Multiple Daily Insulin Injection Therapy Research Articles

Insulin pump treatment vs. multiple daily insulin injections in patients with poorly controlled Type 2 diabetes mellitus: a comparison of cardiovascular effects

AimsBoth hyperglycaemia and large glycaemic variability are associated with worse outcomes in patients with Type 2 diabetes mellitus (T2DM), possibly causing sympatho-vagal imbalance and endothelial dysfunction. Continuous subcutaneous insulin injection (CSII) improves glycemic control compared to multiple daily insulin injections (MDI). We aimed to assess whether CSII may improve cardiac autonomic and vascular dilation function compared to MDI.MethodsWe enrolled T2DM patients without cardiovascular disease with poor glycaemic control, despite optimized MDI therapy. Patients were randomized to continue MDI (with multiple daily peripheral glucose measurements) or CSII; insulin dose was adjusted to achieve optimal target ranges of blood glucose levels. Patients were studied at baseline and after 6 months by: 1) flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the brachial artery; 2) heart rate variability (HRV) by 24-hour ECG Holter monitoring (HM). 7-day continuous glucose monitoring (CGM) was performed in 9 and 8 patients of Group 1 and 2, respectively.ResultsOverall, 21 patients were enrolled, 12 randomized to CSII (Group 1) and 9 to MDI (Group 2). The daily dose of insulin and Hb1AC did not differ significantly between the 2 groups, both at baseline and at follow-up. Glucose variability showed some significant improvement at follow-up in the whole population, but no differences were observed between the 2 groups. Both FMD and NMD, as well as HRV parameters, showed no significant differences between the 2 groups at 6-month follow-up.ConclusionsIn this randomized small study we show that, in T2DM patients, CSII achieves a similar medium-term glycemic control compared to MDI, without any adverse effect on the cardiovascular system.

Advanced decision support system for individuals with diabetes on multiple daily injections therapy using reinforcement learning and nearest-neighbors: In-silico and clinical results

Many individuals with diabetes on multiple daily insulin injections therapy use carbohydrate ratios (CRs) and correction factors (CFs) to determine mealtime and correction insulin boluses. The CRs and CFs vary over time due to physiological changes in individuals' response to insulin. Errors in insulin dosing can lead to life-threatening abnormal glucose levels, increasing the risk of retinopathy, neuropathy, and nephropathy. Here, we present a novel learning algorithm that uses Q-learning to track optimal CRs and uses nearest-neighbors based Q-learning to track optimal CFs. The learning algorithm was compared with the run-to-run algorithm A and the run-to-run algorithm B, both proposed in the literature, over an 8-week period using a validated simulator with a realistic scenario created with suboptimal CRs and CFs values, carbohydrate counting errors, and random meals sizes at random ingestion times. From Week 1 to Week 8, the learning algorithm increased the percentage of time spent in target glucose range (4.0 to 10.0 mmol/L) from 51 % to 64 % compared to 61 % and 58 % with the run-to-run algorithm A and the run-to-run algorithm B, respectively. The learning algorithm decreased the percentage of time spent below 4.0 mmol/L from 9 % to 1.9 % compared to 3.4 % and 2.3 % with the run-to-run algorithm A and the run-to-run algorithm B, respectively. The algorithm was also assessed by comparing its recommendations with (i) the endocrinologist's recommendations on two type 1 diabetes individuals over a 16-week period and (ii) real-world individuals' therapy settings changes of 23 individuals (19 type 2 and 4 type 1) over an 8-week period using the commercial Bigfoot Unity Diabetes Management System. The full agreements (i) were 89 % and 76 % for CRs and CFs for the type 1 diabetes individuals and (ii) was 62 % for mealtime doses for the individuals on the commercial Bigfoot system. Therefore, the proposed algorithm has the potential to improve glucose control in individuals with type 1 and type 2 diabetes.

Insulin pump treatment vs. multiple daily insulin injections in patients with poorly controlled type 2 diabetes mellitus: a comparison of cardiovascular effects

