bluuebunny/crossref_metadata_2025 huggingface dataset:
1194-P: NT-proBNP, Subclinical Diastolic Dysfunction in Patients with DM Type 1 Treated with iSGLT2
Authors: CHERVIAKOVA SVITLANA , SOKOLOVA LIUBOV K. , BELCHINA IILIA , KORZUN IILIA , TRONKO MYKOLA D.
Published: June 2019

Aim: Subclinical diastolic dysfuntion in patients with preclinical heart failure with preserved ejection fraction (HFpEF) has been demonstrated in patients with DM type 1. We investigated the relationship between diastolic dysfunction and NT-proBNP levels in patients with diabetes treated with iSGLT2 (dapagliflozin).

Methods: NT-proBNP and diastolic function were assessed in 35 patients with DM 1 (31 ± 1,6 y, duration of DM 12,0± 1,2 y) and 15 control subjects (mean age - 29,9± 1,8years) without clinical evidence of heart disease. Data presented as M±m. The results were compared using Student’s paired test.

Results: All patients had a normal ejection fraction (53,9±2,3 vs. 56,1± 4,3, (p > 0,05) in those with and without DM, respectively. 34,2% of the diabetic patients had evidence of diastolic dysfunction as assessed by the presence of at least two abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in diabetic compared with control subjects (E/A ratio 0,9±0,05 vs. 1,2± 0,06, p< 0,05), the DT was 257,1±28,2 ms vs. 186±14,6 ms p<0,05, in those with and without DM, respectively. Also, the IRT was increased in diabetic patients compared with control subjects (130±14,0 ms vs. 79,3±6,1 ms, p< 0,05). Median NT-proBNP plasma levels were elevated [189.54 pg/mL (86.16-308.27) and increased with greater severity of the diastolic dysfunction. Median NT-proBNP plasma levels have been decreased - 51.89 pg/mL (29.94-69.71); P<0.001] after 1 month treatment period with dapagliflozin.

Conclusions: DM type 1 patients presenting with normal ejection fraction show disturbed diastolic function and higher NT-proBNP levels. 2. iSGLT2 (dapagliflozin) decreased NT-proBNP levels in DM1 patients with subclinical diastolic dysfunction.

Disclosure

S. Cherviakova: None. L.K. Sokolova: None. I. Belchina: None. I. Korzun: None. M.D. Tronko: None.
12-OR: Trends in Total and Out-of-Pocket Payment on a Yearly Insulin Supply among Private Health Insured U.S. Adults with Diabetes from 2003 to 2016
Authors: SHAO HUI , LAXY MICHAEL , BENOIT STEPHEN R. , CHENG YILING J. , GREGG EDWARD , ZHANG PING
Published: June 2019

High spending, especially out-of-pocket (OOP) payment on insulin, could lead individuals with diabetes to skip or ration doses and worsen future health outcomes. We examined the trends in total and OPP payment on a yearly supply of insulin by type from 2003 to 2016. Using the 2003-2016 MarketScan claims database, we analyzed 1,703,343 adults with diabetes who were continuously enrolled in fee-for-service health plans. Insulin was grouped into 6 types (human insulin, Glargine, Lispro, Aspart, Detemir and Glulisine) using National Drug Code. Total and OOP payment for each drug type were modelled at a 30-day supply level, and later multiplied by 12 to obtain yearly estimates. A joinpoint regression was used to identify inflection points and to estimate trends in each defined segment. Payments were standardized to 2016 USD. The total payment for insulin increased at annual rate of $162 per year from 2003 ($1982) to 2012 ($3686), followed by more than a 3-fold increase in the annual rate of increase to $708 per year between 2013 ($4392) and 2016 ($6250). By type, the annual rate of increases ranged from $64 (2%) for Glulisine to $133 (6%) for Glargine before the inflection point and raised to a range from $631 (16%) for Glargine to $1246 (26%) for Glulisine after the inflection point. OPP payment on a yearly supply of insulin decreased by $6 per year (-1.5%) between 2003 ($390) and 2009 ($384) followed by a 3% ($12) per year increase between 2010 ($405) and 2016 ($451). The annual rate of changes ranged from -$72 (14.8%) for Detemir to -$31 (-6%) for Glulisine before the inflection point and varied from $8 (2%) for Aspart to $41 (7.6%) for Glulisine after the inflection point. Total payment on a yearly supply of insulin had been increasing since 2003 but accelerated after 2011. The OPP payment reversed its trends from a decrease to an increase. But the much smaller increase in OPP payment than the total payment after 2011 suggests that payers bore most of the insulin spending increase.

Disclosure

H. Shao: None. M. Laxy: None. S.R. Benoit: None. Y.J. Cheng: None. E. Gregg: None. P. Zhang: None.
1202-P: Glucose Lowering with an SGLT2I Improves Trabecular Bone but Does Not Correct Bone Brittleness in TallyHo Model of T2D
Authors: THRAILKILL KATHRYN M. , BUNN R. CLAY , UPPUGANTI SASIDHAR , RAY PHILIP D. , POPESCU IULIANA , KALAITZOGLOU EVANGELIA , FOWLKES JOHN , NYMAN JEFFRY S.
Published: June 2019

