bluuebunny/crossref_metadata_2025 huggingface dataset:
228-LB: Obesity Status and Health Information Technology Use in U.S. Adults with Type 2 Diabetes
Authors: WANG SEAMUS , YEH HSIN-CHIEH
Published: June 2019

One of the many goals of the Affordable Care Act is to improve healthcare quality through the use of technology. However, little is known about health information technology (HIT) use among adults with diabetes. We analyzed data from the National Health Interview Survey (2016-2017) to determine the prevalence of HIT use, and to examine whether HIT use differs by obesity status. All analyses were weighted to account for the complex survey design. We identified 4,857 individuals 18 years or older who had type 2 diabetes by self-report. 45.7% were 65 years or older, 43.3% were female, 14.5% were non-Hispanic black, 15.5% were Hispanic, 18.2% had less than high school education, and 5.0% had no health insurance; mean (SE) body mass index (BMI) was 34.1 (0.25) kg/m2. 28.9% normal weight, 36.7% overweight, and 45.8% obese adults with type 2 diabetes reported looking up health information online. Similarly, electronic health service use (defined as filling a prescription online, scheduling appointment with healthcare provider online, or communicating with healthcare provider by email) were more prevalent in patients with overweight (20.5%) or obesity (25.7%), than those with normal weight (17.7%). After adjustments for age, sex, race/ethnicity, education level, and insurance, compared with adults who had normal weight, the odds ratios (OR) of looking up health information online among overweight and obese adults were 1.32 (95% CI, 1.01-1.74) and 1.65 (95% CI, 1.27-2.15), respectively. The adjusted ORs of using electronic health services were 1.12 (95% CI, 0.81 to 1.55) and 1.46 (95% CI, 1.07-1.99) in overweight and obese adults, respectively. This data showed that HIT is under-utilized among people with diabetes. Still, higher proportion of HIT use in patients with higher BMI suggested HIT may serve as an alternative to more traditional methods of obtaining health information or communicating with health care providers, which in turn may help those with obesity to better manage their weight and comorbidity.

Disclosure

S. Wang: None. H. Yeh: None.
2285-PUB: Risk of Developing T2DM in Lebanon: The Role of Health Literacy, Quality of Life, and Dietary Habits
Authors: SUKKARIEH-HARATY OLA ALI , KHARMA JOELLE ABI , FARRAN NATALI , BASSIL MAYA
Published: June 2019

Background: International T2DM Federation (IDF) estimates T2DM prevalence in Lebanese adults around 14%. Identifying people at risk of developing type 2 T2DM mellitus (T2DM) as to prevent rising prevalence and development of T2DM related complications is crucial.

Aim: to identify people at high risk for developing T2DM.

Methods: A convenience sample (N=198) of healthy Lebanese adults, 40 years of age and above, were recruited through snowballing from all over Lebanon. Food Frequency Questionnaire (FFQ), Short Test of Functional Health Literacy in Adults (STOFHLA), World Health Organization Quality of Life-BREF (WHOQoL-BREF), and ARABRISK were administered.

Results: Majority of the participants were 40 to 54 years (74.25%), females (57.58%), married (51.02%), employed (59.90%) and reported having “enough to make ends meet” (64.29%). Significant association resulted between ARABRISK scale score and WHOQoL-BREF scale (β= -1.642, p= 0.001) as well as two of its subscales, physical (β= -2.21, p < 0.001) and psychological (β= -1.17, p= 0.003). Significant association was noted between ARABRISK scale score and demographic characteristics; mainly marital status, particularly being “married” (β= 15.47, p < 0.001) and “widowed/divorced” (β= 25.72, p < 0.001), and employment statuses particularly “not enough to make ends meet” (β= 8.64, p= .021).Significant association resulted between ARABRISK scale score and at whole grain consumption (β= -4.97, p = 0.035) and red meat (β= 13.02, p = 0.003). Marital status, red meat consumption, whole grains consumption, and physical health subscale were significantly associated with ARABRISK in the fully adjusted multiple linear regression model. The combination of the latter variables accounted for 36.83% of the variance of ARABRISK score.

Conclusion: Findings will help health care practitioners to understand the determinants of T2DM risk, which will set the stage for effective preventive measures in reducing the risk and incidence of T2DM.

Disclosure

O.A. Sukkarieh-Haraty: None. J. Abi Kharma: None. N. Farran: None. M. Bassil: None.

Funding

Lebanese American University
2286-PUB: Factors Associated with Stigma toward Antidepressants among Latino Patients with Type 2 Diabetes Mellitus and Comorbid Depression in Safety-Net Clinic
Authors: OH HYUNSUNG , ELL KATHLEEN
Published: June 2019

Stigma toward antidepressants (STA) undermines effectiveness of depression care for Latinos with type 2 diabetes mellitus (T2DM) in safety-net clinics. However, we don’t know who are more susceptible to STA among Latinos with T2DM and comorbid depression in safety-net clinics. To fill this gap, we analyzed cross-sectional data collected from 333 Latino patients recruited from three safety-net clinics located within Latino ethnic enclaves in Los Angeles, California. We analyzed a portion of baseline survey in a randomized clinical trial that tested the effectiveness of community health workers in safety-net clinics, accredited Patient-Centered Medical Home, and participants had to show PHQ-9 score ≥10 to be eligible (56.6 the mean age; 13.8% male; 91.0% Spanish only; 75.4% below high school; 46.8% married). STA was measured by the Latino Scale for Antidepressant Stigma (LSAS). Predictors include patient’s demographic attributes (age, gender, Spanish speaking, education, marital status), depression status (previous diagnosis with major depressive disorder, PHQ-9 score), the Patient Assessment of Chronic Illness Care (PACIC), and the Self-Efficacy for Managing Chronic Disease (SEMCD). When compared patients who endorsed any stigma (LSAS ≥1; N=217) and those who didn’t (LSAS ≥ 0; N=116), those with any stigma were less likely to be married (p<.01) and reported lower PACIC score (p<.01) Multiple regression was used to identify factors associated with STA. The adjusted R square was 0.098, and speaking Spanish (β=.12; p<.05), never married (β =.12; p<.01; ref=married), and SEMCD (β=-.19; p<.01) were associated with STA. When a Latino patient with T2DM was screened for elevated depressive symptoms and is prescribed with antidepressants in a community health center, services helping debunk stigma is recommended to those speaking Spanish, isolated, or presenting lower self-efficacy for managing diabetes.

