The gut microbiome modulates the impact of Anaerobutyricum soehngenii supplementation on glucose homeostasis in mice.

Background There is growing interest in the development of next-generation probiotics to prevent or treat metabolic syndrome. Previous studies suggested that Anaerobutyricum soehngenii may represent a promising probiotic candidate. A recent human study showed that while A . soehngenii supplementation is well tolerated and safe, it resulted in variable responses among individuals with a subset of the subjects significantly benefiting from the treatment. We hypothesized that gut microbiome variation is linked to the heterogeneous responses to A . soehngenii treatment observed in humans. Results We colonized germ-free mice with fecal microbiota from human subjects that responded to A . soehngenii treatment (R65 and R55) and non-responder subjects (N96 and N40). Colonized mice were fed a high-fat diet (45% kcal from fat) to induce insulin resistance, and orally treated with either live A . soehngenii culture or heat-killed culture. We found that R65-colonized mice received a benefit in glycemic control with live A . soehngenii treatment while mice colonized with microbiota from the other donors did not. The glucose homeostasis improvements observed in R65-colonized mice were positively correlated with levels of cecal propionate, an association that was reversed in N40-colonized mice. To test whether the microbiome modulates the effects of propionate, R65- or N40-colonized mice were treated with tripropionin (TP, glycerol tripropionate), a pro-drug of propionate, or glycerol (control). TP supplementation showed a similar response pattern as that observed in live A . soehngenii treatment, suggesting that propionate may mediate the effects of A . soehngenii . We also found that TP supplementation to conventional mice reduces adiposity, improves glycemic control, and reduces plasma insulin compared to control animals supplemented with glycerol. Conclusions These findings highlight the importance of the microbiome on glycemic control and underscore the need to better understand personal microbiome-by-therapeutic interactions to develop more effective treatment strategies.

Re-Cellularization via Electroporation Therapy of the duodenum combined with GPL-1 receptor agonist to replace insulin therapy in patients with type 2 diabetes; 12 months results of a first-in-human study.

BACKGROUND AND AIMS: Studies have shown that hydrothermal duodenal mucosal ablation results in improved glycemic control. Re-Cellularization via Electroporation Therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization. In this study, we aimed to eliminate exogenous insulin treatment in T2D patients through a single ReCET procedure combined with a GLP-1 receptor agonist (GLP-1RA). Feasibility, safety, and (dose) efficacy of ReCET were assessed. METHODS: First-in-human study including patients with T2D on basal insulin (28-75years; BMI 24-40kg/m2, HbA1c ≤64mmol/mol; C-peptide ≥0.2nmol/L). The electroporation dose was optimized during the study, starting with single 600V and ending with double 750V treatments. All patients underwent ReCET, after which insulin was discontinued and semaglutide (GLP-1RA) was initiated. Primary endpoints were: feasibility (procedure time [catheter in-out], technical success rate), safety, and efficacy (patients off insulin at 6 months; HbA1c ≤58mmol/mol). RESULTS: Fourteen patients underwent endoscopic ReCET. Median procedure time was 58 (IQR 49-73) minutes. ReCET demonstrated a technical success rate of 100%. No device related SAEs or severe hypoglycemic events were observed. At 12 months follow up, 12 (86%) patients remained off exogenous insulin therapy with significant improvements in glycemic control, metabolic parameters. The 2 patients in whom insulin therapy was reintroduced both received ReCET at the lowest voltage (single 600V). CONCLUSION: These results suggest that ReCET is feasible and safe. In combination with semaglutide, ReCET may be a promising therapeutic option to replace insulin therapy in selected T2D patients, while improving glycemic control and metabolic health.

Prevalence and predictive features of metabolic dysfunction-associated steatotic liver disease in type 1 diabetes.

