Time In Glucose Range Research Articles

95-OR: Safety and Feasibility Evaluation of Closed-Loop Glycemic Management in Pregnant Women with Type 1 Diabetes

Pregnancy complicated by type 1 diabetes (T1D) is associated with increased maternal and fetal morbidity and mortality. We report results from the first clinical trial testing a closed-loop control (CLC) system specifically designed for pregnant women with T1D in the United States. Eight pregnant women with T1D participated in a 48-hour clinical trial at three US sites (NCT04492566). Women were enrolled in the second trimester after organogenesis was completed. CLC sessions used the interoperable artificial pancreas system (iAPS) running a Zone-Model Predictive Control algorithm designed for stricter glycemic targets for pregnancy. Glycemic target zones were 80-110 mg/dL during the day and 80-100 mg/dL overnight, with assertive insulin delivery in the postprandial period. The primary outcome was sensor glucose time in range (TIR) for pregnancy 63-140 mg/dL as per international consensus guidelines. All enrolled subjects completed the trial. Participants had a mean age of 29.3±3.5 years, gestational age of 22.2±3.6 weeks, weight of 77±12.2 kg, and HbA1c of 5.7±0.5%. Mean sensor TIR 63-140 mg/dL was 79.3±12.8% during CLC, compared to 60.8±18.8% for the week prior in open loop at home (p=0.03, Table 1). Unrestricted carbohydrate intake at meals ranged from 7 to 78 grams during the CLC sessions. No severe hypoglycemia or adverse events occurred. CLC in pregnant women with T1D is safe and effective. Disclosure B. Ozaslan: None. M. Church: None. M. Plesser: None. S. K. Mccrady-spitzer: None. C. Bakus: None. S. J. Ogyaadu: None. K. Nelson: None. C. Reid: None. S. Deshpande: None. W. K. Kremers: Research Support; Self; AstraZeneca, Biogen, Roche Pharma. F. J. Doyle: Advisory Panel; Self; Mode AGC, Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. C. J. Levy: Advisory Panel; Self; Dexcom, Inc., Eli Lilly and Company, Employee; Spouse/Partner; AbbVie Inc., Other Relationship; Self; Dexcom, Inc., Research Support; Self; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. B. Rosenn: None. Y. C. Kudva: Research Support; Self; Dexcom, Inc. E. Dassau: Consultant; Self; Eli Lilly and Company, Employee; Self; Eli Lilly and Company, Research Support; Self; Dexcom, Inc., Tandem Diabetes Care, Speaker’s Bureau; Self; Dexcom, Inc., Roche Diabetes Care, Stock/Shareholder; Self; Eli Lilly and Company. J. E. Pinsker: Advisory Panel; Self; Medtronic, Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care, Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. G. O’malley: Research Support; Self; Abbott Diabetes, Dexcom, Inc., Horizon Therapeutics plc, Tandem Diabetes Care. R. Kaur: None. K. N. Castorino: Consultant; Self; Dexcom, Inc., Research Support; Self; Abbott Diabetes, Abbott Laboratories, Dexcom, Inc., Drawbridge Health, Inc., Lilly Diabetes, Medtronic, Novo Nordisk Inc. C. Levister: Research Support; Self; Abbott Diabetes, Insulet Corporation. M. Trinidad: None. D. Desjardins: None. Funding National Institutes of Health (R01DK120358); Dexcom, Inc. (AP-2020-014)

The effects of professional continuous glucose monitoring as an adjuvant educational tool for improving glycemic control in patients with type 2 diabetes

BackgroundThe study objective was to evaluate the effects of professional continuous glucose monitoring (CGM) as an adjuvant educational tool for improving glycemic control in patients with type 2 diabetes (T2D).MethodsWe conducted a three-month quasi-experimental study with an intervention (IGr) and control group (CGr) and ex-ante and ex-post evaluations in one family medicine clinic in Mexico City. Participants were T2D patients with HbA1c > 8% attending a comprehensive diabetes care program. In addition to the program, the IGr wore a professional CGM sensor (iPro™2) during the first 7 days of the study. Following this period, IGr participants had a medical consultation for the CGM results and treatment adjustments. Additionally, they received an educational session and personalized diet plan from a dietitian. After 3 months, the IGr again wore the CGM sensor for 1 week. The primary outcome variable was HbA1c level measured at baseline and 3 months after the CGM intervention. We analyzed the effect of the intervention on HbA1c levels by estimating the differences-in-differences treatment effect (Diff-in-Diff). Additionally, baseline and three-month CGM and dietary information were recorded for the IGr and analyzed using the Student’s paired t-test and mixed-effects generalized linear models to control for patients’ baseline characteristics.ResultsOverall, 302 T2D patients participated in the study (IGr, n = 150; control, n = 152). At the end of the three-month follow-up, we observed 0.439 mean HbA1C difference between groups (p = 0.004), with an additional decrease in HbA1c levels in the IGr compared with the CGr (Diff-in-Diff HbA1c mean of − 0.481% points, p = 0.023). Moreover, compared with the baseline, the three-month CGM patterns showed a significant increase in the percentage of time in glucose range (+ 7.25; p = 0.011); a reduction in the percentage of time above 180 mg/dl (− 6.01; p = 0.045), a decrease in glycemic variability (− 3.94, p = 0.034); and improvements in dietary patterns, shown by a reduction in total caloric intake (− 197.66 Kcal/day; p = 0.0001).ConclusionProfessional CGM contributes to reducing HbA1c levels and is an adjuvant educational tool that can improve glycemic control in patients with T2D.Trial registrationClinicalTrials.gov: NCT04667728. Registered 16/12/2020

