-
1.
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
Abstract
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.
-
2.
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
Abstract
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.
-
3.
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.
Irwin, A, Igudesman, D, Crandell, J, Kichler, JC, Kahkoska, AR, Burger, K, Zaharieva, DP, Addala, A, Mayer-Davis, EJ
Pediatric diabetes. 2022;(4):516-526
Abstract
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.
-
4.
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
Abstract
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".
-
5.
A multi-component, community-engaged intervention to reduce cardiovascular disease risk in perimenopausal Latinas: pilot study protocol.
Cortés, YI, Berry, DC, Perreira, KM, Stuebe, A, Stoner, L, Giscombé, CW, Crandell, J, Santíago, L, Harris, LK, Duran, M
Pilot and feasibility studies. 2021;(1):10
Abstract
BACKGROUND Cardiovascular disease (CVD) risk increases substantially during perimenopause. Latinas have a significantly worse CVD risk factor profile than non-Hispanic White women, potentially due to multiple sociocultural and environmental factors. To date, interdisciplinary interventions have not focused on improving nutrition, physical activity, stress management, and biologic CVD risk in perimenopausal Latinas. The purpose of this study is to examine the feasibility and initial efficacy of a multi-component intervention to reduce CVD risk in perimenopausal Latinas. METHODS This is a two-group, repeated measures experimental study. Eighty perimenopausal Latinas (age 40-55 years) from two community groups will be randomized: one group will complete the intervention; the other will be a wait-list control. The intervention consists of 12-weekly sessions (education, physical activity, stress management, coping skills training), followed by 3 months of continued support, and 6 months of skill maintenance on their own. The primary outcomes include arterial stiffness, blood pressure, lipids, and blood glucose. Secondary outcomes are health behaviors (nutrition, physical activity, sleep, coping strategies), self-efficacy, and other biological factors related to CVD risk (adiposity, C-reactive protein, hair cortisol, vasomotor symptoms). We will assess changes in outcomes from Time 1 (baseline) to Time 2 (6 months) and Time 3 (12 months) using general linear mixed models to test the hypotheses. We will also evaluate the feasibility of the intervention by assessing enrollment and retention rates, barriers, and facilitators to enrollment, intervention fidelity, the suitability of study procedures, and participant satisfaction with the intervention and study protocol. We hypothesize the intervention group will decrease biologic CVD risk and improve health behaviors and self-efficacy significantly more than the wait-list control. DISCUSSION Results from this study will contribute to knowledge on the feasibility of behavioral interventions, including stress management and coping skills training, which could reduce CVD burden among perimenopausal Latinas. Because Hispanic/Latinos are the largest ethnic minority in the United States (US), progress regarding CVD risk among perimenopausal Latinas may lead to significant improvement in the overall CVD burden in the US. TRIAL REGISTRATION Prospectively registered, NCT04313751 (03/19/2020), Protocol version 1.0.
-
6.
Dietary intake on days with and without hypoglycemia in youth with type 1 diabetes: The Flexible Lifestyle Empowering Change trial.
Igudesman, D, Crandell, J, Zhong, VW, Cristello Sarteau, A, Kahkoska, AR, Corbin, K, Pratley, R, Kosorok, MR, Maahs, DM, Mayer-Davis, EJ
Pediatric diabetes. 2020;(8):1475-1484
-
-
Free full text
-
Abstract
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.
-
7.
Identification of clinically relevant dysglycemia phenotypes based on continuous glucose monitoring data from youth with type 1 diabetes and elevated hemoglobin A1c.
Kahkoska, AR, Adair, LA, Aiello, AE, Burger, KS, Buse, JB, Crandell, J, Maahs, DM, Nguyen, CT, Kosorok, MR, Mayer-Davis, EJ
Pediatric diabetes. 2019;(5):556-566
-
-
Free full text
-
Abstract
BACKGROUND/OBJECTIVE To identify and characterize subgroups of adolescents with type 1 diabetes (T1D) and elevated hemoglobin A1c (HbA1c) who share patterns in their continuous glucose monitoring (CGM) data as "dysglycemia phenotypes." METHODS Data were analyzed from the Flexible Lifestyles Empowering Change randomized trial. Adolescents with T1D (13-16 years, duration >1 year) and HbA1c 8% to 13% (64-119 mmol/mol) wore blinded CGM at baseline for 7 days. Participants were clustered based on eight CGM metrics measuring hypoglycemia, hyperglycemia, and glycemic variability. Clusters were characterized by their baseline features and 18 months changes in HbA1c using adjusted mixed effects models. For comparison, participants were stratified by baseline HbA1c (≤/>9.0% [75 mmol/mol]). RESULTS The study sample included 234 adolescents (49.8% female, baseline age 14.8 ± 1.1 years, baseline T1D duration 6.4 ± 3.7 years, baseline HbA1c 9.6% ± 1.2%, [81 ± 13 mmol/mol]). Three Dysglycemia Clusters were identified with significant differences across all CGM metrics (P < .001). Dysglycemia Cluster 3 (n = 40, 17.1%) showed severe hypoglycemia and glycemic variability with moderate hyperglycemia and had a lower baseline HbA1c than Clusters 1 and 2 (P < .001). This cluster showed increases in HbA1c over 18 months (p-for-interaction = 0.006). No other baseline characteristics were associated with Dysglycemia Clusters. High HbA1c was associated with lower pump use, greater insulin doses, more frequent blood glucose monitoring, lower motivation, and lower adherence to diabetes self-management (all P < .05). CONCLUSIONS There are subgroups of adolescents with T1D for which glycemic control is challenged by different aspects of dysglycemia. Enhanced understanding of demographic, behavioral, and clinical characteristics that contribute to CGM-derived dysglycemia phenotypes may reveal strategies to improve treatment.
