Nocturnal Hypoglycemic Episodes Research Articles

Nocturnal Glucose Patterns with and without Hypoglycemia in People with Type 1 Diabetes Managed with Multiple Daily Insulin Injections.

Nocturnal hypoglycemia (NH) is a potentially dangerous and underestimated complication of insulin therapy. In this study, we aimed to determine which patterns of nocturnal glucose profiles are associated with NH in patients with type 1 diabetes (T1D) managed with multiple daily insulin injections. A dataset of continuous glucose monitoring (CGM) recordings obtained from 395 adult subjects with T1D was used for modeling. The clustering of CGM data was performed using a hierarchical clustering algorithm. Ten clusters without hypoglycemia and six clusters with NH episode(s) were identified. The differences among the clusters included initial and final glucose levels, glucose change during the night, and the presence of uptrends or downtrends. Post-midnight hyperglycemia was revealed in 5 out of 10 clusters without NH; in patterns with downtrends, initially elevated glucose prevented NH episodes. In clusters with initially near-normal glucose levels and downtrends, most episodes of NH were observed from midnight to 4 a.m.; if glucose was initially elevated, the episodes occurred at 2-4 a.m. or 4-6 a.m., depending on the time of the start of the downtrend. The results demonstrate the diversity of nocturnal glucose profiles in patients with T1D, which highlights the need for a differentiated approach to therapy adjustment.

Glucosinolate-rich broccoli sprouts protect against oxidative stress and improve adaptations to intense exercise training

Oxidative stress plays a vital role for the adaptive responses to physical training. However, excessive oxidative stress can precipitate cellular damage, necessitating protective mechanisms to mitigate this effect. Glucosinolates, found predominantly in cruciferous vegetables, can be converted into isothiocyanates, known for their antioxidative properties. These compounds activate crucial antioxidant defence pathways and support mitochondrial function and protein integrity under oxidative stress, in both Nrf2-dependent and independent manners. We here administered glucosinolate-rich broccoli sprouts (GRS), in a randomized double-blinded cross-over fashion to 9 healthy subjects in combination with daily intense exercise training for 7 days. We found that exercise in combination with GRS significantly decreased the levels of carbonylated proteins in skeletal muscle and the release of myeloperoxidase into blood. Moreover, it lowered lactate accumulation during submaximal exercise, and attenuated the severe nocturnal hypoglycaemic episodes seen during the placebo condition. Furthermore, GRS in combination with exercise improved physical performance, which was unchanged in the placebo condition.

Association of Smartphone-Based Activity Tracking and Nocturnal Hypoglycemia in People With Type 1 Diabetes.

Nocturnal hypoglycemia (NH) remains a major burden for people with type 1 diabetes (T1D). Daytime physical activity (PA) increases the risk of NH. This pilot study tested whether cumulative daytime PA measured using a smartphone-based step tracker was associated with NH. Adults with T1D for ≥ 5 years (y) on multiple daily insulin or continuous insulin infusion, not using continuous glucose monitoring and HbA1c 6 to 10% wore blinded Freestyle Libre Pro sensors and recorded total daily carbohydrate (TDC) and total daily dose (TDD) of insulin. During this time, daily step count (DSC) was tracked using the smartphone-based Fitbit MobileTrack application. Mixed effects logistic regression was used to estimate the effect of DSC on NH (sensor glucose <70, <54 mg/dl for ≥15 minutes), while adjusting for TDC and TDD of insulin, and treating participants as a random effect. Twenty-six adults, with 65.4% females, median age 27 years (interquartile range: 26-32) mean body mass index 23.9 kg/m2, median HbA1c 7.6% (7.1-8.1) and mean Gold Score 2.1 (standard deviation 1.0) formed the study population. The median DSC for the whole group was 2867 (1820-4807). There was a significant effect of DSC on NH episodes <70 mg/dl. (odds ratio 1.11 [95% CI: 1.01-1.23, P = .04]. There was no significant effect on NH <54 mg/dl. Daily PA measured by a smartphone-based step tracker was associated with the risk of NH in people with type 1 diabetes.

Real-Time Continuous Glucose Monitoring Immediately After Severe Hypoglycaemia Requiring Emergency Medical Services: A Randomised Controlled Trial.

