bluuebunny/crossref_metadata_2025 huggingface dataset:
2311-PUB: Effectiveness of Incretin-Based Therapies in Children with Early Stage Slowly Progressive Type 1 Diabetes
Authors: URAKAMI TATSUHIKO , AOKI MASAKO , ABE YURIKO
Published: June 2019

In the Japanese population, type 1 diabetes (T1D) exhibits heterogeneity in clinical form: the abrupt onset form and slowly progressive form. Patients with the slowly progressive form of T1D can be managed with a low dose of insulin within one year of diagnosis; nevertheless, insulin supplementation is necessary from diagnosis to maintain optimal glycemic control in pediatric cases. On the other hand, incretin-based therapies might be an option even for T1D patients in whom β-cell function is preserved at the early stage of diabetes. We administered incretin-based therapies to 4 children with slowly progressive T1D as initial treatment and investigated their clinical course. Slowly progressive T1D was detected in 4 children (9-15 years) with mild metabolic decomposition via urine glucose screening at schools. All children showed positivity for β-cell autoantibodies. These children showed preserved endogenous insulin secretion with glucagon-stimulated C-peptide levels of 1.54-2.67 ng/mL. As initial treatment, they received incretin-based therapies: 3 children were treated with glucagon-like peptide-1 receptor agonists and 1 was treated with a dipeptidyl peptidase 4 inhibitor. They sustained postprandial C-peptide levels of 2.29-6.60 ng/mL and maintained hemoglobin A1c levels of 5.6%-6.6% for 8-18 months following diagnosis, without insulin treatment. No problematic adverse events, including hypoglycemia, were observed with administration of the incretin-based therapies. These findings suggest that incretin-based therapies could be effective for safe maintenance of optimal glycemic control and preservation of β-cell function at an early diabetic stage in children with slowly progressive T1D. However, it is necessary to confirm the efficacy and safety of incretin-based therapies in a large number of patients.

Disclosure

T. Urakami: None. M. Aoki: None. Y. Abe: None.
2317-PUB: Diabetic Ketoacidosis in Adult Type 1 Diabetes Mellitus Patients on Insulin Pumps
Authors: AMIR MARYAM , ASHI SULEIMAN AL , LANSANG M. CECILIA , AL-JAGHBEER MOHAMMED
Published: June 2019

Background: Insulin pumps are increasingly being used as a method of insulin delivery in patients with type 1 diabetes mellitus (T1DM). Diabetic ketoacidosis (DKA) is a serious complication of T1DM. This study aims to identify causes of DKA in T1DM patients on insulin pump, and to compare these with patients with T1DM on multiple daily insulin injections (MDII).

Methods: This was a prospective observational pilot study assessing DKA between 2 groups of patients with T1DM: (1) on insulin pump and (2) on MDII. Demographic and clinical data were obtained from chart review. Patients’ knowledge on insulin and diabetes care was assessed with a questionnaire we devised.

Results: We enrolled 17 adult patients - 12 on insulin pump (7 Medtronic, 3 Tandem, 2 Animas) and 5 on MDII - who were admitted to the ICU for DKA management. Eleven (65%) were females, all were Caucasian, with median age in pump users 27.0 years (IQR 22.5,39.5) vs. MDII 38.0 (IQR 32.0,51.0)(p=0.045). The rest of the demographic data were comparable. Majority of the patients on insulin pump had a pump >5 years and had the current pump <5 years. Six were given pump training in the physician’s office and 6 by the insulin pump company. In patients on insulin pump, 41% of DKA cases were pump- and tubing- related, 41% were due to non-adherence and 18% were due to an infection. In contrast, all the MDII patients had DKA due to non-adherence. Insulin pump patients had significantly higher adherence (p= 0.014) and better knowledge of managing hyperglycemia on sick days (p = 0.029) than MDII patients.

Conclusion: A significant proportion of DKA in pump users was due to pump issues. Non-adherence was common in both pump users and MDII. Continued education on pump use may reduce the rate of DKA in pump users.

Disclosure

M. Amir: None. S. Al Ashi: None. M. Lansang: None. M. Al-Jaghbeer: None.
232-LB: Cardiovascular Complications in T1D and T2D Patients Show More Similarities than Differences
Authors: ERIKSSON JAN W. , BODEGARD JOHAN , NORHAMMAR ANNA , THURESSON MARCUS , NATHANSON DAVID , NYSTROM THOMAS
Published: June 2019

The aim was to describe baseline and compare CVD risks between full populations of T1D vs. T2D patients. All T1D and T2D patients in Sweden were identified in nationwide health care registries and followed from year 2013 until death or year 2016, 3 years. The following CVD diagnoses were explored: myocardial infarction (MI), heart failure (HF), stroke and CV mortality and chronic kidney disease (CKD). First, age stratified categories were used to compare baseline CVD and CKD in T1D vs. T2D. Second, age stratified event rates were compared for CVD and CKD in T1D vs. T2D. In total 47,424 T1D and 364,293 T2D patients were identified. Crude baseline showed that T1D patients were younger (40.6 vs. 67.0 years), had less CVD (11.7% vs. 31.0%), and more CKD (3.6% vs. 3.3%) and severe hypoglycaemia (1.7% vs. 0.5%). First, age-stratification at baseline showed that T1D vs. T2D had similar CVD prevalence, where HF prevalence increased markedly from 60 years and older, and MI/stroke from 55 years. CKD prevalence was higher at all ages in T1D vs. T2D. Second, age-stratified CV event rates were similar for T1D vs. T2D, slightly higher for HF and MI in T1D (Figure). CKD event rates were higher in T1D vs. T2D.

In summary, CVD showed similar prevalence and risks in T1D compared to T2D patients. A slightly increased HF and MI risk at younger age was observed in T1D. CKD was both more prevalent and showed greater risk in T1D across all ages.

