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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.
Igudesman, D, Crandell, J, Corbin, KD, Zaharieva, DP, Addala, A, Thomas, JM, Casu, A, Kirkman, MS, Pokaprakarn, T, Riddell, MC, et al
Diabetes, obesity & metabolism. 2023;(3):688-699
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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.
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Associations of Dietary Intake with the Intestinal Microbiota and Short-Chain Fatty Acids Among Young Adults with Type 1 Diabetes and Overweight or Obesity.
Igudesman, D, Crandell, JL, Corbin, KD, Hooper, J, Thomas, JM, Bulik, CM, Pence, BW, Pratley, RE, Kosorok, MR, Maahs, DM, et al
The Journal of nutrition. 2023;(4):1178-1188
Abstract
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.
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Exposure to models' positive facial expressions whilst eating a raw vegetable increases children's acceptance and consumption of the modelled vegetable.
Edwards, KL, Thomas, JM, Higgs, S, Blissett, J
Appetite. 2022;:105779
Abstract
Research has shown that seeing positive facial expressions (FEs) towards food increased children's desire to eat foods rated as disliked. However, the effect of adults' positive FEs whilst eating a raw vegetable on children's acceptance and intake of nutritious foods that are less preferred (e.g., vegetables) remains to be established. This study aimed to examine the effect of models' FEs eating raw broccoli on children's acceptance and intake of raw broccoli. 111 children aged 4-6 years (64 male, 47 female) were randomised to watch a video of unfamiliar adult models eating raw broccoli with a positive or neutral facial expression (FE), or a non-food control video. Children's acceptance and intake of raw broccoli was assessed. Data about parent and child characteristics was provided by parents. There was a main effect of FE type on children's frequency of tastes (p = .03) and intake of broccoli (p = .02). Children who were exposed to models eating broccoli with positive FEs had greater frequency of tastes (p = .04) and intake of broccoli (p = .03), than children in the control condition, but not compared to children in the neutral FE condition (p > .05). There was no effect of positive FEs on children's willingness to try broccoli (p > .05). These findings suggest that observing others enjoy a commonly disliked vegetable can encourage children's tastes and intake of the vegetable. Thus, exposing children to others enjoying vegetables could be a useful strategy for encouraging healthier eating in children. Further work is needed to determine whether a single exposure is sufficient and whether these effects are sustained over time.
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The effect of intranasal insulin on appetite and mood in women with and without obesity: an experimental medicine study.
Schneider, E, Spetter, MS, Martin, E, Sapey, E, Yip, KP, Manolopoulos, KN, Tahrani, AA, Thomas, JM, Lee, M, Hallschmid, M, et al
International journal of obesity (2005). 2022;(7):1319-1327
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BACKGROUND/OBJECTIVES Intranasal (IN) administration of insulin decreases appetite in humans, but the underlying mechanisms are unclear, and it is unknown whether IN insulin affects the food intake of women with obesity. SUBJECTS/METHODS In a double-blind, placebo-controlled, crossover design, participants (35 lean women and 17 women with obesity) were randomized to receive 160 IU/1.6 mL of IN insulin or placebo in a counterbalanced order in the post prandial state. The effects of IN insulin on cookie intake, appetite, mood, food reward, cognition and neural activity were assessed. RESULTS IN insulin in the post prandial state reduced cookie intake, appetite and food reward relative to placebo and these effects were more pronounced for women with obesity compared with lean women. IN insulin also improved mood in women with obesity. In both BMI groups, IN insulin increased neural activity in the insula when viewing food pictures. IN insulin did not affect cognitive function. CONCLUSIONS These results suggest that IN insulin decreases palatable food intake when satiated by reducing food reward and that women with obesity may be more sensitive to this effect than lean women. Further investigation of the therapeutic potential of IN insulin for weight management in women with obesity is warranted.
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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.
Corbin, KD, Igudesman, D, Addala, A, Casu, A, Crandell, J, Kosorok, MR, Maahs, DM, Pokaprakarn, T, Pratley, RE, Souris, KJ, et al
Contemporary clinical trials. 2022;:106765
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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".
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Using repeated visual exposure, rewards and modelling in a mobile application to increase vegetable acceptance in children.
