Time In Glucose Range Research Articles

Novel clinical associations between time in range and microangiopathies in people with type 2 diabetes mellitus on hemodialysis

Aims/hypothesisWe investigated associations among glucose time in range (TIR, 70–180 mg/dL), glycemic markers and prevalence of diabetic microangiopathy in people with diabetes undergoing hemodialysis (HD). MethodsA total of 107 people with type 2 diabetes undergoing HD (HbA1c 6.4 %; glycated albumin [GA] 20.6 %) using continuous glucose monitoring were analyzed in this observational and cross-sectional study. ResultsHbA1c and GA levels significantly negatively correlated with TIR, and positively correlated with time rate of hyperglycemia, but not with time rate of hypoglycemia. TIR of 70 % corresponded to HbA1c of 6.5 % and GA of 21.2 %. The estimated HbA1c level corresponding to TIR of 70 % in this study was lower than that previously reported in people with diabetes without HD. The prevalence of diabetic neuropathy was not significantly different between people with TIR ≥ 70 % and those with TIR < 70 % (P = 0.1925), but the prevalence of diabetic retinopathy in people with TIR ≥ 70 % was significantly lower than in those with TIR < 70 % (P = 0.0071). Conclusion/interpretationTIR correlated with HbA1c and GA levels in people with type 2 diabetes on HD. Additionally, a higher TIR resulted in a lower rate of diabetic retinopathy. Research in contextWhat is already known about this subject?–HbA1c and glycated albumin (GA) are associated with mortality and comorbidity in people with diabetes undergoing hemodialysis (HD).–Continuous glucose monitoring (CGM) revealed high glycemic variability and hypoglycemia related with HD.What is the key question?–There is insufficient evidence to determine whether glucose time in range (TIR; 70–180 mg/dL) by CGM correlates with HbA1c and GA or with other microvascular complications in HD people with diabetes.What are the new findings?–HbA1c and GA levels significantly negatively correlated with TIR, and positively correlated with time rate of hyperglycemia, but not with time rate of hypoglycemia.–Comparing people with TIR ≥ 70 % and TIR < 70 %, there was no difference in the prevalence of neuropathy, but the prevalence of retinopathy was significantly less in people with TIR ≥ 70 %.How might this impact on clinical practice in the foreseeable future?–TIR is also useful as a new glycemic management parameter in people with type 2 diabetes on HD.

Prevaccination Glucose Time in Range Correlates With Antibody Response to SARS-CoV-2 Vaccine in Type 1 Diabetes.

Poor glucose control has been associated with increased mortality in COVID-19 patients with type 1 diabetes (T1D). This work aimed to assess the effect of prevaccination glucose control on antibody response to the SARS-CoV-2 vaccine BNT162b2 in T1D. We studied 26 patients with T1D scheduled to receive 2 doses, 21 days apart, of BNT162b2, followed prospectively for 6 months with regular evaluation of SARS-CoV-2 antibodies and glucose control. Immunoglobulin G (IgG) to spike glycoprotein were assessed by enzyme-linked immunosorbent assay, and serum neutralization by a live SARS-CoV-2 assay (Vero E6 cells system). Glycated hemoglobin A1c (HbA1c) and continuous glucose monitoring (CGM), including time in range (TIR) and above range (TAR), were collected. The primary exposure and outcome measures were prevaccination glucose control, and antibody response after vaccination, respectively. Prevaccination HbA1c was unrelated to postvaccine spike IgG (r = -0.33; P = .14). Of note, the CGM profile collected during the 2 weeks preceding BNT162b2 administration correlated with postvaccine IgG response (TIR: r = 0.75; P = .02; TAR: r = -0.81; P = .008). Patients meeting the recommended prevaccination glucose targets of TIR (≥ 70%) and TAR (≤ 25%) developed stronger neutralizing antibody titers (P < .0001 and P = .008, respectively), regardless of HbA1c. Glucose control along the study time frame was also associated with IgG response during follow-up (TIR: r = 0.93; P < .0001; TAR: r = -0.84; P < .0001). In T1D, glucose profile during the 2 weeks preceding vaccination is associated with stronger spike antibody binding and neutralization, highlighting a role for well-controlled blood glucose in vaccination efficacy.

