Real-world use of glucagon-like peptide-1 receptor agonists in youth with type 2 diabetes is associated with short-term improvements in HbA1c.

AIM: To assess the short-term, real-world use and effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) medications in the management of type 2 diabetes (T2D) in a diverse cohort of youth. METHODS: This multicentre retrospective study analysed youth prescribed a GLP-1RA for the management of T2D at two academic paediatric diabetes centres prior to June 2022. Change in HbA1c and insulin use from baseline to first (median 91 days) and second (median 190 days) follow-up were evaluated for those taking a GLP-1RA. Multivariable linear mixed effects models adjusting for baseline sex, age, race/ethnicity, insurance, insulin regimen, metformin regimen, GLP-1RA dosing frequency and the body mass index Z-score (BMI-Z) examined the change in HbA1c for participants for up to 6 months after baseline. RESULTS: A total of 136 patients with T2D (median age 16.1 [interquartile range 13.9-18.0] years, 54% female, 56% non-Hispanic Black, 24% Hispanic, 77% with public insurance) were prescribed GLP-1RAs and taking them at first or second follow-up. Median HbA1c decreased from 7.9% to 7.6% (P < .001) at a median follow-up of 91 days (n = 109) and, among those with HbA1c available at baseline and second follow-up (n = 83), from 8.4% to 7.4%. The proportion of patients prescribed insulin decreased from baseline to the first follow-up visit (basal 69% to 60% [P = .008], prandial 46% to 38% [P = .03]). In multivariable analysis, there was a mean decrease in HbA1c by 0.09 percentage points per month (P = .005, 95% confidence interval -0.15, -0.03). CONCLUSIONS: Real-world use of GLP-1RAs in youth with T2D is associated with decreased HbA1c levels, despite challenges with access and adherence. GLP-1RA treatment may reduce insulin doses for youth with T2D.

Impact of school-supervised ultra-long-acting basal insulin injections on ketosis in youth with T1D and elevated haemoglobin A1c: A pilot study.

BACKGROUND: In youth with type 1 diabetes (T1D), high haemoglobin A1c (HbA1c) levels are associated with an increased risk for diabetic ketoacidosis (DKA). AIMS: This study examined whether daily school-supervised basal insulin injections were feasible and if they reduced the risk of morning ketosis in children and adolescents with high HbA1c levels. We hypothesized that supervised glargine and degludec would reduce the risk of ketosis and that the prolonged action of degludec would protect from ketosis after consecutive days of unsupervised injections. MATERIALS & METHODS: After a 2-4-week run-in, youth (10-18 years, HbA1c ≥ 8.5%) managing T1D with injections were randomized to school-supervised administration of degludec or glargine for 4 months. School nurses observed daily blood ß-hydroxybutyrate (BHB) and glucose checks. During COVID closures, the research team supervised procedures remotely. RESULTS: Data from 28 youth (age 14.3 ± 2.3 years, HbA1c 11.4 ± 1.9%, 64% F) were analysed. School-supervised injections of both basal insulins for 1-4 days progressively lowered the percent of participants with elevated BHB. The percent of participants with elevated BHB (≥0.6 mmol/L) after 2 days of unsupervised basal insulin doses at home was greater in the glargine than degludec group but had a high p-value (17.2% vs. 9.0%, p = 0.3). HbA1c was unchanged in both groups. DISCUSSION: In youth with T1D at high risk for DKA, daily supervised long-acting insulin administration decreased the probability of elevated ketone levels on subsequent school days, regardless of basal insulin type. A larger sample size may have demonstrated that the longer action profile of degludec would offer additional protection from ketosis during days of not attending school. CONCLUSION: Engaging school-based caregivers in management of youth with T1D on injected insulin may decrease clinically significant ketosis and minimize acute complications of diabetes.

Feasibility and Preliminary Safety of Smartphone-Based Automated Insulin Delivery in Adolescents and Children With Type 1 Diabetes.

