Equitable implementation of a precision digital health program for glucose management in individuals with newly diagnosed type 1 diabetes.

Few young people with type 1 diabetes (T1D) meet glucose targets. Continuous glucose monitoring improves glycemia, but access is not equitable. We prospectively assessed the impact of a systematic and equitable digital-health-team-based care program implementing tighter glucose targets (HbA1c < 7%), early technology use (continuous glucose monitoring starts <1 month after diagnosis) and remote patient monitoring on glycemia in young people with newly diagnosed T1D enrolled in the Teamwork, Targets, Technology, and Tight Control (4T Study 1). Primary outcome was HbA1c change from 4 to 12 months after diagnosis; the secondary outcome was achieving the HbA1c targets. The 4T Study 1 cohort (36.8% Hispanic and 35.3% publicly insured) had a mean HbA1c of 6.58%, 64% with HbA1c < 7% and mean time in the range (70-180 mg dl-1) of 68% at 1 year after diagnosis. Clinical implementation of the 4T Study 1 met the prespecified primary outcome and improved glycemia without unexpected serious adverse events. The strategies in the 4T Study 1 can be used to implement systematic and equitable care for individuals with T1D and translate to care for other chronic diseases. ClinicalTrials.gov registration: NCT04336969 .

"It changed everything we do": A mixed methods study of youth and parent experiences with a pilot exercise education intervention following new diagnosis of type 1 diabetes.

AIMS: This pilot study delivered a comprehensive exercise education intervention to youth with new-onset type 1 diabetes (T1D) and their parents to increase knowledge and confidence with physical activity (PA) shortly after diagnosis. METHODS: Youth initiated continuous glucose monitoring (CGM) and PA trackers within 1 month of diagnosis. Youth and their parents received the 4-session intervention over 12 months. Participants completed self-report questionnaires at baseline, 6- and 12-months. Surveys were analyzed using linear mixed effects models. Semi-structured interviews and focus groups explored experiences with the exercise education intervention. Groups and interviews were audio-recorded, transcribed, and analyzed using content analysis. RESULTS: A total of 16 parents (aged 46 ± 7 years; 88 % female; 67 % non-Hispanic White) and 17 youth (aged 14 ± 2 years; 41 % female; 65 % non-Hispanic White) participated. Worry about hypoglycemia did not worsen throughout the study duration. Parents and youth reported increased knowledge and confidence in managing T1D safely and preventing hypoglycemia during PA following receiving the tailored exercise education intervention. CONCLUSION: This study assessed a novel structured exercise education program for youth and their parents shortly following T1D diagnosis. These results support the broad translation and acceptability of a structured exercise education program in new-onset T1D.

Diabetic Ketoacidosis at Diagnosis in Youth with Type 1 Diabetes Is Associated with a Higher Hemoglobin A1c Even with Intensive Insulin Management.

Introduction: Diabetic ketoacidosis (DKA) at diagnosis is associated with short- and long-term complications. We assessed the relationship between DKA status and hemoglobin A1c (A1c) levels in the first year following type 1 diabetes (T1D) diagnosis. Research Design and Methods: The Pilot Teamwork, Targets, Technology, and Tight Control (4T) study offered continuous glucose monitoring to youth with T1D within 1 month of diagnosis. A1c levels were compared between historical (n = 271) and Pilot 4T (n = 135) cohorts stratified by DKA status at diagnosis (DKA: historical = 94, 4T = 67 versus without DKA: historical = 177, 4T = 68). A1c was evaluated using locally estimated scatter plot smoothing. Change in A1c from 4 to 12 months postdiagnosis was evaluated using a linear mixed model. Results: Median age was 9.7 (interquartile range [IQR]: 6.6, 12.7) versus 9.7 (IQR: 6.8, 12.7) years, 49% versus 47% female, 44% versus 39% non-Hispanic White in historical versus Pilot 4T. In historical and 4T cohorts, DKA at diagnosis demonstrated higher A1c at 6 (0.5% [95% confidence interval (CI): 0.21-0.79; P < 0.01] and 0.38% [95% CI: 0.02-0.74; P = 0.04], respectively), and 12 months (0.62% [95% CI: -0.06 to 1.29; P = 0.07] and 0.39% [95% CI: -0.32 to 1.10; P = 0.29], respectively). The highest % time in range (TIR; 70-180 mg/dL) was seen between weeks 15-20 (69%) versus 25-30 (75%) postdiagnosis for youth with versus without DKA in Pilot 4T, respectively. Conclusions: Pilot 4T improved A1c outcomes versus the historical cohort, but those with DKA at diagnosis had persistently elevated A1c throughout the study and intensive diabetes management did not mitigate this difference. DKA prevention at diagnosis may translate into better glycemic outcomes in the first-year postdiagnosis. Clinical Trial Registration: clinicaltrials.gov: NCT04336969.