Impacto de faster aspart sobre el control glucémico en niños y adolescentes con diabetes tipo 1 en tratamiento con un sistema integrado

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 31 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 = 0.011) and > 250 mg/dL (5.2 ± 4.9 vs. 4.0 ± 3.6; p = 0.04), lower AUC > 180 mg/dL (10.8 ± 6.5 vs. 9.3 ± 6.1; p = 0.03), and increased time in range (71.4 ± 10.0 vs. 74.3 ± 9.2; p = 0.03). 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.

Ultra Rapid-Acting Inhaled Insulin Improves Glucose Control in Patients With Type 2 Diabetes Mellitus

ObjectiveTo determine whether the use of an inhaled insulin would improve HbA1c. MethodsThis study was performed in 20 type 2 diabetes mellitus (T2DM) participants with HbA1c values ≥7.5 (58) to ≤11.5% (102 mmol/mol) on a variety of glucose-lowering regimens. Prandial Technosphere insulin (TI) was rapidly titrated based on a treatment algorithm using postprandial blood glucose to calculate premeal doses. A 2-week baseline period was followed by 12 weeks of active treatment with TI. The primary outcome was change in HbA1c. Secondary outcomes included glucose time in range (time in range: 70-180 mg/dL) obtained by a blinded continuous glucose monitoring during the baseline period and at the end of 12 weeks. Goals were to assess how to rapidly and safely initiate TI intensification, determine dosing requirements, and establish an effective dose range in uncontrolled T2DM. ResultsMean HbA1c decreased by −1.6% (−17 mmol/mol) from 9.0% (75 mmol/mol) at baseline to 7.4% (57 mmol/mol) at 12 weeks (P < .0001). Mean time in range increased from 42.2% to 65.7% (P < .0002). Mean prandial doses of TI were 18 or 19 units for all meals. Time below range was 1.1% baseline and 2.6% post treatment (P = .01). ConclusionTreatment with inhaled TI dosed using a simple algorithm improved glycemic control measured by both HbA1c and time in range, with low rates of hypoglycemia. These data add significantly to understanding TI in the management of T2DM patients for whom prandial insulin is a consideration.

Add-on therapy with dapagliflozin under full closed loop control improves time in range in adolescents and young adults with type 1 diabetes: The DAPADream study.

To investigate the effect of the sodium-glucose co-transporter-2 inhibitor dapagliflozin on glucose levels overnight and during the following day after two unannounced meals under full closed loop (FCL) conditions. For this single-centre, double-blind, randomized, placebo-controlled, cross-over trial, non-obese persons with type 1 diabetes (T1D) were studied twice (10 mg dapagliflozin bid vs. placebo) for 24 hours with two unannounced mixed meal tests 6 hours apart under FCL conditions. Primary outcome was sensor glucose time in range (TIR; 3.9-10 mmol/L). For safety evaluation, ß-hydroxybutyrate (BHB), glucagon, insulin and gastric inhibitory polypeptide were measured. Fifteen adolescents (aged 15.4 ± 1.6 years, diabetes duration 10.0 ± 3.4 years, HbA1c 8.4% ± 0.9% [67.7 ± 10.1 mmol/mol]) and 15 young adults (aged 18.7 ± 0.8 years; diabetes duration 12.5 ± 3.6 years; HbA1c 8.3% ± 0.9% [68.5 ± 11.2 mmol/mol]) completed the trial. TIR was significantly higher in the intervention group compared with placebo (68% ± 6% vs. 50% ± 13%; P < .001); nocturnal glucose was significantly lower with dapagliflozin (6.2 ± 0.7 vs. 7.3 ± 1.7 mmol/L; P = .003) without an increase in time at less than 3.9 mmol/L (3.3% ± 6.0% vs 3.1% ± 5.2%; P = .75). Urinary glucose excretion was increased 3-fold using dapagliflozin (149 ± 42 vs. 49 ± 23 g/24 hours) with a total insulin reduction of 22% (39.7 ± 12.7 vs. 30.6 ± 10.4 U; P = .004). No abnormal elevated BHB values were observed. In adolescents and adults with T1D, dapagliflozin significantly increased TIR on average by 259 minutes/day while reducing glycaemic variability during FCL control without any signs of hypoglycaemia or ketosis.

