bluuebunny/crossref_metadata_2025 huggingface dataset:
1464-P: Optimal Blood Pressure Goals for Cardiovascular Health in Individuals with Type 1 Diabetes
Authors: GUO JINGCHUAN , MILLER RACHEL G. , COSTACOU TINA , ORCHARD TREVOR J.
Published: June 2019

The study was aimed to determine optimal blood pressure (BP) goals for minimizing coronary artery disease (CAD) risk in adults with childhood-onset type 1 diabetes (T1D). The Pittsburgh Epidemiology of Diabetes Complications study participants without known baseline CAD (n=605) were recruited and then followed for 25 years. The associations of time-updated cumulative (mmHg-year) and time-weighted (mmHg) BP measures (systolic [SBP], diastolic [DBP], and mean artery pressure [MAP]) with incident CAD were examined using Cox proportional hazard models. Sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) were summarized by different cut-points of time-weighted BPs. Risk stratification analyses were then undertaken based on time-weighted BP (< vs. ≥ 120/80 mmHg) and time-weighted HbA1c (< vs. ≥ 8%). All time-updated cumulative BP measures independently predicted incident CAD over the follow-up period. A dose-gradient association was observed for categorized time-weighted SBP, DBP and MAP in their association with CAD risk. According to both Cox models and AUCs, the optimal cut-points for SBP, DBP and MAP were approximately 120, 80 and 90 mmHg, respectively. Participants with a BP ≥120/80 mmHg, compared to <120/80 mmHg, were associated with 1.9 (95% CI: 1.4, 2.6) times greater risk of developing CAD. Compared to participants with good control of both BP (<120/80 mmHg) and HbA1c (<8%), the high BP only group (HR: 2.0 [1.1, 3.9]) carried a similar risk as compared to high HbA1c only group (HR: 1.6 [0.97, 2.8]). These findings support that lower BP goals (i.e., 120/80 mmHg) than 2018 ADA recommendations (140/90 mmHg) may be needed for young adults with T1D. Lowering BP may further reduce cardiovascular risk in addition to maintaining good glycemic control in these individuals.

Disclosure

J. Guo: None. R.G. Miller: None. T. Costacou: None. T.J. Orchard: Consultant; Self; Boehringer Ingelheim International GmbH.

Funding

National Institutes of Health
1470-P: EHR-Based vs. Population-Based CVD Risk Predictions for Diabetes Patients
Authors: ZHONG JUDY , BLAUM CAROLINE , YU JAEHONG , FERRIS ROSIE , HA JINKYUNG , XIA YUHE , KABETO MOHAMMED , CIGOLLE CHRISTINE
Published: June 2019

Electronic health records (EHR) are an increasingly common data source for studying disease risks, having large sample sizes and frequently sampled clinical predictors/outcomes. In contrast to population-based cohorts, EHRs are not population-representative random samples, as subjects tend to be sicker, with higher healthcare utilization. We compared risk predictions of the same outcome (time to incident CVD) in the same population of interest (DM2 patients >50 years) using 2 data sources: waves 1993-2014 of the nationally representative Health and Retirement Survey (HRS) and 2009-2017 New Langone Health Epic data. In each dataset, we estimated the incidence rate (IR) of subsequent CVD in DM2 patients and adjusted hazard ratios (HR) of CVD risk factors using the Cox-regression model. The HRS sample included 2,739, of whom 423 developed CVD. The NYU-Epic sample included 9,179, of whom 1,264 developed CVD. The estimated subsequent CVD IRs were 28.5 (95% CI: 25.9-31.3) (HRS) and 67.1 (95% CI: 63.5-90.9) (NYU-Epic) per 1,000 person-years since DM2 onset. HR estimates were comparable between the datasets for most demographic covariates/biomarkers (Table). Our findings showed that the EHR sample was enriched with a higher proportion of sicker DM2 patients. Our study supports EHR use in DM2 research: EHR-based HR estimates of CVD risk factors have promise to be population-generalizable despite higher CVD IRs in the EHR samples.

Disclosure

J. Zhong: None. C. Blaum: None. J. Yu: None. R. Ferris: None. J. Ha: None. Y. Xia: None. M. Kabeto: None. C. Cigolle: None.

Funding

National Institute on Aging
1471-P: Visceral and Subcutaneous Adipose Tissue Attenuation Differs by Type 1 and Type 2 Diabetes Status
Authors: KESHAWARZ AMENA , ALMAN AMY C. , LOW WANG CECILIA C. , MITCHELL STACEY , SCHAUER IRENE E. , REUSCH JANE E.B. , REGENSTEINER JUDITH G. , SNELL-BERGEON JANET K.
Published: June 2019

Adipose tissue (AT) volume and quality may contribute to cardiovascular risk. AT volume and attenuation can be derived from computed tomography (CT) scans, with greater attenuation indicating poor AT quality and increased fibrosis. We examined whether AT quantity and quality were associated with coronary artery calcium (CAC) in a sample of adults without diabetes (non-DM), with type 1 diabetes (T1D), and with type 2 diabetes (T2D).

294 non-DM adults (mean age±SD 55±9 years), 226 adults with T1D (mean age±SD 52±9 years), and 52 adults with T2D (mean age±SD 53±9 years) completed CT scans for CAC measurement and abdominal CT scans at lumbar 4-5 for visceral (VAT) and subcutaneous (SAT) AT volume and attenuation measurement.

Adults with T2D had significantly more VAT and SAT when adjusting for age and sex compared with T1D and non-DM adults, but after adjusting for BMI there was no difference in VAT volume by diabetes status. Adults with T2D had significantly lower SAT volume when adjusted for BMI as compared with both non-DM and T1D adults (157 cm3 vs. 177 cm3 and 183 cm3, p=0.0008). Adults with T1D had significantly higher SAT attenuation as compared with non-DM and T2D adults (p<0.0001 for both). Square root-transformed CAC volume was significantly higher in both T1D (mean volume±SD 10.4±14.7) and T2D (mean volume±SD 9.6±15.9) compared to non-DM adults (mean volume±SD 4.5±8.2). Greater attenuation of VAT and SAT was associated with increased CAC (p=0.03 for both), but there was no association between AT volume and CAC in this sample.

