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Aim: Among people with diabetes those with chronic kidney disease (CKD) have a reduced life expectancy with increased risk of cardiovascular disease (CVD) a major contributor to morbidity and mortality. CKD related to diabetes is growing worldwide and is one of the leading causes of kidney failure globally. Diabetes is associated with accelerated vascular ageing and the related mechanisms and mediators that drive the progression of CKD and CVD disease in people with diabetes may help provide insights into the pathophysiology of cardio-renal complications and guide treatment interventions in people with diabetes., Methods: We conducted a narrative review of the literature using PubMed for English language articles that contained keywords that related to diabetes, chronic or diabetic kidney disease, ageing, cellular senescence, arterial stiffness, Klotho and sirtuins, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, renin angiotensin aldosterone system (RAAS) and glucagon-like peptide-1 (GLP-1) receptor agonists., Results: Progressive kidney disease in diabetes is associated with accelerated ageing driven in part by multiple processes such as cellular senescence, inflammation, oxidative stress and circulating uremic toxins. This accelerated ageing phenotype contributes to increased arterial stiffness, endothelial dysfunction, cognitive decline and muscle wasting, thereby elevating morbidity and mortality in individuals with diabetes and CKD. Deficiency of the kidney-derived anti-ageing hormone Klotho and reduced sirtuin levels play pivotal roles in these ageing pathways. Dietary, lifestyle and pharmacological interventions targeting vascular ageing may help reduce the progression of CKD and associated CVD in people with diabetes. The current standard of care and pillars of treatment for kidney disease such as RAAS inhibitors, SGLT-2 inhibitors and GLP-1 receptor agonists all influence pathways involved in vascular ageing., Conclusions: A multifactorial intervention to prevent the development of CKD by targeting traditional risk factors as well as treatment with novel agents with cardio-renal beneficial effects can prevent accelerated ageing and extend lifespan in people with diabetes., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background & Aims: Obesity is associated with vitamin D (VitD) deficiency. However, previous studies showed mixed effects of VitD (25-hydroxyVitD/calcidiol) supplementation on body weight. The biological actions of VitD require the hydroxylation of inactive VitD into active VitD (1.25-dihydroxyVitD/calcitriol). This step is highly regulated; therefore, supplementing with inactive VitD might not be sufficient to overcome the potential adverse health effects of VitD deficiency. The objective of this study was to conduct a systematic review and individual participant data (IPD) meta-analysis of data acquired from randomised placebo-controlled calcitriol trials (RCTs) to determine the effects of calcitriol on body weight and weight-related parameters., Methods: Studies were identified from MEDLINE, EMBASE, and CENTRAL databases up to January 27, 2024, and excluded those involving dialysis or cancer patients. We obtained IPD from eligible trials and assessed bias using the Cochrane Collaboration risk-of-bias tool and methodological quality using the Heyland Methodological Quality Score. The study was prospectively registered with PROSPERO (CRD42017076202)., Results: Although none of the studies reported information regarding our primary objective, we obtained IPD for 411 patients, with 206 randomised to receive calcitriol and 205 to placebo. This dataset enabled us to conduct an IPD meta-analysis with 17,084 person-months of follow-up (median: 11 months). Meta-analysis showed that calcitriol does not alter body weight, BMI, waist circumference, fat mass or lean body mass compared to placebo. Adjusting for age and sex did not alter the outcomes., Conclusions: In conclusion, this systematic review and IPD meta-analysis indicate that calcitriol does not affect body weight in normal-weight postmenopausal women and lean patients with type 1 diabetes nor in people suffering from obesity, type 2 diabetes and chronic kidney disease. Whether calcitriol lowers body weight in VitD-sufficient people with obesity remains to be elucidated., Competing Interests: Conflict of interest We declare that there are no conflicts of interest regarding this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A growing and significant number of people with diabetes develop chronic kidney disease (CKD). Diabetes-related CKD is a leading cause of end-stage kidney disease (ESKD) and people with diabetes and CKD have high morbidity and mortality, predominantly related to cardiovascular disease (CVD). Despite advances in care over the recent decades, most people with CKD and type 2 diabetes are likely to die of CVD before developing ESKD. Hyperglycaemia and hypertension are modifiable risk factors to prevent onset and progression of CKD and related CVD. People with type 2 diabetes often have dyslipidaemia and CKD per se is an independent risk factor for CVD, therefore people with CKD and type 2 diabetes require intensive lipid lowering to reduce burden of CVD. Recent clinical trials of people with type 2 diabetes and CKD have demonstrated a reduction in composite kidney end point events (significant decline in kidney function, need for kidney replacement therapy and kidney death) with sodium-glucose co-transporter-2 (SGLT-2) inhibitors, non-steroidal mineralocorticoid receptor antagonist finerenone and glucagon-like peptide 1 receptor agonists. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have previously undertaken a narrative review and critical appraisal of the available evidence to inform clinical practice guidelines for the management of hyperglycaemia, hyperlipidaemia and hypertension in adults with type 2 diabetes and CKD. This 2024 abbreviated updated guidance summarises the recommendations and the implications for clinical practice for healthcare professionals who treat people with diabetes and CKD in primary, community and secondary care settings., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