Abstract Background Both hyper- and hypo-glycaemia, as well as large glycaemic variability (GV) are associated with increased cardiovascular events in patients with type 2 diabetes mellitus (T2DM); possible contributing mechanisms of the increased cardiovascular risk include endothelial dysfunction and cardiac sympatho-vagal imbalance. Recent studies suggest that continuous subcutaneous insulin infusion (CSII) improves glycaemic control compared to multiple daily insulin injections (MDI). Purpose In this study, we assessed whether CSII may improve cardiac autonomic and vascular dilation function compared to MDI. Methods We enrolled in a small randomized pilot study consecutive T2DM patients without cardiovascular disease with poor glycaemic control, despite optimized MDI therapy. Patients were randomized to CSII (Group 1) or to continue MDI (Group 2); insulin dose was adjusted to achieve optimal glycaemic target ranges. Patients were studied at baseline and after 6 months by: 1) assessment of flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the brachial artery; 2) heart rate variability (HRV) by 24-hour ECG Holter monitoring; 3) a 7-day continuous glucose monitoring (CGM) was performed at baseline and follow-up in 8 and 7 patients of Group 1 and 2, respectively. Results Overall, 21 patients were enrolled, 12 randomized to CSII and 9 to MDI. Daily insulin dose, glycated hemoglobin levels and CGM parameters did not differ significantly between the 2 groups, both at baseline and at follow-up. Both FMD (6.7±2.5 vs 4.6±2.0 %, p=0.51) and NMD (8.9±3.1 vs 7.0±3.0 %, p=0.18), as well as HRV parameters, showed no significant differences between the 2 groups at 6-month follow-up. No relation between GV and both peripheral dilator function and cardiac autonomic function was also detected. Conclusions In this small, randomized pilot study we show that, in T2DM patients, CSII achieves similar medium-term glycaemic control compared to MDI, without any significant adverse effect on the cardiovascular system.

58-OR: Glycemic Impact of Meal-Dosing Behavior in Users of the InPen Smart Insulin Pen (SIP) Paired with Continuous Glucose Monitoring (CGM)

Background: Data from connected insulin pen therapies are revealing both gaps and opportunities to significantly improve care for people on multiple daily insulin injections therapy. This real-world (RW) data analysis reports on the impact of meal-dosing behavior (missed and late) on glycemia in adult and pediatric InPen users with type 1 (T1D) or type 2 diabetes (T2D). Method: The RW data from 5,153 deidentified individuals who used the InPen SIP and CGM for at least 30 days between January 2020 and December 2021, and who had dosing and CGM data between 30 and 59 days since first bolus date, were analyzed using a meal detection algorithm. Users with <14 days of bolus data or inadequate CGM data (<14 days of 70% or more SG data/day) were excluded. Results: The impact of dosing behavior (≤2 versus >3 doses/day) and missed dose frequency (<20% versus ≥20%) on glycemia was analyzed (Table). A dosing frequency of >3 (including correction-only doses) and a missed dose frequency of <20% were associated with improved glycemic metrics. Overall, the frequency of on-time dosing was significantly correlated with user TIR (r=0.59, p<0.001). Conclusion: Real-world InPen with CGM use data provide insights into the impact of meal-dosing behavior on glycemic outcomes, which may inform counseling strategies for care teams and open the door to precision insulin injection management. Disclosure J.Macleod: Employee; Medtronic. M.Smith: Employee; Medtronic. G.Im: Employee; Medtronic. T.L.Cordero: Employee; Medtronic. R.A.Vigersky: Employee; Medtronic.

Effect of the Chinese New Year Public Holiday on the Glycemic Control of T1DM With Intensive Insulin Therapy.

AimsThere is limited evidence that evaluates the glycemic control of type 1 diabetes mellitus (T1DM) during the Chinese New Year public holiday in China. The Chinese New Year public holiday represents various challenges to glycemic control, especially in T1DM patients, in China. We aimed to assess the effect of the Chinese New Year public holiday on several glucose metrics using flash glucose monitoring (FGM) in patients with T1DM.MethodsComplete FGM data for 1 week before, 1 week during and 1 week after the Chinese New Year public holiday were available for 71 T1DM patients treated with multiple daily insulin injection (MDI) therapy (n = 51) or continuous subcutaneous insulin infusion (CSII) treatment (n = 20). The mean age of the study participants was 13 (9, 30) years. Of note, 59.2% of the patients (n = 42) were adults, and 40.8% of the patients (n = 29) were minors. The interval between each two adjacent periods was one week. The indicators of mean glucose, glucose variability and time in different glycemic ranges were analyzed.ResultsThe Chinese New Year public holiday was associated with an increase in mean blood glucose (8.2 ± 1.9 vs. 8.9± 2.8; P < 0.001) and time above range (TAR) (26.1% ± 18.1% vs. 31.7% ± 23.9%; P < 0.001) but a decrease in time in range (TIR) (65.7% ± 16.8% vs. 59.9% ± 21.1%; P < 0.001) and coefficient of variation (CV) (38.2% ± 8.2% vs. 36.7% ± 7.7%; P =0.037). There was no statistically significant difference in time below range (TBR). The glycemic control deteriorated during the Chinese New Year public holiday in our study population regardless of age. Interestingly, in the CSII group, none of the metrics of glucose control significantly changed during the Chinese New Year public holiday.ConclusionsThese results suggested that less self-management may worsen glycemic control in the short term, indicating a need for more refined management algorithms during the Chinese New Year public holiday for T1DM patients.

Trajectory and predictors of HbA1c in children and adolescents with type 1 diabetes-A Danish nationwide cohort study.

