OBJECTIVE:To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin. RESEARCH DESIGN AND METHODS:A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61). RESULTS:The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference -12 mg/dL, 95% CI -22 to -2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose <70 mg/dL occurred in one participant in each group. CONCLUSIONS:Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users.

Objective: A CGM sensor that is disposable and requires no calibration may make glucose management easier for people living with diabetes. The present study reports on the interim analysis of a new disposable zero-calibration sensor in adults and youth with type 1 (T1D) or type 2 diabetes (T2D) . Methods: A prospective study enrolled individuals (N=123 adults, aged 18-80 years and N=120 youth, aged 2-17 years) with diabetes at 13 sites in the United States. Raw sensor data were compared with a YSI (Yellow Springs Instruments) or blood glucose (BG) reference and involved N=15388 paired points (pps) from the arm of adults, and N=8627pps from the arm and 7781pps from the buttock of youth. Data were processed using a new zero-calibration algorithm. The primary endpoint was agreement within 20%/20mg/dL (sensor glucose [SG] ≥80mg/dL/<80mg/dL) . Multiple secondary and descriptive endpoints included agreement within 15%/15mg/dL (SG ≥70mg/dL/<70mg/dL) and the mean absolute relative difference (MARD) for the adult arm location and youth arm and buttock locations. Results: The overall 20%/20mg/dL agreement rate was 90.6% for adults, and 87.8% and 88.5% for youth arm and buttock, respectively. For adults, the 15%/15mg/dL agreement rates were 90.1% and 87.6% (SG <70 mg/dL and SG >180 mg/dL, respectively) . For youth, the 15%/15mg/dL rates were 93.2% and 86.5% for the arm (SG <70 mg/dL and SG >180 mg/dL, respectively) and 90.3% and 89.5% for the buttock (SG <70 mg/dL and SG>180 mg/dL, respectively) . The MARDs were 10.2% for adults, and 10.7% and 10.1% for youth arm and buttock, respectively. Conclusion: These interim findings on the clinical performance of the new disposable and calibration-free sensor are good and may support non-adjunctive insulin dosing in standalone CGM and automated insulin delivery systems. Disclosure B.W.Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker’s Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. J.Shin: Employee; Medtronic. F.Peng: None. S.Huang: n/a. A.S.Rhinehart: Employee; Medtronic, Stock/Shareholder; Medtronic. R.A.Vigersky: Employee; Medtronic. T.S.Bailey: Advisory Panel; Abbott Diabetes, CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Consultant; LifeScan, Sanofi, Research Support; Abbott Diabetes, Abbott Diagnostics, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Livongo, MannKind Corporation, Medtronic, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita Medical, Senseonics, ViaCyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Becton, Dickinson and Company, Medtronic, Sanofi. K.N.Castorino: Consultant; Lilly Diabetes, Research Support; Abbott Diabetes, Dexcom, Inc., Drawbridge Health, Inc., Eyenuk, Inc., Laxmi Therapeutic Devices, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk, Speaker’s Bureau; Dexcom, Inc. M.P.Christiansen: Research Support; Abbott Diabetes, Ascensia Diabetes Care, AstraZeneca, Biolinq, Dexcom, Inc., Eli Lilly and Company, Helixmith, MannKind Corporation, Medtronic, Merck Sharp & Dohme Corp. S.K.Garg: Advisory Panel; Bayer AG, Medtronic, Zealand Pharma A/S, Consultant; Novo Nordisk, Research Support; Dexcom, Inc., Medtronic. K.B.Kaiserman: Advisory Panel; Medtronic, Consultant; Medtronic, Employee; MannKind Corporation, Research Support; Medtronic, Speaker’s Bureau; Medtronic, Stock/Shareholder; MannKind Corporation. D.R.Liljenquist: None. D.I.Shulman: Advisory Panel; Medtronic. R.H.Slover: None.