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.)

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.)

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.)

Aims/hypothesis: The role of HbA 1c variability in the progression of diabetic kidney disease is unclear, with most studies to date performed in White populations and limited data on its role in predicting advanced kidney outcomes. Our aim was to evaluate if long-term intra-individual HbA 1c variability is a risk factor for kidney disease progression (defined as an eGFR decline of ≥50% from baseline with a final eGFR of <30 ml/min per 1.73 m 2 ) in an ethnically heterogeneous cohort of people with type 1 diabetes with a preserved eGFR ≥45 ml/min per 1.73 m 2 at baseline., Methods: Electronic health record data from people attending outpatient clinics between 2004 and 2018 in two large university hospitals in London were collected. HbA 1c variability was assessed using three distinct methods: (1) SD of HbA 1c (SD-HbA 1c ); (2) visit-adjusted SD (adj-HbA 1c ): SD-HbA 1c /√n/(n-1), where n is the number of HbA 1c measurements per participant; and (3) CV (CV-HbA 1c ): SD-HbA 1c /mean-HbA 1c . All participants had six or more follow-up HbA 1c measurements. The eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration equation and clinical/biochemical results from routine care were extracted from electronic health records., Results: In total, 3466 participants (50% female, 78% White, 13% African Caribbean, 3% Asian and 6% of mixed heritage or self-reporting as 'other') were followed for a median (IQR) of 8.2 (4.2-11.6) years. Of this cohort, 249 (7%) showed kidney disease progression. Higher HbA 1c variability was independently associated with a higher risk of kidney disease progression, with HRs (95% CIs) of 7.76 (4.54, 13.26), 2.62 (1.75, 3.94) and 5.46 (3.40, 8.79) (lowest vs highest HbA 1c variability quartile) for methods 1-3, respectively. Increasing age, baseline HbA 1c , systolic BP and urinary albumin/creatinine ratio were also associated with kidney disease progression (p<0.05 for all). African Caribbean ethnicity was associated with an increased risk of kidney disease progression (HR [95% CI] 1.47 [1.09, 1.98], 1.76 [1.32, 2.36] and 1.57 [1.17, 2.12] for methods 1-3, respectively) and this effect was independent of glycaemic variability and other traditional risk factors., Conclusions/interpretation: We observed an independent association between HbA 1c variability, evaluated using three distinct methods, and significant kidney disease progression in a multi-ethnic type 1 diabetes cohort. Further studies are needed to elucidate the mechanisms that may explain our results and evaluate if HbA 1c variability is a modifiable risk factor for preventing diabetic kidney disease progression., (© 2024. The Author(s).)