AT attenuation was significantly higher in T1D and independently associated with subclinical atherosclerosis in a sample of non-DM, T1D, and T2D adults. AT fibrosis is associated with metabolic dysfunction, decreased angiogenesis, and increased inflammation; our results suggest that despite similar AT volume, T1D adults have adverse fat quality that may indicate fibrosis. This may be a mechanism through which T1D is associated with greater levels of CAC.

Disclosure

A. Keshawarz: None. A.C. Alman: None. C.C. Low Wang: Advisory Panel; Spouse/Partner; Bayer Healthcare, LLC, CSL Behring, Genentech/Roche, Hema Biologics, Novo Nordisk Pharmaceuticals, Inc, Octapharma Pharmazeutika, Shire. Speaker's Bureau; Self; Medical Education Resources. S. Mitchell: None. I.E. Schauer: Other Relationship; Spouse/Partner; Kestrel Labs. J.E.B. Reusch: Board Member; Self; American Diabetes Association. Other Relationship; Self; Merck & Co., Inc. J.G. Regensteiner: None. J.K. Snell-Bergeon: None.

Funding

American Diabetes Association (7-13-CD-10 to J.K.S-B.)
1476-P: Comparison of Cardiovascular Risk Factors between Type 1 and Type 2 Diabetes
Authors: MOSSLEMI MITRA , PARK HANNAH L. , MCLAREN CHRISTINE E. , WONG NATHAN D.
Published: June 2019

The incidences of both T1D and T2D are increasing in the U.S., and CVD is the leading cause of death among both cohorts. Despite differences in the underlying pathophysiology of T1D and T2D, CVD prevention approaches for T1D have been widely extrapolated from T2D studies. A few prior studies have compared CVD incidence and mortality rates between patients with T1D and T2D; however, a comparison of CVD risk factors between T1D and T2D within the same study cohort, as a measure of differences in progression to CVD events, has not been done. We thus compared CVD risk factors between patients with T1D and T2D, among U.S. adults (≥age 20) with self-reported diabetes from NHANES 1999-2016. First, we classified diabetes cases (n=5347) into T1D (n=230) and T2D (n=4677) using a treatment-based approach we developed, regardless of age at diagnosis (n=440 excluded as unassigned). Next, we compared the demographics, classical CVD risk factors and diabetes-related risk factors by diabetes type using bivariate analysis, and stepwise model selection. The final model comprised race, age, education, diabetes duration, triglycerides, CKD, BMI, and HbA1c [Table]. The similarity between the final model and the bivariate association results, suggests that differences in CVD risk factors between T1D and T2D are mainly due to the underlying pathophysiology and cannot merely be explained by demographic and diabetes-related differences between the two types.

Disclosure

M. Mosslemi: None. H.L. Park: None. C.E. McLaren: None. 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.
1484-P: Association between Bariatric Surgery and Cardiovascular Events, Mortality, and Glycemic Control among Diabetes Patients: Evidence from a Large EMR Network
Authors: KURANZ SETH
Published: June 2019

Introduction: Studies show that cardiovascular (CV) risk among patients with type 2 diabetes (T2D) and obesity is not always well managed by lifestyle changes. The following study used RWD to examine the effect of bariatric surgery (BS) on CV outcomes and glycemic control (GC) among high risk T2D patients.

Methods: In a 1:1 matched propensity score (PS) analysis using the TriNetX database, a federated EMR network representing over 40M patients, T2D patients undergoing BS were compared to T2D patients who were not. Definitions were based on ICD9/10, CPT, RxNorm, and LOINC codes. Patients aged 18-90 were required to have two T2D diagnosis codes 6 months apart, no type 1 diabetes, and a BMI ≥ 30 kg/m2 in the year prior to the index event (IE). The IE was defined by the first BS code in the treated group and the first RxNorm or CPT code in the comparison group. Outcomes of interest were a combined CV event (stroke, MI, or angina) and overall survival (OS). GC (HbA1c < 6.5%) was examined among patients with a HbA1c greater than 9% at baseline. Risk ratios (RR; 95% CIs) and KM curves were calculated for each outcome.

Results: In two matched cohorts of 2,972 patients each, a standardized mean difference of <10% was observed for all variables used to calculate the PS. At the time of the IE, patients were 51 (11) and 50 (13) years old, 69% and 68% female, and 62% and 64% white in the BS and comparison groups, respectively. Patients undergoing BS were 60% (70-50%) less likely to experience a CV event (n = 65 events and 173 events, respectively). The 5-year OS was 97% compared to 94% (p<0.01). In a matched subsample of 904 patients with a HbA1c of > 9% in the year prior to the IE, patients undergoing BS were 3.6 (2.4-5.5) times more likely to achieve a HbA1c of < 6.5 in the 12-18 months after the IE.

Conclusion: This analysis provides RWE to support a growing body of literature that BS reduces the risk of CV events and mortality, and increase glycemic control, among high risk T2D patients.

Disclosure

S. Kuranz: Employee; Self; TriNetX, Inc.
1487-P: Comparison of the Framingham Risk Score, SCORE, and UKPDS Risk Engine for Predicting Cardiovascular Disease Complications in People with Diabetes
Authors: HO JOYCE C. , STAIMEZ LISA R. , NARAYAN K.M. VENKAT , SIMPSON ROY L. , HERTZBERG VICKI S.
Published: June 2019

The epidemiology of cardiovascular disease (CVD) complications in people with diabetes is changing with the increasing prevalence of presentations other than coronary heart disease (CHD) (e.g., heart failure (HF), cardiomyopathy (CM)). Existing CVD risk estimators such as the Framingham Risk Score (FRS), SCORE, and UKPDS Risk Engine primarily assess CHD risk. Our goal was to assess the prediction accuracy of HF and CM from these risk equations.

