalbuminuria (1.10/0.0004) risks as well as the recalibrated CHIME equation for predicting renal failure risk (0.95/-0.0014) were improved., Conclusions: Risk equations for prediction of DKD progression in real-world Taiwanese T2D patients were established, which can be incorporated into a multi-state simulation model to project and differentiate individual DKD risks for supporting timely interventions and health economic research., (© 2024. The Author(s).)

Aims: Diabetic nephropathy, vision loss and diabetic retinopathy (DR) are frequent comorbidities among individuals with type 2 diabetes (T2D). The Retinopathy in People Currently On Renal Dialysis (RiPCORD) study sought to examine the epidemiology and risk of vision impairment (VI) and DR among a cohort of Indigenous and non-Indigenous Australians with T2D currently receiving haemodialysis for end-stage renal failure (ESRF)., Methods: A total of 106 Indigenous and 109 non-Indigenous Australians were recruited in RiPCORD across five haemodialysis centres in urban and remote settings. Clinical assessments, questionnaires and medical record data determined the rates of ocular complications and risk factor profiles., Results: Prevalence rates include unilateral VI, 23.5 %; bilateral VI, 11.7 %; unilateral blindness, 14.2 %; and bilateral blindness, 3.7 %, with no significant differences between sub-cohorts (p=0.30). DR prevalence rates were 78.0 % among non-Indigenous Australians and 93.1 % among Indigenous Australians (p=<0.001). Non-Indigenous ethnicity (OR: 0.28) and pre-dialysis diastolic blood pressure (OR: 0.84 per 10-mmHg) were protective, while peripheral vascular disease (OR: 2.79) increased DR risk., Conclusions: Ocular complications among individuals with T2D and ESRF are disproportionately high, especially for Indigenous Australians, and beyond what can be accounted for by risk factor variation. Findings suggest a need to improve screening and preventative efforts within this high-risk population group., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the US, approximately 11% of the population have diagnosed diabetes and nearly 40% have prediabetes. In addition, chronic kidney disease (CKD) affects 14% of the US population including up to 40% of those with diabetes. Cardiovascular disease (CVD) remains the leading cause of death worldwide where it affects approximately half of adults. The presence of CKD or diabetes doubles the risk of cardiovascular events. When both CKD and diabetes occur in the same patient the risks are further increased. The clinical problems of hypertension, hyperglycemia, and hyperlipidemia are all closely related with obesity, metabolic syndrome, Type 2 diabetes, CKD, atherosclerotic cardiovascular disease, heart failure and non-alcoholic fatty liver disease and metabolic dysfunction-associated steatohepatitis. The increasing frequency of obesity has driven increases in all of these medical comorbidities. These conditions frequently cluster together in the same patient exacerbating the risk of morbidity and mortality. They are also associated with cognitive dysfunction/dementia, pulmonary diseases, cancers, gastrointestinal diseases, immune system abnormalities, and inflammatory disorders. Only 6.8% of adults in US meet all targets for cardiovascular risk management with significant disparities based on race and ethnicity. Given the complexity of these multisystem problems in people with diabetes and obesity, it would seem reasonable to attempt to diagnose and treat many of the comorbidities earlier in the course of disease rather than wait for substantial end organ dysfunction to occur. The American Diabetes Association (ADA) has recently published a consensus statement recommending early screening for the diagnosis of heart failure, CKD and diabetes, recognizing both the frequency and gravity of this combination. Likewise, there are recommendations in the guidelines to facilitate screening for microalbuminuria, blood pressure, glycemic control and lipids earlier in patients at risk rather than wait and treat as a secondary prevention program. Thus, the general principle is to facilitate earlier recognition and diagnosis and provide treatment before downstream target organ complications occur. This review will focus on CVD and risk management based on newest recommendations and standards of care in people with diabetes by the ADA. The main considerations in the treatment of people with diabetes are glycemic control, blood pressure, lipids, and the use of medications with proven cardiorenal disease progression capability to prevent or delay., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: The main objective in this study was to determine the prevalence of Chronic Kidney Disease (CKD) in people with Type 2 Diabetes Mellitus (T2DM) in the Autonomous Community (AC) of Aragon (Spain) and to detect whether or not there is under-registration in the patient's history. As a secundary objetive, it was proposed to study the most relevant demographic and clinical characteristics of people with CKD., Methods: Observational and retrospective real world data study of the population over 18 years of age with a diagnosis of T2DM, between January 2017 and December 2021. A descriptive analysis of qualitative and quantitative variables, and a comparison using the parametric Student's t-test or the non-parametric Mann-Whitney U-test between both groups was performed., Results: The prevalence of T2DM was 8.07 % and that of CKD 31.4 %, with an under-reporting of 47 %. The main risk factor associated with CKD was arterial hypertension (p<0.001), followed by dyslipidemia (p<0.001). The main treatment used for diabetes control was metformin, both in patients with and without CKD (p<0.001). A total of 56.81 % of people with T2DM and CKD did not undergo annual monitoring of their renal function (glomerular filtration rate) or determination of albuminuria., Conclusions: The prevalence of CKD increases in patients with T2DM (31.4 %), and in almost half of patients the diagnosis is not registered (47 %). This under-reporting delays the implementation of measures needed to prevent CKD progression., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest in the conduct of this study., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Aims: To compare the time in range (TIR) obtained from self-monitoring of blood glucose (SMBG) with that obtained from continuous glucose monitoring (CGM), and explore the relationship of TIR with microalbuminuria outcome, HOMA-IR and HOMA-β test., Methods: We recruited 400 patients with type 2 diabetes to carry out blood glucose monitoring by both SMBG and CGM for 3 consecutive days. TIR, TAR, TBR and other blood glucose variation indices were calculated respectively through the glucose data achieved from SMBG and CGM. The HOMA-IR and HOMA-β test was evaluated by an oral glucose tolerance test. Urinary microalbumin-to-creatinine ratio completed in the laboratory., Results: The median (25 %, 75 % quartile) of TIR CGM and TIR SMBG were 74.94(44.90, 88.04) and 70.83(46.88, 87.50) respectively, and there was no significant difference, p = 0.489; For every 1 % increase in TIR CGM , the risk of microalbuminuria decreased by 1.6 % (95%CI:0.973, 0.995, p = 0.006) and for every 1 % increase in TIR SMBG , the risk of microalbuminuria decreased by 1.3 % (95%CI:0.975, 0.999, p = 0.033). Stepwise multiple linear regression analysis showed an independent positive correlation between TIR (including TIR CGM and TIR SBMG ) and LnDI30 and LnDI120 levels (p = 0.000)., Conclusions: The TIR calculated by SMBG was highly consistent with that reported by CGM and was significantly associated with the risk of microalbuminuria and the HOMA-β. Higher TIR quartiles were associated with lower incidence of microalbuminuria as well as higher lever of HOMA-β. For patients with limited CGM application, SMBG-derived TIR may be an alternative to CGM-derived TIR, to assess blood glucose control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Aim: To investigate the clinical significance of body weight changes on kidney outcomes among individuals with diabetes using sodium-glucose cotransporter-2 (SGLT2) inhibitors., Materials and Methods: This is a retrospective cohort study using a nationwide epidemiological database, and we conducted an analysis involving 11 569 individuals with diabetes who were newly prescribed SGLT2 inhibitors. The main outcome was the rate of decline in estimated glomerular filtration rate (eGFR), determined through a linear mixed-effects model with an unstructured covariance structure., Results: The median age of the patients was 52 (Q1-Q3: 47-58) years, and the median fasting plasma glucose and glycated haemoglobin (HbA1c) levels were 144 (Q1-Q3: 124-175) mg/dL and 7.4 (Q1-Q3: 6.8-8.3)%, respectively. The median estimated eGFR was 77.7 (Q1-Q3: 67.2-89.1) mL/min/1.73 m 2 . The median follow-up period was 1.7 (Q1-Q3: 1.0-2.6) years. Participants were stratified into three groups based on the body mass index change rate tertiles between baseline and 1 year after (tertile 1: <-4.55%, tertile 2: -4.55% to -1.43%, tertile 3: >-1.43%). The annual change in eGFR was -0.78 (-0.94 to -0.63) mL/min/1.73 m 2 in tertile 1, -0.95 (-1.09 to -0.81) mL/min/1.73 m 2 in tertile 2, and -1.65 mL/min/1.73 m 2 (-1.84 to -1.47) in tertile 3 (p interaction  < 0.001). A variety of sensitivity analyses confirmed the relationship between the 1-year body mass index decrease and favourable kidney outcomes after SGLT2 inhibitor administration., Conclusions: Our analysis of a nationwide epidemiological cohort revealed that kidney outcomes following the initiation of SGLT2 inhibitors would be more favourable, with greater body weight loss observed after the initiation of SGLT2 inhibitors., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: This study aimed to investigate the role of uric acid (UA) in diabetic nephropathy (DN) from epidemiological and genetic perspectives., Methods: We used data from the 2007-2016 National Health and Nutrition Examination Survey to evaluate the relationship between UA and DN risk using weighted multivariate-adjusted logistic regression. Subsequently, a two-sample Mendelian randomization study was conducted using genome-wide association study summary statistics. The main inverse variance weighting (IVW) method and supplementary MR method were used to verify the causal relationship between UA and DN, and sensitivity analysis was conducted to confirm the credibility of the results., Results: Our observational study enrolled 4363 participants with diabetes mellitus from NHANES, among them, 2682 (61.4%) participants were identified as DN. The multivariate logistic regression model showed that compared with those without hyperuricemia, the DN risk of the hyperuricemia population was significantly increased (P < 0.05). The MR results suggest a direct causal effect of hyperuricemia on DN (IVW odds ratio (OR): 1.37 (95% confidence interval 1.07-1.76); P = 0.01), which is consistent with findings from other MR methods., Conclusion: The evidence from observational studies indicates a positive correlation between HUA and the onset of DN. And the causal effects of HUA on DN were supported by the MR analysis., (© 2024. The Author(s).)

