Daily Endocrinology Research Analysis
Early first-trimester OGTT values in a multicentre prospective cohort predicted later gestational diabetes and insulin requirement, linking early dysglycaemia to impaired insulin sensitivity and beta cell function. A double-blind randomized trial found that several common dietary emulsifiers reduced short-chain fatty acids and, for carrageenan, increased intestinal permeability without raising inflammatory markers. Longitudinal data in healthy men showed Trabecular Bone Score declines beginning
Summary
Early first-trimester OGTT values in a multicentre prospective cohort predicted later gestational diabetes and insulin requirement, linking early dysglycaemia to impaired insulin sensitivity and beta cell function. A double-blind randomized trial found that several common dietary emulsifiers reduced short-chain fatty acids and, for carrageenan, increased intestinal permeability without raising inflammatory markers. Longitudinal data in healthy men showed Trabecular Bone Score declines beginning in young adulthood, with greater losses in those with higher adiposity.
Research Themes
- Early prediction of gestational diabetes from first-trimester OGTT
- Dietary emulsifiers impacting gut metabolic milieu and permeability
- Early decline of trabecular bone microarchitecture in men and adiposity determinants
Selected Articles
1. The utility of early gestational OGTT and biomarkers for the development of gestational diabetes mellitus: an international prospective multicentre cohort study.
In a prospective multicentre cohort of 657 pregnancies, first-trimester OGTT glucose values predicted later GDM with AUCs 0.68–0.74 and were linked to impaired insulin sensitivity, beta cell dysfunction, and later insulin requirement. Select biomarkers added modest predictive value.
Impact: Provides pragmatic evidence to stratify GDM risk early in pregnancy using widely available OGTT metrics, potentially informing earlier monitoring and intervention. Links early dysglycaemia to pathophysiology and treatment intensity.
Clinical Implications: Clinicians can consider first-trimester OGTT-derived thresholds to identify high-risk mothers for enhanced surveillance and early lifestyle or pharmacologic strategies, and anticipate insulin needs later in pregnancy.
Key Findings
- First-trimester OGTT glucose predicted later GDM (AUCs: fasting 0.68; 60 min 0.74; 120 min 0.72).
- 12.6% (83/657) developed GDM by standard testing later in pregnancy.
- Early OGTT glucose correlated with impaired insulin sensitivity, beta cell dysfunction, and need for insulin in late pregnancy.
- Biomarkers added significant but modest predictive accuracy beyond OGTT.
Methodological Strengths
- Prospective multicentre design with blinded 75 g OGTT in the first trimester.
- Trial registration and subgroup physiologic assessments linking prediction to mechanism.
Limitations
- Predictive performance was fair-to-good; biomarker added value was modest.
- Cohort limited to Central European centres; not an interventional trial and early GDM diagnosis remains debated.
Future Directions: Validate OGTT-based early risk algorithms across diverse populations, define actionable thresholds, and test whether early targeted interventions reduce GDM progression and insulin requirements.
AIMS/HYPOTHESIS: There is no clear consensus regarding accurate risk stratification in early pregnancy for later developing gestational diabetes mellitus (GDM). Therefore, this study aims to evaluate the predictive performance of an OGTT and several biomarkers in the first trimester of pregnancy. Their association with insulin action, beta cell function and requirement for insulin were additionally assessed. METHODS: In this prospective cohort study, we included 657 pregnant women in six Central European centres. Patient history and anthropometric data were obtained, a blinded 75 g OGTT was performed and biochemical markers were assessed at a median gestational age of 13.4 weeks (IQR 12.7-14.1). Another OGTT was performed in later pregnancy to identify women with GDM. A detailed investigation of glucose homeostasis was performed at both visits in a subgroup of women. RESULTS: Eighty-three women (12.6%) developed GDM. Progression to GDM was fairly well predicted by glucose concentrations during the early OGTT in terms of areas under the receiver operating characteristic curves (OGTT glucose at fasting: 0.68; OGTT glucose at 60 min: 0.74; OGTT glucose at 120 min: 0.72). Some biomarkers showed significant but modest predictive accuracy. Early gestational OGTT glucose concentrations were further associated with impaired insulin sensitivity and beta cell dysfunction, as well as the requirement for insulin in later pregnancy. CONCLUSIONS/INTERPRETATION: Although the accurate diagnosis of GDM before 24 weeks remains an ongoing discussion, dynamically assessed glucose concentrations during an early OGTT were closely associated with impaired glucose homeostasis and showed good predictive accuracy for later development of GDM as well as the requirement for insulin. These findings may be used to develop a protocol to distinguish between low- and high-risk mothers. Trial registration ClinicalTrials.gov NCT02035059.
