Associations of Dietary Intake with the Intestinal Microbiota and Short-Chain Fatty Acids Among Young Adults with Type 1 Diabetes and Overweight or Obesity.

BACKGROUND: Diet, a key component of type 1 diabetes (T1D) management, modulates the intestinal microbiota and its metabolically active byproducts-including SCFA-through fermentation of dietary carbohydrates such as fiber. However, the diet-microbiome relationship remains largely unexplored in longstanding T1D. OBJECTIVES: We evaluated whether increased carbohydrate intake, including fiber, is associated with increased SCFA-producing gut microbes, SCFA, and intestinal microbial diversity among young adults with longstanding T1D and overweight or obesity. METHODS: Young adult men and women with T1D for ≥1 y, aged 19-30 y, and BMI of 27.0-39.9 kg/m2 at baseline provided stool samples at baseline and 3, 6, and 9 mo of a randomized dietary weight loss trial. Diet was assessed by 1-2 24-h recalls. The abundance of SCFA-producing microbes was measured using 16S rRNA gene sequencing. GC-MS measured fecal SCFA (acetate, butyrate, propionate, and total) concentrations. Adjusted and Bonferroni-corrected generalized estimating equations modeled associations of dietary fiber (total, soluble, and pectins) and carbohydrate (available carbohydrate, and fructose) with microbiome-related outcomes. Primary analyses were restricted to data collected before COVID-19 interruptions. RESULTS: Fiber (total and soluble) and carbohydrates (available and fructose) were positively associated with total SCFA and acetate concentrations (n = 40 participants, 52 visits). Each 10 g/d of total and soluble fiber intake was associated with an additional 8.8 µmol/g (95% CI: 4.5, 12.8 µmol/g; P = 0.006) and 24.0 µmol/g (95% CI: 12.9, 35.1 µmol/g; P = 0.003) of fecal acetate, respectively. Available carbohydrate intake was positively associated with SCFA producers Roseburia and Ruminococcus gnavus. All diet variables except pectin were inversely associated with normalized abundance of Bacteroides and Alistipes. Fructose was inversely associated with Akkermansia abundance. CONCLUSIONS: In young adults with longstanding T1D, fiber and carbohydrate intake were associated positively with fecal SCFA but had variable associations with SCFA-producing gut microbes. Controlled feeding studies should determine whether gut microbes and SCFA can be directly manipulated in T1D.

Associations of disordered eating with the intestinal microbiota and short-chain fatty acids among young adults with type 1 diabetes.

BACKGROUND AND AIMS: Disordered eating (DE) in type 1 diabetes (T1D) includes insulin restriction for weight loss with serious complications. Gut microbiota-derived short chain fatty acids (SCFA) may benefit host metabolism but are reduced in T1D. We evaluated the hypothesis that DE and insulin restriction were associated with reduced SCFA-producing gut microbes, SCFA, and intestinal microbial diversity in adults with T1D. METHODS AND RESULTS: We collected stool samples at four timepoints in a hypothesis-generating gut microbiome pilot study ancillary to a weight management pilot in young adults with T1D. 16S ribosomal RNA gene sequencing measured the normalized abundance of SCFA-producing intestinal microbes. Gas-chromatography mass-spectrometry measured SCFA (total, acetate, butyrate, and propionate). The Diabetes Eating Problem Survey-Revised (DEPS-R) assessed DE and insulin restriction. Covariate-adjusted and Bonferroni-corrected generalized estimating equations modeled the associations. COVID-19 interrupted data collection, so models were repeated restricted to pre-COVID-19 data. Data were available for 45 participants at 109 visits, which included 42 participants at 65 visits pre-COVID-19. Participants reported restricting insulin "At least sometimes" at 53.3% of visits. Pre-COVID-19, each 5-point DEPS-R increase was associated with a -0.34 (95% CI -0.56, -0.13, p = 0.07) lower normalized abundance of genus Anaerostipes; and the normalized abundance of Lachnospira genus was -0.94 (95% CI -1.5, -0.42), p = 0.02 lower when insulin restriction was reported "At least sometimes" compared to "Rarely or Never". CONCLUSION: DE and insulin restriction were associated with a reduced abundance of SCFA-producing gut microbes pre-COVID-19. Additional studies are needed to confirm these associations to inform microbiota-based therapies in T1D.

