Background
Faster‐acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with additional excipients (L‐arginine and niacinamide). In adults, faster aspart provides faster ...onset and greater early exposure and action vs IAsp.
Aim
This randomized, double‐blind, 2‐period crossover trial investigated the pharmacological properties of faster aspart vs IAsp in 12 children (6‐11 years), 13 adolescents (12‐17 years), and 15 adults (18‐64 years) with type 1 diabetes mellitus.
Methods
Subjects received 0.2 U/kg subcutaneous dosing (mean of 8.3, 12.8, and 15.6 U, respectively) immediately prior to a standardized meal (17.3 g carbohydrate/100 mL; amount adjusted by body weight).
Results
Consistently across age groups, onset of appearance occurred approximately twice‐as‐fast (5‐7 minutes earlier) and early exposure (AUCIAsp
,0‐30min; area under the IAsp curve from 0 to 30 minutes) was greater (by 78%‐147%) for faster aspart vs IAsp, with no treatment differences in total exposure (AUCIAsp
,0‐t) or maximum concentration (C
max). Two‐hour postmeal plasma glucose excursion was reduced for faster aspart vs IAsp (although only reaching statistical significance in children). In accordance with the absolute dose administered for each age group, AUCIAsp
,0‐t for faster aspart was lower in children (estimated ratio children/adults 95% confidence interval: 0.59 0.50;0.69, P < .001) and adolescents (0.78 0.67;0.90, P = .002) vs adults. No age group differences were seen in C
max (0.91 0.70;1.17, P = .445, and 0.99 0.77;1.26, P = .903). The age effect on AUCIAsp
,0‐t and C
max did not differ statistically significantly between treatments. Faster aspart and IAsp were well‐tolerated.
Conclusion
The current findings in children and adolescents suggest a potential for faster aspart to improve postprandial glycemia over current rapid‐acting insulins also in younger age groups. http://ClinicalTrials.gov identifier: NCT02035371.
Zusammenfassung
In der Pädiatrie finden die stetigen Weiterentwicklungen der Diabetestechnologien sowohl in der klinischen Erprobung als auch der therapeutischen Anwendung aufgrund des fast ...ausschließlichen Anteils an Patienten mit Typ-1-Diabetes schnell den Weg in den Alltag. Als in der Therapie allgegenwärtige Neuerung sind die intermittierend gescannten Glukosewerte, die sich mehr und mehr zur Standardmethode der Glukosebestimmung entwickeln, ein zunehmend evident wirksames Instrument. Auch die schon seit vielen Jahren in Deutschland angewendete vorausschauende Abschaltung der Basalrate in der Pumpentherapie liefert heutzutage Langzeitdaten zur Sicherheit und Effektivität, inzwischen auch von Systemen von mehr als nur einem Hersteller. Die Weiterentwicklung von Hybrid-Closed-Loop-Systemen ist Gegenstand zahlreicher Forschergruppen. Auch wenn viele davon Erfolge in der Anwendung zeigten, gelangte bisher nur ein System auf den Markt, wenn auch leider nicht den deutschen. Dieser Mangel führt mehr und mehr zu einer Nutzung frei verfügbarer Systeme, bei denen die Hardware selbst modifiziert werden muss. Gut informierte Patienten wissen um die Effektivität solcher Verfahren und gehen auch das Risiko der Nutzung nichtstandardisierter Systeme ein, da ihnen der herkömmliche Weg zu langsam erscheint. Doch auch bei diesen Systemen wurde in ersten klinischen Studien eine nachprüfbare Effektivität in der Anwendung festgestellt.
Abstract
The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels ...has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage.
Graphical Abstract
Aims/hypothesis
Hypoglycaemia during and after exercise remains a challenge. The present study evaluated the safety and efficacy of closed-loop insulin delivery during unannounced (to the closed-loop ...algorithm) afternoon physical activity and during the following night in young people with type 1 diabetes.
Methods
A randomised, two-arm, open-label, in-hospital, crossover clinical trial was performed at a single site in Slovenia. The order was randomly determined using an automated web-based programme with randomly permuted blocks of four. Allocation assignment was not masked. Children and adolescents with type 1 diabetes who were experienced insulin pump users were eligible for the trial. During four separate in-hospital visits, the participants performed two unannounced exercise protocols: moderate intensity (55% of
V
⋅
O
2
max
) and moderate intensity with integrated high-intensity sprints (55/80% of
V
⋅
O
2
max
), using the same study device either for closed-loop or open-loop insulin delivery. We investigated glycaemic control during the exercise period and the following night. The closed-loop insulin delivery was applied from 15:00 h on the day of the exercise to 13:00 h on the following day.
