bluuebunny/crossref_metadata_2025 huggingface dataset:
1037-P: Glucose Control following Missed and Late Meal Boluses with a Medtronic Enhanced-Hybrid Closed-Loop (E-HCL) System
Authors: LEE MELISSA H. , VOGRIN SARA , PALDUS BARBORA , JONES HANNAH , OBEYESEKERE VARUNI R. , SIMS CATRIONA M. , WYATT SUE A. , WARD GLENN M. , MCAULEY SYBIL A. , MACISAAC RICHARD , KRISHNAMURTHY BALASUBRAMANIAN , SUNDARARAJAN VIJAYA , JENKINS ALICIA , O'NEAL DAVID N.
Published: June 2019

Background: A missed or late meal insulin bolus can impact glycemia in type 1 diabetes (T1D).

Aim: To study glucose control after missed and late meal boluses in T1D adults using a prototype enhanced hybrid closed-loop (E-HCL) system (Medtronic) providing automated basal insulin and correction boluses.

Methods: Twelve T1D adults (median HbA1c 6.8% [IQR 6.2-7.2] | 51mmol/mol [44-55] participated. After 1-week run-in at home in Open Loop, E-HCL was activated during 1-week supervised hotel phase followed by 3 weeks free-living at-home. Participants consumed a standardized 40g carbohydrate dinner in the supervised phase. Four hours of post-prandial glucose data following a standard bolus pre-meal in E-HCL at home were compared in a pairwise manner to 1) Pre-meal bolus in Open Loop Run-In; 2) 20minute Late bolus in E-HCL supervised; 3) Missed bolus in E-HCL supervised using Wilcoxon Signed-Rank Test.

Results: Late bolus was associated with mild hypoglycemia and higher glucose variability; missed bolus was associated with hyperglycemia (Table). Overall time in CL was 99.98%. E-HCL at home vs. Open Loop (run-in) had greater time-in-70-180mg/dL range (85.3 vs. 75.0%, p=0.003). There was no severe hypoglycemia or ketoacidosis.

Conclusions: While glucose excursions were modest, the administration and timing of meal boluses influenced post-meal glycemia in well-controlled T1D adults using E-HCL.

Disclosure

M.H. Lee: Research Support; Self; Medtronic. Speaker's Bureau; Self; AstraZeneca. S. Vogrin: None. B. Paldus: Other Relationship; Self; Australian Diabetes Society, JDRF, Medtronic. H. Jones: None. V.R. Obeyesekere: None. C.M. Sims: Stock/Shareholder; Self; Medtronic. S.A. Wyatt: Other Relationship; Self; Animas Corporation, Medtronic. G.M. Ward: None. S.A. McAuley: Research Support; Self; JDRF, Medtronic. Speaker's Bureau; Self; Australian Diabetes Society, Eli Lilly and Company. R. MacIsaac: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. Other Relationship; Self; AstraZeneca, Novo Nordisk Inc. B. Krishnamurthy: None. V. Sundararajan: None. A. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. D.N. O'Neal: None.
1041-P: Feasibility Study of a Hybrid Closed-Loop System with Automated Correction Boluses
Authors: NIMRI REVITAL , GROSMAN BENYAMIN , KURTZ NATALIE , ROY ANIRBAN , NIR JUDITH , LOEWENTHAL NETA , KAUFMAN FRANCINE R. , PHILLIP MOSHE
Published: June 2019

Background: Automated insulin delivery, or closed-loop (CL), systems are emerging as a management tool for individuals with T1D. The MiniMed™ 670G system is a single hormone hybrid closed-loop (HCL) system that adjusts basal insulin delivery based on sensor glucose (SG)levels and is already used in clinical practice. An enhanced HCL system (e-HCL) prototype with an automated correction bolus feature was developed and evaluated in a small feasibility study.

Methods: Subjects (n=12) aged a mean±SD of 17.6±2.9 years with T1D and an A1C of 7.3±0.7% (56.5±7.7 mmol/mol) completed a 6-day run-in period with the e-HCL system in open-loop (OL) (i.e., Auto Mode OFF and Suspend before low ON). Thereafter, a supervised hotel period (6 days/5 nights) with CL challenges (missed meal bolus, late meal bolus, and physical activity) was completed, and followed by a 3-week at-home period with Auto Mode and automated correction boluses ON, without restrictions. Glycemic control was compared between the OL run-in period and CL period.

Results: During the at-home period, subjects spent 93±4% of the time in Auto Mode. Time within target glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) increased from 68.8±10.5% to 74±6.1%, time >180 mg/dL reduced from 27.1±11.9% to 23.7±8.8%, and time <70mg/dL dropped from 4.1±3.7% to 3±2.8%. Total daily insulin dose was 56.3±10.9 units and 53.4±12.5 units during the OL run-in and CL periods, respectively. A greater percentage of insulin was delivered as bolus than as basal, during the CL period (54.3±8.9% versus 41.7±4.36%). No serious adverse events occurred.

Conclusions: Incorporating automated correction boluses to an HCL system was safe and effective in controlling day and night glucose levels, during a 3-week at-home period.