BACKGROUND: A smartphone-based automated insulin delivery (AID) controller device can facilitate use of interoperable components and acceptance in adolescents and children. METHODS: Pediatric participants (N = 20, 8F) with type 1 diabetes were enrolled in three sequential age-based cohorts: adolescents (12-<18 years, n = 8, 5F), school-age (8-<12 years, n = 7, 2F), and young children (2-<8 years, n = 5, 1F). Participants used the interoperable artificial pancreas system (iAPS) and zone model predictive control (MPC) on an unlocked smartphone for 48 hours, consumed unrestricted meals of their choice, and engaged in various unannounced exercises. Primary outcomes and stopping criteria were defined using fingerstick blood glucose (BG) data; secondary outcomes compared continuous glucose monitoring (CGM) data with preceding sensor augmented pump (SAP) therapy. RESULTS: During AID, there was no more than one BG <50 mg/dL except in one young child participant; no instance of more than two episodes of BG ≥300 mg/dL lasting longer than 2 hours; and no adverse events. Despite large meals (total of 404.9 grams of carbs) and unannounced exercise (total of 182 minutes), overall CGM percent time in range (TIR) of 70 to 180 mg/dL during AID was statistically similar to SAP (63.5% vs 57.3%, respectively, P = .145). Overnight glucose standard deviation was 43 mg/dL (vs SAP 57.9 mg/dL, P = .009) and coefficient of variation was 25.7% (vs SAP 34.9%, P < .001). The percent time in closed-loop mode and connected to the CGM was 92.7% and 99.6%, respectively. Surveys indicated that participants and parents/guardians were satisfied with the system. CONCLUSIONS: The smartphone-based AID was feasible and safe in sequentially younger cohorts of adolescents and children. CLINICALTRIALS.GOV: NCT04255381 (https://clinicaltrials.gov/ct2/show/NCT04255381).

Safety and Glycemic Outcomes With a Tubeless Automated Insulin Delivery System in Very Young Children With Type 1 Diabetes: A Single-Arm Multicenter Clinical Trial.

OBJECTIVE: Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk for long-term complications and creating an immense management burden for caregivers. We conducted the first evaluation of the Omnipod 5 Automated Insulin Delivery System in this population. RESEARCH DESIGN AND METHODS: A total of 80 children aged 2.0-5.9 years used the investigational system in a single-arm study for 13 weeks following 14 days of baseline data collection with their usual therapy. RESULTS: There were no episodes of severe hypoglycemia or diabetic ketoacidosis. By study end, HbA1c decreased by 0.55% (6.0 mmol/mol) (P < 0.0001). Time with sensor glucose levels in target range 70-180 mg/dL increased by 10.9%, or 2.6 h/day (P < 0.0001), while time with levels <70 mg/dL declined by median 0.27% (P = 0.0204). CONCLUSIONS: Use of the automated insulin delivery system was safe, and participants experienced improved glycemic measures and reduced hypoglycemia during the study phase compared with baseline.

A Pilot Study of Youth With Type 1 Diabetes Initiating Use of a Hybrid Closed-Loop System While Receiving a Behavioral Economics Intervention.

OBJECTIVE: Many youth do not use the hybrid closed-loop system for type 1 diabetes effectively. This study evaluated the impact of financial incentives for diabetes-related tasks on use of the 670G hybrid closed-loop system and on glycemia. METHODS: At auto mode initiation and for 16 weeks thereafter, participants received a flat rate for wearing and calibrating the sensor ($1/day), administering at least 3 mealtime insulin boluses per day ($1/day), and uploading ($5/week). Weekly bonuses were given for maintaining at least 70% of the time in auto mode, which were increased for persistent auto mode use from $3/week to a maximum of $13/week. If a participant failed to maintain auto mode for a week, the rewards were reset to baseline. Data from 17 participants aged 15.9 years ± 2.5 years (baseline hemoglobin A1c [HbA1c] 8.6% ± 1.1%) were collected at 6, 12, and 16 weeks. The reinforcers were withdrawn at 16 weeks, with a follow-up assessment at 24 weeks. RESULTS: With reinforcers, the participants administered an average of at least 3 mealtime insulin boluses per day and wore the sensor over 70% of the time. However, auto mode use waned. HbA1c levels decreased by 0.5% after 6 weeks, and this improvement was maintained at 12 and 16 weeks (P < .05). Upon withdrawal of reinforcers, HbA1c levels increased back to baseline at 24 weeks. CONCLUSION: Compensation for diabetes-related tasks was associated with lower HbA1c levels, consistent administration of mealtime insulin boluses, and sustained sensor use. These results support the potential of financial rewards for improving outcomes in youth with type 1 diabetes.

