Laxative Abuse Is Associated With a Depleted Gut Microbial Community Structure Among Women and Men With Binge-Eating Disorder or Bulimia Nervosa: The Binge Eating Genetics Initiative.

OBJECTIVE: This study assessed the associations of binge eating, compensatory behaviors, and dietary restraint with the composition and diversity of the intestinal microbiota among participants with binge-eating disorder or bulimia nervosa. METHODS: We analyzed data from 265 participants aged 18 to 45 years with current binge-eating disorder or bulimia nervosa enrolled in the Binge Eating Genetics Initiative study. We evaluated the associations of binge-eating frequency; presence/absence and frequency of vomiting, laxative use, and compulsive exercise; and dietary restraint with abundances of gut microbial genera, species, and diversity (Shannon diversity, Faith phylogenetic diversity, and Peilou's evenness) from 16S rRNA gene sequencing. General linear regression models adjusted for potential confounders, including age and current body mass index, were used to test associations; p values were corrected for the false discovery rate. RESULTS: The normalized abundance of four genus- and species-level gut microbes and three diversity indices were lower among Binge Eating Genetics Initiative participants who reported any laxative use compared with those who reported no laxative use. Vomiting frequency was positively associated with the normalized abundance of the genus Escherichia-Shigella , a potential pathobiont, although the association was attenuated to nonsignificance after adjustment for age, body mass index, and binge-eating episodes. CONCLUSIONS: Laxative use was highly and uniformly predictive of a reduced gut microbial diversity including potential commensals and pathobionts, and should be assessed and accounted for in all future studies of eating disorders and the gut microbiota. Future studies should collect data on specific medications-particularly laxatives-and dietary intake to obtain unbiased estimates of the effect of eating disorders on the gut microbiota and identify potential downstream clinical implications.Trial Registration:ClinicalTrials.gov identifier: NCT04162574 .

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.

More hypoglycemia not associated with increasing estimated adiposity in youth with type 1 diabetes.

BACKGROUND: Despite the widespread clinical perception that hypoglycemia may drive weight gain in youth with type 1 diabetes (T1D), there is an absence of published evidence supporting this hypothesis. METHODS: We estimated the body fat percentage (eBFP) of 211 youth (HbA1c 8.0-13.0%, age 13-16) at baseline, 6, and 18 months of the Flexible Lifestyles Empowering Change trial using validated equations. Group-based trajectory modeling assigned adolescents to sex-specific eBFP groups. Using baseline 7-day blinded continuous glucose monitoring data, "more" vs. "less" percent time spent in hypoglycemia was defined by cut-points using sample median split and clinical guidelines. Adjusted logistic regression estimated the odds of membership in an increasing eBFP group comparing youth with more vs. less baseline hypoglycemia. RESULTS: More time spent in clinical hypoglycemia (defined by median split) was associated with 0.29 the odds of increasing eBFP in females (95% CI: 0.12, 0.69; p = 0.005), and 0.33 the odds of stable/increasing eBFP in males (95% CI: 0.14, 0.78; p = 0.01). CONCLUSIONS: Hypoglycemia may not be a major driver of weight gain in US youth with T1D and HbA1c ≥8.0. Further studies in different sub-groups are needed to clarify for whom hypoglycemia may drive weight gain and focus future etiological studies and interventions. IMPACT: We contribute epidemiological evidence that hypoglycemia may not be a major driver of weight gain in US youth with type 1 diabetes and HbA1c ≥8.0% and highlight the need for studies to prospectively test this hypothesis rooted in clinical perception. Future research should examine the relationship between hypoglycemia and adiposity together with psychosocial, behavioral, and other clinical factors among sub-groups of youth with type 1 diabetes (i.e., who meet glycemic targets or experience a frequency/severity of hypoglycemia above a threshold) to further clarify for whom hypoglycemia may drive weight gain and progress etiological understanding of and interventions for healthy weight maintenance.