Severe hypoglycaemia requiring emergency medical services remains prevalent despite advances in all aspects of diabetes self-management. Real-time continuous glucose monitoring (RTCGM) technologies can reduce the risk of severe hypoglycaemia for adults with type 1 diabetes, but the impact of these devices has not been assessed in the acute phase after an episode of severe hypoglycaemia. We recruited and randomised 35 adults with type 1 diabetes in the acute period after an episode of severe hypoglycaemia requiring emergency medical services and randomised participants to RTCGM with alerts and alarms, or usual care with self-monitored blood glucose for 12 weeks with intermittent blinded CGM. The primary outcome was the difference between groups in percentage time spent in hypoglycaemia (≤3.0 mmol/L, 55 mg/dL). Thirty participants completed the study (median (IQR) age, duration of diabetes, and BMI was 43 (36 - 56) years, 26 (19 - 37)years, and 24.9 (21.9 - 29.0) kg/m2 , respectively). Sufficient CGM data was available for 15 participants in RT-CGM group and 8 in SMBG group for the primary outcome analysis. The RTCGM group had a significantly larger reduction in exposure to glucose below 3.0mmol/L (RTCGM -0.16 [-1.23 to 0.01] vs SMBG 1.58 [0.41 to 3.48], p=0.03) and episodes of nocturnal hypoglycaemia (RT-CGM -0.03 [-0.15 to 0.02] vs SMBG 0.05 [-0.03 to 0.40], p=0.02). Episodes of severe hypoglycaemia were significantly lower in the RTCGM group (RTCGM 0.0 vs SMBG 4.0, p 0.04). RTCGM implemented acutely after an episode of severe hypoglycaemia is feasible and clinically effective with important implications for hypoglycaemia management pathways and self-monitoring cost effectiveness.

Management of Glycemia during Acute Aerobic and Resistance Training in Patients with Diabetes Type 1: A Croatian Pilot Study

(1) Background: The increased risk of developing hypoglycemia and worsening of glycemic stability during exercise is a major cause of concern for patients with type 1 diabetes mellitus (T1DM). (2) Aim: This pilot study aimed to assess glycemic stability and hypoglycemic episodes during and after aerobic versus resistance exercises using a flash glucose monitoring system in patients with T1DM. (3) Participants and Methods: We conducted a randomized crossover prospective study including 14 adult patients with T1DM. Patients were randomized according to the type of exercise (aerobic vs. resistance) with a recovery period of three days between a change of groups. Glucose stability and hypoglycemic episodes were evaluated during and 24 h after the exercise. Growth hormone (GH), cortisol, and lactate levels were determined at rest, 0, 30, and 60 min post-exercise period. (4) Results: The median age of patients was 53 years, with a median HbA1c of 7.1% and a duration of diabetes of 30 years. During both training sessions, there was a drop in glucose levels immediately after the exercise (0'), followed by an increase at 30' and 60', although the difference was not statistically significant. However, glucose levels significantly decreased from 60' to 24 h in the post-exercise period (p = 0.001) for both types of exercise. Glycemic stability was comparable prior to and after exercise for both training sessions. No differences in the number of hypoglycemic episodes, duration of hypoglycemia, and average glucose level in 24 h post-exercise period were observed between groups. Time to hypoglycemia onset was prolonged after the resistance as opposed to aerobic training (13 vs. 8 h, p = NS). There were no nocturnal hypoglycemic episodes (between 0 and 6 a.m.) after the resistance compared to aerobic exercise (4 vs. 0, p = NS). GH and cortisol responses were similar between the two sessions, while lactate levels were significantly more increased after resistance training. (5) Conclusion: Both exercise regimes induced similar blood glucose responses during and immediately following acute exercise.

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.

The comparative analysis of efficacy and safety parameters of Insulin Degludec versus Insulin Glargine: A Narrative Review