Disclosure

H. Oh: None. K. Ell: None.

Funding

Patient-Centered Outcomes Research Institute
2287-PUB: Association of Depression Treatment and Glycemic Control in Adults with Diabetes
Authors: FU HELEN N. , RAITER ABAGAIL M. , CARLIN CAROLINE , PETERSON KEVIN A.
Published: June 2019

Patients with diabetes and comorbid depression have an increased risk of complications. In a repeated panel cross-sectional study, we investigated the effect of depression care on glycemic control for adults with diabetes. Local health plan provided secondary data (N=29,227) that contained depression information and overall health risk calculated by Johns Hopkins ACG software using diagnosis code, visits, and medication claims. This data was matched with A1c, demographics, and neighborhood characteristics.

Study outcome is A1c change. Predictor of interest is depression treatment: (1) no depression in either year, (2) new onset is not treated in prior year but treated in sequential year, (3) past is treated in one year and none in sequential year, and (4) persistent is received treatment in both years. Covariates are age, sex, health risk, insurance types, and neighborhood characteristics. The analysis is a multiple linear regression model using a difference-in-differences framework. Adjusting for covariates, new onset of depression treatment was associated with better diabetes control, A1c decreased by 0.072 (p=0.025), compared to no depression. Compared to no depression, past depression treatment was associated with lower diabetes control, A1c increased by 0.071 (p=0.007). Persistent depression treatment had A1c change not different from no depression group (p=0.731).

Among patients with diabetes, past depression treatment appeared to have poorer glycemic control compared with those not depressed. New onset of depression treatment appeared to improve glycemic control. New diagnosis of depression increased patient contact with provider. A decline in diabetes control among patients received depression treatment in the past, may be related to a change in contact with provider. Future studies could investigate whether patient visit with providers was affected by a change in depression and examine if A1c testing rate correlates with health service utilization.

Disclosure

H.N. Fu: None. A.M. Raiter: None. C. Carlin: None. K.A. Peterson: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R18DK110732)
2290-PUB: Depression and Anxiety Screening for Young Adults with Type 1 Diabetes in Transition from Pediatric to Adult Diabetes Care
Authors: NAGRA HARPREET , JOARDER FARAHNAZ , ANDREAS LAURA , KRAUS KIMBERLY
Published: June 2019

Objectives: Mood concerns among young adults with type 1 diabetes (T1D) can interfere with achieving optimal diabetes self-care, particularly during the transition from pediatric to adult care. Presented are the results of depression and anxiety screening for young adults who attended a multidisciplinary transition clinic.

Methods: All attendees of a multidisciplinary clinic for youth ages 17 to 25 with T1D completed measures of depression (PHQ-9) and anxiety (GAD-7).

Results: Of the 26 youth screened, 35% were female and the mean A1c was 9.1% (76 mmol/mol). PHQ-9 and GAD-7 score were not significantly different by gender. No association was found between A1c and PHQ-9 or GAD-7.

Conclusions: Previous research has linked depression and anxiety with poorer treatment adherence among individuals with T1D, however, there are few studies examining depression and anxiety in transition-age youth. Brief screening of young adults with T1D may illuminate potential threats to adherence as well as provide supplemental information to prevent future problems that may impact diabetes management. The study outcomes should be interpreted with caution given the small sample size and the homogeneous sample.

Disclosure

H. Nagra: None. F. Joarder: None. L. Andreas: None. K. Kraus: None.
2294-PUB: Professional Continuous Glucose Monitoring Improves Glucose Control in Type 2 Diabetes
Authors: LEIBOWITZ JONAS , WISOTSKY DANIEL J.
Published: June 2019

Professional continuous glucose monitoring (CGM) systems are thought to provide information about hypoglycemia and glucose variability. There is little data to support its use in the type 2 diabetic population for improving glucose control. We evaluated all patients with type 2 diabetes who wore a professional CGM (IPRO2-Medtronic) over an 18-month period in a clinical endocrinology practice. All patients who had an HbA1c on file within 90 days of wearing the CGM and a follow-up HbA1c 90 to 180 days after wearing the CGM were included in the analysis. The patients were divided into those who used insulin in any therapy combination or those who did not use insulin. There were 92 insulin users who had a baseline A1c of 8.35% which improved to 8.11% after wearing the CGM. The 74 noninsulin users had a baseline A1c of 7.87% which improved to 7.30% after wearing the CGM. Our analysis indicated that type 2 diabetics benefit from the use of a professional CGM to improve glycemic control as lifestyle or medication intervention can be better guided.

Disclosure

J. Leibowitz: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. D.J. Wisotsky: None.
2299-PUB: Liraglutide-Based Therapy Attained A1C Target with Little Risk of Hypoglycemia: Optimization by Average Daily Risk Range Measurement
Authors: KASHIMA KOJI , SHIMIZU HIROYUKI , YAMADA MASANOBU
Published: June 2019

Objective: Attainment of appropriate A1C target is indispensable to reduce the risk of diabetes complications in type 2 diabetic (T2D) patients. The aim of this study is to evaluate the ability of GLP-1 receptor agonist, liraglutide (Lira), to achieve A1C <7.0% without increase of hypoglycemia risk.

Methods: A total of 194 patients (65.5±12.6 year-old) on Lira-based therapy (LBT) with T2D were included in the analysis. Effectiveness was compared before and after introduction of LBT. Glycaemic variability was evaluated by calculating hypoglycemia-sensitive ADRR score in patients who did self-blood glucose monitoring (SMBG). To avoid hypoglycemia, basal insulin was reduced when fasting blood glucose level reached <80mg/dL.