A comparison of two hybrid closed-loop systems in adolescents and young adults with type 1 diabetes (FLAIR): a multicentre, randomised, crossover trial.

BACKGROUND: Management of type 1 diabetes is challenging. We compared outcomes using a commercially available hybrid closed-loop system versus a new investigational system with features potentially useful for adolescents and young adults with type 1 diabetes. METHODS: In this multinational, randomised, crossover trial (Fuzzy Logic Automated Insulin Regulation [FLAIR]), individuals aged 14-29 years old, with a clinical diagnosis of type 1 diabetes with a duration of at least 1 year, using either an insulin pump or multiple daily insulin injections, and glycated haemoglobin (HbA1c) levels of 7·0-11·0% (53-97 mmol/mol) were recruited from seven academic-based endocrinology practices, four in the USA, and one each in Germany, Israel, and Slovenia. After a run-in period to teach participants how to use the study pump and continuous glucose monitor, participants were randomly assigned (1:1) using a computer-generated sequence, with a permuted block design (block sizes of two and four), stratified by baseline HbA1c and use of a personal MiniMed 670G system (Medtronic) at enrolment, to either use of a MiniMed 670G hybrid closed-loop system (670G) or the investigational advanced hybrid closed-loop system (Medtronic) for the first 12-week period, and then participants were crossed over with no washout period, to the other group for use for another 12 weeks. Masking was not possible due to the nature of the systems used. The coprimary outcomes, measured with continuous glucose monitoring, were proportion of time that glucose levels were above 180 mg/dL (>10·0 mmol/L) during 0600 h to 2359 h (ie, daytime), tested for superiority, and proportion of time that glucose levels were below 54 mg/dL (<3·0 mmol/L) calculated over a full 24-h period, tested for non-inferiority (non-inferiority margin 2%). Analysis was by intention to treat. Safety was assessed in all participants randomly assigned to treatment. This trial is registered with ClinicalTrials.gov, NCT03040414, and is now complete. FINDINGS: Between June 3 and Aug 22, 2019, 113 individuals were enrolled into the trial. Mean age was 19 years (SD 4) and 70 (62%) of 113 participants were female. Mean proportion of time with daytime glucose levels above 180 mg/dL (>10·0 mmol/L) was 42% (SD 13) at baseline, 37% (9) during use of the 670G system, and 34% (9) during use of the advanced hybrid closed-loop system (mean difference [advanced hybrid closed-loop system minus 670G system] -3·00% [95% CI -3·97 to -2·04]; p<0·0001). Mean 24-h proportion of time with glucose levels below 54 mg/dL (<3·0 mmol/L) was 0·46% (SD 0·42) at baseline, 0·50% (0·35) during use of the 670G system, and 0·46% (0·33) during use of the advanced hybrid closed-loop system (mean difference [advanced hybrid closed-loop system minus 670G system] -0·06% [95% CI -0·11 to -0·02]; p<0·0001 for non-inferiority). One severe hypoglycaemic event occurred in the advanced hybrid closed-loop system group, determined to be unrelated to study treatment, and none occurred in the 670G group. INTERPRETATION: Hyperglycaemia was reduced without increasing hypoglycaemia in adolescents and young adults with type 1 diabetes using the investigational advanced hybrid closed-loop system compared with the commercially available MiniMed 670G system. Testing an advanced hybrid closed-loop system in populations that are underserved due to socioeconomic factors and testing during pregnancy and in individuals with impaired awareness of hypoglycaemia would advance the effective use of this technology FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases.

Glucose management for rewards: A randomized trial to improve glucose monitoring and associated self-management behaviors in adolescents with type 1 diabetes.