Poor glycemic control in type 1 diabetes increases the risk of chronic complications and it is essential to identify life periods and predictors associated with deteriorating HbA1c . The aim was to describe specific HbA1c trajectories in Danish children and adolescents with type 1 diabetes and study associations with clinical and sociodemographic factors. 5889 children with type 1 diabetes were included from the nationwide Danish Registry of Childhood and Adolescent Diabetes with annual visits during 1996-2019. Trajectories of HbA1c were modeled with linear mixed-effects models (using age as time scale, included as cubic spline) and with an individual-specific random intercept and slope. The following cofactors were included stepwise into the model: sex, age at diagnosis, calendar year, parental education, immigrant status, health care region, blood glucose monitoring (BGM) frequency, treatment modalities: continuous subcutaneous insulin infusion (pump) versus multiple daily insulin injection therapy (pen) and continuous glucose monitoring. HbA1c overall increased during age while there was a significant decreasing secular trend. Older age at diagnosis was associated with a steeper trajectory, and non-Danish origin and shorter parental education were each associated with higher levels of HbA1c across age. A lower BGM frequency was associated with a markedly poorer HbA1c trajectory, while no significant differences were shown for different treatment modalities. Glycemic outcome worsened with age during childhood and adolescence, which is of clinical concern. Important predictors for a poorer glycemic trajectory were later age at diabetes diagnosis, shorter parental education, non-Danish origin and, in particular low BGM frequency.

Continuous subcutaneous insulin infusion therapy is associated with reduced retinopathy progression compared with multiple daily injections of insulin

Aims/hypothesisWe aimed to compare diabetic retinopathy outcomes in people with type 1 diabetes following introduction of continuous subcutaneous insulin infusion (CSII) therapy with outcomes in people receiving continuing therapy with multiple daily insulin injections (MDI).MethodsThis is a retrospective cohort study using the Scottish Care Information – Diabetes database for retinal screening outcomes and HbA1c changes in 204 adults commenced on CSII therapy between 2013 and 2016, and 211 adults eligible for CSII during the same period but who continued on MDI therapy. Diabetic retinopathy progression (time to minimum one-grade worsening in diabetic retinopathy from baseline grading) was plotted for CSII and MDI cohorts using Kaplan–Meier curves, and outcomes were compared using multivariate Cox regression analysis adjusting for age, sex, baseline HbA1c, blood pressure, cholesterol, smoking status and socioeconomic quintile. Impact of baseline HbA1c and change in HbA1c on diabetic retinopathy progression was assessed within CSII and MDI cohorts.ResultsCSII participants were significantly younger, were from less socially deprived areas, and had lower HbA1c and higher diastolic BP at baseline. There was a larger reduction in HbA1c at 1 year in those on CSII vs MDI (−6 mmol/mol [−0.6%] vs −2 mmol/mol [−0.2%], p < 0.01). Diabetic retinopathy progression occurred in a smaller proportion of adults following commencement of CSII vs continued MDI therapy over mean 2.3 year follow-up (26.5% vs 18.6%, p = 0.0097). High baseline HbA1c (75 mmol/mol [9%]) was associated with diabetic retinopathy progression in the MDI group (p = 0.0049) but not the CSII group (p = 0.93). Change in HbA1c at follow-up, irrespective of baseline glycaemic status, did not significantly affect diabetic retinopathy progression in either group.Conclusions/interpretationCSII was associated with reduced diabetic retinopathy progression compared with continued MDI therapy, and may be protective against diabetic retinopathy progression for those with high baseline HbA1c. Progression of diabetic retinopathy over 3 years was not associated with a change in HbA1c.Graphical abstract

Dulaglutide as an Effective Replacement for Prandial Insulin in Kidney Transplant Recipients with Type 2 Diabetes Mellitus: A Retrospective Review.

Dulaglutide, a weekly injectable glucagon-like peptide-1 receptor agonist, has demonstrated effectiveness when combined with basal insulin. We examined whether the efficacy of dulaglutide is comparable to that of prandial insulin in kidney transplant (KT) recipients with type 2 diabetes mellitus (T2DM) undergoing multiple daily insulin injection (MDI) therapy. Thirty-seven patients, who switched from MDI therapy to basal insulin and dulaglutide, were retrospectively analyzed. Changes in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels, body weight, and basal insulin dose were evaluated over 6 months. Dulaglutide was comparable to three injections of prandial insulin in terms of glycemic control (HbA1c 7.1% vs. 7.0%; 95% confidence interval [CI], –0.53 to 0.28; P=0.53). The basal insulin and dulaglutide combination resulted in a reduction in FPG levels by 9.7 mg/dL (95% CI, 2.09 to 41.54; P=0.03), in body weight by 4.9 kg (95% CI, 2.87 to 6.98; P<0.001), and in basal insulin dose by 9.52 IU (95% CI, 5.80 to 3.23; P<0.001). Once-weekly dulaglutide may be an effective alternative for thrice-daily prandial insulin in KT recipients with T2DM currently receiving MDI therapy.