We evaluated FRS, SCORE, and UKPDS to predict 1-year risk of CHD, HF, and CM from electronic health records of 469 diabetes patients seen at Emory Healthcare. Only adults without a prior history of CVD at baseline were included. A patient was denoted as a case if s/he had a subsequent ICD-9 code of HF, CHD, or CM at the next visit within a year, and if not, s/he was denoted as a control. We calculated the C-statistic of each score for each disease type.

Our population had an average age of 71 with 47% females and 58% Caucasian. CHD, HF, and CM annual incidence rates were 54%, 44%, and 38%, respectively. Across FRS, SCORE, and UKPDS, CHD had the highest C-statistic (0.589-0.608) with HF the next highest (0.547-0.578). CM (0.369-0.426) performed worse than chance. Moreover, UKPDS performed the best across the three CVD complications. These results suggest that CVD risk estimators need to be calibrated for variations in disease presentation.

Disclosure

J.C. Ho: None. L.R. Staimez: None. K. Narayan: None. R.L. Simpson: None. V.S. Hertzberg: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024); National Library of Medicine (1K01LM012924-01)
1488-P: HbA1c and Potential Misclassification of Diabetes and Prediabetes Diagnoses in the U.S.
Authors: STAIMEZ LISA R. , KIPLING LAUREN , FORD CHRISTOPHER N. , HAM J. NINA , RHEE MARY K. , PHILLIPS LAWRENCE S.
Published: June 2019

HbA1c levels are widely used for diabetes diagnosis and management but may misrepresent underlying glucose levels. To assess potential misdiagnoses of diabetes (T2DM) and prediabetes (PreDM) by HbA1c, we examined representative samples of non-pregnant adults and youth in the National Health and Nutrition Examination Survey (NHANES), 2005-2016, who had a 75g OGTT. Normal glucose metabolism (NGM), PreDM, and T2DM were defined by ADA criteria. For each glycemic group, a linear regression model of HbA1c vs. glucose (i.e., mean of FPG and 2hrPG) yielded predicted HbA1c for each participant. The Hemoglobin Glycation Index (HGI), defined as observed - predicted HbA1c, was partitioned into tertiles. Of 10,737 adults aged 18-79 year (representing N=199,270,935), 52% female and 10% non-Hispanic black, with mean age 43.7 year and BMI 28.5 kg/m2. By OGTT criteria, 81.2% had NGM, 14.1% PreDM, and 4.6% T2DM. The high HGI tertile had a higher proportion of non-Hispanic black race (17.7%, vs. middle 8.7%, low 7.0%), as well as higher mean BMI and age, all p<0.0001. A higher proportion of black race in the high HGI tertile was also found in adults >65 year (p=0.0016, weighted N=24,142,366) and youth aged 12-17 year (p<0.0001, n=2,218, weighted N=25,302,585). Across HGI tertiles, the distribution among diagnostic categories was similar by OGTT criteria, but differed by HbA1c criteria; those in the high HGI tertile were 53.7% PreDM and 3.5% T2DM - mostly abnormal, while those in the low HGI tertile were 98.0% NGM and 1.0% PreDM - mostly normal, with a similar pattern in older adults and youth, all p<0.0001. Across all age groups, 15% (weighted N=33,569,933) had clinically significant HGI deviations of >0.5%.

Conclusion: Diagnostic classification by HbA1c alone could lead to misdiagnosis in over 33 million Americans, a problem across all age groups. Overdiagnosis is a particular risk in those with black race, higher BMI, and older age. Complementing HbA1c with glucose testing should improve diagnostic classification and management.

Disclosure

L.R. Staimez: None. L. Kipling: None. C.N. Ford: None. J. Ham: None. M.K. Rhee: None. L.S. Phillips: Advisory Panel; Self; Janssen Pharmaceuticals, Inc. Research Support; Self; AbbVie Inc., GlaxoSmithKline plc., Kowa Pharmaceutical Europe Co. Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc. Stock/Shareholder; Self; Diasyst Inc. Other Relationship; Self; Diasyst Inc., Janssen Pharmaceuticals, Inc.
1495-P: Distance to Glycemic Target of Patients (Pts) with Type 2 Diabetes (T2D) and Established Cardiovascular Disease (eCVD) and/or Chronic Kidney Disease (CKD) Failing Metformin Monotherapy in the U.S.
Authors: FERNANDES GAIL , SAWHNEY BAANIE , HANNACHI HAKIMA , WANG TONGTONG , MCNEILL ANN MARIE , IGLAY KRISTY , RAJPATHAK SWAPNIL
Published: June 2019

Previous studies have shown that a large proportion of pts with T2D are not at glycemic target, but the distance to target is not well characterized, including among high risk patients such as those with eCVD/CKD. The objective of the study was to assess the distance to glycemic target by eCVD/CKD status. This retrospective study using GE Centricity Electronic Medical Record database (2016 data) included adult T2D pts on metformin monotherapy with ≥12 months of enrollment prior to index date (initiation of metformin) and prescribed an add-on agent. Distance to target was calculated as median difference from 3 HbA1c targets: <7%, <7.5% and <8%. Of the 1741 included pts, mean age was 57 years, 49% were female, 25% had eCVD/CKD. Table shows the distance to glycemic targets by eCVD/CKD status. Median difference from target ranged from 0.2%-1.2% depending on the specified threshold. 44.6%, 33.6% and 25.6% of pts were ≥1.5% away from targets of 7%, 7.5% and 8%, respectively, at time of add-on therapy. Difference from target and proportion of pts ≥1.5% from target was even higher for those without compared to with eCVD/CKD.

In conclusion, a significant proportion of pts on metformin are more than 1.0% away from glycemic targets at the time of intensification and those without eCVD/CKD are likely to be intensified at much higher HbA1c.

