Fast-acting Insulin Aspart Research Articles

Sensor-derived glycaemic metrics in pregnant women with type 1 diabetes randomised to faster acting insulin aspart or insulin aspart-A secondary analysis of the CopenFast trial.

We compared sensor-derived glycaemic metrics in pregnant women with type 1 diabetes (T1D) randomised to faster acting insulin aspart (faster aspart) or insulin aspart (IAsp). A pre-planned secondary analysis of the CopenFast trial included women with T1D using intermittently scanned continuous glucose monitoring (isCGM) during pregnancy. Glycaemic metrics, including time in range (TIRp, 3.5-7.8 mmol/L) and time below range in pregnancy (TBRp, <3.5 mmol/L), were evaluated in the intervals: from randomisation (median 9.5 weeks, interquartile range 9.0-11.0) to 21 weeks, from 22 to 33 weeks and from 34 to 37 weeks. In total, 113 (91%) of 124 women using isCGM in the original trial were included. At randomisation, glycaemic metrics were comparable in both groups. Women randomised to faster aspart achieved higher TIRp from 22 to 33 weeks (estimated treatment difference 5.1% [95% confidence interval 0.3; 9.7], p = 0.04) and mean TIRp >70% from randomisation to 21 weeks onwards, while this was achieved after 34 weeks in women randomised to IAsp. TBRp remained stable around 4% throughout pregnancy in both groups. One (2%) versus 5 (9%) experienced ≥1 severe hypoglycaemic event (odds ratio 0.93 [-0.2; -0.01], p = 0.04). Infant birthweight standard deviation score was lower in the faster aspart group (estimated treatment difference -0.5 [-0.9; -0.03], p = 0.04); however, this attenuated when adjusting for parity (p = 0.10). Women using faster aspart achieved more TIRp and experienced less severe hypoglycaemia compared to women using IAsp. Infant birthweight was lower and thereby more appropriate in the faster aspart group; however, this attenuated when adjusting for parity.

Simple meal announcements and pramlintide delivery versus carbohydrate counting in type 1 diabetes with automated fast-acting insulin aspart delivery: a randomised crossover trial in Montreal, Canada

In type 1 diabetes, carbohydrate counting is the standard of care to determine prandial insulin needs, but it can negatively affect quality of life. We developed a novel insulin-and-pramlintide closed-loop system that replaces carbohydrate counting with simple meal announcements. We performed a randomised crossover trial assessing 14 days of (1) insulin-and-pramlintide closed-loop system with simple meal announcements, (2) insulin-and-placebo closed-loop system with carbohydrate counting, and (3) insulin-and-placebo closed-loop system with simple meal announcements. Participants were recruited at McGill University Health Centre (Montreal, QC, Canada). Eligible participants were adults (aged ≥18 years) and adolescents (aged 12-17 years) with type 1 diabetes for at least 1 year. Participants were randomly assigned in a 1:1:1:1:1:1 ratio to a sequence of the three interventions, with faster insulin aspart used in all interventions. Each intervention was separated by a 14-45-day wash-out period, during which participants reverted to their usual insulin. During simple meal announcement interventions, participants triggered a prandial bolus at mealtimes based on a programmed fixed meal size, whereas during carbohydrate counting interventions, participants manually entered the carbohydrate content of the meal and an algorithm calculated the prandial bolus based on insulin-to-carbohydrate ratio. Two primary comparisons were predefined: the percentage of time in range (glucose 3·9-10·0 mmol/L) with a non-inferiority margin of 6·25% (non-inferiority comparison); and the mean Emotional Burden subscale score of the Diabetes Distress Scale (superiority comparison), comparing the insulin-and-placebo system with carbohydrate counting minus the insulin-and-pramlintide system with simple meal announcements. Analyses were performed on a modified intention-to-treat basis, excluding participants who did not complete all interventions. Serious adverse events were assessed in all participants. This trial is registered on ClinicalTrials.gov, NCT04163874. 32 participants were enrolled between Feb 14, 2020, and Oct 5, 2021; two participants withdrew before study completion. 30 participants were analysed, including 15 adults (nine female, mean age 39·4 years [SD 13·8]) and 15 adolescents (eight female, mean age 15·7 years [1·3]). Non-inferiority of the insulin-and-pramlintide system with simple meal announcements relative to the insulin-and-placebo system with carbohydrate counting was reached (difference -5% [95% CI -9·0 to -0·7], non-inferiority p<0·0001). No statistically significant difference was found in the mean Emotional Burden score between the insulin-and-pramlintide system with simple meal announcements and the insulin-and-placebo system with carbohydrate counting (difference 0·01 [SD 0·82], p=0·93). With the insulin-and-pramlintide system with simple meal announcements, 14 (47%) participants reported mild gastrointestinal symptoms and two (7%) reported moderate symptoms, compared with two (7%) participants reporting mild gastrointestinal symptoms on the insulin-and-placebo system with carbohydrate counting. No serious adverse events occurred. The insulin-and-pramlintide system with simple meal announcements alleviated carbohydrate counting without degrading glucose control, although quality of life as measured by the Emotional Burden score was not improved. Longer and larger studies with this novel approach are warranted. Juvenile Diabetes Research Foundation.