AIMS/HYPOTHESIS: The prevalence and severity of MASLD in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes, and assessed which clinical features are most important in predicting MASLD severity. METHODS: 453 individuals with type 1 diabetes (41.6±15.0 years, 64% female, BMI 25.4±4.2kg/m2, HbA1c 55.6±12mmol/mol) underwent vibration-controlled transient elastography (VCTE), with a controlled attenuation parameter (CAP) score for steatosis (≥ 280.0dB/m) and a liver stiffness measurement (LMS) for fibrosis (≥ 8.0kPa). A machine-learning Extra-Trees classification model was performed to assess the predictive power of the clinical features associated with type 1 diabetes with respect to steatosis and fibrosis. RESULTS: The prevalence of hepatic steatosis and fibrosis was 9.5% [95% CI 6.8-12.2] and 3.5% [95% CI 1.8-5.2]. Higher LMS was associated with a longer duration of type 1 diabetes (median 30.5 [IQR 18.0-39.3] years vs. 15.0 [IQR 6.0-27.0] years) and individuals were older and had a higher BMI (mean 27.8 ±5.2 vs. 25.3 ±4.1kg/m2), and a higher CAP score (mean 211.4±51.7 dB/m vs. 241.4±75.6 dB/m). The most important predictive features of fibrosis were duration of type 1 diabetes, age, and systolic blood pressure, with a mean± standard deviation (SD) area under the curve of 0.73±0.03. CONCLUSION: Individuals with type 1 diabetes and high blood pressure, older age, BMI and duration of disease could be considered at high-risk for developing MASLD.

Age-Dependent Differences in Postprandial Bile-Acid Metabolism and the Role of the Gut Microbiome.

Ageing changes the impact of nutrition, whereby inflammation has been suggested to play a role in age-related disabilities such as diabetes and cardiovascular disease. The aim of this study was to investigate differences in postprandial bile-acid response and its effect on energy metabolism between young and elderly people. Nine young, healthy men and nine elderly, healthy men underwent a liquid mixed-meal test. Postprandial bile-acid levels, insulin, glucose, GLP-1, C4, FGF19 and lipids were measured. Appetite, body composition, energy expenditure and gut microbiome were also measured. The elderly population showed lower glycine conjugated CDCA and UDCA levels and higher abundances of Ruminiclostridium, Marvinbryantia and Catenibacterium, but lower food intake, decreased fat free mass and increased cholesterol levels. Aging is associated with changes in postprandial bile-acid composition and microbiome, diminished hunger and changes in body composition and lipid levels. Further studies are needed to determine if these changes may contribute to malnutrition and sarcopenia in elderly.

Ethnic variations in metabolic syndrome components and their associations with the gut microbiota: the HELIUS study.

BACKGROUND: The occurrence of metabolic syndrome (MetS) and the gut microbiota composition are known to differ across ethnicities yet how these three factors are interwoven is unknown. Also, it is unknown what the relative contribution of the gut microbiota composition is to each MetS component and whether this differs between ethnicities. We therefore determined the occurrence of MetS and its components in the multi-ethnic HELIUS cohort and tested the overall and ethnic-specific associations with the gut microbiota composition. METHODS: We included 16,209 treatment naïve participants of the HELIUS study, which were of Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish, and Moroccan descent to analyze MetS and its components across ethnicities. In a subset (n = 3443), the gut microbiota composition (16S) was associated with MetS outcomes using linear and logistic regression models. RESULTS: A differential, often sex-dependent, prevalence of MetS components and their combinations were observed across ethnicities. Increased blood pressure was commonly seen especially in Ghanaians, while South-Asian Surinamese and Turkish had higher MetS rates in general and were characterized by worse lipid-related measures. Regarding the gut microbiota, when ethnic-independent associations were assumed, a higher α-diversity, higher abundance of several ASVs (mostly for waist and triglyceride-related outcomes) and a trophic network of ASVs of Ruminococcaceae, Christensenellaceae, and Methanobrevibacter (RCM) bacteria were associated with better MetS outcomes. Statistically significant ethnic-specific associations were however noticed for α-diversity and the RCM trophic network. Associations were significant in the Dutch but not always in all other ethnicities. In Ghanaians, a higher α-diversity and RCM network abundance showed an aberrant positive association with high blood pressure measures compared to the other ethnicities. Even though adjustment for socioeconomic status-, lifestyle-, and diet-related variables often attenuated the effect size and/or the statistical significance of the ethnic-specific associations, an overall similar pattern across outcomes and ethnicities remained. CONCLUSIONS: The occurrence of MetS characteristics among ethnicities is heterogeneous. Both ethnic-independent and ethnic-specific associations were identified between the gut microbiota and MetS outcomes. Across multiple ethnicities, a one-size-fits-all approach may thus be reconsidered in regard to both the definition and/or treatment of MetS and its relation to the gut microbiota.

