Podocyte injury is a hallmark of diabetic nephropathy (DN) and significantly contributes to disease progression. Accumulating evidence suggests that impaired autophagy exacerbates podocyte dysfunction under hyperglycaemic conditions. However, the underlying regulatory mechanisms remain incompletely understood. This study aimed to investigate the role and mechanism of microRNA-10a-5p (miR-10a-5p) in regulating podocyte injury and autophagy in DN. The function of miR-10a-5p was explored in high glucose (HG)-induced murine podocyte (MPC5) cells and streptozotocin (STZ)-induced diabetic mice. Gain- and loss-of-function experiments were conducted using miR-10a-5p mimics or inhibitors. E2F transcription factor 7 (E2f7) was predicted as a downstream target of miR-10a-5p via bioinformatics, and the binding between miR-10a-5p and E2f7 was assessed using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Podocyte injury, cell apoptosis, inflammation and autophagy were assessed using flow cytometry, Western blotting, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining. Rescue experiments were conducted by silencing or overexpressing E2f7 to confirm its role in miR-10a-5p-mediated effects. miR-10a-5p was significantly upregulated in HG-stimulated podocytes and kidney tissues of diabetic mice. Inhibition of miR-10a-5p alleviated HG-induced podocyte injury, as evidenced by enhanced cell viability, reduced apoptosis and inflammatory cytokine production, and restored autophagic activity. E2f7 was identified as a direct target of miR-10a-5p. Notably, silencing E2f7 abrogated the protective effects of miR-10a-5p inhibition on podocyte survival and autophagy, and E2f7 overexpression restored the detrimental effects of miR-10a-5p overexpression on podocytes. Invivo, administration of AntagomiR-10a-5p in STZ-induced diabetic mice ameliorated renal injury and restored autophagic flux, and increased E2f7 expression in mouse renal tissues. This study identifies the miR-10a-5p/E2f7 axis as a critical regulator of podocyte injury and autophagy in DN. Therapeutic inhibition of miR-10a-5p may represent a promising strategy for preserving podocyte function and attenuating DN injury.

In all forms of diabetes, beta cell failure is associated with disproportionate proinsulin secretion, a marker of endoplasmic reticulum stress. Histopathological studies have suggested that defective expression of prohormone convertases may lead to proinsulin becoming the predominant secretory product. We analysed meal-stimulated proinsulin secretion in people with minimal residual C-peptide secretion. We studied a cohort of 320 individuals, among whom 55 exhibited poorly stimulated C-peptide levels (peak <0.3 nmol/L) during a 2-h mixed-meal tolerance test (MMTT; carbohydrates (60 g), lipids (5.5 g), proteins (10 g)). Serum C-peptide (Diasorin, LOQ 0.01 nmol/L) and proinsulin (ELISA, Mercodia, LOQ 0.5 pmol/L) were measured at baseline and at 60 and 120 min. Responses were assessed using peak values and peak-to-basal ratios. Results are expressed as median [interquartile range]. Among these 55 individuals, most had type 1 diabetes (n = 44); other aetiologies included type 2 diabetes (n = 1) and other forms (n = 10). Diabetes duration was 18 [8-25] years, HbA1c was 61 mmol/mol (7.7%), and all subjects were insulin-treated (0.6 [0.47-0.79] U/kg/day). Peak C-peptide was 0.03 [0.001-0.12] nmol/L, peak proinsulin was 0.8 [0.5-1.75] pmol/L. Among participants with non-stimulated C-peptide (n = 14) following MMTT, 5 showed stimulated proinsulin secretion. The presence of stimulated proinsulin secretion in long-standing diabetes with minimal residual C-peptide secretion suggests the persistence of dysfunctional yet meal-responsive beta cells.