820-P: Faster-Acting Insulin Aspart vs. Insulin Aspart for Adults with Type 1 Diabetes Treated with Insulin Pump and Continuous Glucose Monitoring

820-P: Faster-Acting Insulin Aspart vs. Insulin Aspart for Adults with Type 1 Diabetes Treated with Insulin Pump and Continuous Glucose Monitoring

Postprandial Glucose Excursions with Ultra-Rapid Insulin Analogs in Hybrid Closed-Loop Therapy for Adults with Type 1 Diabetes.

Objective: To evaluate postprandial glucose control when applying (1) faster-acting insulin aspart (Fiasp) compared to insulin aspart and (2) ultra-rapid insulin lispro (Lyumjev) compared to insulin lispro using the CamAPS FX hybrid closed-loop algorithm. Research Design and Methods: We undertook a secondary analysis of postprandial glucose excursions from two double-blind, randomized, crossover hybrid closed-loop studies contrasting Fiasp to standard insulin aspart, and Lyumjev to standard insulin lispro. Endpoints included incremental area under curve (iAUC)-2h, iAUC-4h, 4 h postprandial time in target range, time above range, and time below range. It was approved by independent research ethics committees. Results: Two trials with 8 weeks of data from 51 adults with type 1 diabetes were analyzed and 7137 eligible meals were included. During Lyumjev compared with insulin lispro, iAUC-2h and iAUC-4h were significantly decreased following breakfast (mean difference 92 mmol/L per 2 h (95% confidence interval [CI]: 56 to 127); P < 0.001 and 151 mmol/L per 4 h (95% CI: 74 to 229); P < 0.001, respectively) and the evening meal (P < 0.001 and P = 0.011, respectively). Mean time in target range (3.9-10.0 mmol/L) for 4 h postprandially significantly increased during Lyumjev with a mean difference of 6.7 percentage points (95% CI: 3.3 to 10) and 5.7 percentage points (95% CI: 1.4 to 9.9) for breakfast and evening meal, respectively. In contrast, there were no significant differences in iAUC-2h, iAUC-4h, and the other measures of postprandial glucose control between insulin aspart and Fiasp during breakfast, lunch, and evening meal (P > 0.05). Conclusion: The use of Lyumjev with CamAPS FX closed-loop system improved postprandial glucose excursions compared with insulin lispro, while the use of Fiasp did not provide any advantage compared with insulin aspart. Clinical Trial Registration numbers: NCT04055480, NCT05257460.

Effectiveness of Faster Aspart versus Insulin Aspart in Children with Type 1 Diabetes: A Meta-Analysis.

Intensive insulin regimens are recommended to achieve glycemic goals in children and adolescents with type 1 diabetes. Fast-acting insulin aspart (faster aspart) is a new formulation of insulin aspart (IAsp) in which L-arginine and niacinamide are added to assure formulation stability, early absorption, and ultra-fast action. This meta-analysis compares faster aspart with IAsp for blood sugar control in children with type 1 diabetes. This study suggested treating diabetes with insulin, especially in children with type 1 diabetes. PubMed, MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar were searched from 2000 to 2023 without language restrictions. Blood glucose monitoring, HbA1c, care model, insulin aspart, IAsp, faster aspart, type 1 diabetes, and pediatrics are Mesh keywords. Cochrane Q statistics and index tested heterogeneity. To account for heterogeneity, Q=145.99 (P-value < 0.001) and =97.26%, and the random-effect model was used to aggregate primary study results. The meta-analysis of randomized-controlled trials was conducted in accordance with PRISMA standards. The overall estimate measure i.e. mean difference was found to be 5.44 [0.45, 10.44] and 7.71 [7.16, 8.26] which indicate significant reduction in the HbA1C level in the fast acting insulin aspart group as compared to the IAsp in T1D. However, the mean difference with respect to BMI was found to be -0.06 [-0.60, 0.48] which indicate non-significant reduction. Faster aspart had faster onset and more early exposure than IAsp in children and adolescents with greater and more variable anti-insulin antibody levels than adults did. Hence fast-acting insulin aspart may provide better glucose control than IAsp in T1D.

