bluuebunny/crossref_metadata_2025 huggingface dataset:
1377-P: Early Diagnosed Gestational Diabetes Mellitus: Initial Care Is Associated with Improved Prognosis when Fasting Plasma Glucose at Diagnosis Is ≥5.5 Mmol/l
Authors: COSSON EMMANUEL , VICAUT ERIC , BERKANE NARIMANE , BAUDRY CAMILLE , CIUNGANU TIT-LIVIU , VALENSI PAUL , CARBILLON LIONEL
Published: June 2020

Some guidelines recommend immediate care for women with fasting plasma glucose level (FPG) ≥5.1 mmol/L in early pregnancy (early-diagnosed gestational diabetes mellitus: eGDM). As diagnosis and care of hyperglycaemia can be delayed later in pregnancy, we assessed whether immediate vs. no immediate care for eGDM is associated with pregnancy outcomes. We retrospectively selected the women without known diabetes seen in our department (2012-2016) with a FPG level between 5.1 and 6.9 mmol/L before 22 weeks of gestation (WG) and separated them into two groups: (i) 255 who had immediate care; (ii) 268 who did not and performed an oral glucose tolerance test (OGTT) after 22 WG, with subsequent care if hyperglycaemia was present. We compared the occurrence of multiple outcomes including a composite adverse pregnancy outcome (large for gestational age infant, shoulder dystocia, preeclampsia). Among women without immediate care for eGDM, 134 had hyperglycemia after 22 WG. Women receiving immediate care were more likely than women with no immediate care to be insulin-treated (58.0 vs. 20.9%, p<0.00001) and had a lower gestational weight gain (8.6±5.4 vs. 10.8±6.1 kg, p<0.00001). After propensity score modeling and accounting for covariates, the rate of the composite outcome was similar in both groups (13.7 and 14.6% in women with and without immediate care respectively, p=0.87); however, when initial FPG was ≥5.5 mmol/L (n=134), the rates were respectively 8.0 and 17.7%, p=0.02. To conclude, immediate care of women with FPG ≥5.5 mmol/L in early pregnancy might improve pregnancy outcomes.

Disclosure

E. Cosson: None. E. Vicaut: Consultant; Self; Abbott, Boston Scientific, Celgene, Pfizer Inc. N. Berkane: None. C. Baudry: None. T. Ciunganu: None. P. Valensi: None. L. Carbillon: None.
1387-P: Risk of Perinatal Complications across Gestational Blood Pressure Levels in Women with and without Gestational Diabetes (GDM)
Authors: ZHU YEYI , FENG JUANRAN , NGO AMANDA , QUESENBERRY CHARLES , FERRARA ASSIAMIRA
Published: June 2020

Hypertensive disorders in pregnancy and GDM are among the leading causes of maternal and perinatal morbidity. In 2017, the American College of Cardiology/American Heart Association released a new guideline for hypertension: systolic/diastolic blood pressure (SBP/DBP) ≥130/80 vs. previous 140/90 mmHg. However, these new cut-points have not been applied to pregnant women due to the lack of evidence on its impact on perinatal outcomes. We examined in women with and without GDM whether the risk of perinatal complications increased across SBP/DBP levels: normal (<120/80 mmHg, untreated), elevated (120-129/<80, untreated), stage 1 gestational hypertension (GH, 130-139/80-89, untreated), and stage 2 GH (≥140/90, treated or untreated). The study was conducted in 2017-2018 among 6458 women with GDM and 50885 without GDM, who were Kaiser Permanente Northern California members without pre-existing hypertension. Logistic regression examined associations of BP categories with perinatal outcomes, adjusting for sociodemographic, medical, and lifestyle covariates. The prevalences were higher in women with vs. without GDM: elevated BP 21.3% vs. 20.0%, stage 1 GH 18.6 % vs. 16.1%, and stage 2 GH 3.6% vs. 2.6% (all P <0.05). Associations with risk of large-for-gestational age were more pronounced among women with vs. without GDM, with adjusted odds ratios (OR) for elevated BP of 1.54 (95% CI 1.28-1.84) vs. 1.22 (1.13-1.31) and for stage 1 GH of 1.35 (1.11-1.64) vs. 1.21 (1.11-1.31) (P for interaction <0.01). Associations with preterm birth and small-for-gestational age were present only for stage 2 GH among women without GDM: OR 1.56 (1.26-1.91) and 1.59 (1.34-1.88), respectively (P for interaction=0.02 and 0.08, respectively). Although GH was more common in women with GDM, its associations with perinatal complications varied by GDM status. Also, our findings suggest the new guideline may identify women with subclinical high BP in pregnancy at risk of perinatal complications.