PSAT117 Lower Muscle Mass Relative to Body Weight in Pre-pubertal Children with Type 1 Diabetes

Abstract Introduction/Background Type 1 diabetes (T1D) is associated with decreased skeletal muscle mass (SMM) and impaired muscle function in adults. Despite the importance of skeletal muscle in insulin action and metabolic homeostasis, our understanding of skeletal muscle health in children with T1D is very limited. Here we used a novel, non-invasive methodology to compare muscle mass (MM) in children with T1D and sex and age-matched healthy children without diabetes. Objectives We hypothesized that: (a) children with T1D have lower MM than age, sex, and BMI-matched children without T1D; (b) MM in children with T1D correlates with insulin sensitivity and glycemic control. Methods Weight (BW), height, BMI%, body fat% (BF%), daily insulin requirement, CGM data, HbA1c, and total and HMW adiponectin were measured in 24 young children (15 females, 9 males; age 6-11 years) with T1D. BF% and fat-free-mass (FFM) was measured by bioelectrical impedance. Insulin sensitivity was assessed by total and HMW-adiponectin and daily insulin requirements. Glycemic control was assessed by glucose time in range, mean blood glucose, and HbA1c. MM was measured using the D3creatine dilution method in 22 of the children with T1D (14 females, 8 males) and, in a separate study, in 34 children without T1D (17 females and 17 males). This method involves an oral 10 mg dose of deuterated creatine (methyl-d3, D3Cr). Creatine is converted in vivo to creatinine, including D3Cr to D3creatinine, in muscle by an irreversible, nonenzymatic reaction and then excreted. A single fasting urine sample is collected to determine D3creatinine enrichment. MM/BW (%) was calculated to normalize for body weight. Results There were strong positive associations between MM and body weight (r=0.85, p&amp;lt;0.0001), BMI (r=0.61, p=0.0028), and FFM (r=0.72, p=0.0040). Although children with T1D were slightly older (9.2 ±1.3 vs 8.1± 1.2 yo, p=0.003) and had higher BMI (18± 2.3 vs16.0 ±2.0, p=0.001) than controls, they had lower %MM/BW than children without diabetes (37.8± 4.6 vs 43.1±4.5%, p&amp;lt;0.0001). The lower %MM/BW in T1D compared to controls was confirmed in sub-cohorts matched for age and in males and females analyzed separately. Mean daily insulin requirement and HbA1c in the children with T1D were 0.76±0.15 IU/kg/day and 7.1±1.1%, respectively. MM, FFM, %BF, FM, %MM/BW did not correlate with metrics of insulin sensitivity or glycemic control. Conclusions This is the first study to quantitate MM directly in young children with T1D. Our results demonstrate a lower %MM in 6–11-year-old pre-pubertal children with T1D with stable and reasonable glycemic control. The cause for the lower % MM in T1D is not clear; however future studies could examine the rates of muscle protein and fat synthesis and breakdown in healthy and diabetic children along with their relations to insulin administration, metabolic control, growth, and pubertal development. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Variation of glucose time in range in type 1 diabetes.

The aim of the study was to assess the variation of glucose time in range (TIR) for persons with type 1 diabetes who perform intermittently scanned continuous glucose monitoring (isCGM). Glucose data for 8 weeks were analysed for 166 persons. TIR was calculated over four consecutive 2 weeks periods. Sixty-one of the persons had two downloads with an interval of >3months. A total of 140 individuals (84%) used multiple daily injection, and 26 (16%) used continuous insulin infusion. The within-individual standard deviation (SD) for TIR was 6.3% corresponding to 95% limits of agreement for the difference between two TIR values of ±17.6%. Mean TIR calculated from the first and last 2 weeks was 52.2 ± 17.1% and 53.7 ± 16.4%, respectively (difference 1.5%, SD of the difference 10.4%, p=.07). For persons with two downloads separated by months, the SD of the difference in TIR was 12.6%. The 95% limit of agreement for TIR is vast for persons using isCGM. It is difficult to draw firm conclusions regarding systematic differences when individual TIR from 2 weeks are compared. This may not be valid for users of insulin pumps with closed-loop insulin delivery.

Time in range following flash glucose monitoring: Relationship with glycaemic control, diabetes-related distress and resource utilisation in the Association of British Clinical Diabetologists national audit.

The aim of this study was to understand the relationship between time in range (TIR) achieved using the isCGM with changes in glycaemic control, diabetes-related distress (DRD) and resource utilisation in people living with diabetes. Clinicians from 106 National Health System (NHS) UK hospitals submitted isCGM user baseline and follow-up data in a web-based tool held within the UK NHS network. Linear regression analysis was used to identify the relationship between follow-up glucose TIR (3.9-10 mmol/L) categories (TIR% 50-70 and TIR% >70) with change in haemoglobin A1c (HbA1c), DRD and Gold score (measure of hypoglycaemia unawareness, where a score ≥4 suggests impaired awareness of hypoglycaemia). Of 16,427 participants, 1241 had TIR follow-up data available. In this cohort, the mean TIR was 44.8% (±22.5). With the use of isCGM, at 7.9months mean follow-up, improvements were observed in HbA1c (-6.9 [13.5]mmol/mol, p < 0.001), Gold score (-0.35 [1.5], p < 0.001) and Diabetes Distress Screening (-0.73 [1.23], p < 0.001). In the regression analysis restricted to people living with type 1 diabetes, TIR% 50-70 was associated with a -8.9 mmol/mol (±0.6, p < 0.001) reduction in HbA1c; TIR% >70 with a -14 mmol/mol (±0.8, p < 0.001) reduction in HbA1c. Incremental improvement in TIR% was also associated with significant improvements in Gold score and DRD. TIR% >70 was associated with no hospital admissions due to hypoglycaemia, hyperglycaemia/diabetic ketoacidosis, and a 60% reduction in the paramedic callouts and 77% reduction in the incidence of severe hypoglycaemia. In a large cohort of UK isCGM users, we demonstrate a significant association of higher TIR% with improvement in HbA1c, hypoglycaemia awareness, DRD and resource utilisation.

