bluuebunny/crossref_metadata_2025 huggingface dataset:
1424-P: Changes in Device Uptake and Glycemic Control among Pregnant Women with Type 1 Diabetes: Data from the T1D Exchange
Authors: LEVY CAROL J. , FOSTER NICOLE C. , DUBOSE STEPHANIE , AGARWAL SHIVANI , LYONS SARAH , PETERS ANNE L. , UWAIFO GABRIEL I. , DIMEGLIO LINDA , SHERR JENNIFER , POLSKY SARIT
Published: June 2019

We examined characteristics of pregnant women aged 16-40 years with type 1 diabetes (T1D) enrolled in the T1D Exchange clinic registry. We compared characteristics of 3 cohorts of women with data collection periods from: 2010-12 (N=4651), 2011-13 (N=3355), and 2016-18 (N=2818). 2.9%, 2.2%, and 1.7% of women reported being pregnant during 2010-12, 2011-13, and 2016-18, respectively. For pregnant women, there was a trend for a decrease in HbA1c over the 3 time periods from 6.8% to 6.7% to 6.4% (P=0.13 adjusted for age, race/ethnicity, frequency of glucose monitoring, and use of CGM). Self-reported use of CGM while pregnant increased more than 2-fold over the time period (P=0.001 adjusted for age, duration, race/ethnicity, insurance status, and use of pump); conversely, self-reported pump use while pregnant remained unchanged (adjusted P=0.38) (Table). Severe hypoglycemia (seizure/loss of consciousness) was similar across cohorts (adjusted P=0.38).We found in a real-world population of pregnant women in the U.S., lower HbA1c levels compared to those pregnant 5-6 years ago. CGM use in pregnancy appears to have increased over time, with relatively low but stable participant-reported insulin pump use. Further explorations of these findings, ongoing assessment of real-world pregnancy outcomes and comparisons with data on T1D pregnant women from other large registries are needed.

Disclosure

C.J. Levy: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Allergan. N.C. Foster: None. S. DuBose: None. S. Agarwal: None. S. Lyons: None. A.L. Peters: Advisory Panel; Self; Abbott, Becton, Dickinson and Company, Bigfoot Biomedical, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Livongo Health, MannKind Corporation, Medscape, Merck & Co., Inc., Omada Health, Inc., OptumRx, Inc., Sanofi US, Zafgen, Inc. Research Support; Self; AstraZeneca, Dexcom, Inc., Jaeb Center for Health Research, MannKind Corporation, National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc. G.I. Uwaifo: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J. Sherr: Advisory Panel; Self; Bigfoot Biomedical, Eli Lilly and Company, Insulet Corporation. Consultant; Self; Lexicon Pharmaceuticals, Inc., Medtronic, Sanofi. Research Support; Self; Dexcom, Inc., Insulet Corporation. S. Polsky: Consultant; Self; Jaeb Center for Health Research. Research Support; Self; Barbara Davis Center for Diabetes, Children's Diabetes Foundation, Dexcom, Inc., Eli Lilly and Company, JDRF, Leona & Harry Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi US.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
1435-P: Impaired Early-Phase Suppression of Glucagon Secretion after Glucose Load Associated with Insulin Need during Pregnancy in Gestational Diabetes
Authors: HORIE ICHIRO , HARAGUCHI AI , ABIRU NORIO , KAWAKAMI ATSUSHI
Published: June 2019

Aims: The prevalence of gestational diabetes mellitus (GDM) has recently increased all over the world. It is hard to predict insulin need during pregnancy even if the insulin secretory capacity is evaluated when studying 75-g OGTT to screen for GDM. The role of glucagon abnormality has remarked in pathogenesis of type 2 diabetes, however, still unknown in GDM. This study was aimed to evaluate glucagon responses in GDM and to investigate whether measurement of glucagon is useful to anticipate insulin need during pregnancy.

Methods: Forty-nine women diagnosed with GDM based on IADPSG criteria were enrolled into the study and re-studied OGTT during mid-gestation to evaluate glucagon responses. Plasma glucagon levels were measured before and 30, 60, 120 min after glucose load using a sandwich ELISA kit. Insulin treatment was initiated when either a fasting glucose >95 mg/dL or postprandial 2-h glucose >120 mg/dL continues for more than a week after starting diet therapy.

Results: Of 49 patients, fifteen were required insulin (defined as GDM/Insulin) and 34 could be treated with diet therapy alone until delivery (defined as GDM/Diet). GDM/Insulin was started insulin treatment at 29.6±3.6 weeks of gestation and the maximum insulin dose was 39.0±24.8 units/day. There were no significant differences in maternal age, pre-gravid BMI and insulin secretory responses during OGTT between the groups. Although fasting glucagon levels were not different between the groups, paradoxical increases in early-phase glucagon secretion after glucose load were observed in GDM/Insulin but not in GDM/Diet. The changes in glucagon levels (pg/mL) from 0 min to 30 min were significantly different between the groups (1.3±8.1 in GDM/Insulin vs. -4.2±4.0 in GDM/Diet, p<0.01), and the ROC analysis of the value to predict insulin need was -2.01 pg/mL.

Conclusions: Impaired early-phase glucagon suppression might be useful to predict for insulin need during pregnancy in GDM.