Disclosure

R. Nimri: Employee; Self; DreaMed Diabetes. Research Support; Self; Dexcom, Inc., Glooko, Inc., Insulet Corporation, JDRF, Medtronic, National Institutes of Health. Speaker's Bureau; Self; Lilly Diabetes. Stock/Shareholder; Self; DreaMed Diabetes. B. Grosman: Employee; Self; Medtronic. N. Kurtz: Employee; Self; Medtronic MiniMed, Inc. A. Roy: Employee; Self; Medtronic MiniMed, Inc. J. Nir: None. N. Loewenthal: None. F.R. Kaufman: Employee; Self; Medtronic. M. Phillip: Consultant; Self; Qulab Medical, RSP Systems A/S. Research Support; Self; Bristol-Myers Squibb Company, Dexcom, Inc., JDRF, Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., OPKO. Stock/Shareholder; Self; DreaMed Diabetes, Ltd., NG Solutions Ltd., Nutriteen Professional Ltd. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Insulet Corporation, Medtronic MiniMed, Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis.
1049-P: Towards Prolongation of Insulin Pump Catheters Wearing Time Using a Mixture of Insulin and a Nonsteroidal Anti-inflammatory Drug
Authors: ARDILOUZE JEAN-LUC , GOBEIL FERNAND , MENARD JULIE , BOVAN DANIJELA , MESSIER VIRGINIE , SAVARD MARTIN , BAILLARGEON JEAN-PATRICE , RABASA-LHORET RÉMI
Published: June 2019

Recommendation to insulin pump users is to change catheters every 3 days. Convergent data point to inflammation for catheter-related insertion site problems. Objective: to explore if adding a tiny amount of non-steroidal anti-inflammatory drug (NSAID) into insulin solution increases catheter wearing time compare to insulin alone.

Methods: Double-blinded randomized study in insulin pump users with type 1 diabetes. Participants were instructed to keep catheters as long as glycemic control was acceptable and insertion site remained comfortable. Subjects performed 4 experiments: 2 testing lispro and 2 testing the mixed solution (lispro: 90 units/ml + ketorolac: 3 mg/ml), each experimental period separated by a 1-week washout. Safety parameters were measured at entry vs. end of study (including plasma ketorolac concentration). We defined responders as participants wearing catheter ≥ 1 day using lispro+ketorolac vs. lispro.

Results: Fourteen subjects completed the study (males: 7, age: 43.5±18.0 years, diabetes duration: 29.6±13.9 years, pump therapy: 9.0±4.5 years, A1c: 7.1±0.6%). There was no catheter wearing time difference (lispro+ketorolac: 7.45±2.99 vs. lispro: 7.82±2.64 days). The daily doses of insulin and ketorolac were respectively 46.44±12.39 units and 1.55±0.41 mg. Ketorolac plasmatic concentration was at 19.7±17.6 ng/ml (1000 times lower than after clinically indicated doses). From entry vs. end of study, creatinine increased (70±17 vs. 81±19 µmol/L, p=0.018) and glomerular filtration rate declined (119±33 vs. 109±34 ml/min/1.73m2, p=0.028). Wearing time improved in responders (n=7, 50%): 6.04±1.38 vs. 7.97±1.68 days (p=0.018).

Conclusions: While no difference was observed overall, a large sub-group of patients could be responders to the addition of some NSAID to insulin. Due to the small sample size, the true magnitude of kidney function deterioration is unknown and might not be clinically significant.

Disclosure

J. Ardilouze: None. F. Gobeil: None. J. Menard: None. D. Bovan: None. V. Messier: Other Relationship; Self; Eli Lilly and Company. M. Savard: None. J. Baillargeon: None. R. Rabasa-Lhoret: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Novo Nordisk A/S.

Funding

JDRF
1053-P: Automated Adaptation of the Bionic Pancreas while Transitioning from Multiple Daily Injection Insulin Regimens
Authors: SHERWOOD JORDAN , BALLIRO COURTNEY A. , EL-KHATIB FIRAS , EKHLASPOUR LAYA , HSU LIANA , BUCKINGHAM BRUCE A. , DAMIANO EDWARD , RUSSELL STEVEN J.
Published: June 2019

In a random-order, outpatient crossover trial we compared automated glycemic control with the insulin-only bionic pancreas (BP) to usual care in subjects with T1D. Subjects transitioned directly to the BP from CSII or MDI (insulins glargine n=6, detemir n=1, or degludec n=5). The BP continuously adapts to individual insulin needs and was initialized based on body mass only, without information about the baseline insulin regimen. The first 24 hours of BP control was compared to days 3-7 (the 5-day period considered for the primary outcome) to examine the effect of having received long-acting insulin the day prior to initiation of the BP. As shown in the Table, the mean CGM glucose and time-in-range did not differ between the first 24 hours and days 3-7 after starting the BP in subjects on MDI at baseline, while there was a reduction in mean and an increase in time-in-range among those on CSII at baseline. Subjects on MDI at baseline did not experience more hypoglycemia in the first 24 hours despite having long-acting insulin on board. Both subjects on MDI and CSII at baseline achieved good glucose control on the BP (see Table). Surprisingly, there was no difference in the insulin total daily dose (TDD) between the first 24 hours and days 3-7 in the MDI users despite an average TDD of basal insulin at baseline of 15 u/day. These results suggest that BP therapy can be safely initiated directly from MDI regimens.

Disclosure

J. Sherwood: None. C.A. Balliro: None. F. El-Khatib: Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. L. Ekhlaspour: None. L. Hsu: None. 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. E. Damiano: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Beta Bionics. Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. Stock/Shareholder; Spouse/Partner; Beta Bionics. Other Relationship; Self; Ascensia Diabetes Care, Senseonics. S.J. Russell: Advisory Panel; Self; Companion Medical, Unomedical a/s. Consultant; Self; Flexion Therapeutics. Research Support; Self; Beta Bionics, MITRE Corporation, Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Self; ADOCIA, Ascensia Diabetes Care, Ascensia Diabetes Care, Lilly Diabetes, Roche Diabetes Care, Senseonics.

