Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes.

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. CONCLUSIONS: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).

Parent Perspectives of School/Daycare Experiences in Young Children Newly Diagnosed With Diabetes.

OBJECTIVE: A central part of family adjustment to a new diagnosis of type 1 diabetes (T1D) is integrating T1D management into the child's school/daycare. This may be particularly challenging for young children who rely on adults for their diabetes management. This study aimed to describe parent experiences with school/daycare during the first 1.5 years following a young child's T1D diagnosis. METHODS: As part of a randomized controlled trial of a behavioral intervention, 157 parents of young children with new-onset (<2 months) T1D reported on their child's school/daycare experience at baseline and at 9- and 15-month post-randomization. We used a mixed-methods design to describe and contextualize parents' experiences with school/daycare. Qualitative data were collected via open-ended responses, and quantitative data were collected from a demographic/medical from. RESULTS: While most children were enrolled in school/daycare at all time points, over 50% of parents endorsed that T1D affected their child's enrollment, rejection, or removal from school/daycare at 9 or 15 months. We generated five themes related to parents' school/daycare experiences: Child factors, Parent factors, School/Daycare factors, Cooperation between Parents and Staff, and Socio-historical factors. Parents of younger children and those with lower subjective socioeconomic status were significantly more likely to endorse challenges with school/daycare enrollment. CONCLUSIONS: School/daycare settings present challenges for parents of young children with T1D. Changes may need to occur across contexts to support early childhood education, including advocacy resources for parents to navigate school policies, increased training for school staff, and healthcare team outreach initiatives to parents and schools.

Metformin treatment and gastrointestinal symptoms in youth: Findings from a large tertiary care referral center.

OBJECTIVES: Metformin is the only oral therapy for youth with type 2 diabetes, but up to 50% require additional agents within 2 years of diagnosis. Extended-release (XR) metformin formulations may improve adherence and tolerability-important mediators of treatment response-but data in youth is lacking. To evaluate rates of gastrointestinal (GI) symptoms in patients treated with metformin (SR and XR) and the change in GI symptoms after changes in metformin therapy. RESEARCH DESIGN AND METHODS: Retrospective chart review of youth with Type 2 or prediabetes seen in a multidisciplinary clinic during 2016-2019. RESULTS: Of 488 eligible patients, 41.4% and 21.1% were taking metformin SR and XR respectively, with most (58%, n = 178/305) taking a total daily dose of ≥1500 mg/day. Those not on metformin tended to be younger, leaner, and had lower HbA1cs than those taking metformin, p < 0.05. Thirty percentage of patients described GI symptoms, most commonly, abdominal pain and diarrhea. There was no difference in GI symptoms in those on SR versus XR (18.3% vs. 14.6%, p = 0.41). Among patients who initiated metformin, rates of GI symptoms increased (13%-33%, p = 0.001, n = 99), while rates tended to decrease when metformin was discontinued (28%-12%, p = 0.076, n = 50). Rates of GI symptoms were unchanged among those that switched from SR to XR metformin (17% vs. 14%, p = 0.6, n = 58). CONCLUSIONS: GI symptoms are common in youth with type 2 diabetes taking metformin XR and SR. Adjuncts to mitigate GI symptoms in youth on metformin therapy are needed to improve quality of life and medication adherence.

Metformin improves blood glucose by increasing incretins independent of changes in gluconeogenesis in youth with type 2 diabetes.