Higher fracture risk in T2D is attributed to disease specific deficits in micro-structural and material properties of bone. The TallyHO (TH) mouse is a polygenic model of early-onset T2D/obesity analogous to adolescent-onset T2D in humans. Male TH mice commence rapid weight gain at 4 weeks of age and by ∼10-14 weeks insulin resistance progressing to frank hyperglycemia is apparent in ∼75% of mice. Compared to SWR/J control strain, TH mice exhibit lower: 1) bone formation markers; 2) trabecular bone volume; and 3) fracture resistance. Utilizing this model, we examined the impact of glucose-lowering therapy by SGLT2I on diabetic bone. TH male mice (8-10 weeks) with confirmed hyperglycemia and age-matched, nondiabetic, male SWR/J mice were monitored ± canagliflozin (CANA: 125 ppm in chow) for 10 weeks of treatment. At study end, measurements of body weight, BG, HbA1c, serum insulin, and urine calcium/CR were obtained; femurs were harvested for analysis by µCT and three-point bending. At 20 weeks, these severely hyperglycemic TH mice (BG: 687±106 vs. 151±26 mg/dL; p<0.0001) were obese and had longer femurs with increased cortical bone (↑Ct.Ar, Ct.Th; p<0.001 for all) compared to SWR/J. However, trabecular bone was reduced (↓Tb.BV/TV, Conn.D, Tb.N, Tb.TMD; p<0.001 for all) and TH bones were more brittle (↓toughness; p<0.0001). CANA treatment of TH mice significantly lowered BG and HbA1c while increasing weight gain and insulin secretion (p<0.0001 for all). With glycemic improvement, trabecular bone improved (↑Tb.BV/TV, p=0.0002; Tb.Th, p<0.0001; Tb.TMD; p=0.002) compared to untreated TH mice, but toughness was not altered. Unexpectedly, CANA treatment of SWR/J mice lowered toughness of the femur diaphysis. Hypercalciuria was a consistent feature of both groups of TH mice; CANA also increased Ca excretion in SWR/J mice. CANA therapy may protect against elevated fracture risk in T2D with respect to trabecular rich sites but may not be beneficial if bone becomes brittle with duration.

Disclosure

K.M. Thrailkill: None. R. Bunn: None. S. Uppuganti: None. P.D. Ray: None. I. Popescu: None. E. Kalaitzoglou: None. J. Fowlkes: None. J.S. Nyman: Advisory Panel; Self; ActiveLife Scientific, Inc. Consultant; Self; Sanofi Genzyme. Research Support; Self; ActiveLife Scientific, Inc., Sanofi Genzyme.

Funding

National Institutes of Health (R21AR070620, R01DK084045); U.S. Department of Veterans Affairs (1l01BX001018)
1205-P: Baseline Lactate Level Is a Useful Predictor for Weight Loss after Long-Term SGLT2 Inhibitor Treatment
Authors: NOJIMA TOSHIAKI , MATSUBAYASHI YASUHIRO , YOSHIDA AKIHIRO , SUGANAMI HIDEKI , KAKU KOHEI , SONE HIROHITO
Published: June 2019

SGLT2 inhibitors (SGLT2is) reduce body weight. They also reduce insulin levels, which trigger lipolysis leading to subsequent fat-mass loss. Lactate (LAC) was reported to inhibit lipolysis in adipocytes and to mediate insulin-dependent inhibition of lipolysis. However, little is known of the effect of SGLT2is on LAC and its relation to weight loss. We investigated the effect of the SGLT2i tofogliflozin on LAC and explored its relation to subsequent weight loss in patients with type 2 diabetes mellitus (T2DM). Analyzed were 584 T2DM patients receiving tofogliflozin as an add-on to other antidiabetic agents from a Phase 3 trial. Baseline characteristics were: men (66%), age (mean 59y), mean HbA1c (8%), BMI (26kg/m2), LAC (11mg/dL) and eGFR (84mL/min/1.73m2). Patients were divided into two groups based on baseline LAC (bottom quartile [Q1: LAC mean 6mg/dL] and 3 higher quartiles [Q2-4]: 13). Adjusted changes in variables between groups were compared to explore the relation between baseline LAC and weight loss using multivariate analysis. LAC significantly decreased at week 4 (mean, -1.4mg/dL* p<0.01 vs. baseline) and that reduction was maintained toward week 52 (-1.5*). Similar reductions in LAC were seen at week 52 in persons who had (-1.7mg/dL*) and had not received a biguanide (-1.4*). Baseline BMI, eGFR and fasting insulin were lower in Q1, while HbA1c was identical between groups. Mean changes in LAC in Q1 and Q2-4, respectively, were +1.6mg/dL*, and -2.4* at week 52 (p<0.01 between groups). Weight loss in Q1 and Q2-4, respectively, were -3.8%*, and -4.5* at week 24 (p<0.05) and -3.4*, and -4.4* at week 52 (p<0.01) while reductions in HbA1c and fasting insulin at week 52 were identical between groups. Multivariate analysis showed greater weight loss in Q2-4 at week 52 than in Q1. Results suggested that LAC was significantly influenced by togfogliflozin according to baseline LAC. Baseline LAC may be a predictor of weight loss associated with lipolysis via long-term SGLT2i treatment for T2DM.

Disclosure

T. Nojima: Employee; Self; Kowa Co., Ltd. Y. Matsubayashi: None. A. Yoshida: Employee; Self; Kowa Pharmaceutical Co. Ltd. H. Suganami: Employee; Self; Kowa Co., Ltd. K. Kaku: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
1208-P: Empagliflozin and HbA1c Reduction in a National Cohort
Authors: CHANG PO-YIN , HEBERER KENT , LEE JENNIFER
Published: June 2019

Empagliflozin, a sodium-glucose cotransport 2 inhibitor, provides A1c reduction by .6-1.0% in large randomized control trials. These trials included adults with type 2 diabetes (T2D) who had baseline A1c 7-10%. The use of empagliflozin in reducing A1c in clinical practice has not been investigated. We constructed a longitudinal cohort of 16391 adults with T2D who initiated empagliflozin from 11/1/2014 to 3/1/2018 in the Veterans Health Administration and followed them until 10/1/2018. We studied 7792 adults (96% men, 73% non-Hispanic white (NHW), 14% black) who had A1c measures at baseline and during follow-up and who did not change their antidiabetic medication regimens (58% with insulin, 36% without insulin). Linear regression estimated absolute A1c change at 6 months, adjusted for age, sex, race/ethnicity, baseline A1c, categorical BMI, kidney function, and concurrent insulin. At baseline, median A1c was 8.5% (12% with A1c ≥10%), median BMI was 33 kg/m2 (25% of adults with BMI 35-40 kg/m2, 18% BMI >40 kg/m2), and 19% with reduced kidney function. Baseline A1c was 8.9% for black adults and 8.5% for NHW adults. The average reduction in A1c was .74% for black adults and .70% for NHW adults. Overall, average adjusted A1c reduction was .71%. Adults with baseline A1c ≥10% had a greater adjusted reduction compared to adults with baseline A1c 7-10% (1.76% vs. .46%, p<.001). Adults with BMI 35-40 kg/m2 and >40 kg/m2 had a greater adjusted reduction compared to normal and overweight adults (.71% and .75%, vs. .46% and .59%, respectively, p <.001). Adults on a concurrent insulin regimen had a smaller adjusted reduction compared to those with a non-insulin regimen (.50% vs. .72%, p<.001). Empagliflozin decreased A1c in T2D adults across a range of ages, races/ethnicities, BMIs and concurrent insulin prescription. Empagliflozin seems to offer the greatest A1c reduction for T2D adults with A1c ≥10% or BMI >35. This study provides real-world evidence of empagliflozin use and A1c reduction in a large integrated healthcare system.