Anaerobutyricum soehngenii Reduces Hepatic Lipogenic Pathways and Increases Intestinal Gluconeogenic Gene Expression in Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD) Mice.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a growing health problem for which no therapy exists to date. The modulation of the gut microbiome may have treatment potential for MASLD. Here, we investigated Anaerobutyricum soehngenii, a butyrate-producing anaerobic bacterium with beneficial effects in metabolic syndrome, in a diet-induced MASLD mouse model. Male C57BL/6J mice received a Western-type high-fat diet and water with 15% fructose (WDF) to induce MASLD and were gavaged with A. soehngenii (108 or 109 colony-forming units (CFU) 3 times per week) or a placebo for 6 weeks. The A. soehngenii gavage increased the cecal butyrate concentrations. Although there was no effect on histological MASLD scores, A. soehngenii improved the glycemic response to insulin. In the liver, the WDF-associated altered expression of three genes relevant to the MASLD pathophysiology was reversed upon treatment with A. soehngenii: Lipin-1 (Lpin1), insulin-like growth factor binding protein 1 (Igfbp1) and Interleukin 1 Receptor Type 1 (Il1r1). A. soehngenii administration also increased the intestinal expression of gluconeogenesis and fructolysis genes. Although these effects did not translate into significant histological improvements in MASLD, these results provide a basis for combined gut microbial approaches to induce histological improvements in MASLD.

Quantifying the effect of nutritional interventions on metabolic resilience using personalized computational models.

The manifestation of metabolic deteriorations that accompany overweight and obesity can differ greatly between individuals, giving rise to a highly heterogeneous population. This inter-individual variation can impede both the provision and assessment of nutritional interventions as multiple aspects of metabolic health should be considered at once. Here, we apply the Mixed Meal Model, a physiology-based computational model, to characterize an individual's metabolic health in silico. A population of 342 personalized models were generated using data for individuals with overweight and obesity from three independent intervention studies, demonstrating a strong relationship between the model-derived metric of insulin resistance (ρ = 0.67, p < 0.05) and the gold-standard hyperinsulinemic-euglycemic clamp. The model is also shown to quantify liver fat accumulation and ß-cell functionality. Moreover, we show that personalized Mixed Meal Models can be used to evaluate the impact of a dietary intervention on multiple aspects of metabolic health at the individual level.

Differences in Psychological Health and Weight Loss after Bariatric Metabolic Surgery between Patients with and without Pain Syndromes.

PURPOSE: Chronic pain and obesity often co-occur, negatively affecting one another and psychological wellbeing. Pain and psychological wellbeing improve after bariatric metabolic surgery (BMS), however, it is unknown whether psychological wellbeing improves differently after weight loss between patients with and without chronic pain. We investigated whether weight loss is associated with greater psychological wellbeing and functioning change after BMS, comparing patients with and without preoperative pain syndromes. METHODS: Depression, health-related quality of life, self-esteem, self-efficacy to exercise and controlling eating behaviours, physical activity, and food cravings were measured before and 24 months after BMS among 276 patients with obesity. The presence of preoperative chronic pain syndromes was examined as a moderator for the relationship between 24-month weight loss and changes in psychological outcomes. RESULTS: Chronic pain syndromes were present among 46% of patients. Weight loss was associated with greater improvement in health-related quality of life, self-efficacy to exercise and controlling eating behaviours, self-esteem and greater amelioration in food cravings. Pain syndromes only moderated negatively the relationship between the postoperative weight loss and change in self-efficacy to control eating behaviours (b = -0.49, CI [-0.88,-0.12]). CONCLUSION: Patients with and without chronic pain showed similar improvements in weight and psychological wellbeing and behaviours after BMS. The relationship between weight loss and the improvement of self-efficacy to control eating behaviours was weaker among patients with chronic pain syndrome. Further work, measuring pain severity over time, is needed to shed light on the mechanism underlying pain and postoperative change in psychological wellbeing and weight loss.

Role of the Intestine and Its Gut Microbiota in Metabolic Syndrome and Obesity.