Glutamic acid decarboxylase immunotherapy for type 1 diabetes.

To describe recent development of an autoantigen (GAD) treatment towards well tolerated and efficacious precision medicine in type 1 diabetes. Although subcutaneous GAD-alum treatment failed to reach primary endpoint in a phase III trial, metanalyses showed a 97% probability of efficacy, and clear efficacy in patients carrying Hyman Leucoycte Antigen (HLA) DR3DQ2. Efforts have been made to improve efficacy by trying combination therapies with vitamin D + Ibuprofen resp vitamin D + Etanercept (TNF-α inhibition), without any breakthrough until the administration of GAD-alum was changed from subcutaneous to intralymphatic. With a very small dose of GAD-alum (4 μg) given into an inguinal lymph three times with 1 month interval, the efficacy in patients with HLADR3DQ2 has been impressive, with significantly better beta cell preservation than patients who got placebo in a double-blind randomized trial, and clinical efficacy with more patients in partial remission (IDAA1c < 9) and larger proportion of patients with CGM-measured blood glucose Time In Range (TIR), significantly correlated to the C-peptide values. The treatment has been easy for patients and healthcare without treatment-related risk or adverse events. Intralymphatic GAD-alum treatment in type 1 diabetes patients carrying HLA DR3DQ2 seems to be an attractive immune intervention.

105-LB: Glucose Variability with Second-Generation Basal Insulin Analogs Glargine 300 U/mL and Degludec 100 U/mL, Evaluated by CGM in People with T1D—The InRange Randomized Controlled Trial

Background: InRange has previously demonstrated that insulin glargine 300 U/mL (Gla-300) is non-inferior to insulin degludec 100 U/mL (IDeg-100) in terms of time in glucose range 70--180 mg/dL (primary endpoint) and total glucose coefficient of variation (CV) as measured by CGM in people with T1D. Methods: InRange (NCT04075513) was a multicenter, randomized, active-controlled, parallel-group, 12-week open-label trial comparing Gla-300 vs. IDeg-100 in adults with T1D using 20-day CGM profiles (≥10 days evaluable) . Here we present data for within- and between-day CV. Results: Overall, 343 participants were randomized (172 Gla-300, 171 IDeg-100) : mean ± SD age was 42.8 ± 13.3 years and T1D duration was 20.5 ± 12.8 years. Both within-day and between-day glucose CV at Week 12 were similar with Gla-300 and IDeg-100 (Table) . Within-day glucose CV at Week 12 was below the threshold for glycemic stability (36%) in both groups and was also similar in both treatment groups irrespective of glycemic stability at baseline (CV ≤36% or &amp;gt;36%) . The LS mean within-day glucose CV of participants with CV &amp;gt;36% at baseline reached 33.67 (Gla-300) and 35.38 (IDeg-100) at Week 12. Conclusion: Using clinically relevant CGM metrics, InRange shows that Gla-300 and IDeg-100 provide similar within- and between-day glucose variability in people with T1D. Disclosure R. M. Bergenstal: Advisory Panel; Hygieia, Medtronic, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Abbott Diabetes, Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Onduo LLC, Sanofi, United HealthCare Services, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi. T. Battelino: Advisory Panel; Abbott Diabetes, Indigo Diabetes, Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi, Research Support; Medtronic, Novartis Pharmaceuticals Corporation, Novo Nordisk, Zealand Pharma A/S, Speaker’s Bureau; Abbott Diabetes, Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi, Stock/Shareholder; DreaMed Diabetes, Ltd. S. Edelman: Consultant; Abbott Diabetes, Lilly Diabetes, Sanofi-Aventis U. S., Xeris Pharmaceuticals, Inc. P. Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker’s Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. T. Danne: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG, Research Support; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG, Stock/Shareholder; DreaMed Diabetes, Ltd. E. Renard: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Insulet Corporation, LifeScan, Lilly, Novo Nordisk, Roche Diabetes Care, Sanofi, Tandem Diabetes Care, Inc. J. Westerbacka: Employee; Sanofi, Stock/Shareholder; Sanofi. B. Mukherjee: Employee; Sanofi, Stock/Shareholder; Sanofi. P. Picard: n/a. V. Pilorget: None. Funding Sanofi