Funding

National Institutes of Health (NIDDKUC4DK108612)
1055-P: Glucose Management Indicator Results from Real-World Data of 1,838 Patients with Type 1 Diabetes Using the Omnipod® Insulin Management System with Continuous Glucose Monitoring and Cloud-Based Data Management
Authors: LAYNE JENNIFER E. , JANTZ JAY , ZHENG YIBIN , HE JIALUN , BENJAMIN ERIC , LY TRANG T.
Published: June 2019

Glucose Management Indicator (GMI) is a new term for estimating A1C from CGM data which is intended to inform glucose management for people with diabetes. This analysis assessed GMI and glycemic metrics for a large cohort of pediatric, adolescent and adult patients with T1D using data from the Omnipod® Insulin Management System (Insulet Corp, Acton, MA), real-time CGM (Dexcom, San Diego, CA) and data management system (Glooko, Mountain View, CA). Usage data uploaded to the data management system from January 2015 through September 2018 were matched via device serial number to a second database of self-reported demographic data and de-identified. CGM data from patients who used CGM >50% of days over ≥3 months of system use were analyzed. Glycemic profiles and insulin use for 1,838 patients stratified by age < 6 y, 6 to <12 y, 12 to <18 y and ≥18 y are reported in the Table. GMI was 7.8%, 7.5%, 7.4%, 7.0%, respectively, across age groups. Corresponding estimated A1C by ADAG method was 8.2%, 7.7%, 7.6% and 7.0%. Data from this large, real-world cohort of patients with T1D across age groups provide valuable insights to GMI and glycemic metrics, and demonstrate that the use of tubeless insulin pump with CGM is associated with favorable glycemic control when compared to large national registries such as the T1D Exchange.

Disclosure

J.E. Layne: Employee; Self; Insulet Corporation. J. Jantz: Employee; Self; Insulet Corporation. Employee; Spouse/Partner; Insulet Corporation. Y. Zheng: Employee; Self; Insulet Corporation. Stock/Shareholder; Self; Insulet Corporation. J. He: Employee; Self; Insulet Corporation. E. Benjamin: Employee; Self; Insulet Corporation. T.T. Ly: Employee; Self; Insulet Corporation.

Funding

Insulet Corporation
1058-P: The Use of Metabolic Digital Twins to Personalize Mealtime Insulin Dosing in Type 1 Diabetes Clinical Management
Authors: SMITH TENELE A. , SERON MARIA M. , GOODWIN GRAHAM C. , MEDIOLI ADRIAN M. , KING BRUCE R. , SMART CARMEL E. , HARRIS MARK , ONEAL DAVID N. , RAFFERTY JORDAN , HOWLEY PETER
Published: June 2019

Introduction: Type 1 diabetes guidelines recommend that mealtime insulin dosing accounts for fat and protein. However, implementation remains a challenge.

Aim: To evaluate an individual’s glycemic response to a high fat, high protein meal (HFHP) and develop a personalized ‘metabolic digital twin’ (MDTwin) capable of predicting an optimal insulin dose and delivery pattern which accounts for meal fat and protein.

Method: Participants (n=9) using pump therapy; mean age 13.9 ±3.2 years (5 male), T1D duration 4.8 ±3.8 years, and HbA1c 49 mmol/mol (6.7 ±0.6%) wore Dexcom G5 CGMS and were given an insulin dual wave bolus (insulin to carbohydrate ratio [ICR] x1, ICRx1.2, ICRx1.4 or ICRx1.6) and ate a HFHP (C:30g, F:40g, P:50g) on 4 mornings. Individual MDTwins were fitted by System Identification methodology combined with a statistical quantification using the ICRx1 and ICRx1.6 CGMS traces. MDTwins were validated using the ICRx1.2 and ICRx1.4 traces.

Results: The MDTwins identified individual insulin and distribution requirements to achieve optimal postprandial glycemic control (Figure). MDTwins identified marked inter-individual variability in insulin dose and distribution requirements.

Conclusion: MDTwins can potentially be used to inform and individualize insulin dosing strategies for meal fat and protein to produce optimal glycemic outcomes. Further research is required.

Disclosure

T.A. Smith: None. M.M. Seron: None. G.C. Goodwin: None. A.M. Medioli: None. B.R. King: None. C.E. Smart: None. M. Harris: None. D.N. ONeal: None. J. Rafferty: None. P. Howley: None.

Funding

Diabetes Australia
1067-P: Open Source Artificial Pancreas System (APS) vs. Combination Insulin Pump with Flash Glucose Monitoring in Adults with Type 1 Diabetes: An Observational Study
Authors: WILMOT EMMA G. , LANGELAND LINN , MCLAY ALASDAIR , TAYLOR NICOLA ,   ISKANDAR RAUF IDRIS
Published: June 2019

Despite the rising number of Open Source APS (Open APS) users in the UK, little is known about their glucose outcomes in comparison with conventional approved management strategies for type 1 diabetes. We therefore compared glucose outcomes (HbA1c, Time in Range, TIR and Time Below Range, TBR) of people on continuous subcutaneous insulin infusion (CSII) with either Open APS versus FreeStyle Libre (FSL) flash glucose monitor.

Data were extracted from the National Association of British Clinical Diabetologists (ABCD) FSL audit tool for people using CSII and FSL (N=30) and compared with Open APS users (N=9). Demographic parameters were as follows: Open APS users (mean age 44.2; 44% female, diabetes duration 25 years, mean Open APS use of 11 months) and CSII/FSL users (mean age 59.3 years; 78% female; diabetes duration 26 years; mean CSII/FSL use of 5.9 months).

Mean HbA1c in the 12 months prior to initiating Open APS was 7.3±1.4%. This was significantly reduced to 6.2±0.4% post Open APS (P=0.046). Those who started FSL, had a mean pre-FSL HbA1c of 7.6±0.8%, which reduced to 7.2±0.6% at follow-up (P=0.030).

30-day TIR, defined as % of glucose data 3.9-10mmol/l, achieved by Open APS users (N=9) was significantly higher than the FSL users (N=25) (83.6±7.2% vs. 55.9±11.5%; P<0.001). Similarly, 30-day TBR for the Open APS users was significantly lower than the FSL users (2.5±1.8% vs. 5.7±4.7%, P=0.006) respectively. None of the people on Open APS or FSL experienced hospital admissions or severe hypoglycaemic events during this observational period.