Disclosure

J.W. Eriksson: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. J. Bodegard: Employee; Self; AstraZeneca. A. Norhammar: Advisory Panel; Self; Merck Sharp & Dohme Corp. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Foundation. Research Support; Self; AstraZeneca. M. Thuresson: Consultant; Self; AstraZeneca. D. Nathanson: None. T. Nystrom: Board Member; Self; Amgen Inc., Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; AstraZeneca.

Funding

AstraZeneca
2320-PUB: Effects of Sequential Therapy Using Metformin plus Pioglitazone following Short-Term Intensive Insulin Therapy in Patients with Newly Diagnosed T2DM
Authors: LIU LIEHUA , HAI LI , KE WEIJIAN , LI YANBING
Published: June 2019

Aims: Short-term intensive insulin therapy (SIIT) reverses β cell dysfunction in early T2DM, but this effect vanes overtime. This study aimed to investigate the effects of metformin plus pioglitazone sequential therapy on maintenance of the effect of SIIT.

Methods: SIIT were applied in 50 patients with newly diagnosed T2DM to normalize blood glucose for 2 weeks. Patients were then randomly assigned to receive either sequential therapy (metformin 0.5g bid plus pioglitazone 15mg bid) or lifestyle change alone for 3 months. OGTTs were performed with plasma glucose and insulin measured.

Results: As showed in the figure, plasma glucose profiles and insulin response during OGTT were improved similarly by SIIT in both groups. At 3 months of follow-up, GHbA1c (6.2±0.6% vs. 6.5±0.4%, P=0.12) in the sequential treatment group was slightly lower though without statistical significance. In OGTT, blood glucose 30, 60 and 90 minutes was significantly lower in the sequential treatment group, which led to lower AUCglucose (1456.1±266.3 vs. 1644.8±184.5 mmol/L*min, P=0.03) and higher AUCinsulin to AUCglucose ratio (2.5±1.9 vs. 1±1.1, P=0.01). HOMA B, HOMA IR, Mesuda index and ISSI-2 were all similar between the two groups.

Conclusion: Metformin plus pioglitazone as sequential therapy might improve glycemic control and β cell function after SIIT in newly diagnosed T2DM.

Disclosure

L. Liu: None. L. Hai: None. W. Ke: None. Y. Li: None.

Funding

National Key Research and Development Program of China (2018YFC1314102)
2321-PUB: Improved Glycemic Control among Patients Newly Prescribed IDegLira across Various Background Therapies in U.S. Real-World Practice
Authors: EGEDE LEONARD E. , BOGDANOV ALINA , FISCHER LAUREN , DA ROCHA FERNANDES JOAO DIOGO , KALLENBACH LEE
Published: June 2019

IDegLira is a fixed-ratio combination of degludec and liraglutide indicated for the treatment of type 2 diabetes (T2D). This is the first real world study describing change in glycated hemoglobin (HbA1c) among U.S. patients initiating IDegLira. The primary objective was to observe the effect in metabolic control of initiating IDegLira in adult T2D patients previously on basal insulin (Basal), glucagon-like peptide-1 receptor agonist as only injectable (GLP-1), and no injectable therapy (N-INJ) between March 2017 and June 2018 (index date). Patients with HbA1c data 6 months prior to and 6m post index date were included from the Practice Fusion Electronic Health Record database. Of the 1,384 IDegLira patients, 206 patients had baseline, and follow-up HbA1c (180 ± 45 days) data. Changes in clinical outcomes were evaluated by paired t-test. Overall there was significant change in HbA1c of -0.9% (p<.001), and there was an HbA1c reduction in all three background therapy groups, ranging from -0.7 in the Basal to -1.0 in N-INJ (p<0.001). There was no significant change in weight in the overall group despite initiating or intensifying insulin therapy with IDegLira, as expected weight in the GLP-1 subgroup increased (3.0 lb; p<.05). Consistent with previous real-world studies, IDegLira is effective at lowering HbA1c across different background therapies with minimal impact on weight.

Disclosure

L.E. Egede: Consultant; Self; Novo Nordisk Inc. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. A. Bogdanov: None. L. Fischer: None. J. da Rocha Fernandes: Employee; Self; Novo Nordisk A/S. L. Kallenbach: Employee; Self; Veradigm.

Funding

Novo Nordisk
2338-PUB: Metformin Administration Attenuates Dipeptidyl Peptidase-4 Inhibitor-Induced KL-6 Level Elevation
Authors: SHIMODA YOKO , OKADA JUNICHI , YAMADA EIJIRO , OKADA SHUICHI , YAMADA MASANOBU
Published: June 2019

Given the lack of clarity regarding the benefits of metformin in patients with type 2 diabetes mellitus who were prescribed DPP-4 inhibitors (DPP-4is), we compared KL-6 levels in patients who were prescribed DPP-4is and in patients who were prescribed both DPP-4is and metformin. 54 patients were prescribed DPP-4is and KL-6 levels were measured in all of these patients. 25 patients were prescribed metformin. Thus, the patients were categorized into two groups: DPP-4i (DPP-4i without metformin; N = 29) and DPP-4i and met (DPP-4i with metformin; N = 25). The KL-6 levels in the DPP-4i was significantly higher than that of DPP-4i and met groups (300.76 ±155.39 vs223.96 ±73.83 U/mL, mean ±standard deviation, reference range: <500 U/mL, p= 0.0281). Transient elevation in KL-6 levels beyond the upper limit of normal range was observed in four patients in the DPP-4i group only. KL-6 levels were not elevated in any patients in the DPP-4i and met group. Despite the small sample size, this clinical study provides important information. One strength of the current study is that the KL-6 level was measured in all patients with type 2 diabetes mellitus who were prescribed DPP-4is. We confirmed that KL-6 levels were in the normal range before initiating DPP-4i administration. Moreover, KL-6 levels were transiently elevated and normalized after DPP-4i termination. The frequency of KL-6 level elevation due to DPP-4i administration was 7.4% although all of participated patients showed normal study on chest X-ray examination. This incidence was higher than that of statin-induced interstitial pneumonia. Metformin may prevent or delay interstitial lung diseases due to DPP-4i administration. However, KL-6 level in patients with metformin alone needs to be estimated.