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.

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.

Mindfulness, disordered eating, and impulsivity in relation to glycemia among adolescents with type 1 diabetes and suboptimal glycemia from the Flexible Lifestyles Empowering Change (FLEX) intervention trial.

OBJECTIVE: To assess the relationship between mindfulness and glycemia among adolescents with type 1 diabetes (T1D) with suboptimal glycemia, and evaluate the potential mediation by ingestive behaviors, including disordered eating, and impulsivity. RESEARCH DESIGN AND METHODS: We used linear mixed models for hemoglobin A1c (HbA1c) and linear regression for continuous glucose monitoring (CGM) to study the relationship of mindfulness [Child and Adolescent Mindfulness Measure (CAMM)] and glycemia in adolescents with T1D from the 18-month Flexible Lifestyles Empowering Change (FLEX) trial. We tested for mediation of the mindfulness-glycemia relationship by ingestive behaviors, including disordered eating (Diabetes Eating Problem Survey-Revised), restrained eating, and emotional eating (Dutch Eating Behavior Questionnaire); and impulsivity (total, attentional, and motor, Barrett Impulsiveness Scale). RESULTS: At baseline, participants (n = 152) had a mean age of 14.9 ± 1.1 years and HbA1c of 9.4 ± 1.2% [79 ± 13 mmol/mol]. The majority of adolescents were non-Hispanic white (83.6%), 50.7% were female, and 73.0% used insulin pumps. From adjusted mixed models, a 5-point increase in mindfulness scores was associated with a -0.19% (95%CI -0.29, -0.08, p = 0.0006) reduction in HbA1c. We did not find statistically significant associations between mindfulness and CGM metrics. Mediation of the relationship between mindfulness and HbA1c by ingestive behaviors and impulsivity was not found to be statistically significant. CONCLUSIONS: Among adolescents with T1D and suboptimal glycemia, increased mindfulness was associated with lower HbA1c levels. Future studies may consider mindfulness-based interventions as a component of treatment for improving glycemia among adolescents with T1D, though more data are needed to assess feasibility and efficacy.

Impact of Hurricane Matthew on Diabetes Self-Management and Outcomes.

BACKGROUND: Individuals with diabetes require extensive self-management. Little is known about how Hurricane Matthew (Matthew) or Hurricane Florence (Florence) impacted diabetes self-management and outcomes in Robeson County, North Carolina. METHODS: Mixed methods were used to assess the impact of hurricanes on diabetes self-management and outcomes. Individuals with diabetes were recruited for focus groups to understand the perceived impact on diabetes self-management. Health care providers were recruited for parallel key informant interviews. Mean hemoglobin A1c (HbA1c) and frequency of diabetic ketoacidosis (DKA) from hospital data six months before and after Matthew were compared using Student t-tests. RESULTS: A demographic breakdown of 34.25% white, 21.70% Black or African American, and 21.38% American Indian or Alaska Native was observed from focus groups. Qualitative results highlight a limited access to a balanced diet and medications. No significant differences were found between mean HbA1c values before and after Matthew (before Matthew: mean HbA1c 8.34 ± 1.87%; after Matthew: mean HbA1c 8.31 ± 1.93 %; P = .366). The period prevalence (PP) of DKA was higher after Matthew than before (before Matthew: 39 cases out of 4,025 visits, PP = .010; after Matthew: 87 cases out of 3,779 visits, PP = .023; P <.0001). LIMITATIONS: Limitations include non-random sampling and limited sample sizes. Also, the cross-sectional panel approach did not follow the same individuals over time. CONCLUSIONS: The period prevalence of DKA was higher in the six-month time period following Matthew compared to before the hurricane. Future interventions may improve outcomes via increased access to foods and medications recommended for those with diabetes.

Dietary intake on days with and without hypoglycemia in youth with type 1 diabetes: The Flexible Lifestyle Empowering Change trial.