1023-P: Clusters of Depressive Symptoms and Glycemic Outcomes in Youth with Type 1 Diabetes (T1D)

Aim: Depression is a heterogeneous construct that includes various symptoms (e.g., cognitive, somatic) and is linked to worse diabetes outcomes. We examined the associations of depressive symptom clusters with glycemic outcomes using continuous glucose monitoring (CGM) data in youth with T1D. Methods: Participants (N=120) provided blood samples for HbA1c, completed a validated survey for depressive symptoms (CES-DC) , and wore CGM for one week. CGM glucose metrics were derived: % time in range (TIR) 70-180 mg/dL; % time &amp;lt;70 mg/dL; % time &amp;gt;180 mg/dL; % time &amp;gt;250 mg/dL; mean glucose; and glucose variability (GCV) . CES-DC items were categorized as somatic, cognitive, anhedonic, and interpersonal for analyses. Results: Youth (49% male) had a mean (±SD) age of 12.7±2.7 years, T1D duration 6.1±3.5 years, HbA1c 7.9±0.8%. Overall, higher total CES-DC score was associated with higher HbA1c (r=0.21, p=0.02) . In youth with HbA1c ≤8% (n=68) , there were no significant associations between depressive clusters and glycemic outcomes, but several significant associations emerged in youth with HbA1c &amp;gt;8% (n=52) . For those with HbA1c &amp;gt;8%, higher CES-DC total score was associated with higher HbA1c (r=0.55, p&amp;lt;0.0001) , greater % time &amp;gt;250 (r=0.29, p=0.03) , and higher mean glucose (r=0.33, p=0.02) . More symptoms on the cognitive and interpersonal clusters were associated with higher HbA1c (r=0.29, p=0.03; r=0.43, p=0.002, respectively) . More somatic symptoms were associated with greater % time &amp;gt;180 (r=0.34, p=0.01) , less % TIR (r=-0.34, p=0.01) , and higher mean glucose (r=0.31, p=0.03) . Conclusions: In our sample of youth with T1D, associations between depressive symptoms and glucose varied according to overall glycemic control, with notable associations in youth with HbA1c &amp;gt;8%. Somatic depressive symptoms were especially related to uncontrolled glucose levels, highlighting the importance of targeting glucose TIR to reduce adverse physical complaints. Disclosure A.Shapira: None. L.K.Volkening: None. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. Funding T32DK007260, P30DK036836, R01DK089349

Comparison of glucose time in range and area under curve in range in relation to risk of diabetic retinopathy in type 2 diabetes patients.

Aims/introductionWe proposed a novel continuous glucose monitoring (CGM)‐based metric, area under the curve in range (AucIR), for integrating both the amplitude and duration of dysglycemia, and further compared AucIR with the emerging key CGM‐derived metric, time in range (TIR).Materials and methodsA total of 2,030 adult patients with type 2 diabetes were enrolled during May 2020 to October 2021. AucIR and TIR were measured with 7‐day CGM data. Logistic regression analysis and the C‐statistic was carried out to assess the association of AucIR and TIR with diabetic retinopathy (DR).ResultsBoth AucIR (r = −0.89) and TIR (r = −0.95) were strongly correlated with mean glucose levels. Compared with TIR, AucIR showed a tighter relationship with parameters of glycemic variability, including the coefficient of variation (r = −0.56), standard deviation (r = −0.89) and mean amplitude of glycemic excursions (r = −0.70). For each absolute 10% decrease in AucIR, the risk of DR was increased by 7% (95% confidence interval 1.02–1.13) after adjustment for confounders. With respect to TIR, each absolute 10% decrease was associated with an 8% (95% confidence interval 1.03–1.14) increased risk of DR. The model discrimination for DR, as measured by C‐statistic, did not differ significantly between the two metrics (P > 0.05).ConclusionsAucIR did not provide added benefit over TIR in the assessment of DR risk among patients with type 2 diabetes. The potential value of AucIR needs to be explored in future studies.

Comparison of Continuous Glucose Monitoring in Cystic Fibrosis Patients With or Without Pancreatic Exocrine Insufficiency.