-
8.
Dysglycemia among youth with type 1 diabetes and suboptimal glycemic control in the Flexible Lifestyle Empowering Change trial.
Kahkoska, AR, Crandell, J, Driscoll, KA, Kichler, JC, Seid, M, Mayer-Davis, EJ, Maahs, DM
Pediatric diabetes. 2019;(2):180-188
-
-
Free full text
-
Abstract
OBJECTIVE To examine the prevalence and correlates of non-severe hypoglycemia among adolescents with type 1 diabetes and suboptimal glycemic control, an understudied topic in this group. METHODS Seven days of blinded continuous glucose monitor data were analyzed in 233 adolescents at baseline of the Flexible Lifestyle Empowering Change trial (13-16 years, type 1 diabetes duration >1 year, and hemoglobin A1c [HbA1c] 8-13% [64-119 mmol]). Incidence of clinical hypoglycemia (54-69 mg/dL) and clinically serious hypoglycemia (<54 mg/dL) was defined as number of episodes ≥15 minutes. Logistic regression modeling was used to determine the correlates of long duration of hypoglycemia, categorized by median split among those who experienced hypoglycemia. RESULTS The sample was 76.1% non-Hispanic white, 49.8% female, age = 14.9 ± 1.1 years, diabetes duration = 6.4 ± 3.7 years, and HbA1c = 9.6 ± 1.2% (81 ± 13 mmol/mol). Over 7 days, 79.4% of youth experienced ≥1 hypoglycemic episodes of <70 mg/dL, and 55.4% of youth experienced ≥1 hypoglycemic episodes of <54 mg/dL. Among all adolescents, the median duration of clinical hypoglycemia and clinically serious hypoglycemia was 21.9 (range 0-250.2) and 4.3 (range 0-209.7) minutes/day, respectively. Long duration of clinical hypoglycemia (range 1.8-17.4% time overall) and clinically serious hypoglycemia (range 1.2-14.6% time overall) was associated with older age and decreasing HbA1c. Long duration of clinically serious hypoglycemia also was associated with insulin pump use. CONCLUSIONS Almost 80% of adolescents with elevated HbA1c had an episode of clinical hypoglycemia, and >50% had clinically serious hypoglycemia in a week. Increased education alongside access to emerging diabetes technologies may help to prevent hypoglycemia while improving glycemic control.
-
9.
Assessment of a Precision Medicine Analysis of a Behavioral Counseling Strategy to Improve Adherence to Diabetes Self-management Among Youth: A Post Hoc Analysis of the FLEX Trial.