Glycemic control parameters in children with type 1 diabetes treated with fast-acting insulin aspart domestic biosimilar by continuous subcutaneous infusion

Introduction. Type 1 diabetes (T1D) is a chronic autoimmune disease requiring constant insulin therapy under regular continuous monitoring of glycemic parameters. The use of domestic insulin bioanalogues in CSII therapy is currently not sufficiently covered in the literature.Aim. To evaluate glycemic control parameters in children with T1D treated with the domestic fast-acting insulin aspart biosimilar by CSII.Materials and methods. Retrospective study was carried out on the basis of K.A. Raukhfus center St. Petersburg State Medical and Biomedical Center VMT. Fifty-five children with T1D aged 6 to 17 years (mean age 12 ± 4) were examined, including 29 boys (52.7%, mean age 11 ± 3 years) and 26 girls (47.3%, mean age 13 ± 4 years). Insulin therapy was carried out by systems of CSII Glycemic parameters were monitored by continuous and flash glycemic monitoring systems. The center visits frequency was once a month.Results. During dynamic follow-up after 3 and 6 months, children showed statistically significant (p &lt; 0.05) improvement in glycemic control parameters–decrease in HbA1c level from 8.0 ± 1.8% to 7, 1 ± 1.2% and 6.8 ± 0.6%, increase in TIR from 60.4 ± 20.6% to 71.5 ± 13.0% and 75.9 ± 9.4%, decrease in TAR from 31.1 ± 22.1% to 23.0 ± 12.8% and 20.3 ± 9.3%, decrease in TBR from 9.1 ± 8.2% to 5.8 ± 4.3% and 4.1 ± 1.8%, and decrease in CV from 40.0 ± 9.1% to 33.7 ± 6.7% and 32.5 ± 5.6%.Discussion. The use of domestic biosimilar insulin aspart in insulin pumps iis associated with significant improvement in glycemic control in children and adolescents with T1D. Dynamic observation together with therapeutic education contribute to the maintenance of the achieved parameters at a high level.Conclusions. Therapy with the domestic fast-acting insulin aspart biosimilar by CSII allows achieving target glycemic control in children with T1D.

Effect of Postmeal Fast-Acting Insulin Aspart Injection on the Frequency of Hypoglycemia among Pre-School Children with Type 1 Diabetes: An Open-Label, Cross-Over, Randomized Control Trial.

To study the effect of postmeal Fast-acting insulin Aspart (Fiasp®) on the frequency of hypoglycemia compared to premeal injection among preschool children with type 1 diabetes. A single-center trial was conducted among 65 pre-school children (6 mo to 6 y) with Type 1 diabetes for at least 6 mo, on multiple daily insulin injections. Children were randomized to receive their meal bolus postmeal or premeal for the first 3 mo, followed by cross-over at 3 mo. The two groups were compared at the end of 6 mo for the change in frequency of hypoglycemia and hyperglycemia, HbA1c, glycemic variability, and parental satisfaction. Ten children (5 in each group) underwent pharmacokinetic studies. The trial was approved by Institutional Ethics Committee and registered with the Controlled Trial Registry of India vide no CTRI/2020/10/028750. Fifty-four children completed the study, with 27 children in each group. There were no significant differences in the frequency of clinical (p = 0.921), severe (p = 0.167) or serious (p = 0.753) hypoglycemia in the two groups. There were no differences in secondary outcome parameters and pharmacokinetics. The premeal or postmeal injection ofFiasp® does not affect the frequency of hypoglycemia or other glycemic control parameters among pre-school children with Type 1 diabetes. The trial is registered with the Controlled Trial Registry of India vide no CTRI/2020/10/028750.

Faster-acting insulin aspart versus insulin aspart in the treatment of type 1 or type 2 diabetes during pregnancy and post-delivery (CopenFast): an open-label, single-centre, randomised controlled trial

Faster-acting insulin aspart (faster aspart) is considered safe for use during pregnancy and breastfeeding but has not been evaluated in this population. We aimed to evaluate the effect of faster aspart versus insulin aspart on fetal growth, in women with type 1 or type 2 diabetes during pregnancy and post-delivery. This open-label, single-centre, superiority trial was conducted at Rigshospitalet, Copenhagen, Denmark. Participants aged 18 years or older with type 1 or type 2 diabetes were stratified by diabetes type and insulin treatment modality (multiple daily injections or insulin pump), randomly assigned 1:1 to faster aspart or insulin aspart, from 8 weeks and 0 days (8+0) of gestation to 13+6 weeks of gestation, and followed up until 3 months post-delivery. Primary outcome was infant birthweight SD score. Secondary outcomes included HbA1c as well as maternal and fetal outcomes in all participants during the trial. This trial is registered with ClinicalTrials.gov, NCT03770767. Between Nov 11, 2019 and May 10, 2022, 109 participants were included in the faster aspart group and 107 in the insulin aspart group. Primary outcome data were available in 203 (94%) of 216 participants, and no participants discontinued treatment during the trial. Mean birthweight SD score was 1·0 (SD 1·4) in the faster aspart group versus 1·2 (1·3) in the insulin aspart group; estimated treatment difference -0·22 [-0·58 to 0·14]; p=0·23. At 33 weeks of gestation, mean HbA1c was 42 mmol/mol (SD 6 mmol/mol; 6·0% [SD 0·9%]) versus 43 mmol/mol (SD 7 mmol/mol; 6·1% [SD 1·2%]); estimated treatment difference -1·01 (-2·86 to 0·83), p=0·28. No additional safety issues were observed with faster aspart compared with insulin aspart. Treatment with faster aspart resulted in similar fetal growth and HbA1c, relative to insulin aspart, in women with type 1 or type 2 diabetes. Faster aspart can be used in women with type 1 or type 2 diabetes during pregnancy and post-delivery with no additional safety issues. Novo Nordisk. For the Danish translation of the abstract see Supplementary Materials section.