2. Effect of Five Dietary Emulsifiers on Inflammation, Permeability, and the Gut Microbiome: A Placebo-controlled Randomized Trial.
In a double-blind randomized trial following an emulsifier-free run-in, several dietary emulsifiers reduced fecal short-chain fatty acids versus placebo; carrageenan increased transcellular intestinal permeability. Despite microbiome compositional shifts, inflammatory and systemic metabolic markers did not change.
Impact: Provides controlled human evidence that common emulsifiers can alter gut metabolic readouts and barrier function without overt inflammation, informing dietary guidance and mechanistic links between food additives and metabolic health.
Clinical Implications: While not directly changing systemic markers, limiting specific emulsifiers—particularly carrageenan—may benefit gut barrier integrity and metabolic milieu; clinicians can consider advising emulsifier reduction in patients with metabolic or gastrointestinal vulnerability.
Key Findings
- After a 2-week emulsifier-free diet, cholesterol levels decreased (P = 0.00006).
- Emulsifier supplementation reduced fecal short-chain fatty acids versus placebo; strongest effect observed with carboxymethyl cellulose.
- Carrageenan increased transcellular intestinal permeability (P = 0.04) without increasing fecal calprotectin or systemic inflammation.
- No changes in CRP, LBP, serum inflammatory proteins, or other metabolic endpoints at study end.
Methodological Strengths
- Double-blind, randomized, placebo-controlled design with standardized emulsifier-free run-in.
- Comprehensive endpoints including microbiome, permeability, inflammatory and cardiometabolic markers.
Limitations
- Short intervention duration and small sample size of healthy participants limit generalizability to patients with metabolic disease.
- Exploratory trial not powered for clinical endpoints; dietary control outside study brownies may vary.
Future Directions: Longer, adequately powered RCTs in at-risk populations to test clinical metabolic outcomes; mechanistic studies linking SCFA reductions and permeability changes to insulin resistance and inflammation.
BACKGROUND & AIMS: Dietary emulsifier consumption might promote intestinal inflammation, eventually leading to inflammatory bowel diseases. However, human data are scarce and involve a limited number of emulsifiers. We studied the effects of an emulsifier-free diet (EFD) and specific emulsifier supplementation. METHODS: Sixty healthy participants followed an EFD for 2 weeks. Then, using a randomized placebo-controlled trial design, participants continued an EFD for 4 weeks with the addition of either carboxymethyl cellulose, polysorbate-80, carrageenan, soy lecithin, native rice starch, or no additives administered through brownies. Effects on cardiometabolic markers, gut microbiota, intestinal inflammation, and permeability were explored. RESULTS: After 2 weeks of an EFD, cholesterol levels decreased (P = .00006). Under emulsifier supplementation, alpha diversity remained stable, yet microbial composition was affected by treatment and visit. Compared with placebo, concentrations of all short chain fatty acids were lower in those consuming carboxymethyl cellulose, which was mirrored by other emulsifiers, although not all reached significance. No differences in fecal calprotectin, C-reactive protein, serum lipopolysaccharide-binding protein, cholesterol levels, or other metabolic markers were observed between placebo and emulsifiers at the end of the intervention. Serum inflammatory and cardiometabolic proteins remained unchanged. In individuals consuming carrageenan, transcellular intestinal permeability increased (P = .04) compared with baseline. CONCLUSION: In this double-blind placebo-controlled exploratory trial, emulsifier supplementation lowered short chain fatty acid concentration compared with placebo. Emulsifier supplementation did not impact intestinal or systemic inflammation or metabolic endpoints. Cholesterol levels decreased after 2 weeks of an EFD. These results point towards potential intestinal benefits of limiting dietary emulsifiers in the diet, requiring further investigation. CLINICALTRIALS: gov, Number: NCT06552156.