Aim: To assess mortality and complication trends in people with type 1 diabetes during the 11 years before the SARS-CoV2 pandemic (2009-2019)., Materials and Methods: Sequential cohorts of people in England with type 1 diabetes aged ≥20 years from the National Diabetes Audit (2006/2007 to 2016/2017) were analysed. Discretized Poisson regression models, adjusted for age, sex, ethnicity, socioeconomic deprivation and duration of diabetes, were used to calculate mortality and hospitalization rates., Results: Demographic characteristics changed little; average diabetes duration increased. All-cause mortality was unchanged. Cardiovascular and kidney disease mortality declined. Mortality from respiratory disease, diabetes and dementia increased in younger people (aged 20-74 years) as did mortality from liver disease and dementia in the elderly (aged ≥75 years). Younger Asian and Black people had lower all-cause mortality than those of White ethnicity; elderly Mixed, Asian and Black people had lower all-cause mortality. People from more deprived areas had higher all-cause mortality. The deprivation gradient for mortality was steeper at younger ages. In younger people, rates of hospitalization increased for myocardial infarction, stroke, heart failure and kidney disease but only for kidney disease in the elderly. Rates of a composite measure of cardiovascular hospitalizations increased in younger people (rate ratio [RR] 1.07, 95% confidence interval [CI] 1.03-1.11) but declined in the elderly (RR 0.91, 95% CI 0.86-0.95)., Conclusion: Between 2009 and 2019, hospitalizations for cardiovascular disease increased at younger ages (20-74 years) and hospitalizations for kidney disease increased at all ages, but mortality from cardiovascular and kidney disease declined. All-cause mortality rates were unchanged., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To estimate individual treatment effects (ITEs) of sodium-glucose co-transporter-2 inhibitors (SGLT2is) on lowering the risk of developing chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) and to identify those most probable to benefit from treatment., Methods: This study followed a T2D cohort from Ramathibodi Hospital, Thailand, from 2015 to 2022. A counterfactual model was constructed to predict factual and counterfactual risks of CKD if patients did/did not receive SGLT2is. ITEs were estimated by subtracting the factual risk from the counterfactual risk of CKD., Results: There were 1619 and 15 879 patients included in the SGLT2i and non-SGLT2i groups, respectively. The estimated ITEs varied from -1.19% to -17.51% with a median of -4.49%, that is, 50% of patients had a 4.49% or greater lower CKD risk if they received an SGLT2i. Patients who gained the greatest benefit from SGLT2is were more probable to be male, aged at least 60 years, with a history of diabetes duration of at least 3 months, hypertension, peripheral arterial disease, diabetic retinopathy and low high-density lipoprotein cholesterol., Conclusions: Our prediction model provides individualized information that helps target T2D patients who may benefit more from SGLT2is. This could help clinical decision making and implementation of personalized medicine in clinical practice, especially in resource-limited settings., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To provide an overview of the primary outcomes and key clinical implications of the CANVAS Program and CREDENCE trial, which were event-driven, double-blind randomized controlled trials that established the efficacy and safety of canagliflozin in those with type 2 diabetes (T2D) and high cardiovascular risk (CV) or albuminuric chronic kidney disease (CKD)., Methods and Results: The CANVAS programme (CANVAS and CANVAS-R trials) randomized 10 142 people with T2D and high CV risk to canagliflozin or placebo and followed them for a median of 126 weeks. The primary efficacy outcome was met, with canagliflozin treatment associated with a 14% reduction in major adverse CV events (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75 to 0.97; p < 0.001) as compared to placebo. The CREDENCE trial randomized 4401 individuals with T2D and albuminuric CKD to canagliflozin or placebo and followed them for 109 weeks. The CREDENCE trial also met its primary endpoint; canagliflozin treatment was associated with a 30% reduction in the composite of kidney failure, sustained doubling of serum creatinine level, or death from kidney or CV causes (HR 0.70, 95% CI 0.59 to 0.82; p < 0.001). Substantial reductions in hospitalization for heart failure (CANVAS: HR 0.67, 95% CI 0.52 to 0.87; CREDENCE: HR 0.61, 95% CI 0.47 to 0.80) and other key CV and kidney outcomes were also identified. Relative clinical benefits were consistent across subgroups defined by baseline age, sex, kidney function and history of CV disease but absolute benefits were greatest in those at highest baseline risk. Total serious adverse events were less common with canagliflozin treatment. Concerns about amputation and fracture risk observed in the CANVAS Program were not seen in CREDENCE and appear to have been spurious chance findings., Conclusion: Canagliflozin reduced important CV, kidney and mortality outcomes in those with T2D and high CV risk or CKD across diverse patient groups, with a good safety profile. Taken together with the other sodium-glucose cotransporter-2 inhibitor CV and renal outcomes trials, these landmark findings have changed the treatment landscape for patients worldwide., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Chronic kidney disease (CKD) associated with type 2 diabetes (T2DM) is a global challenge; progression to end-stage kidney disease (ESKD) and increased risk of cardiovascular disease (CVD) associated with advancing nephropathy are a significant source of morbidity, mortality, and healthcare expenditure. Until recently, renin-angiotensin system (RAS) blockade was the mainstay of pharmacotherapy in diabetic kidney disease (DKD), representing a therapeutic paradigm shift towards interventions that delay disease progression independently of antihypertensive effects. However, a significant residual risk of DKD progression persisted in patients established on RAS blockade, highlighting the need for additional treatment options. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally licensed as glucose-lowering agents in people with T2DM, serendipitously demonstrated beneficial renal and cardiovascular outcomes in clinical trials designed primarily to evaluate their cardiovascular safety. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial was the first to study the effect of SGLT2 inhibition on a primary composite renal endpoint of ESKD, doubling of serum creatinine, or renal or cardiovascular death in 4401 people with T2DM and CKD established on RAS blockade. The trial was stopped early due to efficacy, demonstrating a 30% relative risk reduction in the primary endpoint in the canagliflozin group (hazard ratio 0.70, 95% confidence interval 0.59-0.82; p = 0.00001). Through discussion of the primary analysis from CREDENCE, and selected post hoc analyses, we review the significant benefits highlighted by this landmark study, its role in shaping clinical guidelines, and in re-establishing interest in interventions that reduce the residual risk of progression of DKD, alongside its interrelation with cardiovascular morbidity and heart failure. We also provide a brief narrative summary of key renal outcome trials since CREDENCE, which indicate emerging avenues for pharmacotherapy beyond SGLT2 inhibition., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims/introduction: The time course of chronic kidney disease in young-onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young-onset (aged ≤40 years) and late-onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort., Materials and Methods: Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young- and late-onset. The primary endpoint was eGFR <60 mL/min/1.73 m 2 , proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence., Results: Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young-onset and 548 (87.6%) had late-onset diabetes. The incidence of eGFR <60 mL/min/1.73 m 2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young-onset type 2 diabetes mellitus group. The Kaplan-Meyer curve showed that young-onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m 2 and an increased HR for proteinuria compared with late-onset type 2 diabetes mellitus. In the multivariate Cox analysis, young-onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03-2.26), but did not change the eGFR <60 mL/min/1.73 m 2 HR., Conclusions: Young-onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m 2 and an increased HR of proteinuria compared with late-onset type 2 diabetes mellitus, indicating that young-onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Competing Interests: Declaration of Competing Interest The author declared no conflict of interest.