Disclosure

I. Horie: None. A. Haraguchi: None. N. Abiru: None. A. Kawakami: None.
1447-P: Epistatic Interactions of Known Gene Variants for Glycated Hemoglobin: Evidence from the Long Life Family Study
Authors: AN PING , THYAGARAJAN BHARAT , LEE JOSEPH H. , SCHUPF NICOLE , ZMUDA JOSEPH M. , PROVINCE MICHAEL
Published: June 2019

HbA1c, an index of chronic glycemic status relevant to IR and T2D, is associated with aging, cognitive performance and mortality. To identify epistatic interactions, we assessed 65 published SNPs associated with levels of HbA1c (n=4,090) and change in HbA1c levels over time (n=2,054) among nondiabetic participants of European ancestry who had complete data from 2 exams collected 7 years apart in the LLFS, a multicenter family study with a clustering of healthy aging and exceptional survival. Both traits were adjusted for age, sex, BMI, field center and principal components, with correction for familial membership. HbA1c change over time was derived using growth curve modeling, taking into account baseline HbA1c. A knowingly more powerful Bayesian approach was used to test SNP association searching for significant (Bayes Factor, BF>3) single SNPs and best (top 1) combinations of interacting SNPs followed by MIXED regression reconfirmation (p<0.05 for main and interaction terms). HK1-rs17476364 (BF=7.8), GCK-rs4607517 (BF=5.7), HK1-rs16926246 (BF=4.8), SPTA1-rs12041363 (BF=4.5), G6PC2-rs560887 (BF=3.6) and SPTA1-rs857691 (BF=3.0) were individually associated with baseline HbA1c. Their best and significant 2-SNP association was found between HK1-rs17476364 and GCK (BF=13.5; p=0.000015, 0.0038 and 0.0093 for main and interaction terms, respectively). The emerged best 3 and 4 SNP combinations were HK1-GCK-SPTA1 (BF=18.1) and HK1-GCK-SPTA1-G6PC2 (BF=22.0), respectively. For HbA1c change over time, no single SNPs were significant; their best SNP combination involved G6PC2, ADCY5, SLC30A8, HK1, PHB2 and FN3KRP. Glucokinase (GCK product) and hexokinase (HK1 product) are isozymes that interactively and uniquely phosphorylate glucose to make G6P, an important intermediate enabling the coordination of the rate of glycolysis. Together, HK1-GCK interaction for HbA1c was observed first in a large family data with familial clustering of exceptional longevity.

Disclosure

P. An: None. B. Thyagarajan: None. J.H. Lee: None. N. Schupf: None. J.M. Zmuda: None. M. Province: None.

Funding

National Institutes of Health
145-OR: Ultra Rapid Lispro (URLi) Improves Postprandial Glucose (PPG) Control vs. Humalog (Lispro) in Patients with Type 2 Diabetes (T2D): PRONTO-T2D
Authors: BLEVINS THOMAS , ZHANG QIANYI , FRIAS JUAN P. , JINNOUCHI HIDEAKI , CHANG ANNETTE M.
Published: June 2019

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. This phase 3, multicenter, treat-to-target, 26-week trial evaluated the efficacy and safety of URLi vs. lispro in patients with T2D. Primary endpoint was A1C change from baseline to week 26, with multiplicity adjusted objectives for PPG excursions (PPGE) with meal test. After 8-week lead-in to optimize basal insulin glargine or degludec and transfer to prandial lispro treatment, patients were randomized to double-blind URLi (n=336) or lispro (n=337) injected 0 to 2 minutes prior to meals. Patients could continue metformin and/or SGLT2 inhibitor.

Non-inferiority for primary endpoint was confirmed for URLi: estimated treatment difference (ETD) 0.06 [95% CI -0.05; 0.16], with mean change in A1C of -0.38% URLi and -0.43% lispro (Figure). Mean A1C at week 26 was 6.92% URLi and 6.86% lispro. URLi was superior to lispro in controlling 1- and 2-h PPGE with standardized meal test at week 26, with lower PPGE from 0.5-4 h with URLi (Figure). There were no significant treatment differences in rates of severe or overall hypoglycemia. Incidence of overall treatment-emergent adverse events was similar between treatments.

URLi in a basal-bolus regimen led to superior PPG control vs. lispro in patients with T2D.

Disclosure

T. Blevins: Research Support; Self; Amgen Inc., Gan and Lee Pharma, Lilly Diabetes, Mylan, Novo Nordisk Inc. Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Lilly Diabetes, Sanofi US. Other Relationship; Self; Medtronic MiniMed, Inc. Q. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J.P. Frias: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Sanofi. Consultant; Self; Echosens, Genentech, Inc., Johnson & Johnson Diabetes Institute, Novo Nordisk Inc., Zafgen, Inc. Research Support; Self; AbbVie Inc., Akcea Therapeutics, Allergan, Amgen Inc., AstraZeneca, Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Cirius Therapeutics, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Enanta Pharmaceuticals, Inc., GENFIT, Intarcia Therapeutics, Inc., Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Oramed Pharmaceuticals, Pfizer Inc., Sanofi, TaiwanJ Pharmaceuticals Co., Ltd., Theracos, Inc. Speaker's Bureau; Self; Merck & Co., Inc., Sanofi. H. Jinnouchi: None. A.M. Chang: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
1462-P: Diabetes-Associated Residual Risk in Statin-Treated Patients with Atherosclerotic Cardiovascular Disease
Authors: WONG NATHAN D. , ZHAO YANGLU , XIANG PIN , ANTONIO J , LOPEZ G
Published: June 2019

Background: Persons with atherosclerotic cardiovascular disease (ASCVD) on statins remain at higher risk of CV events. The added residual risk that diabetes mellitus (DM) confers has not been well-quantified. We examined initial and total ASCVD events in statin treated persons with ASCVD and the added risk of DM.

Methods: We studied 3,271 subjects with ASCVD on statins from the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes trial cohort. We examined rates for first and total ASCVD events. Cox regression examined the risk of first ASCVD events over 3 years with and without DM at baseline.