3. Changes in Trabecular Bone Score and their determinants in young and middle-aged men: a longitudinal observational study.
In a population-based cohort of 465 healthy men followed for 12.5 years, TBS declined by 1.43%, with greater reductions in those with higher baseline BMI and trunk fat. Baseline TBS correlated with free testosterone and estradiol, but neither baseline nor changes in sex steroids or BTMs predicted longitudinal TBS changes.
Impact: Identifies early, measurable decline in trabecular bone microarchitecture in men and implicates adiposity as a modifiable determinant, informing timing and targets for bone health interventions before overt osteoporosis.
Clinical Implications: Routine consideration of TBS in at-risk younger men and addressing adiposity may help preserve bone microarchitecture; findings support early preventive strategies alongside standard BMD monitoring.
Key Findings
- TBS declined by 1.43% over 12.5 years (p<0.001) in healthy men aged 25–45 at baseline.
- Higher baseline BMI and trunk fat predicted greater TBS declines (p=0.01 and p=0.02).
- Baseline TBS positively correlated with free testosterone (p=0.01) and estradiol (p<0.001), but sex steroids and BTMs did not predict longitudinal TBS change.
Methodological Strengths
- Population-based longitudinal design with 12.5-year follow-up.
- High-quality hormone measurements by LC-MS/MS and TBS computed with tissue-thickness correction.
Limitations
- Observational design limits causal inference regarding determinants of TBS decline.
- Findings in healthy European men may not generalize to women, older adults, or other ethnicities.
Future Directions: Interventional studies to test whether reducing adiposity attenuates TBS decline, mechanistic work on early trabecular deterioration, and validation across diverse populations.
OBJECTIVE: To study bone turnover markers (BTM) and sex steroids in relation to Trabecular Bone Score (TBS) in men. MATERIAL AND METHODS: Longitudinal, population-based study in 465 healthy men, aged 25-45 years at baseline. Lumbar spine TBS was calculated with TBS iNsight® version 4 (v19.4.1, core module, Medimaps, Pessac, France), which adjusts for soft tissue thickness correction via DXA measurements. Sex hormone binding globulin (SHBG), C-terminal telopeptide and pro collagen type 1 N-terminal propeptide were measured using immunoassays. Total testosterone (T) and estradiol (E2) were determined by liquid chromatography-tandem mass spectrometry, free T and free E2 calculated. Statistical analyses were conducted via linear mixed-effects modelling. RESULTS: At baseline, TBS was positively associated with free testosterone (p=0.01), free estradiol and total estradiol (both p<0.001), but not with total testosterone nor with BTM. Over a follow-up of 12.5 years, TBS declined by 1.43% (p<0.001). Higher baseline BMI and trunk fat were predictive of greater decreases in TBS (p=0.01 and p=0.02). Baseline levels of sex steroids and BTM nor changes therein were associated with changes in TBS. CONCLUSIONS: TBS already decreases in young and middle-aged healthy men, corroborating earlier studies showing early decrease of trabecular bone volume and changes in trabecular microarchitecture. Although we identified some potentially contributing determinants, the underlying mechanisms of changes in TBS and trabecular bone in young men are yet to be fully elucidated.