Background and aim: Insulin degludec and insuline glargine are the two long-acting insulins most commonly prescribed for the treatment of Diabetes Type 1 as well as Diabetes Type 2. Both insulins were generated to address a clinical need for the basal insulin which produces a more even and flat activity profile and reduces the number of hypoglycemia- a dangerous side effect of insulin therapy. Although glargine and degludec confirmed their superiority in terms of reduced rate of hypoglycemia, especially in comparison with first generations, several studies revealed that degludec is associated with less glycemic variability. Moreover, degludec is more effective in reaching better fasting plasma glucose levels without increasing a risk of nocturnal hypoglycemia. The aim of this study is to compare the five most essential efficacy and safety parameters of insulin degludec versus insulin glargine. Methods: This study used a narrative synthesis of the research findings. The search for existing narrative and systematic reviews on the research topic was conducted through PubMed, Embase, and Google Scholar electronic databases. Reviews were selected according to a study design and methodological quality of the included studies. The reviews published within 2015-2023 period were included. The data on five safety and efficacy parameters (the reduction of fasting plasma glucose level, HbA1c levels, overall and nocturnal hypoglycemia episodes, body weight gain) were retrieved for the analysis. Findings: The analysis of data retrieved out of 10 systematic reviews confirmed superiority of insulin degludec in comparison with insulin glargine in terms of four safety and efficacy parameters. The treatment with degludec was associated with fewer overall and nocturnal hypoglycemia episodes, a better reduction of fasting plasma glucose levels in both Diabetes Type 1 and Diabetes Type 2 groups (insulin naïve and experienced) patients, less weight gain in Diabetes Type 2 insulin experienced group and Diabetes Type 1 groups. Both insulins provided a similar reduction of HbA1c levels among patients with Diabetes Type 1 and Diabetes Type 2. Conclusion: In conclusion, this narrative review revealed that insulin degludec is superior to insulin glargine in terms of four safety and efficacy parameters such as change in fasting plasma glucose, body weight gain, nocturnal and overall hypoglycemia episodes. Degludec and glargine produced similar changes in HbA1c levels. The most pronounced differences in almost all the examined reviews were detected in the variables indicating nocturnal and overall hypoglycemia. The treatment with degludec also resulted in less hypoglycemia, accompanied with a better reduction of fasting plasma glucose levels. This characteristic confirms that degludec produces less glycemic variability and a close to physiological activity profile.

PSUN227 A retrospective comparison of Basal Bolus using Glargine U-300 and Glulisine with Premix Insulin

Abstract Objectives The objective of this retrospective analysis was to compare the occurrence of Level 1 hypoglycaemia, Level 2 hypoglycaemia, nocturnal hypoglycaemia and mean HBA1C reduction in patients treated with premixed insulin 30/70 (Insulin Isophane/NPH 70% + Human Insulin/Soluble Insulin 30%) and after initiating a basal bolus regime using Glargine U-300 and Glulisine. Level 1 hypoglycaemia is blood glucose less than 70 mg/dL but above 54 mg/dL. Level 2 hypoglycaemia is blood glucose less than 54 mg/dL. Methodology and Data Analysis Data was collected retrospectively over 6 months on adult outpatients who were on pre mix insulin 30/70 for at least 2 years and who frequently experienced hypoglycaemic episodes and after transitioning these patients to a basal bolus regime Glargine U-300 and Glulisine. Those were having an underlying etiology which would predispose them to hypoglycaemia were excluded. The exclusion criteria included malignancy, drug induced causes except premix insulin, Chronic Kidney disease stage 4 or 5 and acute or chronic hepatic failure. Blood glucose monitoring was done by a 7 point Self Monitoring of Blood Glucose. A total of 30 cases were randomly chosen and data were sought from patients’ home glucose logs, case notes and Electronic health care records. Data were analysed by Microsoft Excel and was compared with paired-T test. Results The average number of Level 1 hypoglycaemic episodes per week on premix insulin dropped from 6.517 to 0.9655 (t = -10.807456, p&amp;lt;0.00001) after initiating the basal bolus regime. The average number of level 2 hypoglycaemic episodes per week dropped from 2.034 to 0.379 (t = -8.733497, p&amp;lt;0.00001) after changing to basal bolus regime. There was also a reduction in the occurrence of average nocturnal hypoglycaemic episodes from 2.655 on pre mix insulin to 0.2068 on the basal bolus regimen (t = -8.635475, p&amp;lt;0.00001).The mean HbA1C reduction was 3.16% in three months after commencing the basal bolus regime (t = -27.554737, p&amp;lt;0.00001). Conclusions Outpatient treatment with the basal bolus regime consisting of Glargine U -300 and Glulisine as compared to the premix insulin use showed a marked reduction in Level 1 and Level 2 hypoglycaemic episodes and nocturnal hypoglycaemic episodes per week. The decreased hypoglycaemic event rates in hypoglycaemia resulted in better compliance and adherence which was reflected as a significant reduction in HbA1C. In the future more retrospective and prospective studies will be helpful with Glargine U-300 and Glulisine. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Abstract 5: Similar hypoglycemia duration with once-weekly insulin icodec versus insulin glargine U100 in insulin naïve or experienced patients with T2D