Disclosure

Y. Shimoda: None. J. Okada: None. E. Yamada: None. S. Okada: None. M. Yamada: None.
2373-PUB: Overcoming the Challenges in Discovering Celiac Disease in Type 1 Diabetes Mellitus Focusing on Provider Education
Authors: EPPS MICHELLE , FOX MARISSA , JAFARI JASMINE , FIREK ANTHONY
Published: June 2019

Background: Patients with type 1 diabetes mellitus (DM1) are at risk for having autoimmune conditions such as Celiac Disease (CD). Although uncommon, the presence of CD in a patient with DM1 may result in poor glycemic control, gastrointestinal complaints, nutritional deficiencies, osteoporosis and lymphoma. Recognizing CD is problematic as it is often asymptomatic or presents in an atypical fashion. Despite recommendations from both the ADA and the American College of Gastroenterology our experience suggests there is a general lack of recognition of screening recommendations and presentation in CD particularly in patients with DM1.

Methods: Our objectives were three-fold. We first developed a novel on-line assessment program to determine existing knowledge on CD in both medical and family practice residents and faculty. We then developed on-line and direct education to improve knowledge on screening, presentation and diagnosis of CD. Lastly, we have determined the screening rate of adults with a diagnosis of DM1.

Results: Our screening rate of at-risk adults with DM1 is less than 20% indicating a poor recognition of CD as a recognized risk. In addition, we determined that CD is rarely considered in patients with DM1 with poorly controlled diabetes even in the context of GI complaints. Our preliminary survey of residents’ knowledge on screening, diagnosis and complications of CD was poor with less than 35% having adequate knowledge status.

Conclusion: Screening for CD in our DM1 patients is poor due to lack of knowledge of criteria and screening strategy of providers. This may reflect a significant deficit in resident and faculty knowledge of CD. In addition, CD is rarely considered in symptomatic adults with DM1. We propose our education program aimed at both residents and our faculty will overcome our lack of an organized education program addressing CD and is predicted to improve screening, diagnosis and treatment of adults with DM1 suffering from CD within our population.

Disclosure

M. Epps: None. M. Fox: None. J. Jafari: None. A. Firek: None.
2376-PUB: Glycemic Control after Decline of Insulin Therapy by Patients
Authors: FLOREZ LUISA , TURCHIN ALEXANDER
Published: June 2019

Recent evidence shows that many patients with type 2 diabetes (T2DM) initially decline insulin treatment. For some patients this could lead to poor glycemic control, whereas others may be able to lower blood glucose by alternative means. However, it is not currently known what factors affect achievement of glycemic control after decline of insulin therapy by patients.

We conducted a retrospective cohort study to determine patient characteristics predictive of glycemic control after they decline insulin treatment. We studied adults with T2DM treated at two academic medical centers between 1993 and 2014 who rejected insulin therapy recommended by their providers. We compared 150 randomly selected patients whose A1c subsequently decreased to 150 patients whose A1c increased or stayed the same.

Patients whose A1c decreased had a significantly higher baseline A1c (9.5% vs. 8.5%; p < .001), were more likely to implement lifestyle changes (27.3% vs. 7.3%; p < .001) and less likely to be non-adherent to diabetes medications (1.3% vs. 26.7%; p < .001) or to discontinue a non-insulin diabetes medication (8.0% vs. 16.0%; p = 0.03) after they declined insulin therapy.

In a multivariable analysis adjusted for demographics, comorbidities and clustering within providers, higher baseline A1c (OR 1.85; 95% CI 1.41 to 2.42; p <.001) and lifestyle changes (OR 8.49; 95% CI 3.31 to 21.78; p <0.001) were associated with greater, while non-adherence to diabetes medications (OR 0.015; 95% CI 0.0025 to 0.088; p <.001) and discontinuation of a non-insulin diabetes medication (OR 0.30; 95% CI 0.12 to 0.78; p =0.013) were associated with lower probability of A1c decrease after initial decline of insulin therapy by the patient.

We identified patient characteristics and treatment strategies associated with success and failure of glycemic control after insulin therapy decline by the patient. This information can help guide care and assist in design of rigorous interventional studies to evaluate optimal therapeutic approaches for these individuals.

Disclosure

L. Florez: None. A. Turchin: Advisory Panel; Self; Monarch Medical Technologies. Research Support; Self; Eli Lilly and Company. Stock/Shareholder; Self; Brio Systems.
2380-PUB: Factors Associated with Successful Implementation of an Inpatient Glycemic Management Program to Improve Glucose Control for Patients Needing Subcutaneous Insulin
Authors: FREEMAN RASHAYE , GAY WENDY E. , GARTHWAITE THOMAS L. , HOLLIS LAURA , MCCANNON (BUSH) JAMEE , SPENCER-SMITH CAREN , SAMUELSON ERIN E. , MEHTA PRANAV
Published: June 2019

Deployment and maturation of computerized medical records has improved insight into the unintended variability of glucose management in hyperglycemic inpatients. We used expert panels and extensive field testing to design a Glycemic Management Program to simultaneously reduce mean glucose levels and the frequency of hypoglycemic events. Factors observed as contributing to glucose control variation included over-use of sliding scale insulin; inconsistencies in timing, type and dose of insulin; and the alignment of blood glucose testing with meal tray delivery.

We designed our Glycemic Management Program to address these factors with four distinct components: 1) Change management via targeted education; 2) Standardization of the ordering process for nutrition, blood glucose monitoring frequency, and a single subcutaneous insulin order set with decision support; 3) Standardization of workflow, including the timing and coordination of glucose testing and meal tray delivery; and 4) Patient specific, customized ongoing insulin dosing recommendations through FDA-approved decision support software.