This study aimed to compare continuous glucose monitoring (CGM) in cystic fibrosis (CF) according to pancreatic exocrine status.CGM and oral glucose tolerance testing (OGTT) were realized annually over five years in people with CF (pwCF) aged≥10 years without cystic fibrosis-related diabetes (CFRD). CGM parameters in patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and newly diagnosed CFRD were compared according to presence of pancreatic sufficiency (PS) or insufficiency (PI).Overall, 547 OGTTs and 501 CGMs were performed in 147 CF patients, comprising 122 PI and 25 PS. In PS patients, 84% displayed NGT, 12% IGT, and 4% CFRD vs. 58%, 32%, and 10% (p=0.05) in PI. Among participants displaying normal OGTT, time in glucose range (70-140 mg/dl) was significantly increased, 97% (93, 99) vs. 92% (85, 96), p<0.001, and time above glucose range > 140 mg/dl significantly decreased, 1% (0, 2) % vs. 6% (2, 13), in patients with PS compared to those with PI. No significant differences were highlighted in patients with IGT.CGM revealed significant different glucose tolerance abnormalities in PI versus PS, which were undetected by standard 2-hour OGTT glucose.

Relationship Between Glucose Time in Range in Diabetic and Non-Diabetic Patients and Mortality in Critically Ill Patients.

Background: Shorter time spent in specific blood glucose ranges is associated with mortality benefit in critically ill patients. However, various time in range values are reported, each based on a specific blood glucose range. Objective: To evaluate relationship between percentage of time spent at various blood glucose ranges (TIR) and mortality in critically ill patients. Methods: Single-center, retrospective, cohort study that included adult patients admitted to ICU for at least one day. We evaluated the relationship between TIR at prespecified blood glucose ranges and hospital mortality in diabetic and non-diabetic patients Results: Of the 5287 patients included, 3705 (70.0%) were non-diabetic and 1582 were diabetic (29.9%). Diabetic patients had higher in-hospital mortality rate (15.8%) compared to non-diabetic patients (11.3%), p < 0.0001, and with higher incidence of hyperglycemia (77.8% vs. 39.4%) and hypoglycemia (14.3% vs. 10%) compared to non-diabetic patients, p < 0.0001. The highest median TIR for both diabetic [76% (49.1 - 97.8%)] and non-diabetic patients [100% (92.3--100%)] was at blood glucose range of 70-180 mg/dL. In non-diabetic cohort, the only optimal TIR of 40% at blood glucose range of 70-120 mg/dL was identified. Non-diabetic patients stratified into TIR 70-120 mg/dL > 40% reported significantly lower mortality (7.0%) rate compared to patients with TIR 70-120 mg/dL < 40% (15.7%), OR 0.52, 95% CI 0.27-0.97, adjusted-p = 0.03. In diabetic patients, no relationship was detected between TIR at all predefined glucose ranges and hospital mortality. Conclusion: Critically ill non-diabetic patients who spent at least 40% of time in blood glucose range of 70-120 mg/dL had improved survival. This association was not observed in diabetic patients.

Use of intermittently scanned continuous glucose monitoring in young people with high-risk type 1 diabetes-Extension phase outcomes following a 6-month randomized control trial.

To describe the impact of a 12-month intervention using intermittently scanned continuous glucose monitoring (isCGM) on glycaemic control and glucose test frequency in adolescents and young adults with type 1 diabetes (T1D) and high-risk glycaemic control (HbA1c ≥75mmol/mol [≥9.0%]). In total, 64 young people (aged 13-20years, 16.6±2.1years; 48% female; 41% Māori or Pacific ethnicity; mean diabetes duration 7.5±3.8years) with T1D were enrolled in a 6-month, randomized, parallel-group study comparing glycaemic outcomes from the isCGM intervention (n=33) to self monitoring blood glucose (SMBG) controls (n=31). In this 6-month extension phase, both groups received isCGM; HbA1c , glucose time-in-range (TIR), and combined glucose test frequency were assessed at 9 and 12months. At 12months, the mean difference in HbA1c from baseline was -4mmol/mol [-0.4%] (95% confidence interval, CI: -8, 1mmol/mol [-0.8, 0.1%]; p=0.14) in the isCGM intervention group, and -7mmol/mol [-0.7%] (95% CI: -16, 1mmol/mol [-1.5, 0.1%]; p=0.08) in the SMBG control group. No participants achieved ≥70% glucose TIR (3.9-10.0mmol/L). The isCGM intervention group mean rate of daily glucose testing was highest at 9months, 2.4 times baseline rates (p<0.001), then returned to baseline by 12months (incidence rate ratio=1.4; 95% CI: 0.9, 2.1; p=0.091). The use of isCGM in young people with high-risk T1D resulted in transient improvements in HbA1c and glucose monitoring over a 9-month time frame; however, benefits were not sustained to 12months.

Study protocol: Safety and efficacy of smart watch integrated do-it-yourself continuous glucose monitoring in adults with Type 1 diabetes, a randomised controlled trial.

