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.

Relationship Between Moderate-to-Vigorous Physical Activity and Glycemia Among Young Adults with Type 1 Diabetes and Overweight or Obesity: Results from the Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON) Study.

Aims: Using data from the ACT1ON study, we conducted secondary analyses to assess the relationship between minutes of moderate-to-vigorous physical activity (MVPA) and glycemia in adults with type 1 diabetes (T1D) and overweight or obesity. Materials and Methods: Participants (n = 66) with T1D provided measures of glycemia (hemoglobin A1c [HbA1c], percent of time below range <70 mg/dL, time-in-range [TIR 70-180 mg/dL], and time above range [TAR >180 mg/dL]) and self-reported physical activity (Global Physical Activity Questionnaire [GPAQ] and Previous Day Physical Activity Recalls [PDPAR]) at baseline, 3, 6, and 9 months postintervention. Wearable activity data were available for a subset of participants (n = 27). Associations were estimated using mixed effects regression models adjusted for design, demographic, clinical, and dietary covariates. Results: Among young adults 19-30 years of age with a baseline HbA1c of 7.9% ± 1.4% and body mass index of 30.3 (interquartile range 27.9, 33.8), greater habitual weekly MVPA minutes were associated with higher HbA1c through the GPAQ (P < 0.01) and wearable activity data (P = 0.01). We did not observe a significant association between habitual MVPA and any continuous glucose monitoring metrics. Using PDPAR data, however, we observed that greater daily MVPA minutes were associated with more TAR (P < 0.01) and reduced TIR (P < 0.01) on the day following reported physical activity. Conclusions: Among young adults with T1D and overweight or obesity, increased MVPA was associated with worsened glycemia. As physical activity is vital to cardiovascular health and weight management, additional research is needed to determine how to best support young adults with T1D and overweight or obesity in their efforts to increase physical activity. Clinical Trial Registration number: NCT03651622.

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).

Physical Activity and Glycemia among Young Adults with Type 1 Diabetes and Overweight or Obesity-Results from Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON)

The ACT1ON pilot study evaluated the feasibility of three dietary strategies to optimize weight and glycemic management among young adults with T1D and overweight or obesity. As a secondary measure, self-reported physical activity (PA) was collected at baseline, 3-, 6-, and 9-months from 68 young adults with T1D (age 25.5 ± 3.1 years, 72.1% female, HbA1c 7.9 ± 1.8%, BMI 30.4 (27.9 - 33.9)) . Using the Global Physical Activity Questionnaire (GPAQ, n=195) and Previous Day Physical Activity Recalls (PDPAR, n=123) , we estimated weekly minutes of moderate-to-vigorous physical activity (MVPA) . Following the COVID-19 outbreak, a subset of participants wore Garmin Vivosmart4® PA trackers for two weeks at each visit (44 measurements from 27 participants) . Mixed effects regression models assessed the relationship between weekly minutes of MVPA and HbA1c using each PA measure. Median weekly minutes of MVPA were 33% lower following the COVID-19 outbreak compared to pre-pandemic PA levels (p=0.02) per the GPAQ, but not PDPAR (-7.7%, p=0.34) . After adjusting for design, demographic, clinical, and dietary variables, a 1 standard deviation increase in weekly minutes of MVPA (GPAQ) was associated with an absolute increase of 0.27% HbA1c (p>0.001) . A small, statistically non-significant association was observed for PDPAR (β=0.13, p=0.19) ;however, we observed a borderline statistically significant association using the PA tracker data (β=0.231, p=0.08) , despite a smaller sample size (n=44) . These results suggest that among young adults with T1D and overweight and obesity, higher levels of PA may lead to challenges in achieving optimal glycemia. Future work is needed to determine how to best support young adults with T1D and overweight and obesity in attaining both their PA and glycemic management goals.

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.