Disclosure

P. Chang: None. K. Heberer: None. J. Lee: None.

Funding

National Institute on Drug Abuse (T32DK007217); U.S. Department of Veterans Affairs
121-LB: Early Independent View of Quality of Life in Patients with Type 1 Diabetes Using Hybrid Closed-Loop Insulin Delivery System in Real-World Clinical Practice
Authors: ELDIB AHMED H. , TOSCHI ELENA , MAHMOUD NOOR , TASABEHJI MHD WAEL , ASHRAFZADEH SAHAR , TOMAH SHAHEEN , DHAVER SHILTON EDWARD , ATAKOV-CASTILLO ASTRID , ABDUL-GHANI AHMED E. , FARKOUH KATIE , TREVINO RAFAEL , HAMDY OSAMA
Published: June 2019

The MiniMed™ 670G (670 HCL) is the first FDA-approved hybrid closed-loop insulin delivery system device for patients with type 1 diabetes (T1D). This study aimed at evaluating clinical and patient-reported outcomes (PROs) in patients with T1D utilizing this technology.

We evaluated 54 patients with T1D using the 670 HCL in real-world clinical practice (mean age 47.9±13.2 years, 57% females, BMI 28.8±5.9 kg/m2). Data were collected at baseline and after 3 months. Measures of PROs included: Pittsburgh Sleep Quality Index (PSQI), Hypoglycemia Fear Survey Worry (HFS_W) scale, and 36-Item Short-Form Health Survey (SF-36). We also measured changes in A1C after 3 months and % of time in auto-mode (% TIAM) over the two weeks preceding the 3-month visit. Regression analyses were done between these 2 parameters and PROs. Other glycemic and quality-of-life parameters were collected at 3 months and at one year but are not included in this early report.

At 3 months, A1C decreased by 0.4±0.12% from baseline (p=0.0027). Average % TIAM was 63.9±33.1%. Among all surveyed PROs, only fear of hypoglycemia and social functioning improved compared to baseline (p<0.05 for both). There was no association between changes in PROs and reduction in A1C or % TIAM.

In conclusion, patients with T1D using the MiniMed™ 670G hybrid closed-loop system in real-world clinical practice are able to improve their A1C, fear of hypoglycemia, and social functioning but not other PROs included in the SF-36 after 3 months of use. The limited improvement in some of the PROs is not associated with the reduction in A1C or % TIAM.

Disclosure

A.H. Eldib: None. E. Toschi: Advisory Panel; Self; Lexicon Pharmaceuticals, Inc. N. Mahmoud: None. M. Tasabehji: None. S. Ashrafzadeh: None. S. Tomah: Stock/Shareholder; Self; Amarin Corporation. S.E. Dhaver: None. A. Atakov-Castillo: None. A.E. Abdul-Ghani: None. K. Farkouh: None. R. Trevino: None. O. Hamdy: Advisory Panel; Self; AstraZeneca, Sanofi-Aventis. Consultant; Self; Abbott, Merck & Co., Inc. Research Support; Self; National Dairy Council. Stock/Shareholder; Self; Healthimation, LLC.
1214-P: Effect of Short-Term Improvements in Glycemic Control with SGLT2 Inhibitor Therapy on Insulin and Glucagon Secretion: How Does It Differ With or Without Concurrent DPP-4 Inhibitor Therapy
Authors: MATSUI MAKIKO , TAKAHASHI HIROSHI , SAWANO SHOUKO , MORI YUTAKA , UTSUNOMIYA KAZUNORI
Published: June 2019

Objective: We investigated the effect of short-term improvements in glycemic control with SGLT2i therapy on insulin and glucagon secretion with or without concurrent DPP-4 inhibitor (DPP-4i) therapy.

Patients and Methods: 78 type 2 diabetic patients admitted for glycemic control and subjected to meal tolerance tests (MTT) on the next day after admission and immediately before discharge using the same diabetes diet while off treatment were subjected to retrospective analysis. Of these, 41 patients were found to have received SGLT2i after admission, with 15 of these also found to have received concurrent DPP-4i. The patients were divided into those not receiving SGLT2i (n=37), those receiving SGLT2i without concurrent DPP-4i (n=26) and those receiving SGLT2i with DPP-4i (n=15) and were compared for changes in postprandial insulin and glucagon secretion. All patients were evaluated at admission and discharge for insulin secretion in terms of ΔCPR/ΔPG 0-30 min and AUC-CPR 0-2h, and as well as for glucagon (G) secretion in terms of ΔG/ΔPG 0-30 min and AUC-G 0-2h during the MTT.

Results: There was no significant difference between the 3 groups in their HbA1c, C-peptide index, and urinary CPR excretion at admission. With improvements in glycemic control, ΔCPR/ΔPG 0-30min and AUC-CPR 0-2h were significantly increased, and AUC-PG 0-2h were significantly decreased, in all groups. Again, with improvements in glycemic control, AUC-G 0-2h was significantly decreased in those not receiving SGLT2i, increased in those receiving SGLT2i without DPP-4i, and decreased in those receiving both SGLT2i and DPP-4i.