Automated insulin delivery (AID) in people with type 1 diabetes (pwT1D) and end-stage kidney disease (ESKD) on haemodialysis (HD) has not been reported previously. We describe practical considerations and our findings in four pwT1D on HD for ESKD where AID was safely implemented, with significant improvements in time in range., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [SH Honoraria from Medtronic, Abbot \Dexcom, Insulet and Tandem None for JK, TJ, BH, KC and SP.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The contribution of chronic kidney disease (CKD) towards the risk of developing cardiovascular disease (CVD) is magnified with co-existing type 1 or type 2 diabetes. Lipids are a modifiable risk factor and good lipid management offers improved outcomes for people with diabetic kidney disease (DKD).The primary purpose of this guideline, written by the Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) working group, is to provide practical recommendations on lipid management for members of the multidisciplinary team involved in the care of adults with DKD., (© 2024. The Author(s).)

There is limited data on the standards of diabetes care in people on peritoneal dialysis (PD). Our aim was to assess the standards of diabetes care and the burden of hypoglycaemia in people with diabetes on PD. We performed a retrospective study at three university hospitals from December 2021 to January 2022. Clinical data were extracted from electronic health records. Diabetes care of people on PD was compared against recommended standards for people with diabetes on haemodialysis (as there are no agreed standards for PD). The degree of hypoglycaemia awareness was assessed by validated questionnaires. A total of 65 adults (15 type 1, 49 type 2 and 1 monogenic-diabetes) with a mean age of 63 (range 29-88) years were evaluated. Of them, 92% had diabetes retinal screening with annual review. In contrast, in this high-risk group for foot disease, only 77% had annual foot reviews. The rates of diabetes specialist reviews were variable between hospitals at 63-94% and 10 (15%) had impaired hypoglycaemia awareness. Of the cohort, 32% had HbA1c within the acceptable range of 58-80 mmol/mol (7.5-8.5%), 21% had HbA1c below 58 mmol/mol (7.5%) and 21% ( n = 14) reported at least one hypoglycaemic event per month. Our results indicate variation of care within and between different centres, and the need for improved diabetes care in people on PD. Further work is required to establish agreed standards/recommendations of diabetes care in this population. Our findings highlight the necessity of an integrated multidisciplinary approach to improve the standard of diabetes care for people on PD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: To provide an overview of reported cases of new-onset type 1 diabetes mellitus (T1D) following COVID-19 infection., Methods: PubMed and Scopus library databases were screened for relevant case reports published between January 2020 and June 2022. Study design, geographic region or language were not restricted., Results: Twenty studies were identified and involved 37 patients (20 [54%] male, 17 [46%] female). Median age was 11.5 years (range 8 months-33 years) and 31 (84%) patients were aged ≤17 years. Most patients (33, 89%) presented with diabetic ketoacidosis (DKA). In total, 23 (62%) patients presented at the time of positive COVID-19 testing and 14 (38%) had symptoms consistent with COVID-19 infection or a previous positive test (1-56 days). Diabetes symptomatology was provided in 22 cases and (19, 86%) reported polyuria, polydipsia, polyphagia, fatigue, or weight loss or a combination of the aforementioned in the preceding weeks (3 days-12 weeks). Of the 28 patients that had data on acute and long-term treatment, all recovered well and most were managed with basal bolus insulin regimens. Quality assessment showed that most reports were either 'good' or 'moderate quality'., Conclusions: Although uncommon, new-onset T1D is a condition healthcare professionals may expect to see following a COVID-19 infection., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no conflicts of interest.