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.

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).

Disparities in Hemoglobin A1c Levels in the First Year After Diagnosis Among Youths With Type 1 Diabetes Offered Continuous Glucose Monitoring.

Importance: Continuous glucose monitoring (CGM) is associated with improvements in hemoglobin A1c (HbA1c) in youths with type 1 diabetes (T1D); however, youths from minoritized racial and ethnic groups and those with public insurance face greater barriers to CGM access. Early initiation of and access to CGM may reduce disparities in CGM uptake and improve diabetes outcomes. Objective: To determine whether HbA1c decreases differed by ethnicity and insurance status among a cohort of youths newly diagnosed with T1D and provided CGM. Design, Setting, and Participants: This cohort study used data from the Teamwork, Targets, Technology, and Tight Control (4T) study, a clinical research program that aims to initiate CGM within 1 month of T1D diagnosis. All youths with new-onset T1D diagnosed between July 25, 2018, and June 15, 2020, at Stanford Children's Hospital, a single-site, freestanding children's hospital in California, were approached to enroll in the Pilot-4T study and were followed for 12 months. Data analysis was performed and completed on June 3, 2022. Exposures: All eligible participants were offered CGM within 1 month of diabetes diagnosis. Main Outcomes and Measures: To assess HbA1c change over the study period, analyses were stratified by ethnicity (Hispanic vs non-Hispanic) or insurance status (public vs private) to compare the Pilot-4T cohort with a historical cohort of 272 youths diagnosed with T1D between June 1, 2014, and December 28, 2016. Results: The Pilot-4T cohort comprised 135 youths, with a median age of 9.7 years (IQR, 6.8-12.7 years) at diagnosis. There were 71 boys (52.6%) and 64 girls (47.4%). Based on self-report, participants' race was categorized as Asian or Pacific Islander (19 [14.1%]), White (62 [45.9%]), or other race (39 [28.9%]); race was missing or not reported for 15 participants (11.1%). Participants also self-reported their ethnicity as Hispanic (29 [21.5%]) or non-Hispanic (92 [68.1%]). A total of 104 participants (77.0%) had private insurance and 31 (23.0%) had public insurance. Compared with the historical cohort, similar reductions in HbA1c at 6, 9, and 12 months postdiagnosis were observed for Hispanic individuals (estimated difference, -0.26% [95% CI, -1.05% to 0.43%], -0.60% [-1.46% to 0.21%], and -0.15% [-1.48% to 0.80%]) and non-Hispanic individuals (estimated difference, -0.27% [95% CI, -0.62% to 0.10%], -0.50% [-0.81% to -0.11%], and -0.47% [-0.91% to 0.06%]) in the Pilot-4T cohort. Similar reductions in HbA1c at 6, 9, and 12 months postdiagnosis were also observed for publicly insured individuals (estimated difference, -0.52% [95% CI, -1.22% to 0.15%], -0.38% [-1.26% to 0.33%], and -0.57% [-2.08% to 0.74%]) and privately insured individuals (estimated difference, -0.34% [95% CI, -0.67% to 0.03%], -0.57% [-0.85% to -0.26%], and -0.43% [-0.85% to 0.01%]) in the Pilot-4T cohort. Hispanic youths in the Pilot-4T cohort had higher HbA1c at 6, 9, and 12 months postdiagnosis than non-Hispanic youths (estimated difference, 0.28% [95% CI, -0.46% to 0.86%], 0.63% [0.02% to 1.20%], and 1.39% [0.37% to 1.96%]), as did publicly insured youths compared with privately insured youths (estimated difference, 0.39% [95% CI, -0.23% to 0.99%], 0.95% [0.28% to 1.45%], and 1.16% [-0.09% to 2.13%]). Conclusions and Relevance: The findings of this cohort study suggest that CGM initiation soon after diagnosis is associated with similar improvements in HbA1c for Hispanic and non-Hispanic youths as well as for publicly and privately insured youths. These results further suggest that equitable access to CGM soon after T1D diagnosis may be a first step to improve HbA1c for all youths but is unlikely to eliminate disparities entirely. Trial Registration: ClinicalTrials.gov Identifier: NCT04336969.