AIMS/HYPOTHESIS: Metformin is the only approved oral agent for youth with type 2 diabetes but its mechanism of action remains controversial. Recent data in adults suggest a primary role for the enteroinsular pathway, but there are no data in youth, in whom metformin efficacy is only ~50%. Our objectives were to compare incretin concentrations and rates of glucose production and gluconeogenesis in youth with type 2 diabetes before and after short-term metformin therapy compared with peers with normal glucose tolerance (NGT). METHODS: This is a case-control observational study in youth with type 2 diabetes who were not on metformin (n = 18) compared with youth with NGT (n = 10) who were evaluated with a 2 day protocol. A 75 g OGTT was administered to measure intact glucagon-like 1 peptide (iGLP-1), gastric inhibitory polypeptide (GIP) and peptide YY (PYY). Insulinogenic index (IGI) and whole-body insulin sensitivity were calculated using glucose and insulin levels from the OGTT. Basal rates of gluconeogenesis (2H2O), glucose production ([6,6-2H2]glucose) and whole-body lipolysis ([2H5]glycerol) were measured after an overnight fast on study day 2. Youth with type 2 diabetes (n = 9) were subsequently evaluated with an identical 2 day protocol after 3 months on the metformin study. RESULTS: Compared with individuals with NGT, those with type 2 diabetes had higher fasting (7.8 ± 2.5 vs 5.1 ± 0.3 mmol/l, mean ± SD p = 0.002) and 2 h glucose concentrations (13.8 ± 4.5 vs 5.9 ± 0.9 mmol/l, p = 0.001), higher rates of absolute gluconeogenesis (10.0 ± 1.7 vs 7.2 ± 1.1 µmol [kg fat-free mass (FFM)]-1 min-1, p < 0.001) and whole-body lipolysis (5.2 ± 0.9 vs 4.0 ± 1.4 µmol kgFFM-1 min-1, p < 0.01), but lower fasting iGLP-1 concentrations (0.5 ± 0.5 vs 1.3 ± 0.7 pmol/l, p < 0.01). Metformin decreased 2 h glucose (pre metformin 11.4 ± 2.8 vs post metformin 9.9 ± 1.9 mmol/l, p = 0.04) and was associated with ~20-50% increase in IGI (median [25th-75th percentile] pre 1.39 [0.89-1.47] vs post 1.43 [0.88-2.70], p = 0.04), fasting iGLP-1 (pre 0.3 ± 0.2 vs post 1.0 ± 0.7 pmol/l, p = 0.02), 2 h iGLP (pre 0.4 ± 0.2 vs post 1.2 ± 0.9 pmol/l, p = 0.06), fasting PYY (pre 6.3 ± 2.2 vs post 10.5 ± 4.3 pmol/l, p < 0.01) and 2 h PYY (pre 6.6 ± 2.9 vs post 9.0 ± 4.0 pmol/l, p < 0.01). There was no change in BMI, insulin sensitivity or GIP concentrations pre vs post metformin. There were no differences pre vs post metformin in rates of glucose production (15.0 ± 3.9 vs 14.9 ± 2.2 µmol kgFFM-1 min-1, p = 0.84), absolute gluconeogenesis (9.9 ± 1.8 vs 9.7 ± 1.7 µmol kgFFM-1 min-1, p = 0.76) or whole-body lipolysis (5.0 ± 0.7 vs 5.3 ± 1.3 µmol kgFFM-1 min-1, p = 0.20). Post metformin iGLP-1 and PYY concentrations in youth with type 2 diabetes were comparable to levels in youth with NGT. CONCLUSIONS/INTERPRETATION: Overall, the improved postprandial blood glucose levels and increase in incretins observed in the absence of changes in insulin sensitivity and gluconeogenesis, support an enteroinsular mechanistic pathway in youth with type 2 diabetes treated with short-term metformin.

Low cholesterol efflux capacity and abnormal lipoprotein particles in youth with type 1 diabetes: a case control study.