Conclusions: Postprandial insulin secretion was shown to be restored after short-term improvements in glycemic control irrespective of SGLT2i or concurrent DPP-4i, while glucagon secretion was shown to be increased with SGLT2i without DPP-4i but decreased with combined SGLT2i and DPP-4i.

Disclosure

M. Matsui: None. H. Takahashi: None. S. Sawano: None. Y. Mori: None. K. Utsunomiya: None.
1215-P: Adipose Tissue Insulin Resistance Predicts Ketosis via an SGLT2 Inhibitor
Authors: MATSUBAYASHI YASUHIRO , YOSHIDA AKIHIRO , NOJIMA TOSHIAKI , SUGANAMI HIDEKI , FUJIHARA KAZUYA , KAKU KOHEI , SONE HIROHITO
Published: June 2019

Diabetic ketoacidosis characterized by lipolysis due to insulin deficiency is a side effect reported for SGLT2 inhibitors (SGLT2is). However, little is known about predictors of ketosis via SGLT2i. The antilipolytic effect of insulin in adipose tissue can be evaluated as adipose tissue insulin resistance (Adipo-IR). This study investigated predictors of ketosis via the SGLT2i, tofogliflozin (TOFO), in patients with type 2 diabetes (T2D) focusing on Adipo-IR. Analyzed were 304 T2D patients who received TOFO as initial monotherapy in two TOFO phase 2 and 3 studies. Adipo-IR was calculated by the product of fasting insulin (IRI) and fasting free fatty acids (FFA). Baseline characteristics were: males (67%), age (mean: 58 y), HbA1c (8%), BMI (26kg/m2), β-hydroxybutyrate (BHB) (75µmol/L), eGFR (84mL/min/1.73m2) and Adipo-IR (33pmol/L mmol/L). Participants were grouped by tertiles of baseline Adipo-IR levels (T1-T3). Differences across tertiles were analyzed by ANOVA, Kruskal Wallis and ANCOVA. Multivariate analysis explored the predictors of ketosis. In the order of T3-T1, younger age, higher baseline HOMA-IR levels and higher baseline HOMA-β levels were observed, while baseline HbA1c and BHB levels were identical across tertiles. At 24 weeks after TOFO administration, reduced HbA1c and body weight and increased urinary glucose excretion were identical among tertiles. Percent changes in FFA were T1, mean +50.9%* (* p<0.001 vs. baseline); T2, +25.8*; and T3, +6.6 (p<0.001 across tertiles); and those for BHB were T1, median +117.9%*; T2, +126.9*; and T3, +62.0* (p<0.05). Conversely, percent changes in IRI were T1, mean -11.3%*; T2, -24.2* and T3, -28.3* and in Adipo-IR were T1, +31.1%*; T2, -2.9 and T3, -24.1* (p<0.001 across tertiles). Multivariate analysis indicated an independent association of T3 with a weaker increase in BHB than T1 and T2.

In conclusion, high baseline Adipo-IR may attenuate ketosis via SGLT2i through improved Adipo-IR and the antilipolytic effect of insulin despite reduced IRI in T2D.

Disclosure

Y. Matsubayashi: None. A. Yoshida: Employee; Self; Kowa Pharmaceutical Co. Ltd. T. Nojima: Employee; Self; Kowa Co., Ltd. H. Suganami: Employee; Self; Kowa Co., Ltd. K. Fujihara: None. K. Kaku: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
1225-P: The Association between Long-Term Glucose Variability (GV), Cardiovascular (CV) Death, and Heart Failure (HF) Outcomes in the EMPA-REG OUTCOME Trial
Authors: CERIELLO ANTONIO , OFSTAD ANNE PERNILLE , ZWIENER ISABELLA , KASPERS STEFAN , GEORGE JYOTHIS , NICOLUCCI ANTONIO
Published: June 2019

Markers of GV have been associated with CV outcomes in type 2 diabetes (T2D), however, the association of GV with HF outcomes remains unclear. In EMPA-REG OUTCOME, empagliflozin reduced the risk of CV death by 38% and HF hospitalizations (HHF) by 35%. Here we explore the association between GV and CV death/HHF outcomes.

In EMPA-REG OUTCOME, 7,020 patients with T2D and established CV disease received placebo (PBO), empagliflozin (EMPA) 10 mg or 25 mg and were observed for a median period of 3.1 years. We defined within-patient GV as range and standard deviation of HbA1c measurements on-treatment until week 28. The associations with CV death, first HHF, and HHF or CV death were explored in PBO and pooled EMPA arms separately with landmark (LM) analyses at week 28 by Cox regression models adjusted for baseline risk factors including changes in HbA1c from baseline to week 12.

GV levels were lower with EMPA (Table). In the LM analysis, higher GV increased the risk for CV death and CV death or HHF in both treatment arms. For HHF, no significant association could be shown (Table).

In EMPA-REG OUTCOME, EMPA reduced GV. An increase in GV correlated with increased risk of subsequent CV death and CV death or HHF. The association with HHF alone was not significant maybe due to a lower numbers of HHF events, or the assumption that the effects of EMPA on HHF are largely glucose-independent.

Disclosure

A. Ceriello: Advisory Panel; Self; Abbott Laboratories, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk A/S, Vifor Pharma. Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; A. Menarini Diagnostics, AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim Pharmaceuticals, Inc. A. Ofstad: Employee; Self; Boehringer Ingelheim International GmbH. I. Zwiener: Employee; Self; Boehringer Ingelheim Pharma GmbH & Co KG, Merck KGaA. S. Kaspers: Employee; Self; Boehringer Ingelheim International GmbH. J. George: Employee; Self; Boehringer Ingelheim International GmbH. A. Nicolucci: Consultant; Self; AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S. Research Support; Self; Artsana S.p.A., Dexcom, Inc., Novo Nordisk A/S, Sanofi-Aventis.