To establish the rates of and variables associated with glycaemic disturbances in people with type 1 diabetes with a functioning pancreas transplant, and to quantify the association with graft failure. An observational study on routinely collected data from pancreas transplant recipients at University Hospital Wales from January 2013 to April 2019 with glucose tolerance test (GTT) data. Their variables were analysed to assess rates and risk factors for glycaemic disturbance. Of the 96 participants in this study, 30% developed glycaemic disturbance. Hyperglycaemia was twice as common as hypoglycaemia (22% vs. 10%). Recipients who developed hypoglycaemia were predominantly women (90% vs. 26% for those who developed hyperglycaemia, p = 0.001), had a lower mean BMI (23.7 vs. 27.6 kg/m2 for hyperglycaemic individuals, difference: 3.89, CI: 0.77-7.0, p = 0.017). There was no increase in graft failure rates for recipients with glycaemic disturbances (normoglycaemia: 12%, hypoglycaemia: 10%, hyperglycaemia: 4.8%, p = 0.70). Recipients with post-transplantation hypoglycaemia were more likely to be women and of low body weight, which may be due to disordered eating with restricted calorie or carbohydrate intake. Recipients with post-transplantation hyperglycaemia had features of insulin resistance and type 2 diabetes with increased weight and men predominance. Glycaemic disturbance was not associated with graft failure, suggesting it relates to insulin-glucose mismatch rather than rejection. Further follow-up is required to identify the long-term sequelae of glycaemic disturbance after pancreas transplants and if relevant dietary counselling has the potential to attenuate these disturbances.

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, which can cause various complications that threaten health. Long non-coding RNA (lncRNA) is associated with the occurrence and development of diabetes and its complications. The aim is to explore the regulatory mechanism of lncRNA KDM4A-AS1 on T2DM and on the function of pancreatic β cells. We enrolled 98 T2DM patients and 91 healthy controls, measuring serum and cellular factor expression via RT-qPCR. Proliferation was assessed with CCK-8, apoptosis by flow cytometry and insulin secretion by ELISA. We confirmed KDM4A-AS1/miR-423-5p and miR-423-5p/ growth differentiation factor 11(GDF11) interactions using RNA immunoprecipitation and dual-luciferase reporter assays. In the serum of patients with T2DM, the expressions of KDM4A-AS1 and GDF11 were significantly downregulated, while the expression of miR-423-5p was significantly upregulated. The level of KDM4A-AS1 was negatively correlated with fasting plasma glucose (FPG) and glycosylated haemoglobin (HbAlc). KDM4A-AS1 has a good diagnostic value for T2DM. Experiments conducted invitro demonstrated that overexpression of KDM4A-AS1 could promote the expression of insulin synthesis genes Ins1 and Ins2, increase the amount of insulin secretion stimulated by glucose and simultaneously increase the cell proliferation rate and reduce the apoptosis rate. Mechanism studies have confirmed that KDM4A-AS1 can directly target miR-423-5p and exert protective effects on pancreatic β cells by regulating the expression of downstream GDF11. This study reveals that KDM4A-AS1 protects β-cell function through the miR-423-5p/GDF11 axis, providing a new potential target for the diagnosis and treatment of T2DM.

To evaluate the efficacy and safety of automated insulin delivery (AID) systems in very young children with type 1 diabetes (T1D). PubMed, Embase, Scopus, and Web of Science were searched until 10 October 2025. Inclusion criteria were randomized controlled trials (RCTs); T1D populations under 7 years old; comparing AID systems with standard care (SC). Primary efficacy endpoint was the percentage of time-in-range of 70-180 mg/dL (TIR) derived from continuous glucose monitoring (CGM), secondary outcomes included glycated haemoglobin (HbA1c), other CGM metrics, and insulin dose. Safety endpoints included severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA). Four RCTs involving 292 participants were included. The mean age was 4.70 years, with a mean T1D duration of 1.96 years. The study duration ranged from 8 to 16 weeks. Compared with SC, AID significantly improved TIR by mean difference (MD) +9.29% (95% confidence interval [CI]: 7.27-11.30, I2 = 70%, p < 0.001) accompanied by a favourable effect on HbA1c by MD -4 mmol/mol (-0.39%) (95% CI [-6 to -2] (-0.57 to -0.21), I2 = 82%, p < 0.001). A favourable decrease in time-above-range (TAR, >180 mg/dL; >250 mg/dL) and mean blood glucose were also observed in AID over SC (all p < 0.05). No significant differences were observed between AID and SC groups in time in hypoglycaemia, insulin dose, and risk of SH and DKA (all p > 0.05). AID systems may outperform SC in improving short-term glycaemic control (TIR, HbA1c, TAR) in very young children with T1D, without increasing time in hypoglycaemia, insulin dose, or risk of SH and DKA. These preliminary findings support the clinical potential of AID systems and highlight the need for longer term studies.

