Roux-en-Y gastric bypass (RYGB) procedure offers notable efficacy in treating type 2 diabetes mellitus (T2DM). The research focused on the glutamate receptor gene Grin3a in mediating the metabolic benefits of RYGB, particularly regarding lipid metabolism.
Public GEO datasets (GSE2508, GSE12050, and GSE35411) were analysed to assess Grin3a expression and its associated pathways. To assess RYGB efficacy, a T2DM model was induced in rats, with Grin3a knockdown, and AMPK activation. Metabolic parameters, insulin resistance, lipid profiles, adipose tissue morphology, and mitochondrial function in epididymal white adipose tissue (eWAT) were examined. The influence of Grin3a on lipid metabolism and the CaMKKβ/AMPK axis was evaluated in vitro using 3T3-L1 adipocytes.
Bioinformatic analyses revealed that Grin3a was diminished in visceral adipose tissue of obese or diabetic models and up-regulated following RYGB. Its expression was associated with lipid metabolism and oxidative phosphorylation pathways. In vivo, RYGB restored Grin3a levels and improved insulin sensitivity, lipid profiles, mitochondrial function, and adipose browning, while Grin3a knockdown attenuated these effects and AMPK activation partially reversed them. In vitro, Grin3a regulated lipid metabolism and mitochondrial function in adipocytes via the CaMKKβ/AMPK pathway.
RYGB improves lipid metabolism and mitochondrial homeostasis in T2DM by activating the Grin3a–CaMKKβ/AMPK axis, offering a potential target for metabolic intervention beyond surgery.
Continuous glucose monitoring (CGM) has become the standard of care for people with type 1 diabetes (T1D) and some people with type 2 diabetes (T2D). However, there is a lack of data regarding CGM use in people with T2D and chronic kidney disease (CKD), who are at increased risk of hypoglycaemia. We assess the use of CGM and glucose outcomes in this cohort.
Retrospective, observational analysis of adults on CGM attending a tertiary diabetes renal clinic between January 2023 and September 2024. People with T2D on multiple daily insulin injections (defined as 2 or more insulin injections per day) and CKD stage 3–5 (eGFR <60, on renal replacement therapy or post-renal transplant) were included. HbA1c was assessed pre- and post-initiation of CGM. CGM metrics were analysed for percentage times in ranges and other glycaemic metrics.
A total of 177 adults (median (interquartile range)) aged 64.0 (56.0–71.0) years were included. Time below range (<3.9 mmol/L) was significantly reduced (median (interquartile range)) from 1.0 (0.0–2.0)% to 0.0 (0.0–1.0)% following CGM initiation (p = 0.007). Hypoglycaemia leading to an insulin dose reduction was revealed by CGM in 91/177 participants (51.4%). Median HbA1c pre- and post-CGM was 64.0 (53.0–79.0) mmol/mol (8.0, 7.0–9.4%) and 62.0 (51.8–73.0) mmol/mol (7.8, 6.9–8.8%), respectively (p < 0.001). HbA1c reduction was observed in 114/177 participants (64.4%).
CGM use was associated with the identification of hypoglycaemia and improvements in HbA1c in people with T2D and CKD. These real-world data demonstrate the importance of CGM technology to high-risk individuals with diabetes and CKD.
The aim of this study was to examine the psychometric properties and factor structure of the Danish translation of Diabetes Eating Problem Survey – Revised (DEPS-R) among adolescents with type 1 diabetes (T1D).
A total of 131 adolescents (53% women) with T1D aged 11–19 years completed DEPS-R and Youth Eating Disorder Examination Questionnaire (YEDE-Q). Additional anthropometric, biochemical, and medical data were obtained from medical records. Exploratory Factor Analysis was performed to examine the factor structure of DEPS-R.
The DEPS-R demonstrated good internal consistency (Cronbach α = 0.87) and was significantly correlated with YEDE-Q (r = 0.83; p < 0.01), HbA1c (r = 0.35; p < 0.01), zBMI (r = 0.35; p < 0.01), and age (r = 0.20; p < 0.05), indicating high convergent validity. The median DEPS-R score was 10 [5–18] for the entire sample; however, it was significantly higher among women (15 [9–21]) than men (6 [4–10]). Factor analysis revealed a three-factor structure accounting for 58% of the variance and indicated that item 4 contributed less strongly to the overall score.
This study supports the validity of DEPS-R as a screening tool for detecting the risk of disordered eating in adolescents with T1D but challenges the relevance of item 4. Future research is needed on updating the original DEPS-R, including a sensitivity analysis of DEPS-R in detecting the risk of serious eating disorder-related behaviour in T1D.
Severe type 1 diabetes (T1D) poses significant challenges due to absolute insulin deficiency, leading to glycemic instability and severe hypoglycaemic events (SHEs). Despite advancements in insulin therapy, some people experience profound instability and impaired quality of life. This article aims to highlight Lantidra (donislecel), the first FDA-approved allogeneic pancreatic islet cellular therapy, as a novel therapeutic option. The manuscript also discusses Lantidra's safety profile, regulatory pathway, and its therapeutic role within contemporary T1D management frameworks.
