Daily Endocrinology Research Analysis
Three high-impact studies in endocrinology highlight critical care gaps and actionable strategies: a nationwide cohort shows people with intellectual disabilities develop type 2 diabetes at younger ages with poorer care and higher macrovascular complications; among childhood cancer survivors, untreated adult growth hormone deficiency (low IGF1) is linked to broad adverse outcomes and GH therapy remains underused; and SGLT2 inhibitors are associated with lower nephrolithiasis risk versus DPP4 inh
Summary
Three high-impact studies in endocrinology highlight critical care gaps and actionable strategies: a nationwide cohort shows people with intellectual disabilities develop type 2 diabetes at younger ages with poorer care and higher macrovascular complications; among childhood cancer survivors, untreated adult growth hormone deficiency (low IGF1) is linked to broad adverse outcomes and GH therapy remains underused; and SGLT2 inhibitors are associated with lower nephrolithiasis risk versus DPP4 inhibitors or GLP-1 receptor agonists.
Research Themes
- Diabetes inequities and risk in people with intellectual disabilities
- Growth hormone deficiency outcomes and access barriers in cancer survivorship
- SGLT2 inhibitors and kidney stone risk reduction in type 2 diabetes
Selected Articles
1. Type 2 diabetes mellitus in people with intellectual disabilities: Examining incidence, risk factors, quality of care and related complications. A population-based matched cohort study.
In a nationwide matched cohort (n≈495,869), people with intellectual disabilities had a markedly higher adjusted incidence of type 2 diabetes (IRR 6.91), with impaired mobility a strong risk factor (OR 7.72). They received fewer recommended tests and had a 12% higher risk of macrovascular complications, underscoring care inequities.
Impact: This study quantifies substantial diabetes risk and care deficits in a large, underserved population, providing targets for policy and tailored clinical interventions.
Clinical Implications: Implement earlier and more intensive T2DM screening and risk management in people with intellectual disabilities, address mobility-related risks, and ensure equitable delivery of HbA1c/lipid testing and retinopathy/foot examinations to reduce macrovascular complications.
Key Findings
- Adjusted incidence rate ratio for T2DM was 6.91 (95% CI 5.81–8.22) in people with intellectual disabilities versus matched controls.
- Impaired mobility strongly associated with incident T2DM (OR 7.72, 95% CI 5.87–10.15).
- Lower receipt of HbA1c/cholesterol tests and eye/foot exams; 12% higher risk of macrovascular complications.
Methodological Strengths
- Very large population-based matched cohort with comprehensive EHR data (2010–2022).
- Assessment of incidence, risk factors, quality-of-care indicators, and complications with multivariable modeling.
Limitations
- Observational design may have residual confounding and misclassification in EHR coding.
- Follow-up intensity and health care access variability could bias detection of outcomes.
Future Directions: Test targeted screening/care pathways in randomized or quasi-experimental designs for people with intellectual disabilities; evaluate mobility-focused interventions to reduce T2DM risk and complications.
AIMS: People with intellectual disabilities are at higher risk of type 2 diabetes mellitus (T2DM) but there are currently gaps in our understanding related to risk of new onset, care of T2DM and complications. METHODS: We examined electronic health-record data from Jan 2010 to May 2022 in 189,172 people with intellectual disabilities and 306,697 age, sex and family practice matched controls. We estimated incidence rates per 1,000-person-years, incidence rate ratios (IRRs), risk factors for T2DM (odds ratio, OR), indicators of quality of care and complications (hazard ratio, HR). RESULTS: Incidence of T2DM in people with intellectual disabilities was 3.74 compared to 2.21 per 1,000 person-years in controls. After allowing for the younger age of T2DM onset in intellectual disabilities, the adjusted IRR was 6.91 (95 % CI 5.81-8.22). Impaired mobility was associated with T2DM incidence in people with intellectual disabilities (OR = 7.72, 5.87-10.15). People with intellectual disabilities received blood tests for HbA1c and cholesterol, and eye and foot examinations less often; and had a 12 % higher risk of developing macrovascular complications. CONCLUSIONS: People with intellectual disabilities are at increased risk of T2DM at younger ages, have specific risk factors, experience inequities in care and are at risk for macrovascular complications.
2. Adult Growth Hormone Deficiency, Replacement Therapy, and Outcomes in Long-Term Childhood Cancer Survivors.
In 3,902 adult survivors of childhood cancer, only 9% of those with severe adult GH deficiency received GH therapy. Socioeconomic disadvantage was linked to lower GH therapy use, and low IGF1 (≤−2 z-score) was associated with worse neurocognitive function, quality of life, glucose metabolism, and adiposity.
Impact: Provides practice-informing evidence that untreated GH deficiency correlates with multidimensional morbidity and identifies socioeconomic barriers to GH therapy access.
Clinical Implications: Use IGF1 as a screening marker for adult GH deficiency in survivors; consider GH therapy when indicated and proactively address socioeconomic barriers to access. Monitor neurocognitive, metabolic, and body composition outcomes in low-IGF1 survivors.
Key Findings
- Only 9.0% of survivors with severe adult GH deficiency were on GH therapy.
- Socioeconomic disadvantage independently reduced GH therapy use (e.g., income <$40,000 vs ≥$80,000: OR 0.27, 95% CI 0.08–0.84).
- Low IGF1 (z ≤ −2) associated with higher odds of neurocognitive impairment (e.g., verbal reasoning OR 2.79), lower physical functioning (OR 1.97), abnormal glucose metabolism (OR 1.82), and increased fat percentage (OR 3.16).