Real-World Efficacy of the Hybrid Closed-Loop System.

Hybrid closed-loop (HCL) insulin pump therapy (Medtronic 670G) is an emerging technology that is growing in use worldwide. Initial clinical trials demonstrated the effectiveness of HCL in reducing hypoglycemia and improving glucose control; however, these subjects were intensely monitored and supervised. There has been concern regarding the ability of patients to remain in auto mode. We aimed to assess HCL when used in a typical outpatient endocrine clinic. We initially analyzed data from 80 individuals with type 1 diabetes managed in an endocrine clinic by a single certified diabetes educator (CDE). We then included our other providers and had 230 subjects by the end of the study. Patients were either transitioned from traditional insulin pump or multiple daily insulin injection therapy (MDI) to HCL. Patients initiated to HCL pump therapy from July 2017 through February 2020 were studied. Endpoints of change in time in hypoglycemic/hyperglycemic range and time in target range were analyzed. The primary outcome was a change in percent time in the target range during manual mode compared with auto mode. There was an 18.2% increase in average time in target range when comparing manual mode to auto mode (59.3% vs 70.1%, P < .0001). Average time in hyperglycemic range was significantly reduced by 26.7% (39.0% vs 28.6%, P < .0001) but without increasing average time in hypoglycemic range (1.7% vs 1.3%, P = 0.95). HCL was effective in reducing hyperglycemia and increasing time in the target range but did not increase hypoglycemia. These data suggest HCL will improve the metrics of glucose control.

1094-P: Short-Acting Exenatide and Markers of Cardiovascular Disease in Type 1 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Trial

In type 2 diabetes, some glucagon-like peptide 1 receptor agonists (GLP-1RAs) reduce the risk of major adverse cardiovascular events. Whether GLP-1RAs have any effect on cardiovascular disease risk in patients with type 1 diabetes remains to be elucidated. We tested the effect of adding the short-acting GLP-1RA exenatide to insulin treatment on markers of cardiovascular risk in type 1 diabetes. In a randomized, double-blinded, parallel-group trial, 108 individuals with type 1 diabetes aged ≥18 years on multiple daily insulin injection therapy with body mass index &amp;gt;22.0 kg/m2 and HbA1c 7.5-10.0% (59-88 mmol/mol) were randomized (1:1) to preprandial subcutaneous injection of 10 µg exenatide (Byetta®) or placebo three times daily over 26 weeks as add-on treatment to existing insulin therapy. Reported data were secondary endpoints and analyzed in a baseline-adjusted linear mixed model in the intention-to-treat population. Exenatide changed total fat mass by -2.6 kg (95% CI -3.6;-1.6, P&amp;lt;0.0001) and lean body mass by -1.1 kg (95% CI -1.9;-0.4, P=0.01) compared to placebo as assessed by dual-energy X-ray absorptiometry. Central and peripheral fat mass reductions were similar. Exenatide did not change levels of interleukin 2 or 6; tumor necrosis factor alpha; C-reactive protein; N-terminal prohormone of brain natriuretic peptide; or 8-oxo-7,8-dihydroguanosine (RNA oxidation marker) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (DNA oxidation marker). Exenatide added to insulin therapy in type 1 diabetes for 26 weeks resulted in body weight loss primarily from fat mass reduction but had no effect on circulating biomarkers of cardiovascular disease risk. Disclosure N.J. Johansen: Research Support; Self; AstraZeneca. T.F. Dejgaard: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. A. Lund: Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S, Sanofi. C. Schlüntz: None. E. Larsen: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. H.E. Poulsen: Research Support; Self; Boehringer Ingelheim International GmbH. J.P. Gøtze: None. H. Møller: None. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp &amp; Dohme Corp., Sanofi. H.U. Andersen: Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Norgine B.V., Novo Nordisk A/S. Funding AstraZeneca

Continuous subcutaneous insulin infusion reduces the risk of postoperative infection.

Perioperative hyperglycemia was associated with postoperative infection, and proper management of perioperative glucose has become critical in improving the prognosis of patients. A total of 1015 diabetic patients who underwent surgery and received insulin treatment for their hyperglycemia in our hospital were retrospectively reviewed. According to propensity matching, we obtained 253 pairs of patients from the group which received continuous subcutaneous insulin infusion (CSII) therapy (CSII group) and the group which received insulin injection therapy (non-CSII group). Perioperative glucose levels and corresponding outcomes were compared between the two groups. Compared with the non-CSII group, the CSII group had lower fasting and mean glucose levels, lower incidence of fever (operation day: 18.6% vs 10.2%; P = .014; first postoperative day: 55.1% vs 34.7%; P < .001), a positive rate of postoperative secretion culture (6.3% vs 1.2%; P = .004), and a shorter time of antibiotics use (total antibiotics use: P = .002; postoperative antibiotics use: P < .001) and hospital stays (P < .001). However, there was no difference in the total medical expenditure between the two groups (P = .499). Further analysis showed that CSII therapy was superior to multiple daily insulin injection (MDI) therapy in its effect on infection and other postoperative outcomes when 64 pairs of patients from the CSII group and MDI group were compared. CSII therapy provides better perioperative glucose control and a lower risk of postoperative infection without increasing the total medical expenditure.