Isolation, purification, and transplantation protocols of allogeneic pancreatic islets were derived from the pivotal UIH-001 and UIH-002 clinical trials.
Pivotal clinical trials in individuals with brittle T1D and hypoglycaemic unawareness demonstrated that a significant proportion achieved insulin independence, with some lasting over 5 years. This was accompanied by a reduction in SHEs and improved HbA1c. The mechanism relies on islet engraftment in the liver, leading to neovascularization and functional beta-cell (β-cell) contribution to glucose homeostasis. However, the therapy carries substantial risks, including complications from the intraportal infusion and lifelong systemic immunosuppression. Consequently, careful patient selection and meticulous post-transplant management are critical.
Lantidra is currently reserved for highly selected adult T1D people with problematic hypoglycaemia and labile glycaemia unresponsive to other optimized therapies, where benefits may outweigh risks. Future research aims to improve graft survival, minimize immunosuppression, and explore alternative cell sources to expand β-cell replacement therapies.
To explore attitudes of people living with diabetes (PLD) and healthcare professionals (HCP) towards the use of automated retinal image analysis systems using artificial intelligence (AI) in NHS Diabetic Eye Screening Programmes (DESP) and how these perceptions vary by sociodemographic subgroups.
Two anonymous online surveys (28 questions for PLD and 21 for HCP) were developed to assess attitudes towards AI. Data were collected from four English DESPs, diabetes charities and patient groups between September and December 2023. Likert-scale responses were analysed using regression to examine subgroup differences.
A total of 1577 PLD and 262 HCP participated. Fifty-eight per cent of PLD believed AI would perform equally well in all subgroups, compared with 32% of HCP. Seventy-one per cent of HCP disagreed that AI could replace human grading, and 81% of PLD felt humans should remain responsible for screening outcomes. Both groups supported AI's efficiency but had concerns about data security, trust, job security and who would be responsible for AI errors. Linear regression of Likert scores showed women were less accepting of AI; PLD of Black and Asian ethnicities were more cautious of data security and impact on screening experience. HCP of Asian ethnicity generally held more negative views across themes. Those using more online applications had more positive views towards AI.
While both PLD and HCP recognise AI's potential benefits, concerns regarding security, job impact and errors highlight the need for targeted outreach based on sociodemographic factors.
Rates of diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS) have been rising in the US and Europe, but drivers remain unclear. Asian data are limited. This study examines trends and risk factors for DKA and HHS admissions among patients with type 2 diabetes (T2D) in Singapore.
We analysed 47,489 adults (≥18 years) with T2D from a tertiary hospital in Singapore (2013–2022). DKA and HHS admissions were identified via diagnostic codes. Trends in standardized admission rates, HbA1c, and medication use were described. A nested case–control logistic regression model (1:2 incidence-density matched) was used to estimate the effect of HbA1c on the odds of admission for DKA and/or HHS.
DKA and HHS admissions increased from 2013 to 2022 despite declining mean HbA1c, though DKA rates decreased after 2020. Higher HbA1c was significantly associated with admission odds (OR 1.18, 95% CI 1.13–1.23). Other independent risk factors included younger age (OR 0.72, 95% CI 0.70–0.74), lower BMI (OR 0.96, 95% CI 0.95–0.98), social housing (OR 1.50, 95% CI 1.13–1.98), diabetes duration >10 years (OR 1.58, 95% CI 1.14–2.21) and CKD stage ≥3A, with the highest odds in stage 4 (OR 5.81, 95% CI 4.13–8.17).
DKA and HHS admission rates rose despite improving HbA1c. High-risk groups may require closer monitoring and targeted interventions.
This study aims to investigate the effects of isoastragaloside I (IAS-I) on improving diabetic symptoms and its impact on endogenous β-cell mass, and further explore the origins of increased β-cells.
Healthy and diabetic mice received IAS-I treatment (5 or 0.5 mg/kg, respectively) via tail veil injection. The blood glycaemic control, body weight, and glucose/insulin tolerance were evaluated. Safety was assessed via complete blood count and histopathological analysis. Uniformly sampled pancreatic sections (spanning the entire pancreas) were immunohistochemically stained for β-cells, imaged, and analysed by point-counting morphometry to estimate β-cell mass. Furthermore, SOX9-CreERT2; R26-LSL-tdTomato mice were used to trace the pancreatic ductal cell, and conduct multiplex immunohistochemistry to explore the conversion of pancreatic ductal cells into β-cells.
In both healthy and diabetic mice, IAS-I could increase the β-cell mass; especially 0.5 mg/kg IAS-I significantly increased the small islet mass. Using lineage tracing, we demonstrated that IAS-I promoted the generation of β-cells from ductal cells. We also found that IAS-I could improve the fasting blood glucose and insulin resistance in diabetic mice, and the safety of IAS-I in vivo had also been preliminarily demonstrated.
Our results suggest that IAS-I increases β-cell mass and promotes the formation of β-cells from pancreatic ductal cells in vivo. It is also speculated to possess islet-protective activity. These findings provide insight into the potential application of Astragalus membranaceus monomers in diabetic treatment.
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