Insulin icodec* (icodec) is a novel once-weekly basal insulin analog in development. This post hoc analysis explored hypoglycemia duration using double-blinded CGM (Dexcom G6®) data from 2 phase 2, randomized, open-label, treat-to-target 16-week trials. One trial compared 3 titration algorithms of icodec vs. insulin glargine U100 (IGlar U100) in 205 insulin-naïve patients with T2D (NCT03951805), the other assessed 154 basal insulin-treated patients with T2D switching from any daily basal insulin to icodec with or without a 100% loading dose vs. IGlar U100 (NCT03922750). In line with ATTD guidelines, a hypoglycemic episode was defined as a CGM period of interstitial glucose (IG) <70 mg/dL for at least 15 min, ending when IG ≥70 mg/dL for at least 15 min. In the titration trial, hypoglycemia duration was similar across all arms: median overall hypoglycemic episode duration (IQR) was 35.0 (20.0, 70.0) min for icodec titrations A (SMBG 80-130 mg/dL ±21 U/wk) and B (80-130 mg/dL ±28 U/wk) and for IGlar U100 (80-130 mg/dL ±4 U/day), and 39.0 (24.0, 70.0) min for icodec titration C (70-108 mg/dL ±28 U/wk). The distribution pattern of hypoglycemic episodes by duration was similar across all treatment arms. Results were similar for nocturnal hypoglycemic episodes. Similarly, in the switch trial, the duration of hypoglycemia was similar between arms, irrespective of loading dose use: median overall hypoglycemic episode duration (IQR) was 40.0 (20.0, 75.0) min for icodec with loading dose, 40.0 (25.0, 80.0) min for icodec without loading dose, and 35.0 (20.0, 60.0) min for IGlar U100. The distribution pattern of hypoglycemic episodes by duration was similar across treatment arms. Similar results were seen for the nocturnal period.In conclusion, CGM-derived hypoglycemic episode duration was similar with icodec vs. IGlar U100 in insulin-naïve and insulin-experienced patients with T2D, regardless of titration algorithm or initial loading dose use. *Proposed INN.

Influence of Insulin Application Time and High-Intensity Intermittent Exercise on Hypoglycemic Risk in Adolescents With Type 1 Diabetes.

The study analyzed the influence of exercise on hypoglycemia episodes postexercise and in the subsequent 24hours in children and adolescents with type 1 diabetes. Thirty young people performed the same protocol of physical exercises for 1 hour (Ex1h) and 2 hours (Ex2h) after the administration of insulin. They performed 30minutes of exercise on a cycle ergometer with a load of 60% of maximal oxygen uptake, interspersed with maximum intensity sprints lasting 10seconds every 5minutes. Regarding the occurrence of hypoglycemia, in the 8hours following the exercises, there was no occurrence in Ex1h (χ2 = 0.001; P = .0001) and a greater proportion for Ex2h (n = 71 episodes, 53.8%), while Ex1h had a higher number of nocturnal hypoglycemic episodes (n = 60, 71.4%) compared with Ex2h (n = 31, 23.1%, χ2 = 49.521, P = .0001), Ex1h triggered a lower number of hypoglycemia (n = 84) than Ex2h (n = 134, χ2 = 11.504, P = .001). There was a greater reduction in the average amount of fast-acting insulin administered the day after Ex1h compared with Ex2h (P = .031). Intermittent exercise performed 1 hour after insulin administration shows a lower risk of hypoglycemia within 8 hours after exercise, as well as a reduction in insulin the following day.

Comparison of treatment with insulin degludec and glargine U100 in patients with type 1 diabetes prone to nocturnal severe hypoglycaemia: The HypoDeg randomized, controlled, open-label, crossover trial.

AimTo investigate whether the long‐acting insulin analogue insulin degludec compared with insulin glargine U100 reduces the risk of nocturnal symptomatic hypoglycaemia in patients with type 1 diabetes (T1D).MethodsAdults with T1D and at least one episode of nocturnal severe hypoglycaemia during the last 2 years were included in a 2‐year prospective, randomized, open, multicentre, crossover trial. A total of 149 patients were randomized 1:1 to basal‐bolus therapy with insulin degludec and insulin aspart or insulin glargine U100 and insulin aspart. Each treatment period lasted 1 year and consisted of 3 months of run‐in or crossover followed by 9 months of maintenance. The primary endpoint was the number of blindly adjudicated nocturnal symptomatic hypoglycaemic episodes. Secondary endpoints included the occurrence of severe hypoglycaemia. We analysed all endpoints by intention‐to‐treat.ResultsTreatment with insulin degludec resulted in a 28% (95% CI: 9%‐43%; P = .02) relative rate reduction (RRR) of nocturnal symptomatic hypoglycaemia at level 1 (≤3.9 mmol/L), a 37% (95% CI: 16%‐53%; P = .002) RRR at level 2 (≤3.0 mmol/L), and a 35% (95% CI: 1%‐58%; P = .04) RRR in all‐day severe hypoglycaemia compared with insulin glargine U100.ConclusionsPatients with T1D prone to nocturnal severe hypoglycaemia have lower rates of nocturnal symptomatic hypoglycaemia and all‐day severe hypoglycaemia with insulin degludec compared with insulin glargine U100.