Results: 40% of subjects had DM. Those with vs. without DM were slightly older, less likely male, white, currently smoking, had higher systolic but lower diastolic blood pressure, lower HDL-C, LDL-C, lipoprotein (a), but higher triglycerides and BMI (all p<0.01). First and total ASCVD event rates are shown (Figure). Total ASCVD events were about 50% greater than initial events, with the difference largest in men with DM. From fully adjusted analyses, DM conferred a 22% greater risk of first ASCVD events compared to no DM (HR=1.22, 95% CI=1.03-1.44, p=0.02).

Conclusion: Despite statin therapy, DM carries significantly greater residual risk over having ASCVD alone. More aggressive approaches are needed to reduce the increased risk with ASCVD and DM.

Disclosure

N.D. Wong: Advisory Panel; Self; Novartis Pharmaceuticals Corporation. Consultant; Self; Akcea Therapeutics, AstraZeneca. Research Support; Self; Amarin Corporation, Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Y. Zhao: None. P. Xiang: Employee; Self; Amgen Inc. J.G. Lopez: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc.

Funding

Amgen Inc.
1469-P: Associations between Heart Rate, Glycemia, and A1c Levels
Authors: CASAGRANDE SARAH , COWIE CATHERINE C. , SOSENKO JAY M. , MIZOKAMI-STOUT KARA R. , BOULTON ANDREW J. , POP-BUSUI RODICA
Published: June 2019

Previous evidence suggests that heart rate (HR) is a prognostic factor for cardiovascular disease, for which persons with diabetes are at increased risk. We examined the association between heart rate and levels of glycemia in a nationally representative sample of U.S. adults.

This study included 27,602 adults age ≥20 years from the 2011-2014 National Health and Nutrition Examination Surveys. Levels of glycemia were defined as: diagnosed diabetes (self-report); undiagnosed diabetes [fasting plasma glucose (FPG) ≥126mg/dL or A1c ≥6.5%]; prediabetes (FPG 100-125mg/dL or A1c 5.7%-6.4%); normoglycemia (FPG <100mg/dL and A1c <5.7%). Predictive margins regression was used to determine mean HR by participant characteristics and glycemic status; and among those with diagnosed diabetes, by participant characteristics and A1c level. Mean HR was adjusted for age, sex, race/ethnicity, education, poverty income ratio, health insurance, smoking status, body mass index, history of cardiovascular disease, kidney disease, and antihypertensive medications; models by A1c level were additionally adjusted for oral antidiabetic medications. Mean HR was significantly higher for those with diagnosed and undiagnosed diabetes compared to those with normoglycemia (74 bpm vs. 72 bpm, p<0.05, for both). In the fully adjusted model, mean HR remained significantly higher for those with diagnosed (76 bpm) and undiagnosed diabetes (75 bpm) compared to those with normoglycemia (71 bpm, p<0.05 for both). Among persons with diagnosed diabetes, there was a positive association between HR and glycemic levels as measured by A1c (72 bpm, 75 bpm, 77 bpm, and 81 bpm for A1c <7.0%, 7.0%- <9.0%, 9.0%- <11.0%, and A1c ≥11.0%, respectively, p<0.001), and this association remained after adjustment for risk factors.

In conclusion, mean HR was higher among persons with diabetes and increased glycemia, which may reflect subtle autonomic and/or myocardial dysfunction among those with diabetes.

Disclosure

S. Casagrande: None. C.C. Cowie: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen Inc., Fresenius SE & Co. KGaA, General Electric, Johnson & Johnson, Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc. J.M. Sosenko: None. K.R. Mizokami-Stout: None. A.J. Boulton: None. R. Pop-Busui: Consultant; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases
1474-P: Changes in SGLT2i and GLP-1RA Real-World Initiator Profiles following Cardiovascular Outcome Trials—A Danish Nationwide Population-Based Study
Authors: KNUDSEN JAKOB S. , MUNKSGÅRD BAGGESEN LISBETH , LAJER MARIA , NURKANOVIC LARISA , USTYUGOVA ANASTASIA V. , SÔRENSEN HENRIK T. , THOMSEN REIMAR W.
Published: June 2019

Objectives: To investigate changes in clinical characteristics of SGLT2i and GLP-1RA initiators in Denmark before/after landmark trials.

Materials and Methods: Compared first-time SGLT2i (25,070) and GLP-1RA (15,803) initiators to initiators of DPP-4i (without proven cardiovascular benefits), using linked population-based healthcare data to examine initiation incidence, medication patterns, and atherosclerotic cardiovascular disease (ASCVD) during 2014-2017.

Results: Nationwide incidence of SGLT2i initiators increased 3.6-fold (53/100,000 to 172/100,000 per year) vs. a 1.7-fold increase for GLP-1RA. DPP-4i initiation remained stable (Figure). From the end of 2015, SGLT2i was increasingly used as 2nd-line and GLP-1RA as 1st-line therapy. Among SGLT2i users, ASCVD increased slightly from 28% to 30%; age- and gender-adj. prevalence ratio (aPR) = 1.03 (95% CI:0.97-1.10). In contrast, among GLP-1RA initiators, ASCVD declined from 29% to 25% (aPR: 0.87 (95% CI:0.81-0.93)), and in DPP-4i initiators from 31% to 29% (aPR: 0.91 (95% CI:0.88-0.96)).

Conclusion: For SGLT2i, the EMPA-REG OUTCOME trial may have driven earlier adoption i.e., increased 2nd-line use, with minor increases in proportions with ASCVD. For GLP-1RA, we observed increased 1st-line use and decreasing ASCVD despite the LEADER trial, possibly due to anti-obesity treatment launch.

Disclosure

J.S. Knudsen: None. L.M. Baggesen: None. M. Lajer: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. L. Nurkanovic: Employee; Self; Boehringer Ingelheim International GmbH. A.V. Ustyugova: Employee; Self; Boehringer Ingelheim International GmbH. H.T. Sôrensen: None. R.W. Thomsen: None.