BACKGROUND: Patients with type 1 diabetes (T1DM) have increased mortality from cardiovascular disease (CVD). Risk factors for CVD include an elevation of LDL (LDLp) and small HDL (sHDLp) particles, and a decrease in reverse cholesterol transport i.e. HDL-cholesterol efflux capacity (CEC). Our objective was to compare lipoprotein particles and CEC between T1DM and healthy controls (HC) and to explore the associations between NMR lipid particles and cholesterol efflux. METHODS: 78 patients with T1DM and 59 HC underwent fasting lipoprotein profile testing by NMR and measurements of CEC by cell-based method. The associations between NMR lipid particles with CEC were analyzed using multivariable linear regression models. RESULTS: Youth with T1DM had higher total LDLp 724 [(563-985) vs 622 (476-794) nmol/L (P = 0.011)] (Maahs et al. in Circulation 130(17):1532-58, 2014; Shah et al. in Pediatr Diabetes 16(5):367-74, 2015), sHDLp [11.20 (5.7-15.3) vs 7.0 (3.2-13.1) µmol/L (P = 0.021)], and lower medium HDLp [11.20 (8.5-14.5) vs 12.3 (9-19.4), (P = 0.049)] and lower CEC (0.98 ± 0.11% vs 1.05 ± 0.15%, P = 0.003) compared to HC. Moreover, CEC correlated with sHDLp (ß = - 0.28, P = 0.045) and large HDLp (ß = 0.46, P < 0.001) independent of age, sex, ethnicity, BMIz, HbA1c, hsCRP and total HDLp in the diabetic cohort. CONCLUSIONS: Youth with T1DM demonstrated a more atherogenic profile including higher sHDL and LDLp and lower CEC. Future efforts should focus on considering adding lipoprotein particles and CEC in CVD risk stratification of youth with T1DM. Trial registration Clinical Trials Registration Number NCT02275091.

Quantitative Differences in the Urinary Proteome of Siblings Discordant for Type 1 Diabetes Include Lysosomal Enzymes.

Individuals with type 1 diabetes (T1D) often have higher than normal blood glucose levels, causing advanced glycation end product formation and inflammation and increasing the risk of vascular complications years or decades later. To examine the urinary proteome in juveniles with T1D for signatures indicative of inflammatory consequences of hyperglycemia, we profiled the proteome of 40 T1D patients with an average of 6.3 years after disease onset and normal or elevated HbA1C levels, in comparison with a cohort of 41 healthy siblings. Using shotgun proteomics, 1036 proteins were identified, on average, per experiment, and 50 proteins showed significant abundance differences using a Wilcoxon signed-rank test (FDR q-value ≤ 0.05). Thirteen lysosomal proteins were increased in abundance in the T1D versus control cohort. Fifteen proteins with functional roles in vascular permeability and adhesion were quantitatively changed, including CD166 antigen and angiotensin-converting enzyme 2. α-N-Acetyl-galactosaminidase and α-fucosidase 2, two differentially abundant lysosomal enzymes, were detected in western blots with often elevated quantities in the T1D versus control cohort. Increased release of proteins derived from lysosomes and vascular epithelium into urine may result from hyperglycemia-associated inflammation in the kidney vasculature.

The impact of parents' sleep quality and hypoglycemia worry on diabetes self-efficacy.

Parents of young children with type 1 diabetes (T1D) may experience poor sleep quality, possibly impacting their confidence in T1D management. This study investigated sleep characteristics among parents of children with T1D and relationships among parents' sleep quality, hypoglycemia worry, and diabetes self-efficacy. As part of baseline assessment for a randomized clinical trial (RCT) to promote parental management of T1D, 134 parents of children ≤ age 6 reported on demographics, parent sleep characteristics, hypoglycemia worry, and diabetes self-efficacy. Parents reported they slept less time than recommended by the National Sleep Foundation and endorsed greater global sleep problems than standardized norms of healthy adults; one third of parents reported their overall sleep quality was "fairly bad" or "very bad." Hypoglycemia worry and parents' sleep quality were both significantly related to diabetes self-efficacy, but parents' sleep quality did not mediate the relationship of hypoglycemia worry and diabetes self-efficacy. Many parents experience disrupted sleep that impacts their perceived ability to perform T1D management. Interventions designed to improve parental T1D self-efficacy should consider sleep and concerns about children's hypoglycemia.