Disclosure

Y. Zhu: None. J. Feng: None. A. Ngo: None. C. Quesenberry: None. A. Ferrara: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K01DK120807)
1396-P: The Impact of Neighborhood Factors on Glycemic Control for Women with Type 2 Diabetes during Pregnancy
Authors: ZAHEDI-SPUNG LEILAH , POLNASZEK BROCK E. , DUCKHAM HILLARY E. , HERRICK CYNTHIA J. , CARTER EBONY B.
Published: June 2020

Objective: To determine whether women living in highly deprived neighborhoods, defined by Area Deprivation Index (ADI), have worse glycemic control than those in less deprived areas.

Methods: We performed a retrospective cohort study of low-income, previously uninsured pregnant women with T2DM from 2007-2017. We compared women living in high (≥ top quartile) or middle (middle quartiles) ADI neighborhoods to those living in low (≤bottom quartile) ADI neighborhoods. Demographic characteristics were compared and trends in mean A1c throughout pregnancy were tested with repeated measures analysis.

Results: Of 367 women meeting study criteria (ADI range 1-10; IQR 7-10), 81 lived in low, 181 in middle, and 105 in high ADI neighborhoods. Demographics were similar between groups, except the high ADI group had more Black women and more severe diabetes by White Class. All groups achieved significant improvement in HgbA1c; however, the high ADI group was unable to achieve the same level of glycemic control by the third trimester after controlling for race and disease severity. There were no differences in pregnancy outcomes.

Conclusion: Intensive prenatal care was insufficient to overcome neighborhood deprivation with regard to glycemic control; thus, additional neighborhood level interventions are likely needed to overcome this inequality.

Disclosure

L. Zahedi-Spung: None. B.E. Polnaszek: None. H.E. Duckham: None. C.J. Herrick: None. E.B. Carter: None.

Funding

American Diabetes Association/Pathway to Stop Diabetes (1-19-ACE-02 to E.B.C.); Robert Wood Johnson Foundation (74250); Eunice Kennedy Shriver National Institute of Child Health and Human Development (K23HD095075)
1405-P: HbA1c Trajectories across Early Adulthood in the T1D Exchange Registry
Authors: TOSCHI ELENA , BAILEY RYAN , MILLER KELLEE , CALHOUN PETER
Published: June 2020

Glycemic control in adolescents with type 1 diabetes (T1D) is poor; however, it typically improves during early adulthood. Factors related to improvement of glycemic control are unclear. A total of 1,775 participants aged 18-30 years at enrollment in the T1D Exchange Registry followed for an average of 6 years were included in this analysis. Latent class trajectory modeling was used to determine sub-groups following a similar HbA1c trajectory over time. Five distinct trajectories of HbA1c classes were identified: Groups 1 and 2 had low or moderate HbA1c with a gradual decline with age, Group 3 had high HbA1c and remained stable, and Groups 4 and 5 had very high HbA1c with rapid or gradual decline (Figure). Compared with Group 3, Groups 1 and 2 were more likely to be male (P = 0.01), white non-Hispanic (P = 0.02), non-smokers (P = 0.001), check glucose more frequently (P < 0.001), and have higher education (P < 0.001), lower BMI (P = 0.01), and lower daily insulin dose (P < 0.001); if female, those in Group 1 were more likely to have a pregnancy during the time observed (P = 0.04). Group 4 was more likely to increase number of SMBG checks (P = 0.02) and have BMI increase over time (P = 0.02) compared with Group 5. We determined 5 distinct patterns of glycemic control from young adulthood into adulthood. Further evaluation into the modifiable factors associated with a declining A1c trajectory would aid in the development of targeted interventions.