The accumulation of advanced glycation end-products (AGEs) elicits morphofunctional kidney impairment. AGEs levels can be noninvasively estimated by skin autofluorescence (SAF). We explored whether high SAF predicts kidney outcomes in type 2 diabetes (T2D) individuals. The study was conducted as a predefined analysis of the Brazilian Diabetes Study, a prospective single-center cohort of T2D adults. Data from 155 individuals followed for up to 1716 days were considered. The incidence of major adverse kidney events (MAKE) was 9.6%. Individuals with above-median SAF had a higher incidence of MAKEs (4.6% vs. 21%; p = 0.002), with an HR of 3.39 [95% CI: 1.06-10.85; p = 0.040] after adjustment by age and gender. The mean adjusted eGFR change was 1.08 units (SE: 1.15; 95%CI: -1.20, 3.37) in the low SAF and -5.19 units [SE: 1.93; 95%CI: -9.10, -1.29] in the high SAF groups (between-subject difference: F: 5.62, p = 0.019). The high-SAF group had a greater prevalence of rapid decliners than the low-SAF group (36.7% vs. 15.8%; p = 0.028). In conclusion, high SAF was related to increased incidence of MAKEs and faster decline in eGFR among T2D subjects. This should be considered by healthcare providers when identifying individuals more prone to diabetes-related kidney complications.

Background: Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus (DM). Diabetes mellitus contributes to about 66% of CKD cases globally. CKD results in increased morbidity and mortality and advanced stages often require kidney replacement therapy that is unaffordable for the majority of the patients. Developing countries have scanty data regarding CKD burden in diabetic patients., Objectives: This study aimed at determining the prevalence of low estimated glomerular filtration rate (eGFR) and proteinuria and associated clinical and socio-demographic factors among adult diabetic patients attending the diabetic clinic of Mbale Regional Referral Hospital (MRRH)., Methods: A cross-sectional study was conducted at the adult diabetic clinic of MRRH in Eastern Uganda. A total of 374 adult diabetic patients were enrolled. A urine sample for urine albumin creatinine ratio (UACR) determination and a venous blood sample for measurement of serum creatinine were obtained from each participant. The eGFR was determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and CKD was staged according to the Kidney Disease Improving Global Outcomes (KDIGO) classification., Results: A total of 318 (85%) participants had an eGFR of ≤ 60 mL/min/1.73m2, UACR of ≥ 30g/g, or both. Only 6.1% were aware. Age, duration of DM, hypertension, and dyslipidemia were associated with low eGFR and proteinuria., Conclusion: There is a high prevalence of low eGFR and proteinuria among DM patients, 85% of the participants had these markers of CKD and the majority of them were undiagnosed. Over half of the DM patients had an eGFR consistent with advanced CKD. Strengthening routine screening for CKD biomarkers and equipping DM clinics with more diagnostic resources is recommended., (© 2024. The Author(s).)

Background: Nephropathy is one of the most common microvascular impediments of diabetes mellitus. In this study, we aimed to estimate the prevalence of nephropathy in diabetic patients across the North American region., Methods: Eligible studies were screened out from 3 electronic databases, for example, PubMed, Google Scholar, and ScienceDirect using specific search keywords based on the eligibility criteria. Extracting the data from the included studies publication bias, quality assessment, outlier investigation, and meta-analysis was done followed by the subgroup analysis. A total of 11 studies met the study inclusion criteria. Meta-analysis was performed with the extracted data., Results: Pooled prevalence of 28.2% (95% confidence interval [CI]: 19.7-36.7) with a high rate of heterogeneity (I2 = 100%) was identified. The pooled prevalence of nephropathy among diabetic patients in the United States of America, Canada, and Mexico was 24.2% (95% CI: 13.8-34.5), 31.2% (95% CI: 25.8-36.5), and 31.1% (95% CI: 20.8-41.5), respectively., Conclusion: The prevalence of nephropathy among diabetic patients was found lower in the United States of America as compared to Canada and Mexico. Besides, the pooled prevalence of the North American region was found to be lower as compared to the African, European, and Asian regions. Minimizing the pathogenic factors, sufficient diagnostic, healthcare facilities, and awareness are recommended to improve the situation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Individuals with diabetes and chronic kidney disease are at high risk of kidney failure, cardiovascular events and premature mortality and more research is warranted to further improve the prevention and management of complications. The PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy (PRIMETIME) 1 cohort is designed to study clinical characteristics, diagnostic accuracy and prognostic markers in a population with diabetes and kidney disease classified by biopsy., Participants: This retrospective Danish nationwide cohort includes 2586 individuals with diabetes who have undergone a kidney biopsy between the 1980s and 2022., Findings to Date: By combining multiple registries and medical databases, we comprehensively describe the cohort with data on demographics, socioeconomic status, lifestyle, laboratory measurements, medication use and comorbidity at the time of diagnosis of diabetes and at the time of kidney biopsy within types of kidney disease. In individuals with type 1 diabetes, 132 cases of diabetic nephropathy were identified, with 70.5% of them being men, with a median (IQR) age of 50 (41-59) years at biopsy, and a median (IQR) estimated glomerular filtration rate (eGFR) 37 (23-5X) mL/min/1.73 m 2 . Among individuals with type 2 diabetes and diabetic nephropathy (n=599), 76.8% were male aged 61.9 (55-99) years at biopsy and with an eGFR 40 (24-6X) mL/min/1.73 m 2 ., Future Plans: The national population registries in Denmark provide a long follow-up period and a distinct opportunity to use superior registry data. This cohort offers a unique opportunity to study the prognostic value of findings in kidney biopsies, the impact of comorbidity and the effect of therapy at the time of kidney biopsy, with a follow-up period increasing over time with running updates., Competing Interests: Competing interests: KHJ, MM and IB received funding from The Novo Nordisk Foundation. DH reports a research grant from Vifor Pharma and Gedeon Richter and consultancy fees and lecture fees from UCB Nordic, GSK and Astra Zeneca. FP reports receiving honoraria for lectures and consultancy from AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk and Sanofi. IB reports honoraria for lectures from Bayer. PR reports research grants to Steno Diabetes Center Copenhagen from Astra Zeneca, Novo Nordisk and Bayer, and honoraria to Steno Diabetes Center Copenhagen for education and consultancy from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Eli Lily, Novo Nordisk, Novartis and Sanofi. RB reports honoraria for education and consultancy from Astra Zeneca, Bayer, Novo Nordisk and Boehringer Ingelheim. VK reports no conflicts of interest in this work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 m 2 and secondary endpoint eGFR <15 mL/min/1.73 m 2 ., 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 m 2 ) 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiovascular autonomic neuropathy (CAN) is known to affect patients with diabetes mellitus (DM) and cause adverse renal outcomes. We aimed to analyze the association between CAN and diabetic kidney disease (DKD)., Method: We enrolled 254 DM patients (mean age, 56.7 ± 15.2 years; male: female ratio, 1.17:1) with 19 (7.5%) type 1 DM patients and 235 (92.5%) type 2 DM patients. All patients had undergone cardiovascular autonomic function tests between January 2019 and December 2021 in a tertiary hospital in Korea. Cardiovascular autonomic neuropathy was categorized as normal, early, or definite after measuring three heart rate variability parameters. Diabetic kidney disease refers to a persistently elevated urinary albumin-creatinine ratio (uACR ≥30 mg/g) or reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m 2 ). Logistic and Cox regression analyses were performed., Results: Patients with elevated uACR (n=107) and reduced eGFR (n=32) had a higher rate of definite CAN. After adjusting for covariates, definite CAN was associated with elevated uACR (OR=2.4, 95% CI 1.07-5.36) but not with reduced eGFR (OR=3.43, 95% CI 0.62-18.90). A total of 94 patients repeated uACR measurements within 2 years (mean follow-up, 586.3 ± 116.8 days). Both definite and early CAN were independent risk factors for elevated uACR (HR=8.61 and 8.35, respectively; both p <0.05). In addition, high-density lipoprotein cholesterol, ACE inhibitors/angiotensin receptor blockers and glucagon-like peptide-1 receptor agonists were independent protective factors for elevated uACR (HR=0.96, 0.25, and 0.07, respectively; all p <0.05)., Conclusion: Cardiovascular autonomic neuropathy is a potential indicator of DKD. Comprehensive management of DKD in the early stages of CAN may prevent microalbuminuria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cho, Lim, Kwon, Chung, Moon, Yoon and Won.)