Funding

Boehringer Ingelheim
148-LB: Efficacy and Safety of Adding an Oral Hypoglycemic Agent or a GLP-1 Receptor Agonist to Insulin in Patients with Type 1 Diabetes: A Network Meta-analysis
Authors: KIM YOON JI , HWANG SEUN DEUK , LIM SOO
Published: June 2019

Objective: Despite intensive insulin treatment in patients with type 1 diabetes (T1D), their glycemic levels often do not reach the recommended target goal. We performed a network meta-analysis to evaluate the efficacy and safety of additional therapy to insulin in patients with T1D.

Methods: We searched CENTRAL, MEDLINE, and Embase from 1970 until January 2019 to identify randomized controlled trials (RCTs) in T1D patients treated with insulin and oral hypoglycemic agents or glucagon-like peptide-1 receptor agonists. We performed network meta-analyses using Bayesian models and generated rankings of the different hypoglycemic agents by generation mixed treatment comparison.

Results: With 23 RCTs (n =3,839), we performed the network meta-analysis using eight groups; 1) insulin alone, 2) insulin and metformin, 3) insulin and canagliflozin, 4) insulin and dapagliflozin, 5) insulin and empagliflozin, 6) insulin and sotagliflozin, 7) insulin and liraglutide, and 8) insulin and exenatide. Compared with insulin alone, HbA1c was significantly lower in the group treated with insulin and sotagliflozin (mean difference: -0.43%; 95% Crl: -0.66, -0.20). Total daily insulin dose was significantly lower in the insulin and sotagliflozin group by 6.4 U/day than other groups. Compared with insulin alone, body weight was decreased in the group with insulin and canagliflozin by 4.5 kg, insulin and sotagliflozin by 2.8 kg, insulin and liraglutide by 4.5kg, and insulin and exenatide by 5.1 kg, respectively. Severe hypoglycemic episodes did not differ between the groups.

Conclusions: In patients with T1D, sotagliflozin treatment combined with insulin decreased HbA1c levels, insulin dose, and body weight without hypoglycemia compared with insulin monotherapy. Combined treatment of canagliflozin, liraglutide, or exenatide with insulin was also effective in weight loss compared with insulin alone in these patients.

Disclosure

Y. Kim: None. S. Hwang: None. S. Lim: None.
1481-P: Relationship among BMI, WC, and Cardiovascular Disease Risk Factors: Findings from the Korea National Health Insurance System (KNHIS) Health Checkup Data
Authors: SON JANG WON , LEE SEONG-SU , KWON HYUK-SANG , JIB YOO SOON
Published: June 2019

The clinical utility of the combined use of BMI and waist circumference (WC) to indicate the cardiovascular disease (CVD) risk factors in Asians remains unclear. Using a large-scale population-based cohort from the KNHIS health checkup data from 2009 to 2015, we investigated the relationship between BMI, WC and subsequent CVD risk factors (at least one from type 2 diabetes, hypertension or dyslipidemia). BMI was categorized into 5 subgroups at 18.5, 23.0, 25.0 and 30.0kg/m2. The cut-off points of WC for central obesity were 90cm in men and 85cm in women. The participants were subdivided into a total of 10 subgroups according to the presence of central obesity in each of the 5 BMI ranges. The incidence risk of CVD risk factors in each subgroup was comparatively analyzed using a multivariable Cox's proportional hazard model. Participants were 14,170,134 adults above 20 years of age who did not have type 2 diabetes, hypertension or dyslipidemia at the baseline examinations. During a mean follow-up of 5.3 years, CVD risk factors developed in 1,857,307 participants. The HRs for CVD risk factors were increased by 8.2% per 1kg/m2 increment of BMI. The HRs (95% CI) for CVD risk factors across BMI categories were 0.573, 1.0, 1.479, 1.962 and 3.03, respectively, after adjusting for age, sex, smoking, alcohol drinking, physical activity, and monthly income. Compared to the group with BMI of 18.5 to 23 kg/m2 without central obesity, which served as the reference group, the multivariable-adjusted HRs in those with central obesity was significantly increased from 1.00 to 1.27 with a BMI of 18.5 to 23.0 kg/m2, from 1.45 to 1.64 with a BMI of 23.0 to 25.0 kg/m2, from 1.83 to 2.10 with a BMI of 25.0 to 30.0 kg/m2, and from 2.56 to 3.08 with a BMI of 30.0 kg/m2 or over. These findings show that assessment of central obesity provided additional clinical utility beyond BMI for reclassifying the risk of CVD risk factors in Korean populations, even those with a low BMI.

Disclosure

J. Son: None. S. Lee: None. H. Kwon: None. S. Yoo: None.
149-LB: The MetAP2 Inhibitor, ZGN-1061, Improves Insulin Sensitivity and Beta-Cell Function in Patients with Type 2 Diabetes
Authors: FABUNMI ROSALIND , BERGMAN RICHARD N. , PICCININI FRANCESCA , KIM TERRI , ZHUANG DONGLIANG , TAYLOR KRISTIN , KIM DENNIS D.
Published: June 2019