Results
Between 20 January and 16 June 2016, 20 eligible participants (9 female, mean age 14.2 ± 2.0 years, HbA
1c
7.7 ± 0.6% 60.0 ± 6.6 mmol/mol) were included in the trial and performed all trial-mandated activities. The median proportion of time spent in hypoglycaemia below 3.3 mmol/l was 0.00% for both treatment modalities (
p
= 0.7910). Use of the closed-loop insulin delivery system increased the proportion of time spent within the target glucose range of 3.9–10 mmol/l when compared with open-loop delivery: 84.1% (interquartile range 70.0–85.5) vs 68.7% (59.0–77.7), respectively (
p
= 0.0057), over the entire study period. This was achieved with significantly less insulin delivered via the closed-loop (
p
= 0.0123).
Conclusions/interpretation
Closed-loop insulin delivery was safe both during and after unannounced exercise protocols in the in-hospital environment, maintaining glucose values mostly within the target range without an increased risk of hypoglycaemia.
Trial registration
Clinicaltrials.gov
NCT02657083
Funding
University Medical Centre Ljubljana, Slovenian National Research Agency, and ISPAD Research Fellowship
We evaluated the safety and efficacy of day-and-night fully closed-loop insulin therapy using faster (Faster-CL) compared with standard insulin aspart (Standard-CL) in young adults with type 1 ...diabetes.
In a double-blind, randomized, crossover trial, 20 participants with type 1 diabetes on insulin pump therapy (11 females, aged 21.3 ± 2.3 years, HbA
7.5 ± 0.5% 58.5 ± 5.5 mmol/mol) underwent two 27-h inpatient periods with unannounced afternoon moderate-vigorous exercise and unannounced/uncovered meals. We compared Faster-CL and Standard-CL in random order. During both interventions, the fuzzy-logic control algorithm DreaMed GlucoSitter was used. Glucose sensor data were analyzed by intention-to-treat principle with the difference (between Faster-CL and Standard-CL) in proportion of time in range 70-180 mg/dL (TIR) over 27 h as the primary end point.
The proportion of TIR was similar for both arms: 53.3% (83% overnight) in Faster-CL and 57.9% (88% overnight) in Standard-CL (
= 0.170). The proportion of time in hypoglycemia <70 mg/dL was 0.0% for both groups. Baseline-adjusted interstitial prandial glucose increments 1 h after meals were greater in Faster-CL compared with Standard-CL (
= 0.017). The gaps between measured plasma insulin and estimated insulin-on-board levels at the beginning, at the end, and 2 h after the exercise were smaller in the Standard-CL group (
= 0.029,
= 0.003, and
= 0.004, respectively). No severe adverse events occurred.
Fully closed-loop insulin delivery using either faster or standard insulin aspart was safe and efficient in achieving near-normal glucose concentrations outside postprandial periods. The closed-loop algorithm was better adjusted to the standard insulin aspart.
: Increasing evidence points to the importance of achieving low blood glucose variability and also a low hemoglobin A1c (HbA1c) to prevent diabetic late complications. Continuous subcutaneous ...insulin infusion (CSII) is associated with lower blood glucose variability in children. Frequent indications for starting CSII in youth are recurrent hypoglycemia, need for increased flexibility, poor glycemic control, dawn phenomenon, or needle phobia. At our center, about one‐third of all patients across all age groups are currently on CSII. Although the average glycemic control is not very different from those on multiple daily injections, fewer patients are seen in the segment of very high and very low HbA1c with CSII. Across centers, the ‘recipes’ tailoring CSII treatment to individual patients and cultures are based more on experience than on evidence. However, several typical pediatric features have been identified. Patterns of the hourly basal rate and prandial insulin requirements vary with age. While many adolescents have increased requirements at dawn and dusk, young children show increasing needs in the second half of the day. Low insulin requirements, particularly in neonates, may need insulin dilution. The selection of catheters and needles has to be appropriate for the age. The opportunity to have an electronic memory read‐out of all entries and alarms offers new possibilities of therapeutic monitoring, particularly in those youth not keeping good logbooks. This feature can be helpful, if a trustful relationship between the diabetes team and the family is established.