Summary: A Caucasian man in his 60s with recent diagnosis of metastatic renal cell carcinoma presented to the emergency department with a 5-day history of severe polyuria, polydipsia and fatigue and 1-day history of confusion, abdominal pain, nausea and vomiting. Investigations revealed an overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS). He had received the first dose of immunotherapy with nivolumab and ipilimumab 3 weeks prior to this attendance. New-onset type 1 diabetes (T1DM) was confirmed based on the clinical features at presentation, seropositivity for glutamic acid decarboxylase antibodies and significant insulin deficiency. He is currently on a multiple daily injections of insulin and uses intermittent-scanned glucose monitoring. Given the irreversible impact on beta-cell function and clinical response with insulin resulting in improved diabetes control, immunotherapy was resumed for his metastatic cancer with good radiological response. Although rare, new-onset T1DM can present with DKA and HSS overlap after a single dose of nivolumab/ipilimumab in individuals without pre-existing history of diabetes., Learning Points: Although rare, new onset of T1DM after immunotherapy can present with DKA and HSS overlap after a single dose of nivolumab/ipilimumab in individuals without pre-existing history of diabetes and normal glycaemic parameters. Due to the irreversible destruction of beta-cells, treatment with steroids is not indicated in contrast to other settings such as immunotherapy-induced hypophysitis. Presence of low c-peptide levels post-acute presentation is indicative of an irreversible impact on beta-cell function and supports resuming immunotherapy given the significant benefits on cancer prognosis. Clinicians must maintain a high index of suspicion in regards to diagnosis and management of new-onset type 1 diabetes and advice patients on reporting symptoms suggestive of diabetes and/or diabetes-related hyperglycaemic emergencies.

Background: Active vitamin-D deficiency is a potential modifiable risk factor for increased ventricular mass. We explored the effects of active vitamin-D (calcitriol) treatment on left ventricular mass in patients with type-2 diabetes (T2D) and chronic kidney disease (CKD)., Methods: We performed a 48-week duration single center randomized double-blind parallel group trial examining the impact of calcitriol, 0.5 mcg once daily, as compared to placebo on a primary endpoint of change from baseline in left ventricular mass index (LVMI) measured by magnetic resonance imaging . Patients with T2D, CKD stage-3 and raised left ventricular mass on stable renin angiotensin aldosterone system blockade, who all had elevated intact parathyroid hormone were eligible. Secondary endpoints included interstitial myocardial fibrosis, assessed with cardiac magnetic resonance imaging. In total, 45 (male 73%) patients with T2D and stage-3 CKD were studied (calcitriol n = 19, placebo n = 26)., Results: Following 48-weeks calcitriol treatment, the median difference and the (95% CI) of LVMI between the 2 treatment arms was 1.84 (-1.28, 4.96), similar between the 2 groups studied. Intact parathyroid hormone fell only in the calcitriol group from 142 pg/mL (80-293) to 76 pg/mL (41-204)(median, interquartile range, P= .04). No significant differences were observed in interstitial myocardial fibrosis or other secondary endpoints., Conclusions: The study did not provide evidence that treatment with calcitriol as compared to placebo might improve LVMI in patients with T2D, mild left ventricular hypertrophy and stable CKD. Our data does not support the routine use of active vitamin-D for LVMI regression and cardiovascular protection in patients with T2D and stage-3 CKD., Competing Interests: Conflict of interest All authors have read the journal's policy on disclosure of potential conflicts of interest and have no conflict of interest on the topic covered in this manuscript. Authors have access to the data and had a role in the conduction of the study and in the writing of the manuscript., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: There is limited information on the effect of ethnicity on the development of referable sight-threatening diabetic retinopathy (STDR) in people with type 1 diabetes. This study describes the risk factors for STDR in a diverse cohort of people with type 1 diabetes attending a regional diabetes eye screening service., Research Design and Methods: Clinical and digital retinal imaging data from 1,876 people with type 1 diabetes (50% women, 72.1% Caucasian, 17.3% African Caribbean, 2.9% Asian, and 7.6% other) with no retinopathy at baseline, attending surveillance eye screening were reviewed. Referable STDR was defined as the presence of any moderate to severe nonproliferative or preproliferative diabetic retinopathy or proliferative diabetic retinopathy or maculopathy in either eye as per U.K. National Diabetic Eye Screening criteria. Median follow-up was 6 years., Results: The median (interquartile range) age of the cohort was 29 (21, 41) years. Of the cohort of 1,876 people, 359 (19%) developed STDR. People who developed STDR had higher baseline HbA1c, raised systolic blood pressure (SBP), longer diabetes duration, and were more often of African Caribbean origin (24% vs. 15.6%; P < 0.05 for all). In multivariable Cox regression analyses, African Caribbean ethnicity (hazard ratio [HR] 1.39, 95% CI 1.09-1.78, P = 0.009), baseline SBP (HR 1.01, 95% CI 1.00-1.01, P = 0.033), and baseline HbA1c (HR 1.01, 95% CI 1.00-1.01, P = 0.0001) emerged as independent risk factors for STDR., Conclusions: We observed that people with type 1 diabetes of African Caribbean ethnicity are at significantly greater risk of STDR. Further research is required to understand the mechanisms that explain this novel observation., (© 2023 by the American Diabetes Association.)