Weight management in young adults with type 1 diabetes: The advancing care for type 1 diabetes and obesity network sequential multiple assignment randomized trial pilot results.

AIMS: Co-management of weight and glycaemia is critical yet challenging in type 1 diabetes (T1D). We evaluated the effect of a hypocaloric low carbohydrate, hypocaloric moderate low fat, and Mediterranean diet without calorie restriction on weight and glycaemia in young adults with T1D and overweight or obesity. MATERIALS AND METHODS: We implemented a 9-month Sequential, Multiple Assignment, Randomized Trial pilot among adults aged 19-30 years with T1D for ≥1 year and body mass index 27-39.9 kg/m2 . Re-randomization occurred at 3 and 6 months if the assigned diet was not acceptable or not effective. We report results from the initial 3-month diet period and re-randomization statistics before shutdowns due to COVID-19 for primary [weight, haemoglobin A1c (HbA1c), percentage of time below range <70 mg/dl] and secondary outcomes [body fat percentage, percentage of time in range (70-180 mg/dl), and percentage of time below range <54 mg/dl]. Models adjusted for design, demographic and clinical covariates tested changes in outcomes and diet differences. RESULTS: Adjusted weight and HbA1c (n = 38) changed by -2.7 kg (95% CI -3.8, -1.5, P < .0001) and -0.91 percentage points (95% CI -1.5, -0.30, P = .005), respectively, while adjusted body fat percentage remained stable, on average (P = .21). Hypoglycaemia indices remained unchanged following adjustment (n = 28, P > .05). Variability in all outcomes, including weight change, was considerable (57.9% were re-randomized primarily due to loss of <2% body weight). No outcomes varied by diet. CONCLUSIONS: Three months of a diet, irrespective of macronutrient distribution or caloric restriction, resulted in weight loss while improving or maintaining HbA1c levels without increasing hypoglycaemia in adults with T1D.

The Intestinal Microbiota and Short-Chain Fatty Acids in Association with Advanced Metrics of Glycemia and Adiposity Among Young Adults with Type 1 Diabetes and Overweight or Obesity.

Background: Comanagement of glycemia and adiposity is the cornerstone of cardiometabolic risk reduction in type 1 diabetes (T1D), but targets are often not met. The intestinal microbiota and microbiota-derived short-chain fatty acids (SCFAs) influence glycemia and adiposity but have not been sufficiently investigated in longstanding T1D. Objectives: We evaluated the hypothesis that an increased abundance of SCFA-producing gut microbes, fecal SCFAs, and intestinal microbial diversity were associated with improved glycemia but increased adiposity in young adults with longstanding T1D. Methods: Participants provided stool samples at ≤4 time points (NCT03651622: https://clinicaltrials.gov/ct2/show/NCT03651622). Sequencing of the 16S ribosomal RNA gene measured abundances of SCFA-producing intestinal microbes. GC-MS measured total and specific SCFAs (acetate, butyrate, propionate). DXA (body fat percentage and percentage lean mass) and anthropometrics (BMI) measured adiposity. Continuous glucose monitoring [percentage of time in range (70-180 mg/dL), above range (>180 mg/dL), and below range (54-69 mg/dL)] and glycated hemoglobin (i.e., HbA1c) assessed glycemia. Adjusted and Bonferroni-corrected generalized estimating equations modeled the associations of SCFA-producing gut microbes, fecal SCFAs, and intestinal microbial diversity with glycemia and adiposity. COVID-19 interrupted data collection, so models were repeated restricted to pre-COVID-19 visits. Results: Data were available for ≤45 participants at 101 visits (including 40 participants at 54 visits pre-COVID-19). Abundance of Eubacterium hallii was associated inversely with BMI (all data). Pre-COVID-19, increased fecal propionate was associated with increased percentage of time above range and reduced percentage of time in target and below range; and abundances of 3 SCFA-producing taxa (Ruminococcus gnavus, Eubacterium ventriosum, and Lachnospira) were associated inversely with body fat percentage, of which two microbes were positively associated with percentage lean mass. Abundance of Anaerostipes was associated with reduced percentage of time in range (all data) and with increased body fat percentage and reduced percentage lean mass (pre-COVID-19). Conclusions: Unexpectedly, fecal propionate was associated with detriment to glycemia, whereas most SCFA-producing intestinal microbes were associated with benefit to adiposity. Future studies should confirm these associations and determine their potential causal linkages in T1D.This study is registered at clinical.trials.gov (NCT03651622; https://clinicaltrials.gov/ct2/show/NCT03651622).

