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An Overview of Diet and Physical Activity for Healthy Weight in Adolescents and Young Adults with Type 1 Diabetes: Lessons Learned from the ACT1ON Consortium.
Bishop, FK, Addala, A, Corbin, KD, Muntis, FR, Pratley, RE, Riddell, MC, Mayer-Davis, EJ, Maahs, DM, Zaharieva, DP
Nutrients. 2023;(11)
Abstract
The prevalence of overweight and obesity in young people with type 1 diabetes (T1D) now parallels that of the general population. Excess adiposity increases the risk of cardiovascular disease, which is already elevated up to 10-fold in T1D, underscoring a compelling need to address weight management as part of routine T1D care. Sustainable weight management requires both diet and physical activity (PA). Diet and PA approaches must be optimized towards the underlying metabolic and behavioral challenges unique to T1D to support glycemic control throughout the day. Diet strategies for people with T1D need to take into consideration glycemic management, metabolic status, clinical goals, personal preferences, and sociocultural considerations. A major barrier to weight management in this high-risk population is the challenge of integrating regular PA with day-to-day management of T1D. Specifically, exercise poses a substantial challenge due to the increased risk of hypoglycemia and/or hyperglycemia. Indeed, about two-thirds of individuals with T1D do not engage in the recommended amount of PA. Hypoglycemia presents a serious health risk, yet prevention and treatment often necessitates the consumption of additional calories, which may prohibit weight loss over time. Exercising safely is a concern and challenge with weight management and maintaining cardiometabolic health for individuals living with T1D and many healthcare professionals. Thus, a tremendous opportunity exists to improve exercise participation and cardiometabolic outcomes in this population. This article will review dietary strategies, the role of combined PA and diet for weight management, current resources for PA and glucose management, barriers to PA adherence in adults with T1D, as well as findings and lessons learned from the Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON).
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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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Reprogramming the Human Gut Microbiome Reduces Dietary Energy Harvest.
Corbin, KD, Carnero, EA, Dirks, B, Igudesman, D, Yi, F, Marcus, A, Davis, TL, Pratley, RE, Rittmann, BE, Krajmalnik-Brown, R, et al
Research square. 2023
Abstract
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.
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Indices of hepatic steatosis and fibrosis in prediabetes and association with diabetes development in the vitamin D and type 2 diabetes study.
Corbin, KD, Pittas, AG, Desouza, C, Grdinovac, KK, Herzig, KH, Kashyap, SR, Kim, SH, Nelson, J, Rasouli, N, Vickery, EM, et al
Journal of diabetes and its complications. 2023;(6):108475
Abstract
AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity that leads to poor outcomes in people at high risk for development of type 2 diabetes (T2D). Vitamin D is a possible mediator. In the vitamin D and type 2 diabetes study (D2d), we investigated the relationship of baseline indices of NAFLD with incident T2D and whether the effect of vitamin D on diabetes was modified by NAFLD. METHODS Cross-sectional associations of indices of NAFLD with glycemia and vitamin D status were assessed in 3972 individuals screened for the D2d study. In those with prediabetes randomized to vitamin D or placebo (n = 2423), we examined longitudinal associations of NAFLD indices with incident T2D. We used validated non-invasive scores to assess steatosis [(hepatic steatosis index (HSI); NAFLD-liver fat score (NAFLD-LFS)] and advanced fibrosis [fibrosis-4 (FIB-4) index; AST to Platelet Ratio Index (APRI)]. RESULTS Eighty-five percent of screened participants had likely steatosis by HSI and 71 % by NAFLD-LFS; 3 % were likely to have advanced fibrosis by FIB-4 and 1.2 % by APRI. FIB-4 indicated that 20.4 % of individuals require further follow up to assess liver health. Steatosis and fibrosis scores were higher among participants with worse glycemia. The NAFLD-LFS and APRI predicted development of diabetes (hazard ratios [95%CI] 1.35 [1.07, 1.70]; P = 0.012) and 2.36 (1.23, 4.54; P = 0.010), respectively). The effect of vitamin D on diabetes risk was not modified by baseline NAFLD indices. Individuals with likely steatosis had a smaller increase in serum 25-hydroxyvitamin D level in response to vitamin D than those without steatosis. CONCLUSIONS The predicted high prevalence of steatosis, the need for further fibrosis workup, and the relationship between liver health and incident T2D suggest that routine screening with clinically accessible scores may be an important strategy to reduce disease burden.
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Glucagon-like peptide-1/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: A randomized trial.