In conclusion, despite a lower initial HbA1c, the cohort of Open APS users achieved a greater reduction in HbA1c, significantly greater TIR and less TBR, compared with CSII/FSL users. Further work is required to explore the potential benefits of Open Source APS compared to conventional approved strategies.

Disclosure

E.G. Wilmot: Advisory Panel; Self; Dexcom, Inc. Research Support; Self; Diabetes UK. Speaker's Bureau; Self; Abbott, Eli Lilly and Company, Novo Nordisk Inc., Sanofi. L. Langeland: None. A. McLay: Speaker's Bureau; Self; Eli Lilly and Company. N. Taylor: None. I.R. Idris: None.
1070-P: Assessment of Effectiveness and Satisfaction of Use of the Automatic Injection System GensuPen 2
Authors: CYPRYK KATARZYNA , ZURAWSKA-KLIS MONIKA
Published: June 2019

Success in treating diabetes is highly dependent on the patient's satisfaction with the therapy. The aim of the study was to assess the effectiveness and satisfaction of the use of Automatic Injection System GensuPen2 device which is a pen with a spring-assisted insulin release mechanism and a laterally located trigger. 4707 adult insulin treated diabetic patients (50.44% women) from all over Poland took part in the study. For 42% of subjects, the previously used pen was changed to the GensuPen2. During the first visit demographic and medical data were gathered. HbA1c was measured and the questionnaires concerning the satisfaction with the currently used pen and evaluation of pain severity, satisfaction with the treatment (all three are 5-point scales), and the health-related quality of life (HRQoL) were filled out twice - at the beginning and after 12 weeks of the study. The mean age was 64.8±10.1 years and duration of diabetes was 9.9±6.5 years. Impaired visual function was found in 13.7% and 12.3% of the subjects had an impaired manual efficiency. After 12 weeks, HbA1c level dropped from 8.26±1.17% to 7.72±0.89% (P <0.001). Satisfaction with the use of pen increased from on average 3.33 to 4.31 points (P <0.001) after switching to GensuPen2. Evaluation of pain severity revealed that discomfort and pain related to insulin injection decreased from on average 3.82 to 2.41 points (P <0.001). Insulin therapy with the use of GensuPen2 was comfortable for 94.48% of patients. More than half of the patients were more satisfied with GensuPen2 than with the previously used pen, and 98.63% of subjects declared that they did not want to return to previous pen. Satisfaction with diabetes treatment raised from 81.2% to 94.5% (P <0.001). The HRQoL increased from on average 5.81 to 7.39 points (P <0.001). The use of the GensuPen2 by diabetes patients improved metabolic control, increased satisfaction with diabetes treatment and the use of insulin pen, reduced the pain during injection, and improved their quality of life.

Disclosure

K. Cypryk: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S. Speaker's Bureau; Self; Abbott, Servier. M. Zurawska-Klis: Speaker's Bureau; Self; Polfa Tarchomin S.A. Other Relationship; Self; Berlin-Chemie AG, Lilly Diabetes, Novo Nordisk Inc.

Funding

Bioton
1071-P: Uptake of Continuous Subcutaneous Insulin Infusion Therapy by Adults with Type 1 Diabetes
Authors: GAJEWSKA KATARZYNA ANNA , SREENAN SEAMUS , BIESMA REGIEN , BENNETT KATHLEEN
Published: June 2019

Introduction: Continuous Subcutaneous Insulin Infusion (CSII) treatment for people with type 1 diabetes (T1D) is fully funded in Ireland via the Long-Term Illness scheme (LTI) and, similarly as in some other developed countries such as Germany, Sweden or the UK, does not involve any out-of-pocket expenses for the person with T1D. Uptake of CSII in adults has been reported to vary from 6.7% (Wales, 2018), through 15.6% (England, 2018) up to >50% in the United States (in 2012). However, available evidence on the uptake of CSII, particularly in adults, is scarce.

The aim of this study was to estimate the uptake of CSII in Ireland.

Methods: A retrospective cross-sectional study was conducted utilizing the Irish Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) national pharmacy claims database data from the years 2011-2016. Individuals with T1D were identified by co-prescription of insulin and glucometer test strips without any prolonged course (>12 months) of oral hypoglycemic agents prior to commencing insulin. Individuals using CSII were identified by a prescription of infusion sets.

Results: Of all adults with T1D (>18 years of age) meeting our criteria (n=19,551), only 5.84% (n=1141) were claiming infusion sets (95% CI 5.51% - 6.16%). The uptake of CSII varied geographically across Ireland from as low as 1.68% to 8.35%.

Conclusions: In comparison to other countries where CSII therapy is fully covered, uptake of CSII was low in Irish adults. The determinants of the uptake (barriers to and facilitators in accessing this diabetes-related technology) are under more in-depth investigation.

Disclosure

K.A. Gajewska: None. S. Sreenan: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Other Relationship; Self; Eli Lilly and Company. R. Biesma: None. K. Bennett: None.

Funding

Health Research Board (SPHeRE/2013/1)
1089-P: Ultra Rapid Lispro (URLi) Improves Postprandial Glucose (PPG) Control and Time in Range (TIR) in T1D Compared with Humalog (Lispro): PRONTO-T1D Continuous Glucose Monitoring (CGM) Substudy
Authors: BODE BRUCE W. , CAO DACHUANG , LIU RONG , HARDY THOMAS , BUE-VALLESKEY JULIANA M.
Published: June 2019

Ambulatory glucose profiles were evaluated in 269 (22%) patients (pts) in PRONTO-T1D assigned to double-blind URLi (n=97) or lispro (n=99) given at start of the meal, or open-label URLi (n=73) given 20 min after the meal (URLi +20). Primary endpoint was incremental AUC0-2h (iAUC) after breakfast. Blinded CGM (Dexcom G4 Platinum) was worn for 14 days before baseline and week 26. Pts reflected main study population: mean A1C at week 26 was 7.15% - URLi, 7.12% - lispro, 7.35% - URLi+20.