OBJECTIVE: To address a common perception that hypoglycemia is associated with increased dietary intake, we examined calorie and carbohydrate consumption on days with and without hypoglycemia among adolescents with type 1 diabetes (T1D). METHODS: Days (N = 274) with 24-hour dietary recalls and continuous glucose monitoring were available for 122 adolescents with T1D in the Flexible Lifestyle Empowering Change trial (age 13-16 years, diabetes duration >1 year, hemoglobin A1c 8%-13%). Days with no hypoglycemia, clinical hypoglycemia (54-69 mg/dL) or clinically serious hypoglycemia (<54 mg/dL) were further split into night (12-5:59 am) and day (6 am-11:59 pm). Mixed models tested whether intake of calories or carbohydrates was greater on days with than without hypoglycemia. RESULTS: Fifty-nine percent, 23% and 18% of days had no hypoglycemia, clinical hypoglycemia and clinically serious hypoglycemia, respectively. Intake of calories and carbohydrates was not statistically significantly different on days with clinical hypoglycemia (57.2 kcal [95% CI -126.7, 241.5]; 12.6 g carbohydrate [95% CI -12.7, 38.0]) or clinically serious hypoglycemia (-74.0 kcal [95% CI -285.9, 137.9]; (-7.8 g carbohydrate [95% CI -36.8, 21.1]), compared to days without hypoglycemia. Differences by day and night were not statistically significant. CONCLUSIONS: Among adolescents with T1D, daily intake of calories and carbohydrates did not differ on days with and without hypoglycemia. It is possible that hypoglycemic episodes caused by undereating relative to insulin dosing, followed by overeating, leading to a net neutral difference. Given the post-hoc nature of these analyses, larger studies should be designed to prospectively test the hypoglycemia-diet relationship.

The interplay of type 1 diabetes and weight management: A qualitative study exploring thematic progression from adolescence to young adulthood.

BACKGROUND: The impact of weight management in persons with type 1 diabetes (T1D) from childhood into adulthood has not been well described. The purpose of the study was to explore qualitative themes presented by young adults with T1D with respect to the dual management of weight and T1D. METHODS: We analyzed focus group data from 17 young adults with T1D (65% female, age 21.7 ± 2.1 years, HbA1c 8.1% ± 1.5) via inductive qualitative analysis methods. Major themes were compared to themes presented by youth with T1D ages 13-16 years in previously published study in order to categorize thematic progression from early adolescence through adulthood. RESULTS: Themes from young adults with T1D, when compared to those from youth were categorized as: (a) persistent and unchanged themes, (b) evolving themes, and (c) newly reported themes. Hypoglycemia and a sense of futility around exercise was an unchanged theme. Importance of insulin usage and a healthy relationship with T1D evolved to gather greater conviction. Newly reported themes are unique to integration of adulthood into T1D, such as family planning and managing T1D with work obligations. Young adults also reported negative experiences with providers in their younger years and desire for more supportive provider relationships. CONCLUSIONS: Issues identified by youth regarding the dual management of T1D and weight rarely resolve, but rather, persist or evolve to integrate other aspects of young adulthood. Individualized and age-appropriate clinical support and practice guidelines are warranted to facilitate the dual management of weight and T1D in persons with T1D.

Impaired Awareness of Hypoglycemia in Older Adults With Type 1 Diabetes: A Post Hoc Analysis of the WISDM Study.