'Much more convenient, just as effective': Experiences of starting continuous glucose monitoring remotely following Type 1 diabetes diagnosis.

AIM: Initiating continuous glucose monitoring (CGM) shortly after Type 1 diabetes diagnosis has glycaemic and quality of life benefits for youth with Type 1 diabetes and their families. The SARS-CoV-2 pandemic led to a rapid shift to virtual delivery of CGM initiation visits. We aimed to understand parents' experiences receiving virtual care to initiate CGM within 30 days of diagnosis. METHODS: We held focus groups and interviews using a semi-structured interview guide with parents of youth who initiated CGM over telehealth within 30 days of diagnosis during the SARS-CoV-2 pandemic. Questions aimed to explore experiences of starting CGM virtually. Groups and interviews were audio-recorded, transcribed and analysed using thematic analysis. RESULTS: Participants were 16 English-speaking parents (age 43 ± 6 years; 63% female) of 15 youth (age 9 ± 4 years; 47% female; 47% non-Hispanic White, 20% Hispanic, 13% Asian, 7% Black, 13% other). They described multiple benefits of the virtual visit including convenient access to high-quality care; integrating Type 1 diabetes care into daily life; and being in the comfort of home. A minority experienced challenges with virtual care delivery; most preferred the virtual format. Participants expressed that clinics should offer a choice of virtual or in-person to families initiating CGM in the future. CONCLUSION: Most parents appreciated receiving CGM initiation education via telehealth and felt it should be an option offered to all families. Further efforts can continue to enhance CGM initiation teaching virtually to address identified barriers.

Advancements and future directions in the teamwork, targets, technology, and tight control-the 4T study: improving clinical outcomes in newly diagnosed pediatric type 1 diabetes.

PURPOSE OF REVIEW: The benefits of intensive diabetes management have been established by the Diabetes Control and Complications Trial. However, challenges with optimizing glycemic management in youth with type 1 diabetes (T1D) remain across pediatric clinics in the United States. This article will review our Teamwork, Targets, Technology, and Tight Control (4T) study that implements emerging diabetes technology into clinical practice with a team approach to sustain tight glycemic control from the onset of T1D and beyond to optimize clinical outcomes. RECENT FINDINGS: During the 4T Pilot study and study 1, our team-based approach to intensive target setting, education, and remote data review has led to significant improvements in hemoglobin A1c throughout the first year of T1D diagnosis in youth, as well as family and provider satisfaction. SUMMARY: The next steps include refinement of the current 4T study 1, developing a business case, and broader implementation of the 4T study. In study 2, we are including a more pragmatic cadence of remote data review and disseminating exercise education and activity tracking to both English- and Spanish-speaking families. The overall goal is to create and implement a translatable program that can facilitate better outcomes for pediatric clinics across the USA.