Compared to lispro, URLi had significantly smaller breakfast iAUC0-2h with estimated treatment difference (ETD) -28.1 mg.h/dL, p=0.048; more daytime TIR (71-180 mg/dL) ETD +43.6 min, p=0.020; and similar nighttime TIR. Time <50 mg/dL and >180 mg/dL were both numerically lower with URLi in daytime, with less time <50 mg/dL at nighttime vs. lispro: 7.0 vs. 12.6 min, p=0.023.

PPG control in pts who marked meal times improved with URLi, while URLi +20 showed greater PPG variability (Figure). Glucose variability via CV and SD metrics was similar between groups, but less glucose variability was noticeable in CGM profiles of pts treated with URLi.

When injected at the start of the meal, URLi resulted in significantly better PPG control and increased daytime TIR vs. lispro without increasing time in hypoglycemia. CGM results augment findings from PRONTO-T1D.

Disclosure

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. D. Cao: Employee; Self; Eli Lilly and Company. R. Liu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. T. Hardy: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J.M. Bue-Valleskey: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
1091-P: Association between Mild and Severe Hypoglycemia in People with T1 and T2 Diabetes Enrolled in Randomized Controlled Trials for Assessing Insulin Therapy
Authors: ROUSSEL RONAN , MOUTAIROU ABDUL , RIVELINE JEAN-PIERRE , GAUTIER JEAN-FRANCOIS , POTIER LOUIS
Published: June 2019

Background and Aims: Hypoglycemia is a major threat of insulin therapy, but only severe events are often considered as valid endpoints. Surrogates are required; mild events are logical candidates. The International Hypoglycemia Study Group (IHSG) proposed thresholds (3.9 and 3.0 mmol/L) for representative mild events, but evidence is scarce.

Materials and Methods: We studied the correlation of the rate (or the incidence) of non-severe events with the rate (or the incidence) of severe events in a study-level systematic analysis of published data (1/1/00-6/1/18) in insulin-treated patients. Mild event was defined as either “any hypoglycemia,” or “severe or confirmed <3.9 mmol/L,” or “severe or confirmed <3.0,” with a tolerance of +/-0.4 mmol/L to manage the multiplicity of definitions. Nocturnal period was defined as per study design, therefore not homogeneously. Severe events were mostly defined as per IHSG.

Results and Conclusion: 127 out of 15570 studies were eventually included. Pearson R² are presented (Figure). The mild hypoglycemia were usually better correlated with incidence rather than rate of severe events. Incidence of severe or confirmed <3.0 mmol/L, especially if limited to the night, appeared to be the best surrogate for incidence of severe events.

Disclosure

R. Roussel: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Physiogenex. Research Support; Self; Janssen Pharmaceuticals, Inc. A. Moutairou: None. J. Riveline: Board Member; Self; Abbott, Lilly Diabetes, Novo Nordisk Inc. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Air Liquide, Amgen Inc. Speaker's Bureau; Self; Abbott, Lilly Diabetes, Sanofi. J. Gautier: None. L. Potier: Advisory Panel; Self; Merck Sharp & Dohme Corp. Consultant; Self; Sanofi.

Funding

Sanofi
1092-P: Effect of Inappropriate Resuspension of Insulin Pen on Amount of Dispensed Insulin
Authors: DECHATES BOTHAMAI , JUNNU SARAWUT , KONGMALAI TANAWAN , SRISAWAT CHATCHAWAN , SRIWIJITKAMOL APIRADEE
Published: June 2019

Background: Inappropriate resuspension of NPH insulin resulted in inaccurate dose of insulin, however those studies estimated the amount of insulin based on the cloudiness of insulin, which did not correctly reflex the amount of insulin.

Objective: To study the effect of inappropriate resuspension of premixed insulin pen on the amount of dispensed insulin which was directly determined using a more accurate Ultra-High performance Liquid Chromatography (UHPLC) technique.

Methods: The premixed 70/30 autopen was used in this study. Four methods of insulin resuspension were evaluated (n=5, for each method), i.e., upright position without resuspension (upright), horizontal position without resuspension (horizon), resuspension by tipping over 5x (5x), and 20x (20x, control). 30 unit of insulin from 1st injection of each pen were collected. Then, 30 units of insulin in each pen were discarded every 20 minutes for 8 times, each pen were kept in the initial resuspension method between each injection, and the last 30 unit of insulin in each pen were collected. Collected insulin were analyzed by UHPLC.

Results: Table showed the UHPLC results.

Conclusions: Inappropriate insulin pen resuspension or the lack thereof have significantly affect the amount of dispensed insulin by 3-6%, and this resulted in inaccurate dose of insulin throughout the used of that pen.

Disclosure

B. Dechates: None. S. Junnu: None. T. Kongmalai: None. C. Srisawat: None. A. Sriwijitkamol: None.
11-LB: Nonsevere Hypoglycemia Predicts Increased Risk of Subsequent Severe Events in Patients with Type 2 Diabetes
Authors: HELLER SIMON R. , HACHMANN-NIELSEN ELISE , KVIST KAJSA
Published: June 2019

It is well-known that higher rates of non-severe hypoglycemic episodes (NSHEs) associate with a greater risk of severe hypoglycemic episodes (SHEs) in patients with type 1 diabetes. We investigated whether a similar association existed in patients with type 2 diabetes (T2D). We explored if annual rate of NSHEs was associated with time to first SHE, cardiovascular (CV) death, time to first major adverse CV event (MACE), and all cause death in patients with T2D using data from LEADER, a CV outcomes trial with 9340 patients with T2D.We used a Cox proportional hazards model adjusted for randomized treatment arm, and annual rate of NSHE as a time-dependent covariate with three levels; A: <2 NSHEs per year (reference), B: 2−11 NSHEs, or C: ≥12 NSHEs. Hazard ratios were used to estimate the association between NSHE and each of the outcomes. Higher rates of NSHE were associated with a higher rate of severe hypoglycemia, MACE, CV death, and all-cause death in patients with T2D (Figure); our results suggest that in this T2D population, a high rate of NSHEs may be associated with more harmful outcomes.