Efficacy and Safety of Faster Aspart in Comparison to Insulin Aspart Among Indian Women with Gestational Diabetes.

The present study aimed to compare the pregnancy outcomes, efficacy, and safety of faster aspart with insulin aspart among Indian women with gestational diabetes. In several countries, fast-acting insulin aspart (faster aspart) has been approved for use in pregnancy. There is a lack of data related to maternal glycemic control and fetal and perinatal outcomes with faster aspart in gestational diabetes among the Indian population. To compare and evaluate the efficacy and safety of faster aspart and insulin aspart in the management of gestational diabetes. This retrospective study evaluated the medical records of 60 pregnant women diagnosed with gestational diabetes and managed with faster aspart or insulin aspart at a tertiary care center, between March 2019 and September 2020. Self-monitored blood glucose levels recorded at 4 timepoints (fasting, and 1 hour post breakfast, lunch, and dinner) during 6 consecutive days any time before delivery were analyzed. Pregnancy and neonatal outcomes across both groups were compared. The mean postprandial glucose value following dinner was significantly lesser in the faster aspart group compared to the insulin aspart group (123.61 ± 2.52 mg/dL vs. 125.87 ± 2.98 mg/dL, respectively; p=0.0024). Women in the faster aspart group had significantly lower glycemic variability (fluctuations). Lesser number of hypoglycemic events were noted in the faster aspart group (10 vs. 20; p=0.0595). Faster aspart was associated with better glycemic control compared to insulin aspart among women with gestational diabetes. Further large-scale studies are needed to validate the outcomes.

Fast-Acting Insulin Aspart in Patients with Type1 Diabetes in Real-World Clinical Practice: A Noninterventional, Retrospective Chart and Database Study.

This study utilized continuous glucose monitoring data to analyze the effects of switching to treatment with fast-acting insulin aspart (faster aspart) in adults with type1 diabetes (T1D) in clinical practice. A noninterventional database review was conducted in Sweden among adults with T1D using multiple daily injection (MDI) regimens who had switched to treatment with faster aspart as part of basal-bolus treatment. Glycemic data were retrospectively collected during the 26weeks before switching (baseline) and up to 32weeks after switching (follow-up) to assess changes in time in glycemic range (TIR; 70-180mg/dL), mean sensor glucose, glycated hemoglobin (HbA1c) levels, coefficient of variation, time in hyperglycemia (level1, > 180 to ≤ 250mg/dL; level2, > 250mg/dL), and time in hypoglycemia (level1, ≥ 54 to < 70mg/dL; level2, < 54mg/dL) (ClinicalTrials.gov Identifier NCT03895515). Overall, 178 participants were included in the study cohort. The analysis population included 82 individuals (mean age 48.5years) with adequate glucose sensor data. From baseline to follow-up, statistically significant improvements were reported for TIR (mean increase 3.3%-points [approximately 48min/day]; p = 0.006) with clinically relevant improvement (≥ 5%) in 43% of participants. Statistically significant improvements from baseline were observed for mean sensor glucose levels, HbA1c levels, and time in hyperglycemia (levels1 and 2), with no statistically significant changes in time spent in hypoglycemia. Switching to faster aspart was associated with improvements in glycemic control without increasing hypoglycemia in adults with T1D using MDI in this real-world setting.

176-OR: CopenFast Trial—Fetal Growth and Glycemic Control in Pregnant Women with Type 1 or Type 2 Diabetes Using Faster-Acting Insulin Aspart or Insulin Aspart—A Randomized Controlled Trial