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.
1499-P: Apolipoprotein C-III as a Novel Predictor for T2D Incidence in Amerindians
Authors: HSUEH WEN-CHI , WALTER MARY , NELSON ROBERT , KNOWLER WILLIAM C. , HANSON ROBERT L.
Published: June 2019

Amerindians, particularly Pima Indians, are at high risk for type 2 diabetes (T2D). Our previous studies have shown that lipid levels (high triglycerides or TG, and low HDL-cholesterol, or HDL-C) are important predictors of T2D incidence. There are few data on the extent to which apolipoprotein levels, particularly apolipoprotein CIII (apoC-III), which is a potential therapeutic target to treat high TG, predict T2D. Thus, we examined whether circulating apolipoprotein levels predict T2D risk in addition to known risk factors. We measured serum TG, HDL-C and 5 apolipoprotein levels (apoA-I, apoA-V, apoB100, apoC-III, apoE), in 1,916 nondiabetic Pima Indians at baseline (mean age=31.2±10 years, 43% male). After mean follow-up of 6.26 years, ∼24% of subjects (n=454) developed T2D.

BMI, HDL-C and TG predicted T2D, when adjusted for sex and age (hazard ratio [HR] per s.d. unit was 1.05, 0.74 and 1.18, respectively; all p<0.0005). TG had moderate correlation with apoC-III (r=0.68), apoE (r=0.56) and HDL-C (r=-0.31). With adjustment for age and sex, only apoA-V predicted T2D incidence (HR=1.12 P=0.02). When effects of BMI, HDL-C, TG and each one of 5 apoliproteins were evaluated together, the apoA-V effect was attenuated (HR=1.09, p=0.08). However, higher apoC-III was protective for T2D incidence (HR for apoC-III=0.83, p=0.007; HR=1.43, 0.87, and 1.29 for BMI, HDL-C, and TG, respectively, all p<0.05). Formal significance testing for apoC-III effect showed that it has distinct predictive value for T2D incidence in addition to TG (0.008). As TG and apoC-III are positively correlated, apoC-III may be a risk factor for T2D. However, our findings suggest that, controlled for BMI, TG and HDL-C levels, apoA-I, apoA-V, apoB100 and apoE add little information about T2D risk prediction, whereas higher apoC-III is associated with reduced T2D risk. The mechanisms underlying this association are not presently known.

Disclosure

W. Hsueh: None. M. Walter: None. R. Nelson: None. W.C. Knowler: None. R.L. Hanson: None.

Funding

National Institutes of Health
15-OR: Renal Outcomes from the DECLARE-TIMI 58 Trial: Quantifying the Health-Care Implications
Authors: MCEWAN PHILIP , KARTMAN BERNT , BENNETT HAYLEY , EDMONDS CHRISTOPHER , GAUSE-NILSSON INGRID ANNA
Published: June 2019

Chronic kidney disease (CKD) and end stage renal disease (ESRD) pose a significant global health burden. Approximately 40% of people with type 2 diabetes develop CKD. The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial showed a reduced rate of the composite endpoint of sustained decrease of ≥40% in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73m2, ESRD, or renal death when comparing dapagliflozin (DAPA) to placebo (PBO) (hazard ratio 0.53; 95% CI 0.43, 0.66). This study aimed to quantify the implications of renal outcomes from DECLARE-TIMI 58, in terms of direct healthcare costs and resource use. DECLARE-TIMI 58 event rates were used to characterize expected numbers of patients experiencing sustained decrease of ≥40% in eGFR to <60 mL/min/1.73m2 (‘CKD progression’) or ESRD, per 1,000 patients over a 4-year time horizon. Renal replacement therapy (RRT) was assumed following the incidence of ESRD events only and the distribution of RRT modalities based on U.S. Renal Data. Published annual U.S. costs (2017 $) of ESRD and excess healthcare associated with CKD stage 3 versus CKD stage 2 were applied and discounted at 3% annually. Per 1,000 patients, PBO was associated with 25.6 CKD progression events and 2.4 ESRD events over four years, while DAPA was associated with 11.8 (-46%) and 1.6 (-67%) fewer events, respectively. Consequently, over 4 years DAPA was estimated to avoid 1,126 days of RRT per 1,000 patients, of which over 70% relate to a need for dialysis. The estimated cost of CKD progression and ESRD associated with PBO was $460,277 per 1,000 patients over 4 years, while costs associated with DAPA were an estimated $285,444 lower (-62% versus PBO). Economic modelling utilizing renal outcomes data from DECLARE-TIMI 58 indicate that treatment with DAPA may translate into renal cost savings within a short-term horizon. Potential delays to ESRD may have a more profound impact on patients’ quality of life, cost savings, and service delivery over the longer-term.

Disclosure

P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. B. Kartman: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. C. Edmonds: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca.

Funding

AstraZeneca
150-LB: Software Modeling of Dorzagliatin for Artificial Intelligence Management of Type 2 Diabetes
Authors: ALLEN SYDNEY , BENNETT BRITTANY , EILERMAN BRADLEY , TESTA LEONARD J.
Published: June 2019

Introduction: The use of Artificial Intelligence to make clinical decisions is a strategy of increasing interest to improve the cost and effectiveness of diabetes management. GlucosePATH is software which uses massively parallel processing to sort through millions of possible combinations to medications specified to patient specific variables. As new medicine classes become available, the baseline characteristic of the medication must be defined. As dorzagliatin enters phase 3 trials, modeling the pharmacologic properties of the molecule will represent the first example of the glucokinase activator class.

Methods: The first step in drug modeling defines the base characteristics of the molecule. Dorzagliatin is modeled mechanistically as a glucokinase activator which acts as a secretagog. This preventins mechanistic overlap and allows for modification of efficacy based on projected beta cell reserve. A dose of 75 mg daily was selected as it was the most efficacious dose in the phase 3 monotherapy trial.