Objectives: We aim to evaluate estimated glomerular filtration rate (eGFR) patterns of progression in a multiethnic cohort of people with type I diabetes mellitus and with baseline eGFR ≥45 mL/min/1.73 m 2 ., Design: Observational cohort., Setting: People with a clinical diagnosis of type 1 diabetes, attending two university hospital-based outpatient diabetes clinics, in South London between 2004 and 2018., Participants: We studied 1495 participants (52% females, 81% white, 12% African-Caribbean and 7% others)., Primary and Secondary Outcome Measures: Clinical measures including weight and height, systolic blood pressure, diastolic blood pressure and laboratory results (such as serum creatinine, urine albumin to creatinine ratio (ACR), HbA1c were collected from electronic health records (EHRs) and eGFR was estimated by the Chronic Kidney Disease-Epidemiology Collaboration. Ethnicity was self-reported., Results: Five predominantly linear patterns/groups of eGFR trajectories were identified. Group I (8.5%) had a fast eGFR decline (>3 mL/min/1.73 m 2 year). Group II (23%) stable eGFR, group III (29.8%), groups IV (26.3%) and V (12.4%) have preserved eGFR with no significant fall. Group I had the highest proportion (27.6%) of African-Caribbeans. Significant differences between group I and the other groups were observed in age, gender, HbA1C, systolic and diastolic blood pressure, body mass index, cholesterol and urine ACR, p<0.05 for all. At 10 years of follow-up, 33% of group I had eGFR <30 and 16.5%<15 (mL/min/1.73 m 2 )., Conclusions: Distinct trajectories of eGFR were observed in people with type 1 diabetes. The group with the highest risk of eGFR decline had a greater proportion of African-Caribbeans compared with others and has higher prevalence of traditional modifiable risk factors for kidney disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: The prevalence of type 2 diabetes mellitus (T2DM) and bone metabolism disorders increase with age. Diabetic kidney disease (DKD) is one of the most serious microvascular complications of T2DM, and bone metabolism disorders are closely linked to the occurrence of DKD. The relationship between bone turnover markers(BTMs) and the kidney disease in elderly patients with T2DM remains unclear. Therefore, this study aims to investigate the association between common BTMs and DKD in a large sample of elderly patients. The goal is to provide a basis for early identification of high-risk individuals for DKD among elderly T2DM patients from a bone metabolism perspective., Methods: In this cross-sectional study, BTMs were collected from a cohort of 2,051 hospitalized Chinese patients. The relationships between 25-hydroxyvitamin D (25-OH-D), β-CrossLaps (β-CTX), osteocalcin (OSTEOC), intact parathyroid hormone (iPTH), and total type I collagen N-terminal propeptide (TP1NP), and DKD, as well as urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were analyzed using regression analysis and restrictive cubic spline (RCS) curves., Results: Higher 25-OH-D levels were independently linked to a lower incidence of DKD and decreased UACR. The RCS curves showed a linear association of 25-OH-D and DKD, approaching the L-shape. β-CTX was independently and positively correlated with UACR. There is an independent positive correlation between OSTEOC and UACR and a negative correlation with eGFR. iPTH is independently and positively correlated with DKD incidence and UACR, and negatively correlated with eGFR. Additionally, the RCS curves showed a non-linear association of OSTEOC and iPTH and DKD, approaching the J-shape, and the point of inflection is 10.875 ng/L and 34.15 pg/mL respectively. There is an independent positive correlation between TP1NP and UACR incidence, and a negative correlation with eGFR. Risk estimates significantly increase with higher TP1NP levels in the RCS model., Conclusion: BTMs are closely associated with kidney disease in elderly patients with T2DM. These discoveries potentially assist clinicians in establishing more preventive measures and targeted treatment strategies for elderly patients with T2DM., (© 2024. The Author(s).)

Introduction: Diabetes is linked to neurodegenerative diseases (NDs), but data in type 1 diabetes are scarce. Our aim was to assess the standardized incidence ratios (SIRs) of different NDs in type 1 diabetes, and to evaluate the impact of diabetic vascular complications and age at diabetes onset., Research Design and Methods: In this observational cohort study, we included 4261 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy study, and 11 653 matched population-based controls without diabetes. NDs were identified from registers until the end of 2017. Diabetic complications were assessed at the baseline study visit. SIRs were calculated from diabetes onset, except for impact of complications that was calculated from baseline study visit., Results: The SIRs for NDs were increased in type 1 diabetes: any dementia 2.24 (95% CI 1.79 to 2.77), Alzheimer's disease 2.13 (95% CI 1.55 to 2.87), vascular dementia 3.40 (95% CI 2.08 to 5.6), other dementias 1.70 (95% CI 1.22 to 2.31), and Parkinson's disease 1.61 (95% CI 1.04 to 2.37). SIR showed a twofold increased incidence already in those without albuminuria (1.99 (1.44-2.68)), but further increased in presence of diabetic complications: kidney disease increased SIR for Alzheimer's disease, while cardiovascular disease increased SIR for both Alzheimer's disease and other dementias. Diabetes onset <15 years, compared with ≥15 years, increased SIR of Alzheimer's disease, 3.89 (2.21-6.35) vs 1.73 (1.16-2.48), p<0.05, but not the other dementias., Conclusions: ND incidence is increased 1.7-3.4-fold in type 1 diabetes. The presence of diabetic kidney disease and cardiovascular disease further increased the incidence of dementia., Competing Interests: Competing interests: MIE is a shareholder of BCB Medical. P-HG reports receiving lecture fees from Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Elo Water, Genzyme, Medscape, Merck, Sharp & Dohme, Mundipharma, Novartis, Novo Nordisk, PeerVoice, Sanofi, and Sciarc. P-HG reports being an advisory board member for AbbVie, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, Medscape, Merck, Sharp & Dohme, Mundipharma, Nestlé, Novartis, Novo Nordisk, and Sanofi., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Chronic kidney disease (CKD) etiology varies greatly between developed and developing countries. In addition, differences in underlying pathogenesis and therapeutic options affect the progression towards advanced-CKD. This meta-analysis aims to identify the etiology of advanced-CKD in Southeast Asia., Methods: A systematic search in four electronic-databases and complementary search on national kidney registries and repository libraries was conducted until July 20, 2023. The risk of bias was assessed using Newcastle-Ottawa Scale for observational studies and Version-2 of Cochrane for intervention studies. A random-effects model was used to estimate pooled prevalence. The protocol is registered in the International Prospective Register of Systematic Reviews PROSPERO; Registration ID:CRD42022300786., Results: We analyzed 81 studies involving 32,834 subjects. The pooled prevalence of advanced-CKD etiologies are diabetic kidney disease (DKD) 29.2% (95%CI 23.88-34.78), glomerulonephritis 20.0% (95%CI 16.84-23.38), hypertension 16.8% (95%CI 14.05-19.70), other 8.6% (95%CI 6.97-10.47), unknown 7.5% (95%CI 4.32-11.50), and polycystic kidney disease 0.7% (95%CI 0.40-1.16). We found a significant increase in DKD prevalence from 21% (9.2%, 95%CI 0.00-33.01) to 30% (95%CI 24.59-35.97) before and after the year 2000. Among upper-middle-income and high-income countries, DKD is the most prevalent (26.8%, 95%CI 21.42-32.60 and 38.9%, 95%CI 29.33-48.79, respectively), while glomerulonephritis is common in lower-middle-income countries (33.8%, 95%CI 15.62-54.81)., Conclusion: The leading cause of advanced-CKD in Southeast Asia is DKD, with a substantial proportion of glomerulonephritis. An efficient screening program targeting high-risk populations (diabetes mellitus and glomerulonephritis) is needed, with the aim to delay CKD progression., (© 2024. The Author(s).)