Type 1 diabetes (T1D) management requires regular monitoring of glucose levels and judicious therapeutic administration of insulin to prevent both microvascular and macrovascular complications. Few people with diabetes are able to sustain the self-monitored blood glucose measurements needed for optimal care, and those that do, typically experience significant diabetes-related distress. Both intermittently scanned continuous glucose monitoring (isCGM) and continuous glucose monitoring (CGM) offer alternatives to reduce the overall burden, but both still have limitations. Given the expense of CGM, smart watch integrated do-it-yourself (DIY)-CGM has been developed as an alternative to commercial isCGM and CGM technologies. This study has been designed to evaluate the clinical efficacy of smart watch integrated DIY-CGM compared with isCGM in adults with T1D. This multicentre, randomised, crossover study will be conducted in New Zealand and aims to recruit 60 adults with established T1D who currently use isCGM. DIY-CGM will be compared to usual care with isCGM. Participants will be randomised to either arm of the study for 8weeks followed by a 4-week washout period before crossing over to the other study arm for a further 8weeks. The primary endpoint is glucose time in range (TIR) defined as percentage of time interstitial glucose is spent between 3.9 to 10mmol/L for the entire intervention period. Secondary endpoints include diabetes-related quality of life, distress, and sleep quality in participants and their partners. The results of this study will provide clinical trial data regarding smart watch integrated DIY-CGM versus isCGM for improving glycaemic control in adults with T1D, and also report a variety of key secondary outcomes, including changes in subjective outcome measures for both people with diabetes and their partners. Australian New Zealand Clinical Trials Registry (ACTRN12621000648820,31 May 2021); World Health Organisation International Clinical Trial Registry Platform (U1111-1262-2784, 3rd December 2020).

The impact of “faster aspart” on blood glucose control in children and adolescents with type 1 diabetes treated using a sensor-augmented insulin pump

Background and aimsPost-prandial glucose control is essential to achieve metabolic goals in patients with type 1 diabetes mellitus (T1DM). The new “faster aspart” insulin has a pharmacological profile noted for its faster absorption and onset of action, and increased early availability, resulting in improved blood glucose control after meals. The main objective of the study was to analyse the efficacy of “faster aspart” vs. “insulin aspart” in children and adolescents with DM1 on sensor-augmented pump treatment. Patients and methodsMulticentre, longitudinal and prospective analytical trial evaluating the use of faster aspart insulin for three months in children with T1DM with MiniMed640G® sensor-augmented pumps previously treated with aspart insulin. At the beginning and end of the study the following variables were analysed for subsequent comparison: mean sensor glucose, percentage of time in range, hypoglycaemia and hyperglycaemia, area under the curve (AUC) <70 and >180 mg/dL, mean sensor glucose pre- and postprandial in main meals, daily insulin requirements, basal/bolus percentage, and HbA1c. Acute complications, adverse events and satisfaction survey were assessed. ResultsThe study included 32 patients with a mean of 13.49 ± 2.42 years of age and with T1DM of 7.0 ± 3.67 years of onset. The use of faster aspart was associated with lower time in hyperglycaemia >180 mg/dL (25.8 ± 11.3 vs. 22.4 ± 9.5; p = .011) and >250 mg/dL (5.2±4.9 vs. 4.0 ± 3.6; p = .04), lower AUC >180 mg/dL (10.8 ± 6.5 vs. 9.3 ± 6.1; p = .03), and increased time in range (71.4 ± 10.0 vs. 74.3 ± 9.2; p = .03). No significant changes in hypoglycaemia, HbA1c, insulin requirements, and basal/bolus percentages were detected. Faster aspart was safe and well-evaluated by patients and caregivers. ConclusionsFaster aspart achieves better glycaemic control by increasing glucose time in range in children and adolescents with T1DM on treatment with sensor-augmented pumps.

Association of sleep quality with glycemic variability assessed by flash glucose monitoring in patients with type 2 diabetes