The metabolic syndrome (MetSyn) is currently one of the biggest global health challenges because of its impact on public health. MetSyn includes the cluster of metabolic disorders including obesity, high blood pressure, hyperglycemia, high triglyceride levels, and hepatic steatosis. Together, these abnormalities increase the cardiovascular risk of individuals and pose a threat to healthcare systems worldwide. To better understand and address this complex issue, recent research has been increasingly focusing on unraveling the delicate interplay between metabolic disorders and the intestines and more specifically our gut microbiome. The gut microbiome entails all microorganisms inhabiting the gastrointestinal tract and plays a pivotal role in metabolic processes and overall health of its host. Emerging evidence proves an association between the gut microbiome composition and aspects of MetSyn, such as obesity. Understanding these relationships is crucial because they offer valuable insights into the mechanisms underlying development and progression of metabolic disorders and possible treatment options. Yet, how should we interpret this relationship? This review focuses on the interplay between the gut and MetSyn. In addition, we have reviewed the existing evidence of the gut microbiome and its association with and impact on metabolic disorders, in an attempt to understand the complex interactions and nature of this association. We also explored potential therapeutic options targeting the gut to modify metabolic disorders and obesity.

Differences in gut microbiota between Dutch and South-Asian Surinamese: potential implications for type 2 diabetes mellitus.

Gut microbiota, or the collection of diverse microorganisms in a specific ecological niche, are known to significantly impact human health. Decreased gut microbiota production of short-chain fatty acids (SCFAs) has been implicated in type 2 diabetes mellitus (T2DM) disease progression. Most microbiome studies focus on ethnic majorities. This study aims to understand how the microbiome differs between an ethnic majority (the Dutch) and minority (the South-Asian Surinamese (SAS)) group with a lower and higher prevalence of T2DM, respectively. Microbiome data from the Healthy Life in an Urban Setting (HELIUS) cohort were used. Two age- and gender-matched groups were compared: the Dutch (n = 41) and SAS (n = 43). Microbial community compositions were generated via DADA2. Metrics of microbial diversity and similarity between groups were computed. Biomarker analyses were performed to determine discriminating taxa. Bacterial co-occurrence networks were constructed to examine ecological patterns. A tight microbiota cluster was observed in the Dutch women, which overlapped with some of the SAS microbiota. The Dutch gut contained a more interconnected microbial ecology, whereas the SAS network was dispersed, i.e., contained fewer inter-taxonomic correlational relationships. Bacteroides caccae, Butyricicoccus, Alistipes putredinis, Coprococcus comes, Odoribacter splanchnicus, and Lachnospira were enriched in the Dutch gut. Haemophilus, Bifidobacterium, and Anaerostipes hadrus discriminated the SAS gut. All but Lachnospira and certain strains of Haemophilus are known to produce SCFAs. The Dutch gut microbiome was distinguished from the SAS by diverse, differentially abundant SCFA-producing taxa with significant cooperation. The dynamic ecology observed in the Dutch was not detected in the SAS. Among several potential gut microbial biomarkers, Haemophilus parainfluenzae likely best characterizes the ethnic minority group, which is more predisposed to T2DM. The higher prevalence of T2DM in the SAS may be associated with the gut dysbiosis observed.

Intrapancreatic fat deposition is unrelated to liver steatosis in metabolic dysfunction-associated steatotic liver disease.

Background & Aims: Individuals with obesity may develop intrapancreatic fat deposition (IPFD) and fatty pancreas disease (FPD). Whether this causes inflammation and fibrosis and leads to pancreatic dysfunction is less established than for liver damage in metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, the interrelations of FPD and MASLD are poorly understood. Therefore, we aimed to assess IPFD and fibro-inflammation in relation to pancreatic function and liver disease severity in individuals with MASLD. Methods: Seventy-six participants from the Amsterdam MASLD-MASH cohort (ANCHOR) study underwent liver biopsy and multiparametric MRI of the liver and pancreas, consisting of proton-density fat fraction sequences, T1 mapping and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). Results: The prevalence of FPD was 37.3%. There was a clear correlation between pancreatic T1 relaxation time, which indicates fibro-inflammation, and parameters of glycemic dysregulation, namely HbA1c (R = 0.59; p <0.001), fasting glucose (R = 0.51; p <0.001) and the presence of type 2 diabetes (mean 802.0 ms vs. 733.6 ms; p <0.05). In contrast, there was no relation between IPFD and hepatic fat content (R = 0.03; p = 0.80). Pancreatic IVIM diffusion (IVIM-D) was lower in advanced liver fibrosis (p <0.05) and pancreatic perfusion (IVIM-f), reflecting vessel density, inversely correlated to histological MASLD activity (p <0.05). Conclusions: Consistent relations exist between pancreatic fibro-inflammation on MRI and endocrine function in individuals with MASLD. However, despite shared dysmetabolic drivers, our study suggests IPFD is a separate pathophysiological process from MASLD. Impact and implications: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and 68% of people with type 2 diabetes have MASLD. However, fat infiltration and inflammation in the pancreas are understudied in individuals with MASLD. In this cross-sectional MRI study, we found no relationship between fat accumulation in the pancreas and liver in a cohort of patients with MASLD. However, our results show that inflammatory and fibrotic processes in the pancreas may be interrelated to features of type 2 diabetes and to the severity of liver disease in patients with MASLD. Overall, the results suggest that pancreatic endocrine dysfunction in individuals with MASLD may be more related to glucotoxicity than to lipotoxicity. Clinical trial number: NTR7191 (Dutch Trial Register).