Results: 1) Before change to LBT, even on insulin based basal-bolus therapy (BBT) (n=21) only 23.8% of the patients achieved the target, and on pre-mixed insulin therapy (MIX) (n=34), 20.6%. 2) Change to LBT improved the average of A1C from 9.7% to 7.1%, and the target was achieved in 55.7% of all patients (n=108/194). 3) Further, all patients were analyzed after divided into 3 groups by the treatment: Lira mono-injection (n=71), Lira+basal insulin (n=106), Lira+BBT/MIX therapy (n=17) group. In Lira mono-injection group, A1C was markedly improved from 10.1% to 6.6%, although the duration of diabetes was shortest (6.7±8.0 years) among 3 groups. The proportion of patients who achieved the target was 69.0%, 50.0%, and 35.3%, respectively. 4) 61.8% of patients at age of 70s also achieved the target by LBT. 5) To optimize blood glucose excursion, SMBG was done in 59.3% of patients. In patients who achieved A1C <7.0%, 82.2% (37/45) showed ADRR scores less than 10. Moreover, in patients who achieved more stringent A1C <6.0%, 73.3% (11/15) of patients showed much lower ADRR scores less than 5, indicating marked reduction of hypoglycemia risk.

Conclusion: LBT makes it easier to achieve lower A1C target without risking hypoglycemia in all ages.

Disclosure

K. Kashima: None. H. Shimizu: None. M. Yamada: None.
2300-PUB: The Efficacy and Safety of Combinations of SGLT2 Inhibitors and GLP-1 Receptor Agonists in the Treatment of Type 2 Diabetes: A Systematic Review and Meta-analysis
Authors: GUO MAN , GU JUNLING , LI JINGSONG , XU YONG
Published: June 2019

Objective: The aim of this study was to evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM).

Methods: We searched clinical trials indexed in PubMed, Embase, CENTRAL, Web of Science, and Scopus from inception through December 3, 2018. A meta-analysis was conducted of trials involving patients receiving SGLT2 inhibitors and GLP-1 agonists using Stata 12.0 software.

Results: A total of 9 clinical trials, including 5 randomized controlled trials (RCTs), that enrolled 1369 participants were identified for meta-analysis. Compared with the control/placebo group, the combination therapy group had significantly reduced fasting plasma glucose level by 0.78 mmol/L (95% confidence interval [CI]: -1.36, -0.2), 2-h postprandial glucose level by 0.47mmol/L (95% CI: -0.69, -0.24), glycosylated hemoglobin (HbA1c) by 0.73% (95% CI: -1.45, 0); body weight that was lower by 0.39 kg (95% CI: -0.59, -0.18) (4 non-randomized controlled trials indicated a larger reduction in body weight of 3.53 kg), and systolic blood pressure (SBP) that was lower by 0.26 mmHg (95% CI: -0.40, -0.11). The total incidence of adverse events (AEs) and genital and urinary infections in the therapy group did not significantly differ from those in the control group, with relative risks (RRs) of 1.06 (95% CI: 0.96, 1.17) and 1.19 (95% CI: 0.69, 2.07), respectively. An increased incidence of hypoglycemia was seen in the combination therapy group (RR=2.49; 95% CI: 1.40, 4.45).

Conclusions: SGLT2 inhibitor and GLP-1 agonist combination treatment improved glycemic control, reduced body weight, and decreased SBP without an increase in total AEs or genital and urinary infections in patients with T2DM. However, the risk of hypoglycemia should be carefully monitored in future clinical trials.

Disclosure

M. Guo: None. J. Gu: None. J. Li: None. Y. Xu: None.

Funding

National Natural Science Foundation of China (81800741)
2314-PUB: No Clinical Factors, Except Baseline HbA1c, Can Predict Glycemic Response to Dulaglutide: Real-World Data in Korean Patients
Authors: YOON JEEHEE , HONG A. RAM , KIM HEEKYUNG , KANG HO-CHEOL
Published: June 2019

Background: Dulaglutide, a once weekly glucagon-like peptide-1 receptor agonist, demonstrated efficacy and safety through several randomized controlled trials. The aim of our study was to evaluate glycemic response and to find the clinical factors useful in predicting glycemic response to dulaglutide in Korean patients with type 2 diabetes mellitus (T2DM).

Materials and Methods: We retrospectively reviewed medical records of T2DM patients treated with dulaglutide over 6 months in Chonnam National University Hwasun Hospital. Only patients who had baseline and serial HbA1c results (3 months and 6 months) after starting dulaglutide were included. We defined the good response as achieving HbA1c reduction ≥1.0% after 6-months’ treatment with dulaglutide. Clinical factors analyzed for prediction of glycemic response included age, sex, duration of T2DM, HbA1c, BMI, HOMA-β, and HOMA-IR.

Results: Among 77 patients, 38 patients (49.4%) achieved HbA1c reduction ≥1.0% after 6 months. Mean HbA1c level decreased from 8.78% at baseline to 8.03% at 6 months after treatment. Mean HbA1c reduction was -1.06% (95% confidence interval (CI); -1.45 and -0.67) at 3 months and -0.75% (95% CI; -1.27and -0.24) at 6 months after treatment. Mean weight reduction was 3.2 kg at 6 months. In subgroup analysis for predicting glycemic response to dulaglutide, only baseline HbA1c was associated with good response to dulaglutide in multivariate logistic regression analysis.

Conclusion: Dulaglutide is effective for glycemic control and higher baseline HbA1c is associated with good glycemic response to dulaglutide in Korean type 2 DM patients.

Disclosure

J. Yoon: None. A. Hong: None. H. Kim: None. H. Kang: None.
232-OR: The Joint Contribution of Social Determinants Factors to Mortality Risk in Adults with Diabetic Kidney Disease
Authors: OZIEH MUKOSO N. , GARACCI EMMA , EGEDE LEONARD E.
Published: June 2019

Introduction: No studies have examined whether social determinants of health (SDOH) have a synergistic effect on health outcomes. The study aim is to examine the synergistic impact of socioeconomic status (SES), psychosocial and neighborhood factors on mortality in U.S. adults with diabetes and CKD.