OBJECTIVE: Up to one-third of older adults with type 1 diabetes experience impaired awareness of hypoglycemia (IAH), yet the factors associated with IAH remain underexplored in older adults. RESEARCH DESIGN AND METHODS: This post hoc analysis evaluated the clinical and glycemic correlates of IAH in adults ≥60 years old with type 1 diabetes in the WISDM study. IAH and normal awareness of hypoglycemia (NAH) were defined by a Clarke score of ≥4 or <4, respectively. Demographic, clinical, and glycemic metrics were compared in those with IAH and NAH at baseline and in whom IAH did or did not improve over 26 weeks, using descriptive statistics and a multiple logistic regression variable selection procedure. RESULTS: Of the 199 participants (age 68.1 ± 5.7 years, 52% female), 30.6% had IAH. At baseline, participants with IAH had a longer diabetes duration and greater daytime hypoglycemia and glycemic variability, and more participants had nondetectable C-peptide levels than those with NAH. Logistic regression associated longer diabetes duration (odds ratio [OR] 1.03, 95% CI 1.01-1.05; P = 0.008) and greater daytime hypoglycemia (OR 1.31, 95% CI, 1.15-1.51; P < 0.0001) with a greater odds of IAH. A similar modeling procedure identified less daytime hypoglycemia (OR per additional percentage point 0.55, 95% CI 0.32-0.94; P = 0.029) and shorter diabetes duration (OR per additional year 0.96, 95% CI 0.91-1.004; P = 0.07) as predictors of restored awareness at 26 weeks, although the effect size for diabetes duration was not statistically significant. CONCLUSIONS: In older adults with type 1 diabetes, longer diabetes duration and greater daytime hypoglycemia are drivers of IAH. Dedicated research can personalize IAH management.

Eating behaviors and estimated body fat percentage among adolescents with type 1 diabetes.

AIMS: Estimate associations between select eating behaviors and estimated body fat percentage (eBFP) and explore effect modification by sex among adolescents with type 1 diabetes (T1D). METHODS: This analysis included 257 adolescents (mean age 14.9 ± 1.14 years; 49.8 % female) with baseline hemoglobin A1c (HbA1c) between 8 and 13 % (64 mmol/mol-119 mmol/mol) from a randomized trial designed to improve glycemia. Eating behaviors and eBFP were determined from surveys and validated equations respectively. Linear mixed models were used to estimate associations. Effect modification was assessed via stratified plots, stratified associations, and interaction terms. RESULTS: Disordered eating, dietary restraint, and eBFP were significantly higher among females while external eating was higher among males. Disordered eating (ß: 0.49, 95 %CI: 0.24, 0.73, p = 0.0001) and restraint (ß: 1.11, 95 %CI: 0.29, 1.92, p = 0.0081) were positively associated with eBFP while external eating was not (ß: -0.19, 95 %CI: -0.470, 0.096, p = 0.20). Interactions with sex were not significant (p-value range: 0.28-0.64). CONCLUSION: Disordered eating and dietary restraint were positively associated with eBFP, highlighting the potential salience of these eating behaviors to cardiometabolic risk for both female and male adolescents. Prospective studies should investigate whether these eating behaviors predict eBFP longitudinally to inform obesity prevention strategies in T1D.

24-h energy expenditure in people with type 1 diabetes: impact on equations for clinical estimation of energy expenditure.

BACKGROUND/OBJECTIVES: Type 1 diabetes (T1D) is associated with an increase in resting metabolic rate (RMR), but the impact of T1D on other components of 24-h energy expenditure (24-h EE) is not known. Also, there is a lack of equations to estimate 24-h EE in patients with T1D. The aims of this analysis were to compare 24-h EE and its components in young adults with T1D and healthy controls across the spectrum of body mass index (BMI) and derive T1D-specific equations from clinical variables. SUBJECTS/METHODS: Thirty-three young adults with T1D diagnosed ≥1 year prior and 33 healthy controls matched for sex, age and BMI were included in this analysis. We measured 24-h EE inside a whole room indirect calorimeter (WRIC) and body composition with dual x-ray absorptiometry. RESULTS: Participants with T1D had significantly higher 24-h EE than healthy controls (T1D = 2047 ± 23 kcal/day vs control= 1908 ± 23 kcal/day; P < 0.01). We derived equations to estimate 24-h EE with both body composition (fat free mass + fat mass) and anthropometric (weight + height) models, which provided high coefficients of determination (R2 = 0.912 for both). A clinical model that did not incorporate spontaneous physical activity yielded high coefficients of determination as well (R2 = 0.897 and R2 = 0.880 for body composition and anthropometric models, respectively). CONCLUSION: These results confirm that young adults with established T1D have increased 24-h EE relative to controls without T1D. The derived equations from clinically available variables can assist clinicians with energy prescriptions for weight management in patients with T1D.