The next step in drug modeling is defining the clinical characteristics of the drug. At the dose defined, dorzagliatin is modeled with a HgA1c reduction of 1.2. This is modeled on the phase 3 monotherapy Weight change and hypoglycemia were modeled as neutral. The only adverse event of significance which was modeled was a mild penalty for fatty infiltration of the liver. All of these characteristics were drawn from the composites of phases 1 through 3 available on literature review.

Results: Medications available in the market are described in terms of cost and insurance coverage. For the purpose of modeling dorzagilatin in a population, a cost of $300 monthly was entered as the low end of a new to market diabetes medication. Modeled on a population of 366 patients in the GlucosePATH database, the medicine was recommended in 4 patients. No significance difference between control and study population in mean HgA1c (both 7.3), cost ($629.99 vs. $629.79), or composite score out of 100 (82.65 vs. 82.64).

Disclosure

S. Allen: None. B. Bennett: None. B. Eilerman: Advisory Panel; Self; Dexcom, Inc., Medtronic. Speaker’s Bureau; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Corcept Therapeutics, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc. Stock/Shareholder; Self; PATH Decision Support Software LLC. L.J. Testa: Stock/Shareholder; Self; PATH Decision Support Software LLC.
1504-P: Low Normal Free Thyroxine Levels Are Associated with Prediabetes in Euthyroid Subjects
Authors: KIM SUNG-WOO , JEON EONJU , LEE JI-HYUN , SHON HO-SANG , PARK KEUN-GYU
Published: June 2019

Background: Although the association between low-normal thyroid function and metabolic syndrome was well documented, little is known about the effect of thyroid hormone within the physiological range on carbohydrate metabolism. This study aimed to determine whether free thyroxine (FT4) influences serum glucose concentration and the prevalence of prediabetes in euthyroid subjects.

Methods: This was a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 4,767 participants of >20 years of age who were euthyroid and nondiabetic.

Results: Prediabetic participants had lower FT4 concentrations than those without prediabetes, but thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, HbA1c levels significantly decreased with FT4 tertile, whereas FBG was not associated with FT4 both in men and in women. The prevalence of prediabetes was significantly higher in T1 than in T3.

Conclusion: Subjects with low-normal serum FT4 had high HbA1c and were more likely to have the prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes, even though thyroid function is within the normal range. Thus, screening for prediabetes in subjects with low-normal FT4 should involve the measurement of HbA1c.

Disclosure

S. Kim: None. E. Jeon: None. J. Lee: None. H. Shon: None. K. Park: None.
1507-P: Baseline Metabolite Profiles of Incident Type 2 Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program (DPP)
Authors: CHEN ZSU-ZSU , LIU JINXI , MORNINGSTAR JORDAN , HECKMAN-STODDARD BRANDY M. , LEE CHRISTINE , DAGOGO-JACK SAMUEL , FERGUSON JANE F. , HAMMAN RICHARD F. , KNOWLER WILLIAM C. , MATHER KIEREN J. , PERREAULT LEIGH , FLOREZ JOSE C. , WANG THOMAS , CLISH CLARY B. , TEMPROSA MARINELLA , GERSZTEN ROBERT E. ,   DPP RESEARCH GROUP
Published: June 2019

Novel biomarkers of T2D and preventative treatment response could predict outcomes in high-risk individuals. We used Cox models to assess the association of 334 profiled metabolites in 2,019 baseline plasma samples with incident T2D after 3.2 years in a DPP substudy. We further assessed if associations out of the 334 metabolites differed by treatment (lifestyle (ILS), metformin (MET), and placebo (PLA)) and if, after stratification into concentration quartiles, the metabolite levels modified treatment effect in pair-wise treatment comparisons. We found 69 metabolites associated with incident T2D in the entire cohort (FDR-q<0.05) including the novel association of cytosine, which had the lowest risk (HR of 0.77 per 1 SD, 95% CI 0.67-0.89, FDR-q 0.008). The associations of 35 metabolites differed across the three treatments (p for homogeneity <0.05) and the quartiles of several of these metabolites modified treatment effects in pair-wise comparisons (Table 1). For example, individuals in higher quartiles of specific phospholipids had decreased T2D risk with ILS compared to PLA and MET, but not with MET when compared to PLA.

In conclusion, we identified baseline metabolites associated with T2D risk prediction and efficacy of prevention interventions. This motivates further studies to validate interactions between biomarkers and diabetes prevention strategies.

Disclosure

Z. Chen: None. J. Liu: None. J. Morningstar: None. B.M. Heckman-Stoddard: None. C. Lee: None. S. Dagogo-Jack: Board Member; Self; Jana Care Inc. Consultant; Self; Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Stock/Shareholder; Self; Dance Biopharm Holdings Inc. J.F. Ferguson: None. R.F. Hamman: None. W.C. Knowler: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. L. Perreault: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. J.C. Florez: None. T. Wang: None. C.B. Clish: None. M. Temprosa: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Other Relationship; Self; Merck KGaA. R.E. Gerszten: None. DPP Research Group: None.
1508-P: Trends in Treatment Initiation and Management of Type 2 Diabetes Mellitus: Analysis of 20 Years of Real-World Data
Authors: COHEN CHELI MELZER , SHALEV VARDA , CHODICK GABRIEL
Published: June 2019

In the past 20 years, significant updates in diabetes management guidelines were performed. In this study we aimed to evaluate long-term trends in the treatment initiation and management of type 2 diabetes mellitus (T2DM). In this retrospective study, a computerized clinical database from Maccabi Healthcare Services, a 2.3 million member in Israel, was used. Included were adults T2DM patients who initiated antihyperglycemic medication between 1999 and 2018 (N=153,168). Fasting plasma glucose (FPG) and HbA1c levels were evaluated at treatment initiation and after 6, 12 and 24 months. In addition, first and second line treatment regimen were examined. Over twenty years of observation, FPG at therapy initiation decreased from 167.3±68.7 mg/dl (mean±SD) in 1999-2002 to 136.1±53.6 mg/dl in 2015-2018 (Figure). The respective decrement in HbA1c was from 7.8±2.1% to 6.8±1.8%. There was a tremendous difference in treatment regimen: In 1999-2002, metformin and sulfonylurea were the leading first line medications (63.5% and 37.0%, respectively) while in 2015-2018, the leading first line medications were metformin and DPP-4i (94.2% and 9.9% of patients, respectively). Study result indicate a clear trend of initiating antidiabetic treatment at lower FPG and HbA1c levels, and the fast disappearance of sulfonylurea from the clinical practice.