Disclosure

E. Toschi: None. R. Bailey: None. K. Miller: None. P. Calhoun: Stock/Shareholder; Self; Dexcom, Inc.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust (G-2016PG-T1D053)
141-LB: The Reality of Diabetic Ketoacidosis in Patients with Type 2 Diabetes Using SGLT2 Inhibitors Revealed by a Nationwide Claim-Based Database in Japan
Authors: HORII TAKESHI , OIKAWA YOICHI , HIGASHIYAMA TOMOKO , ATSUDA KOICHIRO , SHIMADA AKIRA
Published: June 2020

Objective: Using a nationwide claim-based database in Japan, we investigated the reality of diabetic ketoacidosis (DKA) in patients with type 2 diabetes (T2D) treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors.

Research Design and Methods: We identified initiators of SGLT2 inhibitors in the claims data from April 2014 to June 2019, and investigated the incidence of DKA in patients with T2D. Moreover, in multivariable-adjusted Cox proportional hazard models, hazard ratio (HR) was calculated using age, sex, body mass index (BMI) and the use of continuous subcutaneous insulin infusion (herein referred to as insulin pumps). Furthermore, regarding DKA events as the objective variable, receiver operating characteristic (ROC) analysis was conducted to calculate a cut-off value for the periods from the initiation of the SGLT2 inhibitors.

Results: During the observation period, among 173,025 initiators of SGLT2 inhibitors, patients with a diagnosis of DKA were 1,848 (1.1%), and those requiring inpatient treatment were 247 (0.14%). Factors associated with the diagnosis of DKA were 60- < 70years of age (HR, 1.59), BMI < 25kg/m2 (HR, 1.22) and the use of insulin pumps (HR, 4.61). Moreover, Factors associated with DKA requiring inpatient treatment were 60-70 years of age (HR, 2.64) and BMI < 25kg/m2 (HR, 1.31). As for the DKA events, ROC analysis revealed that the cut-off value was 60 days from the initiation of the SGLT2 inhibitors.

Conclusions: This survey revealed that the risk of DKA calculated using real-world database was particularly pronounced among 60- < 70years of age and BMI < 25kg/m2 patients. Furthermore, it became clear that special attention should be paid to the onset of DKA for about 60 days from the initiation of the SGLT2 inhibitors. This information would provide guidance to avoid DKA with SGLT2 inhibitors and optimize the treatment of T2D, especially in Asian descent.

Disclosure

T. Horii: None. Y. Oikawa: None. T. Higashiyama: None. K. Atsuda: None. A. Shimada: Advisory Panel; Self; Astellas Pharma Inc. Speaker’s Bureau; Self; Eli Lilly Japan K.K., Novo Nordisk Inc., Sanofi-Aventis.
141-OR: Efficacy and Safety of Naltrexone/Bupropion as Add-On to Incretin Agents in Patients with Obesity and T2DM
Authors: WHARTON SEAN , YIN PETER , CAMACHO FERNANDO , BURROWS MELONIE , BLAVIGNAC JESSICA , BARAKAT MAXIME
Published: June 2020