Kahkoska, AR, Lawson, MT, Crandell, J, Driscoll, KA, Kichler, JC, Seid, M, Maahs, DM, Kosorok, MR, Mayer-Davis, EJ
JAMA network open. 2019;(5):e195137
-
-
Free full text
-
Abstract
IMPORTANCE The Flexible Lifestyles Empowering Change (FLEX) trial, an 18-month randomized clinical trial testing an adaptive behavioral intervention in adolescents with type 1 diabetes, showed no overall treatment effect for its primary outcome, change in hemoglobin A1c (HbA1c) percentage of total hemoglobin, but demonstrated benefit for quality of life (QoL) as a prespecified secondary outcome. OBJECTIVE To apply a novel statistical method for post hoc analysis that derives an individualized treatment rule (ITR) to identify FLEX participants who may benefit from intervention based on changes in HbA1c percentage (primary outcome), QoL, and body mass index z score (BMIz) (secondary outcomes) during 18 months. DESIGN, SETTING, AND PARTICIPANTS This multisite clinical trial enrolled 258 adolescents aged 13 to 16 years with type 1 diabetes for 1 or more years, who had literacy in English, HbA1c percentage of total hemoglobin from 8.0% to 13.0%, a participating caregiver, and no other serious medical conditions. From January 5, 2014, to April 4, 2016, 258 adolescents were recruited. The post hoc analysis excluded adolescents missing outcome measures at 18 months (2 participants [0.8%]) or continuous glucose monitoring data at baseline (40 participants [15.5%]). Data were analyzed from April to December 2018. INTERVENTIONS The FLEX intervention included a behavioral counseling strategy that integrated motivational interviewing and problem-solving skills training to increase adherence to diabetes self-management. The control condition entailed usual diabetes care. MAIN OUTCOMES AND MEASURES Subgroups of FLEX participants were derived from an ITR estimating which participants would benefit from intervention, which would benefit from control conditions, and which would be indifferent. Multiple imputation by chained equations and reinforcement learning trees were used to estimate the ITR. Subgroups based on ITR pertaining to changes during 18 months in 3 univariate outcomes (ie, HbA1c percentage, QoL, and BMIz) and a composite outcome were compared by baseline demographic, clinical, and psychosocial characteristics. RESULTS Data from 216 adolescents in the FLEX trial were reanalyzed (166 [76.9%] non-Hispanic white; 108 teenaged girls [50.0%]; mean [SD] age, 14.9 [1.1] years; mean [SD] diabetes duration, 6.3 [3.7] years). For the univariate outcomes, a large proportion of FLEX participants had equivalent predicted outcomes under intervention vs usual care settings, regardless of randomization, and were assigned to the muted group (HbA1c: 105 participants [48.6%]; QoL: 63 participants [29.2%]; BMIz: 136 participants [63.0%]). Regarding the BMIz univariate outcome, mean baseline BMIz of participants assigned to the muted group was lower than that of those assigned to the intervention and control groups (muted vs intervention: mean difference, 0.48; 95% CI, 0.21 to 0.75; P = .002; muted vs control: mean difference, 0.86; 95% CI, 0.61 to 1.11; P < .001); this group also had a higher proportion of individuals with underweight or normal weight using weight status cutoffs (95 [69.9%] in muted group vs 24 [54.6%] in intervention group and 11 [30.6%] in control group; χ24 = 24.67; P < .001). The approach identified subgroups estimated to benefit based on HbA1c percentage (54 participants [25.0%]), QoL (89 participants [41.2%]), and BMIz (44 participants [20.4%]). Regarding the HbA1c percentage outcome, participants expected to benefit from the intervention did not have significantly higher baseline HbA1c percentages than those expected to benefit from usual care (9.4% vs 9.2%; difference, 0.2%; 95% CI, -0.16% to 0.56%; P = .44). However, participants in the muted group had higher mean HbA1c percentages at baseline than those assigned to the intervention or control groups (muted vs intervention: 9.9% vs 9.4%; difference, 0.5%; 95% CI, 0.13% to 0.89%; P = .02; muted vs control; 9.9% vs 9.2%; difference, 0.7%; 95% CI, 0.34% to 1.08%; P = .001). No significant differences were found between subgroups estimated to benefit in terms of the composite outcome from the FLEX intervention (91 participants [42.1%]) vs usual care (125 participants [57.9%]). CONCLUSIONS AND RELEVANCE The precision medicine approach represents a conceptually and analytically novel approach to post hoc subgroup identification. More work is needed to understand markers of positive response to the FLEX intervention. TRIAL REGISTRATION ClinicalTrial.gov identifier: NCT01286350.
-
10.
The Flexible Lifestyle Empowering Change (FLEX) intervention for self-management in adolescents with type 1 diabetes: Trial design and baseline characteristics.
Kichler, JC, Seid, M, Crandell, J, Maahs, DM, Bishop, FK, Driscoll, KA, Standiford, D, Hunter, CM, Mayer-Davis, E
Contemporary clinical trials. 2018;:64-73
-
-
Free full text
-
Abstract
The Flexible Lifestyle Empowering Change (FLEX) Intervention Study is a multi-site randomized controlled trial to test the efficacy of an adaptive behavioral intervention to promote self-management for youth with type 1 diabetes mellitus (T1D). This paper details FLEX design, demographic characteristics of the sample, and outcome variables at baseline. Participants were randomized to either an intervention or control arm after their baseline standardized measurement visit. Baseline data for the primary (glycemic levels) and secondary outcome variables (e.g., motivation and problem-solving, health-related quality of life, risk factors associated with T1D complications) as well as the potential mediator variables (e.g., self-management behavior, family conflict and responsibility) suggest that the study sample was representative of the general population of adolescents with T1D and their parents. The FLEX adaptive intervention is an innovative application of a tailored treatment intervention designed to be readily adopted in real-world practice to meet each adolescent's individualized T1D self-management goals.