Feasibility of the SMART Project: A Text Message Program for Adolescents With Type 1 Diabetes.

This study investigated response rates to the Self-Management and Research Technology Project, a 6-week text message program for adolescents with type 1 diabetes designed to provide diabetes self-management reminders and education. The rate of response to texts was high, with 78% of texts responded to during the 6-week period. Girls and participants who self-reported sending a large number of personal daily texts had higher response rates; other demographic and medical variables were unrelated to text response rates. Inclusion of mobile health technologies such as text messages in clinical care may be a unique, relevant method of intervention for youths with type 1 diabetes, regardless of age, socioeconomic status, or glycemic control.

Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes.

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and ß-cell function after therapy in AA Y-T2D. METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. ß-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2-hour oral glucose tolerance test. RESULTS: At baseline, gluconeogenesis, glucose production, and fasting and 2-hour glucose were comparable in both groups, though Met + Lira had higher hemoglobin A1C. Met + Lira had a greater decrease from baseline in fasting glucose (-2.0 ± 1.3 vs -0.6 ± 0.9 mmol/L, P = .008) and a greater increase in sigma (0.72 ± 0.68 vs -0.05 ± 0.71, P = .03). The change in fractional gluconeogenesis was similar between groups (Met + Lira: -0.36 ± 9.4 vs Met: 0.04 ± 12.3%, P = .9), and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r = 0.63, P = .003) but not gluconeogenesis or mSI. CONCLUSION: Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance ß-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed.

Effects of Low-Calorie Sweetener Restriction on Glycemic Variability and Cardiometabolic Health in Children with Type 1 Diabetes: Findings of a Pilot and Feasibility Study.

Low-calorie sweeteners (LCS) are commonly consumed by children with type 1 diabetes (T1D), yet their role in cardiometabolic health is unclear. This study examined the feasibility, acceptability, and preliminary effects of 12 weeks of LCS restriction among children with T1D. Children (n = 31) with T1D completed a two-week run-in (n = 28) and were randomly assigned to avoid LCS (LCS restriction, n = 15) or continue their usual LCS intake (n = 13). Feasibility was assessed using recruitment, retention, and adherence rates percentages. Acceptability was assessed through parents completing a qualitative interview (subset, n = 15) and a satisfaction survey at follow-up. Preliminary outcomes were between-group differences in change in average daily time-in-range (TIR) over 12 weeks (primary), and other measures of glycemic variability, lipids, inflammatory biomarkers, visceral adiposity, and dietary intake (secondary). Linear regression, unadjusted and adjusted for age, sex, race, and change in BMI, was used to compare mean changes in all outcomes between groups. LCS restriction was feasible and acceptable. No between-group differences in change in TIR or other measures of glycemic variability were observed. However, significant decreases in TNF-alpha (-0.23 ± 0.08 pg/mL) and improvements in cholesterol (-0.31 ± 0.18 mmol/L) and LDL (-0.60 ± 0.39 mmol/L) were observed with usual LCS intake, compared with LCS restriction. Those randomized to LCS restriction did not report increases in total or added sugar intake, and lower energy intake was reported in both groups (-190.8 ± 106.40 kcal LCS restriction, -245.3 ± 112.90 kcal usual LCS intake group). Decreases in percent energy from carbohydrates (-8.5 ± 2.61) and increases in percent energy from protein (3.2 ± 1.16) and fat (5.2 ± 2.02) were reported with usual LCS intake compared with LCS restriction. Twelve weeks of LCS restriction did not compromise glycemic variability or cardiometabolic outcomes in this small sample of youth with T1D. Further examination of LCS restriction among children with T1D is warranted.

Authoritative parenting, parenting stress, and self-care in pre-adolescents with type 1 diabetes.