Corbin, KD, Carnero, EA, Allerton, TD, Tillner, J, Bock, CP, Luyet, PP, Göbel, B, Hall, KD, Parsons, SA, Ravussin, E, et al
Obesity (Silver Spring, Md.). 2023;(2):350-362
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OBJECTIVE This study tested the hypothesis that treatment with the glucagon-like peptide-1/glucagon receptor agonist SAR425899 would lead to a smaller decrease in sleeping metabolic rate (SMR; kilocalories/day) than expected from the loss of lean and fat mass (metabolic adaptation). METHODS This Phase 1b, double-blind, randomized, placebo-controlled study was conducted at two centers in inpatient metabolic wards. Thirty-five healthy males and females with overweight and obesity (age = 36.5 ± 7.1 years) were randomized to a calorie-reduced diet (-1000 kcal/d) and escalating doses (0.06-0.2 mg/d) of SAR425899 (n = 17) or placebo (n = 18) for 19 days. SMR was measured by whole-room calorimetry. RESULTS Both groups lost weight (-3.68 ± 1.37 kg placebo; -4.83 ± 1.44 kg SAR425899). Those treated with SAR425899 lost more weight, fat mass, and fat free mass (p < 0.05) owing to a greater achieved energy deficit than planned. The SAR425899 group had a smaller reduction in body composition-adjusted SMR (p = 0.002) as compared with placebo, but not 24-hour energy expenditure. Fat oxidation and ketogenesis increased in both groups, with significantly greater increases with SAR425899 (p < 0.05). CONCLUSIONS SAR425899 led to reduced selective metabolic adaptation and increased lipid oxidation, which are believed to be beneficial for weight loss and weight-loss maintenance.
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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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More hypoglycemia not associated with increasing estimated adiposity in youth with type 1 diabetes.
Sarteau, AC, Kahkoska, AR, Crandell, J, Igudesman, D, Corbin, KD, Kichler, JC, Maahs, DM, Muntis, F, Pratley, R, Seid, M, et al
Pediatric research. 2023;(3):708-714
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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.
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Cardiorenal outcomes by indices of liver steatosis and fibrosis in individuals with type 2 diabetes and atherosclerotic cardiovascular disease: Analyses from VERTIS CV, a randomized trial of the sodium-glucose cotransporter-2 inhibitor ertugliflozin.
Corbin, KD, Dagogo-Jack, S, Cannon, CP, Cherney, DZI, Cosentino, F, Frederich, R, Liu, J, Pong, A, Lin, J, Cater, NB, et al
Diabetes, obesity & metabolism. 2023;(3):758-766
Abstract
AIM: To conduct a post hoc analysis to explore indices of hepatic steatosis/fibrosis and cardiorenal outcomes in the VERTIS CV study. MATERIALS AND METHODS Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. Liver steatosis and fibrosis were assessed post hoc using the hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) index to explore associations with cardiorenal outcomes (ertugliflozin and placebo data pooled, intention-to-treat analysis set). Cardiorenal outcomes (major adverse CV events [MACE]; hospitalization for heart failure [HHF]/CV death; CV death; HHF; and a composite kidney outcome) were stratified by baseline HSI and FIB-4 quartiles (Q1-Q4). Change in liver indices and enzymes over time were assessed (for ertugliflozin vs. placebo). RESULTS Amongst 8246 participants, the mean age was 64.4 years, body mass index 32.0 kg/m2 , HSI 44.0 and FIB-4 score 1.34. The hazard ratios (HRs) for MACE, HHF/CV death, CV death, and HHF by FIB-4 score quartile (Q4 vs. Q1) were 1.48 (95% confidence interval [CI] 1.25, 1.76), 2.0 (95% CI 1.63, 2.51), 1.85 (95% CI 1.45, 2.36), and 2.94 (95% CI 1.98, 4.37), respectively (P < 0.0001 for all). With HSI, the incidence of HHF was higher in Q4 versus Q1 (HR 1.52 [95% CI 1.07, 2.17]; P < 0.05). The kidney composite outcome did not differ across FIB-4 or HSI quartiles. Liver enzymes and HSI decreased over time with ertugliflozin. CONCLUSION In VERTIS CV, higher FIB-4 score was associated with CV events. HSI correlated with HHF. Neither measure was associated with the composite kidney outcome. Ertugliflozin was associated with a reduction in liver enzymes and HSI.
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Weight Loss and Weight Regain in Usual Clinical Practice: Results From the TARGET-NASH Observational Cohort.
Malespin, MH, Barritt, AS, Watkins, SE, Schoen, C, Tincopa, MA, Corbin, KD, Mospan, AR, Munoz, B, Trinh, HN, Weiss, LM, et al
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022;(10):2393-2395.e4
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First-line treatment for nonalcoholic fatty liver disease (NAFLD) focuses on weight loss through lifestyle modifications.1,2 Weight loss ≥5% results in reduction of steatosis and weight loss ≥10% has been associated with improvement in hepatic inflammation and fibrosis.3 The incidence and sustainability of weight loss among patients with NAFLD were estimated and associating factors identified.
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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".