Associations of Skeletal Muscle Mass, Muscle Fat Infiltration, Mitochondrial Energetics, and Cardiorespiratory Fitness With Liver Fat Among Older Adults.

BACKGROUND: Muscle mass loss may be associated with liver fat accumulation, yet scientific consensus is lacking and evidence in older adults is scant. It is unclear which muscle characteristics might contribute to this association in older adults. METHODS: We associated comprehensive muscle-related phenotypes including muscle mass normalized to body weight (D3-creatine dilution), muscle fat infiltration (magnetic resonance imaging), carbohydrate-supported muscle mitochondrial maximal oxidative phosphorylation (respirometry), and cardiorespiratory fitness (VO2 peak) with liver fat among older adults. Linear regression models adjusted for age, gender, technician (respirometry only), daily minutes of moderate-to-vigorous physical activity, and prediabetes/diabetes status tested main effects and interactions of each independent variable with waist circumference (high: women-≥88 cm, men-≥102 cm) and gender. RESULTS: Among older adults aged 75 (interquartile range: 73, 79 years; 59.8% women), muscle mass and liver fat were not associated overall (N = 362) but were positively associated among participants with a high waist circumference (ß: 25.2; 95% confidence intervals [95% CI]: 11.7, 40.4; p = .0002; N = 160). Muscle fat infiltration and liver fat were positively associated (ß: 15.2; 95% CI: 6.8, 24.3; p = .0003; N = 378). Carbohydrate-supported maximum oxidative phosphorylation (before adjustment) and VO2 peak (after adjustment; ß: -12.9; 95% CI: -20.3, -4.8; p = .003; N = 361) were inversely associated with liver fat; adjustment attenuated the estimate for maximum oxidative phosphorylation although the point estimate remained negative (ß: -4.0; 95% CI: -11.6, 4.2; p = .32; N = 321). CONCLUSIONS: Skeletal muscle-related characteristics are metabolically relevant factors linked to liver fat in older adults. Future research should confirm our results to determine whether trials targeting mechanisms common to liver and muscle fat accumulation are warranted.

Reprogramming the Human Gut Microbiome Reduces Dietary Energy Harvest.

The gut microbiome is emerging as a key modulator of host energy balance1. We conducted a quantitative bioenergetics study aimed at understanding microbial and host factors contributing to energy balance. We used a Microbiome Enhancer Diet (MBD) to reprogram the gut microbiome by delivering more dietary substrates to the colon and randomized healthy participants into a within-subject crossover study with a Western Diet (WD) as a comparator. In a metabolic ward where the environment was strictly controlled, we measured energy intake, energy expenditure, and energy output (fecal, urinary, and methane)2. The primary endpoint was the within-participant difference in host metabolizable energy between experimental conditions. The MBD led to an additional 116 ± 56 kcals lost in feces daily and thus, lower metabolizable energy for the host by channeling more energy to the colon and microbes. The MBD drove significant shifts in microbial biomass, community structure, and fermentation, with parallel alterations to the host enteroendocrine system and without altering appetite or energy expenditure. Host metabolizable energy on the MBD had quantitatively significant interindividual variability, which was associated with differences in the composition of the gut microbiota experimentally and colonic transit time and short-chain fatty acid absorption in silico. Our results provide key insights into how a diet designed to optimize the gut microbiome lowers host metabolizable energy in healthy humans.

Host-diet-gut microbiome interactions influence human energy balance: a randomized clinical trial.