Funding

Boehringer Ingelheim; Eli Lilly and Company
1230-P: Addition of Canagliflozin to Insulin Improves Glycemic Control and Reduces Insulin Dose in Patients with Type 2 Diabetes Mellitus: A Study Based on Continuous Glucose Monitoring
Authors: TORIMOTO KEIICHI , OKADA YOSUKE , SATO YASUNORI , TANAKA YOSHIYA
Published: June 2019

Background and Aims: No studies have compared insulin dose or hypoglycemic risks between type 2 diabetes mellitus (T2DM) treated with and without Sodium glucose cotransporter-2 (SGLT2) inhibitors using defined criteria for insulin dose adjustment to achieve the same level of glycemic control. The aim of this study was to evaluate the efficacy of canagliflozin in reducing the required insulin dose and the risk of hypoglycemia in T2DM.

Materials and Methods: This randomized, two-group comparative study was conducted in 34 patients treated with insulin alone or combined with oral hypoglycemic agents. They were randomly assigned to the control (n=17, insulin) and canagliflozin (n=17, insulin plus 100 mg/day) groups and wore a continuous glucose monitoring (CGM, ipro2®) for 14 days. In both groups, a defined insulin dose adjustment protocol was applied to achieve the same level of glycemic control.

Results: The change from baseline in daily insulin dose was significantly smaller in the canagliflozin group (3.9 units/day) than control group (13.4 units/day; p = 0.040). Low blood glucose index (LBGI) and predicted % of blood glucose (BG) <70 mg/dL, which are hypoglycemia-related parameters, worsened significantly in the control group, but both remained unchanged in the canagliflozin group. The SD for nighttime BG levels improved significantly only in the canagliflozin group. Participants’ body weight (BW) decreased in both groups, but the change in BW showing a significant decrease in the canagliflozin group.

Conclusion: Supplementation of insulin therapy with 100 mg canagliflozin in patients with T2DM reduced the required insulin dose and hypoglycemic risk and flattened nighttime glycemic fluctuations while maintaining the same level of glycemic control. The addition of SGLT2 inhibitors may provide several benefits to patients on insulin therapy, enabling them to maintain strict glycemic control.

Disclosure

K. Torimoto: None. Y. Okada: None. Y. Sato: None. Y. Tanaka: None.
1235-P: Effects of Medicaid Expansion on Uninsured Rates: Diabetes Belt vs. Non-Belt Counties
Authors: LOBO JENNIFER M. , KIM SOYOUN , OCKER GABRIELLE M. , KANG HYOJUNG , MCMURRY TIMOTHY L. , SOHN MIN-WOONG
Published: June 2019

Objective: To examine trends in insurance rates in 2012-2016 among low-income adults aged <65 and determine whether Medicaid expansion helped reduce the gap in uninsured rates between Diabetes Belt (DB) and non-DB counties. The Diabetes Belt is a region with elevated rates of diabetes that includes 644 counties across 15 southeastern states.

Methods: Data for 1,180 county-level data from the Small Area Health Insurance Estimates and Area Health Resources File were used to analyze the trends in uninsured rates in populations with household income ≤138% federal poverty line (FPL). Multivariable analysis adjusted for county percent population aged 50-64 years, females, married, distress county index, and rurality.

Results: Crude uninsured rates were 5% higher in DB compared to non-DB counties (39% vs. 34%, p < 0.001) in 2012. Uninsured rates declined rapidly in both DB and non-DB counties to 13% and 15% in 2016. Adjusted changes in uninsured rates between 2012 and 2016 were 31% in DB (p < 0.001) and 21% in non-DB counties (p < 0.001) with the adjusted uninsured rates being 16% in both areas in 2016. Figure below shows the trends.

Discussion: Medicaid expansion had the intended effects on reducing uninsured rates in both DB and non-DB counties. Initial disparities in uninsured rates between the two areas were completely eradicated by 2016. Medicaid expansion may have helped improve uptake of preventive care in the Diabetes Belt.

Disclosure

J.M. Lobo: None. S. Kim: None. G.M. Ocker: None. H. Kang: None. T.L. McMurry: None. M. Sohn: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK113295)
1236-P: Hospitalizations Rates among Homeless Children with Diabetes Mellitus in New York
Authors: SAKAI-BIZMARK RIE , YEE JENNIFER K.
Published: June 2019

Background: Diabetes mellitus (DM) is increasing in prevalence among U.S. children. Disparity across race and socioeconomic status for DM incidence as well as DM outcomes have been reported. Homeless youth live under unique circumstances that may lead to challenges in self-care. We hypothesized that homelessness may be associated with difficulties in blood glucose management, and therefore would lead to increased healthcare utilization. The aim of this study was to assess healthcare utilization related to DM among homeless youth.

Methods: This secondary data analysis identified homeless and non-homeless pediatric patients (<18 years) with a primary diagnosis of DM from the New York statewide inpatient database between 2009 and 2014. Hospitalization rates, readmission rates, hospitalizations with ketoacidosis, admissions through the emergency department (ED), and hospitalization costs and lengths of stay (LOS) were used as outcomes.

Results: We identified 11,202 DM-related hospitalizations, yielding 4.26 and 0.41 hospitalizations per 1,000 homeless and non-homeless children, respectively. Readmissions accounted for 21.0% of homeless and 14.6% of non-homeless hospitalizations (p< .01). Compared with non-homeless patients, homeless patients were more likely to be admitted from ED: Odds Ratio (OR) 1.53, p<.01. Stratified analyses by DM type revealed that homeless patients with DM1 had longer LOS than non-homeless patients: Incidence Rate Ratio (IRR) 1.23, p<.01, whereas a difference in LOS was not detected among patients with DM2. No other outcomes were associated with homelessness.

Conclusions: Homeless youth experience 10.4 times higher DM hospitalization rates than non-homeless youth, with higher rates of readmission. Healthcare utilization was especially high for homeless youth with DM1. Further studies are needed to examine the factors contributing to increased healthcare utilization in order to develop tailored management strategies for homeless youth with diabetes.