Type 1 diabetes is associated with an increase in cholesterol absorption markers but a decrease in cholesterol synthesis markers in a young adult population.

BACKGROUND: To optimize treatment and prevent cardiovascular disease in subjects with type 1 diabetes, it is important to determine how cholesterol metabolism changes with type 1 diabetes. OBJECTIVE: The objective of the study was to compare plasma levels of campesterol and ß-sitosterol, markers of cholesterol absorption, as well as lathosterol, a marker of cholesterol synthesis, in youth with and without type 1 diabetes. METHODS: Serum samples were obtained from adolescent subjects with type 1 diabetes (n = 175, mean age 15.2 years, mean duration of diabetes 8.2 years) and without diabetes (n = 74, mean age 15.4 years). Campesterol, ß-sitosterol, and lathosterol, were measured using targeted liquid chromatography tandem mass spectrometry, compared between groups, and correlated with the available cardiometabolic variables. RESULTS: Campesterol and ß-sitosterol levels were 30% higher in subjects with type 1 diabetes and positively correlated with hemoglobin A1c levels. In contrast, lathosterol levels were 20% lower in subjects with type 1 diabetes and positively correlated with triglycerides, body mass index, and systolic blood pressure. CONCLUSION: Plasma markers suggest that cholesterol absorption is increased, whereas cholesterol synthesis is decreased in adolescent subjects with type 1 diabetes. Further studies to address the impact of these changes on the relative efficacy of cholesterol absorption and synthesis inhibitors in subjects with type 1 diabetes are urgently needed.

Elevated copeptin, arterial stiffness, and elevated albumin excretion in adolescents with type 1 diabetes.

OBJECTIVE: We sought to evaluate copeptin concentrations in adolescents with and without type 1 diabetes (T1D) and examine the associations between copeptin and measures of arterial stiffness and kidney dysfunction. RESEARCH DESIGN AND METHODS: This analysis included 169 adolescents with T1D (12-19 years of age, 59% girls, mean HbA1c 9.0 ± 1.5% and diabetes duration of 8.6 ± 2.9 years), in addition to 61 controls without T1D. Arterial stiffness including carotid-femoral pulse wave velocity (CF-PWV), carotid-radial PWV (CR-PWV), augmentation index normalized to heart rate of 75 bpm (AIx@HR75), and brachial artery distensibility (BAD). Serum copeptin, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) by serum creatinine and cystatin C were also assessed. RESULTS: Compared to controls, adolescents with T1D had higher median (Q1-Q3) copeptin (7.5 [5.2-11.3] vs 6.4 [4.8-8.3] pmol/L, P = .01), mean ± SD eGFR (121 ± 23 vs 112 ± 16 mL/min/1.73m2 , P = .002) and lower BAD (7.1 ± 1.3 vs 7.2 ± 1.2%, P = .02). Adolescents with T1D in the in high tertile copeptin group (>9.1 pmol/L) had higher AIx@HR75 (10.7 ± 1.2 vs 5 ± 1.2, P = .001), CR-PWV (5.30 ± 1.0 vs 5.18 ± 1.0 m/s, P = .04), and UACR (12 ± 1 vs 8 ± 1 mg/g, P = .025) compared to those in low tertile (<5.8 pmol/L) after adjusting for age, sex, and eGFR. Copeptin inversely associated with CF-PWV independent of age, sex, eGFR, SBP, and HbA1c in T1D adolescents. CONCLUSIONS: Our data demonstrate that elevated copeptin was associated with worse arterial stiffness in adolescents with T1D. These findings suggest that copeptin could improve CVD risk stratification in adolescents with T1D.

Serum uromodulin is associated with urinary albumin excretion in adolescents with type 1 diabetes.

Early diabetic kidney disease (DKD) occurs in adolescents with type 1 diabetes (T1D). Lower serum uromodulin (SUMOD) predicts DKD progression in adults with T1D. In this study, we demonstrate that lower SUMOD is associated with urinary albumin excretion in adolescents with T1D, suggesting a potential relationship between SUMOD and early kidney dysfunction in T1D youth.