1060-P: Effect of Dulaglutide and Long-Acting Insulin Combination Therapy in Patients with Type 2 Diabetes

Objective: Glucagon-like peptide-1 receptor agonists (GLP-1-RA) are assumed to decrease the number of injections and improve blood glucose control in patients with type 2 diabetes (T2D). We aimed to evaluate the effects of switching from multiple daily insulin injection therapy (MDI) to combination therapy involving a long-acting GLP-1-RA, dulaglutide, and long-acting insulin on glycemic control. Methods: We examined patients with T2D who admitted to our department and underwent blood glucose management with MDI, followed by flash glucose monitoring. The treatment was subsequently switched to dulaglutide + long-acting insulin combination therapy. We evaluated the blood glucose excursion after MDI and 1 and 24 weeks after dulaglutide + long-acting insulin combination therapy. Furthermore, we evaluated hemoglobin A1c (HbA1c) after 12 and 24 weeks of dulaglutide + long-acting insulin combination therapy. Results: We enrolled 20 patients (mean age: 68.6 ± 11.7 years; HbA1c value: 10.1% ± 2.8%; previous MDI: n = 4). Mean blood glucose levels after MDI and 1 and 24 weeks after dulaglutide + long-acting insulin combination therapy were 124.8 ± 35.6, 122.5 ± 30.4, and 119 ± 21.3 mg/dl, respectively. Blood glucose level was significantly lower 24 weeks after dulaglutide + long-acting insulin combination therapy than shortly after MDI (P = 0.0048). Furthermore, blood glucose excursion tended to decrease after switching to dulaglutide + long-acting insulin combination therapy. After 12 and 24 weeks of the switch, HbA1c value significantly decreased (−3.6% ± 0.78%, P = 0.0003 and −3.7% ± 0.78%, P = 0.0002, respectively). Conclusions: The switch from MDI to dulaglutide + long-acting insulin combination therapy resulted in better blood glucose control, with reductions in blood glucose excursion and the number of self-injections; moreover, the effects continued for 24 weeks. Disclosure K. Ito: None. S. Satoh: None. Y. Kondo: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Shionogi &amp; Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Shionogi &amp; Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.

123-LB: Continuous Subcutaneous Insulin Infusion from Diagnosis of Type 1 Diabetes Improves Intermediate Glycaemic Variability in Children

Background: Glucose variability (GV) may be reflected by variation in either the short-term glucose levels (assessed by continuous glucose monitoring (CGM)) or the long-term by HbA1c or intermediate by 1,5-anhydroglucitol (1,5-AG). In patients with T1DM management by continuous subcutaneous insulin infusion (CSII) is usually associated with improved glycaemia compared to multiple daily insulin injections (MDI). Serum 1,5-anhydroglucitol (1,5-AG) correlates with GV on CGM in adult and pediatric T1D groups. It is not known whether CSII therapy without CGM improves intermediate GV. Methods: Blood was obtained from children (mean age 14.1 +/- 1.3 years) within 3-months of T1D diagnosis. Children were treated with CSII (n=12) or MDI (n=15) and followed for a further 1 to 3 time points (median, LQ-UQ 535, 519-563 days follow-up). GV was assessed measuring 1,5-anhydroglucitol (1,5-AG) (GlycoMark, Inc., Winston-Salem, NC). The mean difference, standard deviation (SD) and coefficient of variation (CV) of 1,5-AG and HbA1c was compared between treatment arms. Results: There was no difference between treatment modalities in baseline HbA1c (median, LQ-UQ 11.8, 10.2-13.5 % (105, 87-124 mmol/mol) vs. 12.6, 10.3-14.0 % (114, 89-130 mmol/mol) CSII vs. MDI) nor baseline 1,5-AG (median, LQ-UQ 2.8, 1.8-4.0 μg/mL vs. 3.6, 2.1-12.1 μg/mL CSII vs. MDI). 1,5-AG improved more (increased) in the CSII vs. MDI group (3.1 +/- 4.1 vs. -2.2 +/- 7.0 μg/ml respectively, P=0.029). This difference persisted following adjustment for the duration of follow-up. There was no significant difference in the HbA1c improvement between the CSII and MDI groups. There was no significant difference in the SD or CV of 1,5-AG or HbA1c between groups. Conclusions: Early use of CSII post-T1D-diagnosis in a pediatric population is associated with a higher 1,5-AG than with MDI therapy implying reduced glycaemic variability. Disclosure E.S. Scott: None. A.S. Januszewski: None. G. Fulcher: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Research &amp; Development, Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Research &amp; Development, Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc. Research Support; Self; Novo Nordisk Inc. T. Jones: Research Support; Self; Dexcom, Inc., Medtronic MiniMed, Inc. Speaker's Bureau; Self; Eli Lilly and Company, Roche Diabetes Care. E.A. Davis: None. A.J. 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.