Introduction: Aortic pulse wave velocity (Ao-PWV) predicts cardiovascular and kidney disease in type 2 diabetes (T2D). Klotho is a circulating antiaging hormone (sKlotho) with putative cardiorenal protective effects. The relationship between sKlotho and Ao-PWV in diabetic kidney disease (DKD) is unknown., Methods: In a cross-sectional cohort study, the correlation of sKlotho measured by a validated immunoassay, and Ao-PWV measured by applanation tonometry, was investigated in 172 participants with T2D and early stage DKD (all had estimated glomerular filtration rate [eGFR] >45 ml/min) on stable renin angiotensin system (RAS) inhibition. In cultured human aortic smooth muscle cells (HASMCs) stimulated with angiotensin II (AngII), the effects of recombinant human sKlotho pretreatment were assessed on intracellular calcium ([Ca 2+ ] i ) responses and expression of proteins associated with proosteogenic HASMC phenotypes., Results: Mean (range) age of the cohort was 61.3 years (40-82) and 65% were male. Mean (±SD) Ao-PWV was 11.4 (±2.3) m/s, eGFR 78.8 (±23.5) and median (interquartile range) sKlotho of 358.5 (194.2-706.3) pg/ml. In multivariable linear regression analyses, we observed a statistically significant inverse relationship between sKlotho and Ao-PWV, which was independent of clinical risk factors for cardiorenal disease. Pretreatment of cultured HASMC with sKlotho significantly attenuated AngII-stimulated [Ca 2+ ] i transients and reduced osteogenic collagen (Col1a2) expression., Conclusions: In individuals with T2D and early DKD, lower levels of sKlotho are associated with increased Ao-PWV. Taken together with the direct effect of sKlotho on mediators of aortic wall stiffness in vitro , these findings may explain the enhanced risk of cardiorenal disease in DKD., (© 2023 Published by Elsevier Inc. on behalf of the International Society of Nephrology.)

Diabetes is the commonest cause of end-stage kidney disease in many parts of the world, and many people on dialysis programmes live with diabetes. Such people are vulnerable to complications from their diabetes, and their care may be fragmented due to the many specialists involved. This updated guidance from the Joint British Diabetes Societies aims to review and update the 2016 guidance, with particular emphasis on glycaemic monitoring in the light of recent advances in this area. In addition, the guidance covers clinical issues related to the management of diabetes in people on peritoneal dialysis, along with acute complications such as hypoglycaemia and ketoacidosis, and chronic complications such as foot and eye disease., (© 2022 Diabetes UK.)