ZGN-1061 is a second-generation methionine aminopeptidase 2 (MetAP2) inhibitor in development for treatment of T2D. Full results of a Phase 2 clinical trial of ZGN-1061 vs. placebo (PBO) administered SC for 12 weeks on change from baseline in A1C in subjects with T2D are reported elsewhere. Baseline (ITT population N=175) A1C 8.6±1.1%, BMI 37±7 kg/m2, T2D duration 8±6 y. ZGN-1061 was generally well tolerated; 93% completed the trial. LS mean±SE A1C change was 0.2±0.1% for PBO vs. ±0.4±0.1% and -0.9±0.2% for 0.9 and 1.8 mg ZGN-1061 (both p<0.001 vs. PBO). PBO weight change was -0.6±0.3 kg vs. -1.4±0.3 kg (p=ns) and ±2.8±0.5 kg (p<0.001) for 0.9 and 1.8 mg ZGN-1061. This analysis included a subset of subjects who participated in a mixed-meal tolerance test (MMTT) at baseline and week 12. ZGN-1061 produced dose-dependent improvements in fasting and postprandial glucose (p<0.05 vs. PBO). Minimal model analysis showed improvements in insulin sensitivity (SI) and disposition index (DI_OB; a measure of β-cell compensation) from baseline to week 12 with ZGN-1061 (Table). In an exploratory combined analysis of 0.9+1.8 mg ZGN-1061, SI and DI_OB increased (p=0.02 and p=0.07). SI and DI_OB were unchanged with PBO. In patients with T2D, improved glycemic control with ZGN-1061 may be driven by changes in insulin sensitivity and β-cell function. These results support future assessments using other definitive methods.

Disclosure

R. Fabunmi: None. R.N. Bergman: Consultant; Self; Zafgen, Inc. F. Piccinini: None. T. Kim: Employee; Spouse/Partner; Celgene Corporation. Employee; Self; Zafgen, Inc. D. Zhuang: Employee; Self; Zafgen, Inc. K. Taylor: Employee; Self; Zafgen, Inc. D.D. Kim: Employee; Self; Zafgen, Inc.

Funding

Zafgen, Inc.
1492-P: Patients with Diabetes: Perspectives on Obesity Management
Authors: HUQ SABRINA , TODKAR SUPRIYA , LAHIRI SHARON
Published: June 2019

In 2018 we surveyed our Endocrinology Clinic’s non-pregnant patients with diabetes, age ≥18, and BMI >30 kg/m2. Findings with 54 respondents indicated most were middle-aged, female, black, with an income <$50,000. BMI was ≥40 kg/m2 in 33.3%, 35-39.9 kg/m2 in 37%, and 30-34.9 kg/m2in 29.6%. Nearly all (95%) agreed that obesity is related to heart disease, early death, diabetes, and hypertension. Despite being obese, 62% selected overweight and 5.7% normal weight. About half (56.6%) were aware of their BMI. For why it is important to lose weight, most answered better physical function (86.8%), decreased medications (75.5%), improved self-esteem (56.6%) and physical appearance (55%). Half (52%) said they asked their health care providers (HCPs) about obesity treatment, and more (73%) recalled their HCP discussing obesity. Respondents discussed obesity with Primary Care (75.7%), Endocrinology (56.8%), Bariatric Surgery (19%), other subspecialty (10.8%), and OB/GYN (5.4%). Not discussing obesity was explained by knowing what to do (62.5%) and self-responsibility to manage weight (37.5%). None said clinic visit time was insufficient. Few (2%) reported referral to a specialty that manages obesity, anti-obesity medications (5.7%), or bariatric surgery (15%). Barriers to dietary changes were lack of time (35%), high cost (41%), knowledge (25%), or motivation (22%). Barriers to exercise were lack of time (47%) or inability to exercise due to health problems (27%). Barriers to anti-obesity medications included lack of knowledge (43%) and concern with side effects (29%). Barriers to bariatric surgery included risk of complications (35.3%), expense (17.6%), and lack of knowledge (15.7%). Barriers to initiating weight loss were a preference for unhealthy food (52.8%) and lack of exercise (67.9%). These findings reveal an excellent awareness of obesity as a health problem and the need for improved knowledge and discussion on anti-obesity medications and bariatric surgery.

Disclosure

S. Huq: None. S. Todkar: None. S. Lahiri: None.
1496-P: Clinical Inertia in Relation to Sociodemographic Factors among Patients with Type 2 Diabetes (T2D) in the United States
Authors: FERNANDES GAIL , SAWHNEY BAANIE , HANNACHI HAKIMA , WANG TONGTONG , MCNEILL ANN MARIE , IGLAY KRISTY , RAJPATHAK SWAPNIL
Published: June 2019

Several studies focused on clinical inertia in the U.S. T2D population have demonstrated a significant delay in treatment intensification in real-world clinical practice. The objective of this study was to evaluate if there is a disparity in clinical inertia based on sociodemographic factors. The GE Centricity Electronic Medical Record database (2015 data) was used to identify T2D patients on dual therapy with metformin and another oral antihyperglycemic agent (OAHA). Included patients had ≥12 months of continuous enrollment prior to index date (initiation of dual therapy), further intensified therapy within 2 years following the index date and had an HbA1c measure available within 6 months prior to intensification. Treatment intensification was defined as addition of another OAHA or initiation of insulin/GLP-1RA. 991 patients met the inclusion criteria; mean age of 57.9 years and 47.4% were female. Table lists the distribution of sociodemographic factors by HbA1c categories. Results suggest that older patients were less likely to be intensified at higher HbA1c compared to younger patients. Furthermore, compared to whites, black patients were more likely to be intensified at higher HbA1c levels with no apparent pattern of intensification by region.

In conclusion, decision to intensify in clinical practice may be associated with sociodemographic factors such as age and race.