Status and trends in the use of insulin analogs, insulin delivery systems and their association with glycemic control: comparison of the two consecutive recent cohorts of Japanese children and adolescents with type 1 diabetes mellitus.

Background Treatment for type 1 diabetes mellitus (T1DM) has greatly changed by the general use of insulin analogs and continuous subcutaneous insulin infusion (CSII). To investigate whether these advances have been translated into continued improvement in glycemic control in Japanese children and adolescents, we analyzed the registration data of the two consecutive recent cohorts of Japanese childhood-onset T1DM patients. Methods The registration data including hemoglobin A1c (HbA1c), hypoglycemia and insulin regimen were compared between the two cohorts (862 patients in the 2008 cohort and 1090 in the 2013 cohort). Results The proportion of subjects with multiple daily insulin injection therapy (MDI) and CSII significantly increased (p<0.0001) from 67.4% and 9.7% to 71.8% and 23.4%, respectively. In the 2013 cohort, almost all patients were treated with basal-bolus treatment using insulin analogs. The use of CSII increased in all age groups, especially in the age group 0-5 years. The rates of overall, moderate and severe hypoglycemia significantly declined from 10.24, 10.18 and 0.056 events/100 persons/period in the 2008 cohort to 0.66, 0.62 and 0.033 in the 2013 cohort (p<0.0001, <0.0001, 0.04), respectively. Contrarily, there were no significant changes in HbA1c values between the two cohorts. Conclusions The popularization of the basal-bolus treatment using insulin analogs hascontributed to a significant decrease in hypoglycemia. In contrast, the intensive insulin treatment may not be enough for the satisfactory improvement of glycemic control in Japanese children and adolescents with T1DM. Considerable points remain, such as diabetic education and support to motivate patients.

Real-World Data from the MiniMed™ 670G System Commercial Launch—Patients Previously Using MDI Therapy

The Medtronic MiniMed™ 670G hybrid closed-loop system with SmartGuard™ technology was released for commercial use in the U.S. in March 2017. Data from patients previously managing their diabetes with multiple daily insulin injections (MDI) therapy who transitioned to the MiniMed™ 670G system are reported. MiniMed™ 670G system data from patients who voluntarily uploaded to CareLink™ Personal software, from 3/17/17 to 12/14/17 (n=158), were de-identified and analyzed if there were ≥7 days of sensor wear. Comparisons were made of glycemic metrics between 4,529 patient-days in the initial open-loop Manual Mode and 14,1patient-days after initiating closed-loop Auto Mode features. The Table shows glycemic metrics during Manual Mode and after Auto Mode start and that time spent in target range increased, while time spent in low and high glucose levels decreased. Real-world findings from patients previously using MDI who transitioned to the MiniMed™ 670G system demonstrated increased TIR and reduced time in hypoglycemia and hyperglycemia, consistent with pivotal trial1 results in patients previously using pump therapy +/- CGM. Prior MDI patients also showed greater TIR the more time spent in Auto Mode. Disclosure S. Gopalakrishnan: Employee; Self; Medtronic. P. Agrawal: None. M. Stone: None. C. Fogel: Employee; Self; Medtronic. S.W. Lee: Employee; Self; Medtronic.

Intervention of the Flash Glucose Sensing Technology on Glycemic Control and Treatment Satisfaction in Patients with Type 2 Diabetes Treated Intensively by Insulin—A Randomized Controlled Trial