IntroductionThis prospective observational study sought to establish the glycemic, physiological and dietary demands of strenuous exercise training as part of a 9-day performance camp in a professional cycling team with type 1 diabetes (T1D).Research design and methodsSixteen male professional cyclists with T1D on multiple daily injections (age: 27±4 years; duration of T1D: 11±5 years; body mass index: 22±2 kg/m2; glycated hemoglobin: 7%±1% (50±6 mmol/mol); maximum rate of oxygen consumption: 73±4 mL/kg/min) performed road cycle sessions (50%–90% of the anaerobic threshold, duration 1–6 hours) over 9 consecutive days. Glycemic (Dexcom G6), nutrition and physiological data were collected throughout. Glycemic data were stratified into predefined glycemic ranges and mapped alongside exercise physiology and nutritional parameters, as well as split into daytime and night-time phases for comparative analysis. Data were assessed by means of analysis of variance and paired t-tests. A p value of ≤0.05 (two-tailed) was statistically significant.ResultsHigher levels of antecedent hypoglycemia in the nocturnal hours were associated with greater time spent in next-day hypoglycemia overall (p=0.003) and during exercise (p=0.019). Occurrence of nocturnal hypoglycemia was associated with over three times the risk of next-day hypoglycemia (p<0.001) and a twofold risk of low glucose during cycling (p<0.001). Moreover, there was trend for a greater amount of time spent in mild hypoglycemia during the night compared with daytime hours (p=0.080).ConclusionThe higher prevalence of nocturnal hypoglycemia was associated with an increased risk of next-day hypoglycemia, which extended to cycle training sessions. These data highlight the potential need for additional prebed carbohydrates and/or insulin dose reduction strategies around exercise training in professional cyclists with T1D.Trial registration numberDRKS00019923.

We investigated the pharmacodynamics (PD) and pharmacokinetics (PK) of BioChaperone insulin Lispro (BCLIS), faster insulin aspart (FIA) and insulin aspart (ASP) in patients with type 1 diabetes using an insulin pump. In this randomized, double‐blind, three‐way crossover glucose clamp study, 43 patients received a bolus dose of each insulin (0.15 U/kg) in addition to a basal rate (0.01 U/kg/h), delivered via an insulin pump. With BCLIS, the AUC‐GIR,0–60 minutes (primary endpoint) was improved compared to ASP (least square means ratio, 1.63; 95% CI, 1.44–1.88; P < 0.0001) and was similar compared to FIA (least square means ratio, 1.06; 95% CI, 0.94–1.18; P = 0.4609). BCLIS showed faster‐on PD (tearly0.5GIRmax) than ASP and faster‐off PD (tlate0.5GIRmax) than both FIA and ASP. BCLIS also demonstrated significantly higher early exposure (AUCins, 0–60 minutes) and lower late exposure (AUCins,120–600 minutes) than both other insulins. In patients with type 1 diabetes using an insulin pump, BCLIS better mimics prandial insulin secretion and action than ASP and shows a faster off‐PD than FIA.

BACKGROUNDThe cytokine IL-7 is critical for T cell development and function. We performed a Phase Ib study in patients with type 1 diabetes (T1D) to evaluate how blockade of IL-7 would affect immune cells and relevant clinical responses.METHODSThirty-seven subjects with T1D received s.c. RN168, a monoclonal antibody that blocks the IL -7 receptor α (IL7Rα) in a dose-escalating study.RESULTSBetween 90% and 100% IL-7R occupancy and near-complete inhibition of pSTAT5 was observed at doses of RN168 1 mg/kg every other week (Q2wk) and greater. There was a significant decline in CD4+ and CD8+ effector and central memory T cells and CD4+ naive cells, but there were fewer effects on CD8+ naive T cells. The ratios of Tregs to CD4+ or CD8+ effector and central memory T cells versus baseline were increased. RNA sequencing analysis showed downmodulation of genes associated with activation, survival, and differentiation of T cells. Expression of the antiapoptotic protein Bcl-2 was reduced. The majority of treatment-emergent adverse events (TEAEs) were mild and not treatment related. Four subjects became anti-EBV IgG+ after RN168, and 2 had symptoms of active infection. The immunologic response to tetanus toxoid was preserved at doses of 1 and 3 mg/kg Q2wk but reduced at higher doses.CONCLUSIONSThis trial shows that, at dosages of 1-3 mg/kg, RN168 selectively inhibits the survival and activity of memory T cells while preserving naive T cells and Tregs. These immunologic effects may serve to eliminate pathologic T cells in autoimmune diseases.TRIAL REGISTRATIONNCT02038764.FUNDINGPfizer Inc.