Networks of gut bacteria relate to cardiovascular disease in a multi-ethnic population: the HELIUS study.

AIMS: Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVDs). The composition and abundance of gut microbiota trophic networks differ between ethnicities. We aim to evaluate the relationship between gut microbiotal trophic networks and CVD phenotypes. METHODS AND RESULTS: We included cross-sectional data from 3860 individuals without CVD history from 6 ethnicities living in the Amsterdam region participating in the prospective Healthy Life in Urban Setting (HELIUS) study. Genetic variants were genotyped, faecal gut microbiota were profiled, and blood and anthropometric parameters were measured. A machine learning approach was used to assess the relationship between CVD risk (Framingham score) and gut microbiota stratified by ethnicity. Potential causal relationships between gut microbiota composition and CVD were inferred by performing two-sample Mendelian randomization with hard CVD events from the Pan-UK Biobank and microbiome genome-wide association studies summary data from a subset of the HELIUS cohort (n = 4117). Microbial taxa identified to be associated with CVD by machine learning and Mendelian randomization were often ethnic-specific, but some concordance across ethnicities was found. The microbes Akkermansia muciniphila and Ruminococcaceae UCG-002 were protective against ischaemic heart disease in African-Surinamese and Moroccans, respectively. We identified a strong inverse association between blood lipids, CVD risk, and the combined abundance of the correlated microbes Christensenellaceae-Methanobrevibacter-Ruminococcaceae (CMR). The CMR cluster was also identified in two independent cohorts and the association with triglycerides was replicated. CONCLUSION: Certain gut microbes can have a potentially causal relationship with CVD events, with possible ethnic-specific effects. We identified a trophic network centred around Christensenellaceae, Methanobrevibacter, and various Ruminococcaceae, frequently lacking in South-Asian Surinamese, to be protective against CVD risk and associated with low triglyceride levels.

Socio-economic disparities in hospital care among Dutch patients with diabetes mellitus.

AIM: Socio-economic status (SES) influences diabetes onset, progression and treatment. In this study, the associations between SES and use of hospital care were assessed, focusing on hospitalizations, technology and cardiovascular complications. MATERIALS AND METHODS: This was an observational cohort study comprising 196 695 patients with diabetes (all types and ages) treated in 65 hospitals across the Netherlands from 2019 to 2020 using reimbursement data. Patients were stratified in low, middle, or high SES based on residential areas derived from four-digit zip codes. RESULTS: Children and adults with low SES were hospitalized more often than patients with middle or high SES (children: 22%, 19% and 15%, respectively; p < .001, adults: 28%, 25% and 23%; p < .001). Patients with low SES used the least technology: no technology in 48% of children with low SES versus 40% with middle SES and 38% with high SES. In children, continuous subcutaneous insulin infusion (CSII) and real-time continuous glucose monitoring (rtCGM) use was higher in high SES {CSII: odds ratio (OR) 1.54 [95% confidence interval (CI) 1.35-1.76]; p < .001; rtCGM OR 1.39 [95% CI 1.20-1.61]; p < .001} and middle SES [CSII: OR 1.41 (95% CI 1.24-1.62); p < .001; rtCGM: OR 1.27 (95% CI 1.09-1.47); p = .002] compared with low SES. Macrovascular (OR 0.78 (95% CI 0.75-0.80); p < .001) and microvascular complications [OR 0.95 (95% CI 0.93-0.98); p < .001] occurred less in high than in low SES. CONCLUSIONS: Socio-economic disparities were observed in patients with diabetes treated in Dutch hospitals, where basic health care is covered. Patients with low SES were hospitalized more often, used less technology, and adults with high SES showed fewer cardiovascular complications. These inequities warrant attention to guarantee equal outcomes for all.