Disclosure

S.R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi-Aventis, Takeda Pharmaceutical Company Limited, Zealand Pharma A/S. Consultant; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. E. Hachmann-Nielsen: Employee; Self; Novo Nordisk A/S. K. Kvist: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S.

Funding

Novo Nordisk
1107-P: Ultra Rapid Lispro (URLi) Accelerates Insulin Lispro Absorption and Insulin Action vs. Humalog (Lispro) in Patients with T1D
Authors: LINNEBJERG HELLE , ZHANG QIANYI , LABELL ELIZABETH S. , REDDY SHOBHA , COUTANT DAVID E. , HOEVELMANN ULRIKE , PLUM-MOERSCHEL LEONA , HERBRAND THERESA , LEOHR JENNIFER
Published: June 2019

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. This randomized, double-blind, 2 period, crossover, 10 h euglycemic clamp study assessed PK and glucodynamics after one 15U SC dose of URLi and lispro in 41 patients with T1D (mean ± SD age, 32.0 ± 6.8 y; duration of T1D, 17.7 ± 9.3 y; HbA1c, 7.2 ± 0.6%; BMI, 24.8 ± 2.4 kg/m2).

After dosing URLi, onset of insulin lispro appearance in the serum was faster (1.3 vs. 6.8 min; p<0.0001) and early insulin lispro exposure was greater (7.2 fold in the first 15 min and 2.7-fold in the first 30 min; both p<0.0001) vs. lispro. The duration of exposure, when serum lispro levels fell below the limit of quantification, was 74 min shorter with URLi (p<0.0001).

Onset of insulin action was also faster (20 vs. 31 min; p=0.0007) and early action was increased 2.8 fold (p<0.001) in the first 30 min for URLi vs. lispro. Late insulin action (glucose infused from 4 h to end of the clamp) was reduced by 54% (p<0.0001) and duration of action was 43.6 min shorter with URLi (Figure).

Total insulin lispro exposure and glucose infused during the clamp did not differ and tolerability was similar between URLi vs. lispro.

In patients with T1D, URLi accelerated insulin absorption with a reduced late exposure and overall shorter duration vs. lispro, resulting in faster onset of insulin action and reduced late insulin action.

Disclosure

H. Linnebjerg: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Q. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. E.S. LaBell: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company, Johnson & Johnson, Novartis AG. S. Reddy: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. D.E. Coutant: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. U. Hoevelmann: None. L. Plum-Moerschel: None. T. Herbrand: None. J. Leohr: Employee; Spouse/Partner; Accenture. Employee; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Accenture. Stock/Shareholder; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
1117-P: Metformin Increases Blood Lactic Acid in Elderly Diabetic Veterans with Stage 3 CKD
Authors: GOSMANOV AIDAR R. , GOSMANOVA ELVIRA
Published: June 2019

Aim: Recently, the FDA endorsed metformin (MET) use in type 2 diabetes (T2D) patients with stage 3 CKD (CKD3). However, MET safety in elderly T2D subjects with CKD3 is unknown.

Methods: We studied lactic acid (LA) levels in ambulatory elderly male U.S. Veterans with stable nondiabetic CKD3 (eGFR 30-59ml/min/1.73m2) (Group 1) and diabetic CKD3 not on MET (Group 2) and on MET (Group 3) for at least 6 months. Hyperlactatemia was defined as LA >2mmol/L. Patients with history of HIV, advanced CHF, alcohol abuse, and liver cirrhosis were excluded. Clinical and biochemical characteristics were analyzed using ANOVA, χ2 test and Fisher’s exact tests.

Results: Mean LA levels were similar at 1.3±0.3 and 1.3±0.4 mmol/L in Group 1 (N=24, age 74.9±6.4 years, BMI 29.5±4.0kg/m2) and Group 2 (N=28, age 74.4±6.2 years, BMI 32.5±5.8kg/m2), respectively; while, LA was significantly higher in Group 3 (N=40, age 71.7±5.0 years, BMI 33.9±7.5kg/m2) at 2.0±1.0mmol/L compared with Group 2 subjects (P<0.001). Only 1 patient in each Group 1 (4.2%) and Group 2 (3.6%) had hyperlactatemia, as compared with 17 pts in Group 3 (42.5%) (P<0.05). Mild lactic acidosis (LA 5.2mmol/L, bicarbonate 18meq/L, anion gap 16) resolving with MET discontinuation was diagnosed in one Group 3 subject. Average daily MET dose in Group 3 was 1325±581mg and glycemic control was equal in Groups 2 and 3 (HbA1c 7.5±1.3 vs. 7.6±1.3%). There was no difference in mean LA level or frequency of hyperlactatemia between Group 3 pts with CKD stage 3A (eGFR 45-59, MET 1394±619mg/day) and stage 3B (eGFR 30-44, MET 1000±0mg/day). No differences in age, BMI, weight, eGFR, and HbA1c were seen in Group 3 pts with and without hyperlactatemia except trend towards higher MET dose in the hyperlactatemia patients (1500±560 vs. 1196±574 mg/day, P=0.1).

Conclusions: MET increases risk of hyperlactatemia in elderly men with T2D and CKD3 without clear predisposing factors while not offering explicit therapeutic advantage. We recommend using lower MET doses in elderly diabetic men with stage 3 CKD.