Farrow, C, Belcher, E, Coulthard, H, Thomas, JM, Lumsden, J, Hakobyan, L, Haycraft, E
Appetite. 2019;:104327
Abstract
Children are not consuming the recommended amounts of fruit and vegetables. Repeated visual exposure, modelling, and rewards have been shown to be effective at increasing vegetable acceptance in young children. The aim of this study was to assess the effectiveness of an evidence-based mobile application (Vegetable Maths Masters) which builds on these principles to increase children's liking and acceptance of vegetables. Seventy-four children (37 male, 37 female) aged 3-6 years old were randomised to play with either the vegetable app or a similar control app that did not include any foods. Children played their allocated game for 10 min. Liking and acceptance of the vegetables used in Vegetable Maths Masters (carrot and sweetcorn) and other vegetables which were not used in the game (yellow pepper and tomato) were measured pre- and post-play in both groups. Parents provided data about their child's food fussiness and previous exposure to the foods being used. Children who played with the Vegetable Maths Masters app consumed significantly more vegetables after playing with the app and reported significant increases in their liking of vegetables, relative to the control group. The effect of the Vegetable Maths Masters app on the change in consumption of vegetables was mediated by the change in liking of vegetables. These findings suggest that evidence-based mobile apps can provide an effective tool for increasing children's liking and consumption of vegetables in the short-term. Further work is now required to establish whether these effects are maintained over time.
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The 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) reduces palatable food consumption and BOLD fMRI responses to food images in healthy female volunteers.
Thomas, JM, Dourish, CT, Tomlinson, J, Hassan-Smith, Z, Hansen, PC, Higgs, S
Psychopharmacology. 2018;(1):257-267
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RATIONALE Brain 5-HT2C receptors form part of a neural network that controls eating behaviour. 5-HT2C receptor agonists decrease food intake by activating proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, but recent research in rodents has suggested that 5-HT2C receptor agonists may also act via dopaminergic circuitry to reduce the rewarding value of food and other reinforcers. No mechanistic studies on the effects of 5-HT2C agonists on food intake in humans have been conducted to date. OBJECTIVES The present study examined the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) on food consumption, eating microstructure and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to food pictures in healthy female volunteers. METHODS In a double-blind, placebo-controlled, crossover design, participants were randomized immediately after screening to receive oral mCPP (30mg) in a single morning dose, or placebo, in a counterbalanced order. Test foods were served from a Universal Eating Monitor (UEM) that measured eating rate and fMRI BOLD signals to the sight of food and non-food images were recorded. RESULTS mCPP decreased rated appetite and intake of a palatable snack eaten in the absence of hunger but had no significant effect on the consumption of a pasta lunch (although pasta eating rate was reduced). mCPP also decreased BOLD fMRI responses to the sight of food pictures in areas of reward-associated circuitry. A post hoc analysis identified individual variability in the response to mCPP (exploratory responder-non-responder analysis). Some participants did not reduce their cookie intake after treatment with mCPP and this lack of response was associated with enhanced ratings of cookie pleasantness and enhanced baseline BOLD responses to food images in key reward and appetite circuitry. CONCLUSIONS These results suggest that 5-HT2C receptor activation in humans inhibits food reward-related responding and that further investigation of stratification of responding to mCPP and other 5-HT2C receptor agonists is warranted.
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Targeting risk factors for type 2 diabetes in American Indian youth: the Tribal Turning Point pilot study.
Sauder, KA, Dabelea, D, Bailey-Callahan, R, Kanott Lambert, S, Powell, J, James, R, Percy, C, Jenks, BF, Testaverde, L, Thomas, JM, et al
Pediatric obesity. 2018;(5):321-329
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BACKGROUND American Indian (AI) youth are at high risk for type 2 diabetes. OBJECTIVES To partner with Eastern Band of Cherokee Indians and Navajo Nation to develop a culturally sensitive behavioural intervention for youth (Tribal Turning Point; TTP) and assess feasibility in an 8-month randomized pilot study. METHODS We enrolled 62 overweight/obese AI children (7-10 years) who participated with ≥1 parent/primary caregiver. Intervention participants (n = 29) attended 12 group classes and five individual sessions. Control participants (n = 33) attended three health and safety group sessions. We analysed group differences for changes in anthropometrics (BMI, BMI z-score, waist circumference), cardiometabolic (insulin, glucose, blood pressure) and behavioural (physical activity and dietary self-efficacy) outcomes. RESULTS Study retention was 97%, and intervention group attendance averaged 84%. We observed significant treatment effects (p = 0.02) for BMI and BMI z-score: BMI increased in control (+1.0 kg m-2 , p < 0.001) but not intervention participants (+0.3 kg m-2 , p = 0.13); BMI z-score decreased in intervention (-0.17, p = 0.004) but not control participants (0.01, p = 0.82). There were no treatment effects for cardiometabolic or behavioural outcomes. CONCLUSIONS We demonstrated that a behavioural intervention is feasible to deliver and improved obesity measures in AI youth. Future work should evaluate TTP for effectiveness, sustainability and long-term impact in expanded tribal settings.
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Efficacy of the Flexible Lifestyles Empowering Change intervention on metabolic and psychosocial outcomes in adolescents with type 1 diabetes (FLEX): a randomised controlled trial.