More Time in Glucose Range During Exercise Days than Sedentary Days in Adults Living with Type 1 Diabetes.

Objective: This study analysis was designed to examine the 24-h effects of exercise on glycemic control as measured by continuous glucose monitoring (CGM). Methods: Individuals with type 1 diabetes (ages: 15-68 years; hemoglobin A1c: 7.5% ± 1.5% [mean ± standard deviation (SD)]) were randomly assigned to complete twice-weekly aerobic, high-intensity interval, or resistance-based exercise sessions in addition to their personal exercise sessions for a period of 4 weeks. Exercise was tracked with wearables and glucose concentrations assessed using CGM. An exercise day was defined as a 24-h period after the end of exercise, while a sedentary day was defined as any 24-h period with no recorded exercise ≥10 min long. Sedentary days start at least 24 h after the end of exercise. Results: Mean glucose was lower (150 ± 45 vs. 166 ± 49 mg/dL, P = 0.01), % time in range [70-180 mg/dL] higher (62% ± 23% vs. 56% ± 25%, P = 0.03), % time >180 mg/dL lower (28% ± 23% vs. 37% ± 26%, P = 0.01), and % time <70 mg/dL higher (9.3% ± 11.0% vs. 7.1% ± 9.1%, P = 0.04) on exercise days compared with sedentary days. Glucose variability and % time <54 mg/dL did not differ significantly between exercise and sedentary days. No significant differences in glucose control by exercise type were observed. Conclusion: Participants had lower 24-h mean glucose levels and a greater time in range on exercise days compared with sedentary days, with mode of exercise affecting glycemia similarly. In summary, this study offers data supporting frequency of exercise as a method of facilitating glucose control but does not suggest an effect for mode of exercise.

Efficacy and safety of Chinese herbal medicine on blood glucose fluctuations in patients with type 2 diabetes mellitus: A protocol of systematic review and meta-analysis.

Background:As one of the major chronic diseases that seriously threaten human health, type 2 diabetes mellitus (T2DM) has become a global public health problem. Blood glucose fluctuation is a risk factor independent of hyperglycemia. At present, the measures to treat blood glucose fluctuations in patients with T2DM are insufficient in effectiveness and safety. Medical practice and clinical studies have proved that Chinese herbal medicine has obvious advantages in reducing blood glucose fluctuations. In this systematic review, we will assess the efficacy and safety of Chinese herbal medicine in the treatment of blood glucose fluctuations in patients with T2DM.Methods:We will search related literature of PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database, and will manually search grey documents such as literature such as conference articles and references articles. Eligible randomized controlled trials will be screened based on inclusion criteria, and data extraction, risk of bias assessment, publication bias assessment, subgroup analysis, and quality assessment will be performed. Review Manager version 5.3 software and stata version 13 software will be used for data analysis. Each process is independently conducted by 2 researchers, and if there is any objection, it will be submitted to the third researcher for resolution.Results:This study will provide evidence for the efficacy and safety of Chinese herbal medicine in the treatment of blood glucose fluctuations in patients with T2DM. Outcome measures include mean amplitude of glycemic excursions, 24 hours mean blood glucose, standard deviations of blood glucose, mean of daily differences, coefficient of variation, glucose time in range, fasting blood glucose, 2 hours postprandial blood glucose, glycated hemoglobin, HOMA-β, HOMA-IR, quality of life questionnaire, traditional Chinese medicine syndrome score, and adverse event.

Effect of 12-week continuous positive airway pressure therapy on glucose levels assessed by continuous glucose monitoring in people with type 2 diabetes and obstructive sleep apnoea; a randomized controlled trial.