There is significant overlap between obesity and type 2 diabetes (T2DM). Incretin agents (dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs)) are recommended as second-line to metformin in patients with T2DM due to their glucose-lowering effects, low risk of hypoglycemia, and favorable effect on weight. Naltrexone/bupropion (NB) is a combination therapy approved in North America and Europe for chronic weight management. This is an exploratory analysis of the efficacy and safety of NB in T2DM subjects enrolled in two double-blind, placebo-controlled Phase III studies (N=1344), that were stable on an incretin agent prior to randomization. At 1 year, mean weight change was -4.6% ± 0.21% in NB (N=700) compared to -1.1% ± 0.15% in placebo (N=644). In subjects randomized to NB that achieved at ≥5% weight loss at week 16 (early responders, N=269), mean weight change at 1 year was -8.8% ± 0.34%. An analysis of covariance using LOCF adjusting for age, sex, baseline BMI, baseline weight, and responder status revealed no significant interaction between incretin agent and weight treatment medication (p=0.1317), a significant treatment NB vs. placebo effect (p<0.0001), but not a significant incretin agent effect (p=0.1388). Safety and tolerability profiles were in line as previously observed in the broader population.

In conclusion, NB is efficacious and safe in reducing weight in patients with obesity and T2DM on DPP-4 inhibitors and GLP-1RAs, and may be an effective addition when weight loss is a focus in treatment.

Disclosure

S. Wharton: Advisory Panel; Self; Bausch Health Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. P. Yin: Employee; Self; Bausch Health. F. Camacho: Consultant; Self; Bausch + Lomb, Janssen Pharmaceuticals, Inc. M. Burrows: Employee; Self; Bausch Health. J. Blavignac: Employee; Self; Bausch Health Canada. M. Barakat: Employee; Self; Bausch Health.
1410-P: Genetics of TG/HDL-C Ratio and Its Change over Time in Nondiabetic Subjects
Authors: AN PING , LU YANLI , THYAGARAJAN BHARAT , KUIPERS ALLISON L. , ANEMA JASON A. , MILJKOVIC IVA , DAW EDWARD W. , PROVINCE MICHAEL
Published: June 2020

TG/HDL-C ratio (THR) represents a single inherited surrogate predictor of hyperinsulinemia or insulin resistance that is associated with frank development of T2D, premature aging processes and increased mortality. To identify gene variants for THR and its change over time (THRGC), we conducted GWAS among subjects of European ancestry who had complete data from two exams collected ∼7 years apart from the LLFS (n = 3091), a study with familial clustering of exceptional longevity in the U.S. and Denmark. We sought replication in the FamHS (n = 3108, ∼7 years apart between two visits). Subjects with T2D or using medications for dyslipidemia were excluded from this analysis. THRGC was derived using growth curve modeling. Each phenotype was adjusted for age, sex, PCs and familial membership, and then log-transformed to approximate normality. EPACTS with make-kin and emmax options for familial clustering assuming additive genetic effects was used. P<5e-8 was used to declare genome-wide significance. Heritability estimates reached 38% for THR and 46% for THRGC in the LLFS. GWAS identified two significant loci for THR (LPL-rs328, stop gain, coding sequence variant, MAF=0.11, p=8e-9, replication p=4e-9; BUD13-ZNF259-APOA5-rs2072560, intron variant, MAF=0.07, p=2e-8, replication p=8e-14) and one locus for THRGC (LPL-rs78458743, ∼20 kb downstream, MAF=0.1, p=4e-8, replication p=0.01). The LPL gene encodes lipoprotein lipase that hydrolyzes chylomicrons and VLDL-C. Additionally, linkage scan identified a significant (Lods>3) locus on 3q28 (Lods=4.1) for THRGC in the LLFS. Further query of sequence elements under the linkage peak is underway.

In conclusion, this first GWAS of THR identified the LPL gene (including a functional variant rs328) and the BUD13-ZNF259-APOA5 gene cluster for THR variation. The new findings highlight the importance of the LPL and APOA5 gene regulation of THR in subjects without diabetes selected for exceptional survival and healthy aging.

Disclosure

P. An: None. Y. Lu: None. B. Thyagarajan: None. A.L. Kuipers: None. J.A. Anema: None. I. Miljkovic: None. E.W. Daw: None. M. Province: None.