Background: The MiniMed™ 670G system is FDA-approved and CE-marked for patients with T1D aged ≥7 years. Glycemic outcomes of patients aged 2-75 years with T1D using the system at home for 3 months were evaluated and compared. Methods: Data from 151 children (n=46, 2-6 years and n=105, 7-13 years) enrolled at 9 sites; and 124 adolescents and adults (n=30, 14-21 years and n=94, 22-75 years) enrolled at 10 sites, during 2-week Manual Mode use (run-in phase) followed by 3-month Auto Mode use (study phase) were analyzed. Glycemic outcomes (HbA1c, time spent at sensor glucose [SG] ranges, SG, and SG variability, etc.) were compared across age groups. Results: Data from run-in and study phases are shown (Table). Across age groups there was a 0.4% to 0.5% decrease in HbA1c and a 5.5% to 8.8% increase in time in range. During the study phases of the pediatric (2-13 years) and older cohort (14-75 years) trials, there were no episodes of severe hypoglycemia or DKA, and no serious device-related adverse events. Conclusions: These findings indicate that 3-month MiniMed™ 670G Auto Mode use in patients as young as two years of age with T1D, similar to older cohorts using the system, can safely improve glycemic outcomes compared to 2-week open-loop Manual Mode. Disclosure T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker's Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics. B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research & Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Novo Nordisk Inc., Profusa, Inc. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Beta Bionics, ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Other Relationship; Self; Insulet Corporation, Tandem Diabetes Care. G.P. Forlenza: Advisory Panel; Self; Dexcom, Inc. Consultant; Self; Medtronic MiniMed, Inc., Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. O. Pinhas-Hamiel: None. K.K. Kaiserman: Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Medtronic MiniMed, Inc. Speaker's Bureau; Self; Medtronic MiniMed, Inc. D.R. Liljenquist: None. D.I. Shulman: None. M.A. Wood: None. X. Chen: None. J. Shin: Employee; Self; Medtronic. T.L. Cordero: Employee; Self; Medtronic. S.W. Lee: Employee; Self; Medtronic. F.R. Kaufman: Employee; Self; Medtronic.

OBJECTIVE To confirm efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp), both with basal insulin degludec, in a pediatric population with type 1 diabetes. RESEARCH DESIGN AND METHODS After a 12-week run-in, this treat-to-target, 26-week, multicenter trial randomized participants (1 to <18 years) to double-blind mealtime faster aspart (n = 260), mealtime IAsp (n = 258), or open-label postmeal faster aspart (n = 259). The primary end point was change from baseline in glycated hemoglobin (HbA1c) after 26 weeks of treatment. All available information regardless of treatment discontinuation was used for the evaluation of treatment effect. RESULTS At week 26, mealtime and postmeal faster aspart were noninferior to IAsp regarding change from baseline in HbA1c (P < 0.001 for noninferiority [0.4% margin]), with a statistically significant difference in favor of mealtime faster aspart (estimated treatment difference −0.17% [95% CI −0.30; −0.03], −1.82 mmol/mol [−3.28; −0.36]; P = 0.014). Change from baseline in 1-h postprandial glucose increment significantly favored mealtime faster aspart versus IAsp at breakfast, main evening meal, and over all meals (P < 0.01 for all). No statistically significant differences in the overall rate of severe or blood glucose–confirmed hypoglycemia were observed. Mean total daily insulin dose was 0.92 units/kg for mealtime faster aspart, 0.92 units/kg for postmeal faster aspart, and 0.88 units/kg for mealtime IAsp. CONCLUSIONS In children and adolescents with type 1 diabetes, mealtime and postmeal faster aspart with insulin degludec provided effective glycemic control with no additional safety risks versus IAsp. Mealtime faster aspart provided superior HbA1c control compared with IAsp.

