Daily Endocrinology Research Analysis
Across endocrinology, three studies stand out: a systematic review and meta-analysis shows that continuous glucose monitoring improves glycemic outcomes even in noninsulin-treated type 2 diabetes; a nationwide cohort of over 1 million adolescents links lower adolescent BMI and adverse weight trajectories to higher adult osteoporosis risk; and cosyntropin-stimulated indices during adrenal vein sampling predict postoperative outcomes in primary aldosteronism.
Summary
Across endocrinology, three studies stand out: a systematic review and meta-analysis shows that continuous glucose monitoring improves glycemic outcomes even in noninsulin-treated type 2 diabetes; a nationwide cohort of over 1 million adolescents links lower adolescent BMI and adverse weight trajectories to higher adult osteoporosis risk; and cosyntropin-stimulated indices during adrenal vein sampling predict postoperative outcomes in primary aldosteronism.
Research Themes
- Digital diabetes technologies improving outcomes beyond insulin users
- Lifecourse determinants of skeletal health and osteoporosis risk
- Precision endocrinology for surgical decision-making in primary aldosteronism
Selected Articles
1. Continuous glucose monitoring in noninsulin-treated type 2 diabetes: A critical review of reported trials with an updated systematic review and meta-analysis of randomised controlled trials.
This systematic review and meta-analysis of 8 RCTs (n=541) shows that CGM reduces HbA1c by 0.37% versus BGM/usual care in noninsulin-treated T2D, with supportive evidence for improved patient experience, cost-effectiveness, and reduced healthcare utilization. Benefits were generally consistent across CGM types in predefined subgroup analyses.
Impact: Synthesizing RCT data for noninsulin-treated T2D fills a key evidence gap and may influence coverage and guideline recommendations for CGM beyond insulin users.
Clinical Implications: Clinicians can consider CGM to improve glycemic control and patient engagement in noninsulin-treated T2D, advocating for access and reimbursement while matching CGM type to patient needs.
Key Findings
- Meta-analysis of 8 RCTs (n=541) found CGM reduced HbA1c versus BGM/usual care (WMD −0.37%; 95% CI −0.49 to −0.24; p<0.00001).
- Observational and mixed-population RCTs support benefits on glycemic and non-glycemic outcomes, with reduced healthcare resource utilization and acceptable cost-effectiveness.
- Predefined subgroup analyses by CGM type showed generally consistent benefits.
Methodological Strengths
- Systematic review and meta-analysis restricted to RCTs in noninsulin-treated T2D
- Predefined subgroup analyses by CGM type
Limitations
- Overall sample size across trials remains modest
- Heterogeneity in trial designs, follow-up durations, and CGM modalities
Future Directions: Head-to-head RCTs comparing CGM modalities, longer-term outcomes (hypoglycemia, complications), and cost-utility across diverse healthcare systems are warranted.
AIMS: We aimed to review the observational and randomised clinical trial evidence and provide pragmatic recommendations for using continuous glucose monitoring (CGM) in individuals living with noninsulin-treated type 2 diabetes (T2DM). MATERIALS AND METHODS: We first undertook a narrative review of observational studies that enrolled noninsulin-users or mixed populations of noninsulin and insulin-users with T2DM as well as randomised controlled trials (RCTs) that enrolled mixed populations with T2DM. We then performed a systematic review of the RCTs that specifically enrolled noninsulin-treated populations with T2DM and compared CGM to BGM/usual care. A meta-analysis of glycaemic outcomes was conducted with predefined subgroups based on CGM type. RESULTS: RCTs in mixed populations and observational studies demonstrated a largely consistent benefit of CGM on glycaemic and nonglycaemic outcomes with cost effectiveness and reduced healthcare resource utilisation. The meta-analysis of RCTs in noninsulin users included 8 studies encompassing 541 participants, among whom 297 (55%) were assigned to the CGM group. CGM was associated with significantly reduced HbA1c (weighted mean difference [WMD] -0.37%; 95% CI -0.49, -0.24; p < 0.00001; I
2. Adolescent Body Mass Index, Weight Trajectories to Adulthood, and Osteoporosis Risk.
In over 1.08 million Israeli adolescents followed through 2022, lower adolescent BMI and persistent underweight trajectories were strongly associated with higher adult osteoporosis risk, while higher BMI lowered risk in women but not clearly in men. Results were consistent across multiple models and restrictions.
Impact: The unprecedented sample size with decades of follow-up provides robust lifecourse evidence linking adolescent weight status and trajectories to adult osteoporosis risk, informing early prevention strategies.
Clinical Implications: Screening for persistent underweight and optimizing nutrition and weight during adolescence may reduce future osteoporosis risk; sex-specific strategies may be needed given differential associations.
Key Findings
- Inverse association between adolescent BMI and adult osteoporosis risk across 1,083,491 adolescents and 19,400,208 person-years.
- Crude osteoporosis incidence decreased from 330.2/100,000 person-years (extreme underweight) to 78.9 (obesity).
- Adjusted HRs vs normal BMI: women 1.88 (low) to 0.83 (obesity); men 1.82 (low) to 1.04 (obesity), indicating sex-specific differences.
- Highest risk in individuals remaining underweight from adolescence into adulthood.
Methodological Strengths
- Massive population-based cohort with objective BMI measures at adolescence
- Rigorous adjustment including baseline health status and incident comorbidities
Limitations
- Retrospective design with potential residual confounding
- Generalizability to non-Israeli populations may be limited; lacks bone density measures
Future Directions: Prospective studies with bone density and fracture outcomes, exploration of mechanistic pathways, and intervention trials targeting underweight adolescents are needed.