Mayer-Davis, EJ, Maahs, DM, Seid, M, Crandell, J, Bishop, FK, Driscoll, KA, Hunter, CM, Kichler, JC, Standiford, D, Thomas, JM, et al
The Lancet. Child & adolescent health. 2018;(9):635-646
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BACKGROUND Adolescents with type 1 diabetes commonly have poor glycaemic control. We aimed to test the efficacy of a newly developed adaptive behavioral intervention (Flexible Lifestyles Empowering Change; FLEX) on metabolic and psychosocial outcomes in adolescents with type 1 diabetes. METHODS Young people (13-16 years, type 1 diabetes duration >1 year, HbA1c of 64-119 mmol/mol [8·0-13·0%], and without other serious medical conditions or pregnancy) from two clinical sites (Colorado and Ohio, USA) were eligible for enrolment. One caregiver was required to participate actively in the study. Adolescent participants were randomly assigned to the FLEX intervention, which used motivational interviewing and problem-solving skills training to enhance patients' self-management, or usual care control. Intervention fidelity was assessed by a behavioral psychologist with specific expertise in motivational interviewing and who was not otherwise involved in the study via audiotaped sessions. The primary outcome was measurement of glycated haemoglobin A1c (HbA1c) at 18 months. Secondary outcomes included motivation and intention, problem solving skills, self-management behaviors, symptoms of depression, health related quality of life, fear of hypoglycemia, diabetes family conflict, risk factors for T1D complications (BMI, blood pressure, and plasma lipids), and hypoglycemia derived from continuous glucose monitoring (percent time below 3·0 and 3·9 mmol/l [54 and 70 mg/dl]). Intention-to-treat analyses used mixed effects models, with fixed effects including site, timepoint, intervention group, intervention by timepoint, and baseline level of primary (HbA1c) or secondary outcomes (α=0·05). FLEX is registered on clinicaltrials.gov, number NCT01286350. FINDINGS Young people recruited from May 1, 2014 to April 4, 2016 were randomly assigned to FLEX (n=130) or usual care control (n=128). Mean diabetes duration was 6·4 (SD 3·8) years, and 71% (181 out of 256) of patients used insulin pump therapy. Retention was 93%, with 241 out of 258 completing the 18-month assessment. The intervention fidelity score was 4·40 of 5·00 for motivational interviewing and 97% for session content. At 18 months, HbA1c was not significantly different between intervention (83 [13] mmol/mol at baseline; 84 [19] mmol/mol at follow-up); and control (80 [14] mmol/mol at baseline; 82 [17] mmol/mol at follow-up); change in intervention versus control was -0·7 mmol/mol (95% CI -4·7 to 3·4, p=0·75). The intervention was associated with improved scores for motivation (p=0·011), problem solving (p=0·024), diabetes self-management profile (p=0·013), youth report of overall quality of life (p=0·0089), selected domains related to fear of hypoglycaemia (p=0·036 for youth's helplessness or worry; p=0·0051 for parent's efforts to maintain high blood glucose), parent report of diabetes family conflict (p=0·0001), total cholesterol (p=0·038), and diastolic blood pressure (p=0·015). A total of 54 serious adverse events were identified; 34 of these were diabetes-related, including low blood glucose requiring assistance (n=3) and high blood glucose with diabetic ketoacidosis and emergency response (n=25). INTERPRETATION The FLEX intervention did not significantly change HbA1c among these adolescents with elevated HbA1c, but did positively affect several psychosocial outcomes over 18 months. Further analyses will provide information regarding drivers of positive response to the intervention and will point to future directions for improvement in the approach. FUNDING National Institutes of Health and National Institute of Diabetes Digestive Diseases and Kidney and the Helmsley Charitable Trust.
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Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women.
Alway, SE, McCrory, JL, Kearcher, K, Vickers, A, Frear, B, Gilleland, DL, Bonner, DE, Thomas, JM, Donley, DA, Lively, MW, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2017;(12):1595-1606
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Older men (n = 12) and women (n = 18) 65-80 years of age completed 12 weeks of exercise and took either a placebo or resveratrol (RSV) (500 mg/d) to test the hypothesis that RSV treatment combined with exercise would increase mitochondrial density, muscle fatigue resistance, and cardiovascular function more than exercise alone. Contrary to our hypothesis, aerobic and resistance exercise coupled with RSV treatment did not reduce cardiovascular risk further than exercise alone. However, exercise added to RSV treatment improved the indices of mitochondrial density, and muscle fatigue resistance more than placebo and exercise treatments. In addition, subjects that were treated with RSV had an increase in knee extensor muscle peak torque (8%), average peak torque (14%), and power (14%) after training, whereas exercise did not increase these parameters in the placebo-treated older subjects. Furthermore, exercise combined with RSV significantly improved mean fiber area and total myonuclei by 45.3% and 20%, respectively, in muscle fibers from the vastus lateralis of older subjects. Together, these data indicate a novel anabolic role of RSV in exercise-induced adaptations of older persons and this suggests that RSV combined with exercise might provide a better approach for reversing sarcopenia than exercise alone.