Activation of “suspend before low” in the Medtronic PLGM algorithm stops insulin delivery when sensor glucose (SG) is predicted to reach or fall below a preset low glucose limit in 30min. Basal insulin delivery automatically resumes once the algorithm detects an increasing SG trend. We evaluated the “suspend before low” feature of the MiniMed™ 670G with SmartGuard™ technology in children with T1D. Participants (N=105, aged 7-13 years) underwent an overnight in-clinic evaluation. Hypoglycemia was defined as 2 or more consecutive events of YSI or fingerstick blood glucose reference values ≤65 mg/dL (≤3.6 mmol/L). Children had exercise in the afternoon, no increase in basal insulin delivery, and were not in Auto Mode. Of the 1experiments, there were 79 with PLGM activation. Hypoglycemia was prevented 79.7% of the time (63/79). Mean duration of a suspension was 85.6±32.4min. The Table shows mean reference glucose values with respect to the start of automated insulin suspension and resumption, as well as 2 and 4 hours after insulin resumption. Rates of change (ROC) at insulin suspension and resumption start are also shown. All were evaluated by TDD and duration of diabetes, and stratified in quartiles. The “suspend before low” feature of the MiniMed™ 670G system reduced hypoglycemia events without rebound hyperglycemia in children with T1D regardless of TDD or duration of diabetes. Disclosure D.I. Shulman: Other Relationship; Self; Novo Nordisk Inc.. Research Support; Self; Medtronic MiniMed, Inc.. Board Member; Self; Pediatric Endocrine Society. Research Support; Self; Versartis, Inc. M.A. Wood: Research Support; Self; Medtronic MiniMed, Inc. G.P. Forlenza: Advisory Panel; Self; Dexcom, Inc.. Research Support; Self; Medtronic, Tandem Diabetes Care, Inc., Insulet Corporation, Dexcom, Inc., Novo Nordisk Inc., Bigfoot Biomedical. B. Buckingham: Advisory Panel; Self; Novo Nordisk Inc., ConvaTec Inc.. Research Support; Self; Medtronic, Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc.. Consultant; Self; Tandem Diabetes Care, Inc., Becton, Dickinson and Company. T.S. Bailey: Research Support; Self; Abbott. Consultant; Self; Abbott. Speaker's Bureau; Self; Abbott. Research Support; Self; Ambra BioScience, Ascensia Diabetes Care, Becton, Dickinson and Company. Consultant; Self; Becton, Dickinson and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical. Consultant; Self; Calibra Medical. Research Support; Self; Companion Medical, Dexcom, Inc., Glooko, Inc., GlySens Incorporated, Lexicon Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Medtronic MiniMed, Inc.. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Senseonics. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Versartis, Inc., Xeris Pharmaceuticals, Inc., MannKind Corporation. T.L. Cordero: Employee; Self; Medtronic. B.W. Bode: Research Support; Self; Abbott. Advisory Panel; Self; ADOCIA. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk Inc., Diasome Pharmaceuticals, Inc., Sanofi US, Eli Lilly and Company, MannKind Corporation, Dexcom, Inc., OmniPod, Senseonics. X. Chen: Employee; Self; Medtronic. J. Shin: Employee; Self; Medtronic.