BACKGROUND: This randomized, controlled trial evaluated a monetary-based reinforcement intervention for increasing self-monitoring of blood glucose (SMBG) among youth with poorly controlled type 1 diabetes. METHODS: After a 2-week baseline, 60 participants were randomized to enhanced usual care (EUC) or Reinforcers. The Reinforcers group earned monetary rewards for SMBG and associated behaviors such as uploading glucose meters. Reinforcers were withdrawn at 24 weeks. A follow-up evaluation occurred at 36 weeks. RESULTS: Participants in the reinforcers group increased the proportion of days they completed ≥4 SMBG from 14.6% at baseline to 64.4%, 47.5%, and 37.8% at 6, 12, and 24 weeks, respectively. In contrast, EUC participants declined from 22.7% at baseline to 17.5%, 10.5%, and 11.1% (Ps < .01 vs EUC at all time points). Group differences were attenuated but remained significant after withdrawal of reinforcers. Effect sizes for SMBG were very large during reinforcement and large after withdrawal of reinforcers. In the reinforcers group, mean A1c dropped from 9.5% ± 1.2% at baseline to 9.0% ± 1.3% at week 6 and 9.0% ± 1.4% at week 12. For EUC, A1c was 9.2% ± 0.2% at baseline and ranged from 9.2% ± 1.5% to 9.6% ± 1.6% throughout the study (P < .05 vs EUC). Group differences in A1c were no longer significant at weeks 24 and 36. Effect sizes for A1c were small during reinforcement and also after withdrawal of reinforcement. CONCLUSIONS: Monetary-based reinforcement of adolescents with type 1 diabetes caused durable increases in SMBG. Modification of the reinforcement structure may be needed to sustain improved metabolic control in this challenging age group.

Schooling diabetes: Use of continuous glucose monitoring and remote monitors in the home and school settings.

BACKGROUND: Despite significant advances in type 1 diabetes (T1D) management, achieving targeted glycemic control in pediatric patients remains a struggle. Continuous glucose monitoring (CGM) with remote access holds the promise to address this challenge by allowing caregivers to monitor glucose, even when the child is not directly under their supervision. OBJECTIVE: To explore real-time and remote CGM practices in homes and schools, including caregiver expectations regarding this technology. SUBJECTS: Parents and daytime caregivers. METHODS: Respondents answered an anonymous survey assessing characteristics of CGM use. Cross-sectional data were collected and analyzed using quantitative and qualitative methods. RESULTS: Thirty-three parents and 17 daytime caregivers responded. Threshold alerts (alerts when patients reached certain pre-set high or low limits) were used most frequently, followed by rate of change alerts. Most parents and daytime caregivers responded to low- and high-threshold CGM alerts by confirming with a glucose meter prior to treatment; while about one-third endorsed treating lows without a confirmatory test. Most parents expected their child's daytime caregiver to respond to CGM alerts and daytime caregivers felt the parent's expectations of them were reasonable. All parents and most caregivers reported decreased overall worry/stress. Parents felt positive about CGM use and daytime caregivers felt comfortable with CGM. CONCLUSION: The positive and collaborative management reported by parents and daytime caregivers sets the stage for CGM to play an important role in the management of children with T1D both in the home and in the school settings.

An Effective Diabetic Ketoacidosis Prevention Intervention in Children With Type 1 Diabetes.

The objective of this study was to evaluate the effectiveness of a brief, office-based educational intervention to increase parent or patient recognition of the early warning signs and symptoms of diabetic ketoacidosis (DKA). Forty-two patients aged > 13 years and 34 parents of children aged ≤ 13 years were given a pretest questionnaire about their knowledge of signs and symptoms of DKA and sick day management practices. They received a brief refresher course on sick day management specific to their treatment modality (pump vs. injection) and were given a take-home flow sheet of guidelines for diabetes sick day management. Subjects were retested with the same knowledge questionnaire after 6 to 12 months. Patients or parents scored higher on the posttest than the pretest and called the emergency line for assistance more frequently (p = .032) following the intervention. Emergency department visits were significantly reduced in adolescents (p = .024). A short educational intervention and printed management tool is effective in improving sick day and DKA knowledge and appears to be effective in reducing emergency department visits by increasing utilization of a diabetes emergency line for early outpatient intervention.

Pramlintide but Not Liraglutide Suppresses Meal-Stimulated Glucagon Responses in Type 1 Diabetes.