AimObstructive sleep apnoea (OSA) is frequent in type 2 diabetes (T2D). The aim was to investigate the effect of a 12‐week treatment with continuous positive airway pressure (CPAP) on glycaemic control assessed by continuous glucose monitoring (CGM), HbA1c and fasting blood glucose in patients with T2D and newly detected OSA.MethodsIn a randomized controlled multicentre study, 72 participants with T2D and moderate to severe OSA (78% male, age 62 ± 7, AHI 35 ± 15) were recruited from outpatient clinics in three Danish hospitals and were randomized to CPAP intervention or control. The main outcome was glycaemic control assessed by 6 days CGM at baseline and after 12‐week therapy, as well as by HbA1c and fasting blood glucose.ResultsNo significant changes were found in average glucose levels, time in glucose range, time with hypoglycaemia, time with hyperglycaemia or coefficient of variability. HbA1c decreased 0.7 mmol/mol (0.07%; P = .8) in the CPAP group and increased 0.8 mmol/mol (0.08%; P = .6) in the control group (intergroup difference, P = .6). Fasting blood glucose increased by 0.2 mmol/L (P = .02) in the CPAP group and by 0.4 mmol/L (P = .01) in the control group (intergroup difference, P = .7). In a prespecified subgroup analysis comparing participants with high adherence (minimum usage of four hours/night for 70% of all nights) to CPAP to the control group, no significant changes were observed either, although these participants had a tendency towards better glycaemic indices.ConclusionsCPAP treatment for 12 weeks does not significantly change glycaemic control in patients with type 2 diabetes and OSA.

28-LB: Improved Time in Glucose Range over One Year Is Associated with Reduced Albuminuria in Sensor-Augmented Insulin Pump–Treated Type 1 Diabetes

Objective: To investigate the association between treatment induced change in continuous glucose monitored (CGM) time in range (TIR) and microalbuminuria in persons with type 1 diabetes (T1D) treated with sensor-augmented pumps (SAP). Methods: In an open labelled controlled trial, 60 participants with T1D treated with multiple daily injections (MDI) and history of albuminuria were randomised to MDI- or SAP-therapy for 1 year. During the study, the SAP group wore a CGM (Enlite®, Medtronic). The MDI group wore blinded CGMs (Ipro2®, Medtronic) for 6 days at baseline and study end. Anthropometrics, CGM data, blood and urine samples were collected at 0, 1, 3, 6, 9, and 12-month visits. Based on CGM data collected between each visit, the percentage of time spent within 3.9-10.0 mmol/l (%TIR) was calculated. Urine albumin creatinine ratio (UACR) was measured in 3 samples at all visits. Only CGM data for the SAP group were included in the analysis. A linear mixed model with a participant-specific random intercept was used to analyse the effect of %TIR during 1 year after start of SAP on UACR, adjusting for changes in mean arterial pressure (MAP), HbA1c and body mass index. Results: Twenty-six participants were assigned to the SAP group and had a baseline median (interquartile range) age of 51.5 (45.9; 62.1) years, HbA1c of 66 (58; 77) mmol/mol, UACR of 78.8 (37; 205) mg/g and 51Cr-EDTA-GFR 85.0 (73.0; 96.5) ml/min/1.73m2. From baseline to study end, the mean improvement (95% CI) in %TIR was 11.3 (6.0; 16.6) %, HbA1C was -14.4 (-17.5; -11.2) mmol/mol and UACR was -13 (-33; -22) %; all p&amp;lt;0.001. HbA1c decreased with 4.7 mmol/mol per 10% increase in %TIR (p&amp;lt;0.001). The UACR decreased with 13% per 10% increase in %TIR (p=0.038), with 15% per 10 mmol/mol decrease in HbA1c (p=0.071), and with 31 % per 10 mmHg decrease in MAP (p&amp;lt;0.001). Conclusion: In this longitudinal study, treatment induced increase in CGM-derived %TIR were significantly associated with decrease in albuminuria in T1D. Disclosure A. Ranjan: None. S. Rosenlund: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. T.W. Hansen: None. P. Rossing: Advisory Panel; Self; Sanofi. Consultant; Self; Astellas Pharma Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Eli Lilly and Company. Stock/Shareholder; Self; Novo Nordisk A/S. S. Andersen: None. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. Funding Novo Nordisk Foundation (NNF17SA0031406); Medtronic A/S

1295-P: Newly Diagnosed Pediatric Patients with Type 1 Diabetes Show Steady Decline in Glucose Time-in-Range (TIR) over 1 Year: Pilot Study