Aim: To evaluate the effect of faster-acting insulin aspart (faster aspart) vs. insulin aspart (IAsp) on fetal growth and glycemic control in pregnant women with type 1 or type 2 diabetes. Methods: In a single-center, open-label trial from November 2019 to May 2022 women were stratified by diabetes type and insulin treatment modality (multiple daily injections or insulin pump) and randomized to faster aspart or IAsp from 8 to 13 weeks. Primary outcome was offspring birthweight standard deviation (SD) score. Secondary outcomes included mild hypoglycemia (managed by the woman) in the previous week, HbA1c at inclusion, 21, 33, and 35 weeks, and severe hypoglycemia (requiring third party assistance) reported in a structured interview. Results: In total, 216 women were included and randomized to faster aspart or IAsp (n=109 vs. n=107). Baseline data were comparable in both groups. Primary outcome data were available in 94% (71% type 1 (of which 19% on insulin pump), 29% type 2 diabetes). Offspring birthweight SD score was median 0.7 (interquartile range -0.3-2.0) vs. 1.1 (0.4-1.9), mean difference -0.2 (95% confidence interval -0.6-0.1), p=0.23 with 41% vs. 46% large for gestational age infants (p=0.39). From randomization to delivery 1 (1%) vs. 7 (7%) women reported severe hypoglycemia (p=0.07) with fewer events reported by women using faster aspart compared to IAsp (1 vs. 10 events, p=0.03). At 33 weeks, women using faster aspart reported fewer mild hypoglycemic events in the previous week compared to IAsp (2.0 (0.8 - 4.0) vs. 3.0 (1.0 - 5.0), p=0.03), while HbA1c was 41 (38-46) vs. 43 (39-46) mmol/mol, p=0.28. Prevalence of preeclampsia was 15% vs. 12% (p=0.51) and preterm delivery &amp;lt;37 weeks 19% vs. 22% (p=0.64). No perinatal deaths were reported. Conclusion: In pregnant women with type 1 or type 2 diabetes, use of faster aspart resulted in comparable fetal growth and HbA1c with less severe hypoglycemia compared to IAsp. Disclosure S.K.Noergaard: Research Support; Novo Nordisk A/S. E.R.Mathiesen: Advisory Panel; Novo Nordisk, Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk. K.Nørgaard: Advisory Panel; Medtronic, Novo Nordisk, Research Support; Medtronic, Dexcom, Inc., Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; Medtronic, Novo Nordisk, Stock/Shareholder; Novo Nordisk. T.D.Clausen: None. J.Søholm: Research Support; Novo Nordisk A/S. P.Holmager: None. N.C.Do: Research Support; Novo Nordisk Foundation. P.Damm: Other Relationship; Novo Nordisk A/S. L.Ringholm: Research Support; Novo Nordisk A/S. Funding Novo Nordisk A/S (U1111-1209-6358)

Faster-acting insulin aspart reduces glycaemic variability in sensor-augmented pump treated type 1 diabetes patients

AimTo evaluate the effect of faster aspart over glycaemic variability in type 1 diabetes (T1D) patients treated with sensor-augmented pump (SAP) in a real-world scenario. MethodsObservational study with SAP-treated adult T1D patients treated with faster aspart for three months. The primary endpoint was the mean amplitude of glucose excursions (MAGE). ResultsFifty patients were treated with faster aspart. Eleven patients (23%) withdrew during the follow-up mainly due to worsening of diabetes control (9 patients). Mean age was 41.2 yrs. (range 21–59) and T1D duration 22.4±10.0 yrs. Mean SAP treatment duration was 3.6±3.1 yrs. We detected a reduction of -7.0 (95% CI −1.1, −12.9; p=0.021) in MAGE at the end of the study. Other glycemic variability indices were also improved: standard deviation of mean interstitial glucose (−3mg/dl; 95% CI, −1, −5; p=0.01), CONGA4 (−2.2; 95% CI −0.3, −4.2; p=0.029), CONGA6 (−2.6; 95% CI −0.6, −4.6; p=0.011), GRADE (−0.5; 95% CI −0.1, −0.9; p=0.022), HBGI (−0.7; 95% CI −0.2, −1.3; p=0.013), J-index (−2.9; 95% CI −0.7, −5.0; p=0.011) and MODD (−5.7; 95% CI −1.7, −9.7; p=0.006). A slight reduction in mean glucose management indicator was also detected (−0.14%; 95% CI, −0.02, −0.27; −1.4mmol/mol; 95% CI −0.1, −3.3; p=0.03). ConclusionsIn SAP-treated T1D patients, faster aspart insulin was associated with reduced glycaemic variability, but also a high percentage of dropouts due to worsened glycaemic control. NCT04233203.

Fast-acting insulin aspart in pediatric type 1 diabetes mellitus patients in a tertiary care center: Indian experience

Background: The objective of this retrospective study was to evaluate the effectiveness and safety of fast-acting insulin aspart with additional drug excipients (L-arginine and niacinamide) in the Indian pediatric population. Methods: Data of pediatric type 1 diabetes mellitus (T1DM) outpatients in the age group of 1 to 18 years on treatment with injection degludec as long-acting Insulin OD and faster aspart as rapid-acting mealtime insulin 5-minutes before the meal for 20-weeks, was collected from the medical records of subjects. The primary endpoint was the mean change in glycated hemoglobin (HbA1c) and the secondary endpoints were mean changes in fasting plasma glucose (FPG) and 1 and 2-hour postprandial glucose (PPG), from baseline to 20-weeks post-treatment. The safety of treatment was also evaluated. Results: Data of 30 pediatric patients (Male: Female-14:16) with a mean age of 7.98 years was considered for this retrospective data analysis. Compared to baseline, there was a significant decline (p&lt;0.001) in mean HbA1c levels by -0.72, in FPG by -32.87 mg/dl, in 1-hour PPG levels by -8.57 mg/dl, and 2-hour PPG levels by -11.3 mg/dl, after 20-weeks of treatment. Three and two patients reported symptomatic undocumented hypoglycemia and symptomatic documented hypoglycemia respectively, and one patient each reported local site reaction, and lipodystrophy. No episodes of nocturnal hypoglycemia were reported. Conclusions: In Indian pediatric T1DM patients 20-weeks mealtime faster aspart along with insulin degludec provided effective glycemic control, and treatment resulted in lower HbA1c, FPG, and 1 and 2-hour PPG levels. Conclusions: In Indian pediatric T1DM patients 20-weeks mealtime faster aspart along with insulin degludec provided effective glycemic control, and treatment resulted in lower HbA1c, FPG, and 1 and 2-hour PPG levels.