Disclosure

A.R. Gosmanov: None. E. Gosmanova: Advisory Panel; Self; Amgen Inc.
113-OR: ADA Presidents' Select Abstract: Dishabituation with High Intensity Exercise Improves Epinephrine Response and Symptomatic Awareness to Hypoglycemia in People with Type 1 Diabetes and Impaired Awareness of Hypoglycemia
Authors: FARRELL CATRIONA M. , WEST DANIEL J. , HAPCA SIMONA M. , JONES TIMOTHY , MCNEILLY ALISON D. , MCCRIMMON RORY J.
Published: June 2019

Impaired awareness of hypoglycemia (IAH) affects approx. 20-25% of all people with type 1 diabetes (T1D) and is a major risk factor for severe hypoglycemia. We recently proposed that IAH may develop as a form of adaptive memory to repeated hypoglycemia; referred to as Habituation. Consistent with this hypothesis, we demonstrated restoration of defective counterregulatory (CRR) responses to hypoglycemia in a rodent model of IAH following introduction of a novel stress stimulus [high intensity exercise (HIT)]; referred to as Dishabituation. In this study we sought to further test our hypothesis by examining whether a single episode of HIT would amplify counterregulatory response to subsequent hypoglycemia in people with T1D who had IAH (assessed by Gold score ≥4, Modified Clark score≥4 or DAFNE hypoglycaemia awareness rating 2 or 3). We recruited 12 participants to a single-centre, randomized, cross-over study. Individuals were randomized to one episode of HIT (4 x 30 s cycle sprints [2 min recovery] at 150% of max Watts achieved during VO2peak assessment) or rest. The following day they underwent a 90-minute hyperinsulinaemic hypoglycemic clamp study at 2.5 mmol/l with measurement of hormonal CRR and symptom scores. Each clamp study was separated by at least 2-weeks. We found that a single episode of HIT led to a 30% increase in the epinephrine response [mean (SEM) 418.8 +/- 62.84 vs. 541.1 +/- 70.5 pg/ml; p<0.05] accompanied by a significant increase in total symptom scores (Edinburgh Hypoglycemia scale: 24.25 +/- 2.96 vs. 27.5 +/- 3.9, p<0.05) during equivalent hypoglycemia induced the following day. These findings are consistent with the hypothesis that IAH develops in people with T1D as a habituated response and that introduction of a novel stressor can restore, at least partially, the CRR response to hypoglycemia. HIT may represent a novel therapeutic intervention for people with IAH.

Disclosure

C.M. Farrell: None. D.J. West: Research Support; Self; Arla Foods Ingredients, Dexcom, Inc. S.M. Hapca: None. T. Jones: Research Support; Self; Dexcom, Inc., Medtronic MiniMed, Inc. Speaker's Bureau; Self; Eli Lilly and Company, Roche Diabetes Care. A.D. McNeilly: None. R.J. McCrimmon: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; The Leona M. and Harry B. Helmsley Charitable Trust.

Funding

JDRF; Diabetes UK
1133-P: Four Days of Hyperoxia Exposure Confers Sustained Improvement in Glucose Homeostasis
Authors: JAIN SHALINI , HARRISON ALEXANDRIA V. , LORENZO FELIPE , MCCLAIN DON
Published: June 2019

Obesity and type 2 diabetes are co-morbidities, and their prevalence is continually growing. In obesity, in the face of lipid accumulation, adipose tissue become hypoxic with reduced blood flow, accompanied by low grade inflammation and insulin resistance. We therefore hypothesized that exposure to high oxygen (hyperoxia) could improve glucose homeostasis in obesity. We treated normal and fast-food diet (40% fat)-induced obese mice (10 months old) with hyperoxia (95%) for 4 days and quantified the effects on glucose homeostasis and insulin sensitivity. We found that immediately after the hyperoxic treatment, glycemia was modestly higher compared to pretreatment levels. However, both fasting and post-challenge blood glucose levels were significantly decreased after 6 days of hyperoxia treatment in both normal (28±8%; p=0.01) and obese mice (36±4%; p=0.007)). Plasma insulin levels decreased by 41% in both normal (p=0.0026) and obese (p=0.0033) mice and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) values were also significantly decreased (63±4%; p=0.0009 in normal and 55±13%; p=0.0049 in obese mice)after hyperoxia treatment, indicating that the improvements in glucose homeostasis were associated with improved insulin sensitivity. Surprisingly, these metabolic improvements were maintained more than one month after hyperoxia treatment, and occurred without significant effects on weight. These results demonstrate that exposure to hyperoxia improves fasting blood glucose levels, glucose tolerance and insulin sensitivity, suggesting that the hyperoxia treatment may provide a new approach for supportive treatment of diabetes and obesity.

Disclosure

S. Jain: None. A.V. Harrison: None. F. Lorenzo: None. D. McClain: None.

Funding

U.S. Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases
1142-P: Efficacy and Safety of Antidiabetes Treatment in Adjunct to Insulin in Type 1 Diabetes
Authors: CAI XIAOLING , YANG WENJIA , ZHANG SIMIN , JI LINONG
Published: June 2019

Aims: To evaluate the efficacy and safety of antidiabetes treatment in adjunct to insulin in type 1 diabetes.

Methods: A systematic search of MEDLINE, Embase and Cochrane Central Register of Controlled Trials was made from the beginning date to June 2018.

Results: A total of 48 studies were included in the meta-analysis. Compared with placebo, treatment with metformin, treatment with a-glucosidase inhibitor (AGI), treatment with GLP-1 receptor agonist, treatment with SGLT2 inhibitor, treatment with pramlintide all showed significant decrease in HbA1c from baseline (Table 1). Compared with placebo, treatment with metformin, treatment with GLP-1 receptor agonist, treatment with SGLT2 inhibitor, treatment with pramlintide all resulted in significant decrease in insulin dosage from baseline (Table 1).