Autonomic cardiac regulation during spontaneous nocturnal hypoglycemia in children with type 1 diabetes.

BackgroundHypoglycemia is the most common complication in insulin treated diabetes. Though mostly mild, it can be fatal in rare cases: It is hypothesized that hypoglycemia related QTc prolongation contributes to cardiac arrhythmia.ObjectiveTo evaluate influence of nocturnal hypoglycemia on QTc and heart rate variability (HRV) in children with T1D.MethodsChildren and adolescents with T1D for at least 6 months participated in an observational study using continuous glucose monitoring (CGM) and Holter electrocardiogram for five consecutive nights. Mean QTc was calculated for episodes of nocturnal hypoglycemia (<3.7 mmol/L) and compared to periods of the same duration preceding hypoglycemia. HRV (RMSSD, low and high frequency power LF and HF) was analyzed for different 15 min intervals: before hypoglycemia, onset of hypoglycemia, before/after nadir, end of hypoglycemia and after hypoglycemia.ResultsMean QTc during hypoglycemia was significantly longer compared to euglycemia (412 ± 15 vs. 405 ± 18 ms, p = 0.005). HRV changed significantly: RMSSD (from 88 ± 57 to 73 ± 43 ms) and HF (from 54 ± 17 to 47 ± 17nu) decreased from before hypoglycemia to after nadir, while heart rate (from 69 ± 9 to 72 ± 12 bpm) and LF (from 44 ± 17 to 52 ± 21 nu) increased (p = 0.04).ConclusionA QTc lengthening effect of nocturnal hypoglycemia in children with T1D was documented. HRV changes occurred even before detection of nocturnal hypoglycemia by CGM, which may be useful for hypoglycemia prediction.

Arrhythmias and diabetes: heart block, ventricular arrhythmias, and death

Arrhythmias and diabetes: heart block, ventricular arrhythmias, and death

Effect of insulin degludec versus insulin glargine U100 on time in range: SWITCH PRO, a crossover study of basal insulin-treated adults with type 2 diabetes and risk factors for hypoglycaemia.

AimsTo compare time in range (TIR) with use of insulin degludec U100 (degludec) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes.Materials and MethodsWe conducted a randomized, crossover, multicentre trial comparing degludec and glargine U100 in basal insulin‐treated adults with type 2 diabetes and ≥1 hypoglycaemia risk factor. There were two treatment periods, each with 16‐week titration and 2‐week maintenance phases (with evaluation of glucose using blinded professional continuous glucose monitoring). The once‐weekly titration (target: 3.9–5.0 mmol/L) was based on pre‐breakfast self‐measured blood glucose. The primary endpoint was percentage of TIR (3.9─10.0 mmol/L). Secondary endpoints included overall and nocturnal percentage of time in tight glycaemic range (3.9–7.8 mmol/L), and mean glycated haemoglobin (HbA1c) and glucose levels.ResultsAt baseline, participants (n = 498) had a mean (SD) age of 62.8 (9.8) years, a diabetes duration of 15.1 (7.7) years and an HbA1c level of 59.6 (11.0) mmol/mol (7.6 [1.0]%). Noninferiority and superiority were confirmed for degludec versus glargine U100 for the primary endpoint, with a mean TIR of 72.1% for degludec versus 70.7% for glargine U100 (estimated treatment difference [ETD] 1.43% [95% confidence interval (CI): 0.12, 2.74; P = 0.03] or 20.6 min/d). Overall time in tight glycaemic range favoured degludec versus glargine U100 (ETD 1.5% [95% CI: 0.15, 2.89] or 21.9 min/d). Degludec also reduced nocturnal time below range (TBR; <3.9 mmol/L) compared with glargine U100 (ETD −0.88% [95% CI: −1.34, −0.42] or 12.7 min/night; post hoc) and significantly fewer nocturnal hypoglycaemic episodes of <3.0 mmol/L were observed.ConclusionsDegludec, compared with glargine U100, provided more TIR and time in tight glycaemic range, and reduced nocturnal TBR in insulin‐treated people with type 2 diabetes.