Methodological Strengths
- Large survivor cohort with detailed socioeconomic variables and standardized IGF1 z-scores.
- Multivariable logistic regression adjusting for confounders across multiple outcome domains.
Limitations
- Cross-sectional associations limit causal inference regarding GH therapy benefits.
- IGF1 is a surrogate of GH action; potential misclassification without dynamic testing.
Future Directions: Prospective interventional studies to test GH therapy effects on neurocognitive and metabolic outcomes in low-IGF1 survivors; health services research to remove socioeconomic barriers.
CONTEXT: The consequences of untreated adult growth hormone deficiency (aGHD) among childhood cancer survivors are not well defined. The lack of evidence and socioeconomic factors may contribute to underutilization of growth hormone therapy (GHT) among survivors with aGHD. OBJECTIVES: This work aimed to examine the association of GHT use with socioeconomic factors and to assess the effect of untreated aGHD in survivors using insulin-like growth factor-1 (IGF1) as a marker of GH action. METHODS: A total of 3902 five-year survivors of childhood cancer aged 18 years and older were included. The associations between GHT use and socioeconomic factors (health insurance coverage, income, area deprivation index), and associations between IGF1 levels and prevalences of adverse physical, neurocognitive, and psychosocial outcomes were assessed cross-sectionally by multivariable logistic regression adjusting for potential confounders. RESULTS: Among 354 survivors with severe aGHD, 9.0% were on GHT. Socioeconomic disadvantages were independently associated with less use of GHT (eg, odds ratio [OR] of GHT use 0.27; 95% CI, 0.08-0.84 for annual household income <$40 000 vs ≥$80 000). The low IGF1 group (z score ≤ -2) experienced significantly higher prevalences of various adverse outcomes compared to the normal IGF1 group (z score >0), including various neurocognitive impairment (eg, verbal reasoning [OR 2.79; 95% CI, 1.95-3.98]), diminished health-related quality of life (eg, physical functioning [1.97; 1.35-2.86]), abnormal glucose metabolism (1.82; 1.21-2.71), and abnormal fat percentage (3.16; 1.98-5.26). CONCLUSION: Untreated aGHD potentially contributes to multidimensional adverse outcomes, and GHT may provide health benefits among survivors, though socioeconomic disadvantage may limit their access to GHT.
3. SGLT2 inhibitors and nephrolithiasis risk in patients with type 2 diabetes: A cohort study and meta-analysis.
Across up to 500,000 matched pairs in real-world data, SGLT2 inhibitor initiation was associated with a lower nephrolithiasis risk than DPP4 inhibitors (HR 0.86) and GLP-1 receptor agonists (HR 0.90), with meta-analysis confirming the association.
Impact: Suggests a clinically meaningful, non-glycemic benefit of SGLT2 inhibitors that may influence antihyperglycemic agent selection, especially in patients with kidney stone risk.
Clinical Implications: Consider SGLT2 inhibitors preferentially in T2D patients with nephrolithiasis history or high stone risk, while acknowledging observational design; counsel on hydration and monitor renal status.
Key Findings
- SGLT2 inhibitors vs DPP4 inhibitors: lower nephrolithiasis risk (HR 0.86; 95% CI 0.83–0.90).
- SGLT2 inhibitors vs GLP-1 receptor agonists: lower nephrolithiasis risk (HR 0.90; 95% CI 0.86–0.94).
- Meta-analysis of five real-world studies corroborated reduced stone risk with SGLT2 inhibitor use.
- Follow-up up to 5 years across 64 U.S. healthcare organizations in TriNetX network.
Methodological Strengths
- Very large matched cohorts with two active comparator classes and up to 5-year follow-up.
- Confirmation via meta-analysis combining multiple real-world studies.
Limitations
- Observational data subject to residual confounding and confounding by indication despite matching.
- Outcome capture may be influenced by diagnostic coding and detection bias.
Future Directions: Mechanistic and prospective studies to elucidate how SGLT2 inhibitors reduce stone risk; evaluate effects in high-risk subgroups (e.g., recurrent stone formers, CKD).
AIMS: This study aimed to evaluate the relationship between sodium-glucose cotransporter 2 inhibitor (SGLT2i) use and nephrolithiasis risk. METHODS: In this real-world cohort study, we analyzed electronic health records from the TriNetX Analytics Network, which includes patients from 64 U.S. healthcare organizations. Adult patients with type 2 diabetes (T2D) who initiated SGLT2is, dipeptidyl peptidase-4 inhibitors (DPP4is), or glucagon-like peptide-1 receptor agonists (GLP-1RAs) between January 2015 and December 2023 were included. Comparisons were made between SGLT2is and DPP4is and between SGLT2is and GLP-1RAs. Patients were followed-up for up to 5 years. A meta-analysis was further conducted to synthesize available evidence. RESULTS: The cohort study included 500,000 patients (250,000 pairs) for SGLT2is vs. DPP4is comparisons and 482,284 patients (241,142 pairs) for SGLT2is vs. GLP-1Ras comparisons. The risk of nephrolithiasis was significantly lower in SGLT2i users compared with DPP4i (HR: 0.86; 95% CI: 0.83-0.90) and GLP-1RA users (HR: 0.90; 95% CI: 0.86-0.94). A meta-analysis combining our study with four additional real-world studies further supported these findings. CONCLUSIONS: This study suggests that SGLT2is may provide benefits beyond glycemic control by reducing nephrolithiasis risk, offering an advantage when selecting glucose-lowering therapies for patients with T2D.