Conclusion: Compared with placebo, in type 1 diabetes patients, in adjunctive to insulin treatment, treatment with metformin, treatment with GLP-1 receptor agonist, treatment with SGLT2 inhibitor, treatment with pramlintide all resulted in significant decrease in HbA1c and insulin dosage from baseline.

Disclosure

X. Cai: None. W. Yang: None. S. Zhang: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi.
1157-P: Two-Year Results of Multicenter, Prospective Study of Metabolic Surgery in Obese Type 2 Diabetes Mellitus Subjects in China
Authors: BAO YUQIAN , LIANG HUI , ZHANG PIN , WANG CUNCHUAN , JIANG TAO , ZHANG NENGWEI , ZHU JIANGFAN , YU HAOYONG , HAN JUNFENG , LIN SHIBO , YANG JINGGE , YANG WAH , CHEN SHU , DU DEXIAO , MA YINGZHANG , FEGELMAN ELLIOTT J. , SCHWIERS MICHAEL , WAGGONER JASON , YANG TENGFEI , ZHANG RONGRONG , JIA WEIPING
Published: June 2019

Introduction: Metabolic surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), is the only proven means of sustained weight loss and type diabetes mellitus (T2DM) remission/control but data are limited in China.

Method: Patients underwent laparoscopic RYGB or SG at 6 Chinese sites from Aug 2014 to Jan 2016 and returned for follow-up regularly after surgery. We evaluated the impact on a composite measure of glycemic control, which was defined as Complete Remission: HbA1c < 6% and FPG < 5.6 mmol/L for 1 year absent antidiabetic medications; Partial Remission: HbA1c 6 - 6.4% and FPG 5.6 - 6.9 mmol/L for 1 year absent antidiabetic medications; Improvement: Reduction in HbA1c (> 1%) or FPG (>1.4 mmol/L) or reduction accompanied by a decrease in antidiabetic medication for at least 1 year; Unchanged: Absence of remission or improvement; Recurrence: HbA1c or FPG in the diabetic range or need for antidiabetic medication after initial remission.

Results: There were 101 procedures completed. The mean (±SD) age of the patients was 37.1±9.7 years, and 52% were women. The mean BMI was 35.0±5.0 and mean HbA1c was 8.1±1.7% at baseline. Outcomes at 2-year follow-up were available for 80 patients (63 RYGB and 17 SG) and showed substantial improvements. Complete or partial remission at 2 years was achieved in at least 83% of patients in two groups (33 [53.2%] and19 [30.6%] in RYGB; 12 [70.6%] and 3 [17.6%] in SG), less than 5% were unchanged and recurrence was not seen in either group. There was a significant reduction in HbA1c from baseline in both RYGB and SG (-2.4 ± 1.8% [P>0.001] and -2.1 ± 1.8% [P>0.001]). Concurrent significant improvements in cardiometabolic parameters such as triglycerides and blood pressure, and reductions in antidiabetic medication usage were also observed.

Conclusion: The 2 years data demonstrate a clinically meaningful impact on a composite measure of glycemic control with a majority of patients demonstrating complete remission of T2DM in both groups.

Disclosure

Y. Bao: None. H. Liang: None. P. Zhang: None. C. Wang: None. T. Jiang: None. N. Zhang: None. J. Zhu: None. H. Yu: None. J. Han: None. S. Lin: None. J. Yang: None. W. Yang: None. S. Chen: None. D. Du: None. Y. Ma: None. E.J. Fegelman: Employee; Self; Ethicon US, LLC. M. Schwiers: Employee; Self; Ethicon, Inc. J. Waggoner: Employee; Self; Ethicon, Inc. T. Yang: Employee; Self; Johnson & Johnson Medical Devices Companies. R. Zhang: None. W. Jia: None.

Funding

Ethicon Inc.
1173-P: Therapeutic Response to Metformin Monotherapy in Type 2 Diabetes Is Associated with Butyrate-Producing Gut Microbiota
Authors: HUNG WEI-WEN , HUNG WEI CHUN
Published: June 2019

Type 2 diabetes is the fifth leading cause of death in Taiwan. The metabolic derangements in type 2 diabetes have been attributed to the compositional changes of the gut microbiota. Metformin, as the first-line treatment for type 2 diabetes, has been found to exert its antidiabetic actions through modulations of the gut microbiota. However, to our knowledge, no literature reported the associations between the therapeutic response to metformin monotherapy and the compositions of the gut microbiota. Thus, we hypothesized that the compositions of gut microbiota differ in type 2 diabetes with failure and success of metformin monotherapy. We had recruited 381 type 2 diabetes diagnosed for more than two years in a university hospital. Then based on medical records, we identified 12 subjects as the metformin-failure group and 14 as the metformin-success group, who maintained HbA1C>7% with not only metformin or with metformin monotherapy, respectively. We collected the biochemical data and analyzed the gut microbiota by Illumina sequencing of 16S rRNA gene. The result showed that while the two groups having similar clinical characteristics, the gut microbiota were significantly different by principal coordinates analysis. In addition, the metformin-success group had decreased richness and evenness. Furthermore, butyrate-producing gut microbiota including Butyrivibrio and Blautia producta increased in the metformin-success group. The short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, are produced by gut microbiota. The imbalance in the ratio of the SCFAs, such as decrease in butyrate and increase in acetate, leads to metabolic derangements in type 2 diabetes. Our finding showed that the metformin-success group were associated with butyrate-producing gut microbiota.

In conclusion, the gut microbiota that can reverse the imbalance of SCFAs might be the key for diabetes to have sustained metabolic benefits with metformin monotherapy.

Disclosure

W. Hung: None. W. Hung: None.

Funding

Kaohsiung Medical University