Two-step recruitment process optimizes retention in FLEX clinical trial.

INTRODUCTION: The Flexible Lifestyle Empowering Change Study (FLEX) is a multi-site randomized controlled trial to test the efficacy of an adaptive behavioral intervention to promote self-management and improve glycemic control for adolescents with type 1 diabetes mellitus. A two-step recruitment process was used to optimize study retention by facilitating informed decision-making regarding participation. METHODS: Those who expressed interest at first contact were given more detailed study information followed by telephone calls to the adolescents and their parents to answer questions and explore potential barriers to participation before making a decision regarding study enrollment. RESULTS: Of 694 eligible adolescents who were invited to participate, 397 (57.2%) expressed interest when initially contacted (Step 1). Upon completion of the follow-up telephone calls (Step 2), 276 (39.8%) still agreed to participate; and 258 (37.2%) enrolled and completed a baseline visit with a parent/guardian. Completion rates for measurement visits remained high throughout the study, with an end-of-study retention rate of 93.4%; and only 12 (4.7%) families withdrew from the study. CONCLUSION: The two-step recruitment process encourages potential participants to thoughtfully evaluate their willingness to participate, as well as their ability to make a commitment to the full completion of study requirements. When demonstrating the efficacy of a randomized controlled trial, it may be preferable to accept lower recruitment rates in order to optimize retention rates. The additional time and effort required to implement this two-step process is worthwhile. With a high retention rate, we can be more confident that the outcomes of the randomized controlled trial actually reflect the impact of the intervention.

Efficacy of the Flexible Lifestyles Empowering Change intervention on metabolic and psychosocial outcomes in adolescents with type 1 diabetes (FLEX): a randomised controlled trial.

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.

Understanding antagonism and synergism: A qualitative assessment of weight management in youth with Type 1 diabetes mellitus.

AIMS: No current clinical guidelines focus on weight management in youth with type 1 diabetes mellitus (T1DM). Our aim was to characterize the patient-perceived experience and barriers to weight management in youth with T1DM. METHODS: Participants were recruited from the University of North Carolina (n = 16, 56% female, 60% White, 50% insulin pump users, mean age 14.8 years, mean HbA1c 8.5% (69 mmol/mol)) and the University of Colorado (n = 18, 50% female, 80% white, 53% pump users, mean age 15.3 years, mean HbA1c 9.3% (78 mmol/mol)). Focus groups were stratified by sex and weight status (BMI cutoff = 25). Discussions were guided by a standardized set of questions, audio-taped, transcribed, and analyzed thematically using inductive qualitative methods. RESULTS: Youth with T1DM expressed four interrelated themes of antagonism between type 1 diabetes and weight management: dysregulated appetite, disruption of blood glucose levels associated with changing diet/exercise, hypoglycemia as a barrier to weight loss, and the overwhelming nature of dual management of weight and glycemic control, and two interrelated themes of synergism: improvement in shared, underlying heath behaviors and exercise as a tool for weight and glycemic control. Variation in emphasis of specific thematic elements was greatest across sex. Youth identified five major components of a weight management program for T1DM: intensified glucose management, healthy diet with known carbohydrate content, exercise, individualization and flexibility, and psychosocial and peer support. CONCLUSIONS: There is critical need for personalized, T1DM-specific weight recommendations to overcome disease-specific barriers to weight management in the context of T1DM.

Dynamic changes in retinal vessel diameter during acute hyperglycemia in type 1 diabetes.