Disclosure

C. Melzer Cohen: None. V. Shalev: None. G. Chodick: None.
151-LB: High Risk of Krebs Von Den Lungen-6 (kL-6) Elevation when Dipeptidyl Peptidase-4 Inhibitors and Amiodarone Are Prescribed Simultaneously
Authors: OKADA JUNICHI , OKADA SHUICHI , YAMADA MASANOBU
Published: June 2019

Amiodarone-caused pulmonary toxicity including interstitial lung diseases is a well-known side effect and its incidence was reported as approximately 5.7%. Also, dipeptidyl peptidase-4 inhibitors (DPP-4is) recently attracted physicians’ attention as a cause of drug-induced interstitial lung diseases. On the other hand, there must be patients who are prescribed both DPP-4is and amiodarone simultaneously. In this case, they might have an increased risk for interstitial lung disease. Given the lack of clarity regarding the risk for drug induced interstitial lung disease under the combination therapy of DPP-4is and amiodarone, we estimated serum Krebs von den Lungen-6 (KL-6) levels in patients who were prescribed amiodarone without DPP-4is, DPP-4is without amiodarone, and both DPP-4is and amiodarone simultaneously. 47 patients were prescribed amiodarone without DPP-4is (amiodarone group). 44 patients were prescribed DPP-4is without amiodarone (DPP-4is group). 15 patients were prescribed both amiodarone and DPP-4is (DPP-4is and amiodarone group). Elevation in KL-6 levels beyond the upper limit of normal range (reference range; <500 U/mL) was observed in 3 patients in the amiodarone group, 3 patients in DPP-4is group, and 3 patients in DPP-4is and amiodarone group respectively. Thus, the frequency of KL-6 levels beyond the upper limit of normal range in amiodarone group was 6.4%, 6.8% in DPP-4is group, but 20% in DPP-4is and amiodarone group respectively. We confirmed that KL-6 levels were in the normal range before initiating DPP-4is and/or amiodarone administration. Moreover, KL-6 levels were transiently elevated and normalized within one year after DPP-4is and/or amiodarone termination. All of participated patients showed normal study on chest X-ray examination through the observation period. Thus, when physicians prescribe DPP-4is, physicians should probably concern whether patients are prescribed amiodarone.

Disclosure

J. Okada: None. S. Okada: None. M. Yamada: None.
1516-P: A Comparison of the Contributions of Impaired Insulin Secretion and Insulin Resistance to the Development of Type 2 Diabetes in a Japanese Community: The Hisayama Study
Authors: YOSHINARI MASAHITO , HIRAKAWA YOICHIRO , HATA JUN , HIGASHIOKA MAYU , HONDA TAKANORI , YOSHIDA DAIGO , MUKAI NAOKO , NAKAMURA UDAI , KITAZONO TAKANARI , NINOMIYA TOSHIHARU
Published: June 2019

Objective: Impaired insulin secretion (IIS) and insulin resistance (IR) are the two main mechanisms for type 2 diabetes (T2D), but IIS has been reported to contribute to incident T2D more than IR in Asian populations. However, we assumed that the impact of IR on the incident T2D was being greater in the recent Japanese population, because the burden of obesity increased. Herein, we addressed the magnitude of the contribution of IIS and IR to the development of T2D in a Japanese community.

Methods: In 2007, a total of 2,108 residents aged 40-79 years (participation rate 77.1%) without diabetes at baseline underwent health examination including 75g OGTT, insulinogenic index (IGI), and HOMA-IR. Subjects were divided into 4 groups according to the presence or absence of IIS (IGI ≤ 0.4) and IR (1.6 ≤ HOMA-IR) and were followed-up prospectively for a median of 6.9 years. A Cox’s proportional hazards model was used to estimate the hazard ratios and 95% confidential intervals (CIs) for incident T2D with adjustment for confounders. The population attributable fraction (PAF) for the development of diabetes due to IS, IR and their combination were calculated.

Result: At baseline, the proportions of subjects with neither of IIS nor IR, isolated IIS, isolated IR, and both IIS and IR were 45.5%, 21.0%, 28.7%, and 4.8%, respectively. During follow-up period, 273 subjects developed T2D. The risk of incident T2D was 5.3 (95% CI 3.6-7.9) times higher in subjects with isolated IIS, 4.1 (2.8-6.2) times higher in subjects with isolated IR, and 13.5 (8.5-21.5) times higher in subjects with both IIS and IR than subjects with neither of IIS nor IR. The PAFs on the excess risk of T2D among subjects with isolated IIS, isolated IR and both IIS and IR were 25.8%, 29.1%, and 15.9%, respectively.

Conclusion: Our finding suggests that IIS and IR contributed equally to the development of T2D in the recent general Japanese population.