Methods: We analyzed data from NHANES (2005-2010) for adults linked to mortality follow-up. Primary outcome was all-cause mortality. CKD stage was based on eGFR and albumin-to-creatinine ratio. Diabetes was based on self-report or HbA1c ≥6.5%. Cox proportional hazards models was used to estimate the association between SES (poverty income ratio(PIR)), psychosocial (depression) and neighborhood factors (food insecurity-FI) on all-cause mortality as independent predictors and in a joint-effect model while controlling for covariates.

Results: This study included 994 adults (representing 8,188,150 U.S. adults) with diabetes. The sample mean age was 66 years, 40% Non-Hispanic white, 27% Non-Hispanic black, 68% had a ≤high school degree, 39% had PIR of ≤130%, 49% with CKD stage 1-2 and 51% with CKD stage 3-5. In individuals with diabetes and CKD, an increase in PIR was associated with 19% lower mortality (unadjusted HR=0.81, 95% CI=0.68-0.96) while food insecurity (unadjusted HR=0.92, 95% CI=0.72-1.18) and depression (unadjusted HR=1.03, 95% CI=0.98-1.08) did not have a significant effect. After adjusting for demographics, lifestyle, access to care, risk factor control and comorbidities, FI was associated with a 29% higher mortality (adjusted HR=1.29, 95% CI=1.04-1.60); PIR was associated with 22% lower mortality (adjusted HR=0.78, 95% CI=0.61-1.01), marginally significant and depression remained non-significant (adjusted HR=1.02, 95% CI=0.98-1.07). SDOH factors such as FI are an important determinant of mortality risk in this population independent of other SDOH such as SES, psychosocial factor etc. and non-SDOH factors such as lifestyle, access to care, diabetes control etc.

Disclosure

M.N. Ozieh: None. E. Garacci: None. L.E. Egede: Consultant; Self; Novo Nordisk Inc. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases.
2324-PUB: Assessment of the Effectiveness of Risk Minimization Measures for Concentrated Insulin Lispro 200 Units/ml: A Multinational Study
Authors: ALI AYAD K. , EWING MELISSA
Published: June 2019

This study evaluated the impact of additional risk minimization measures on healthcare professional (HCP) and patient understanding and behavior regarding the risk of hypoglycemia and/or hyperglycemia due to medication errors associated with administration of insulin lispro 200 units/ml (U-200) in U.S. and EU. The additional risk minimization measures for U-200 included a direct HCP letter, and a patient communication. Web and telephone cross-sectional surveys were administered to HCPs involved in the treatment and management of patients with diabetes who are aware of U-200, and adult patients with diabetes who have been prescribed U-200 in France, Germany, Sweden, and U.S.

A total of 424 HCPs (278 in U.S., 146 in EU) and 307 patients (300 in U.S., 7 in EU) completed the surveys. Among HCPs, 46% (U.S.=56%, 95% CI=50%-62%; EU=27%, 95% CI=20%-35%) were aware U-200 is not approved for transfer to different insulin delivery device; however, HCPs knowledge of appropriate U-200 prescribing was high: 95% indicating correct strength on prescription (U.S.=98%, 95% CI=95%-99%; EU=91%, 95% CI=85%-95%); and 73% answered that dose conversion is not necessary when changing patients between insulin lispro strengths (U.S.=80%, 95% CI=75%-84%; EU=60%, 95% CI=51%-68%). The vast majority of patients in U.S. (97%, 95% CI=94%-99%) were aware that U-200 should only be injected using the prefilled pen in which it is supplied. In U.S., 78% (95% CI=73%-83%) of patients and 92% (95% CI=88%-95%) of HCPs indicated it is always necessary to carry a backup pen.

In conclusion, this study showed in general that the additional risk minimization measures effectively communicated the key safety messages to the majority of HCPs. Patient recruitment in EU was challenging due to the stringent data protection regulations which makes the collection of meaningful pharmacovigilance-related data for patients in EU very difficult.

Disclosure

A.K. Ali: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. M. Ewing: Employee; Self; Eli Lilly and Company.
2326-PUB: The Correction Factor (CF) and Carbohydrate-to-Insulin Ratio (CIR) Are More Correlated to Each Other than to the Total Daily Dose (TDD)
Authors: SOCHA JILLAINE , KING ALLEN B.
Published: June 2019

The accepted bolus dosing factor estimation formulas are CIR = 450/TDD and CF = 1700/TDD. These formulas were not based on controlled studies. We have combined two of our previously published well-controlled studies to reevaluate these relationships. Both studies (30 pump treated T1DM and 11 pump- or multiple daily dose-treated T1 or 2 subjects) established the basal insulin dose by frequent glucose testing while on a controlled diet and meal omissions to assess the post-meal period. Then CIR was determined by the return of the 2-4 h post meal plasma glucose (PG) to ± 20% of the pre-meal and the CF was independently determined by greatest PG reduction during the 2-4th hour after a corrective bolus following hyperglycemia induced by a reduction (about 30%) of the basal insulin. CIR = CF/4.49 (r = 0.940), CIR = 295/TDD (r =0.720) and CIR = 107/TBD (r = 0.7310). The strong relationship between CIR and CF may be explained by CF is a measure of the ∆ PG/U and CIR is a measure of the anticipated ∆ PG/U and both are expressions of the insulin sensitivity of the same tissue bed. If one bolus dosing factor is established, the other could better be estimated using CF = CIR*4.5 than from TDD. The usual order of titration is TBD, then CIR and CF and finally TDD is calculated. After TBD is established and before bolus dosing factors and TDD, CIR = 100/TBD would be a better estimate than 450/TDD.