We implemented our Glycemic Management Program pilot in a 325 bed community hospital in the southeastern United States. Since its launch, 2277 patients have been managed on the program. By six months post-implementation, the rate of severe hypoglycemia (<54mg/dL) decreased 32.2% and basal-bolus insulin usage increased 135%. Average daily glucose values decreased without increasing the rate of hypoglycemia. Decreases were observed in overall length of stay (79%), complication rate (25.3%) and ICU length of stay (60%).

A comprehensive program that incorporates decision support with attention to workflow, provider engagement, and education can result in improved glucose management in an inpatient setting. Feedback has led to programmatic changes to maximize positive outcomes and ensure sustainability.

Disclosure

R. Freeman: None. W.E. Gay: None. T.L. Garthwaite: Advisory Panel; Self; Ondine Biomedical. L. Hollis: None. J. McCannon (Bush): None. C. Spencer-Smith: None. E.E. Samuelson: None. P. Mehta: None.
2383-PUB: Improved Medication Adherence among Diverse Participants in a Virtual Behavioral Therapy Program for Adults with Diabetes
Authors: GREENBERGER HEIDI M. , ANDREOPOULOS EVIE , BELL SOPHIE A. , PANDE REENA L.
Published: June 2019

Background: Virtual cognitive behavioral therapy (i.e., delivered by telephone or video) increases access to mental health treatment, but few studies describe the impact of virtual therapy on medication adherence among individuals with diabetes. We aimed to evaluate changes in medication adherence among adults with diabetes and common behavioral health issues such as depression or anxiety participating in a nationally available 8-week treatment program (AbleTo).

Methods: This retrospective cohort study included 524 participants consecutively enrolled between 1/1/2017-12/31/2017 of which 369 had complete adherence data for inclusion in the analytic sample (59% female, 43% non-white race/ethnicity, mean age 54+10 years). Prescription medications were documented at baseline (week 1); polypharmacy was defined as >5 medication types. Adherence was measured at weeks 1 and 8 using the standardized question, “Did you miss any doses this week?”; non-adherence was defined as missing any doses. Associations between adherence and participant characteristics (medication count, sex, race/ethnicity, age) were assessed using logistic regression. Change in medication adherence from weeks 1 to 8 was evaluated by McNemar’s test for paired nominal data.

Results: Baseline medication adherence was 86%. Adherence was lower among participants with polypharmacy (82% vs. 91%; p=.02), but did not differ by sex, race/ethnicity (white vs. non-white) or age group (>55 vs. <55 years). Non-adherence significantly improved from 14% to 8% at week 8 (-42%; p=.005). Improvements were observed in all subgroups and were statistically significant among participants with polypharmacy, females, and non-whites (p<.05).

Conclusion: Medication adherence was improved among participants in an 8-week virtual behavioral therapy program supporting the positive clinical impact of novel care delivery models for adults with diabetes and behavioral health conditions.

Disclosure

H.M. Greenberger: Employee; Self; AbleTo. E. Andreopoulos: None. S.A. Bell: None. R.L. Pande: Employee; Self; AbleTo, Inc. Stock/Shareholder; Self; AbleTo, Inc.
2387-PUB: Effect of Pre-op Carb-Loaded Beverage in Bariatric Surgery Patients with Pre-DM and DM as Part of ERAS Protocol
Authors: BARTHELMESS KRISTI L. , TALAVERA LAURA , PHILIS-TSIMIKAS ATHENA
Published: June 2019

The enhanced recovery after surgery (ERAS) protocol is a perioperative care pathway adopted in health systems across the nation as part of quality improvement efforts. A bundle of 20 elements demonstrated improved clinical and financial outcomes. A key element promotes carbohydrate loading a few hours before surgery using beverages such as Boost or ClearFast. There is limited data on pre-DM and DM patients and no clear guidelines on use in these populations.

Scripps Health, a large health system in Southern California, adopted the ERAS protocol as a systemwide approach for care improvement in the perioperative process in 2018. Pre-DM and DM patients were represented more commonly in the bariatric surgery group thus providing an opportunity to compare outcomes in these patients receiving a carbohydrate loaded beverage pre and post implementation of the standardized ERAS protocol.

We compared N=97 bariatric pre-DM and DM patients who did not receive Clearfast from Jan-Sept 2017 to N=64 bariatric pre-DM and DM patients who received Clearfast from Jan-Sept 2018. See Table 1.

Interestingly, in patients with pre-DM and DM, there was a substantial increase in pre-op hyperglycemia but a post-op decrease was noted when a carb-loaded beverage-Clearfast was given to patients prior to bariatric surgery when compared to the previous year when ERAS and carb loading were not part of the perioperative preparation process.

Disclosure

K.L. Barthelmess: None. L. Talavera: None. A. Philis-Tsimikas: Advisory Panel; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Dexcom, Inc., Glooko, Inc., National Institute of Diabetes and Digestive and Kidney Diseases. Stock/Shareholder; Spouse/Partner; Ionis Pharmaceuticals, Inc., Novo Nordisk Inc.
2388-PUB: App-Based Diabetes Management Plan: An Analogy between Diabetes Awareness and Plan Adoption
Authors: MISHRA SWATI , KANODIA LALIT , GUPTA VARUN , VERMA PRATEEK , AGARWAL GAURAV , TANDON PRASHANT , GUPTA UTKARSH
Published: June 2019

Background: A Government-led screening of Indian population mentions that 70% Indians have no clue that they have diabetes. This lack of awareness can act as a serving point for digital healthcare platforms to provide understandable and accessible self-care. Aim: This study was conducted to explore if diabetes awareness acts as a motivation to employ patient-centric diabetes management plans on digital healthcare platforms.