131-OR: ADA Presidents’ Select Abstract: Effect of Insulin Degludec vs. Insulin Glargine U100 on Occurrence of Nocturnal Hypoglycemia Assessed by Nocturnal Plasma Glucose Profiles in People with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia

Background and Aims: The risk of nocturnal hypoglycemia (NH) is a limiting factor for achieving good glycemic control in people with type 1 diabetes (T1D). Insulin degludec (IDeg) is proven to lower the risk of self-reported NH. As most episodes of NH are asymptomatic, we assessed differences in occurrence of NH by hourly plasma glucose (PG) measurements at treatments with IDeg or insulin glargine U100 (IGlar) in people with T1D suffering from recurrent nocturnal severe hypoglycemia. Materials and Methods: Pre-defined optional substudy of the HypoDeg trial, a 2-year investigator-initiated, randomized, cross-over trial where 149 participants with T1D were randomized to treatment with IDeg or IGlar. Fifty-one participants (mean (SD) age 58 (13) years, diabetes duration 28 (14) years and HbA1c 7.8 (1) %) were admitted for two nights for hourly blinded plasma glucose measurements for a minimum of one night (23:00h to 07:00h) during each 1-year treatment period. The primary endpoints were NH at level 1 (PG ≤ 3.9 mmol/L) and level 2 (PG &amp;lt; 3.0 mmol/L). Results: We collected data from 196 nights. A total of 57 nights (regardless of level) in 33 participants were hypoglycemic, including 20 nights with symptomatic hypoglycemia. The incidence of NH at level 1 was lower when treated with IDeg [17 events in 97 nights (18%)] as compared to IGlar [36 events in 99 nights (36%)], corresponding to a hazard ratio (HR) of 0.39 (95% CI: 0.22-0.71; p=0.002) during treatment with IDeg. At level 2, the incidence of NH was also lower during treatment with IDeg [8 events in 97 nights (8%)] as compared to IGlar [20 events in 99 nights (20%)], corresponding to an HR of 0.36 [95% CI: 0.16-0.80; p=0.013] during treatment with IDeg. Conclusion: In people with T1D and recurrent nocturnal severe hypoglycemia, treatment with IDeg as compared to IGlar results in a clinically significant lower rate of NH at both levels of hypoglycemia. Disclosure J. M. Brøsen: None. S. Lerche: None. K. Nørgaard: Advisory Panel; Self; Medtronic, Other Relationship; Self; Novo Nordisk Inc., Zealand Pharma A/S, Speaker’s Bureau; Self; Medtronic. H. D. Parving: None. L. Tarnow: None. B. Thorsteinsson: None. U. Pedersen-bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Consultant; Self; Abbott, Speaker’s Bureau; Self; Novo Nordisk A/S. R. Agesen: Employee; Self; Novo Nordisk. P. L. Kristensen: Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company. A. Alibegovic: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. H. U. Andersen: Stock/Shareholder; Self; Novo Nordisk A/S. P. Gustenhoff: None. C. Hedetoft: None. T. Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. C. B. Juhl: None. Funding Novo Nordisk

191-OR: Similar Hypoglycemia Duration with Once-Weekly Insulin Icodec vs. Insulin Glargine U100 in Insulin Naïve or Experienced Patients with T2D

Insulin icodec* (icodec) is a novel once-weekly basal insulin analog in development. This post hoc analysis explored hypoglycemia duration using double-blinded CGM (Dexcom G6®) data from 2 phase 2, randomized, open-label, treat-to-target 16-week trials. One trial compared 3 titration algorithms of icodec vs. insulin glargine U100 (IGlar U100) in 205 insulin-naïve patients with T2D (NCT03951805), the other assessed 154 basal insulin-treated patients with T2D switching from any daily basal insulin to icodec with or without a 100% loading dose vs. IGlar U100 (NCT03922750). In line with ATTD guidelines, a hypoglycemic episode was defined as a CGM period of interstitial glucose (IG) &amp;lt;70 mg/dL for at least 15 min, ending when IG ≥70 mg/dL for at least 15 min. In the titration trial, hypoglycemia duration was similar across all arms: median overall hypoglycemic episode duration (IQR) was 35.0 (20.0, 70.0) min for icodec titrations A (SMBG 80-130 mg/dL ±21 U/wk) and B (80-130 mg/dL ±28 U/wk) and for IGlar U100 (80-130 mg/dL ±4 U/day), and 39.0 (24.0, 70.0) min for icodec titration C (70-108 mg/dL ±28 U/wk). The distribution pattern of hypoglycemic episodes by duration was similar across all treatment arms. Results were similar for nocturnal hypoglycemic episodes. Similarly, in the switch trial, the duration of hypoglycemia was similar between arms, irrespective of loading dose use: median overall hypoglycemic episode duration (IQR) was 40.0 (20.0, 75.0) min for icodec with loading dose, 40.0 (25.0, 80.0) min for icodec without loading dose, and 35.0 (20.0, 60.0) min for IGlar U100.The distribution pattern of hypoglycemic episodes by duration was similar across treatment arms. Similar results were seen for the nocturnal period. In conclusion, CGM-derived hypoglycemic episode duration was similar with icodec vs. IGlar U100 in insulin-naïve and insulin-experienced patients with T2D, regardless of titration algorithm or initial loading dose use. *Proposed INN. Disclosure R. J. Silver: Advisory Panel; Self; Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. M. Asong: Employee; Self; Novo Nordisk A/S. K. Begtrup: None. M. M. Koefoed: Employee; Self; Novo Nordisk. S. R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Zealand Pharma A/S, Consultant; Self; Zealand Pharma A/S, Other Relationship; Self; Dexcom, Inc., Eli Lilly and Company, MannKind Corporation, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi.