Disclosure

J. Socha: None. A.B. King: None.
2329-PUB: Transitioning T2DM Patients to Basal-Bolus Insulin Leads to Sustainable A1C Improvement
Authors: BARRY ROMIYA , JOHNS DON , REES BUDDUG
Published: June 2019

This is a post hoc analysis of a multi-country study of adults with type 2 diabetes transitioned from basal-only to basal-bolus insulin therapy. Patients were randomized 1:1 to deliver mealtime insulin using either a wearable delivery device (PAQ Meal) or a pen (NovoLog FlexPen®). We report the proportion of patients overall who achieved A1C ≤8% and A1C ≤7% by Week 24 and sustained the improvement through Week 44 when using a basal-bolus regimen. Baseline A1C ranged from 7.0 - 11.8% (patients, n=274). By week 24, 84.7% (232/274) of patients achieved A1C ≤ 8% (LOCF) which continued at 84.8% (184/217 completers) at Week 44. Overall, 77.9% (169/217) of patients saw a reduction of at least 1% in A1C by Week 44. Although, patients with higher baselines achieved a greater reduction of A1C, patients with lower baselines were significantly more likely to achieve A1C ≤ 7%. Reduction in A1C ≤ 7% was sustained by 63.6% (138/217) of patients through Week 44. Initiating a basal-bolus regimen and titrating based on morning and mealtime blood glucose levels saw the mean total daily dose increase from 47IU (basal only) at study entry to 121IU (basal-bolus) at Week 24 (0.8:1 basal:bolus). Only 6 severe hypoglycemic events occurred during the study. This study shows that transitioning from basal insulin-alone to basal-bolus insulin therapy, regardless of delivery mechanism, safely reduces and manages A1C levels in T2DM patients.

Disclosure

R. Barry: Consultant; Self; CeQur Corporation. D. Johns: Consultant; Self; CeQur Corporation. B. Rees: None.
2331-PUB: Effectiveness of Insulin Glargine 300 units/mL in Treating Patients with T2DM Uncontrolled by Basal Insulin in Real-Life Settings in the Czech Republic (TOPAZ Study)
Authors: PRAZNY MARTIN , FLEKAč MILAN , JELINEK PETR , MASKOVA JANA
Published: June 2019

Objective: To evaluate the clinical effectiveness of Gla-300 units/mL (Gla-300) in the treatment of patients with type 2 diabetes (T2DM) uncontrolled by basal insulin in real-life clinical settings in the Czech Republic (TOPAZ study).

Methods: TOPAZ was a prospective, multi-centric, non-interventional, 6-month study. Of the 312 patients screened, 289 were evaluated at month 6. The primary objective was the change of HbA1c after 6 months. The proportion of patients with HbA1c <7% DCCT (<53 mmol/mol), and those with a decrease of at least 0.5% of HbA1c at month 6, change in FPG, body weight and insulin dose at months 3 and 6 were analysed as secondary objectives. Incidence of hypoglycaemia, adverse events and patient treatment satisfaction (DTSQ) were also assessed.

Results: HbA1c decreased significantly after 6 months (mean change 0.9 ± 1.1% DCCT [-9.9 ± 11.6 mmol/mol], p < 0.0001). HbA1c target < 7% DCCT was achieved in 17.6% of patients, 66.1% of patients showed mean HbA1c decrease of -1.5 ± 0.8%. At month 6, FPG decreased (mean change from baseline -1.8 ±3.1 mmol/L) as well as the incidence of hypoglycaemia decreased by 49% (p ˂ 0.0001) while no weight gain was observed. No significant safety signals were identified. Patients reported significantly better satisfaction with the treatment with Gla-300 (p < 0.0001).

Conclusion: In a real-world setting, switching to Gla-300 in T2DM patients uncontrolled with any other basal insulin was associated with improved glycemic control and reduced risk of hypoglycaemia without weight gain, while patients′ satisfaction with treatment increased.

Disclosure

M. Prazny: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis, Takeda Pharmaceutical Company Limited. Board Member; Self; Bayer AG. Consultant; Self; Medtronic, Roche Diabetes Care. Speaker's Bureau; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis, Servier, Teva Pharmaceutical Industries Ltd. M. Flekac: None. P. Jelinek: Employee; Self; Sanofi. J. Maskova: Other Relationship; Self; Sanofi-Aventis.

Funding

Sanofi; Neox Clinical Research
2334-PUB: Evolution of the Designs of the Sitagliptin (SITA) Pediatric Clinical Studies
Authors: SHANKAR R. RAVI , POZHARSKAYA VERONIKA P. , LEIGHT KELLIE , NEWFIELD RON S. , DEEB ASMA , GARCIA RAYMUNDO , ROSARIO CARMEN A. , SAHA CHANDAN K. , SHEHADEH NAIM , SAMOILOVA YULIA , ENGEL SAMUEL S. , JALALUDIN MUHAMMAD Y. , ZEITLER PHILIP , KAUFMAN KEITH D.
Published: June 2019

Approved antihyperglycemic therapies for pediatric patients with T2D are currently limited to metformin (MET) and insulin. SITA is being evaluated in 3 studies in patients 10-17 years of age with T2D: SITA as initial oral therapy, MK-0431 P083; SITA as add-on to MET administered as a fixed dose combination (FDC), MK-0431A P170; and SITA as add-on to MET extended-release administered as a FDC of SITA and MET XR, MK-0431A XR P289. The studies, conducted to fulfill post-marketing requirements, and a Pediatric Investigation Plan (EU), were initiated between 2011 and 2013; enrollment completed in 2018. Study protocols were amended since initiation to accommodate regulatory agency requirements, reduce patient burden related to study conduct, and improve patient accrual. Major amendments to the protocols, their rationales, and their impacts are summarized (Table) and demonstrate the flexibility that may be required to enroll such studies. The impact on enrollment of 2 amendments common to all 3 studies were quantifiable. Of patients randomized after approval of an amendment that broadened the A1C entry criterion (from lower limit of 7.0% to 6.5%), ∼34% in P083, ∼20% in P170 and ∼20% in P289 had a baseline A1C between 6.5% and 6.9%. Of patients randomized after approval of an amendment to include patients on background insulin, 11% of patients in P083, 22% in P170, and 19% in P289 enrolled on background insulin.