AIMS: To investigate changes in retinal vessel diameter during acute hyperglycemia in patients with type 1 diabetes. METHODS: We conducted a study on 11 subjects with type 1 diabetes. Euglycemia was maintained for 3h followed by induction of hyperglycemia and simultaneous bolus of rapid acting insulin. Two fundus photos were captured during euglycemia and five fundus photos, blood glucose and blood pressure were taken every 30min for 2.5h post-prandial. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were measured over the study visit and examined using generalized linear mixed models. RESULTS: In a multivariate mixed model, mean CRAE and CRVE were reduced at 90min post-prandial in both zones B and C. In repeated measures analysis, arterioles exhibited a significant association with change in vessel caliber per change in blood glucose. Inconsistent effects of blood pressure on vessel diameter were also measured. CONCLUSIONS: We document a change in retinal vessel diameter during acute hyperglycemia in persons with type 1 diabetes. Larger controlled studies are required to further investigate this phenomenon and to more accurately assess if hyperglycemia has direct effects on retinal vessel diameter.

The Flexible Lifestyle Empowering Change (FLEX) intervention for self-management in adolescents with type 1 diabetes: Trial design and baseline characteristics.

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.

Biopsychosocial Aspects of Weight Management in Type 1 Diabetes: a Review and Next Steps.

PURPOSE OF REVIEW: This review aims to summarize the type 1 diabetes (T1D) and weight literature with an emphasis on barriers associated with weight management, the unique T1D-specific factors that impact weight loss success, maladaptive and adaptive strategies for weight loss, and interventions to promote weight loss. RECENT FINDINGS: Weight gain is associated with intensive insulin therapy. Overweight and obese weight status in individuals with T1D is higher than the general population and prevalence is rising. A variety of demographic (e.g., female sex), clinical (e.g., greater insulin needs), environmental (e.g., skipping meals), and psychosocial (e.g., depression, stress) factors are associated with overweight/obese weight status in T1D. Fear of hypoglycemia is a significant barrier to engagement in physical activity. Studies evaluating adaptive weight loss strategies in people with T1D are limited. There is a growing literature highlighting the prevalence and seriousness of overweight and obesity among both youth and adults with T1D. There is an urgent need to develop evidence-based weight management guidelines and interventions that address the unique concerns of individuals with T1D and that concurrently address glycemic control.

Influences of gender on cardiovascular disease risk factors in adolescents with and without type 1 diabetes.

BACKGROUND: Women with type 1 diabetes (T1D) have a four-fold increased risk for cardiovascular disease (CVD) compared to non-diabetic (non-DM) women, as opposed to double the risk in T1D men compared to non-DM men. It is unclear how early in life CVD risk differences begin in T1D females. Therefore, our objective was to compare CVD risk factors in adolescents with and without T1D to determine the effects of gender on CVD risk factors. METHODS: The study included 300 subjects with T1D (age 15.4±2.1 years, 50 % male, 80 % non-Hispanic White (NHW), glycated hemoglobin (A1c) 8.9±1.6 %, diabetes duration 8.8±3.0 years, BMI Z-score 0.62±0.77) and 100non-DM controls (age 15.4±2.1 years, 47 % male, 69 % NHW, BMI Z-score 0.29±1.04). CVD risk factors were compared by diabetes status and gender. Multivariate linear regression analyses were used to determine if relationships between diabetes status and CVD risk factors differed by gender independent of differences in A1c and BMI. RESULTS: Differences in CVD risk factors between T1D subjects and non-DM controls were more pronounced in girls. Compared to boys with T1D and non-DM girls, T1D girls had higher A1c (9.0 % vs. 8.6 % and 5.1 %, respectively), BMI Z-score (0.70 vs. 0.47 and 0.27), LDL-c (95 vs. 82 and 81 mg/dL), total cholesterol (171 vs. 153 and 150 mg/dL), DBP (68 vs. 67 and 63 mmHg), and hs-CRP (1.15 vs. 0.57 and 0.54 mg/dL) after adjusting for Tanner stage, smoking status, and race/ethnicity (p <0.05 for all). In T1D girls, differences in lipids, DBP, and hs-CRP persisted even after adjusting for centered A1c and BMI Z-score. Testing interactions between gender and T1D with CVD risk factors indicated that differences were greater between girls with T1D and non-DM compared to differences between boys with T1D and non-DM. Overall, observed increases in CVD risk factors in T1D girls remained after further adjustment for centered A1c or BMI Z-score. CONCLUSIONS: Interventions targeting CVD risk factors in addition to lowering HbA1c and maintaining healthy BMI are needed for youth with T1D. The increased CVD risk factors seen in adolescent girls with T1D in particular argues for earlier intervention to prevent later increased risk of CVD in women with T1D.