BackgroundDeterioration of sleep quality has been reported to contribute to the incidence of diabetes and may be responsible for glycemic status in diabetes. The present study explored the relationship between sleep quality and glycemic variability in patients with type 2 diabetes (T2D).MethodsWe recruited 111 patients with T2D for this cross-sectional study. Each patient underwent flash glucose monitoring for 14 days to obtain glycemic variability parameters, such as standard deviation of glucose (SD), coefficient of variation of glucose (CV), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), and time in glucose range of 3.9–10 mmol/L (TIR3.9–10). After 14 days of flash glucose monitoring, each patient received a questionnaire on the Pittsburgh Sleep Quality Index (PSQI) to evaluate subjective sleep quality. HbA1c was also collected to assess average glucose.ResultsHbA1c was comparable among the subgroups of PSQI score tertiles. Across ascending tertiles of PSQI scores, SD, CV and MAGE were increased, while TIR3.9–10 was decreased (p for trend < 0.05), but not MODD (p for trend = 0.090). Moreover, PSQI scores were positively correlated with SD, CV, MODD and MAGE (r = 0.322, 0.361, 0.308 and 0.354, respectively, p < 0.001) and were inversely correlated with TIR3.9–10 (r = − 0.386, p < 0.001). After adjusting for other relevant data by multivariate linear regression analyses, PSQI scores were independently responsible for SD (β = 0.251, t = 2.112, p = 0.041), CV (β = 0.286, t = 2.207, p = 0.033), MAGE (β = 0.323, t = 2.489, p = 0.018), and TIR3.9–10 (β = − 0.401, t = − 3.930, p < 0.001) but not for MODD (β = 0.188, t = 1.374, p = 0.177).ConclusionsIncreased glycemic variability assessed by flash glucose monitoring was closely associated with poor subjective sleep quality evaluated by the PSQI in patients with T2D.

Glucose Regulation Beyond HbA1c in Type 2 Diabetes Treated With Insulin: Real-World Evidence From the DIALECT-2 Cohort.

OBJECTIVETo investigate glucose variations associated with glycated hemoglobin (HbA1c) in insulin-treated patients with type 2 diabetes.RESEARCH DESIGN AND METHODSPatients included in Diabetes and Lifestyle Cohort Twente (DIALECT)-2 (n = 79) were grouped into three HbA1c categories: low, intermediate, and high (≤53, 54–62, and ≥63 mmol/mol or ≤7, 7.1–7.8, and ≥7.9%, respectively). Blood glucose time in range (TIR), time below range (TBR), time above range (TAR), glucose variability parameters, day and night duration, and frequency of TBR and TAR episodes were determined by continuous glucose monitoring (CGM) using the FreeStyle Libre sensor and compared between HbA1c categories.RESULTSCGM was performed for a median (interquartile range) of 10 (7–12) days/patient. TIR was not different for low and intermediate HbA1c categories (76.8% [68.3–88.2] vs. 76.0% [72.5.0–80.1]), whereas in the low category, TBR was higher and TAR lower (7.7% [2.4–19.1] vs. 0.7% [0.3–6.1] and 8.2% [5.7–17.6] vs. 20.4% [11.6–27.0], respectively; P < 0.05). Patients in the highest HbA1c category had lower TIR (52.7% [40.9–67.3]) and higher TAR (44.1% [27.8–57.0]) than the other HbA1c categories (P < 0.05), but did not have less TBR during the night. All patients had more (0.06 ± 0.06/h vs. 0.03 ± 0.03/h; P = 0.002) and longer (88.0 [45.0–195.5] vs. 53.4 [34.4–82.8] minutes; P < 0.001) TBR episodes during the night than during the day.CONCLUSIONSIn this study, a high HbA1c did not reduce the occurrence of nocturnal hypoglycemia, and low HbA1c was not associated with the highest TIR. Optimal personalization of glycemic control requires the use of newer tools, including CGM-derived parameters.

Patient-Reported Outcomes in a Randomized Trial of Closed-Loop Control: The Pivotal International Diabetes Closed-Loop Trial.

Background: Closed-loop control (CLC) has been shown to improve glucose time in range and other glucose metrics; however, randomized trials >3 months comparing CLC with sensor-augmented pump (SAP) therapy are limited. We recently reported glucose control outcomes from the 6-month international Diabetes Closed-Loop (iDCL) trial; we now report patient-reported outcomes (PROs) in this iDCL trial. Methods: Participants were randomized 2:1 to CLC (N = 112) versus SAP (N = 56) and completed questionnaires, including Hypoglycemia Fear Survey, Diabetes Distress Scale (DDS), Hypoglycemia Awareness, Hypoglycemia Confidence, Hyperglycemia Avoidance, and Positive Expectancies of CLC (INSPIRE) at baseline, 3, and 6 months. CLC participants also completed Diabetes Technology Expectations and Acceptance and System Usability Scale (SUS). Results: The Hypoglycemia Fear Survey Behavior subscale improved significantly after 6 months of CLC compared with SAP. DDS did not differ except for powerless subscale scores, which worsened at 3 months in SAP. Whereas Hypoglycemia Awareness and Hyperglycemia Avoidance did not differ between groups, CLC participants showed a tendency toward improved confidence in managing hypoglycemia. The INSPIRE questionnaire showed favorable scores in the CLC group for teens and parents, with a similar trend for adults. At baseline and 6 months, CLC participants had high positive expectations for the device with Diabetes Technology Acceptance and SUS showing high benefit and low burden scores. Conclusion: CLC improved some PROs compared with SAP. Participants reported high benefit and low burden with CLC. Clinical Trial Identifier: NCT03563313.