Optimal glycemic control is associated with improved T1D outcomes. However, in the U.S. over the last decade, glycemic control has worsened. We aimed to monitor glucose time-in-range (TIR) in the first year after diagnosis in pediatric T1D to identify the time when glucose control worsens. Newly diagnosed patients (N=67) with T1D were commenced on continuous glucose monitoring (CGM). Data was uploaded to Dexcom Clarity and analyzed retrospectively. Sample size differences at each time period vary due to patient enrollment start dates. All data was analyzed by mixed model and Tukey’s multiple comparison test. In 67 children (mean age 10±5 yrs, A1c at onset 12.1±1.9%) glucose TIR decreased from 64±21% to 55±18% at 10±9 days to 361±23 days post-diagnosis (P=0.03, Table). Mean glucose increased from 146±28 mg/dL at nadir to 172±29 mg/dL at 361±23 days post-diagnosis (P=0.001). CGM wear time also increased from 83±20% to 95±9% at 10±9 days to 361±23 days post-diagnosis (P=0.04). Time spent &amp;lt;70 mg/dL was 2±3% throughout. Newly diagnosed pediatric T1D patients continue to wear CGM throughout the first year of diagnosis. The apparent increase in mean CGM glucose and decrease in TIR as early as 205±9 days post-diagnosis presents an opportunity for more frequent monitoring and unified education by healthcare providers to target tighter glucose control for this population. Disclosure D. Zaharieva: Speaker’s Bureau; Self; Ascensia Diabetes Care, Insulet Corporation, Medtronic. P. Prahalad: None. A. Addala: None. D. Scheinker: None. M. Desai: None. K.K. Hood: Research Support; Self; Dexcom, Inc. Speaker’s Bureau; Self; LifeScan, Inc., MedIQ. B. Leverenz: None. D.M. Maahs: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk A/S. Consultant; Self; Abbott, Sanofi. Research Support; Self; Bigfoot Biomedical, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care.

96-LB: Diabeloop Closed-Loop System Allows Patients with Type 1 Diabetes (T1D) to Significantly Improve Their Glycemic Control in Real-Life Situation, without Serious Adverse Events: A 6-Month Follow-Up

Objective: Previous trials demonstrated an improvement of glycemic control with the single hormone closed-loop system Diabeloop DBLG1. Therefore, efficacy assessment of this system in real life situation is eagerly awaited. A preliminary analysis of glucose TIR (time-in-range) after a mean of 20 weeks of follow-up was previously communicated. The aim of this report is to present results of TIR and HbA1c after 6-month of follow-up. Methods: After a run-in period with G6 sensor and usual pump, 25 patients with T1D in Corbeil-Essonne and Grenoble diabetes centers (France) were provided with the commercial setting of DBLG1 System (G6 sensor and Kaleido pump). They were taught to manage it during a one to five days hospitalization. Data on system parameters and glycemic control were collected from a cloud platform. We present here the results of TIR and HbA1c after 6 months of follow-up. Results: Mean age of patients was 43 years (25-72) with a mean duration of diabetes of 19 years (2-43). All patients were already insulin pump users and 76% of patients were women. The run-in period lasted an average of 7 days (4-15). The mean HbA1c and TIR 70-180 mg/dL before DBLG1 System initiation were respectively 7.9% (5.6 to 8.5 %) [63mmol/mol, 38 to 69 mmol/mol] and 53% (21 to 85%). One patient decided to stop using the system after 2 months due to repeated system disconnections and was therefore excluded from the 6-months analysis. After a mean follow-up of 6 months, mean HbA1c decreased from 7.9% to 7.1% [63 to 54 mmol/mol] (p&amp;lt; 0.001*) and TIR 70-180 mg/dL increased from a mean of 53 to 67% (p&amp;lt;0.0001*). Moreover, TIR &amp;lt; 70 mg/dL decreased from a mean of 2.4 to 1.3% (p = 0.03*). No adverse event was reported. Closed loop was in functional mode for 85% of time. Conclusions: The DBLG1 System confirms its ability to significantly improve glycemic control in real life situation without serious adverse events. Disclosure C. Amadou: None. S. Franc: Consultant; Self; Diabeloop SA. P.Y. Benhamou: Consultant; Self; Abbott, Diabeloop SA, Eli Lilly and Company, Insulet Corporation, Novo Nordisk Inc., Sanofi. S. Lablanche: None. E. Huneker: Stock/Shareholder; Self; Diabeloop SA. G. Charpentier: Board Member; Self; Diabeloop SA. A. Penfornis: None.