Disclosure

G. Fernandes: None. B. Sawhney: Consultant; Self; Merck & Co., Inc. H. Hannachi: Employee; Self; Merck & Co., Inc. T. Wang: Employee; Spouse/Partner; Johnson & Johnson. Employee; Self; Merck & Co., Inc. A. McNeill: Employee; Self; Merck & Co., Inc. K. Iglay: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. S. Rajpathak: None.
1498-P: Multilevel Variation in Diabetes Screening within an Integrated Health System
Authors: OBINWA UDOKA C. , LINGVAY ILDIKO , MENEGHINI LUIGI , HALM ETHAN , BOWEN MICHAEL E.
Published: June 2019

Although many individuals eligible for diabetes screening go untested, little is known about the contribution of patient, provider, and clinic level factors to variation in screening in clinical practice. We used electronic health record (EHR) data from an integrated safety net health system to create a retrospective cohort of non-pregnant, primary care patients age 18-64 years without diagnosed diabetes who completed ≥ 2 primary care visits from 2010-2015 across 12 clinics. Hierarchical nested 3-level and cross-classified models were used to evaluate multilevel variation in screening at the patient (age, sex, race, insurance, family history, BMI, HTN, HLD, CVD etc.), provider (attending, physician in training, advanced practitioner), and clinic (teaching vs. non-teaching) level. Of 56,818 patients, 70.4% completed screening over 3 years of follow-up with nearly two-fold variation across clinics (51-92%; p<0.001). Of those meeting ADA (69%) and U.S. Preventive Services Task Force (36%) screening criteria, three-quarters were screened (73%,74%) with almost two-fold variation across clinics (ADA 53-92%; USPSTF 49-93%). Nearly 70% of patients not eligible for guideline-based screening were also tested. Overall yield of guideline-indicated screening was similar between USPSTF and ADA guidelines for diabetes (11% vs. 9%) and prediabetes (38% vs. 36%). Among those not meeting screening criteria, the USPSTF guideline missed more cases of diabetes (6% vs. 3%) and prediabetes (26% vs. 19%) than ADA. Even after adjustment for patient, provider, and clinic factors and accounting for clustering, there was unexplained two-fold variation in screening by clinic (Median OR 1.97; intra-class correlation 0.13). Screening rates vary widely in an integrated health system and are not fully accounted for by patient, provider, and clinic factors available in the EHR. Clinical decision support and other system level interventions are needed to optimize screening practices across clinics.

Disclosure

U.C. Obinwa: None. I. Lingvay: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., MannKind Corporation. Consultant; Self; AstraZeneca, Novo Nordisk Inc., Sanofi, TARGET PharmaSolutions, Valeritas, Inc. Research Support; Self; Merck & Co., Inc., Mylan, Novo Nordisk Inc., Pfizer Inc. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. L. Meneghini: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Sanofi-Aventis. Consultant; Self; Sanofi-Aventis. Other Relationship; Self; American Diabetes Association. E. Halm: None. M.E. Bowen: None.

Funding

National Institutes of Health (DK104065)
1506-P: Breast Cancer as a Risk Factor for New Diabetes
Authors: SHAH REEMA , GERSTEIN HERTZEL , KOMJÁTHIN SZÉPLIGETI SZIMONETTA , SÔRENSEN HENRIK T. , THOMSEN REIMAR W.
Published: June 2019

While diabetes is an important risk factor for breast cancer, less is known regarding whether a breast cancer diagnosis is associated with increased risk of subsequent diabetes. We therefore assessed the effect of a breast cancer diagnosis on incident diabetes, using population-level data from Danish healthcare registries during 2005-2016. Our study population comprised 33,909 women aged >50 years with new-onset breast cancer and 313,998 comparison cohort members matched by age and the breast cancer diagnosis date (index date) from the general population, all with no prior history of cancer or diabetes. Women with breast cancer and their comparison cohort members were followed for up to 12 years, to ascertain a first occurrence of glucose-lowering drug treatment or hospital-diagnosed diabetes. The hazard of breast cancer for subsequent diabetes was computed using Cox proportional hazard models, adjusting for a range of comorbidities and medications. Mean age at baseline was 66.0 in cancer patients and 65.8 in the comparison cohort. The rate of developing diabetes was 15% greater in breast cancer patients than in the comparison cohort during the first year after breast cancer diagnosis/index date (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.01-1.30). During total follow-up (median 5.2 years), the diabetes rate was 23% greater in women with breast cancer (aHR 1.23, 95% CI 1.16-1.30), corresponding to 8.4 new cases of diabetes per 1000 women per year vs. 6.8 among comparison cohort members. Breast cancer patients were more likely to be treated with an insulin-based regimen (4.8%) compared to comparison cohort members (2.1%). Our findings suggest that breast cancer is an important risk factor for diabetes. Breast cancer patients may benefit from targeted screening for diabetes and counseling regarding risk factor modification.

Disclosure

R. Shah: None. H. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Sanofi. S.K. Szépligeti: None. H.T. Sôrensen: None. R.W. Thomsen: None.
1511-P: Trend in the Prevalence of Diabetes between 2002-2009 in Populations in Qingdao, China
Authors: ZHANG LEI , GAO WEIGUO , WANG NA , WANG JUN , YIN XIAOYAN , ZHU YAMEI , DONG YANHU
Published: June 2019