There is an increasing number of people with diabetes on peritoneal dialysis (PD) worldwide. However, there is a lack of guidelines and clinical recommendations for managing glucose control in people with diabetes on PD. The aim of this review is to provide a summary of the relevant literature and highlight key clinical considerations with practical aspects in the management of diabetes in people undergoing PD. A formal systematic review was not conducted because of the lack of sufficient and suitable clinical studies. A literature search was performed using PubMed, MEDLINE, Central, Google Scholar and ClinicalTrials.gov., from 1980 through February 2022. The search was limited to publications in English. This narrative review and related guidance have been developed jointly by diabetologists and nephrologists, who reviewed all available current global evidence regarding the management of diabetes in people on PD.We focus on the importance of individualized care for people with diabetes on PD, the burden of hypoglycemia, glycemic variability in the context of PD and treatment choices for optimizing glucose control. In this review, we have summarized the clinical considerations to guide and inform clinicians providing care for people with diabetes on PD., (© 2023 Published by Elsevier, Inc.)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were first used as antidiabetic agents that lower the blood glucose levels by promoting glycosuria. In recent years, randomised clinical trials have demonstrated that SGLT2i reduce cardiovascular-renal events and all-cause mortality in people with and without diabetes. The cardio-renal benefits observed are independent of glucose lowering effect and multiple mechanisms have been proposed for these results. SGLT2i can exert anti-ageing effects on the vasculature and other body organs through several signalling pathways including the activation of the nuclear factor erythroid-2-related factor 2 and the induction of antioxidant enzymes. We speculate that the pro-longevity effects of the SGLT2i are mediated by soluble Klotho, an anti-ageing kidney-derived hormone and an emerging therapeutic target for cardio-renal diseases., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: Active vitamin D deficiency is associated with increased aortic-pulse wave velocity (Ao-PWV) in people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). There are no randomised controlled trials investigating the effect of active vitamin D treatment on Ao-PWV in people with T2DM and CKD., Methods: A 48-week duration single-centre randomised double-blind parallel-group trial examined the impact of oral 1,25 dihydroxyvitamin D (calcitriol 0.25 mcg OD) as compared to placebo on a primary endpoint of Ao-PWV. People with T2DM and stable stage 3 CKD with intact parathyroid hormone (iPTH) level >30 pg/mL were eligible., Results: In total, 127 (70% male) people were randomised (calcitriol n = 64 or placebo n = 63). There was no change in Ao-PWV observed, mean ± standard deviation (SD), in the calcitriol group of 11.79 (±2.5) to 12.08 (3.0) m/s as compared to 10.90 (±2.4) to 11.39 (±2.6) m/s with placebo. The between-treatment group adjusted mean (95% confidence interval [(CI]] change was 0.23 (-0.58 to 1.05) m/s, P = .57. No effect of calcitriol was observed on central arterial pressures, albuminuria, serum calcium or phosphate levels. However, iPTH fell with calcitriol treatment (mean [95% CI] between-group difference of -27.8 (-42.3 to -13.2) pg/mL, P < .001., Conclusion: In T2DM and stage 3 CKD, calcitriol as compared to placebo does not improve Ao-PWV or other markers of arterial stiffness. Our study does not provide evidence for the use of active vitamin D for improving arterial stiffness in T2DM with stage 3 CKD., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