1005 Characterizing Sleep and Glycemia in Emerging Adults with Type 1 Diabetes

Abstract Introduction Type 1 Diabetes (T1D) affects 1.25 million Americans, and only 14% of emerging adults (ages 18-30 years) achieve targets for glycemic control (A1C &amp;lt; 7.0%). Sleep deficiency, less than 6.5 hours total sleep time (TST), is associated with poorer glycemic control. Methods Emerging adults with T1D wore a wrist actigraph and their own or provided continuous glucose monitor (CGM) concurrently 24 hours/day for 6-8 days. Participants completed a 10-minute psychomotor vigilance test (PVT) on a device, 3-minute Trail Making Test on paper, and questionnaires including twice daily Pittsburgh sleep diaries in Research Electronic Data Capture (REDCap). TST, sleep onset latency (SOL), sleep efficiency (SE), wake after sleep onset (WASO), and sleep fragmentation index (SFI) were determined via actigraphy, glycemic control via A1C, and glucose variability via CGM. The purpose of this descriptive study was to explore associations between TST, sleep variability (SD of TST), neurocognitive function (psychomotor vigilance and executive function) and diabetes outcomes (glycemia and distress). Results The sample included 36 emerging adults (mean age 22.8±3.1; 30.6% male; 91.7% White, 86.1% non-Hispanic; A1C mean 7.1±1.0%, BMI 27.3±4.8 kg/m2). Mean TST was 7.1±1.2 hours, SOL was 19.7±13.5 minutes, SE was 85.5±4.6%, WASO was 34.7±18.2 minutes, and SFI was 17.7±6.2. Shorter TST was associated with more severe sleepiness (r=-0.48,p=0.004) and more diabetes distress (r=-0.37, p=0.03). More sleep variability was associated with more severe sleepiness (r=0.36, p=0.03), longer response times (RT) ≥ 500ms (rho=0.39, p=0.02) measured via PVT, more nocturnal glucose variability (r=0.38, p=0.04), greater mean daily differences in glucose levels (r=0.42, p=0.02). Shorter mean RT was associated with more time in glucose range (rho=-0.37, p=0.04). Conclusion Improving TST and sleep variability are potential therapeutic targets to improve glucoregulation in this high-risk population. Researchers should consider within-person multi-level modeling to inform our understanding of the true nature of the sleep-glucose association in emerging adults with T1D. Support T32 NR0008346, Sigma Theta Tau International, Dexcom provided continuous glucose monitors (G4) free of charge for participants who did not have their own device.

Glucose Time In Range, Time Above Range, and Time Below Range Depend on Mean or Median Glucose or HbA1c, Glucose Coefficient of Variation, and Shape of the Glucose Distribution.

Background: Examine the expected relationships between time in range (%TIR), time above range (%TAR), and time below range (%TBR) with median glucose (or %HbA1c) and %coefficient of variation (%CV) of glucose for various shapes of the glucose distribution. Methods: We considered several thresholds defining hypoglycemia and hyperglycemia and examined wide ranges of median glucose and %CV using three models for the glucose distribution: gaussian, log-gaussian, and a modified log-gaussian distribution. Results: There is a linear relationship between %TIR and median glucose for any specified %CV when median glucose is well removed from the threshold for hypoglycemia. %TIR reaches a peak when median glucose is close to 120 mg/dL and declines both at higher and lower median glucose values. There is a nearly linear relationship for %TAR and median glucose for a wider range of glucose (80-220 mg/dL). Risk of hypoglycemia is minimal when %CV is below 20%, but rises exponentially as %CV increases or as median glucose decreases. Similar results were obtained for a wide range of possible shapes of glucose distribution. These simulations are consistent with results from clinical studies. Conclusion: Both %TIR and %TAR are approximately linearly related to mean and median glucose (or %HbA1c). %TAR provides linearity over a wider range than %TIR. Risk of hypoglycemia (%TBR) is critically dependent on both glycemic variability (%CV) and mean or median glucose. These relationships support the use of %TIR, %TAR, and %TBR as metrics of quality of glycemic control for clinical, research, and regulatory purposes.

Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease

​ObjectiveCompared with hemoglobin A1c (HbA1c), continuous glucose monitoring (CGM) may better capture risk of diabetes complications in patients with chronic kidney disease (CKD), including diabetic peripheral neuropathy (DPN). We hypothesized...

Improved glycaemic variability and time in range with dapagliflozin versus gliclazide modified release among adults with type 2 diabetes, evaluated by continuous glucose monitoring: A 12-week randomized controlled trial.

To evaluate whether there is a difference between the effects of dapagliflozin and gliclazide modified release (MR) on glycaemic variability (GV) and glycaemic control, as assessed by continuous glucose monitoring (CGM), in individuals with uncontrolled type 2 diabetes. This randomized, open-label, active-controlled study was conducted in individuals with uncontrolled type 2 diabetes who were drug-naïve or on steady-dose metformin monotherapy. Participants were treated once daily with 10 mg dapagliflozin or 120 mg gliclazide MR. CGM and GV index calculations were performed at baseline and after 12 weeks. In total, 97 participants (age 57.9 ± 8.7 years, 50.5% men, baseline glycated haemoglobin 63 ± 9.8 mmol/mol [7.9 ± 0.9%]) were randomized, and 94 completed the 12-week protocol. Intention-to-treat (ITT) and per-protocol (PP) analyses showed that the reduction in GV, as measured by the mean amplitude of glycaemic excursions, was superior in the dapagliflozin group versus the gliclazide MR group (-0.9 mmol/L [95% CI -1.5, -0.4] vs -0.2 mmol/L [95% CI -0.6, 0.3]; P = 0.030 [ITT]). The reductions in GV estimated by the coefficient of variation and SD were greater in the dapagliflozin group. Moreover, dapagliflozin increased the glucose time in range (TIR; 3.9-10 mmol/L) by 24.9% (95% CI 18.6, 31.2) vs. 17.4% (95% CI 11.6, 23.3) in the gliclazide MR group (P = 0.089 [ITT]; P = 0.041 [PP]). Dapagliflozin improved GV and increased TIR more efficiently than gliclazide MR in individuals with type 2 diabetes over 12 weeks, as demonstrated by CGM.