Disclosure

R. Shankar: Employee; Spouse/Partner; AstraZeneca. Employee; Self; Merck & Co., Inc. Employee; Spouse/Partner; NGM Biopharmaceuticals. V.P. Pozharskaya: Employee; Self; Merck & Co., Inc. K. Leight: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. R.S. Newfield: Research Support; Self; Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Eli Lilly and Company, University of California and Rady Children's Hospital, San Diego. A. Deeb: None. R. Garcia: None. C.A. Rosario: None. C.K. Saha: Research Support; Self; Indiana University School of Medicine. N. Shehadeh: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. Y. Samoilova: None. S.S. Engel: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. M.Y. Jalaludin: Advisory Panel; Self; Novo Nordisk Inc. Research Support; Self; Merck Sharp & Dohme Corp., Novo Nordisk Inc. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc. K.D. Kaufman: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc.

Funding

Merck & Co., Inc.
2337-PUB: Impact of Treatment with Insulin and Other Hypoglycemic Drugs on 5'-AMP-Activated Protein Kinase Activity in Leukocytes of Patients with Type 2 Diabetes
Authors: PUSHKAREV VIKTOR V. , SOKOLOVA LIUBOV K. , PUSHKAREV VOLODYMIR M. , VATSEBA TAMARA , TRONKO MYKOLA D.
Published: June 2019

Background: The leukocytes play an essential role in the development of pathological conditions such as diabetes and its complications. The 5'-adenosine monophosphate-activated protein kinase (AMPK), which usually is inhibited in T2D, controls the energy balance of the cell.

Aim: To study the phosphorylation of AMPK α-subunit (Thr172), and thus its activation, in blood cells at combined T2D patients treatment with insulin, metformin and dapagliflozin.

Methods: To determine the amount of phospho-AMPK (phospho-threonine 172) enzyme-linked immunosorbent assay (ELISA) kit ab154468 (Abcam, UK) was used. The results of the study are presented as M ± SD, n = 3-6. To compare the data groups, Student's t-test was used. Values of P ≤ 0.05 were considered as significant.

Results: It has been shown that metformin increased the activity of AMPK in the leukocytes of patients with T2D more than 3-6 times compared with patients before treatment. Dapagliflozin increases the activity of AMPK and enhances the effect of metformin in the leucocytes of patients with T2D. The mechanisms of drug interaction and the consequences of their antagonism are discussed.

Conclusion: AMPK activity in leukocytes may be additional indicator of the effectiveness of the hypoglycemic drugs action and status of the disease.

Disclosure

V.V. Pushkarev: None. L.K. Sokolova: None. V.M. Pushkarev: None. T. Vatseba: None. M.D. Tronko: None.
2339-PUB: Effect of IDegLira on HbA1c and Weight: Data from the Association of British Clinical Diabetologists (ABCD) IDegLira Audit
Authors: NORONHA SEAN , LUMB ALISTAIR N. , BICKERTON ALEX , SIM SING YEE , GALLEN IAN W. , ADAMSON KAREN , RYDER ROBERT E.
Published: June 2019

Unique in the UK armoury of injectable agents for diabetes, the combination IdegLira offers the clinical advantages of degludec and liraglutide, with the convenience of a once daily injection. The ABCD IDegLira audit, commenced in April 2017, is a nationwide audit evaluating whether the favourable effects of IDegLira on HbA1c and weight previously shown in clinical trials translate into similar advantages when the agent is used in real clinical practice. Data to date has been obtained nationwide via two routes: a physician populated online audit tool and a cloud-based IT system (Eclipse), capable of integrating with existing primary care systems to facilitate audit, risk stratification and patient empowerment. The inclusion criteria were people with type 2 diabetes started on IDegLira, who had HbA1c and weight measured at baseline and 6 months into treatment. Baseline values were defined as the most recent values in the 6-month period prior to initiation of IDegLira. Endpoint data was accepted within a collection window of +/- 45 days. We identified thirty-five patients for HbA1c (15M, 20F, mean ± SD age 57.4 ± 8.2) and twenty-eight patients for weight (13M, 15F, mean ± SD age 75.0 ± 8.6). Baseline HbA1c and weight were compared with the 6-month values with 2-sided p-values using a paired T Test. Mean ± SD HbA1c fell by 1.43% ± 2.04, from 10.17% ± 1.93 to 8.73% ± 1.74 (p<0.0005). Mean ± SD weight fell by 0.53kg ± 5.77, from 105.24kg ± 24.44 to 104.71kg ± 24.17 (p=0.63). These findings confirm that real world experience with IDegLira is consistent with trial evidence, showing statistically significant reductions in HbA1c and a lack of weight gain. IDegLira is therefore a valuable option when treatment intensification is required in patients with type 2 diabetes. Given that the total yearly cost of IDegLira is less than separate degludec and liraglutide at the equivalent dose, these data would support use of the combination product.

Disclosure

S. Noronha: None. A.N. Lumb: Advisory Panel; Self; Dexcom, Inc., Novo Nordisk A/S. Consultant; Self; LifeScan, Inc. Speaker's Bureau; Self; Abbott, Novo Nordisk A/S. Other Relationship; Self; Abbott. A. Bickerton: Employee; Self; MyWay Digital Health. S. Sim: None. I.W. Gallen: None. K. Adamson: None. R.E. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest.

Funding

Association of British Clinical Diabetologists
234-LB: Incidence Trends of Diabetic Ketoacidosis at and after Diagnosis of Type 1 Diabetes in British Columbia, Canada
Authors: KAO KUNG-TING , ISLAM NAZRUL , FOX DANYA A. , AMED SHAZHAN
Published: June 2019

Objective: Diabetic ketoacidosis (DKA) is a preventable complication in youth with type 1 diabetes (T1D). This study aimed to estimate the incidence trend of DKA at T1D diagnosis (DKA-AT, defined as DKA within 14 days of T1D diagnosis) and after T1D diagnosis (DKA-AFTER, defined as DKA after 14 days of T1D diagnosis) from 2002 to 2012 in British Columbia, Canada.

Methods: We used a previously described population-based cohort of individuals diagnosed with T1D at <20 years of age. DKA episodes were identified using ICD9/10 codes (250.1X/E101X). Incidence rate ratio (IRR) was estimated using Poisson regression and trends in DKA rates were examined using Joinpoint regression analyses.