Context: Postprandial hyperglycemia remains a challenge in type 1 diabetes (T1D) due, in part, to dysregulated increases in plasma glucagon levels after meals. Objective: This study was undertaken to examine whether 3 to 4 weeks of therapy with pramlintide or liraglutide might help to blunt postprandial hyperglycemia in T1D by suppressing plasma glucagon responses to mixed-meal feedings. Design: Two parallel studies were conducted in which participants underwent mixed-meal tolerance tests (MMTTs) without premeal bolus insulin administration before and after 3 to 4 weeks of treatment with either pramlintide (8 participants aged 20 ± 3 years, hemoglobin A1c 6.9 ± 0.5%) or liraglutide (10 participants aged 22 ± 3 years, hemoglobin A1c 7.6 ± 0.9%). Results: Compared with pretreatment responses to the MMTT, treatment with pramlintide reduced the peak increment in glucagon from 32 ± 16 to 23 ± 12 pg/mL (P < 0.02). In addition, the incremental area under the plasma glucagon curve from 0 to 120 minutes dropped from 1988 ± 590 to 737 ± 577 pg/mL/min (P < 0.001), which was accompanied by a similar reduction in the meal-stimulated increase in the plasma glucose curve from 11,963 ± 1424 mg/dL/min pretreatment vs 2493 ± 1854 mg/dL/min after treatment (P < 0.01). In contrast, treatment with liraglutide had no effect on plasma glucagon and glucose responses during the MMTT. Conclusions: Adjunctive treatment with pramlintide may provide an effective means to blunt postmeal hyperglycemia in T1D by suppressing dysregulated plasma glucagon responses. In contrast, plasma glucose and glucagon responses were unchanged after 3 to 4 weeks of treatment with liraglutide.

Disordered Eating Behaviors in Emerging Adults With Type 1 Diabetes: A Common Problem for Both Men and Women.

INTRODUCTION: Emerging adults (EA) with disordered eating behaviors (DEBs) and Type 1 diabetes (T1D) are at increased risk for severe complications of T1D, and these behaviors have been reported in EA women with T1D. Few studies, though, have included men. This study assessed the prevalence of DEB in both EA men and women with T1D. METHODS: DEB was measured with the diabetes-specific Diabetes Eating Problem Survey-Revised (DEPS-R); scores of 20 or greater indicate need for further evaluation for DEB. RESULTS: A total of 27 women and 33 men (age range = 21 ± 2.5 years) completed the DEPS-R; 27% of women and 18% of men had scores of 20 or greater (p = .23). Hemoglobin A1c level was significantly higher in subjects with elevated DEPS-R scores (10.4 ± 2.1% vs. 7.8 ± 1.3%; p < .001), and DEPS-R scores correlated with increased body mass index values (r = 0.27, p < .05). DISCUSSION: Clinicians should assess for DEB in both male and female emerging adults with T1D, especially overweight patients with poor glycemic control.

Mitigating Reductions in Glucose During Exercise on Closed-Loop Insulin Delivery: The Ex-Snacks Study.

OBJECTIVE: To assess whether snacking could be used with closed-loop (CL) insulin delivery to avoid exercise-induced reductions in plasma glucose (PG), as well as elevations in PG at the end of exercise. RESEARCH DESIGN AND METHODS: Twelve type 1 diabetes (T1D) subjects (age 13-36 years, duration 10.7 ± 8.4 years, A1c 7.4% ± 0.8% [57 ± 8.7 mmol/mol]) underwent two 105-min exercise studies while under CL control: CL alone and CL+snack. Exercise, commenced at 3 PM, consisted of four 15-min periods of brisk treadmill walking to 65%-70% HRmax (separated by three 5-min rest periods), followed by a 30-min recovery period. Fifteen to 30 g carbohydrate (Gatorade) was provided on snacking visits just before and midway through the exercise period. PG and insulin were measured every 15-20 min during the exercise studies. RESULTS: Baseline PG levels were similar for CL alone (164 ± 16 mg/dL) versus CL+snack (172 ± 11 mg/dL). During exercise, PG levels fell by 53 ± 10 mg/dL without snacking versus a modest 10 ± 13 mg/dL increase in PG with snacking (P = 0.0005); similar differences in the change in PG levels were observed at the end of recovery period. Hypoglycemia requiring rescue treatment (PG ≤60 mg/dL) during exercise occurred in three nonsnacking visits versus none with snacking. During the 75-min exercise period, insulin delivered was 1.8 ± 0.4 U for the CL+snack admission compared to 0.7 ± 0.1 U during CL alone (P = 0.002). CONCLUSION: These results support the use of a simple snacking strategy to avoid exercise-induced lowering of PG while on CL insulin delivery. Persistent insulin infusion during exercise with snacking also appears to be effective in limiting increases in PG at the end of exercise.