1191-P: Sotagliflozin Reduces Glucose Variability and Risk for Hyperglycemia in Adults with Type 1 Diabetes

Individuals with type 1 diabetes (T1D) face daily challenges in achieving optimal glycemic control by reducing hyperglycemia while avoiding hypoglycemia. Optimization is reflected by the High/Low Blood Glucose Indices (HBGI/LBGI) - established metrics using self-monitored blood glucose, or continuous glucose monitoring (CGM) data, to assess glycemic variability (GV) and predict the risks of hyper- and hypoglycemia with intensification of therapy. In the phase 3 inTandem1 and 2 studies, sotagliflozin (SOTA), a dual SGLT1 and 2 inhibitor used as adjunct to optimized insulin therapy in adults with T1D, reduced HbA1c vs. placebo. Significant improvement of glucose time in range (70-180 mg/dL) without increasing time &amp;lt;70 mg/dL was previously reported in the pooled CGM substudy. In this analysis (N=265), we evaluated hyper- and hypoglycemic risks with SOTA 200 mg and 400 mg, both taken once daily, using LBGI and HBGI computed from CGM data. Compared with placebo, HBGI values were lower with SOTA 400 mg at study weeks 4, 12, and 24, and SOTA 200 mg at weeks 4 and 12 (p&amp;lt;0.0001) (Figure). The percentage of adults in moderate (4.5-9) or high-risk (&amp;gt;9) HBGI categories was reduced with SOTA throughout the study for both dosages, and minimal changes were seen in LBGI values and risk categories. The CGM profile showed that SOTA reduced GV through a favorable impact on HBGI without changing LBGI. Disclosure B. Kovatchev: Advisory Panel; Self; Sanofi. Board Member; Self; TypeZero Technologies, Inc. Consultant; Self; Sanofi, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care. Speaker's Bureau; Self; Dexcom, Inc. Stock/Shareholder; Self; TypeZero Technologies, Inc. Other Relationship; Self; Johnson &amp; Johnson, Sanofi. S. Wang: Employee; Self; Sanofi US. J.H. Oliveira: Employee; Self; Sanofi. Employee; Spouse/Partner; Sanofi. J.A. Stewart: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. P. Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. R. Castro: Employee; Self; Sanofi US. Funding Lexicon Pharmaceuticals, Inc.; Sanofi

259-LB: Stable Graft Function and Glycemic Control after Clinical Islet Transplantation on the Omentum

We have shown safety and efficacy of islet transplantation (ITx) in the omentum using a biological scaffold in 3 subjects with type 1 diabetes (T1D). Two subjects (#1 and #3) achieved primary outcome at 1 year (A1c ≤6.5%; No severe hypoglycemia). Subject 1 developed progressive decline in C-peptide after 15 months likely attributed to change in immunosuppression. Subject 3 has had stable graft function for over 2 years. We report on 18 month follow-up data for subject 3. A 46 y/o woman with T1D of 26 years duration underwent single ITx on the omentum (12,648 IEQ/Kg) using a biologic scaffold under ATG induction and combination mycophenolate sodium and tacrolimus maintenance. Pre-ITx insulin dose was 0.45 units/Kg/day and A1c 6.3%. At 18 months, 90 min C-peptide was 1.49 ng/mL, A1c 5.7%, and insulin dose 0.18 units/Kg/day; 14-day continuous glucose monitoring (Guardian Sensor 3, Medtronic) showed glucose 109±28mg/dL (mean±SD), 92% time in glucose range 70-180 mg/dL, 6% time in &amp;lt;70mg/dL, and 0% time in &amp;lt;54 mg/dL. Mixed meal tolerance test data is shown in Table 1. Decline in BETA-2 score was observed by 1 year followed by stabilization. ITx resulted in stable graft function, excellent glycemic control, minimal glycemic variability, and reduction in hypoglycemia over 2 years. Strategies to improve oxygen delivery and neo-vascularization and minimize immunosuppression are needed to improve long-term outcomes at this site. Disclosure D. Baidal: None. D.M. Berman: None. C. Ricordi: Advisory Panel; Self; Zone Labs. A.M. Alvarez Gil: None. N. Padilla: None. G. Ciancio: None. E. Linetsky: None. R. Alejandro: None. Funding JDRF; The Leona M. and Harry B. Helmsley Charitable Trust; Diabetes Research Institute Foundation, State of Florida; University of Miami Clinical and Translational Science Institute; Sanofi Genzyme