Real-world performance of hybrid closed loop in youth, young adults, adults and older adults with type 1 diabetes: Identifying a clinical target for hybrid closed-loop use.

To describe real-world hybrid closed loop (HCL) use and glycaemic outcomes across the lifespan and identify a clinical threshold for HCL use associated with meeting the internationally recommended target of 70% sensor glucose time in range (TIR; 70-180 mg/dL). Mixed models examined MiniMed 670G HCL use and glycaemic outcomes in 276 people with type 1 diabetes from four age groups: youth (aged <18 years), young adults (18-25 years), adults (26-49 years) and older adults (≥50 years) for 1 year. ROC analysis identified the minimum percentage HCL use associated with meeting the TIR goal of 70%. HCL use at month 1 was 70.7% ± 2.9% for youth, 71.0% ± 3.8% for young adults, 78.9% ± 2.1% for adults and 84.7% ± 3.8% in older adults. HCL use declined significantly at 12 months to 49.3% ± 3.2% in youth (P < .001) and 55.7% ± 4.3% in young adults (P=.002). HCL use was sustained at 12 months in adults (76.4% ± 2.2%, P=.36) and older adults (80.4% ± 3.9%, P=.36). HCL use of 70.6% was associated with 70% TIR (sensitivity 58.3%, specificity 85%, AUC 0.77). Older age, 80% or higher continuous glucose monitor use and four or more blood glucose checks per day were associated with attaining the HCL-use threshold. HCL use of 70% or higher may be a useful target for clinicians to use to assist people with diabetes in attaining glycaemic goals. Youth may struggle with HCL use more than adults and require clinical intervention to help sustain HCL use across time.

1267-PUB: Sustained Reduction of A1C through Use of AI Digital Coach and Consumer-Friendly Glucose Measurement

Management of diabetes has always depended upon sustained self-management by the person with diabetes. Data continues to show that people do a poor job of diabetes management. Many telehealth solutions achieve short-term, but not sustained results. This investigated platform implements two unique elements to improve the ability to achieve sustained self-management. One element is an Artificial Intelligence (AI) digital coach that exists in the mobile app--keeping the right behaviors in front of people with diabetes and encouraging continual engagement. The second element is an integrated glucose meter with a dramatically more friendly user experience--defined by smaller size, discreet (no visible assembly), and less painful. The platform has been commercialized for more than 12 months. A clinical registry has been established and currently includes 50 commercial users of the platform and more than 25,000 glucose tests are included. Demographics include both type 1 and type 2, 42% male, 58% female, with ages ranging from 24 to 69 years old. With use of the platform, Figure 1 shows a significant decrease in A1C, as calculated from glucose measurements, of 1.4 points (p = 0.0001) in early use to a sustained reduction of 0.9 points (p=0.0001). These results may indicate that easier visibility of results causes immediate reduction of glucose and that this easier visibility combined with the AI coach may sustain results. These results potentially demonstrate that a simpler experience for self-management will improve sustained diabetes management results. Future studies of the registry data will include improved compliance toward ADA guidelines and glucose time in range. Disclosure T. Balder: Advisory Panel; Self; POPS Diabetes Care.

Examination of the Igls Criteria for Defining Functional Outcomes of β-cell Replacement Therapy: IPITA Symposium Report.

The Igls criteria were developed to provide a consensus definition for outcomes of β-cell replacement therapy in the treatment of diabetes during a January 2017 workshop sponsored by the International Pancreas & Islet Transplant Association (IPITA) and the European Pancreas & Islet Transplant Association. In July 2019, a symposium at the 17th IPITA World Congress was held to examine the Igls criteria after 2 years in clinical practice, including validation against continuous glucose monitoring (CGM)-derived glucose targets, and to propose future refinements that would allow for comparison of outcomes with artificial pancreas system approaches. Utilization of the criteria in various clinical and research settings was illustrated by population as well as individual outcome data of 4 islet and/or pancreas transplant centers. Validation against CGM metrics was conducted in 55 islet transplant recipients followed-up to 10 years from a fifth center. The Igls criteria provided meaningful clinical assessment on an individual patient and treatment group level, allowing for comparison both within and between different β-cell replacement modalities. Important limitations include the need to account for changes in insulin requirements and C-peptide levels relative to baseline. In islet transplant recipients, CGM glucose time in range improved with each category of increasing β-cell graft function. Future Igls 2.0 criteria should consider absolute rather than relative levels of insulin use and C-peptide as qualifiers with treatment success based on glucose assessment using CGM metrics on par with assessment of glycated hemoglobin and severe hypoglycemia events.