People with diabetes and chronic kidney disease (CKD) are predisposed to bone mineral disorders and increased fracture risk. There is limited data on the effect of calcitriol on bone turnover markers (BTMs) in people with type 2 diabetes (T2DM) and stage 3 CKD. In a pre-specified secondary endpoint analysis of a 48-week randomized placebo controlled double-blind trial, we studied the effects of oral calcitriol 0.25 μg once daily on circulating BTMs that included osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTXI), procollagen type I N-propeptide (PINP) and fibroblast growth factor-23 (FGF-23). Inclusion criteria were people with T2DM with stable stage 3 CKD stage and intact parathyroid hormone (iPTH) >30 pg/ml. In total, 127 people [calcitriol (n = 64), placebo (n = 63)] were eligible for analyses. Baseline median (interquartile range) age of the cohort was 67 (60.5-70) years, iPTH (median range) 73.9 (55, 105) pg/ml and eGFR 40 (33, 48.5) ml/min. Calcitriol treatments resulted in a significant fall in iPTH, CTX, PINP and OCN levels and rise FGF-23, with mean (95 % confidence interval) between group differences in iPTH [-27.8 pg/ml; 95 % CI (-42.3 to -13.2); p < 0.001], FGF-23 [30.6 pg/ml; 95 % CI (14.8 to 46.3); p < 0.001], CTX [0.12 μg/l; 95 % CI (-0.19 to -0.06); (p < 0.001) and OCN [-4.03 ng/ml; 95 % CI (-7.8 to -0.27); p = 0.036]. Similarly we observed with calcitriol, as between treatment percentage change, a reduction of -38 % for iPTH, -34 % for CTX, and -28 % for OCN levels respectively (p < 0.05 for all). In people with T2DM and stage 3 CKD, calcitriol reduces the levels of CTX, OCN, PINP and iPTH. Further studies are needed to assess the clinical significance of our findings and the related long term impact on bone health., Competing Interests: Declaration of competing interest The authors declare that there is no duality/conflict of interest associated with the manuscript., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objective: We tested the hypothesis that impaired awareness of hypoglycemia (IAH) is independently associated with symptoms of anxiety and depression in type 1 diabetes., Research Design and Methods: In this cross-sectional observational study in 950 adults with type 1 diabetes, associations were examined using multiple regression models, adjusting for sociodemographic and clinical characteristics., Results: Prevalence for probable anxiety, depression, and IAH were 9.4%, 9.8%, and 22.6%, respectively. When included in separate regression models, both depression and anxiety were independently associated with an increased odds of IAH and robust to adjustment (odds ratio 3.64 [95% CI 2.19-6.04] and 2.46 [1.46-4.14], respectively). Further analysis demonstrated a dose-response relationship between increased severity of probable mental disorder and increased odds of having IAH (P < 0.001)., Conclusions: The robust independent relationship between probable anxiety and depression with IAH demonstrates the need for routine psychological assessment and management of people with type 1 diabetes and IAH., (© 2022 by the American Diabetes Association.)

Objective: The mechanisms that explain the cardio-renal benefits of sodium glucose co-transporter 2 (SGLT-2) inhibitors are unknown. The effect of SGLT-2 inhibitors on arterial aging, measured by Aortic Pulse Wave Velocity (Ao-PWV) and Soluble Klotho (s-Klotho), a circulating anti-aging biomarker of arterial health are also unclear., Design/setting: A 24-week single center randomized controlled trial (registry number/ EudraCT Number: 2013-004042-42) comparing Dapagliflozin and Ramipril (D+R) versus Ramipril (R) on the primary endpoint of urine albumin excretion rate (AER) and pre-specified secondary endpoints of Ao-PWV and biomarkers of arterial aging [s-Klotho and Fibroblast Growth Factor 23 (FGF-23)]. People with type 2 diabetes who had estimated glomerular filtration rate (eGFR) > 60 ml/min and residual microalbuminuria on maximum tolerated renin angiotensin system (RAS) inhibition were included in this study., Results: In total, 33 participants (male 73%) were randomized to either D+R ( n = 17) or R ( n = 16) arms. After 24 weeks of treatment, Ao-PWV (mean ± SD) did not change significantly from baseline D +R [9.06 ± 1.91 m/s to 9.13 ± 2.03 m/s], and R [9.88 ± 2.12 m/s to 10.0 ± 1.84 m/s]. AER fell significantly by 43.5% (95% CI: -57.36%, -29.56%; p < 0.01) in people in the D+ R arm only. We do not observe any significant changes in FGF-23 or s-Klotho. HbA1c and Angiotensin 1-7 fell significantly only in D + R arm., Conclusions: The combination of Dapagliflozin and Ramipril had no effects on Ao-PWV and s-Klotho which are biomarkers of arterial aging and cardio-renal risk. Our data suggest that the early cardio-renal benefits observed with SGLT-2 inhibitors are unlikely to be related to an improvement in arterial aging., 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 © 2022 Karalliedde, Fountoulakis, Stathi, Corcillo, Flaquer, Panagiotou, Maltese, Mangelis, Ayis and Gnudi.)