Insulin sensitivity and beta cell function after Duodenal Mucosal Resurfacing (DMR): An Open-Label, Mechanistic, Pilot Study.

BACKGROUND AND AIMS: The duodenum has been shown to play a key role in glucose homeostasis. Duodenal mucosal resurfacing (DMR) is an endoscopic procedure for patients with type 2 diabetes (T2D) in which the duodenal mucosa is hydrothermally ablated. DMR improves glycemic control, but the underlying mechanisms remain unclear. Here, we report changes in glucoregulatory hormones and indices of insulin sensitivity and beta cell function after DMR. METHODS: We included 28 patients on non-insulin glucose lowering medications who underwent open-label DMR and a mixed meal test (MMT) in Revita-1 or Revita-2. Inclusion criteria were hemoglobin A1c (HbA1c) 7.6-10.4% and BMI 24-40kg/m2. Baseline and 3-months MMT data included plasma glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) concentrations. Glucoregulatory hormones, insulin sensitivity indices (homeostatic model assessment for insulin resistance [HOMA-IR], Matsuda index [MI] and hepatic insulin resistance [HIR]), and beta cell function (insulinogenic index [IGI], disposition index [DI] and insulin secretion rate [ISR]) were assessed. RESULTS: Fasting insulin, glucagon, and C-peptide decreased significantly. Insulin sensitivity (HOMA-IR, MI, and HIR) and beta cell function (DI and ISR) all improved significantly. Decline in postprandial glucose, mainly driven by a decrease in fasting levels, was observed, as well as a decline in postprandial glucagon whereas GLP-1 and GIP did not change. CONCLUSIONS: Insulin sensitivity and insulin secretion improved 3 months after DMR. It is unlikely that incretin changes are responsible for improved glucose control after DMR. These data add to the growing evidence validating the duodenum as a therapeutic target for patients with T2D.

Does size matter? Hospital volume and resource use in paediatric diabetes care.

AIMS: Paediatric diabetes care has become increasingly specialised due to the multidisciplinary approach and technological developments. Guidelines recommend sufficient experience of treatment teams. This study evaluates associations between hospital volume and resource use and hospital expenditure in Dutch children with diabetes. METHODS: Retrospective cohort study using hospital claims data of 5082 children treated across 44 Dutch hospitals (2019-2020). Hospitals were categorised into three categories; small (≥20-100 patients), medium (≥100-200 patients) and large (≥200 patients). All-cause hospitalisations, consultations, technology and hospital expenditure were analysed and adjusted for age, sex, socio-economic status (SES) and hospital of treatment. RESULTS: Fewer hospitalisations were observed in large hospitals compared to small hospitals (OR 0.48; [95% CI 0.32-0.72]; p < 0.001). Median number of yearly paediatrician visits was 7 in large and 6 in small hospitals, the significance of which was attenuated in multilevel analysis (OR ≥7 consultations: 1.89; [95%CI 0.74-4.83]; p = 0.18). Technology use varies between individual hospitals, whereas pump usage and real-time continuous glucose monitoring showed no significant differences between hospital volumes. Mean overall expenditure was highest in medium-sized centres with €6434 per patient (IQR €2555-7955); the difference in diabetes care costs was not significant between hospital patient volumes. CONCLUSIONS: Care provision patterns vary by hospital patient volume. Large hospitals had the lowest hospitalisation rates. The use of diabetes technology was not different between hospital patient volumes. Medium-sized hospitals showed the highest overall expenditure, but diabetes care costs were similar across hospital volumes.

Comparative Analysis of Taxonomic and Functional Gut Microbiota Profiles in Relation to Seroconversion of Thyroid Peroxidase Antibodies in Euthyroid Participants.