Disclosure

R. Sakai-Bizmark: None. J.K. Yee: None.
1244-P: Diabetes Screening to Appropriate Follow-Up: Are Patients Getting Timely Diagnoses and Treatment?
Authors: STEMPNIEWICZ NIKITA , CIEMINS ELIZABETH L. , RATTELMAN CORI R. , CUDDEBACK JOHN K.
Published: June 2019

Objective: To measure time from positive diabetes screening test to appropriate follow-up action, i.e., diagnosis, pharmacologic treatment, or negative confirmatory test, using a large, geographically diverse clinical dataset.

Study Design: Retrospective descriptive analysis in a clinical database with over 25 million patient records.

Population Studied: From 2013-2017, 61,162 patients aged 18-75 from 23 health care organizations (HCOs) with ≥ 1 outpatient visit in last 12 months of data, a laboratory finding of HbA1c ≥ 6.5 or fasting plasma glucose (FPG) ≥ 126 in the last 12-24 months, and no prior diabetes diagnosis or prescriptions (except metformin).

Principal Findings: Positive diabetes tests were indicated by HbA1c (28%), FPG (61%), or both (11%). A total of 5.7% of patients had an FPG ≥ 200, and 6.9% had an HbA1c ≥ 8.0. Sixty-five percent (range 55-77% across 23 HCOs) had appropriate action in 3 months following a positive screening: 35% had a diagnosis or prescription for an antidiabetes medication; 30% had neither diagnosis nor prescription but had a subsequent negative diabetes test result. The remaining 35% had no diagnosis nor prescription, and either re-tested positive for diabetes or had no follow-up. By 12 months, 83% of all patients received appropriate follow-up. Among patients with HbA1c ≥ 8.0, 92% and 96% had appropriate follow-up within 3 and 12 months, respectively. Most initial prescriptions were for metformin (84%) with variation in use of 2nd or 3rd line diabetes medications: sulfonylurea, 1-12%; DPP-4, 0-10%; SGLT2, 0-10%; GLP-1, 0-3%; and insulin, 1-12%.

Conclusions: Within a year of a positive diabetes screen, most patients received appropriate action. Those with higher lab values were more likely to receive appropriate action sooner. Among those with prescriptions, most were for metformin. The proportion of patients with appropriate action, time to action, and type of action, e.g., use of 2nd and 3rd line agents, all varied considerably across HCOs.

Disclosure

N. Stempniewicz: None. E.L. Ciemins: None. C.R. Rattelman: None. J.K. Cuddeback: None.

Funding

Novo Nordisk
1256-P: Assessing Truck Drivers with Diabetes: The Clinician's Role
Authors: LORBER DANIEL , HATHAWAY KATIE
Published: June 2019

In 2018 the Department of Transportation (DOT) published a new rule on the requirements for medical certification of commercial motor vehicle (CMV) drivers with insulin-treated diabetes mellitus. This rule eliminates significant obstacles for those drivers, thus potentially enabling thousands of drivers to pursue careers that had previously been unavailable to them.

This poster reviews the process of CMV medical certification for drivers with insulin-treated diabetes and provides resources and guidance for the assessment process. The new rule requires an assessment by a treating clinician (defined as a healthcare professional who manages, and prescribes insulin for, treatment of the individual’s diabetes mellitus as authorized by the healthcare professional’s applicable state licensing authority). The components of this assessment include:

• A minimum of 3 months of blood glucose self-monitoring records measured with a glucometer that stores all readings from which data can be downloaded.

• Hypoglycemia history.

• Hemoglobin A1C measurements.

• Complications of diabetes.

The treating clinician completes an assessment form to determine whether the driver meets the physical qualification standards of the Federal Motor Carrier Safety Administration (FMCSA) to operate a CMV. Additional assessment by the treating clinician may be required if the driver has recently experienced a motor vehicle accident or severe hypoglycemic episode. The treating clinician is required to attest the driver maintains a “stable insulin regimen” and “proper control of his/her diabetes mellitus.” The American Diabetes Association provides a useful online calculator to assess the risk of a diabetes related motor vehicle accident (professional.diabetes.org/RADD)

Although the rule requires an opinion from a treating clinician, the final decision on medical certification for any individual CMV driver is made by a certified medical examiner listed on the National Registry of Certified Medical Examiners.

Disclosure

D. Lorber: None. K. Hathaway: None.
1257-P: Quality Improvement Project to Increase Insulin Pump Use in Pediatric Type 1 Diabetes
Authors: LYONS SARAH , CANADA NICKI L. , HERNANDEZ KEVIN , SEGOVIA JAMIE E. , BARTZ SARA K. , DESALVO DANIEL J. , MCKAY SIRIPOOM , SONABEND RONA
Published: June 2019

Background: Insulin pump therapy in type 1 diabetes (T1D) has been associated with lower hemoglobin A1c than multiple daily injections. In the T1D Exchange, 63% of pediatric patients <18 years old in 2013-14 used pumps. However, pump use at our institution in 2015 was much lower at 39.4% (551 of 1399 patients <18 years old with T1D duration ≥1 year attending clinic at least twice yearly). A multidisciplinary team of pediatric endocrinologists, diabetes educators, and hospital leaders implemented a QI initiative aimed to increase pump use to ≥50%.

Methods: Pump use was extrapolated from diabetes providers’ visits in the electronic medical record (EMR) and tracked via a run chart. A series of plan-do-study-act (PDSA) cycles were implemented, including:

1. Creation of introductory and advanced pump handouts for patients.

2. Quarterly technology sessions for providers and clinic staff to improve pump knowledge.

3. Creation of pump start orders in the EMR.

4. Certification of the clinic’s diabetes educators in all commonly used pumps.

5. Scheduled diabetes educator visits for all patients after pump initiation.

Results: Pump use increased from 39.4% (551 of 1399 patients) in 2015 to 50.6% (730 of 1442 patients) in 2018 (Image 1).

Conclusion: The aim of increasing pump use to ≥50% of our clinic’s population was achieved over 3 years. Building on this success, future direction is to evaluate impact on bolus frequency and association with HbA1c.