Objective: To determine the satisfaction from treatment and effectiveness of flash glucose monitoring system (FGM) in patients with type 2 diabetes. Design and Methods: 101 individuals with type 2 diabetes on multiple daily insulin injection (MDI) therapy for ≥1 year (mean duration 21.81±7.65 years) and HbA1c 7.4-10.2% (57-88 mmol/mol) were randomized to the intervention (n=53) or the standard care group (n=48). Those in the intervention group were instructed to use FGM and once a week 7-points BG assessment to confirm any a symptomatic hypoglycemia. The control group continued the routine BG measurement as before the study and add once a week 7-points BG measurement at constant day. For 12 weeks, both groups were instructed to adjust insulin dose in the frequent face-to-face and telephone visits. Satisfaction from treatment, quality of life, comfort using FGM, HbA1c and hypoglycemia events were evaluated. Results: The mean age was 66.75 ± 7.55; 64.35% were male. Total treatment satisfaction increased in the intervention group (p=0.053). At the 12 week of the study, subjects in the intervention group found treatment significantly more flexible (p=0.019), convenient (p=0.052), and would recommend it more to their counterparts (p=0.023). The mean HbA1c was 8.51 ± 0.81%. After 10 weeks, HbA1c changes were -0.82% in the intervention group and -0.29% in the control (p=0.0013). 67.9% subjects from the intervention study and 27.1% from the control group reduced HbA1c ≥0.5% HbA1c (p&amp;lt;0.001); and 39.6% subjects from the intervention and 16.7% from the control group reduced HbA1c≥1.0% (p=0.0076) without increasing frequency of hypoglycemia. Conclusion: FGM potentially produces a modification of behavior/life style and improves treatment satisfaction. It improves glycemic control in subjects with type 2 diabetes treated by MDI without increased frequency of hypoglycemia. Disclosure M. Yaron: None. E. Roitman: Speaker's Bureau; Self; Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; GlucoMe. Stock/Shareholder; Self; GlucoMe. G. Aharon-Hananel: None. Z. Landau: None. T. Ganz: None. M. Karp: None. M. Ish-Shalom: None. J. Singer: None. J. Wainstein: None. I. Raz: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Stock/Shareholder; Self; DarioHealth. Advisory Panel; Self; Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Orgenesis Inc., Pfizer Inc., Sanofi R&amp;D, SmartZyme Biopharma. Consultant; Self; Bristol-Myers Squibb Company. Speaker's Bureau; Self; Bristol-Myers Squibb Company, Johnson &amp; Johnson Diabetes Institute, LLC., Merck Sharp &amp; Dohme Corp., Novartis Pharma K.K., Sanofi-Aventis. Consultant; Self; FuturRx Ltd, Insuline Medical,Camereyes Ltd, Exscopia, Medial EarlySign Ltd. Stock/Shareholder; Self; Glucome Ltd, InsuLine Medical Ltd.. Consultant; Self; Dermal Biomics Inc. Stock/Shareholder; Self; Orgenesis Inc.. Speaker's Bureau; Self; Teva Pharmaceutical Industries Ltd.. Advisory Panel; Self; Concenter BioPharma/Silkim Ltd, Camereyes Ltd. Stock/Shareholder; Self; CameraEyes Ltd. Advisory Panel; Self; Breath of Life PharmaLtd, Panaxia.

Satisfaction of switching to combination therapy with lixisenatide and basal insulin in patients with type 2 diabetes receiving multiple daily insulin injection therapy: A randomized controlled trial.

Aims/IntroductionWe compared the satisfaction levels of patients with type 2 diabetes undergoing combination therapy with lixisenatide (LIX) and basal insulin with that of patients undergoing multiple daily insulin injection (MDI) therapy.Materials and MethodsThe study was a 12‐week open‐label, randomized, multicenter, controlled trial. Participants were Japanese patients with type 2 diabetes receiving MDI for >3 months. Patients were randomly assigned to each treatment cohort: (i) a group that continued MDI (MDI group); and (ii) a group that switched from MDI to combination therapy with LIX and basal insulin (LIX group). The primary outcome was change in Diabetes Treatment Satisfaction Questionnaire scores from baseline to 12 weeks between these two groups. Key secondary outcomes were glycated hemoglobin and body weight changes.ResultsA total of 31 patients were initially enrolled in the study, and 26 of them completed the study. The change in Diabetes Treatment Satisfaction Questionnaire scores in the LIX group was significantly greater compared with that in the MDI group. Mean changes in glycated hemoglobin levels were −0.05 ± 0.37% in the MDI group and 0.04 ± 0.38% in the LIX group (P = 0.36). Mean changes in body weight were +0.6 ± 1.8 kg in the MDI group and −2.5 ± 1.8 kg in the LIX group (P < 0.01).ConclusionsSwitching from MDI to combination therapy with LIX and basal insulin improved satisfaction levels while maintaining glycemic control in Japanese patients with type 2 diabetes.

Continuous Glucose Monitoring in Older Adults With Type 1 and Type 2 Diabetes Using Multiple Daily Injections of Insulin: Results From the DIAMOND Trial.