Objective: Tubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D)., Research Design and Methods: We performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning ∼30 years, with incident macroalbuminuria ("severely elevated albuminuria," urinary albumin excretion rate [AER] ≥300 mg/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR <60 mL/min/1.73 m2) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. Biomarkers included KIM-1 and sTNFR1 in serum/plasma, MCP-1 and EGF in urine, and a composite tubular secretion score reflecting secreted solute clearance. We assessed biomarkers using single values, as mean values from consecutive time points, and as change over consecutive time points, each as time-updated exposures., Results: At baseline, mean diabetes duration was 5.9 years, with mean HbA1c 8.9%, eGFR 125 mL/min/1.73 m2, and AER 16 mg/day. There were 4.8 and 3.5 cases per 1,000 person-years of macroalbuminuria and low eGFR, respectively. Assessed according to single biomarker values, KIM-1 was associated with risk of subsequent macroalbuminuria and low eGFR (hazard ratio [HR] per 20% higher biomarker 1.11 [95% CI 1.06, 1.16] and 1.12 [1.04, 1.21], respectively) and sTNFR1 was associated with subsequent macroalbuminuria (1.14 [1.03, 1.25]). Mean KIM-1 and EGF-to-MCP-1 ratio were associated with subsequent low eGFR. In slope analyses, increases in KIM-1 and sTNFR1 were associated with subsequent macroalbuminuria (per 20% biomarker increase, HR 1.81 [1.40, 2.34] and 1.95 [1.18, 3.21]) and low eGFR (2.26 [1.65, 3.09] and 2.94 [1.39, 6.23])., Conclusions: Serial KIM-1 and sTNFR1 are associated with incident macroalbuminuria and sustained low eGFR in T1D., (© 2024 by the American Diabetes Association.)

Background: We examined the trajectory of estimated glomerular filtrate rate (eGFR), associated risk factors, and its relationship with end-stage kidney disease (ESKD) among a multiethnic patient population with type 2 diabetes in Singapore., Methods: A follow-up study included 62 080 individuals with type 2 diabetes aged ≥18 years in a multi-institutional SingHealth Diabetes Registry between 2013 and 2019. eGFR trajectories were analyzed using latent class linear mixed models. Factors associated with eGFR trajectories were evaluated using multinomial logistic regression. The association of eGFR trajectories with ESKD was assessed via competing risk models., Results: Trajectory of kidney function, determined by eGFR, was nonlinear. The trajectory pattern was classified as stable initially then gradual decline (75%), progressive decline (21.9%), and rapid decline (3.1%). Younger age, female sex, Malay ethnicity, lower-income housing type, current smoking, higher glycated hemoglobin, lower low-density lipoprotein, higher triglyceride, uncontrolled blood pressure, albuminuria, cardiovascular disease, hypertension, and higher eGFR levels each were associated with progressive or rapid decline. Compared with the trajectory of stable initially then gradual eGFR decline, progressive decline increased the hazard of ESKD by 6.14-fold (95% confidence interval [CI]: 4.96-7.61)) and rapid decline by 82.55 folds (95% CI: 55.90-121.89)., Conclusions: Three nonlinear trajectory classes of kidney function were identified among multiethnic individuals with type 2 diabetes in Singapore. About one in four individuals had a progressive or rapid decline in eGFR. Our results suggest that eGFR trajectories are correlated with multiple social and modifiable risk factors and inform the risk of ESKD., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Purpose: The current study investigated the correlation between dietary iron intake and diabetic kidney disease among diabetic adults., Methods: This cross-sectional study enrolled 8118 participants who suffered from diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Dietary iron intake was obtained from 24 h recall interviews, and diabetic kidney disease was defined as eGFR < 60 mL/min per 1.73 m 2 or albumin creatinine ratio (ACR) ≥ 30 mg/g. Three weighted logistic regression models were utilized to investigate odd ratio (OR) and 95% CIs for diabetic kidney disease. Stratified analyses were performed by gender, age, BMI, HbA1c, hypertension status, and smoking status, and diabetes types., Results: Among 8118 participants (51.6% male, mean age 61.3 years), 40.7% of participants suffered from diabetic kidney disease. With the adjustment of potential covariates, we found that ≥ 12.59 mg of dietary iron was related to a lower risk of diabetic kidney disease (OR = 0.78, 95% CI: 0.63 to 0.96; OR = 0.79, 95% CI: 0.63 to 0.98). In stratified analyses, higher iron intake was negatively related to diabetic kidney disease, especially among those who were male, < 60 years, those with hypertension, those with HbA1c < 7.0%, and those who were ex-smokers. The result remained robust in sensitivity analyses., Conclusion: We found that ≥ 12.59 mg of dietary iron is associated with a lower risk of diabetic kidney disease, especially in those who were male, younger, heavier weight, have better blood sugar control, and those who were ex-smokers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) in the population. In patients with diabetes mellitus, the incidence of non-diabetic nephropathy (NDNP) has been estimated to range from 3% to 69.5%. Personal judgment is frequently employed while deciding whether or not to do a kidney biopsy (KB) on diabetic patients. NDNP alters the prognosis and course of treatment for people with DM. In our study, we examined the incidence of NDNP concurrent with the progression of diabetes mellitus, as well as the laboratory and clinical indicators that could be utilized to forecast it., Methods: A retrospective analysis of 76 diabetic patients who underwent KB was conducted. Based on the pathological diagnoses of these patients, they were categorized as DNP (diabetic nephropathy) or NDNP. The definition of HbA1c variability was determined by calculating the mean HbA1c and the average value of the HbA1c measurements, as well as the standard deviation (SD) for each participant., Results: NDNP was detected in 50% of 76 patients. Among patients with NDNP, 36.8% had focal segmental glomerulosclerosis (FSGS), 23.6% had membranous glomerulonephritis, and 7.8% had IgA nephritis. The NDNP group exhibited significantly higher rates of female gender, absence of diabetic retinopathy, shorter time to diagnosis of diabetes mellitus, chronic kidney disease, and proteinuria, less intensive medication for diabetes mellitus, presence of hematuria and leukociduria, immunological serological marker positivity, and non-HbA1C variability. Risk factors for predicting non-diabetic nephropathy, as determined by multivariate analysis, included female gender, the absence of diabetic retinopathy, non-HbA1c variability and a positive immunological serological test., Conclusion: In this study, a significant number of diabetic patients with chronic kidney disease were diagnosed with NDNP. Identifying these patients allows for treatment of the specific underlying disease. Factors such as the absence of DR, non-HbA1c variability, female gender, and immunological serological test positivity can predict NDNP and guide the clinician's decision on kidney biopsy. Further prospective studies are warranted to validate the efficacy of potential predictive factors like HbA1c variability., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM)., Design, Patients and Measurements: This retrospective single-centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut-off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia., Results: The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p = .001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = -.117, r = -.131, r = .117, p < .001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p < .001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76-7.52, p = .001)., Conclusion: Albuminuria is more frequently observed in patients with hypomagnesemia., (© 2024 John Wiley & Sons Ltd.)

Aims: To assess the relationship of longitudinal changes in fat mass (FM), lean mass (LM) and waist circumference (WC) with incident kidney outcomes in people with overweight/obesity and type 2 diabetes mellitus (T2DM)., Materials and Methods: A total of 3927 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 from the Look AHEAD (Action for Health in Diabetes) trial were included. The primary outcome was kidney outcomes, defined as a decrease in eGFR of at least 40% from baseline at follow-up visit, or end-stage kidney disease., Results: During a median follow-up of 8.0 years, 450 kidney outcomes were documented after the first 1 year. In the intensive lifestyle intervention (ILI) group, reductions in FM (per 10% decrease, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69-0.94) and WC (per 10% decrease, adjusted HR 0.72, 95% CI 0.59-0.88) from baseline to 1-year follow-up were significantly associated with a lower risk of kidney outcomes. The change in LM was not significantly associated with risk of kidney outcomes (per 10% decrease, adjusted HR 0.78, 95% CI 0.58-1.06). In the diabetes support and education group (control group), no significant association was found between changes in body composition and kidney outcomes. Similar results were observed for the 4-year changes in body composition., Conclusions: In this post hoc analysis of the Look AHEAD trial, longitudinal declines in FM and WC were associated with a lower risk of kidney outcomes in the ILI group in participants with overweight/obesity and T2DM., (© 2024 John Wiley & Sons Ltd.)