The current study aims to determine the secular trend of prevalence of type 2 diabetes and prediabetes and risk factors for diabetes from 2002 to 2009. We conducted 3 population-based surveys for diabetes in individuals aged 35-74 years in Qingdao in 2002, 2006 and 2009, respectively, with random-sampling approach. The sample size was 1792, 4549 and 4310 in 2002, 2006 and 2009, respectively. We performed a questionnaire-based survey to collect general information. All participants underwent standardized 2-h 75-g oral glucose tolerance tests (OGTTs). The 1999 WHO diagnostic criteria for diabetes and prediabetes was applied. Age-standardized prevalence of diabetes was calculated. Multiple non-conditional logistic regression were applied to analyze the risk factors for diabetes, taking diabetes as the dependent variable. In 2002, the age-standardized prevalence of diabetes was 12.32%, the corresponding prevalence was 16.57% and 18.01%, respectively, in 2006 and 2009. The prevalence of diabetes increased from 2002 to 2009 (p<0.05). The age-standardized prevalence of prediabetes in 2002, 2006 and 2009 was 16.18%, 24.56% and 28.25%, respectively (P for trend < 0.05). Multiple non-conditional logistic regression analysis showed that the risk factor for diabetes were age, waist, systolic blood pressure (SBP), total cholesterol, triglyceride, and family history of diabetes in both 2002 and 2006. The risk factor for diabetes included age, waist, SBP, total cholesterol, triglyceride, and family history of diabetes in 2009. High density lipoprotein cholesterol was negatively associated with increased risk for diabetes. The prevalence of diabetes and prediabetes in Qingdao increases from 2002 to 2009, implying an epidemic of diabetes in this area. The common risk factors contributing to the increasing trend are age, waist, SBP, total cholesterol, triglyceride, and family history of diabetes.

Disclosure

L. Zhang: None. W. Gao: None. N. Wang: None. J. Wang: None. X. Yin: None. Y. Zhu: None. Y. Dong: None.
1523-P: Variation in Diabetes Prevalence by Sex and Weight in Middle-Aged Chinese and Filipino Adults
Authors: GU KRISTINE , GORDON NANCY P. , CHANDRA MALINI , LAU GENE , GONZALEZ JOEL R. , LO JOAN C.
Published: June 2019

Background: Contemporary data comparing weight status and diabetes (DM) prevalence among U.S. East Asians and Filipinos are limited.

Methods: Among 23,050 Chinese and 28,201 Filipinos aged 45-64 years (mean age 55±6) with a 2016 outpatient visit in a U.S. integrated healthcare delivery system, body mass index (BMI) and DM prevalence (based on clinical diagnosis and pharmacotherapy) were ascertained. BMI was classified using Asian-specific thresholds: healthy or underweight (BMI <23), overweight (23-27.4) and obese (≥27.5 kg/m2). Differences were examined by subgroups and log-binomial regression was used to examine the independent association of ethnicity and DM risk.

Results: Among Chinese women (14,871) and men (8,179) and Filipino women (18,406) and men (9,795), overweight/obesity was higher in men vs. women and Filipino vs. Chinese (Figure, BMI distribution). Obesity was highest in Filipino men (50%). DM prevalence was highest in those with obesity; however, Filipinos of both sexes had higher DM prevalence across all weight categories (Figure) compared to Chinese, with a relative risk of 1.7 (CI 1.6-1.8), adjusting for age, BMI and sex.

Conclusion: Filipino adults have substantially higher BMI and independently higher risk of DM compared to Chinese adults. While limited to adults receiving healthcare, the data highlight the need for heightened DM surveillance and targeted care in high risk ethnic populations.

Disclosure

K. Gu: None. N.P. Gordon: None. M. Chandra: None. G. Lau: None. J.R. Gonzalez: None. J.C. Lo: Research Support; Self; Amgen Inc. Research Support; Spouse/Partner; GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Sanofi-Aventis. Research Support; Self; Sanofi-Aventis.

Funding

Kaiser Permanente Northern California
1531-P: Spontaneous Ketonuria Is Associated with Reduced Incidence of Diabetes
Authors: CHO SUNG J. , LEE INKUK , LEE SANG BAE , KANG EUN SEOK , FERRANNINI ELE , LEE YONG-HO , KIM GYURI , CHA BONG-SOO
Published: June 2019

Objective: Ketones may be regarded as a thrifty fuel for peripheral tissues, but their clinical prognostic significance still remains unclear. We investigated the association between spontaneous fasting ketonuria and incident diabetes in conjunction with changes in metabolic parameters in a large population-based, observational study.

Research Design and Methods: We analyzed a total of 8,703 individuals free of diabetes at baseline in the Korean Genome and Epidemiology Study, a community-based, 12-year prospective study. Subjects with (n=195) or without fasting ketonuria were 1:4 matched by propensity score. Incident diabetes was defined as: fasting plasma glucose ≥126 mg/dL, 2-hour glucose ≥200 mg/dL on biennial 75g oral glucose tolerance test, or current antidiabetic medication. Using Cox regression models, hazard ratios for developing diabetes associated with the presence of ketonuria at baseline were analyzed.

Results: Over 12 years, of the 925 subjects in the propensity score matched cohort, 190 (20.5%) developed diabetes. The incidence rate of diabetes was significantly lower in subjects with spontaneous ketonuria compared to those without ketonuria (adjusted hazard ratio 0.64 [95% confidence interval=0.42-0.99]. This result was replicated in the whole cohort (HR 0.67 [95% CI: 0.46-0.98] after multivariate adjustment). During follow-up, subjects with ketonuria at baseline maintained lower 1-hour and 2-hour glucose levels, and a higher insulinogenic index during follow-up despite comparable baseline values.

Conclusions: The presence of spontaneous fasting ketonuria was significantly associated with a reduced incidence rate of diabetes, independently of metabolic parameters. Our findings suggest spontaneous fasting ketonuria is a stable phenotype and a novel signature in the modulation of glucose metabolism.

Disclosure

S.J. Cho: None. I. Lee: None. S. Lee: None. E. Kang: None. E. Ferrannini: None. Y. Lee: None. G. Kim: None. B. Cha: None.
1536-P: Parametric Survival Analysis of Complications from Type 1 Diabetes
Authors: BARBOSA CAROLINA , MACK NICOLE , BOBASHEV GEORGIY , KING GRANT A. , LIU YIYAN , HILSCHER RAINER , NEUWAHL SIMON , HOERGER THOMAS J.
Published: June 2019

Aim: To develop novel models of the risk of fatal and non-fatal complications for individuals with type 1 diabetes (T1D). Models used two 30 years’ follow-up studies: Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) and Epidemiology of Diabetes Complications (EDC).