Disclosure

M. Yoshinari: None. Y. Hirakawa: None. J. Hata: None. M. Higashioka: None. T. Honda: None. D. Yoshida: None. N. Mukai: None. U. Nakamura: None. T. Kitazono: None. T. Ninomiya: Research Support; Self; Asahi Kasei Corporation, Denka Company Limited, DeSC Healthcare, Inc, Mochida Pharmaceutical Co., Ltd., Suntory Beverage & Food Limited, Sysmex Corporation.
1520-P: All-Cause Mortality in Chinese Adults with Diabetes in Association with New Indicator Generated by the 2-h Plasma Glucose Level Subtract Fasting Plasma Glucose Level
Authors: ZHAO ZHENPING , ZHANG MEI , QI JINLEI , ZHANG XIAO , LIU YUNNING , WANG LIJUN , ZHOU MAIGENG , WANG LIMIN ,   CCDRF WORKING GROUP
Published: June 2019

Background and Aims: Reducing the increased risk of death among diabetes patients is highly valued in regard to quality care of diabetes. We aim to identify practical indicator to estimate the hazard of all-cause mortality for Chinese population with diabetes.

Method: The Chinese Chronic Disease and Risk Factor Surveillance 2010 (CCDRF) selected a national representative sample of Chinese population aged ≥18 years using a multistage sampling design. CCDRF included a mortality follow-up by December 2018. A retrospective cohort of 10,388 Chinese subjects who diagnosed as diabetes was selected. Indicator ‘2hPG-FBG’ was created using 2-h Plasma Glucose Level (2hPG) of the OGTT subtract fasting plasma glucose (FBG) level for each individual. Subjects were classified into four groups (2hPG-FBG <=0, 0-4, 4-10, and >10 mmol/l). The Kaplan-Meier curve with log rank test and multivariate Cox proportional regression were employed to assess the group differences.

Results: A total of 10,388 participants were included, with 53.8% male and mean age 52.2 years. During the 8-year follow-up, 292 subject dead. Kaplan-Meier curves comparing the four groups showed significant differences (p <.01). After adjusting for age, sex, smoking status, alcohol drinking and FBG, compared to group whose 2hPG≤ FBG, the hazard of the group (2hPG-FBG 0-4mmol/l) is similar but slight elevated (adjusted hazard ratio [AHR]=1.5; 95% CI, 0.9-2.4; p=0.11); the hazards are significantly higher for group (2hPG-FBG 4-10 mmol/l) (AHR= 2.0; 95% CI, 1.3-3.1; p<0.01) and for group (2hPG-FBG >10 mmol/l)(AHR=2.6; 95% CI, 1.6-4.3; p <0.01).

Conclusions: The hazard of all-cause mortality doubled among Chinese population with diabetes whose 2hPG-FBG higher than 4 mmol/l, compared to those whose 2hPG≤ FBG.

Public health significant: Personalized target of 2hPG may be set based on patients’ FBG to reduce the increased risk of death among adults with diabetes.

Disclosure

Z. Zhao: None. M. Zhang: None. J. Qi: None. X. Zhang: None. Y. Liu: None. L. Wang: None. M. Zhou: None. L. Wang: None.
1529-P: Higher Rates of Disease Progression among Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) Patients with Advanced Fibrosis (AF) and Diabetes Mellitus (DM)
Authors: YOUNOSSI ZOBAIR , KACHRU NANDITA , SHREAY SANATAN , LOOMBA ROHIT
Published: June 2019

Objective: Prevalence of NAFLD/NASH is high in DM patients. Presence of DM has been suggested to potentially accelerate liver disease progression among these patients. The study aimed to assess the adverse events among NAFLD/NASH patients with AF (F3 and compensated cirrhosis/F4) stratified by DM status.

Methods: Adult NAFLD/NASH-AF patients with available lab results were identified from Optum Research claims data (2008-2016), to calculate their Fibrosis-4 (FIB-4) scores. Using the score, patients were categorized as F3 or F4 (first date of cut-off score as index date), and then stratified by DM. Events were measured as first date of FIB-4 score/diagnosis consistent with F4, or presence of decompensated cirrhosis (DCC) after initial diagnosis of NAFLD/NASH with F3 or F4.

Results: Among 91,122 NAFLD/NASH patients with FIB-4 scores, 2,482 (2.7%) had F3 and 939 (1.0%) had F4 stage of fibrosis. 36% of F3 and 35% of F4 patients had DM. Overall, incident event rates for patients with NAFLD/NASH - F3 and F4 with DM were higher than those without DM (Figure). Incident DCC rates were also higher in NAFLD/NASH with DM [F3 (33.9%) (p=0.19) and F4 (70.1%) (p=0.04)] than without DM.

Conclusions: NAFLD/NASH patients with AF and DM have higher rates of adverse events. These patients must be identified early for close monitoring and management.

Disclosure

Z. Younossi: Consultant; Self; Gilead Sciences, Inc. N. Kachru: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. S. Shreay: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. R. Loomba: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc.
1533-P: Detecting Diabetes in Africans Is Improved by Both Modifying the A1C Threshold and Adding Glycated Albumin
Authors: MUGENI REGINE , BRIKER SARA M. , ADUWO JESSICA Y. , DUBOSE CHRISTOPHER , SUMNER ANNE E. , HORLYCK-ROMANOVSKY MARGRETHE F.
Published: June 2019

A1C at the standard threshold of 6.5% has been a poor predictor of diabetes (DM) in Africans. Reasons for the poor performance of A1C are myriad and include hemoglobinopathies and anemia. To begin to address challenges with A1C as a diagnostic test for Africans, there needs to be a determination that the threshold for A1C of 6.5% is appropriate. In addition, there could be value in determining if glycated albumin (GA), a non-fasting marker of glycemia not affected by hemoglobinopathies and anemia, would improve detection of DM. Therefore, we tested in Africans (a) the ability of A1C and GA independently and combined to predict DM and (b) the optimal cut-points for A1C and GA. OGTT were performed in 366 African-born blacks (age 38±10 (mean± SD); BMI 27.5 ±4.4 kg/m2) who self-identified as healthy and currently living in the Washington, DC area. Diagnosis of DM was based on glucose criteria for the OGTT. Ability of A1C and GA to predict DM was estimated by area under the receiver operating characteristic curve (AROC). Youden index established optimal cut-points for A1C and GA. Diabetes was newly diagnosed in 6% (23/366). For the prediction of DM by A1C the AROC was 0.78 (95% CI 0.68-0.88), and the optimal cut point was ≥5.8%. For the prediction of DM by GA the AROC was 0.73 (95% CI 0.61-0.85), and the optimal cut point was ≥14.05%. At these cut-points, DM was identified by A1C in 61% (14/23) (sensitivity 61%, specificity of 82%), and by GA in 65% (15/23) (sensitivity 65%, specificity 72%). The combination of A1C and GA identified DM in 83% (19/23) (sensitivity 83%, specificity 60%). Overall, the combination of A1C ≥5.8% and GA ≥14.05% markedly improved the detection of undiagnosed diabetes in Africans. Combining two non-fasting markers of glycemia at African-specific thresholds may be an important innovation in healthcare delivery.