From Determining Brain Insulin Resistance in a Sporadic Alzheimer's Disease Model to Exploring the Region-Dependent Effect of Intranasal Insulin.

Impaired response to insulin has been linked to many neurodegenerative disorders like Alzheimer's disease (AD). Animal model of sporadic AD has been developed by intracerebroventricular (icv) administration of streptozotocin (STZ), which given peripherally causes insulin resistance. Difficulty in demonstrating insulin resistance in this model led to our aim: to determine brain regional and peripheral response after intranasal (IN) administration of insulin in control and STZ-icv rats, by exploring peripheral and central metabolic parameters. One month after STZ-icv or vehicle-icv administration to 3-month-old male Wistar rats, cognitive status was determined after which rats received 2IU of fast-acting insulin aspart intranasally (CTR + INS; STZ + INS) or saline only (CTR and STZ). Rats were sacrificed 2h after administration and metabolic and glutamatergic parameters were measured in plasma, CSF, and the brain. Insulin and STZ increased amyloid-β concentration in plasma (CTR + INS and STZ vs CTR), while there was no effect on glucose and insulin plasma and CSF levels. INS normalized the levels of c-fos in temporal cortex of STZ + INS vs STZ (co-localized with neurons), while hypothalamic c-fos was found co-localized with the microglial marker. STZ and insulin brain region specifically altered the levels and activity of proteins involved in cell metabolism and glutamate signaling. Central changes found after INS in STZ-icv rats suggest hippocampal and cortical insulin sensitivity. Altered hypothalamic metabolic parameters of STZ-icv rats were not normalized by INS, indicating possible hypothalamic insulin insensitivity. Brain insulin sensitivity depends on the affected brain region and presence of metabolic dysfunction induced by STZ-icv administration.

Comparative assessment of modern parameters of glycemic control in children with type 1 diabetes after switching to fast-acting insulin aspart using Flash Glucose Monitoring in real clinical practice

BACKGROUND: Postprandial hyperglycaemia contributes significantly to the lack of glycaemic control in patients with type 1 diabetes mellitus (DM1). At least a quarter of patients forget to inject insulin before meals once a week, and more than 40% of them inject bolus insulin immediately before meals, which does not correspond to the pharmacokinetic effects of ultrashort insulins and determines the need to use insulins with better imitations of physiological insulin secretion.AIM: To assess the effect of fast acting insulin aspart (FIAsp) on the current parameters of glycaemic control in children with DM1 after switching from insulin Asp (iAsp) using continuous glucose monitoring.MATERIALS AND METHODS: A multicenter observational 12-week prospective open-label uncontrolled comparative study was initiated. A group of insufficiently controlled patients were identified (n = 48) including a group on multiple insulin injections therapy (MII) (insulin degludec and IAsp) and a group on continuous subcutaneous insulin infusion (CSII) of iAsp. Three 14-day flash glucose monitoring (FMG) were performed: before transferring patients to FiAsp and after 2 and 12 weeks of the transfer. Key endpoints: HbA1c after 2 and 12 weeks on FiAsp relative to baseline, analysis of 5 FMG target glucose ranges, presented as an ambulatory glycemic profile. Additional indicators: dynamics of insulin daily dose, frequency of glucose self- monitoring, the number of severe hypoglycemia, adverse events that occurred during treatment.RESULTS: 2 weeks after the transfer from IAsp to FIAsp, TIR increased in the entire group of patients: from 53% [44.3; 66.5] to 57% [47.4; 71.0] (p-value = 0.010) and TAR decreased from 38% [24.8; 50.2] to 30.5% [22.0; 45, 0] (p-value = 0.0124). Maintaining and increase time spent in the target glucose ranges during a 12-week observation period, in parallel with a significant decrease in hypoglycemic episodes &lt;3.9 mmol / L per week, on FIAsp therapy naturally leads to an improvement in diabetes control: a decrease in HbA1c from 8.15% up to 7.75% (p-value = 0.0224), more pronounced in the group of patients on CSII — from 7.9% to 7.5% (p-value = 0.028).CONCLUSION: Switching from IAsp to BDIAsp in routine clinical practice in the MII and CSII regimen in children and adolescents with type 1 diabetes allows achieving better glycemic control compared to the previous generation prandial insulin analog Iasp. The better diabetes control is associated with an increase or a trend towards an increase in TIR and a decrease or a trend towards a decrease in TAR and TBR, as well as a significant decrease in episodes of hypoglycemia.

A Multicenter Randomized Trial Evaluating Fast-Acting Insulin Aspart in the Bionic Pancreas in Adults with Type 1 Diabetes.

Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) using fast-acting insulin aspart (Fiasp®) in adults with type 1 diabetes (T1D). Research Design and Methods: In this multicenter, randomized trial, 275 adults with T1D (18-83 years old, baseline HbA1c 5.3%-14.9%) were randomly assigned 2:2:1 to use the BP with fast-acting insulin aspart (BP-F group, N = 114), BP with aspart or lispro (BP-A/L group, N = 107), or a control group using their standard-care insulin delivery (SC group, N = 54) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. The BP-F versus SC comparison was considered primary and BP-F versus BP-A/L secondary. Results: Mean ± standard deviation (SD) HbA1c decreased from 7.8% ± 1.2% at baseline to 7.1% ± 0.6% at 13 weeks with BP-F versus 7.6% ± 1.2% to 7.5% ± 0.9% with SC (adjusted difference = -0.5%, 95% CI -0.7 to -0.3, P < 0.001). CGM-measured percent time <54 mg/dL over 13 weeks with BP-F was noninferior to SC (adjusted difference = 0.00%, 95% CI -0.07 to 0.05, P < 0.001 for noninferiority based on a prespecified noninferiority limit of 1%). Over 13 weeks, mean time in range 70-180 mg/dL (TIR) increased by 14% (3.4 h/day) and mean CGM glucose was reduced by 18 mg/dL with BP-F compared with SC (P < 0.001). Analyses of time >180 mg/dL, time >250 mg/dL, and the SD of CGM glucose all favored BP-F compared with SC (P < 0.001). Differences between BP-F and BP-A/L were minimal, with no difference in HbA1c at 13 weeks (adjusted difference = -0.0%, 95% CI -0.2 to 0.1, P = 0.67) or mean glucose (adjusted difference = -2.0 mg/dL, 95% CI -4.3 to 0.4, P = 0.10). Mean TIR was 2% greater with BP-F than BP-A/L (95% CI 1 to 4, P = 0.005), but the percentages of participants improving TIR by ≥5% were not significantly different (P = 0.49) and there were no significant differences comparing BP-F versus BP-A/L across nine patient-reported outcome surveys. The rate of severe hypoglycemia events did not differ among the three groups. Conclusions: In adults with T1D, HbA1c was improved with the BP using fast-acting insulin aspart compared with standard care without increasing CGM-measured hypoglycemia. However, the effect was no better than the reduction observed with the BP using aspart or lispro. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

Perioperative Fully Closed-Loop Insulin Delivery in Patients Undergoing Elective Surgery: An Open-Label, Randomized Controlled Trial.

Perioperative management of glucose levels remains challenging. We aimed to assess whether fully closed-loop subcutaneous insulin delivery would improve glycemic control compared with standard insulin therapy in insulin-requiring patients undergoing elective surgery. We performed a single-center, open-label, randomized controlled trial. Patients with diabetes (other than type 1) undergoing elective surgery were recruited from various surgical units and randomly assigned using a minimization schedule (stratified by HbA1c and daily insulin dose) to fully closed-loop insulin delivery with fast-acting insulin aspart (closed-loop group) or standard insulin therapy according to local clinical practice (control group). Study treatment was administered from hospital admission to discharge (for a maximum of 20 days). The primary end point was the proportion of time with sensor glucose in the target range (5.6-10.0 mmol/L). Forty-five patients were enrolled and assigned to the closed-loop (n = 23) or the control (n = 22) group. One patient (closed-loop group) withdrew from the study before surgery and was not analyzed. Participants underwent abdominal (57%), vascular (23%), orthopedic (9%), neuro (9%), or thoracic (2%) surgery. The mean proportion of time that sensor glucose was in the target range was 76.7 ± 10.1% in the closed-loop and 54.7 ± 20.8% in the control group (mean difference 22.0 percentage points [95% CI 11.9; 32.0%]; P < 0.001). No episodes of severe hypoglycemia (<3.0 mmol/L) or hyperglycemia with ketonemia or any study-related adverse events occurred in either group. In the context of mixed elective surgery, the use of fully closed-loop subcutaneous insulin delivery improves glucose control without a higher risk of hypoglycemia.

Faster-acting insulin aspart reduces glycaemic variability in sensor-augmented pump treated type 1 diabetes patients

AimTo evaluate the effect of faster aspart over glycaemic variability in type 1 diabetes (T1D) patients treated with sensor-augmented pump (SAP) in a real-world scenario. MethodsObservational study with SAP-treated adult T1D patients treated with faster aspart for three months. The primary endpoint was the mean amplitude of glucose excursions (MAGE). ResultsFifty patients were treated with faster aspart. Eleven patients (23%) withdrew during the follow-up mainly due to worsening of diabetes control (9 patients). Mean age was 41.2 yrs. (range 21–59) and T1D duration 22.4±10.0 yrs. Mean SAP treatment duration was 3.6±3.1 yrs. We detected a reduction of -7.0 (95% CI −1.1, −12.9; p=0.021) in MAGE at the end of the study. Other glycemic variability indices were also improved: standard deviation of mean interstitial glucose (−3mg/dl; 95% CI, −1, −5; p=0.01), CONGA4 (−2.2; 95% CI −0.3, −4.2; p=0.029), CONGA6 (−2.6; 95% CI −0.6, −4.6; p=0.011), GRADE (−0.5; 95% CI −0.1, −0.9; p=0.022), HBGI (−0.7; 95% CI −0.2, −1.3; p=0.013), J-index (−2.9; 95% CI −0.7, −5.0; p=0.011) and MODD (−5.7; 95% CI −1.7, −9.7; p=0.006). A slight reduction in mean glucose management indicator was also detected (−0.14%; 95% CI, −0.02, −0.27; −1.4mmol/mol; 95% CI −0.1, −3.3; p=0.03). ConclusionsIn SAP-treated T1D patients, faster aspart insulin was associated with reduced glycaemic variability, but also a high percentage of dropouts due to worsened glycaemic control. NCT04233203.