The gut microbiome is emerging as a key modulator of human energy balance. Prior studies in humans lacked the environmental and dietary controls and precision required to quantitatively evaluate the contributions of the gut microbiome. Using a Microbiome Enhancer Diet (MBD) designed to deliver more dietary substrates to the colon and therefore modulate the gut microbiome, we quantified microbial and host contributions to human energy balance in a controlled feeding study with a randomized crossover design in young, healthy, weight stable males and females (NCT02939703). In a metabolic ward where the environment was strictly controlled, we measured energy intake, energy expenditure, and energy output (fecal and urinary). The primary endpoint was the within-participant difference in host metabolizable energy between experimental conditions [Control, Western Diet (WD) vs. MBD]. The secondary endpoints were enteroendocrine hormones, hunger/satiety, and food intake. Here we show that, compared to the WD, the MBD leads to an additional 116 ± 56 kcals (P < 0.0001) lost in feces daily and thus, lower metabolizable energy for the host (89.5 ± 0.73%; range 84.2-96.1% on the MBD vs. 95.4 ± 0.21%; range 94.1-97.0% on the WD; P < 0.0001) without changes in energy expenditure, hunger/satiety or food intake (P > 0.05). Microbial 16S rRNA gene copy number (a surrogate of biomass) increases (P < 0.0001), beta-diversity changes (whole genome shotgun sequencing; P = 0.02), and fermentation products increase (P < 0.01) on an MBD as compared to a WD along with significant changes in the host enteroendocrine system (P < 0.0001). The substantial interindividual variability in metabolizable energy on the MBD is explained in part by fecal SCFAs and biomass. Our results reveal the complex host-diet-microbiome interplay that modulates energy balance.

Associations of Skeletal Muscle Mass, Muscle Fat Infiltration, Mitochondrial Energetics, and Cardiorespiratory Fitness with Liver Fat Among Older Adults.

Background: Muscle mass loss may be associated with liver fat accumulation, yet scientific consensus is lacking and evidence in older adults is scant. It is unclear which muscle characteristics might contribute to this association in older adults. Methods: We associated comprehensive muscle-related phenotypes including muscle mass normalized to body weight (D 3 -creatine dilution), muscle fat infiltration (MRI), carbohydrate-supported muscle mitochondrial maximal oxidative phosphorylation (respirometry), and cardiorespiratory fitness (VO 2 peak) with liver fat among older adults. Linear regression models adjusted for age, gender, technician (respirometry only), daily minutes of moderate to vigorous physical activity, and prediabetes/diabetes status tested main effects and interactions of each independent variable with waist circumference (high: women-≥88 cm, men-≥102 cm) and gender. Results: Among older adults aged 75 (IQR 73, 79 years; 59.8% women), muscle mass and liver fat were not associated overall but were positively associated among participants with a high waist circumference (ß: 25.2; 95%CI 11.7, 40.4; p =.0002; N=362). Muscle fat infiltration and liver fat were positively associated (ß: 15.2; 95%CI 6.8, 24.3; p =.0003; N=378). Carbohydrate-supported maximum oxidative phosphorylation and VO 2 peak (adjusted ß: -12.9; 95%CI -20.3, -4.8; p =0.003; N=361) were inversely associated with liver fat; adjustment attenuated the estimate for maximum oxidative phosphorylation although the point estimate remained negative (ß: -4.0; 95%CI -11.6, 4.2; p =0.32; N=321). Conclusions: Skeletal muscle-related characteristics are metabolically relevant factors linked to liver fat in older adults. Future research should confirm our results to determine whether trials targeting mechanisms common to liver and muscle fat accumulation are warranted.

Intake and adherence to energy and nutrient recommendations among women and men with binge-type eating disorders and healthy controls.