BACKGROUND:This study evaluated the safety and performance of the Guardian™ continuous glucose monitoring (CGM) system in children and adolescents with type 1 diabetes (T1D).MATERIALS AND METHODS:Subjects 2-18 years of age (mean ± standard deviation [SD] 13.1 ± 3.9 years) with T1D and duration of diagnosis ≥1 year were enrolled at 11 sites in the United States and wore two Guardian Sensor 3 sensors in the abdomen and/or buttock. Sensors were connected to a transmitter paired with either a Guardian Connect system (i.e., mobile device with software application allowing display of sensor glucose [SG] values) or a Guardian Link 3 transmitter used as a Glucose Sensor Recorder (GSR). There were 145 participants who underwent a 6-h in-clinic frequent sample testing (FST) on day 1 (n = 54), day 3 (n = 48), or day 7 (n = 43) postsensor insertion. During FST, SG values were compared with a Yellow Springs Instrument (YSI) plasma reference every 5-15 min (n = 124, 7-18 years of age; n = 2, 2-6 years of age), or to a self-monitoring of blood glucose (SMBG) reference every 5-30 min (n = 19, 2-6 years of age).RESULTS:The overall mean absolute relative difference (ARD ± SD) between SG and reference values (YSI or SMBG) when calibrating approximately every 12 h, was 10.9% ± 10.7% (3102 paired points) for sensors communicating with the Guardian Connect system and 11.1% ± 10.6% (2624 paired points) for sensors connected to the GSR. The overall percentage of SG values within ±20% of reference values >80 mg/dL or within 20 mg/dL of reference values ≤80 mg/dL was 87.8% for the Guardian Connect system and 86.7% for the GSR, respectively. There was one device-related adverse event of contact dermatitis, but no serious device-related adverse events.CONCLUSIONS:The Guardian CGM system demonstrated good accuracy in children and adolescents. These findings support its use in sensor-integrated insulin pump platforms, as well as a standalone technology, for managing diabetes in pediatric populations.

BACKGROUND:Gestational tight glycemic control is critical for women with type 1 diabetes (T1D). Limited data exist on the adoption and retention of diabetes technologies among women in different parity strata.METHODS:We compared T1D management between T1D Exchange clinic registry participants (mean age 28 ± 9 years, 84% white non-Hispanic, and median T1D duration 13 years) who were pregnant at enrollment or year 1 follow-up ("recently pregnant" between 2010 and 2013, n = 214), ever (but not recently) pregnant (n = 1540), and never pregnant (n = 2586). We examined self-reported maternal and fetal outcomes in 130 women who delivered a baby within the last year.RESULTS:Recently pregnant women had the lowest hemoglobin A1c (6.5% pregnant vs. 7.8% ever pregnant vs. 8.0% never pregnant, P < 0.001). Recently pregnant women reported the highest use of continuous subcutaneous insulin infusion (74% vs. 60% vs. 58%, adjusted P < 0.001) and continuous glucose monitor (CGM) (36% vs.17% vs. 12%, adjusted P < 0.001) therapies compared with ever or never pregnant women, respectively, after adjusting for age, diabetes duration, and socioeconomic status. Among women 18-25 years old, CGM use was highest among recently pregnant women (adjusted P = 0.0022). Never pregnant women 26-45 years old had a higher use of CGM compared with younger counterparts (adjusted P < 0.001). Adverse maternal and fetal outcomes were common.CONCLUSIONS:Despite high uptake levels of advanced diabetes technologies among pregnant women, rates of adverse maternal and fetal outcomes remain high. More studies are needed to determine how these technologies could be best used in pregnancy and postpartum to improve health outcomes among women with T1D.

OBJECTIVE Evaluate the efficacy and safety of the dual sodium–glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS The inTandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo (n = 268), sotagliflozin 200 mg (n = 263), or sotagliflozin 400 mg (n = 262) after 6 weeks of insulin optimization. The primary end point was HbA1c change from baseline at 24 weeks. HbA1c, weight, and safety were also assessed through 52 weeks. RESULTS From a mean baseline of 7.57%, placebo-adjusted HbA1c reductions were 0.36% and 0.41% with sotagliflozin 200 and 400 mg, respectively, at 24 weeks and 0.25% and 0.31% at 52 weeks (all P < 0.001). Among patients with a baseline HbA1c ≥7.0%, an HbA1c <7% was achieved by 15.7%, 27.2%, and 40.3% of patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively (P ≤ 0.003 vs. placebo) at 24 weeks. At 52 weeks, mean treatment differences between sotagliflozin 400 mg and placebo were −1.08 mmol/L for fasting plasma glucose, −4.32 kg for weight, and −15.63% for bolus insulin dose and −11.87% for basal insulin dose (all P < 0.001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points with sotagliflozin versus placebo (P < 0.001) at 24 weeks. Genital mycotic infections and diarrhea occurred more frequently with sotagliflozin. Adjudicated diabetic ketoacidosis (DKA) occurred in 9 (3.4%) and 11 (4.2%) patients receiving sotagliflozin 200 and 400 mg, respectively, and in 1 (0.4%) receiving placebo. Severe hypoglycemia occurred in 17 (6.5%) patients from each sotagliflozin group and 26 (9.7%) patients receiving placebo. CONCLUSIONS In a 1-year T1D study, sotagliflozin combined with optimized insulin therapy was associated with sustained HbA1c reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, NCT02384941).