Aims: Japan started the Diabetic Nephropathy Aggravation Prevention Program. Its early impact was assessed in this study., Methods: This study used the Kokuho Database of patients with type 2 diabetes from program-implementing and non-implementing municipalities (fiscal years [FYs] 2015-2021). Implementing municipalities facilitated clinic visits and provided education to eligible patients. Average treatment effects on the treated in FYs 2016 and 2018 were evaluated using the inverse probability of treatment weighting. Comparison included intervened vs. non-intervened patients in program-implementing municipalities (Comparison A), intervened patients in program-implementing vs. eligible patients in non-implementing municipalities (Comparison B), and eligible patients in implementing and non-implementing municipalities (Comparison C)., Results: Overall, 89,611/89,685 patients from FY 2016/2018 were eligible. Among 68,125/68,170 patients in program-implementing municipalities, 1,470/1,819 were intervened. In Comparison A, the estimated effect of the program on ΔeGFR at 3 years were -0.4 (95 % confidence interval; -1.0, 0.2)/-0.4 (-0.9, 0.1) mL/min/1.73 m 2 in FY 2016/2018. Comparisons B and C demonstrated similar tendency; distribution of %change in eGFR varied between municipalities., Conclusions: Early in the program, renal function did not improve in the intervened patients or program-implementing municipalities. Diverse eGFR changes across municipalities highlighted diverse intervention outcomes, emphasizing the need of program refinement., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takehiro Sugiyama reports financial support was provided by Government of Japan Ministry of Health, Labour and Welfare. Kazuyo Tsushita reports financial support was provided by Government of Japan Ministry of Health, Labour and Welfare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: We estimated overall refill adherence to all antihypertensive [AHT] and/or lipid-lowering drugs in the treatment regimen and its association with cardiovascular disease (CVD) in adults with type 1 diabetes, taking kidney disease into account., Methods: This Finnish Diabetic Nephropathy Study involved 1,558 adults with type 1 diabetes who had purchased AHT and/or lipid-lowering drugs within ± 0.5 year from baseline and were followed until their first CVD event, death, or end of 2015. Proportion of days covered (PDC) method was used to calculate adherence. The adherence was classified as good (≥80 %), intermediate (≥50 and <80%) or poor (<50%)., Results: Median adherence rate was 74% (IQR 63-84 %). Both good (OR 0.55 [95% CI 0.33, 0.92], P=0.02) and intermediate (0.47 [0.29, 0.77], P=0.003) adherence were associated with lower odds of CVD, compared to poor adherence. Moreover, the higher the adherence percentage point in those with moderate albuminuria, the lower was the odds for CVD (0.81 [0.67, 0.98], P=0.03, per 10 unit increase in adherence)., Conclusions: In adults with type 1 diabetes, refill adherence of 50% or more to cardio-protective medications is associated with lower odds of incident CVD. Our findings highlight the relevance of going beyond prescribing protective CVD drugs, ensuring, and improving medication adherence matters., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: P-H.G. has received lecture honoraria from Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, EloWater, Genzyme, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, Peer Voice, Sanofi and Sciarc. PHG is an advisory board member for AbbVie, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Medscape, MSD, Mundipharma, Nestlé, Novartis, Novo Nordisk, and Sanofi. PHG has received investigator-initiated grants from Eli Lilly and Roche. EBPreports receiving lecture honorariums from Eli Lilly, Abbott, Astra Zeneca, Sanofi, and Boehringer Ingelheim. She was an advisory board member of Sanofi, and since February 2024 she has been a Boehringer-Ingelhiememployee. No other potential conflicts of interest relevant to this article were reported. The funding sources were not involved in the design or conduct of the study. All other authors declare that there is no duality of interest associated with this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The relationship between thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and diabetic kidney disease (DKD) is still controversial, and this study analyzed the correlation between TSH, FT3, FT4 and DKD in patients with type 2 diabetes mellitus (T2DM)., Methods: T2DM patients (1216) were divided into five groups based on serum TSH, FT3, and FT4 levels, differences in urinary albumin excretion rate (UACR), estimated glomerular filtration rate (eGFR) were compared. Binary logistic regression verified independent correlations among TSH, FT3, FT4 and UACR, eGFR. TSH and FT3 predictive values for DKD were analyzed using receiver operating characteristic (ROC) curves., Results: The prevalence of albuminuria with decreased eGFR was higher in T2DM patients with subclinical hypothyroidism and overt hypothyroidism than that in patients with normal thyroid function. TSH positively correlated with UACR (r = 0.133, p < 0.001) and positively correlated with eGFR (r = -0.218, p < 0.001), FT3 negatively correlated with UACR (r = -0.260, p < 0.001) and positively correlated with eGFR (r = 0.324, p < 0.001). With the change from the lower normal level to the increased level of TSH and the change from the higher normal level to the reduced level of FT3, the prevalence of albuminuria gradually increased, the prevalence of decreased eGFR gradually increased in TSH groups and FT3 groups. After adjusting for age, BMI, duration of diabetes, TPOAb, TGAb, smoking, drinking, hypertension, the use of anti-diabetic medications (metformin, sodium-glucose cotransporter 2 inhibitors), HbA1c, CRP, TC, TG, LDL-C, and HDL-C, both TSH and FT3 correlated with increased UACR (TSH: OR 1.253, p = 0.001; FT3: OR 0.166, p < 0.001) and decreased eGFR (TSH: OR 1.245, p < 0.001, FT3: OR 0.579, p < 0.001), but this correlation of TSH with eGFR < 60 mL/min/1.73 m 2 was not found in male. The area under the ROC curve (AUC) for FT3 was greater than that for TSH (FT3: 0.64; TSH: 0.61)., Conclusions: Increased TSH and reduced FT3 levels were associated with DKD in T2DM patients, but in a sex-dependent manner. FT3 had a higher predictive value for DKD., (© 2024. The Author(s).)

Introduction: The impact of coronavirus disease 2019 (COVID-19) on diabetic kidney disease (DKD) patients in China is not fully understood. This study aimed to investigate infection status in a DKD cohort post-renal biopsy and analyze vaccination and infection rates, as well as symptom severity, across various renal pathologies in DKD patients., Methods: This epidemiological survey, centered on COVID-19, employed a Chinese DKD and renal puncture follow-up cohort. A customized questionnaire enabled standardized data gathering. It collected data on clinical characteristics, vaccination and infection statuses, and diverse pathological types. The study analyzed the relationship between vaccination and infection statuses across various pathological types, evaluating characteristics and treatment outcomes in patients with infections., Results: In total, 437 patients with DKD from 26 Chinese provinces were followed up for a median of 44.6 ± 20 months. COVID-19 infection, vaccination, and novel coronavirus pneumonia (NCP) rates were 73.68%, 59.3%, and 6.63%, respectively. Ten patients with NCP had severe pneumonia or died of COVID-19. Renal pathology revealed that 167 (38.22%) patients had diabetic nephropathy (DN), 171 (39.13%) had non-diabetic renal disease (NDRD), and 99 had DN and NDRD (22.65%). The DN group had the lowest vaccination (54.5%), highest all-cause mortality (3.6%), and highest endpoint rates (34.10%). Compared to patients who were not vaccinated pre-infection (117 cases), vaccinated patients (198 cases) had reduced NCP (6.6% vs. 13.7%), severity (1.0% vs. 3.4%), and endpoint (9.10% vs. 31.60%) rates., Conclusion: Vaccination can prevent infection and diminish COVID-19 severity in patients with DKD; therefore, increasing vaccination rates is particularly important., Clinical Trial Registration: ClinicalTrails.gov, NCT05888909., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Dong, Zhang, Zheng, Lyu, Zhang, Huang, Liu, Wang, Zhang, Cao, Wu, Zhou, Cai and Chen.)

