Daily Endocrinology Research Analysis

AIMS: The landscape of insulin delivery is evolving, transitioning from hybrid automated insulin delivery (AID) to more sophisticated fully AID systems. We aimed to compare the efficacy of fully AID systems with any insulin delivery method in type 1 diabetes (T1D). MATERIALS AND METHODS: Following registration in PROSPERO, CRD42024528669, PubMed, Embase, Cochrane Library and Web of Science were searched up to 26 February 2025 for randomised clinical trials comparing fully AID systems to any insulin delivery method in T1D. The control treatments included conventional insulin therapy (multiple daily injections, continuous subcutaneous insulin infusion and sensor-augmented pumps) and hybrid AID systems. The primary outcome was the mean difference (MD) in the percentage of time blood glucose concentration remained in the target range (3.9-10.0 mmol/L or 4.0-10.0 mmol/L), assessed by random-effects models. RESULTS: We identified 1308 reports; after exclusions, 16 trials (669 patients) were included. Time in range (TIR) was higher using fully AID systems than control treatments (MD 9.99% [95% confidence interval, 3.75% to 16.22%], p = 0.002). This improvement was accompanied by increased diabetes treatment satisfaction (MD 3.70 points [95% confidence interval, 0.22 points to 7.18 points], p = 0.04). Fully AID systems exhibited a favourable effect on TIR when compared with conventional insulin therapy, while exhibiting an opposite effect when compared with hybrid AID (17.44% vs. -3.05%, p < 0.001). Younger patients with T1D, as well as patients with a shorter diabetes duration, exhibited more significant glycaemic improvements with fully AID systems therapy. CONCLUSIONS: Fully AID systems improved glycaemic control and diabetes treatment satisfaction compared with other non-AID methods in patients with T1D, especially for younger patients. However, to achieve or exceed the desired benefits of hybrid AID, algorithm upgradation, along with the synergistic integration of multiple hormones, will be crucial for next-generation fully AID systems.

As global aging accelerates, the incidence of thyroid diseases, particularly hypothyroidism, is rising in the elderly. The thyroid-stimulating hormone (TSH) levels increase in healthy elderly populations. However, whether the thyroid undergoes cellular senescence and how this relates to thyroid hormone (TH) synthesis remain unclear. To investigate the molecular and functional characteristics of thyroid aging, we performed scRNA-seq on human thyroids from young, middle-aged, and old groups, identifying thousands of aging-related differentially expressed genes and revealing the early onset of aging in the middle-aged group. As aging progresses, the expression levels of genes related to TH synthesis increase, suggesting that epithelial cells (EPI) adjust their gene expression in response to elevated TSH levels. Additionally, the senescence-associated secretory phenotype (SASP) in EPI cells is progressively enhanced with aging. We identified a subgroup of epithelial cells (CDKN1A_EPI) characterized by reduced functionality and significantly elevated levels of cellular senescence. We found that the core circadian rhythm gene BMAL1 (ARNTL) is downregulated during aging. We further validated this finding using the thyroid-specific Bmal1 knockout mouse model, showing that the downregulation of Bmal1 inhibits the expression of Nfkbia (NF-κB inhibitor alpha), thereby accelerating cellular senescence and impairing hormone synthesis. Finally, through cell line experiments and transcriptome sequencing, we confirmed that BMAL1 knockout leads to decreased NFKBIA expression, promoting thyroid cellular senescence. Our study demonstrates that circadian rhythm disruption accelerates cellular senescence in the thyroid and exacerbates the decline of thyroid function, providing a novel theoretical foundation for understanding thyroid aging mechanisms and maintaining thyroid function stability.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease (NAFLD), is a growing but often unrecognized medical problem for people with diabetes (particularly type 2 diabetes, especially when associated with obesity). Liver health has not been at the forefront of complications tracked for disease prevention, as traditionally done for diabetic retinopathy, nephropathy, or neuropathy. However, liver steatosis affects approximately two out of three people with type 2 diabetes and places them at an increased risk for metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, hepatocellular carcinoma (HCC), and overall liver-related mortality. MASLD is also associated with extrahepatic cancers, atherosclerotic cardiovascular disease, and progression from prediabetes to type 2 diabetes and negatively impacts health-related quality of life. However, most individuals and their health care professionals remain unaware of the severe hepatic or extrahepatic health risks associated with MASLD and the need for early identification. In recognition of this knowledge gap and the rising prevalence of MASLD, this consensus report is a call to action to screen for liver fibrosis and risk stratify people with prediabetes or type 2 diabetes, in particular if obesity is also present. This consensus report explains the rationale for the recent MASLD nomenclature change, how to best risk stratify, current treatment and long-term monitoring options, the value of an interprofessional approach to disease management, and the impact of alcohol intake on liver health. More awareness about the health risks associated with MASLD and broad adoption of screening for liver fibrosis as a new standard of care hold promise for a future without cirrhosis for people with prediabetes and type 2 diabetes.