Managing diabetes during exercise remains challenging, particularly in settings of sustained physical activity such as diabetes-camps. This study aimed to evaluate the efficacy and safety of a diabetes-camp protocol including an adaptive algorithm for prandial bolus reduction and the use of automated insulin delivery (AID) exercise modes in children with type 1 diabetes (CwD). Data from two 7-day camps for 77 CwD aged 8-14 years using 780G, Control-IQ, or CamAPS were evaluated. Exercise modes were active throughout each camp, and meal boluses were adjusted by an adaptive algorithm. Continuous glucose monitoring metrics were evaluated and compared among AID systems and the 14-day pre-camp period. Hypoglycemia episodes and carbohydrates were recorded. Median time in range (TIR) was 80% during the camps, with time below range 3% (level 1; TBR1) and 1% (level 2; TBR2). Participants experienced a median of 2 hypoglycemia episodes/day. No severe hypoglycemia or diabetic ketoacidosis occurred. Median prandial bolus reduction in comparison with the calculated bolus was 45% (range 10-110%). Outcomes were similar across AID systems. TIR increased (80% vs. 78%, p = 0.015) and TBR rose modestly (TBR1 3% vs. 2%, p < 0.001; TBR2 1% vs. 0%, p = 0.002) compared to the pre-camp period. The protocol provided a safe and effective option to achieve glycemic targets across assessed AID systems during sustained physical activity at diabetes camps.

This systematic review aimed to systematically evaluate the methodological quality and predictive performance of existing prognostic models for diabetic kidney disease (DKD) outcomes. A systematic search of PubMed, Web of Science, Cochrane Library, Ovid Embase, China National Knowledge Infrastructure (CNKI), Wanfang, Vip and SinoMed was conducted from database inception to 30 April 2026. Two reviewers independently screened studies, extracted data using the CHARMS checklist and assessed risk of bias with PROBAST. A total of 27 studies were included, comprising 80 prediction models. Among them, two were prospective studies and 25 were retrospective studies. The primary outcomes included renal-related events, all-cause mortality and cardiovascular endpoints. Twenty-two studies used traditional regression methods, five applied machine learning algorithms and four combined both approaches for model development. The most frequently used predictors were age, estimated glomerular filtration rate (eGFR), urine-albumin-creatinine ratio (UACR), urinary total protein (UTP), body mass index (BMI), haemoglobin and systolic blood pressure (SBP). Only eight studies performed external validation, and most models showed acceptable discrimination, with area under the curve (AUC)/C-statistic ranging from 0.70 to 0.90. All studies were judged to have a high risk of bias, and 21 were considered to have high concerns regarding applicability, mainly due to single-centre design and restrictive inclusion criteria. Current DKD prognostic models demonstrate acceptable discrimination but lack adequate calibration and external validation, highlighting the need for more rigorous study designs to enhance reliability and clinical applicability.