Background: Persistent use of real-time continuous glucose monitoring (CGM) improves diabetes control in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D). Methods: PRECISE II was a nonrandomized, blinded, prospective, single-arm, multicenter study that evaluated the accuracy and safety of the implantable Eversense CGM system among adult participants with T1D and T2D (NCT02647905). The primary endpoint was the mean absolute relative difference (MARD) between paired Eversense and Yellow Springs Instrument (YSI) reference measurements through 90 days postinsertion for reference glucose values from 40 to 400mg/dL. Additional endpoints included Clarke Error Grid analysis and sensor longevity. The primary safety endpoint was the incidence of device-related or sensor insertion/removal procedure-related serious adverse events (SAEs) through 90 days postinsertion. Results: Ninety participants received the CGM system. The overall MARD value against reference glucose values was 8.8% (95% confidence interval: 8.1%-9.3%), which was significantly lower than the prespecified 20% performance goal for accuracy (P<0.0001). Ninety-three percent of CGM values were within 20/20% of reference values over the total glucose range of 40-400mg/dL. Clarke Error Grid analysis showed 99.2% of samples in the clinically acceptable error zones A (92.4%) and B (6.8%). Ninety-one percent of sensors were functional through day 90. One related SAE (1.1%) occurred during the study for removal of a sensor. Conclusions: The PRECISE II trial demonstrated that the Eversense CGM system provided accurate glucose readings through the intended 90-day sensor life with a favorable safety profile.

Background The benefit of initiation of insulin pump therapy (continuous subcutaneous insulin infusion; CSII) in patients with type 1 diabetes using continuous glucose monitoring (CGM) has not been studied. We aimed to assess glycaemic outcomes when switching from multiple daily injections (MDI) to CSII in adults with type 1 diabetes using CGM.Methods In this multicentre, randomised controlled trial, 75 adults with type 1 diabetes in the CGM group of the DIAMOND trial were randomly assigned via the study website using a computer-generated sequence to continue MDI or switch to CSII, with continuation of CGM, for 28 weeks. The primary outcome was CGM-measured time in the glucose concentration range of 70-180 mg/dL (3.9-10.0 mmol/L). This study is registered with ClinicalTrials.gov, number NCT02282397.Findings Between April 14, 2015, and May 5, 2016, 37 participants were randomly assigned to the CGM plus CSII group and 38 participants were randomly assigned to the CGM plus MDI group. The study was completed by 36 (97%) of 37 participants in the CGM plus CSII group and 35 (92%) of 38 participants in the CGM plus MDI group. Mean CGM use was 6.7 days per week (SD 0.8) in the CGM plus CSII group and 6.9 days per week (0.3) in the CGM plus MDI group (p=0.86). No participants in the CGM plus CSII group who completed the trial discontinued CSII. Over the follow-up period, mean time in the glucose concentration range of 70-180 mg/dL (3.9-10.0 mmol/L) was 791 min per day (SD 157) in the CGM plus CSII group and 741 min per day (225) in the CGM plus MDI group (adjusted mean treatment group difference: 83 min, 95% CI 17-149; p=0.01). Participants in the CGM plus CSII group had a greater reduction in CGM-measured mean glucose (p=0.005) and hyperglycaemia (on four metrics: p=0.007 for >180 mg/dL [>10.0 mmol/L], p=0.02 for >250 mg/dL [>13.9 mmol/L], p=0.04 for >300 mg/dL [>16.6 mmol/L], and p=0.02 for the area under the curve for 180 mg/dL [10.0 mmol/L]), but also an increase in CGM-measured hypoglycaemia (p=0.0001 for <70 mg/dL [<3.9 mmol/L], p=0.0002 for <60 mg/dL [<3.3 mmol/L], p=0.0009 for <50 mg/dL [<2.8 mmol/L], p=0.0002 for the area over the curve for 70 mg/dL [3.9 mmol/L]). Mean HbA1c change from baseline to 28 weeks was 0.3% (SD 0.9; 3.3 mmol/mol [SD 9.8]) in the CGM plus CSII group and 0.1% (0.4; 1.1 mmol/mol [4.4]) in the CGM plus MDI group (p=0.32). Severe hypoglycaemia occurred in one participant in the CGM plus MDI group, and diabetic ketoacidosis and severe hyperglycaemia occurred in one participant each in the CGM plus CSII group.Interpretation Our findings show that glycaemic control measured by time in the glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) is improved by initiation of CSII in adults with type 1 diabetes. However, biochemical hypoglycaemia also was increased in the study, which will be important to consider when incorporating these results into clinical practice.