BACKGROUND & AIMS: Research quantifying dietary intake in individuals with bulimia nervosa and binge-eating disorder (i.e., binge-type eating disorders) is surprisingly scant. We assessed the dietary intake of women and men with binge-type eating disorders in a large case-control study and compared them with healthy controls. We also evaluated the extent to which their dietary intake adhered to the Nordic Nutrition Recommendations. Among cases, we assessed the relationship of binge eating frequency with energy and macronutrient intake. METHODS: We derived the total daily energy, macro-, and micronutrient intake of 430 cases with binge-type eating disorders (women: n = 391, men: n = 39) and 1227 frequency-matched controls (women: n = 1,213, men: n = 14) who completed the MiniMeal-Q, a validated food frequency questionnaire. We calculated mean intake for men and women and, in women, compared mean intake of energy and nutrients between cases and controls using linear regression. We calculated the proportion of women and men who met the recommended intake levels from the NNR, and compared these proportions in female cases and controls using logistic regression. We used linear regression to examine energy and macronutrient intake of women with varying frequencies of current binge-eating. RESULTS: Female, but not male cases, had a higher mean intake of total energy/day compared with controls and higher intake than recommended. The majority in all groups (male and female cases and controls) exceeded saturated fat recommendations, and did not meet recommendations for omega-3 fatty acid intake. Among all groups, adherence was low for vitamin D, selenium, and salt. Iron and folate intake was low among the majority of women, especially controls. Female cases with ≥4 binge-eating episodes in the past 28 days had higher intake of energy and percent carbohydrates, and lower intake of percent fat, compared to cases with no binge-eating episodes in the past month. CONCLUSIONS: Higher than recommended total daily energy intake among women with binge-type eating disorders may lead to weight gain and downstream health complications, if persistent. In most women, iron and folate intake was insufficient, which may have negative consequences for reproductive health. We found suboptimal adherence for key nutrients that are important to limit (saturated fat and salt) or meet (omega-3 fatty acids) for cardiovascular and overall health in all groups. Nutrition counseling should form an important pillar of treatment to assist with normalization of eating patterns and may also benefit individuals without eating disorders to optimize nutrient intake for long term health promotion.

Design of the Advancing Care for Type 1 Diabetes and Obesity Network energy metabolism and sequential multiple assignment randomized trial nutrition pilot studies: An integrated approach to develop weight management solutions for individuals with type 1 diabetes.

Young adults with type 1 diabetes (T1D) often have difficulty co-managing weight and glycemia. The prevalence of overweight and obesity among individuals with T1D now parallels that of the general population and contributes to dyslipidemia, insulin resistance, and risk for cardiovascular disease. There is a compelling need to develop a program of research designed to optimize two key outcomes-weight management and glycemia-and to address the underlying metabolic processes and behavioral challenges unique to people with T1D. For an intervention addressing these dual outcomes to be effective, it must be appropriate to the unique metabolic phenotype of T1D, and to biological and behavioral responses to glycemia (including hypoglycemia) that relate to weight management. The intervention must also be safe, feasible, and accepted by young adults with T1D. In 2015, we established a consortium called ACT1ON: Advancing Care for Type 1 Diabetes and Obesity Network, a transdisciplinary team of scientists at multiple institutions. The ACT1ON consortium designed a multi-phase study which, in parallel, evaluated the mechanistic aspects of the unique metabolism and energy requirements of individuals with T1D, alongside a rigorous adaptive behavioral intervention to simultaneously facilitate weight management while optimizing glycemia. This manuscript describes the design of our integrative study-comprised of an inpatient mechanistic phase and an outpatient behavioral phase-to generate metabolic, behavioral, feasibility, and acceptability data to support a future, fully powered sequential, multiple assignment, randomized trial to evaluate the best approaches to prevent and treat obesity while co-managing glycemia in people with T1D. Clinicaltrials.gov identifiers: NCT03651622 and NCT03379792. The present study references can be found here: https://clinicaltrials.gov/ct2/show/NCT03651622 https://clinicaltrials.gov/ct2/show/NCT03379792?term=NCT03379792&draw=2&rank=1 Submission Category: "Study Design, Statistical Design, Study Protocols".