Glycaemic efficacy and safety of mealtime faster-acting insulin aspart administered by injection as compared to insulin aspart in people with diabetes mellitus: A meta-analysis of randomized controlled trials.

To summarize all relevant randomized controlled trials (RCTs) and provide precise effect estimates of glycaemic efficacy/safety of faster-acting insulin aspart administered by injection as compared to insulin aspart in people with diabetes mellitus. PubMed/Cochrane Library were systematically searched till October 10, 2020, to identify RCTs with duration ≥16weeks, evaluating efficacy/safety of mealtime injections of faster aspart compared to insulin aspart in people with type 1 diabetes mellitus and type 2 diabetes mellitus. Studies using faster aspart as continuous subcutaneous insulin infusion were excluded. Continuous and dichotomous outcome variables (expressed as estimated treatment difference and rate ratio in RCTs, respectively) were pooled using generic inverse variance method with fixed/random-effects model. For each outcome variable, subgroup analysis between type 1 diabetes mellitus and type 2 diabetes mellitus was performed. We included five RCTs; three of type 1 diabetes mellitus (n=1963) and two of type 2 diabetes mellitus (n=1780). All had low risk of bias. Faster aspart was associated with small but significant improvement in HbA1c than insulin aspart (MD: -0.06%, 95% CI: -0.10, -0.02, p=0.005, I2 =19%). HbA1c reduction was statistically significant only in type 1 diabetes mellitus on subgroup analysis (MD: -0.08%, 95% CI: -0.14, -0.02, p=0.005, I2 =47%). Besides, faster aspart was associated with reduced postprandial plasma glucose (PPG) increment at 1h/2h after meal test and increased 1,5-anhydroglucitol compared to insulin aspart. Early postprandial hypoglycaemic episodes were higher with faster aspart; however, overall and nocturnal hypoglycaemic episodes were not different from insulin aspart. Faster aspart is associated with reduced HbA1c , PPG increment and comparable overall hypoglycaemic episodes with regard to insulin aspart.

Continuous Glucose and Heart Rate Monitoring in Young People with Type 1 Diabetes: An Exploratory Study about Perspectives in Nocturnal Hypoglycemia Detection.

A combination of information from blood glucose (BG) and heart rate (HR) measurements has been proposed to investigate the HR changes related to nocturnal hypoglycemia (NH) episodes in pediatric subjects with type 1 diabetes (T1D), examining whether they could improve hypoglycemia prediction. We enrolled seventeen children and adolescents with T1D, monitored on average for 194 days. BG was detected by flash glucose monitoring devices, and HR was measured by wrist-worn fitness trackers. For each subject, we compared HR values recorded in the hour before NH episodes (before-hypoglycemia) with HR values recorded during sleep intervals without hypoglycemia (no-hypoglycemia). Furthermore, we investigated the behavior after the end of NH. Nine participants (53%) experienced at least three NH. Among these nine subjects, six (67%) showed a statistically significant difference between the before-hypoglycemia HR distribution and the no-hypoglycemia HR distribution. In all these six cases, the before-hypoglycemia HR median value was higher than the no-hypoglycemia HR median value. In almost all cases, HR values after the end of hypoglycemia remained higher compared to no-hypoglycemia sleep intervals. This exploratory study support that HR modifications occur during NH in T1D subjects. The identification of specific HR patterns can be helpful to improve NH detection and prevent fatal events.