IMPORTANCE: There are limited data regarding adolescent weight among healthy individuals and their trajectory through early adulthood with respect to bone health. OBJECTIVE: To assess the association between adolescent body mass index (BMI) and osteoporosis risk while accounting for BMI change during early adulthood. DESIGN, SETTING, AND PARTICIPANTS: A retrospective population-based cohort study from 1967 to 2019. Participants were Israeli-born adolescents aged 16 to 19 years who were evaluated for military service. Data were analyzed from January 2023 to March 2025. EXPOSURE: Weight and height were measured to calculate BMI at adolescence, and additional sociodemographic and medical data were collected. Health status at baseline and incident cancer and diabetes throughout adulthood were strictly controlled. MAIN OUTCOMES AND MEASURES: Osteoporosis diagnosis until 2022, recorded in the osteoporosis registry of Maccabi Healthcare Services (the second-largest Israeli health care system). Cox proportional hazard models were applied. Adult BMI measurement was available for 74% of the study population and was used to assess the association between adolescence-to-adulthood weight trajectory and incident osteoporosis. RESULTS: In this cohort study of 1 083 491 adolescents, 21 497 (4.58%) women and 6929 (1.13%) men were enrolled in the osteoporosis registry during a cumulative follow-up of 19 400 208 person-years (mean [SD] age at follow-up, 23.7 [8.5] years). There was a consistent inverse association between adolescent BMI and osteoporosis risk in adulthood. The crude incidence rate of osteoporosis decreased from 330.2 per 100 000 person-years among those with extreme underweight (<3rd percentile) to 78.9 among those with obesity (≥95th percentile). Adjusted hazard ratios for osteoporosis ranged from 1.88 (95% CI, 1.74-2.04) to 0.83 (95% CI, 0.77-0.89) in women and from 1.82 (95% CI, 1.64-2.01) to 1.04 (95% CI, 0.93-1.16) in men, using normal BMI as the reference. A sex-specific difference in osteoporosis risk was notable, with obesity not showing a protective association in men compared with women. The findings were robust across multiple models and sample restrictions, and the highest risk was observed in individuals who remained underweight from adolescence into adulthood. CONCLUSIONS AND RELEVANCE: In this cohort study, BMI at a young age and its trajectory to adulthood were significantly associated with risk for osteoporosis in adult life.
3. Cosyntropin-Stimulated Aldosterone Reserve of the Nondominant Adrenal Predicts Surgical Outcomes in Primary Aldosteronism.
In 434 PA patients undergoing AVS with and without cosyntropin, higher contralateral aldosterone reserve ratios in the nondominant adrenal predicted lack of PA cure and bilateral disease. Cosyntropin-stimulated indices thus stratify residual disease risk after adrenalectomy.
Impact: Identifying a physiologic predictor from routine AVS enhances surgical decision-making and patient counseling in PA, aligning with precision endocrine surgery.
Clinical Implications: Patients with high contralateral aldosterone reserve may benefit from more cautious selection for adrenalectomy, consideration of medical therapy, or postoperative monitoring for residual disease.
Key Findings
- Among 434 PA patients, AVS lateralized at baseline only (12%), post-cosyntropin only (11%), both (38%), with 39% bilateral PA.
- Higher contralateral aldosterone reserve ratios were observed in non-cured and bilateral PA (median 11.2 and 17.8) compared with cured patients (median 4.9).
- Cosyntropin stimulation during AVS reveals nondominant adrenal reserve that predicts postoperative outcomes.
Methodological Strengths
- Large single-center cohort with standardized AVS before and after cosyntropin
- Clinically meaningful outcome classification (cure vs non-cure) linked to physiologic indices
Limitations
- Retrospective design from a single tertiary center
- Incomplete reporting of cure definitions and potential selection bias
Future Directions: Prospective validation of reserve thresholds, integration into surgical decision algorithms, and external replication across centers.
BACKGROUND: Adrenal vein sampling (AVS) is commonly used to direct therapy of primary aldosteronism (PA). We hypothesized that cosyntropin stimulation during AVS exposes the reserve of aldosterone-producing cells in the nondominant adrenal gland and might predict postoperative outcomes. METHODS: Patients with PA who underwent successful AVS before and after cosyntropin stimulation between January 2015 and December 2024 in a tertiary-referral center were included. The nondominant adrenal aldosterone reserve was assessed with (1) contralateral aldosterone reserve ratio (=aldosterone postcosyntropin-to-baseline ratio in the nondominant adrenal vein) and (2) lateralization index (LI) ratio (=LI RESULTS: Four hundred thirty-four patients (57% men; mean age, 53±12 years) were included. AVS lateralized only at baseline in 52 (12%) patients, only after cosyntropin in 46 (11%), and in both protocols in 166 (38%); 170 (39%) patients had bilateral PA. PA severity decreased from cases lateralized in both protocols, to postcosyntropin only, baseline only, and consistently bilateral; conversely, the contralateral aldosterone reserve increased across these groups. The contralateral aldosterone reserve ratio was higher in patients without PA cure and bilateral PA (median [interquartile range], 11.2 [5.0-23.5] and 17.8 [9.1-32.0], respectively, versus 4.9 [2.5-9.4] in those cured; CONCLUSIONS: Cosyntropin stimulation during AVS unveils the aldosterone reserve of the nondominant adrenal gland, exposing the risk of residual disease after adrenalectomy.