Testing for rewards: a pilot study to improve type 1 diabetes management in adolescents.

OBJECTIVE: To evaluate the effectiveness of monetary reinforcement to increase the frequency of self-monitoring blood glucose (SMBG). RESEARCH DESIGN AND METHODS: Ten adolescents with poorly controlled diabetes enrolled in a 12-week program in which they earned monetary reinforcers based on SMBG frequency ($0.10 per test, with bonuses for ≥4 tests per day, and $251.40 maximum). RESULTS: SMBG increased from 1.8 ± 1.0 to 4.9 ± 1.0 tests per day (P < 0.001) with 90% completing four or more tests per day. Mean A1C fell from 9.3 ± 0.9% to 8.4 ± 1.5% (P = 0.05). Adolescents and parents reported high satisfaction with procedures. CONCLUSIONS: Reinforcing adolescents for SMBG may increase testing and improve A1C.

Safety of nighttime 2-hour suspension of Basal insulin in pump-treated type 1 diabetes even in the absence of low glucose.

OBJECTIVE: An integrated sensor-augmented pump system has been introduced that interrupts basal insulin infusion for 2 h if patients fail to respond to low-glucose alarms. It has been suggested that such interruptions of basal insulin due to falsely low glucose levels detected by sensor could lead to diabetic ketoacidosis. We hypothesized that random suspension of basal insulin for 2 h in the overnight period would not lead to clinically important increases in blood ß-hydroxybutyrate levels despite widely varying glucose values prior to the suspension. RESEARCH DESIGN AND METHODS: Subjects measured blood glucose and blood ß-hydroxybutyrate levels using a meter each night at 9:00 p.m., then fasted until the next morning. On control nights, the usual basal rates were continued; on experimental nights, the basal insulin infusion was reprogrammed for a 2-h zero basal rate at random times after 11:30 p.m. RESULTS: In 17 type 1 diabetic subjects (mean age 24 ± 9 years, diabetes duration 14 ± 11 years, A1C level 7.3 ± 0.5% [56 mmol/mol]), blood glucose and blood ß-hydroxybutyrate levels were similar at 9:00 p.m. on suspend nights (144 ± 63 mg/dL and 0.09 ± 0.07 mmol/L) and nonsuspend nights (151 ± 65 mg/dL and 0.08 ± 0.06 mmol/L) (P = 0.39 and P = 0.47, respectively). Fasting morning blood glucose levels increased after suspend nights compared with nonsuspend nights (191 ± 68 vs. 141 ± 75 mg/dL, P < 0.0001), and the frequency of fasting hypoglycemia decreased the morning following suspend nights (P < 0.0001). Morning blood ß-hydroxybutyrate levels were slightly higher after suspension (0.13 ± 0.14 vs. 0.09 ± 0.11 mmol/L, P = 0.053), but the difference was not clinically important. CONCLUSIONS: Systems that suspend basal insulin for 2 h are safe and do not lead to clinically significant ketonemia even if the blood glucose level is elevated at the time of the suspension.

A review of short bowel syndrome and palliation: a case report and medication guideline.

While patients with short bowel syndrome are not common in palliative care, they can present challenges for palliative care professionals. The case presented highlights a specific difficulty encountered. Many medications are poorly absorbed from a short bowel and alternative routes of administration need to be considered. A search was conducted to identify reviews, reports, and other articles from January 1960 to February 2004. MEDLINE, Cochrane Library, and CINAHL (Cumulative Index of Nursing and Allied Health Library) and MIMs (Medimedia Australia) databases were searched. A review of major textbooks was also conducted. Information on the site of absorption, time to peak plasma concentration, alternate routes, and pharmacokinetic information is summarized and presented in table form. This case report and review should assist practitioners with the palliative management of patients with short bowel syndrome.