Disclosure

S. Lyons: None. N.L. Canada: None. K. Hernandez: None. J.E. Segovia: Consultant; Self; Insulet Corporation. S.K. Bartz: None. D.J. DeSalvo: Consultant; Self; Dexcom, Inc., Insulet Corporation. S. Mckay: None. R. Sonabend: None.
1287-P: Demographics, Socioeconomic Characteristics, and Quality of Life Accompaniments of Pain in Diabetic Polyneuropathy
Authors: LAPIN BRITTANY , MORRISON SHANNON , SCHUSTER ANDREW , JOHNSON KRISTEN , BOULOS FERNANDA , THAKORE NIMISH J. , MILINOVICH ALEX
Published: June 2019

A subset of patients with diabetic polyneuropathy (DPN) have significant pain. There is little information on how patients with painful diabetic polyneuropathy (DPN+P) differ from those with DPN without pain (DPN-P). The objective was to determine differences in demographics, socioeconomic characteristics, and patient-reported quality-of-life (QoL) between DPN+P and DPN-P patients. We used an algorithm of high sensitivity (90%) and moderate specificity (60%) to electronically classify patients within our institution between 2009 and 2016 as no DPN, DPN+P, or DPN-P. QoL was assessed as part of standard of care using PROMIS Global Health mental and physical summary scores, and PHQ-9 depression screen. We report clinically and statistically significant (p<0.05) differences between DPN+P and DPN-P. Independent associations with DPN+P were evaluated using multivariable logistic regression models.Of 43,945 patients with type 2 diabetes, 13,910 (32%) had DPN, of whom 9,104 patients had DPN+P (65%) and 4,806 had DPN-P (35%). Patients with DPN+P were significantly younger than DPN-P (68±13 vs. 66±13), and more likely to be female (55% vs. 44%). Compared to DPN-P, DPN+P patients were less frequently white (67% vs. 72%), less frequently married (47% vs. 54%), had lower median household income ($50.6k vs. $55.5k), and were more likely to be covered by Medicaid (14% vs. 7%) and less likely to have private health insurance (21% vs. 29%). QoL measures, PROMIS and PHQ-9 scores, were significantly worse for patients with DPN+P vs. DPN-P. Younger age, female sex, and worse QoL remained independently associated with DPN+P after adjustment. Demographic, socioeconomic, and QoL associations could be causative of pain, perhaps mediated through poorer diabetes care, and could be consequences of pain, mediated through loss of productivity. This reciprocal effect and the economic magnitude of the problem warrant longitudinal study of the risk factors and natural history of pain in DPN.

Disclosure

B. Lapin: None. S. Morrison: None. A. Schuster: None. K. Johnson: Employee; Self; Novartis Pharmaceuticals Corporation. F. Boulos: Employee; Self; Novartis Pharmaceuticals Corporation. N.J. Thakore: Research Support; Self; Novartis Pharmaceuticals Corporation. A. Milinovich: Research Support; Self; Amgen Inc., Celgene Corporation, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Otsuka Pharmaceutical Co., Ltd.
129-OR: Diabetes Prevention through Yoga-Based Lifestyle: A Pan-India Randomized Controlled Trial
Authors: NAGARATHNA RAGHURAM , VENKATA S. RAM C. , RAJESH SASIDHARAN K. , SINGH AMIT , MAJUMDAR VIJAYA , PATIL SUCHITRA , NAGENDRA HONGASANDRA R.
Published: June 2019

Objective: The study tested the potency of yoga-based intervention on risk reduction of diabetes.

Research Design and Methods: This study is an offshoot of a large, 2 group cluster randomized, translational research trial on 11,212 individuals, aged >20 years, with high-risk (>60) for diabetes on IDRS (Indian diabetes risk score) and type 2 diabetes. The present study included a subgroup of 3,366 prediabetes individuals [A1C range of 5.70-6.49% (39-47 mmol/mol)]. Eligible individuals were selected by community-based (rural and urban) screening from 29 states/union Indian territories and were cluster randomized. The wait list control group received lifestyle advice. The experimental group performed a validated yoga-based lifestyle intervention developed by a group of 16 yoga and diabetes experts using the Delphi method. The study outcomes, diabetes incidence/prediabetes remission were obtained by respective A1c values >6.5% (48 mmol/mol) or <5.7% (38 mmol/mol) (normoglycemia) at 3 months of follow-up.

Results: At 3 months of follow-up, 11.2% of the yoga-intervention group and 21.6% of the control group developed diabetes (p<0.05); the relative risk reduction (RRR) was 47% (95% CI: 26-70). Interestingly, the intervention resulted in an effective shift to a normal range of A1c values in 52.0% of individuals as compared to only 39.9% in the control (p<0.05). Yoga-intervention was found to be beneficial for both the normal BMI (<23 Kg/m2) and the overweight/obese sub-groups (≥23 Kg/m2), as indicated by the respective RRRs of 69% (95% CI: 52-85) and 51% (95% CI: 32-70).

Conclusion: This is the first report on the effectiveness of a yoga-based life style intervention for remission of prediabetes and prevention of diabetes. The intervention was adequately effective for normal and overweight/obese subgroups. The short-term findings demand the need for longer follow-up. We speculate positive long-term outcomes based on the reported effects of yoga on self-control and feeding behavior.

Disclosure

Raghuram Nagarathna: None. C. Venkata Ram: None. Sasidharan Rajesh: None. Amit Singh: None. Vijaya Majumdar: None. Suchitra Patil: None. Hongasandra Nagendra: None.

Funding

The Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy; Government of India Ministry of Health and Family Welfare
1290-P: Achieving and Sustaining Inpatient Glycemic Goals by Employing Targeted Strategies that Include Daily Surveillance and Real-Time Communication
Authors: THOMPSON ELAINA L. , EVERHART BRIDGET
Published: June 2019

Background: Approximately 30% of inpatient admissions require glycemic management at our 680 bed academic hospital. The Inpatient Diabetes (DM) Program created internal glycemic goals, employed targeted strategies to meet and sustain these goals, and began participation in a national database for comparative benchmarking.