Results: 2615 incident cases of T1D were identified between 2002 and 2012, of which 847 (32.4%) were diagnosed with DKA-AT. 52% were male. The rates of DKA-AT by year ranged between 24.1% (2008) and 37.3% (2006). No sex differences were observed. The IRR was 2.0 (95% CI: 1.6, 2.5; p<0.001) for those diagnosed with T1D at 0-4 years compared to those diagnosed at 15-19 years old, after adjusting for the trend by fiscal year. In the same period, 1886 episodes of DKA-AFTER were identified with a consistent increase from 5.3% (2002) to 9.5% (2012). The IRR for DKA-AFTER in children 0-4 years old at diabetes diagnosis was 9.13 (95% CI: 7.73, 10.77; p<0.001). After adjusting for the increasing trend by fiscal year, females had higher rates of DKA-AFTER than males (IRR 1.45, 95% CI: 1.33, 1.59; p<0.001). The average annual percent change for DKA-AFTER was 4.91% (95% CI: 2.69, 7.18; p<0.001).

Conclusions: DKA-AT incidence remained unchanged while the incidence of DKA-AFTER increased over time, with the greatest burden in those diagnosed at a younger age. Targeted interventions are needed to raise public awareness to prevent DKA-AT and to educate patients and families in preventing DKA-AFTER.

Disclosure

K. Kao: None. N. Islam: None. D.A. Fox: None. S. Amed: None.
234-OR: Modified Endothelial Progenitor Cell (EPC) Transplantation May Improve Diabetic Kidney Disease (DKD)
Authors: KUNDU NABANITA , ASICO LAUREANO D. , BANERJEE JAIDEEP , JOSE PEDRO A. , SEN SABYASACHI
Published: June 2019

Introduction: Diabetic kidney disease (DKD) is a major complication of diabetes, which is associated with sclerotic glomerular disease and poor perfusion. Therefore, improving the renal perfusion may help to halt or reverse the kidney injury. We want to investigate whether transplanting genetically modified EPC by silencing apoptosis gene p53 may promote vasculogenesis and improve renal perfusion. We also wanted to compare p53shEPC with another possible cell therapy such as mesenchymal stromal cell (MSC) (unmodified).

Method: Hyperglycemia and proteinuria in STZ-induced type1-diabetic mice were confirmed at 8 weeks post STZ, followed by transplantation of 0.3 million p53shEPCs, NullEPCs, mouse MSC (mMSC) or saline (control) under each kidney capsule. Urine protein and plasma creatinine were estimated weekly. Perfusion was measured by laser Doppler at sacrifice at week 4 followed by renal histology and qRTPCR.

Results: Reduction of proteinuria was observed in p53shEPC transplantation group compared to null (1.3 fold). Plasma creatinine of p53sh-EPCs group was less than nullEPC (2.7 fold) but similar to MSC transplanted animals (1.5 fold). Increased perfusion was noted p53sh-EPC group compared to NullEPC, MSC and saline (1.2, 2.4 and 3.0 fold respectively). Markers for angiogenesis, such as eNOS (2.6, 1.6 fold respectively) and VEGFA (1.2, 1.5 fold respectively) increased more with post p53shEPC transplantation compared to nullEPC and MSC. We noted heart rate (HR) reduction post p53shEPCs transplantation compared to null whereas HR actually increased in mMSC transplanted mice. Kidney histology following Isolectin-β4 staining showed significant improvement in sclerosed glomerular vascular tufts, with p53shEPC delivery, compared to null, MSC and saline.

Conclusion: Transplantation of p53sh-EPC improved proteinuria, perfusion, and vascular gene mRNAs compared to NullEPCs, MSCs and saline. Modified EPC transplantation may have a prominent cell therapy role in DKD.

Disclosure

N. Kundu: None. L.D. Asico: None. J. Banerjee: Employee; Self; Osiris Therapeutics, Inc. P.A. Jose: None. S. Sen: None.

Funding

American Heart Association
2343-PUB: Reduction of HbA1c after SGLT2 Inhibitors Correlate with Change in Plasma Osmolarity but Not with Elevation of Hematocrit in Japanese Patients with Type 2 Diabetes
Authors: WADA YOSHIHARU , HAMAMOTO YOSHIYUKI , NAKATANI YOSHIHISA , FUJIKAWA JUN , IWASAKI YORIHIRO , YOSHIJI SATOSHI , AIZAWA-ABE MEGUMI , IWASAKI KANAKO , HONJO SACHIKO , HAMASAKI AKIHIRO
Published: June 2019

Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors is expected its hematopoietic effect for treatment of the anemia in chronic renal failure. However, it is still unclear whether the effect is independent from its antidiabetic effect. In this study, we investigated correlations between hematocrit elevation, HbA1c reduction or parameters reflecting diuretic change in patients with type 2 diabetes (T2D). A total of 46 patients (male: n = 33, age: 54.6 ± 10.4 [mean ± SD] years, BMI: 29.2 ± 4.3 kg/m2, HbA1c: 8.7 ± 1.0%) with T2D who were newly administered SGLT2 inhibitors from July 2014 to November 2016 were retrospectively identified. The patients with HbA1c less than 7.0% at the baseline or who showed decrease in hematocrit or increase in HbA1c were excluded. Changes in HbA1c, hematocrit, urine specific gravity, uric acid, serum creatinine and plasma osmolarity levels between before and 30 days after the administration of the drugs were evaluated. Plasma osmolarity was calculated by the formula (2 x (Na [mEq/l] + K [mEq/l])) + (BUN [mg/dl]/2.8) + (glucose [mg/dl]/18). HbA1c was decreased (-0.68 ± 0.50%; p = 0.001) and hematocrit (2.1 ± 1.4%; p = 0.002) and urine specific gravity (0.008 ± 0.009 g/ml; p < 0.001) were increased significantly. However, uric acid, serum creatinine and plasma osmolarity did not show change. Changes in HbA1c and plasma osmolarity showed significant correlation (r = -0.31; p = 0.03) whereas changes in hematocrit and plasma osmolarity did not (r = -0.01; p = 0.94). HbA1c showed no significant correlation with hematocrit, serum creatinine, uric acid or urine specific gravity; hematocrit also did not have significant correlation with serum creatinine, uric acid or urine specific gravity.