Parent involvement in type 1 diabetes (T1DM) care leads to improved adherence; however, the manner in which parents approach illness management interactions with children must also be considered. It was hypothesized that greater use of an authoritative parenting style and less parenting stress would be associated with greater behavioral adherence and better metabolic control. Ninety-five primary caregivers of preadolescents (ages 8-11) with T1DM completed questionnaires assessing parenting style, pediatric parenting stress, and child behavioral adherence. Caregivers primarily self-identified as using an authoritative parenting style. Greater authoritative parenting was associated with greater behavioral adherence and less difficulty with pediatric parenting stress; no differences in metabolic control were observed. Greater engagement in authoritative parenting behaviors may contribute to increased age-appropriate child behavioral adherence and less pediatric parenting stress. Interventions highlighting diabetes-specific authoritative parenting techniques may enhance health outcomes and improve overall family functioning.

Promoting glycemic control in young children with type I diabetes: Results from a pilot intervention for parents.

OBJECTIVE: Nutrition and physical activity are key components of daily diabetes care in young children with type I diabetes (T1D). Normative developmental behavioral challenges related to nutrition and physical activity complicate management of T1D. The current pilot study evaluated the feasibility, acceptability, and indications of behavior change of an intervention aimed at improving nutrition and physical activity in young children with T1D. METHOD: Thirty-6 parents of young children (ages 2-5 years, M = 4.2) with T1D from 2 clinics in the Washington, DC area were randomized to receive the type One Training (TOTs) program or Usual Care (UC). Assessments included recruitment and completion rates, participant acceptability, and outcomes including glycemic variability via continuous glucose monitoring, nutritional intake via remote food photography, physical activity via accelerometers, and parental report on behavior and psychosocial functioning. RESULTS: Despite recruitment challenges, the TOTs program was feasible to administer, with high program and assessment completion rates. Acceptability ratings were very high but differed by recruitment site. Participants randomized to TOTs had an increase in percent of time in target glycemic range and reduction in behavioral feeding problems between baseline and follow-up while those randomized to UC did not. Participants in UC demonstrated a decrease in in moderate to vigorous physical activity at follow-up. CONCLUSIONS: The TOTs program demonstrated preliminary feasibility and acceptability. Future research will examine components of treatment for evidence of efficacy and target the intervention to those most likely to benefit. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Impacts of the COVID-19 Pandemic on Pediatric Type 1 Diabetes Management: A Qualitative Study.

PURPOSE: The purpose of this study was to understand impacts of the coronavirus (COVID-19) pandemic on pediatric type 1 diabetes management. METHODS: In-depth qualitative interviews were conducted with 15 parents of children (age 6-12 years) with type 1 diabetes. Parents responded to 8 open-ended questions about their experiences managing their children's type 1 diabetes during the COVID-19 pandemic. All interviews were transcribed, coded, and analyzed using qualitative thematic methods. RESULTS: Parents reported both positive and negative aspects of managing their children's type 1 diabetes during the COVID-19 pandemic. Facilitators of diabetes management included spending more time together at home and enhanced convenience of telehealth appointments and online supply ordering. Parents also described difficulties managing their children's type 1 diabetes during the COVID-19 pandemic, including a lack of structure in their child's daily routine, which led to increases in sedentary behavior. Furthermore, they reported psychosocial challenges of type 1 diabetes management, which were exacerbated by the pandemic. CONCLUSION: While the COVID-19 pandemic was described as having overall positive impacts on pediatric type 1 diabetes management, efforts to support parents in increasing children's physical activity and reducing screen time are needed, along with readily accessible mental health resources for both parents and their children with type 1 diabetes.

First STEPS: Primary Outcomes of a Randomized, Stepped-Care Behavioral Clinical Trial for Parents of Young Children With New-Onset Type 1 Diabetes.