Methods: A diabetes management product, Diabetes Care Plan (DCP) was developed by 1mg Technologies Pvt. Ltd. Post three months of launch, a targeted survey with 12 question items (covering general information, diet, and monitoring) was pushed to all users (DCP and non-DCP) on 1mg mobile app. Responses were collated over three consecutive days and analyzed.

Results: A total of 3,168 users took the survey (visitors) with 2,533 users completing it (responders). Of these responders, the overall awareness was significantly higher in DCP users (90%) as compared to non-DCP users (64%). Also, DCP users seemed to have higher awareness regarding diabetes (91%), effects of diet (70%), and monitoring (90%) as compared to non-DCP users.

Conclusion: An aware user is more receptive to choose digital diabetes care plans. Empowering consumers with relevant information and structured program can create a one-stop solution for their health needs, improved self-care, and pursuit of better clinical outcomes

Disclosure

S. Mishra: Employee; Self; 1mg Technologies Pvt. Ltd. L. Kanodia: Employee; Self; 1MG Technologies Pvt. Ltd. V. Gupta: Employee; Self; 1MG Technologies Pvt. Ltd. P. Verma: Employee; Self; 1mg Technologies Pvt Ltd. G. Agarwal: Board Member; Self; 1MG Technologies Pvt. Ltd. P. Tandon: Board Member; Self; 1MG Technologies Pvt. Ltd. U. Gupta: Employee; Self; 1mg Technologies Pvt. Ltd.
2395-PUB: Is Drug Treatment Required in All Youth with T2D Early in the Disease?
Authors: TAMBORLANE WILLIAM V. , CHENG PEIYAO , GAL ROBIN L. , BEAULIEU LINDSEY C. , KOLLMAN CRAIG , VAN NAME MICHELLE A. , ISGANAITIS ELVIRA M. , MASTRANDREA LUCY D. , KLINGENSMITH GEORGEANNA J.
Published: June 2019

Background: While consensus guidelines indicate that all youth with T2D should be treated with metformin ± insulin at diagnosis, >10% of patients were treated solely with diet/lifestyle on enrollment in the Pediatric Diabetes Consortium (PDC) T2D Registry.

Methods: Clinical data was collected on 1,324 Registry patients (age 6 to <21 years) from medical records and interviews. Data in patients not receiving drug treatment were compared to those receiving antidiabetic drug treatment using logistic regression models.

Results: Of the 1,324 Registry patients, 163 (12%) were treated with diet/lifestyle alone on enrollment. Of these, 73% of were initially treated with metformin ± insulin at diagnosis. The diet/lifestyle and drug-treated groups did not differ by age, gender, diabetes duration, or BMI (Table). However, mean A1c was lower and the proportion of patients with A1c <7.5% was higher in the diet/lifestyle alone group compared to the drug-treated group at enrollment and diagnosis (p<0.001, Table). There were site differences in prescribing drug-treatment (p<0.001) and a greater proportion of patients in the diet/lifestyle alone group were without health insurance.

Conclusion: These data indicate that a substantial proportion of youth with T2D can maintain target A1c levels <7.5% despite being weaned off glucose lowering drugs during the first 1-2 years after diagnosis

Disclosure

W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited. P. Cheng: None. R.L. Gal: None. L.C. Beaulieu: None. C. Kollman: None. M.A. Van Name: Research Support; Self; Novo Nordisk Inc. E.M. Isganaitis: None. L.D. Mastrandrea: Advisory Panel; Self; Pediatric Diabetes Consortium. Research Support; Self; AstraZeneca, JDRF, Novo Nordisk Inc., Sanofi-Aventis, T1D Exchange. Other Relationship; Self; Novo Nordisk Inc. G.J. Klingensmith: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited. Research Support; Self; Novo Nordisk Foundation. Stock/Shareholder; Spouse/Partner; Dexcom, Inc.

Funding

Boehringer Ingelheim; Novo Nordisk; Takeda Pharmaceutical Company Limited
2401-PUB: High Rates of Unrecognized Ketosis in Youth with T1D and Elevated A1c Levels
Authors: NALLY LAURA M. , ELAHI SHABNAM , VAN NAME MICHELLE A. , STEFFEN AMY , TICHY EILEEN M. , URBAN ANDREA DANN , WEYMAN KATE , TAMBORLANE WILLIAM V.
Published: June 2019

Youth with type 1 diabetes (T1D) who have A1c levels ≥ 9% have a 13-fold higher rate of diabetic ketoacidosis (DKA) than youth with A1c <7.5% and the rate of DKA is 2-fold higher with multiple daily injections (MDI) than with pump therapy. However, the frequency of mild to moderate ketosis (the gateway to DKA in these high-risk patients) is largely unknown and such knowledge is essential to evaluate strategies aimed at DKA prevention.

Methods: Youth ages 8-18 years with uncontrolled T1D (A1c> 8.5%) on MDI treatment were enrolled in the study. Blood glucose (BG) and blood β-hydroxybutyrate (BHB) levels were measured by school personnel in the AM on arrival to school.

Results: 14 patients (age 15 ± 2.3 years) enrolled in the study had A1c 10.7 ± 1.5% (range 8.8 - 14.0%). BHB or urine ketones were measured on 125 school days; ketone levels were small (0.6-0.9 mmol/L) on 6.4% of days (mean BHB 0.7+0.1 mmol/L) and moderate/large (>0.9 mmol/L) on 10.4% of days (mean BHB 2.1+1.4 mmol/L) (Figure). BG ranged between 147 to >600 mg/dL on days with elevated BHB levels; all were without other signs or symptoms of DKA.