Introduction: People with diabetes are at risk of developing chronic kidney disease. However, limited data are available to quantify their risk of kidney function decline in South Asia. This study evaluates the rate and predictors of kidney function decline among people with type 2 diabetes in South Asia., Research Design and Methods: We analyzed data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) Trial to quantify the rate of decline in estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (n=1146) over 2.5 years of follow-up. The CARRS Trial evaluated a multicomponent intervention of decision-supported electronic health records and non-physician care coordinator to improve diabetes management at 10 diabetes clinics in India and Pakistan. We used linear mixed models to estimate eGFR slope among all participants and tested the association of eGFR slope with demographic, disease-related, and self-care parameters, accounting for randomization and site., Results: The mean age of participants was 54.2 years, with a median duration of diabetes of 7.0 years (IQR: 3.0 - 12.0) and median CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) eGFR of 83.6 (IQR: 67.7 to 97.9) mL/min/1.73 m 2 . The overall mean eGFR slope was -1.33/mL/min/1.73 m 2 /year. There were no differences in the eGFR slope by treatment assignment to intervention versus usual care. In the adjusted regression model, pre-existing diabetic retinopathy (slope difference: -2.11; 95% CI: -3.45 to -0.77), previous cardiovascular disease (-1.93; 95% CI: -3.45 to -0.40), and statins use (-0.87; 95% CI: -1.65 to -0.10) were associated with faster eGFR decline., Conclusions: People with diabetes receiving care at urban diabetes clinics in South Asia experienced annual eGFR decline at two times higher rate than that reported from other contemporary international diabetes cohorts. Risk factors for faster decline were similar to those previously established, and thus care delivery models must put an additional emphasis on kidney protective therapies among subgroups with microvascular and macrovascular diabetes complications., Trial Registration Number: NCT01212328., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Previous studies examined the association of Helicobacter pylori infection (H. pylori) with complications of diabetes, but the results have been inconsistent. The aim of this study of patients with type-2 diabetes (T2D) was to determine the association of H. pylori infection with the major complications of diabetes., Methods: This single-center retrospective study examined patients with T2D who received H. pylori testing between January 2016 and December 2021. Logistic regression analyses were used to evaluate the association of H. pylori infection with four major complications of diabetes., Results: We examined 960 patients with T2D, and 481 of them (50.1%) were positive for H. pylori. H. pylori infection was significantly associated with diabetic nephropathy (odds ratio [OR] = 1.462; 95% confidence interval [CI]: 1.006,2.126; P = 0.046). In addition, the co-occurrence of H. pylori positivity with hypertension (OR = 4.451; 95% CI: 2.351,8.427; P < 0.001), with glycated hemoglobin A1c (HbA1c) of at least 8% (OR = 2.925; 95% CI: 1.544,5.541; P = 0.001), and with diabetes duration of at least 9 years (OR = 3.305; 95% CI:1.823,5.993; P < 0.001) further increased the risk of diabetic nephropathy. There was no evidence of an association of H. pylori infection with retinopathy, neuropathy, or peripheral vascular disease., Conclusions: Our study of T2D patients indicated that those with H. pylori infections had an increased risk of nephropathy, and this risk was greater in patients who also had hypertension, an HbA1c level of 8% or more, and diabetes duration of 9 years or more., (© 2024. The Author(s).)

Aims: To assess the comparative cardiovascular and renal effectiveness and safety of empagliflozin vs. dapagliflozin among patients with type 2 diabetes in routine clinical practice., Methods and Results: Cohort study using data from nationwide registers in Sweden, Denmark, and Norway, from June 2014 to June 2021 included 141 065 new users of empagliflozin and 58 306 new users of dapagliflozin. Coprimary outcomes were major cardiovascular events (myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure) and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Secondary outcomes were the individual components of the primary outcomes, any cause death, and diabetic ketoacidosis. Use of empagliflozin vs. dapagliflozin was associated with similar risk of major cardiovascular events [adjusted incidence rate: 15.9 vs. 15.8 events per 1000 person-years; HR 1.02, (95% confidence interval 0.97-1.08)], heart failure [6.5 vs. 6.3 events per 1000 person-years; HR 1.05 (0.97-1.14)] and serious renal events [3.7 vs. 4.1 events per 1000 person-years; HR 0.97 (0.87-1.07)]. In secondary outcome analyses, the HRs for use of empagliflozin vs. dapagliflozin were 1.00 (0.93-1.07) for myocardial infarction, 1.03 (0.95-1.12) for stroke, 1.01 (0.92-1.13) for cardiovascular death, 1.06 (1.00-1.11) for any cause death, 0.77 (0.60-0.99) for renal replacement therapy, 1.20 (0.75-1.93) for renal death, 1.01 (0.90-1.12) for hospitalization for renal events and 1.12 (0.94-1.33) for diabetic ketoacidosis., Conclusion: Use of empagliflozin and dapagliflozin was associated with similar risk of cardiovascular and renal outcomes, mortality, and diabetic ketoacidosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Visceral adiposity index (VAI) is a reliable indicator of visceral adiposity. However, no stu-dies have evaluated the association between VAI and DKD in US adults with diabetes. Theref-ore, this study aimed to explore the relationship between them and whether VAI is a good pr-edictor of DKD in US adults with diabetes. Our cross-sectional study included 2508 participan-ts with diabetes who were eligible for the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Univariate and multivariate logistic regression were used to an-alyze the association between VAI level and DKD. Three models were used to control for pot-ential confounding factors, and subgroup analysis was performed for further verification. A tot-al of 2508 diabetic patients were enrolled, of whom 945 (37.68%) were diagnosed with DKD. Overall, the VAI was 3.36 ± 0.18 in the DKD group and 2.76 ± 0.11 in the control group. VAI was positively correlated with DKD (OR = 1.050, 95% CI 1.049, 1.050) after fully adjusting for co-nfounding factors. Compared with participants in the lowest tertile of VAI, participants in the highest tertile of VAI had a significantly increased risk of DKD by 35.9% (OR = 1.359, 95% CI 1.355, 1.362). Through subgroup analysis, we found that VAI was positively correlated with the occurrence of DKD in all age subgroups, male(OR = 1.043, 95% CI 1.010, 1.080), participants wit-hout cardiovascular disease(OR = 1.038, 95% CI 1.011, 1.069), hypertension (OR = 1.054, 95% CI 1.021, 1.090), unmarried participants (OR = 1.153, 95% CI 1.036, 1.294), PIR < 1.30(OR = 1.049, 95% CI 1.010, 1.094), PIR ≧ 3 (OR = 1.085, 95% CI 1.021, 1.160), BMI ≧ 30 kg/m 2 (OR = 1.050, 95% CI 1.016, 1.091), former smokers (OR = 1.060, 95% CI 1.011, 1.117), never exercised (OR = 1.033, 95% CI 1.004, 1.067), non-Hispanic white population (OR = 1.055, 95% CI 1.010, 1.106) and non-Hipanic black population (OR = 1.129, 95% CI 1.033, 1.258). Our results suggest that elevated VAI levels are closely associated with the development of DKD in diabetic patients. VAI may be a simpl-e and cost-effective index to predict the occurrence of DKD. This needs to be verified in furt-her prospective investigations., (© 2024. The Author(s).)

Objectives: To determine how plasma fibrinogen levels impact the severity of microvascular complications in people with type 2 diabetes while focussing on the molecular mechanisms of fibrinogen's role in such complications., Methods: The analytical, cross-sectional study was conducted from September 2022 to March 2023 at the Department of Medicine, Mardan Medical Complex and Teaching Hospital, Khyber Pakhtunkhwa, Pakistan, and comprised adult patients of either gender who had been diagnosed with type 2 diabetes and microvascular complications. Each patient was subjected to an evaluation of microvascular complications, including diabetic retinopathy, nephropathy and neuropathy, using validated diagnostic criteria and clinical examinations. Data was analysed using SPSS 26., Results: Of the 174 patients 97(%) were males and 77(%) were females. Retinopathy was found in 57(32.7) patients with median age 53 years (interquartile range: 46-63 years). Nephropathy was found in 55(31.6%) subjects with median age 54 years (interquartile range: 50-61 years). Neuropathy was found in 62(35.6%) patients with median age 53 years (interquartile range: 48-58 years). Diabetic neuropathy was significantly associated with elevated plasma fibrinogen levels and various biomarkers, such as creatinine, urea, fasting blood glucose, glycated haemoglobin and estimated average glucose (p<0.05). Diabetic retinopathy was significantly linked with higher levels of fibrinogen, which manifested through symptoms, like floaters or dark spots, impaired colour vision, difficulty seeing at night, blurred or fluctuating vision and vision loss (p<0.05). Diabetic nephropathy and the progression of its severity was significantly associated with increased fibrinogen levels, as well as markers, like albuminuria, creatinine, urea, fasting blood glucose, glycated haemoglobin and estimated average glucose (p<0.05)., Conclusions: Elevated plasma fibrinogen levels in patients with type 2 diabetes significantly correlated with increased microvascular complications, underscoring the importance of monitoring and managing fibrinogen levels to mitigate diabetes-associated vascular pathologies.