Continuous Glucose Monitoring for the Detection of Hypoglycemia in Patients With Diabetes of the Exocrine Pancreas.

Detailed evaluations of hypoglycemia and associated indices based on continuous glucose monitoring (CGM) are limited in patients with diabetes of the exocrine pancreas. Our study sought to evaluate the frequency and pattern of hypoglycemic events and to investigate hypoglycemia-specific indices in this population. This was a cross-sectional study comprising 83 participants with diabetes of the exocrine pancreas. CGM and self-monitoring of blood glucose (SMBG) were performed on all participants for a minimum period of 72 hours. The frequency and pattern of hypoglycemic events, as well as hypoglycemia-related indices, were evaluated. Hypoglycemia was detected in 90.4% of patients using CGM and 38.5% of patients using SMBG. Nocturnal hypoglycemic events were more frequent (1.9 episodes/patient) and prolonged (142 minutes) compared with day-time events (1.1 episodes/patient; 82.8 minutes, P < 0.05). The mean low blood glucose index was 2.1, and glycemic risk assessment diabetes equation hypoglycemia was 9.1%. The mean time spent below (TSB) <70 mg/dL was 9.2%, and TSB <54 mg/dL was 3.7%. The mean area under curve (AUC) <70 mg/dL was 1.7 ± 2.5 mg/dL/hour and AUC <54 mg/dL was 0.6 ± 1.3 mg/dL/hour. All of the CGM-derived hypoglycemic indices were significantly more deranged at night compared with during the day (P < 0.05). Patients with diabetes of the exocrine pancreas have a high frequency of hypoglycemic episodes that are predominantly nocturnal. CGM is superior to SMBG in the detection of nocturnal and asymptomatic hypoglycemic episodes. CGM-derived hypoglycemic indices are beneficial in estimating the risk of hypoglycemia.

765-P: The Effects of CLC on Indirect Users: Sleep Improvement in Parents of Young Children with T1D

Background and Aim: Studies have increasingly identified sleep disturbances in people with T1D. Parents of young children with T1D may also be a particularly vulnerable population to sleep disturbances. Anecdotally, it is reported that use of CLC improves sleep quality and quantity in users but objective data on indirect users are not available. This study assesses sleep outcomes of CLC compared to SAP therapy in parents of children with T1D. Methods: Thirteen parents and their young children (ages 6-10) on insulin pump therapy were enrolled. Children completed an initial 4-week study with SAP using their own pump and a study CGM (Dexcom G6) followed by a 4-week phase of CLC (Control-IQ, Tandem Diabetes Care). Sleep was assessed in parents using actigraphy watches worn the last 10 days of each study phase. The Pittsburgh Sleep Quality Index (PSQI) questionnaire and the Hypoglycemia Fear Survey (HFS) were administered at baseline (BL) and following each study phase. Results: A statistically significant decrease was noted from BL to the end of the CLC phase of PSQI score (p=0.009) and the behavioral (p=0.005) and worry (p=0.045) HFS subscales. Even though statistical power was reduced by the number of participants, actigraphy data showed strong trends on several variables including an average increase of 14 minutes of total sleep time from SAP to CLC (p=0.068) and in people with high PSQI scores at BL (&amp;gt;median) a higher sleep efficiency (p=0.098) and lower wake after sleep onset (p=0.100). Notably, children significantly reduced their time spent in hypoglycemia (&amp;lt;70 mg/dl) at night from SAP to CLC (p=0.015). Conclusions: Though preliminary, these results suggest that use of CLC has a positive impact on both the quality and quantity of sleep in parents of children with T1D. A decrease in fear of hypoglycemia, endorsed by fewer nocturnal hypoglycemic episodes, might be associated with sleep improvement since previous studies have reported poorer sleep quality in parents with high levels of fear of hypoglycemia. Disclosure A. Bisio: None. S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. R. McFadden: None. H. Bonner: None. P.L. Yu: None. D.R. Cherñavvsky: Employee; Self; Dexcom, Inc. M.D. DeBoer: Research Support; Self; Tandem Diabetes Care. O. Khurshid: None. N. Kurtz: None. M.C. Oliveri: None. M. Pajewski: None. M. Schoelwer: Research Support; Self; Tandem Diabetes Care. M.K. Voelmle: Consultant; Self; Dexcom, Inc. C.A. Wakeman: Stock/Shareholder; Self; Dexcom, Inc., Tandem Diabetes Care. L. Gonder-Frederick: Other Relationship; Self; HFS-Global, LLC. Funding Virginia Research Investment Fund