Diabetes Technology & TherapeuticsVol. 18, No. 5 Letters to the EditorResponse to the Comment on “The Performance and Usability of a Factory-Calibrated Flash Glucose Monitoring System” by Bailey et al.Timothy S. Bailey, Shridhara Alva, Bruce W. Bode, Mark P. Christiansen, and Leslie J. KlaffTimothy S. BaileyAMCR Institute, Escondido, California.Search for more papers by this author, Shridhara AlvaDepartment of Clinical Affairs, Abbott Diabetes Care, Alameda, California.Search for more papers by this author, Bruce W. BodeAtlanta Diabetes Associates, Atlanta, Georgia.Search for more papers by this author, Mark P. ChristiansenDiablo Clinical Research, Walnut Creek, California.Search for more papers by this author, and Leslie J. KlaffRainier Clinical Research Center, Renton, Washington.Search for more papers by this authorPublished Online:9 May 2016https://doi.org/10.1089/dia.2016.0093AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Response to the Comment on “The Performance and Usability of a Factory-Calibrated Flash Glucose Monitoring System” by Bailey et al.." Diabetes Technology & Therapeutics, 18(5), pp. 336–337FiguresReferencesRelatedDetailsCited byEvaluation of continuous flash glucose monitoring in a pediatric ICU setting3 September 2019 | Journal of Clinical Monitoring and Computing, Vol. 34, No. 4Data Reliability and Quality in Body Area Networks for Diabetes Monitoring19 December 2018Replacement of Blood Glucose Measurements by Measurements With Systems for Real-Time Continuous Glucose Monitoring (rtCGM) or CGM With Intermittent Scanning (iscCGM): A German View9 July 2017 | Journal of Diabetes Science and Technology, Vol. 11, No. 4 Volume 18Issue 5May 2016 InformationCopyright 2016, Mary Ann Liebert, Inc.To cite this article:Timothy S. Bailey, Shridhara Alva, Bruce W. Bode, Mark P. Christiansen, and Leslie J. Klaff.Response to the Comment on “The Performance and Usability of a Factory-Calibrated Flash Glucose Monitoring System” by Bailey et al..Diabetes Technology & Therapeutics.May 2016.336-337.http://doi.org/10.1089/dia.2016.0093Published in Volume: 18 Issue 5: May 9, 2016Online Ahead of Print:April 20, 2016PDF download

Aims. To examine the association of the serum levels of TNF receptors, adhesion molecules, and inflammatory mediators with diabetic retinopathy (DR) in T1D patients. Methods. Using the multiplex immunoassay, we measured serum levels of eight proteins in 678 T1D subjects aged 20–75 years. Comparisons were made between 482 T1D patients with no complications and 196 T1D patients with DR. Results. The levels of sTNFR-I, sTNFR-II, CRP, SAA, sgp130, sIL6R, sVCAM1, and sICAM1 were significantly higher in the T1D patients with DR as compared to T1D patients with no complications. Multivariate logistic regression analysis revealed significant association for five proteins after adjustment for age, sex, and disease duration (sTNFR-I: OR = 1.57, sgp130: OR = 1.43, sVCAM1: OR = 1.27, sICAM1: OR = 1.42, and CRP: OR = 1.15). Conditional logistic regression on matched paired data revealed that subjects in the top quartile for sTNFR-I (OR = 2.13), sTNFR-II (OR = 1.66), sgp130 (OR = 1.82), sIL6R (OR = 1.75), sVCAM1 (OR = 1.98), sICAM1 (OR = 2.23), CRP (OR = 2.40) and SAA (OR = 2.03), had the highest odds of having DR. Conclusions. The circulating markers of inflammation, endothelial injury, and TNF signaling are significantly associated with DR in patients with T1D. TNFR-I and TNFR-II receptors are highly correlated, but DR associated more strongly with TNFR-I in these patients.