Improved Time in Range and Glycemic Variability With Sotagliflozin in Combination With Insulin in Adults With Type 1 Diabetes: A Pooled Analysis of 24-Week Continuous Glucose Monitoring Data From the inTandem Program

To evaluate effects of the dual sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibitor sotagliflozin in combination with insulin on glucose time in range (TIR) and glucose excursions, postprandial glucose (PPG), and other glycemic metrics in adults with type 1 diabetes using masked continuous glucose monitoring (CGM). Data sets from the inTandem1 (clinical trial reg. no. NCT02384941) and inTandem2 (clinical trial reg. no. NCT02421510) double-blind randomized trials evaluating sotagliflozin versus placebo in adults with type 1 diabetes treated with optimized insulin were pooled for analyses of masked CGM data from a subset of participants in each trial. The pooled cohort included patients randomized to receive placebo (n = 93), sotagliflozin 200 mg (n = 89), or sotagliflozin 400 mg (n = 96). The primary outcome was change from baseline to week 24 in glucose TIR (3.9-10.0 mmol/L [70-180 mg/dL]). Secondary end points included time below and above the target range and 2-h PPG level assessed after a standardized mixed meal. Mean percentage of glucose TIR/percentage time spent at <3.9 mmol/L (<70 mg/dL) during week 24 was 51.6%/5.9%, 57.8%/5.5%, and 64.2%/5.5% with placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively, which corresponded to a placebo-adjusted change from a baseline of +5.4%/-0.3% (P = 0.026; +1.3/-0.1 h/day) for sotagliflozin 200 mg and +11.7%/-0.1% (P < 0.001; +2.8/-0.02 h/day) for sotagliflozin 400 mg. Placebo-adjusted PPG reductions were 1.9 ± 0.7 mmol/L (35 ± 13 mg/dL; P = 0.004) and 2.8 ± 0.7 mmol/L (50 ± 13 mg/dL; P < 0.001) with sotagliflozin 200 and 400 mg, respectively. Combined with optimized insulin in type 1 diabetes, sotagliflozin significantly increased glucose TIR without increasing time spent at <3.9 mmol/L and reduced PPG, thereby improving glycemic control.

Use of continuous glucose monitoring for sport in type 1 diabetes

BackgroundThe benefits of exercise for patients with type 1 diabetes (T1D) are difficult to balance with associated glycaemic excursions. The aim of this cohort study was to show that continuous...

Improvements in A1C and Time-in-Range in DIY Closed-Loop (OpenAPS) Users

Overview: We performed a retrospective study that analyzed outcomes from a subset (n=20) of the Do It Yourself (DIY) closed loop community. This already well-controlled, highly motivated T1D population realized further improvements in A1c and glucose time in range (TIR), and a reduction in time spent high and low during all timeframes after beginning a DIY hybrid closed loop “artificial pancreas” system. Objective: To compare mean BG, TIR (70-180 mg/dl), and time above and below clinically meaningful thresholds before and after OpenAPS initiation. Methods: We performed a retrospective cross-over analysis of continuous BG readings recorded during 2-week segments 4-6 weeks before and after initiation of OpenAPS (Johns Hopkins IRB00121066). Mean BG and TIR were analyzed overall, as well as by day (7am-11pm) and night (11pm-7am), and statistical significance was assessed using paired t-tests. Results: Mean BG and TIR improved in every time category. Overall, mean BG (mg/dl) improved (135.7 to 128.3); as did mean estimated HbA1c (6.4 to 6.1%). TIR increased from 75.8 to 82.2% overall. Overnight, BG time &amp;lt;70 was reduced from 6.4 to 4.2%, and time &amp;lt;50 was reduced from 2.3 to 1.0%. Overall, BG excursions &amp;gt;300 were reduced from 1.7 to 0.35%. Conclusion: Even with tight initial control, persons with T1D saw meaningful improvements in estimated A1c, TIR, and a reduction in time spent high and low, during the day and at night, after initiating OpenAPS. Disclosure D.M. Lewis: Consultant; Self; Tandem Diabetes Care, Inc.. R.S. Swain: None. T.W. Donner: Research Support; Self; Novo Nordisk Inc., Viacyte, Inc..