OBJECTIVE: Despite the emotional challenges of parental adjustment to a child's type 1 diabetes diagnosis and the unique complexities of early childhood, there are few programs designed to meet the needs of parents of young children at new onset. This study evaluated First STEPS (Study of Type 1 in Early childhood and Parenting Support), a stepped-care behavioral intervention designed to support parents' psychosocial functioning and promote children's glycemic outcomes. RESEARCH DESIGN AND METHODS: Using a two-site randomized clinical trial design, parents (n = 157) of children aged 1-6 years completed baseline data within 2 months of diabetes diagnosis and were randomly assigned to intervention (n = 115) or usual care (n = 42) for 9 months. Intervention steps included: 1) peer parent coaching, with step-ups to 2) structured behavioral counseling and 3) professional consultations with a diabetes educator and psychologist, based on parent mood and child HbA1c. Participants completed follow-ups at 9 and 15 months postrandomization. Primary outcomes were parent depressive symptoms and child HbA1c. RESULTS: Depressive symptoms improved in both groups, and intervention parents had significantly lower depressive symptoms at the 9- and 15-month follow-ups compared with usual care. HbA1c decreased in both groups, but there were no between-group differences at 9 or 15 months. CONCLUSIONS: First STEPS improved parents' mood following young children's type 1 diabetes diagnosis. Results indicate likely benefits of parent coach support, supplemented by intervention intensifications, including behavioral intervention and diabetes education. This model has high potential for patient engagement. The absence of a medical intervention component may explain null findings for HbA1c; incorporating targeted behavioral support for intensive diabetes treatment may maximize intervention impact.

WITHDRAWN: Positive Impact of the Bionic Pancreas on Diabetes Control in Youth 6-17 Years Old with Type 1 Diabetes: A Multicenter Randomized Trial.

The publisher of Diabetes Technologies & Therapeutics officially withdraws the Just Accepted version of the article entitled, "Positive Impact of the Bionic Pancreas on Diabetes Control in Youth 6-17 Years Old with Type 1 Diabetes: A Multicenter Randomized Trial," by Laurel H Messer, et al. (epub 28 Jun 2022; DOI: 10.1089/dia.2022.0201) due to its erroneous release before being finalized. The correct version will be republished in due course. The publisher extends its sincerest apologies to the authors of the article and to the journal's readership for this regrettable mishap.

Positive Impact of the Bionic Pancreas on Diabetes Control in Youth 6-17 Years Old with Type 1 Diabetes: A Multicenter Randomized Trial.

Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) in youth 6-17 years old with type 1 diabetes (T1D). Research Design and Methods: In this multicenter, randomized, controlled trial, 165 youth with T1D (6-17 years old; baseline HbA1c 5.8%-12.2%; 35% using multiple daily injections, 36% using an insulin pump without automation, 4% using an insulin pump with low glucose suspend, and 25% using a hybrid closed-loop system before the study) were randomly assigned 2:1 to use BP (n = 112) with insulin aspart or insulin lispro (BP group) or to a control group (n = 53) using their personal standard care insulin delivery (SC group) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. Results: Mean HbA1c decreased from 8.1% ± 1.2% at baseline to 7.5% ± 0.7% at 13 weeks with BP versus 7.8% ± 1.1% at both baseline and 13 weeks with SC (adjusted difference = -0.5%, 95% CI -0.7% to -0.2%, P < 0.001). Participants with baseline HbA1c ≥9.0% (n = 34) decreased mean HbA1c from 9.7% ± 0.8% to 7.9% ± 0.6% after 13 weeks with BP compared with 9.7% ± 0.5% to 9.8% ± 0.8% with SC. Over 13 weeks, mean time in range (TIR) 70-180 mg/dL increased by 10% (2.4 h per day) and mean CGM glucose was reduced by 15 mg/dL with BP compared with SC (P < 0.001). Analyses of time >180 mg/dL, time >250 mg/dL, and standard deviation of CGM glucose favored BP (P < 0.001). Time <54 mg/dL was low at baseline (median 0.2%) and not significantly different between groups over 13 weeks (P = 0.24). A severe hypoglycemia event occurred in 3 (2.7%) participants in the BP group and in 1 (1.9%) in the SC group. Conclusions: In youth 6-17 years old with T1D, use of insulin-only configuration of BP improved HbA1c, TIR, and hyperglycemic metrics without increasing CGM-measured hypoglycemia compared with standard of care. Improvement in glycemic metrics was most pronounced in participants with high baseline HbA1c levels. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