CONTEXT:Previous studies have attempted to elucidate the potential role of various cytokines and chemokines in human type 1 diabetes (T1D); however, the precise role of these serum proteins in T1D is still controversial and undetermined primarily due to the small sample sizes of the previous studies. We profiled a panel of serum cytokines and chemokines using a large-scale, two-stage study design for the discovery and validation of the serum proteins associated with T1D.PARTICIPANTS:The participants were patients with T1D and islet autoantibody-negative control subjects from the Phenome and Genome of Diabetes Autoimmunity study.MAIN OUTCOME MEASURES:Thirteen cytokines and chemokines were measured in serum of 4424 subjects using multiplex immunoassays.RESULTS:Using 1378 samples in Stage 1, we found that four of the 13 proteins are significantly lower in patients with T1D than controls (IL8: odds ratio [OR] = 0.40; P = 5.7 × 10(-19); IL-1Ra: OR = 0.42; P = 1.1 × 10(-13); MCP-1: OR = 0.60; P = 6.7 × 10(-9); and MIP-1β: OR = 0.63; P = 4.2 × 10(-7)). Our confirmation data with 3046 samples in Stage 2 further confirmed the significant negative associations of these four proteins with T1D (IL8: OR = 0.43; P = 8.9 × 10(-32); IL-1Ra: OR = 0.56, P = 3.7 × 10(-27); MCP-1: OR = 0.61, P = 4.3 × 10(-17); and MIP-1β: OR = 0.69, P = 2.4 × 10(-13)). Quartile analyses also suggested that significantly more T1D cases have protein levels in the bottom quartile than in the top quartile for all four proteins: IL8 (OR = 0.09), IL-1Ra (OR = 0.18), MCP-1 (OR = 0.38), and MIP-1β (OR = 0.44). Furthermore, the negative associations between T1D and serum levels of all four proteins are stronger in genetically high-risk groups compared with the moderate and low-risk groups.CONCLUSIONS:IL8, IL-1Ra, MCP-1, and MIP-1β are significantly lower in patients with T1D than controls.

Abstract Introduction: The purpose of the study was to evaluate the performance and usability of the FreeStyle® Libre™ Flash glucose monitoring system (Abbott Diabetes Care, Alameda, CA) for interstitial glucose results compared with capillary blood glucose results. Materials and Methods: Seventy-two study participants with type 1 or type 2 diabetes were enrolled by four U.S. clinical sites. A sensor was inserted on the back of each upper arm for up to 14 days. Three factory-only calibrated sensor lots were used in the study. Sensor glucose measurements were compared with capillary blood glucose (BG) results (approximately eight per day) obtained using the BG meter built into the reader (BG reference) and with the YSI analyzer (Yellow Springs Instrument, Yellow Springs, OH) reference tests at three clinic visits (32 samples per visit). Sensor readings were masked to the participants. Results: The accuracy of the results was demonstrated against capillary BG reference values, with 86.7% of sensor results within Consensus Error Grid Zone A. The percentage of readings within Consensus Error Grid Zone A on Days 2, 7, and 14 was 88.4%, 89.2%, and 85.2%, respectively. The overall mean absolute relative difference was 11.4%. The mean lag time between sensor and YSI reference values was 4.5±4.8 min. Sensor accuracy was not affected by factors such as body mass index, age, type of diabetes, clinical site, insulin administration, or hemoglobin A1c. Conclusions: Interstitial glucose measurements with the FreeStyle Libre system were found to be accurate compared with capillary BG reference values, with accuracy remaining stable over 14 days of wear and unaffected by patient characteristics.