In conclusion, our data suggest that the elevation of hematocrit and decrease in HbA1c after the administration of SGLT2 inhibitors have different relation with parameters reflecting diuretic effects.

Disclosure

Y. Wada: None. Y. Hamamoto: Speaker’s Bureau; Self; Novo Nordisk A/S. Y. Nakatani: None. J. Fujikawa: None. Y. Iwasaki: None. S. Yoshiji: None. M. Aizawa-Abe: None. K. Iwasaki: None. S. Honjo: None. A. Hamasaki: None.
2357-PUB: Dapagliflozin for 52 Weeks Improves Diastolic Dysfunction and Vascular Reactivity in T2D
Authors: D'IPPOLITO ILENIA , DE CARLI ELISA , ANDREADI AIKATERINI , ROMANO MARIA , GALLI ANGELICA , CAPRIA AMBROGIO , MASSARO MICHELLE , SBRACCIA PAOLO , DELLA-MORTE DAVID , BELLIA ALFONSO , LAURO DAVIDE
Published: June 2019

Background: SGLT2i proved efficacy in reducing cardiovascular morbidity and mortality in T2D patients at high cardiovascular risk.

Aims: In real-word setting, we prospectively evaluated long-term effects of Dapagliflozin (DAPA) on left diastolic ventricular function (LDVF) and vascular reactivity in T2D patients without known cardiovascular disease.

Population, Study and Methods: 13 patients (9 male, 57± 8 years, BMI 29.6± 3.6, HbA1c 8.9±1.2%, years of T2D 9±5, fasting glucose 185±51 mg/dl) initiated DAPA 10 mg daily as add-on to metformin. Following data were collected at baseline (T0), after 12 weeks (T1) and 52 weeks (T2) of treatment: blood pressure, anthropometrics, fasting glucose, HbA1c, eGFR and lipids. Ratio of the early (E) to late (A) ventricular filling velocities (E/A) was used to evaluate LDVF. Arterial stiffness was evaluated by Pulse Wave Velocity (PWV) and Augmentation Index (AIxHR75) with radial approach (SphygmoCor System). Endothelial function was assessed by non-invasive flow mediated dilatation (FMD).

Results: We observed significant percent variation in HbA1c (T1 vs. T0 -17.9%, p=0.001; T2 vs. T0 -17.4%, p=0.01), fasting glucose (T1 vs. T0 -25.9%, p=0.002, T2 vs. T0 -31.8%, p=0.005) systolic blood pressure (T1 vs. T0 -6.7%, p=0.03; T2 vs. T0 -10.2% p=0.02) and BMI (T1 vs. T0 -3.3%, p=0.001; T2 vs. T0 -3%, p=0.02). Significant improvements from baseline of E/A ratio (T1 vs. T0 +15%, p=0.03; T2 vs. T0 +27.5%, p=0.003) and brachial FMD (T1 vs. T0 +50.7%, p=0.02; T2 vs. T0 +39.4%, p=0.04) were also seen. No significant changes in eGFR, lipids and arterial stiffness measures were seen.

Conclusions: Intensification of treatment with DAPA 10 mg was accompanied by significant improvements in LVDF and endothelial-dependent vasodilation measures, which persist after 52 weeks of treatment. These preliminary observational results shed light on potential mechanisms responsible for cardiovascular protection with SGLT2i in T2D patients, even in absence of overt cardiovascular disease.

Disclosure

I. D'ippolito: None. E. De Carli: None. A. Andreadi: None. M. Romano: None. A. Galli: None. A. Capria: None. M. Massaro: None. P. Sbraccia: None. D. Della-Morte: None. A. Bellia: None. D. Lauro: None.

Funding

University of Rome
2362-PUB: Comparative Efficacy of Ertugliflozin (ERTU) + Sitagliptin (SITA) vs. Other Sodium-Glucose Cotransporter 2 Inhibitor (SGLT2i) + Dipeptidyl Peptidase-4 Inhibitor (DPP-4i) Combinations: Model-Based Meta-analysis (MBMA) of HbA1c Lowering
Authors: FEDIUK DARYL , MANDEMA JAAP , SWEENEY KEVIN , TERRA STEVEN G. , SAHASRABUDHE VAISHALI
Published: June 2019

Background: An ERTU/SITA fixed-dose combination is approved for the treatment of adults with type 2 diabetes mellitus (T2DM). As several SGLT2i + DPP-4i combinations are commercially available, MBMA of the HbA1c-lowering effect of these combinations was undertaken to assess their comparative effectiveness.

Methods: MBMA quantified the time course of dose vs. HbA1c response of SGLT2i + DPP-4i combinations and evaluated the impact of covariates including baseline HbA1c, estimated glomerular filtration rate (eGFR) and background diabetes treatment on HbA1c efficacy. Of the 496 randomized controlled trials (RCTs) in the database, 261 RCTs representing >87,000 T2DM patients were with SGLT2 inhibitors and/or DPP-4 inhibitors, including 2 RCTs for ERTU + SITA.

Results: For SGLT2i + DPP-4i combinations, the HbA1c efficacy increased with higher baseline HbA1c and decreased with declining renal function. Additionally, the HbA1c efficacy was greater on a diet background alone relative to a background of oral antidiabetic treatment.

Conclusion: This MBMA allowed an indirect comparison of SGLT2i + DPP-4i efficacy across trials (Table). Overall, ERTU 5 or 15 mg + SITA 100 mg doses were of comparable or numerically greater efficacy to other SGLT2i + DPP-4i combinations.

Disclosure

D. Fediuk: Employee; Self; Pfizer Inc. J. Mandema: Consultant; Self; Merck & Co., Inc., Pfizer Inc., Sanofi. K. Sweeney: Employee; Self; Pfizer Inc. S.G. Terra: Employee; Self; Pfizer Inc. V. Sahasrabudhe: Employee; Self; Pfizer Inc.

Funding

Pfizer Inc.; Merck Sharp & Dohme Corp.