Aims/hypothesis: The aim of this study was to evaluate the association of chronic complications with time in tight range (TITR: 3.9-7.8 mmol/l) and time in range (TIR: 3.9-10.0 mmol/l) in people with type 1 diabetes., Methods: The prevalence of microvascular complications (diabetic retinopathy, diabetic nephropathy and diabetic peripheral neuropathy [DPN]) and macrovascular complications according to sensor-measured TITR/TIR was analysed cross-sectionally in 808 adults with type 1 diabetes. Binary logistic regression was used to evaluate the association between TITR/TIR and the presence of complications without adjustment, with adjustment for HbA 1c , and with adjustment for HbA 1c and other confounding factors (sex, age, diabetes duration, BMI, BP, lipid profile, smoking, and use of statins and renin-angiotensin-aldosterone system inhibitors)., Results: The mean TITR and TIR were 33.9 ± 12.8% and 52.5 ± 15.0%, respectively. Overall, 46.0% had any microvascular complication (34.5% diabetic retinopathy, 23.8% diabetic nephropathy, 16.0% DPN) and 16.3% suffered from any macrovascular complication. The prevalence of any microvascular complication, diabetic retinopathy, diabetic nephropathy and a cerebrovascular accident (CVA) decreased with increasing TITR/TIR quartiles (all p trend <0.05). Each 10% increase in TITR was associated with a lower incidence of any microvascular complication (OR 0.762; 95% CI 0.679, 0.855; p<0.001), diabetic retinopathy (OR 0.757; 95% CI 0.670, 0.856; p<0.001), background diabetic retinopathy (OR 0.760; 95% CI 0.655, 0.882; p<0.001), severe diabetic retinopathy (OR 0.854; 95% CI 0.731, 0.998; p=0.048), diabetic nephropathy (OR 0.799; 95% CI 0.699, 0.915; p<0.001), DPN (OR 0.837; 95% CI 0.717, 0.977; p=0.026) and CVA (OR 0.651; 95% CI 0.470, 0.902; p=0.010). The independent association of TITR with any microvascular complication (OR 0.867; 95% CI 0.762, 0.988; p=0.032), diabetic retinopathy (OR 0.837; 95% CI 0.731, 0.959; p=0.010), background diabetic retinopathy (OR 0.831; 95% CI 0.705, 0.979; p=0.027) and CVA (OR 0.619; 95% CI 0.426, 0.899; p=0.012) persisted after adjustment for HbA 1c . Similar results were obtained when controlling for HbA 1c and other confounding factors., Conclusions/interpretation: TITR and TIR are inversely associated with the presence of microvascular complications and CVA in people with type 1 diabetes. Although this study was not designed to establish a causal relationship, this analysis adds validity to the use of TITR and TIR as key measures in glycaemic management., Trial Registration: ClinicalTrials.gov NCT02601729 and NCT02898714., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To conduct a post hoc subgroup analysis of patients with type 2 diabetes (T2D) from the RECAP study, who were treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor and glucagon-like peptide 1 receptor agonist (GLP-1RA) combination therapy, focusing only on those patients who had chronic kidney disease (CKD), to examine whether the composite renal outcome differed between those who received SGLT2 inhibitor treatment first and those who received a GLP-1RA first., Methods: We included 438 patients with CKD (GLP-1RA-first group, n = 223; SGLT2 inhibitor-first group, n = 215) from the 643 T2D patients in the RECAP study. The incidence of the composite renal outcome, defined as progression to macroalbuminuria and/or a ≥50% decrease in estimated glomerular filtration rate (eGFR), was analysed using a propensity score (PS)-matched model. Furthermore, we calculated the win ratio for these composite renal outcomes, which were weighted in the following order: (1) both a ≥50% decrease in eGFR and progression to macroalbuminuria; (2) a decrease in eGFR of ≥50% only; and (3) progression to macroalbuminuria only., Results: Using the PS-matched model, 132 patients from each group were paired. The incidence of renal composite outcomes did not differ between the two groups (GLP-1RA-first group, 10%; SGLT2 inhibitor-first group, 17%; odds ratio 1.80; 95% confidence interval [CI] 0.85 to 4.26; p = 0.12). The win ratio of the GLP-1RA-first group versus the SGLT2 inhibitor-first group was 1.83 (95% CI 1.71 to 1.95; p < 0.001)., Conclusion: Although the renal composite outcome did not differ between the two groups, the win ratio of the GLP-1RA-first group versus the SGLT2 inhibitor-first group was significant. These results suggest that, in GLP-1RA and SGLT2 inhibitor combination therapy, the addition of an SGLT2 inhibitor to baseline GLP-1RA treatment may lead to more favourable renal outcomes., (© 2024 John Wiley & Sons Ltd.)

Aim: Among multi-ethnic Asians, type 2 diabetes (T2D) clustered in three subtypes; mild obesity-related diabetes (MOD), mild age-related diabetes with insulin insufficiency (MARD-II) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII) had differential cardio-renal complication risk. We assessed the proteomic profiles to identify subtype specific biomarkers and its association with diabetes complications., Methods: 1448 plasma proteins at baseline were measured and compared across the T2D subtypes. Multivariable cox regression was used to assess associations between significant proteomics features and cardio-renal complications., Results: Among 645 T2D participants (SIRD-RII [19%], MOD [45%], MARD-II [36%]), 295 proteins expression differed significantly across the groups. These proteins were enriched in cell adhesion, neurogenesis and inflammatory response processes. In SIRD-RII group, ADH4, ACY1, THOP1, IGFBP2, NEFL, ENTPD2, CALB1, HAO1, CTSV, ITGAV, SCLY, EDA2R, ERBB2 proteins significantly associated with progressive CKD and LILRA5 protein with incident heart failure (HF). In MOD group, TAFA5, RSPO3, EDA2R proteins significantly associated with incident HF. In MARD-II group, FABP4 protein significantly associated with progressive CKD and PTPRN2 protein with major adverse cardiovascular events. Genetically determined NEFL and CALB1 were associated with kidney function decline., Conclusions: Each T2D subtype has unique proteomics signature and association with clinical outcomes and underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The prevalence of diabetic kidney disease (DKD) is increasing annually. Damage to and loss of podocytes occur early in DKD. tRNA-derived fragments (tRFs), originating from tRNA precursors or mature tRNAs, are associated with various illnesses. In this study, tRFs were identified, and their roles in podocyte injury induced by high-glucose (HG) treatment were explored. High-throughput sequencing of podocytes treated with HG was performed to identify differentially expressed tRFs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The expression levels of nephrin, podocin, and desmin were measured in podocytes after overexpression of tRF-1:24-Glu-CTC-1-M2 (tRF-1:24) and concomitant HG treatment. A total of 647 tRFs were identified, and 89 differentially expressed tRFs (|log2FC| ≥ 0.585; p  ≤ .05) were identified in the HG group, of which 53 tRFs were downregulated and 36 tRFs were upregulated. The 10 tRFs with the highest differential expression were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and these results were consistent with the sequencing results. GO analysis revealed that the biological process, cellular component, and molecular function terms in which the tRFs were the most enriched were cellular processes, cellular anatomical entities, and binding. KEGG pathway analysis revealed that tRFs may be involved in signaling pathways related to growth hormones, phospholipase D, the regulation of stem cell pluripotency, and T-/B-cell receptors. Overexpression of tRF-1:24, one of the most differentially expressed tRFs, attenuated podocyte injury induced by HG. Thus, tRFs might be potential biomarkers for podocyte injury in DKD.