Conclusions: Unrecognized mild to moderate ketosis during regular school attendance is common in youth with uncontrolled T1D on MDI therapy. Novel strategies, such as having school personnel supervise injections of long-acting basal insulin, are needed to support reliable insulin dosing to prevent ketosis in youth with uncontrolled T1D at risk for DKA

Disclosure

L.M. Nally: None. S. Elahi: None. M.A. Van Name: Research Support; Self; Novo Nordisk Inc. A. Steffen: None. E.M. Tichy: None. A.D. Urban: None. K. Weyman: None. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited.

Funding

Novo Nordisk
2417-PUB: High-Risk of Metabolic Syndrome after Delivery in Pregnancies Complicated by Gestational Diabetes
Authors: HU GANG , LI WEIQIN , LENG JUNHONG , SHEN YUN , ZHANG SHUANG , LIU HUIKUN , LI WEI , WANG LEISHEN , TIAN HUIGUANG , CHEN JINBO , QI LU , YANG XILIN , YU ZHIJIE , TUOMILEHTO JAAKKO
Published: June 2019

The objective of this study was to investigate the risk of postpartum metabolic syndrome in women with GDM compared with those without GDM in a Chinese population. Tianjin GDM observational study included 1263 women with a history of GDM and 705 women without GDM. Multivariate logistic regression was used to assess risks of postpartum metabolic syndrome between women with and without GDM. Postpartum metabolic syndrome was diagnosed by two commonly used criteria. During a mean 3.53 years of follow-up, 256 cases of metabolic syndrome were identified by using the NCEP ATPIII criteria and 244 cases by using the IDF criteria. Multivariable-adjusted odds ratios of metabolic syndrome in women with GDM compared with those without GDM were 3.66 (95% confidence interval [CI] 2.02-6.63) for NCEP ATPIII criteria and 3.90 (95% CI 2.13-7.14) for IDF criteria. Women with GDM had higher multivariable-adjusted odds ratios of central obesity, hypertriglyceridemia, and high blood pressure than women without GDM. The multivariable-adjusted odds ratios of low HDL cholesterol and hyperglycemia were not significant between women with and without GDM, however, the multivariable-adjusted odds ratio of hyperglycemia became significant when we used the modified criteria. The present study indicated that women with prior GDM had significantly higher risks for postpartum metabolic syndrome, as well as its individual components.

Disclosure

G. Hu: None. W. Li: None. J. Leng: None. Y. Shen: None. S. Zhang: None. H. Liu: None. W. Li: None. L. Wang: None. H. Tian: None. J. Chen: None. L. Qi: None. X. Yang: None. Z. Yu: None. J. Tuomilehto: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; AstraZeneca. Research Support; Self; Bayer AG.

Funding

European Foundation for the Study of Diabetes; Chinese Diabetes Society; Lilly Program for Collaborative Diabetes Research between China and Europe; Tianjin Women’s and Children’s Health Center; Tianjin Public Health Bureau; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100790 to G.H.); National Institute of General Medical Sciences (U54GM104940 to G.H.)
2420-PUB: Demographics of Women with Type 2 Diabetes Attending a Diabetes and Pregnancy Clinic, 2000-2002, 2010-2012, and 2014-2016
Authors: CHOW LINDSEY , ANUKAM KINGSLEY , KHANNA PARUL , BRYDGES EVAN , LIU SELINA L. , MAHON JEFFREY , JOY TISHA R. , MCMANUS RUTH M.
Published: June 2019

Background: The numbers of women attending Diabetes and Pregnancy Clinics (DPC) are increasing. Some of the increase may reflect obesity effects on GDM prevalence, but numbers and characteristics of women with type 2 (T2DM) diabetes are unknown. The DPC in London Ontario sees all pregnant women with diabetes within the catchment area with stable clinic structures and procedures. Longitudinal characteristics of women with T2DM were documented for demographic insights.

Methods: DPC pregnancy charts were assessed for 2000-2002, 2010-2012 and 2014-2016. Data were abstracted for: age; weight, A1C and medication use. Continuous results were analyzed by one-way analysis of variance (ANOVA); non-parametric results by Chi-square testing; p≤ 0.05 signifying significance.

Conclusions: Numbers of pregnant women with T2DM increased significantly by 40% with time. Mean weights were lower in the second and third time interval. A1C values were lower by final visit in all time periods. Oral agent use increased in the final time period coincident with increased clinical comfort using metformin.

Disclosure

L. Chow: None. K. Anukam: None. P. Khanna: None. E. Brydges: None. S.L. Liu: Consultant; Self; Novo Nordisk Inc., Sanofi. Research Support; Self; Physicians' Services Inc. Foundation. J. Mahon: None. T.R. Joy: Speaker's Bureau; Self; Amgen Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; Amgen Inc., AstraZeneca, Novo Nordisk Inc. R.M. McManus: None.
243-OR: ADA Presidents' Select Abstract: Dapagliflozin Reduces Measured GFR by Reducing Renal Efferent Arteriolar Resistance in Type 2 Diabetes
Authors: VAN BOMMEL ERIK J. , MUSKIET MARCEL A. , VAN BAAR MICHAEL JACOBUS , KRAMER MARK H. , NIEUWDORP MAX , JOLES JAAP A. , VAN RAALTE DANIËL H.
Published: June 2019

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) improve hard renal outcomes in type 2 diabetes (T2D) patients. An acute and reversible drop in eGFR that stabilizes over time, as with RAS inhibitors, suggests involvement of a beneficial renal hemodynamic mechanism. In hyperfiltering T1D patients, SGLT2i lowered GFR by increasing afferent arteriolar resistance, possibly by activating tubuloglomerular feedback. We studied the renal hemodynamic effects of SGLT2i dapagliflozin in T2D patients like those included in recent outcome trials.