Method: Models were developed for: Microalbuminuria, Macroalbuminuria, End-Stage Renal Disease, Impaired Glomerular Filtration Rate, Non-proliferative Diabetic Retinopathy, Proliferative Diabetic Retinopathy, Clinically Significant Macular Edema, Ketoacidosis, Hypoglycemia, Ulcers, Diabetic Peripheral Neuropathy, Amputations, Cardiovascular (CVD) Major Adverse Cardiac Event (MACE), CVD non-MACE, Death after CVD MACE, Death after CVD non-MACE, and Death with no history of CVD. Each model considered 44 risk factors, including demographics, time-varying clinical measures, and other T1D complications. Bivariate associations, followed by stepwise regression, were used for variable selection. Interval-censored Weibull and Gompertz survival models were chosen for non-fatal and fatal complications, respectively. Final models combined optimal statistical prediction and expert knowledge for model interpretability.

Results: All models included age, gender, diabetes duration, and HbA1C, with HbA1c significantly increasing the risk of most complications. Across all models, the highest predictor of a complication was history of another complication(s). Blood pressure (e.g., systolic, diastolic), pulse rate, and lipid variables (e.g., triglycerides, LDL, HDL, total cholesterol) were significantly predictive of most complications. Cumulative hazard plots comparing predicted and actual hazards indicated good accuracy of prediction for all models.

Conclusion: Our risk equations highlight the importance of accounting for the time-varying nature of many risk factors and the impact that history of diabetes complications has on a different complication.

Disclosure

C. Barbosa: None. N. Mack: None. G. Bobashev: None. G.A. King: None. Y. Liu: None. R. Hilscher: None. S. Neuwahl: None. T.J. Hoerger: Research Support; Self; Sanofi.

Funding

Centers for Disease Control and Prevention
154-LB: Accelerating Clinical Development of Janagliflozin, a Novel Antidiabetic Drug, Using Model-Informed Drug Development Strategy
Authors: LIU DONGYANG , SONG LING , WANG XIAOXU , LIU XU , CAO FANGRUI , LIU HONGZHONG , DING YANHUA , XIAO XINHUA , JIANG JI , HU PEI
Published: June 2019

Objectives: To accelerate clinical development of Janagliflozin (JANA), an active inhibitor of sodium-glucose cotransporter 2 (SGLT2), using model-informed drug development (MiDD) strategy.

Methods: Firstly, after receiving the SAD PK and PD (change from baseline in urinary glucose excretion, ∆UGE) profiles in healthy subjects (HS), a PK/PD model was developed and optimized by MAD data in HS. Secondly, we projected PK/∆UGEc/FPG/HbA1c profiles based on HS data using the established quantitative relationship between HS and T2DM patients, where ∆UGEc, FPG corrected ∆UGE, was a novel translational biomarker. Thirdly, the predicted PK/PD profiles were confirmed in a 2-week MAD study in T2DM patients and the dose-HbA1c relationship in T2DM patients after 6-month treatment was predicted.

Results: The predicted PK/PD profiles of JANA in T2DM patients were within 2-fold of the observed data. Prediction performance was showed in Figure 1 and a Phase III trial was allowed after the 2-week MAD study.

Conclusion: This MiDD strategy exhibited a good capability to accelerate early phase clinical development of JANA after confirmation from short-term clinical trials.

Disclosure

D. Liu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. L. Song: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. X. Wang: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. X. Liu: Research Support; Self; XuanZhu Pharma Co.Ltd,Jinan,Shandong,China. F. Cao: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. H. Liu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. Y. Ding: None. X. Xiao: None. J. Jiang: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. P. Hu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China.

Funding

XuanZhu Pharma Co., Ltd.
1543-P: Trends in U.S. Diabetes Care Management, 1999-2016
Authors: MERCADO CARLA , BULLARD KAI M. , ALI MOHAMMED K. , IMPERATORE GIUSEPPINA , SAYDAH SHARON , GREGG EDWARD
Published: June 2019

Clinical guidelines and national programs recommend control of ABCS risk factors [glycohemoglobin (A1c), Blood pressure, Cholesterol, and Smoking] to reduce diabetes-related comorbidities and mortality. We investigated changes in meeting the ABCS goals (A1c <8.0%, blood pressure (BP) <140/90 mmHg, non-HDL cholesterol <160 mg/dL, and current non-smoker) among U.S. adults with diagnosed diabetes (DM). Proportion and changes of adults aged ≥18 years with DM and who met each and all ABCS goals were estimated using data on 5,534 participants from the National Health and Nutrition Examination Survey, 1999-2016. In U.S. adults with DM from 1999-2004 to 2011-2016, there was an increase in the proportion meeting the goals of: BP (67% to 73%, p=0.003), non-HDL cholesterol (59% to 77%, p<0.001), and current non-smoking (74% to 81%, p<0.001). However, meeting the A1c goal increased (p=0.001) from 70% in 1999-2004 to 78% in 2005-2010 then decreased (p=0.004) to 71% in 2011-2016 (A1c goal 1999-2004 versus 2011-2016, p=0.53). The proportion of adults with diabetes meeting all four ABCS risk factors goals significantly increased from 18% in 1999-2004 to 32% in 2011-2016 (p<0.001). Control of risk factors for DM complications has improved during 1999-2016 with about a 15% point increase of U.S. adults with DM meeting all four ABCS risk factors goals. Thus, long-term improvements in ABCS appear to be continuing with the exception of A1c levels.

Disclosure

C. Mercado: None. K.M. Bullard: None. M.K. Ali: None. G. Imperatore: None. S. Saydah: None. E. Gregg: None.