The objective was to determine the effectiveness of real-time continuous glucose monitoring (CGM) in adults ≥ 60 years of age with type 1 (T1D) or type 2 (T2D) diabetes using multiple daily insulin injections (MDI). A multicenter, randomized trial was conducted in the United States and Canada in which 116 individuals ≥60 years (mean 67 ± 5 years) with T1D (n = 34) or T2D (n = 82) using MDI therapy were randomly assigned to either CGM (Dexcom™ G4 Platinum CGM System® with software 505; n = 63) or continued management with self-monitoring blood glucose (SMBG; n = 53). Median diabetes duration was 21 (14, 30) years and mean baseline HbA1c was 8.5 ± 0.6%. The primary outcome, HbA1c at 24 weeks, was obtained for 114 (98%) participants. HbA1c reduction from baseline to 24 weeks was greater in the CGM group than Control group (-0.9 ± 0.7% versus -0.5 ± 0.7%, adjusted difference in mean change was -0.4 ± 0.1%, P < .001). CGM-measured time >250 mg/dL ( P = .006) and glycemic variability ( P = .02) were lower in the CGM group. Among the 61 in the CGM group completing the trial, 97% used CGM ≥ 6 days/week in month 6. There were no severe hypoglycemic or diabetic ketoacidosis events in either group. In adults ≥ 60 years of age with T1D and T2D using MDI, CGM use was high and associated with improved HbA1c and reduced glycemic variability. Therefore, CGM should be considered for older adults with diabetes using MDI.

Continuous Glucose Monitoring Use in Type 1 Diabetes: Longitudinal Analysis Demonstrates Meaningful Improvements in HbA1c and Reductions in Health Care Utilization.

Real-time continuous glucose monitoring (rtCGM) improves glycemic control in type 1 diabetes (T1D) patients treated with continuous subcutaneous insulin infusion (CSII). However, the benefits of rtCGM in T1D patients treated with multiple daily insulin injection (MDI) therapy has not been well studied. We explored the effects of rtCGM versus self-monitoring of blood glucose (SMBG) on clinical outcomes within a large T1D population treated with either CSII or MDI therapy. This retrospective, longitudinal analysis utilized datasets from T1D patients enrolled in a commercial health plan to assess changes in HbA1c in 187 naïve to rtCGM users and 6260 SMBG users. Propensity score modeling was used to assess inpatient admissions, emergency room (ER) visits in 1130 patients (565 rtCGM, 565 SMBG). Differences in HbA1c reduction (rtCGM+MDI vs rtCGM+CSII) were evaluated. Larger, clinically meaningful HbA1c reductions were seen among rtCGM versus SMBG users: -0.5% ( P = .004) versus -0.2% ( P < .0001); 0.3% diff in diff, P = .03. All-cause inpatient admissions were lower for rtCGM users: -42%, P = .013. Emergency room visits coded for diabetic ketoacidosis (DKA) were four times higher for SMBG patients than rtCGM patients: 17 versus 4, P = .0318. HbA1c reductions were most notable with rtCGM+MDI versus rtCGM+CSII treatment: -0.6% ( P = .01) versus -0.3% ( P = .16). Use of rtCGM in T1D patients facilitates greater HbA1c improvements and reduced health care system utilization compared with traditional SMBG use regardless of insulin administration method. Treatment with rtCGM in conjunction with MDI confers similar or greater glycemic benefits without the additional costs associated with CSII therapy.

Effects of advanced carbohydrate counting guided by an automated bolus calculator in Type 1 diabetes mellitus (StenoABC): a 12‐month, randomized clinical trial

To test whether concomitant use of an automated bolus calculator for people with Type 1 diabetes carrying out advanced carbohydrate counting would induce further improvements in metabolic control. We conducted a 12-month, randomized, parallel-group, open-label, single-centre, investigator-initiated clinical study. We enrolled advanced carbohydrate counting-naïve adults with Type 1 diabetes and HbA1c levels 64-100 mmol/mol (8.0-11.3%), who were receiving multiple daily insulin injection therapy. In a 1:1-ratio, participants were randomized to receive training in either advanced carbohydrate counting using mental calculations (MC group) or advanced carbohydrate counting using an automated bolus calculator (ABC group) during a 3.5-h group training course. For 12 months after training, participants attended a specialized diabetes centre quarterly. The primary outcome was change in HbA1c from baseline to 12 months. Between August 2012 and September 2013, 168 participants (96 men and 72 women) were recruited and randomly assigned to the MC group (n = 84) and the ABC group (n = 84). Drop-out rates were 23.8 and 21.4%, respectively (P = 0.712); 130 participants completed the study. The baseline HbA1c was 75 ± 9 mmol/mol (9.0 ± 0.8%) in the MC group and 74 ± 8 mmol/mol (8.9 ± 0.7%) in the ABC group. At 12 months, change in HbA1c was significant within both groups: MC group: -2 mmol/mol (95% CI -4 to -1) or -0.2% (95% CI -0.4 to -0.1; P = 0.017) and ABC group: -5 mmol/mol (95% CI -6 to -3) or -0.5% (95% CI -0.6 to -0.3; P < 0.0001), but HbA1c reductions were significantly greater in the ABC group (P = 0.033). No episodes of severe hypoglycaemia were reported. People with Type 1 diabetes initiating advanced carbohydrate counting obtained significantly greater HbA1c reductions when guided by an automated bolus calculator (NCT02084498).