Association of Insulin Regimen and Estimated Body Fat Over Time among Youths and Young Adults with Type 1 Diabetes: The SEARCH for Diabetes in Youth Study.

AIMS: To explore how changes in insulin regimen are associated with estimated adiposity over time among youths and young adults with type 1 diabetes and whether any associations differ according to sex. MATERIALS AND METHODS: Longitudinal data were analyzed from youths and young adults with type 1 diabetes in the SEARCH for Diabetes in Youth study. Participants were classified according to insulin regimen categorized as exclusive pump ("pump only"), exclusive injections ("injections only"), injection-pump transition ("injections-pump"), or pump-injection transition ("pump-injections") for each follow-up visit completed. Estimated body fat percentage (eBFP) was calculated using validated equations. Sex-specific, linear mixed effects models examined the relationship between the insulin regimen group and change in eBFP during follow-up, adjusted for baseline eBFP, baseline insulin regimen, time-varying insulin dose, sociodemographic factors, and baseline HbA1c (≥9.0% vs. <9.0%). RESULTS: The final sample included 284 females and 304 males, of whom 80% were non-Hispanic white with mean diagnosis age of 12.7 ± 2.4 years. In fully adjusted models for females, exclusive pump use over the study duration was associated with significantly greater increases in eBFP compared to exclusive use of injections (difference in rate of change = 0.023% increase per month, 95%CI = 0.01, 0.04). Injection-to-pump transitions and pump-to-injection transitions were also associated with greater increases in eBFP compared to exclusive use of injections (difference in rate of change = 0.02%, 95%CI = 0.004, 0.03, and 0.02%; 95%CI = 0.0001, 0.04, respectively). There was no relationship between the insulin regimen and eBFP among males. CONCLUSIONS: Among females with type 1 diabetes, exclusive and partial pump use may have the unintended consequence of increasing adiposity over time compared to exclusive use of injections, independent of insulin dose.

Trends in Glycemic Control Among Youth and Young Adults With Diabetes: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: To describe temporal trends and correlates of glycemic control in youth and young adults (YYA) with youth-onset diabetes. RESEARCH DESIGN AND METHODS: The study included 6,369 participants with type 1 or type 2 diabetes from the SEARCH for Diabetes in Youth study. Participant visit data were categorized into time periods of 2002-2007, 2008-2013, and 2014-2019, diabetes durations of 1-4, 5-9, and ≥10 years, and age groups of 1-9, 10-14, 15-19, 20-24, and ≥25 years. Participants contributed one randomly selected data point to each duration and age group per time period. Multivariable regression models were used to test differences in hemoglobin A1c (HbA1c) over time by diabetes type. Models were adjusted for site, age, sex, race/ethnicity, household income, health insurance status, insulin regimen, and diabetes duration, overall and stratified for each diabetes duration and age group. RESULTS: Adjusted mean HbA1c for the 2014-2019 cohort of YYA with type 1 diabetes was 8.8 ± 0.04%. YYA with type 1 diabetes in the 10-14-, 15-19-, and 20-24-year-old age groups from the 2014-2019 cohort had worse glycemic control than the 2002-2007 cohort. Race/ethnicity, household income, and treatment regimen predicted differences in glycemic control in participants with type 1 diabetes from the 2014-2019 cohort. Adjusted mean HbA1c was 8.6 ± 0.12% for 2014-2019 YYA with type 2 diabetes. Participants aged ≥25 years with type 2 diabetes had worse glycemic control relative to the 2008-2013 cohort. Only treatment regimen was associated with differences in glycemic control in participants with type 2 diabetes. CONCLUSIONS: Despite advances in diabetes technologies, medications, and dissemination of more aggressive glycemic targets, many current YYA are less likely to achieve desired glycemic control relative to earlier cohorts.