Hyperfiltration and uricosuria in adolescents with type 1 diabetes.

BACKGROUND: Urine uric acid (UUA) has been implicated in the pathogenesis of diabetic nephropathy via its effect on tubular cells. We hypothesized that the UUA level would be higher in adolescents with type 1 diabetes (T1D) than in those without T1D. We also hypothesized that UUA and fractional uric acid excretion (FeUA) would be higher in adolescents with T1D and hyperfiltration [estimated glomerular filtration rate (eGFR) ≥141 mL/min/1.73 m(2)] than in those without hyperfiltration. METHODS: The UUA concentration was determined and FeUA calculated in adolescents with (n = 239) and without T1D (n = 75). The eGFR was calculated using the Zappitelli equation based on serum creatinine and cystatin C concentrations. RESULTS: Compared to the non-diabetic adolescents enrolled in the study, those with T1D had a higher eGFR (mean ± standard deviation: 120 ± 22 vs. 112 ± 16 mL/min/1.73 m(2); p = 0.0006), lower urine pH (6.2 ± 0.8 vs. 6.5 ± 1.0; p = 0.01), and higher UUA (37.7 ± 18.6 vs. 32.8 ± 18.1 mg/dL; p = 0.049) and FeUA (median [interquartile range]: 6.2 [4.3-8.7] vs. 5.2 [3.6-7.0] %; p = 0.02). Among adolescents with T1D, those with hyperfiltration had higher median FeUA (8.6 [5.2-9.9] vs. 6.0 [4.2-8.3] %; p = 0.02) than those without hyperfiltration. CONCLUSIONS: The adolescents with T1D enrolled in the study had higher eGFR, higher UUA and more acidic urine than the non-diabetic controls, which may have increased their risk of UUA crystallization. Adolescents with T1D and hyperfiltration had higher FeUA than those without hyperfiltration. These hypothesis-generating observations may suggest a potential pathophysiologic association between uricosuria and hyperfiltration.

Periodontal Microorganisms and Cardiovascular Risk Markers in Youth With Type 1 Diabetes and Without Diabetes.

BACKGROUND: A subset of periodontal microorganisms has been associated with cardiovascular disease (CVD), which is the leading complication of type 1 diabetes (t1DM). The authors therefore evaluated the association between periodontal microorganism groups and early markers of CVD in youth with t1DM. METHODS: A cross-sectional analysis was conducted among youth aged 12 to 19 years at enrollment; 105 had t1DM for ≥5 years and were seeking care at the Barbara Davis Center, University of Colorado, from 2009 to 2011, and 71 did not have diabetes. Subgingival plaque samples were assessed for counts of 41 periodontal microorganisms using DNA-DNA hybridization. Microorganisms were classified using cluster analysis into four groups named red-orange, orange-green, blue/other, and yellow/other, modified from Socransky's color scheme for periodontal microorganisms. Subsamples (54 with t1DM and 48 without diabetes) also received a periodontal examination at the University of Colorado School of Dental Medicine. RESULTS: Participants were ≈15 years old on average, and 74% were white. Mean periodontal probing depth was 2 mm (SE 0.02), and 17% had bleeding on probing. In multivariable analyses, glycated hemoglobin (HbA1c) was inversely associated with the yellow/other cluster (microorganisms that are not associated with periodontal disease) among youth with t1DM. Blood pressure, triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol were not associated with microorganism clusters in this group. HbA1c was not associated with periodontal microorganism clusters among youth without diabetes. CONCLUSION: Among youth with t1DM who had good oral health, periodontal microorganisms were not associated with CVD risk factors.