Purpose: The purpose of the Inpatient Diabetes Program is to lead evidence-based diabetes care to achieve glycemic outcomes for hospitalized patients.

Method: The DM Program uses targeted strategies to meet glycemic outcomes, including daily surveillance, real-time communication with providers, maximization of the Electronic Health Record (EHR), provision of varied educational formats, and empowerment of front line staff in decision making. Daily real-time communication occurs with the prescribing provider (e.g., resident/advanced practice provider and the attending provider regarding recurrent hypoglycemia and persistent hyperglycemia. Follow-up surveillance is completed to evaluate if there was a treatment change. Maximization of the EHR has facilitated standardization of care with the creation of order sets, reports and real-time surveillance. Staff education is provided using various platforms including focused courses, a DM share-point site, videos, and a DM newsletter.

Results/Outcomes: The rate of hyperglycemia (BG >180 mg/dL) has decreased in the previous 3 years from 25% to 20% for point of care glucose values, without an increase in hypoglycemia. The hypoglycemia rate has consistently remained at 2% with a severe hypoglycemia rate of 0.1%. Day weighted mean BGs in both critical care and non-critical care meet the national benchmark targets.

Implications for Practice: Using targeted interventions that are “active” strategies like frequent surveillance and real-time communication helps achieve inpatient glucose goals.

Disclosure

E.L. Thompson: None. B. Everhart: None.
1294-P: Detection and Intervention of Prediabetes in a Large Urban Health System: Systematic Failure or Looming Opportunity?
Authors: NEWBOLD EMILY , CARLSON SUSAN E. , SULLIVAN DEBRA K. , ROBBINS DAVID C. , BELTRAMO ALVIN , LOWRANCE MAREN , WAITMAN LEMUEL R.
Published: June 2019

Efficient early detection of prediabetes is critical in order to intervene and reduce conversion to T2DM since lifestyle interventions and/or metformin are proven to reduce progression. Retrospective data from a nationally-ranked tertiary academic medical center were analyzed to determine diagnosis rates, frequency of lifestyle and prescription interventions, and to assess characteristics of patients who were most likely to be clinically identified or treated.

Data from the EpicCare EMR were analyzed using the University of Kansas Medical Center i2b2-based clinical data repository (HERON). Data were collected for 69,781 patients established in academically affiliated primary care clinics between 2015 and 2017. After excluding for previous diabetes/prediabetes diagnoses or use of glucose lowering agents, 46,855 patients remained to assess for incident prediabetes (ADA criteria). Clinical recognition of the prediabetes diagnosis, nutrition or weight management referral, and metformin prescription were assessed.

Incident prediabetes occurred in 2,581 patients (5%). Thirty eight percent of those received a charted prediabetes diagnosis, 9% received either a referral to nutrition or weight management, and 4% received a metformin prescription. Females (OR 1.57) or those who had higher BMI (OR 1.02) or A1c values (OR 5.67) had higher odds of receiving clinical recognition (p<0.0001).

We conclude that relatively few people with prediabetes are clinically noted and even fewer receive interventions that may reduce the conversion to T2DM. There are gender and weight biases; patients with higher BMI, higher A1c values, and females were more likely to have documentation for diagnosis and treatment for prediabetes. These low rates of recognition and treatment are likely to be similar among health care systems across the country. The low rates of recognizing, documenting, and intervening are opportunities to better utilize the EMR and reduce conversion to T2DM.

Disclosure

E. Newbold: None. S.E. Carlson: Advisory Panel; Self; DSM. Other Relationship; Self; MeadJohnson Nutrition (RB). D.K. Sullivan: None. D.C. Robbins: None. A. Beltramo: None. M. Lowrance: None. L.R. Waitman: None.
1297-P: Mortality and Glycemic Control among Patients with Endometrial Cancer and Diabetes Mellitus: A Case-Control Study
Authors: KARLIN NINA , VERONA PATRICIA M. , BURAS MATTHEW R. , KOSIOREK HEIDI E. , COOK CURTISS
Published: June 2019

Background: The aim of this study was to examine the impact of diabetes mellitus (DM) on survival in endometrial cancer patients, and the impact of endometrial cancer on glycemic control in DM.

Methods: Patients with newly diagnosed endometrial cancer with DM (n=48) were identified from the Institutional Cancer Registry and matched to 48 endometrial cancer patients without DM according to age, gender and year of cancer diagnosis (2006 to 2016). The electronic medical record provided information on DM, cancer therapies and laboratory results. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared by Cox regression analysis using stratification for matched pairs. Mixed models were used to compare hemoglobin A1c (HbA1c) and glucose during the year following cancer diagnosis.

Results: Mean age of the entire cohort was 67 years, 85% were white, and 76% had stage I disease. BMI was significantly different between DM and non-DM patients (39.6 versus 29.3; p<0.001). More patients without DM were treated with chemotherapy (33% versus 13%; p=0.04). Among those with DM, mean HbA1c during the year following cancer diagnosis was 7.2%. For glucose, DM group status was significant (p<0.001) as DM pts had higher glucose overall compared to non-DM pts (147 mg/dL vs. 106 mg/dL, p<0.001) and there was a time effect (p=0.03) as well. In both groups, glucose decreased during the year following diagnosis. Median follow-up time was 47 months (range 1.2 - 115.6 months) in living patients. 5-year survival estimated at 91% for DM patients versus 95% in non-DM pts by Kaplan Meier method (p=0.25 log rank test). OS Hazard ratio was 1.50 (95% CI: 0.25 - 8.98; p=0.66). 5-year PFS was estimated at 89% for both groups PFS Hazard ratio was 0.75 (95% CI: 0.17 -3.35; p=0.71).

Conclusions: Endometrial cancer and its treatment did not affect glycemic control. DM did not adversely impact survival in patients with endometrial cancer.

Disclosure

N. Karlin: None. P.M. Verona: None. M.R. Buras: None. H.E. Kosiorek: None. C. Cook: None.