OBJECTIVE
To describe the diabetes phenotype in Wolfram syndrome compared with type 1 diabetes, to investigate the effect of glycemic control on the neurodegenerative process, and to assess the ...genotype-phenotype correlation.
RESEARCH DESIGN AND METHODS
The clinical data of 50 patients with Wolfram syndrome-related diabetes (WSD) were reviewed and compared with the data of 24,164 patients with type 1 diabetes. Patients with a mean HbA1c during childhood and adolescence of ≤7.5 and >7.5% were compared with respect to the occurrence of additional Wolfram syndrome symptoms. The wolframin (WFS1) gene was screened for mutations in 39 patients. WFS1 genotypes were examined for correlation with age at onset of diabetes.
RESULTS
WSD was diagnosed earlier than type 1 diabetes (5.4 ± 3.8 vs. 7.9 ± 4.2 years; P < 0.001) with a lower prevalence of ketoacidosis (7 vs. 20%; P = 0.049). Mean duration of remission in WSD was 2.3 ± 2.4 vs. 1.6 ± 2.1 in type 1 diabetes (NS). Severe hypoglycemia occurred in 37 vs. 7.9% (P < 0.001). Neurologic disease progression was faster in the WSD group with a mean HbA1c >7.5% (P = 0.031). Thirteen novel WSF1 mutations were identified. Predicted functional consequence of WFS1 mutations correlated with age at WSD onset (P = 0.028).
CONCLUSIONS
Endoplasmic reticulum stress–mediated decline of β-cells in WSD occurs earlier in life than autoimmune-mediated β-cell destruction in type 1 diabetes. This study establishes a role for WFS1 in determining the age at onset of diabetes in Wolfram syndrome and identifies glucose toxicity as an accelerating feature in the progression of disease.
Most screening programs to identify individuals at risk for type 1 diabetes have targeted relatives of people living with the disease to improve yield and feasibility. However, ∼90% of those who ...develop type 1 diabetes do not have a family history. Recent successes in disease-modifying therapies to impact the course of early-stage disease have ignited the consideration of the need for and feasibility of population screening to identify those at increased risk. Existing population screening programs rely on genetic or autoantibody screening, and these have yielded significant information about disease progression and approaches for timing for screening in clinical practice. At the March 2021 Type 1 Diabetes TrialNet Steering Committee meeting, a session was held in which ongoing efforts for screening in the general population were discussed. This report reviews the background of these efforts and the details of those programs. Additionally, we present hurdles that need to be addressed for successful implementation of population screening and provide initial recommendations for individuals with positive screens so that standardized guidelines for monitoring and follow-up can be established.
Despite the increasing adoption of insulin pumps and continuous glucose monitoring devices, most people with type 1 diabetes do not achieve their glycemic goals
. This could be related to a lack of ...expertise or inadequate time for clinicians to analyze complex sensor-augmented pump data. We tested whether frequent insulin dose adjustments guided by an automated artificial intelligence-based decision support system (AI-DSS) is as effective and safe as those guided by physicians in controlling glucose levels. ADVICE4U was a six-month, multicenter, multinational, parallel, randomized controlled, non-inferiority trial in 108 participants with type 1 diabetes, aged 10-21 years and using insulin pump therapy (ClinicalTrials.gov no. NCT03003806). Participants were randomized 1:1 to receive remote insulin dose adjustment every three weeks guided by either an AI-DSS, (AI-DSS arm, n = 54) or by physicians (physician arm, n = 54). The results for the primary efficacy measure-the percentage of time spent within the target glucose range (70-180 mg dl
(3.9-10.0 mmol l
))-in the AI-DSS arm were statistically non-inferior to those in the physician arm (50.2 ± 11.1% versus 51.6 ± 11.3%, respectively, P < 1 × 10
). The percentage of readings below 54 mg dl
(<3.0 mmol l
) within the AI-DSS arm was statistically non-inferior to that in the physician arm (1.3 ± 1.4% versus 1.0 ± 0.9%, respectively, P < 0.0001). Three severe adverse events related to diabetes (two severe hypoglycemia, one diabetic ketoacidosis) were reported in the physician arm and none in the AI-DSS arm. In conclusion, use of an automated decision support tool for optimizing insulin pump settings was non-inferior to intensive insulin titration provided by physicians from specialized academic diabetes centers.
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