Diabetes mellitus is associated with perioperative dysglycaemia and post-operative complications. Aboriginal and Torres Strait Islander people have higher rates of diabetes mellitus and post-operative complications than non-Indigenous Australians, yet data on their perioperative glycaemic profiles are lacking. The aim of this study was therefore to comprehensively describe perioperative glycaemic profiles in Aboriginal and Torres Strait Islander people with diabetes mellitus. We conducted a retrospective multicentre cohort study of 16,396 adults with diabetes mellitus undergoing surgery in South Australia (2018-2023). Patient demographics, comorbidities, anti-hyperglycaemic agents, glycated haemoglobin (HbA1c) levels, and perioperative blood glucose levels (BGL) were compared between Aboriginal and Torres Strait Islander people and non-Indigenous Australians using chi-squared tests for categorical data, and non-parametric tests for numerical data. Aboriginal and Torres Strait Islander people (n = 1065, 6.5% of the cohort) were younger (54.3 vs. 68.2 years, p < 0.001), more likely to be female (52.1% vs. 41.6%, p < 0.001), and experienced greater preoperative comorbidity (coronary artery disease: 26.8% vs. 14.8%, p < 0.001) (chronic kidney disease: 21.9% vs. 15.2%, p < 0.001) than non-Indigenous Australians. Although their pre-admission HbA1c was higher (68.5 mmol/L (8.4%) vs. 62.1 mmol/mol (7.8%), p < 0.001), their perioperative patient-day mean BGL (8.7 vs. 8.8 mmol/L, p = 0.032), glycaemic variability (coefficient of variation: 21.3% vs. 21.6%, p = 0.045) and perioperative glycaemic ratios (1.24 vs. 1.28, p = 0.382) were similar. However, higher rates of hypoglycaemia were observed amongst Aboriginal and Torres Strait Islander people (14.6% vs. 10.3%, p < 0.001), coinciding with greater inpatient use of sulphonylureas and insulin. Despite being 14 years younger and having greater preoperative comorbidity and higher HbA1c levels, Aboriginal and Torres Strait Islander people demonstrated higher rates of perioperative hypoglycaemia, but otherwise broadly comparable perioperative glycaemic profiles to their non-Indigenous Australian counterparts. Further research should ideally be Indigenous-led, and prospectively evaluate interventions to both reduce cumulative glycaemic burden and optimise perioperative glycaemia using modern diabetes technologies in Aboriginal and Torres Strait Islander people both with and without diabetes mellitus.

The type 1 diabetes population is ageing. Frailty is the age-related physiological decline that occurs across organ systems, increasing the body's vulnerability to stressors. Current consensus-based guidelines, derived from evidence in type 2 diabetes, prioritise hypoglycaemia avoidance, which increases falls, hospitalisation and mortality risk in older adults. This study assesses whether frailty is associated with increased hypoglycaemia in older adults with type 1 diabetes. Participants were over 65, with type 1 diabetes, confirmed by C-peptide measurement. Frailty was categorized as robust, prefrail or frail as per Fried Frailty Phenotype (gait speed, weight loss, hand-grip strength, exhaustion and physical activity). Secondary analyses used Clinical Frailty Scale and Short Physical Performance Battery. Cognition was assessed using Montreal Cognitive Assessment score (MoCA). Blinded continuous glucose monitors (CGM), Dexcom G6/G7, were worn for 10 days. CGM metrics were compared between frailty categories, focusing on percentage time below range (%TBR). 83 participants met the inclusion criteria. 38 were robust (45.8%), 29 prefrail (34.9%) and 16 frail (19.3%). Frail participants were older, with more comorbidities and diabetes complications. Frailty was associated with higher HbA1c (p = 0.025) and lower MoCA scores (p = < 0.001). There was no difference between any CGM-derived glycaemic parameter across the frailty spectrum, regardless of frailty assessment used. While frailty is often associated with hypoglycaemia in diabetes, this was not demonstrated in our type 1 diabetes cohort. Raised HbA1c levels with frailty may reflect recommendations to relax glucose targets. However, no difference was found in %TBR with frailty.

To describe the clinical characteristics of patients with Wolfram syndrome (WFS) and diabetes mellitus (DM) in Aotearoa, New Zealand. Review of response to therapy in those treated with glucagon-like peptide-1 receptor agonists (GLP1RA). This retrospective cohort study describes 7 patients with WFS1 genetic variants (1 patient with WFS-like syndrome), and DM from 5 New Zealand families (age range 5-33 years, 4 females, 3 males). All are receiving insulin. In 5 patients receiving GLP1RA therapy, we described their pre- and post-treatment biometric parameters, glycaemic control and visual acuity. Genetic testing identified compound heterozygous variants in the WFS1 gene (inherited from each parent) in five patients. Another two were heterozygous carriers of a single WFS1 missense variant, one of which was associated with uniparental disomy. Among patients receiving GLP1RA therapy, reductions were seen in HbA1c (mean 11.6 mmol/mol) and total daily insulin dose (mean 0.25 units/kg/day). We report genotypic and phenotypic variability in association with clinical features, including age of onset and severity. GLP1RA therapy was associated with improvements in diabetic control. Longer-term follow-up is required to monitor for sustained benefit and for progression or improvement in other WFS clinical features.