Daily Endocrinology Research Analysis
Three papers stand out today in endocrinology and metabolism: a large RCT-based meta-analysis shows GLP-1 receptor agonists reduce serious and total infections; metabolic and bariatric surgery is associated with improved survival in adults ≥69 years; and a Ghanaian case-control study reveals substantial residual C-peptide in clinically diagnosed long-term type 1 diabetes, challenging classification in resource-limited settings.
Summary
Three papers stand out today in endocrinology and metabolism: a large RCT-based meta-analysis shows GLP-1 receptor agonists reduce serious and total infections; metabolic and bariatric surgery is associated with improved survival in adults ≥69 years; and a Ghanaian case-control study reveals substantial residual C-peptide in clinically diagnosed long-term type 1 diabetes, challenging classification in resource-limited settings.
Research Themes
- Pleiotropic effects of incretin therapies on infection risk
- Surgical obesity treatment and survival in older adults
- Diabetes phenotyping using C-peptide and immunogenetics in sub-Saharan Africa
Selected Articles
1. Association of glucagon-like peptide-1 receptor agonist use with risk of infections: A systematic review and meta-analysis.
Across 136 RCTs with 164,322 participants, GLP-1 receptor agonists reduced serious, non-serious, and total infections, including respiratory, skin/subcutaneous, musculoskeletal, vascular infections and COVID-19. Risk reductions correlated with greater weight loss, HbA1c reduction, and higher GLP-1 RA doses.
Impact: This is the most comprehensive RCT-based synthesis linking GLP-1 RAs to lower infection risk across organ systems and COVID-19, suggesting pleiotropic benefits beyond glycemic control.
Clinical Implications: In patients at high infection risk, choosing a GLP-1 RA may confer incremental protection while improving weight and glycemia. Guideline committees may consider infection outcomes in benefit–risk assessments, though causality and mechanisms warrant confirmation.
Key Findings
- Reduced serious infections: RR 0.89 (95% CI 0.86–0.93); absolute risk difference −30 per 10,000 persons/year; I² = 0%
- Lower serious respiratory (RR 0.84), skin/subcutaneous (RR 0.77), musculoskeletal (RR 0.79), vascular (RR 0.65), and COVID-19 infections (RR 0.82), all with I² = 0%
- Dose–response signals: greater weight loss (β = −0.011), HbA1c reduction (β = −0.229), and higher GLP-1 RA dose (RR 0.87) associated with lower infection risk
Methodological Strengths
- Large-scale meta-analysis of 136 RCTs with 164,322 participants and PRISMA-adherent methods
- Consistent effects with zero heterogeneity for serious infections and organ-specific serious infections
Limitations
- Infections were not primary endpoints in many trials, raising potential reporting bias
- Trial-level meta-regression cannot confirm individual-level mediation; high heterogeneity for non-serious/total infections
Future Directions: Pursue individual participant data meta-analyses and pragmatic trials with prespecified infection endpoints to confirm causality and elucidate immunometabolic mechanisms.
2. Metabolic and bariatric surgery in adults aged 69 years and older in England: a matched survival retrospective cohort study.
In a matched retrospective cohort from a UK tertiary center, metabolic and bariatric surgery in adults ≥69 years was independently associated with improved survival with acceptable perioperative risk. The study used Mahalanobis distance matching and Cox regression to mitigate confounding.
Impact: This study challenges age-based exclusion for MBS by demonstrating a survival advantage in older adults, informing surgical candidacy discussions as populations age.
Clinical Implications: Chronological age alone should not preclude MBS referral; comprehensive risk stratification can identify older candidates who may gain survival benefits. Shared decision-making should incorporate functional status and comorbidities rather than age cutoffs.
Key Findings
- Retrospective matched cohort (n=186; 44 underwent MBS) with median age 71 years (IQR 70–74) and median BMI 41 kg/m²
- MBS was independently associated with improved overall survival after 1:1 Mahalanobis matching and Cox regression
- Perioperative risk deemed acceptable in the specialist setting; results support reconsidering age-based exclusions
Methodological Strengths
- Mahalanobis distance matching on key clinical covariates to reduce confounding
- Cox proportional hazards modelling for survival with real-world electronic health records
Limitations
- Single-center retrospective design with a relatively small surgical cohort (n=44)
- Residual confounding and selection bias cannot be excluded; detailed follow-up duration and hazard ratios are not reported in the abstract
Future Directions: Prospective multicenter studies and pragmatic trials assessing survival, complications, and quality of life in older adults undergoing MBS with standardized geriatric assessments.
3. Heterogeneity in clinically diagnosed type 1 diabetes: characterising a unique cohort with maintained C-peptide secretion in Ghana.
In Ghana, only 28.9% of clinically diagnosed, insulin-treated long-term type 1 diabetes cases had low C-peptide, whereas 71.1% retained mid-to-high C-peptide with low autoantibodies and protective HLA, resembling controls. Onset ketosis occurred most frequently in the high C-peptide group, underscoring misclassification risks.
Impact: This well-powered case-control study integrates C-peptide, autoantibodies, HLA, and metabolomics to reveal profound heterogeneity in clinically diagnosed type 1 diabetes in sub-Saharan Africa, challenging current diagnostic pathways.
Clinical Implications: Routine C-peptide testing and selective autoimmunity/HLA assessment can improve diabetes classification in resource-limited settings, avoiding misclassification of ketosis-prone or lean type 2 diabetes as type 1 diabetes.
Key Findings
- Among 266 clinically diagnosed long-term type 1 diabetes cases, only 28.9% had low C-peptide (<0.2 nmol/L); 34.6% mid (0.2–0.6) and 36.5% high (>0.6)
- Low C-peptide group: youngest, leanest, enriched for HLA class II risk haplotypes and GAD/ZnT8 autoantibodies
- Mid/high C-peptide groups: low autoantibody titres and a protective HLA class II haplotype; ketosis at onset most prevalent in high C-peptide group
- Aromatic and branched-chain amino acids correlated positively with C-peptide across diabetes subgroups
Methodological Strengths
- Comprehensive phenotyping: C-peptide stratification combined with HLA class II, islet autoantibodies, inflammatory and metabolomic profiling
- Well-sized case-control design (266 cases and 266 controls) in an understudied population
Limitations
- Single random C-peptide measurement may misclassify residual insulin secretion
- Case-control design limits causal inference; external validity beyond Ghana requires caution
Future Directions: Prospective longitudinal studies with standardized mixed-meal tolerance tests and genotyping across African settings to refine diagnostic algorithms.