Methods: Forty-four T2D patients on metformin monotherapy, (62.9±7.0 years, HbA1c 7.38±0.63%, GFR 113±19 mL/min) were randomized to 12 weeks dapagliflozin 10mg (DAPA, n=24) or gliclazide 30mg (GLIC, n=20) QD to achieve glycemic equipoise. At baseline and week 12, GFR and renal plasma flow (RPF) were measured by gold-standard inulin and para-aminohippurate clearances. The measurements were performed 1) in the fasting state, 2) during clamped euglycemia (90 mg/dL) and 3) hyperglycemia (270 mg/dL). Renal vascular resistance (RVR) and filtration fraction (FF) were calculated using GFR, RPF, Ht and MAP. Afferent and efferent arteriolar resistances were estimated by Gomez’ equations.

Results: HbA1C decreased similarly (0.47% with DAPA and 0.65% with GLIC; p=ns), while only DAPA significantly reduced MAP by approximately 6 mmHg. DAPA reduced GFR during all three conditions by 8.9 (p<0.01), 9.0 (p=0.01) and 13.4 mL/min (p<0.001), respectively, without altering RPF, thus also reducing FF. Importantly, DAPA lowered RVR and efferent arteriolar resistance. GLIC did not alter any renal hemodynamic variables.

Conclusion: We confirm that SGLT2i induces beneficial renal hemodynamic changes in T2D beyond glycemic control that are characterized by reduced GFR and FF. However, in contrast to standing opinion, this is mediated by efferent arteriolar dilation rather than afferent arteriolar constriction.

Disclosure

E.J. van Bommel: None. M.A. Muskiet: Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. M.J. van Baar: None. M.H. Kramer: None. M. Nieuwdorp: Advisory Panel; Self; Caelus health. J.A. Joles: None. D.H. van Raalte: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Sanofi.

Funding

AstraZeneca Nederland BV
2439-PUB: Ethnic Differences in Plasma Glucose on Emergency Admission to Hospital in People with No Prior Diagnosis of Diabetes
Authors: GHOSH SANDIP , SUSARLA RADHIKA , ROUND RACHEL A. , NIGHTINGALE PETER , WILLIAMS JOHN A. , STRATTON IRENE M. , GKOUTOS GEORGIOS , WEBBER JONATHAN , HANIF WASIM , ROBERTS GRAHAM , MANLEY SUSAN E.
Published: June 2019

Objective: Glucose is measured on hospital admission as an emergency as elevated glucose is associated with an eight-fold risk of dying in hospital. This study reports on admission plasma glucose by ethnicity in people without prior diabetes.

Research Design and Methods: A clinical audit CARMS-12031 of electronic patient records for 113,097 admissions to hospital over 1 year from April 2014 to March 2015 identified 43,201 emergency admissions with glucose unavailable for 11,274 (26%). Of 5,867 admissions with prior diabetes coding, 5,523 (94%) had glucose recorded. First attendances were analyzed for emergency admissions with no record of diabetes.

Results: Of these 18,965 people admitted, 75% were White Europeans WE who were older than South Asians SA 12%, unknown/other ethnic groups U 9%, and Afro-Caribbeans AC 4%. 1,003 people admitted as an emergency had glucose in ‘diabetes range’ (≥11.1mmol/L) and 3,042 in ‘at risk’ range (7.8 to 11.0mmol/L). More SA 8% had glucose in diabetes range than WE 5% and also than U 5%; there were significantly more WE 17% in ‘at risk’ range than U 14% or AC 11%. Higher glucose was observed in SA and U men than women, p = 0.005 and p = 0.018, respectively.

Conclusions: Protocols should target people requiring additional HbA1c testingto diagnose undiagnosed diabetes on hospital admission especially younger SA and AC individuals, and outline appropriate clinical intervention.

Disclosure

S. Ghosh: Advisory Panel; Self; Abbott. Other Relationship; Self; Mylan. R. Susarla: None. R.A. Round: None. P. Nightingale: None. J.A. Williams: None. I.M. Stratton: Consultant; Self; Novo Nordisk A/S. Research Support; Self; Bayer AG, Boehringer Ingelheim International GmbH. G. Gkoutos: None. J. Webber: None. W. Hanif: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Consultant; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca, Janssen Diagnostics, Sanofi. Speaker's Bureau; Self; AstraZeneca, Novartis AG, Novo Nordisk A/S. G. Roberts: None. S.E. Manley: None.
2444-PUB: Bone Mineral Density and Bone Biomarkers in Women with Type 2 Diabetes Mellitus of Buryat Ethnic Group
Authors: BARDYMOVA TATIANA , MISTIAKOV MAKSIM , BEREZINA MARINA , TSYRETOROVA SESEG , VELM VLADIMIR
Published: June 2019

There is a difference of bone tissue state of women belonging to various ethnic groups. We have conducted a study of bone tissue state among postmenopausal women of Buryat origin. Buryats are a main northern group of Mongolians, they are a core population of Siberia with a compact residence close to Lake Baikal. We have examined the associations between bone mineral density (BMD), trabecular bone score (TBS) and bone biomarkers in 17 postmenopausal women with T2D (59 years, diabetes duration 5.2 years, A1c <8.0%) and 21 postmenopausal women without diabetes (56 years). Collagen type 1 cross-linked C-telopeptide (CTX), 25-hydroxyvitamin D, ionized calcium (iCa), femoral neck BMD were similar between two groups. T2D postmenopausal women had lower osteocalcin (OC), procollagen type 1 N propeptide (P1NP), TBS and higher BMD total hip, BMD lumbar spine 1-4 (L1-L4) compared to the controls (Table). Total hip BMD in women with T2D was associated with body mass index (BMI). TBS was positively correlated with iCa. Twenty-five-hydroxyvitamin D was associated with lower OC, P1NP and CTX. Total hip BMD and BMD L1-L4 were positively correlated with BMI in women without diabetes. Femoral neck BMD was positively correlated with P1NP and inversely correlated with women’s age. T2D in Buryat women is associated with low levels of osteosynthesis markers, TBS and higher BMD. TBS was positively correlated only with iCa.