96-LB: Safety of Glucose Regulation by the Bionic Pancreas without Continuous Glucose Monitoring Input

The bionic pancreas (BP) continues to make all insulin dosing decisions autonomously when continuous glucose monitoring (CGM) data is not available. Basal insulin is given based on a profile determined autonomously by the BP when CGM data was available. Meals are announced as Breakfast, Lunch, or Dinner and by relative size (Usual, Less, More) ; insulin dosing is based on adaptation that occurred when CGM data was available. Insulin may be delivered, or temporarily suspended, autonomously by the BP in response to entered blood glucose (BG) values. At the end of the 13-week Pivotal RCT of the BP in type 1 diabetes, participants in the BP group could participate in a study testing the BP without CGM input. Unblinded CGM was replaced by blinded CGM not connected to the BP for ∼49.5 hours. Participants were to enter fingerstick BG values every ∼2 hours during the day and once overnight. Adherence with BG entry requirements by the 54 participants (aged 7-70) was high. There was no severe hypoglycemia or DKA. The frequency of CGM-measured hypoglycemia was similar during the BG Period to the RCT and Pre-Randomization periods. Hyperglycemia metrics were nominally higher during the BG Period than the RCT, but nominally lower than the Pre-randomization Baseline period. The BP can autonomously determine all insulin doses and achieve safe glucose control without CGM input when intermittent BG values are provided by the user. Disclosure C. A. Balliro: Consultant; Beta Bionics, Inc., Zealand Pharma A/S. Funding Funding from National Institute of Diabetes and Digestive and Kidney Diseases (#1UC4DK108612-01) . Funding and bionic pancreas devices from Beta Bionics, Inc. Fast-acting insulin aspart and insulin aspart provided by Novo Nordisk Insulin lispro by Eli LillyBlood glucose meters and test strips (Contour Next One Blood Glucose Monitoring System) provided by Ascensia Diabetes Care, Basel, CH. Continuous glucose monitor sensors and transmitters were purchased from Dexcom, Inc. at a discounted price.

98-LB: Outcomes from the Insulin-Only Bionic Pancreas Pivotal Extension Study

The bionic pancreas (BP) is initialized with body weight only, makes all insulin dosing decisions autonomously, and uses meal announcements without carbohydrate counting. After completing a Pivotal RCT, 90 of the 107 (aged 6-71) participants who were randomized to the 13-week baseline standard-care (SC) arm in the RCT participated in the 13-week Insulin-Only BP Pivotal Extension Study (ES) . Visit completion rate was 100%. During the baseline SC period, 1 adult participant had 2 severe hypoglycemia (SH) events; the same participant had 2 additional SH events during the ES. During the baseline SC period there were no DKA events; 1 pediatric participant had a DKA event due to infusion set failure during the ES. A decrease of HbA1c, mean CGM glucose, percent of time &amp;lt;70 mg/dl, percent of time &amp;gt;180 mg/dl, and glucose coefficient of variability (CV) , and increased percent of time in range (TIR) occurred in the Extension Study when compared to the baseline SC period. Changes from baseline were similar in adult (N=42) and pediatric (N=48) participants, except for reductions in time &amp;lt;70 mg/dl and CV, which were statistically significant in the pediatric but not adult sub-groups (Table) . The 90 participants who randomized to a 13-week baseline SC period and transitioned to the 13-week ES had statistically significant improvements in HbA1c and CGM outcomes following transition to the Insulin-Only BP without increases in hypoglycemia. Disclosure J. L. Lynch: Consultant; Novo Nordisk, Novo Nordisk, Novo Nordisk, Research Support; Beta Bionics, Inc., Beta Bionics, Inc., Beta Bionics, Inc., Jaeb Center for Health Research, Jaeb Center for Health Research, Jaeb Center for Health Research. Funding Funding from National Institute of Diabetes and Digestive and Kidney Diseases (grant #1UC4DK108612-01) Funding and bionic pancreas devices from Beta Bionics, Inc. Fast-acting insulin aspart and insulin aspart provided by Novo Nordisk Insulin lispro by Eli LillyBlood glucose meters and test strips (Contour?Next One Blood Glucose Monitoring System) provided by Ascensia Diabetes Care, Basel, CH. Continuous glucose monitor sensors and transmitters were purchased from Dexcom, Inc. at a discounted price.