Daily Endocrinology Research Analysis

IMPORTANCE: Hyperglycemia-related pregnancy complications occur in 50% of pregnant women with type 1 diabetes. Closed-loop insulin systems improve glycemia outside of pregnancy but have had limited testing in pregnancy. OBJECTIVE: To assess the efficacy of a closed-loop system in pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Open-label trial enrolling pregnant women with type 1 diabetes at 14 clinical centers in Canada and Australia before 14 weeks' gestation with follow-up until 6 weeks postpartum. Enrollment occurred between June 2021 and July 2024 and follow-up was completed in March 2025. INTERVENTIONS: Participants were randomized 1:1 to closed-loop therapy (n = 46) or standard care (insulin pump or multiple daily insulin injections) (n = 45) with continuous glucose monitoring. MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage of time spent in the pregnancy-specific glucose range (63-140 mg/dL), measured by continuous glucose monitoring from 16 to 34 weeks' gestation. RESULTS: Among 94 enrolled participants, 3 experienced pregnancy loss prior to randomization, 91 were randomized (mean age, 31.7 [SD, 5.2] years; early pregnancy hemoglobin A1c, 7.4% [SD, 1.0%]), and 88 were included in the primary analysis. The mean percentage of time spent in the pregnancy-specific glucose range from 16 to 34 weeks' gestation was 65.4% in the closed-loop group and 50.3% in the standard care group (mean adjusted difference, 12.5 [95% CI, 9.5-15.6] percentage points; P < .001). There was 1 episode of severe hypoglycemia in the closed-loop group, and there were 2 episodes of diabetic ketoacidosis in the closed-loop group and 1 in the standard care group. CONCLUSION AND RELEVANCE: Pregnant women with type 1 diabetes using a closed-loop system spent significantly more time in the pregnancy-specific glucose range than those receiving standard care. These findings support the use of this closed-loop system in pregnant women with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04902378.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual agonists have been shown to induce histological improvements in patients with metabolic dysfunction-associated steatohepatitis (MASH). However, current clinical evidence on their effectiveness in improving hepatic fibrosis and cardiovascular outcomes remains limited and inconsistent. METHODS: This study synthesized randomized controlled trials (RCTs) from major databases up to August 30, 2025, focusing on patients with biopsy-confirmed MASH. Pooled mean differences were calculated using either a fixed-effects or random-effects model, depending on the degree of heterogeneity observed among the studies. RESULTS: Six studies including 1,726 participants were analyzed. Compared with placebo, GLP-1RAs and dual agonists significantly increased the likelihood of histological improvement in MASH without worsening hepatic fibrosis. (OR: 4.51, 95% CI: 3.68 to 5.52). It was associated with a ≥1-stage improvement in hepatic fibrosis without worsening MASH (OR: 1.78; 95% CI: 1.47to2.16). In addition, it contributed to MASH resolution accompanied by a ≥1-stage improvement in hepatic fibrosis (OR: 7.42; 95% CI: 2.98to18.48). In subgroup analyses based on post-treatment weight loss, GLP-1RAs and dual agonists demonstrated significant efficacy in promoting hepatic fibrosis resolution without worsening MASH among patients achieving a ≥10% weight loss (OR: 9.59; 95% CI: 4.01to15.18). However, in patients with <10% weight loss, GLP-1RAs and dual agonists did not demonstrate significant differences (OR: 1.30; 95% CI: 0.92to1.83). Moreover, GLP-1RAs and dual agonists achieved a significant pooled reduction in cardiovascular parameters, including total cholesterol (WMD: -4.15 mmol/L; 95% CI: -13.13 to 4.82) and triglycerides (WMD: -17.70 mmol/L; 95% CI: -21.95 to -13.44). Nevertheless, no significant improvement was observed in Low-Density Lipoprotein Cholesterol (LDL-C) levels (WMD: -0.67 mmol/L; 95% CI: -6.55 to 5.21). CONCLUSION: In patients with MASH who achieve a ≥10% weight loss, GLP-1RAs and dual agonists are associated with significant improvements in hepatic fibrosis, whereas their effect is limited in those with <10% weight loss. However, a significant reduction in LDL-C was observed only among patients achieving substantial (≥10%) weight loss. This finding suggests that for patients requiring comprehensive cardiovascular risk management, additional lipid-lowering strategies may be needed to optimize the effectiveness of the intervention. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42025640318.

AIM/HYPOTHESIS: Chronotype reflects an individual's circadian rhythm, which may be associated with lifestyle habits and metabolic profiles. A few studies have shown that disruptions in circadian rhythms may contribute to the pathogenesis of diabetic retinopathy. This prospective observational study aimed to investigate the association between lifestyle habits, including chronotype, and the incidence and progression of diabetic retinopathy. METHODS: The study participants were 731 Japanese outpatients with type 2 diabetes and no apparent history of cardiovascular disease. Lifestyle habits were assessed using questionnaires, including the Morningness-Eveningness Questionnaire (MEQ), to determine chronotype at baseline and at years 2 and/or 5. The composite endpoint of this study was the incidence and progression of diabetic retinopathy. The mean values of lifestyle factors were calculated by averaging the values from baseline to the date of endpoint onset or the end of the follow-up period. A Cox proportional hazards model was used to determine the association between lifestyle habits and the composite endpoint. RESULTS: During the median follow-up period of 7.56 years (IQR 6.04-7.95), the composite endpoint was observed in 57 participants. Multivariate Cox models showed a significant negative association between the mean MEQ scores and the composite endpoint (HR 0.95; 95% CI 0.91, 0.99). In a sensitivity analysis in which the participants were divided into three groups based on mean MEQ scores, the 'more evening' chronotype group had a 2.29-fold higher risk (95% CI 1.15, 4.55) of the composite endpoint compared with the 'neither' group. Compared with the 'more morning' chronotype group, the more evening chronotype group had a 2.09-fold higher risk of the composite endpoint (95% CI 1.05, 4.13). Participants with the more evening chronotype experienced worsening glucose management over time compared with those with other chronotypes. However, a significant negative association between the mean MEQ scores and the composite endpoint was still observed after adjusting for the mean HbA CONCLUSIONS/INTERPRETATION: People with type 2 diabetes and an evening chronotype have worsened glucose management and are at a higher risk of incidence and/or progression of diabetic retinopathy. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000010932.