Background: Previous studies have reported gut microbiome alterations in Hashimoto's autoimmune thyroiditis (HT) patients. Yet, it is unknown whether an aberrant microbiome is present before clinical disease onset in participants susceptible to HT or whether it reflects the effects of the disease itself. In this study, we report for the first time a comprehensive characterization of the taxonomic and functional profiles of the gut microbiota in euthyroid seropositive and seronegative participants. Our primary goal was to determine taxonomic and functional signatures of the intestinal microbiota associated with serum thyroid peroxidase antibodies (TPOAb). A secondary aim was to determine whether different ethnicities warrant distinct reference intervals for accurate interpretation of serum thyroid biomarkers. Methods: In this cross-sectional study, euthyroid participants with (N = 159) and without (N = 1309) TPOAb were selected from the multiethnic (European Dutch, Moroccan, and Turkish) HEalthy Life In an Urban Setting (HELIUS) cohort. Fecal microbiota composition was profiled using 16S rRNA sequencing. Differences between the groups were analyzed based on the overall composition (alpha and beta diversity), as well as differential abundance (DA) of microbial taxa and functional pathways using multiple DA tools. Results: Overall composition showed a substantial overlap between the two groups (p > 0.05 for alpha-diversity; p = 0.39 for beta-diversity), indicating that TPOAb-seropositivity does not significantly differentiate gut microbiota composition and diversity. Interestingly, TPOAb status accounted for only a minor fraction (0.07%) of microbiome variance (p = 0.545). Further exploration of taxonomic differences identified 138 taxa nominally associated with TPOAb status. Among these, 13 taxa consistently demonstrated nominal significance across three additional DA methods, alongside notable associations within various functional pathways. Furthermore, we showed that ethnicity-specific reference intervals for serum thyroid biomarkers are not required, as no significant disparities in serum thyroid markers were found among the three ethnic groups residing in an iodine-replete area (p > 0.05 for thyrotropin, free thyroxine, and TPOAb). Conclusion: These findings suggest that there is no robust difference in gut microbiome between individuals with or without TPOAb in terms of alpha and beta-diversity. Nonetheless, several taxa were identified with nominal significance related to TPOAb presence. Further research is required to determine whether these changes indeed imply a higher risk of overt HT.

Potency of quality indicators in Dutch and international diabetes registries.

BACKGROUND: Diabetes mellitus forms a slow pandemic. Cardiovascular risk and quality of diabetes care are strongly associated. Quality indicators improve diabetes management and reduce mortality and costs. Various national diabetes registries render national quality indicators. We describe diabetes care indicators for Dutch children and adults with diabetes, and compare them with indicators established by registries worldwide. METHODS: Indicator scores were derived from the Dutch Pediatric and Adult Registry of Diabetes Indicator sets of other national diabetes registries were collected and juxtaposed with global and continental initiatives for indicator sets. RESULTS: This observational cohort study included 3738 patients representative of the Dutch diabetic outpatient population. The Dutch Pediatric and Adult Registry of Diabetes harbors ten quality indicators comprising treatment volumes, HbA1c control, foot examination, insulin pump therapy, and real-time continuous glucose monitoring. Worldwide, nine national registries record quality indicators, with great variety between registries. HbA1c control is recorded most frequently, and no indicator is reported among all registries. CONCLUSIONS: Wide variety among quality indicators recorded by national diabetes registries hinders international comparison and interpretation of quality of diabetes care. The potential of quality evaluation will be greatly enhanced when diabetes care indicators are aligned in an international standard set with variation across countries taken into consideration.

Intestinal acetate and butyrate availability is associated with glucose metabolism in healthy individuals.

Animal studies suggest that short-chain fatty acids acetate and butyrate are key players in the gut-brain axis and may affect insulin sensitivity. We investigated the association of intestinal acetate and butyrate availability (measured by butyryl-coenzyme A transferase (ButCoA) gene amount) with insulin sensitivity and secretion in healthy subjects from the HELIUS cohort study from the highest 15% (N = 30) and the lowest 15% (N = 30) intestinal ButCoA gene amount. The groups did not differ in insulin sensitivity or secretion. However, the high ButCoA group showed lower glucose and insulin peaks during the first 60 min after a meal and a higher nadir during the second 60 min (p < 0.01), suggesting delayed glucose adsorption from the small intestine. Our data suggest that chronically increased acetate and butyrate availability may improve glucose metabolism by delaying gastric emptying and intestinal adsorption. Future studies should further investigate the effect of acetate and butyrate interventions.

Early-life microbiota as a baby metabolic guardian.

Early-life microbiota have a crucial role in healthy development. Antibiotics, on the other hand, can disrupt this beneficial interaction and have been linked to increased adiposity in children. Shelton and collaborators went deeper into the mechanism by which microbiota protect against lipid metabolic dysfunction and diet-induced obesity. The results highlight the long-term metabolic risk of early antibiotic exposure.