Disclosure

T. Bardymova: None. M. Mistiakov: None. M. Berezina: None. S. Tsyretorova: None. V. Velm: None.
2448-PUB: A Diagnostic Data-Based Comparative Analysis of Patterns of Uropathogens and Their Antimicrobial Sensitivity Status against Commonly Used Antibiotics
Authors: SINGH MANMOHAN , THAKUR RAJAT
Published: June 2019

Background: Urinary tract infections are common among diabetic patients. High antimicrobial resistance of urinary pathogens against commonly used antimicrobial agents made it very difficult to treat these infections. This analysis was conducted to assess patterns of urinary pathogens among diabetes and nondiabetes patients and to assess their antimicrobial sensitivity patterns against commonly used antibiotics.

Methods: Big diagnostic data of urinary cultures from 56 diagnostic labs across 21 states in India was analyzed to assess patterns of urinary pathogens among diabetic and nondiabetic patients. Diagnosis of diabetes was ascertained by using ADA criteria. Culture positivity rate and overall antimicrobial resistance status are compared between diabetics and nondiabetics.

Results: There were 51,907 urine samples, in which culture and sensitivity test was done. Proportion of diabetics was 24.8%. Culture positivity rate was 15.0% overall. Diabetes patients have statistically significant (p<0.05) high positivity rate (20.3%) in comparison to nondiabetics (13.2%). Urinary isolates (overall) from diabetics have low sensitivity than nondiabetics against common antibiotics. Sensitivity of isolates among diabetics was significantly (p<0.05) low than nondiabetics for amoxicillin, amoxicillin-clavulanic acid, ampicillin, meropenem, imipenem, nitrofurantoin, cotrimoxazole, ciprofloxacin, levofloxacin, ampicillin, cefepime, cefixime, cefotaxime, cefuroxime, ceftriaxone and norfloxacin but not for fosfomycin and cotrimoxazole. Overall sensitivity for carbapenems and fosfomycin was >80% among both categories of patients, while it was <80% for all other antibiotics mentioned above.

Disclosure

M. Singh: None. R. Thakur: None.
2454-PUB: Hypoglycemic Symptoms in the Absence of Diabetes: Pilot Evidence of Clinical Hypoglycemia in Young Healthy Women
Authors: MONGRAW-CHAFFIN MORGANA , MCCLAIN DON , BEAVERS DANIEL P.
Published: June 2019

Background: Hypoglycemic symptoms in the absence of diabetes remains a common complaint in endocrinology practices, but remains understudied and lacks clinical definition and evidence-based recommendations for diagnosis or treatment. Our goal was to pilot test the concordance of hypoglycemic symptoms with low glucose values in young healthy individuals.

Methods: We recruited 8 individuals who reported regularly experiencing symptoms consistent with hypoglycemia to wear a blinded Dexcom continuous glucose monitor and report symptoms for seven days. We excluded individuals with diabetes or other known causes of hypoglycemia.

Results: All participants experienced glucose values <70mg/dL and half (4/8) experienced glucose <50mg/dL for at least 15 minutes or 3 consecutive readings. Lower glucose values were significantly associated with higher odds of experiencing hypoglycemic symptoms (OR=1.15 (1.06-1.24) for every 5mg/dL, p<0.001) from mixed effects models for repeated measures (Figure). All participants also reported reduced quality of life and engaging in potentially obesogenic behaviors in order to avoid symptoms.

Conclusions: Individuals with hypoglycemic symptoms in the absence of diabetes experience clinical hypoglycemia, indicating the need to understand the etiology, behavioral responses, and other health risks that might be associated with this condition.

Disclosure

M. Mongraw-Chaffin: None. D. McClain: None. D.P. Beavers: None.

Funding

National Center for Advancing Translational Sciences (UL1TR001420)
2488-PUB: The Role of GLP-1 in Metabolic Responses during Sepsis
Authors: DAVIS ELLEN M. , HUTCH CHELSEA , KIM KI-SUK , MAERZ BASMA , LEHRKE MICHAEL , SANDOVAL DARLEEN A.
Published: June 2019

Sepsis is characterized by a dysregulated immune response that can result in end organ damage and is the number one cause of death in the ICU. Among the hormones that are altered by sepsis, there is an increase in the gut peptide glucagon-like peptide-1 (GLP-1). Traditionally, GLP-1 is important for regulating glucose homeostasis and has previously been linked to appetite inhibition. However, its function during sepsis remains unknown. GLP-1 is coded by the preproglucagon gene (Gcg) and is expressed not only by intestinal endocrine cells but also in pancreatic α-cells. Previously, we have shown increases in plasma GLP-1 in response to LPS are contributed to by both pancreatic and intestinal sources and that either pancreatic or intestinal sources of GLP-1 are sufficient to maintain glucose responses to LPS. Because T2DM patients have an increased susceptibility to sepsis, the goal of this study was to determine if high-fat diet and impaired glucose tolerance change the metabolic or appetitive inhibition response during sepsis. To model sepsis, we administered lipopolysaccharide (LPS) to C57BL/6 mice who had been on high-fat diet (HFD) or chow for 12 weeks. We observed that compared to vehicle treatment, LPS significantly increased plasma levels of GLP-1 in both HFD and chow-fed mice, but plasma GLP-1 was significantly higher in HFD mice compared to chow-fed. HFD mice also had a greater decrease in glucose in response to LPS. Furthermore, we observed that HFD mice had increased and prolonged appetite inhibition in response to LPS. Future directions will explore tissue-specific changes in GLP-1 response, source, and effectiveness during sepsis under the conditions of high-fat diet and impaired glucose control.

Disclosure

E.M. Davis: None. C. Hutch: None. K. Kim: None. B. Maerz: None. M. Lehrke: Consultant; Self; Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. D.A. Sandoval: Research Support; Self; MedImmune, Novo Nordisk A/S, Zafgen, Inc.