The Advancing Care for T1D Obesity Network (ACT1ON) Sequential Multiple Assignment Randomized Trial Pilot Re-randomization Results

Background: Sequential Multiple Assignment Randomized Trials (SMARTs) efficiently address practical treatment comparison questions and adapt dynamically based on response. They may be useful for development of approaches to co-manage weight and glycemia T1D, which is critical yet challenging. Methods: Our SMART pilot with three diet periods enrolled young adults with T1D (BMI 27-39.9 kg/m²) . Participants were re-randomized after ∼3 months on the hypocaloric Look AHEAD (Low Fat) or Low Carbohydrate (Low Carb) ;or Mediterranean (Med, not calorie restricted) diet if <2% weight was lost, HbA1c increased ≥0.5%, diet was unacceptable, or hypoglycemia increased. We present descriptive statistics for weight, HbA1c, and re-randomization for diet period 1 pre-COVID before shifting to a virtual protocol. Results: The proportion re-randomized was 57.9% and did not vary by diet. Weight was lost overall but insufficient weight loss was the most common reason for re-randomization for Low Fat and Med. An HbA1c increase ≥0.5% was most common on Med. Low diet acceptability was the most common reason for re-randomization on Low Carb. Conclusions: We achieved safe weight loss among young adults with T1D but observed heterogeneity in reasons for re-randomization by diet, although differences were not statistically significant. A fully-powered efficacy trial may confirm our findings.

Development and validation of multivariable prediction models for adverse COVID-19 outcomes in patients with IBD.

OBJECTIVES: Develop an individualised prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD). DESIGN AND SETTING: This study developed and validated prognostic penalised logistic regression models using reports to the international Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease voluntary registry from March to October 2020. Model development was done using a training data set (85% of cases reported 13 March-15 September 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported 16 September-20 October 2020). PARTICIPANTS: We included 2709 cases from 59 countries (mean age 41.2 years (SD 18), 50.2% male). All submitted cases after removing duplicates were included. PRIMARY AND SECONDARY OUTCOME MEASURES: COVID-19 related: (1) Hospitalisation+: composite outcome of hospitalisation, ICU admission, mechanical ventilation or death; (2) Intensive Care Unit+ (ICU+): composite outcome of ICU admission, mechanical ventilation or death; (3) Death. We assessed the resulting models' discrimination using the area under the curve of the receiver operator characteristic curves and reported the corresponding 95% CIs. RESULTS: Of the submitted cases, a total of 633 (24%) were hospitalised, 137 (5%) were admitted to the ICU or intubated and 69 (3%) died. 2009 patients comprised the training set and 700 the test set. The models demonstrated excellent discrimination, with a test set area under the curve (95% CI) of 0.79 (0.75 to 0.83) for Hospitalisation+, 0.88 (0.82 to 0.95) for ICU+ and 0.94 (0.89 to 0.99) for Death. Age, comorbidities, corticosteroid use and male gender were associated with a higher risk of death, while the use of biological therapies was associated with a lower risk. CONCLUSIONS: Prognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of patients with IBD. A free online risk calculator (https://covidibd.org/covid-19-risk-calculator/) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with patients with IBD.