Disclosure

R. Mugeni: None. S.M. Briker: None. J.Y. Aduwo: None. C. DuBose: None. A.E. Sumner: None. M.F. Horlyck-Romanovsky: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Minority Health and Health Disparities
1538-P: Quality of Life Decrements for Complications of Type 2 Diabetes
Authors: NEUWAHL SIMON , HOERGER THOMAS J.
Published: June 2019

To estimate the quality of life decrement associated with complications of type 2 diabetes, we combined public-use data on type 2 diabetes patients from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, its follow-on ACCORDION study, and the Action for Health in Diabetes (Look AHEAD) trial. The ACCORD trial administered the Health Utilities Index Mark 3 (HUI-3) instrument periodically, while the Look AHEAD trial administered the HUI-3 every 6 months. Measurements less than 1 year after a complication were associated with the complication event, and measurements more than 1 year after a complication were associated with a history of the complication. We used a fixed-effects model and included controls for BMI, duration of diabetes, and smoking. In total, there were 99,594 person-visit observations in our estimation sample, representing 14,899 unique persons with an average follow-up of 7.5 years. All complication events and complication history indicators negatively affected quality of life. The largest effects were observed for stroke (event year: 0.086; history: 0.056), congestive heart failure (event year: 0.043; history: 0.054), eGFR<30 mg/g (event year: 0.059), and myocardial infarction (MI) (event year: 0.024) (p<0.05). More modest effects were observed for revascularization (event year: 0.014), and eGFR<60 mg/g (event year: 0.008; history: 0.010) (p<0.05). Decrements for angina, history of angina, history of MI, history of revascularization, and history of eGFR<30 mg/g were not statistically significant. This combined analysis of the ACCORD, ACCORDION, and Look AHEAD trials illustrates the negative health impacts of diabetes complications in the year they occur and in subsequent years. Some complications had a large and persistent negative impact on quality of life, such as stroke and eGFR<30 mg/g. In some cases, the quality of life decrement was larger in subsequent years (CHF and angina), possibly because of the chronic and progressive nature of these complications.

Disclosure

S. Neuwahl: None. T.J. Hoerger: Research Support; Self; Sanofi.

Funding

Centers for Disease Control and Prevention
1551-P: Baseline Characteristics of Patients in the First Pan-India, Prospective, Longitudinal Study to Assess Management and Outcomes of T2D in Real-World Settings—LANDMARC
Authors: GHOSH ROMIK , DAS ASHOK KUMAR , UNNIKRISHNAN AMBIKA GOPALAKRISHNAN , KALRA SANJAY , THACKER HEMANT ,   LANDMARC STUDY GROUP
Published: June 2019

Background and Aims: LANDMARC (LongitudinAl NationwiDe StuDy On Management And Real World OutComes of Diabetes In India, CTRI/2017/05/008452) is the first prospective, observational, longitudinal study to understand the development of diabetes complications over a 3-year (yr) period in India with high number of sites (450) and a larger cohort of patients.

Methods: Adult subjects with T2D treated with ≥2 antihyperglycemic drugs (controlled/uncontrolled on A1c) were enrolled for assessment and baseline characteristics were analyzed using descriptive statistics.

Results: Of 6332 enrolled subjects, 6280 were eligible for baseline assessment. Mean (SD) age, BMI, and T2D duration were 52.12 (9.15) yr, 27.21 (4.59) kg/m2, and 8.57 (5.62) yr, respectively. Baseline A1c (n=4613; mean [SD]) was 8.0 (1.6) % and 1331 subjects (29%) hadA1c <7.0%. Mean (SD) FPG (n=5176) and PPG (n=5067) were 142.6 (50.4) mg/dL and 205.2 (71.8) mg/dL, respectively. Approximately 70% of subjects (n=4556) received only oral antihyperglycemic drugs OADs and 1687 subjects received both OADs and injectables (INJ). Biguanides (n=5829, 92.8%) and sulfonylureas (n=4785, 76.2%) were the most frequently prescribed OADs, and majority of subjects (n=2766, 44.3%) were prescribed two OAD classes. The mean (SD) duration (yr) of T2D was shorter in subjects receiving OADs (7.58 [4.88]) than INJ (11.01 [6.69]) or OAD+INJ (11.21 [6.57]). Most of the eligible subjects (n/N=3266/6280) had ≥1 CV risk factors; hypertension (n=2566, 40.9%) and dyslipidemia (n=1619, 25.8%) being most prevalent. Subjects with baseline A1c >7% to ≤8% had higher incidence of hypertension and dyslipidemia than other A1c groups. Neuropathy was the most common complication (n/N=728/6280, 11.6%) followed by nephropathy (n/N=153/6280, 2.44%).

Conclusion: These real-world data provide first insights on the epidemiology and treatment landscape of people with T2D in India.

Disclosure

R. Ghosh: Employee; Self; Sanofi. A.K. Das: None. A. Unnikrishnan: Other Relationship; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dr. Reddys Laboratories, Eli Lilly and Company, Eris Pharmaceuticals, Ipca Laboratories Ltd., MSD, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi. S. Kalra: None. H. Thacker: None.

Funding

Sanofi