Rationale and design of DRINK-T1D: A randomized clinical trial of effects of low-calorie sweetener restriction in children with type 1 diabetes.

BACKGROUND: Low-calorie sweeteners (LCSs) provide sweetness without sugar or calories and are used to replace added sugars by many children with type 1 diabetes (T1D). However, the role of LCSs in diabetes management and cardiometabolic health is unclear. OBJECTIVE: The Diabetes Research in Kids Study (DRINK-T1D) aims to investigate effects of LCS restriction on glycemic variability, visceral adiposity, lipid profiles, and systemic inflammation among children 6-12 years old with T1D. METHODS: Children with T1D, who report habitual consumption of foods and beverages containing LCSs, are recruited from the Washington Nationals Diabetes Care Complex (DCC) at Children's National Hospital (CNH) in Washington, DC. Following a phone screening and two-week run-in period involving continuation of usual LCS intake, children are randomized to 12 weeks of LCS restriction (replacement of diet beverages with still or sparkling water and avoidance of other sources of LCSs) or continued usual LCS intake (control). The primary outcome is the difference in change in glycemic variability in the LCS restriction group versus the control group. Change in glycemic variability will be assessed as the difference in daily average time-in-range (TIR), measured using continuous glucose monitoring (CGM) during two weeks at the end of the 12-week intervention, compared with during the two-week run-in period prior to randomization. Participants also complete a variety of anthropometric, metabolic, dietary, and behavioral assessments throughout the 14-week study. CONCLUSIONS: DRINK-T1D is an innovative, randomized controlled trial, evaluating effects of LCS restriction on glycemic variability and cardiometabolic health in children with T1D. Findings of DRINK-T1D will support or challenge the common practice of recommending LCS use in this patient population and will have clinically relevant implications for pediatric T1D management. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04385888.

Blood pressure during sleep is associated with arterial stiffness and urine microalbumin to creatinine ratio in youth with type 1 diabetes.

AIMS: To determine whether sleep blood pressure (BP) is associated with increased cardiovascular disease (CVD) risk in youth with type 1 diabetes (T1DM). METHODS: We enrolled youth with T1DM, 12-21 years old. Carotid-femoral Pulse Wave Velocity (PWVcf) assessed arterial stiffness, a CVD marker. Sleep systolic and diastolic BP variables were obtained from 24-hour BP Monitoring. Linear regression models analyzed the relationship of each BP variable with PWVcf, adjusted for HbA1c. Correlation of sleep BP with urine microalbumin-to-creatinine ratio (UAC) was examined. RESULTS: Nocturnal hypertension was found in 36% and abnormal dipping in 48% of the 25 participants, aged 17.7 ±â€¯2.2 years old. Sleep systolic BP [beta = 0.039, 95% Confidence Interval (CI; 0.006-0.073)], diastolic BP [beta = 0.058, 95% CI (0.003-0.114)], Mean Arterial Pressure (MAP) [beta = 0.075, 95% CI (0.018-0.131)] and MAP index [beta = 3.547, 95% CI (0.867-6.227)] were significantly associated with PWVcf. Sleep diastolic BP, load, MAP correlated with UAC. CONCLUSIONS: Blood pressure alterations during sleep are common in youth with T1DM and they are associated with arterial stiffness and UAC. Larger studies are needed to confirm our results and examine whether interventions that target sleep and night-time BP could decrease CVD risk.