Funding

National Institute on Aging (U01AG023712, U01AG023744, U01AG023746, U01AG023749, U01AG023755)
1414-P: Characteristics Associated with Sulfonylureas and Basal Insulin Use following Metformin in Older Adults
Authors: DECARLO KRISTEN E. , O’BRIEN MATTHEW , LISS DAVID T. , KANG RAYMOND , COOPER ANDREW J. , CHERUPALLY MANISHA , PARKER EMILY D. , AIKMAN CASSANDRA , ACKERMANN RONALD T. , WALLIA AMISHA
Published: June 2020

Sulfonylureas (SFU) and basal insulin (BI) are to be used with caution in older adults due to safety risk (eg hypoglycemia). Using 2013-2017 data from a national insurer, we studied 84,720 Medicare Advantage adults ≥ 65 years (yrs) who started one of six antidiabetic medication (ADM) classes after metformin monotherapy. Outcomes were new start of SFU (vs. GLP-1 receptor agonists [GLP-1], SGLT2 inhibitors [SGLT2], thiazolidinediones [TZD], DPP-4 inhibitors [DPP-4]); or BI (vs. GLP-1, SGLT2, TZD, DPP-4). Multivariable logistic regression models examined associations between prescriber and patient characteristics (demographics, cognitive impairment [none, mild and severe], and diabetes related complications [diabetes complications severity index, DSCI score]). Most older adults received SFU followed by DPP-4, while few received GLP-1 and SGLT2 (SFU N=45,734 [54%], DPP-4 N=15,790 [19%], BI N=12,165 [14%], GLP-1 N=3,298 [4%], SGLT2 N=3,365 [4%], and TZD N=4,368 [5%]). Older subcategories of adults were increasingly more likely to receive SFU than those 65-67 yrs (70-74 yrs, OR1.08, 1.04-1.12; 75-79 yrs OR1.2, 1.13-1.25; ≥80 yrs OR1.35, 1.27-1.42). No differences in SFU use were seen in those with cognitive impairment and minority groups. For those receiving BI, females (vs. male OR 1.10, 1.05-1.15) and blacks (vs. whites OR1.26, 1.17-1.15) were more likely to receive BI. Those with severe cognitive impairment (vs. none OR1.98, 1.75-2.24) and high DSCI score (3+) (vs. 0 OR1.40, 1.31-1.50) were more likely to receive BI. Older subcategories of adults were less likely to receive insulin than 65-67 yrs of age (68-70 yrs, OR0.83, 0.77-0.89; 70-74 yrs, OR0.85, 0.80-0.90; 75-79 yrs OR0.93, 0.87-0.99). Older subcategories of adults were increasingly more likely to receive SFU; younger, cognitively impaired and those with diabetes complications were more likely to receive basal BI. Further research is needed to elucidate factors underlying differences in SFU and BI prescribing patterns.

Disclosure

K.E. DeCarlo: None. M. O’Brien: Research Support; Self; UnitedHealth Group. D.T. Liss: None. R. Kang: Research Support; Self; UnitedHealth Group. A.J. Cooper: None. M. Cherupally: None. E.D. Parker: None. C. Aikman: None. R.T. Ackermann: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, UnitedHealth Group. A. Wallia: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc., UnitedHealth Group.

Funding

UnitedHealth Group (SP0036847)
1418-P: Increased Risk of Incident Heart Failure and All-Cause Mortality in Insulin-Resistant People with Type 2 Diabetes in the United Kingdom Prospective Diabetes Study (UKPDS)
Authors: WAMIL MALGORZATA , COLEMAN RUTH L. , ADLER AMANDA , MCMURRAY JOHN J. , HOLMAN RURY R.
Published: June 2020

Background and Aims: Insulin resistance (IR) is a possible mediator for development of heart failure (HF). We examined prospectively whether IR in people with newly-diagnosed type 2 diabetes (T2D) increased their risk of a composite endpoint of incident HF or all-cause mortality (ACM) (as death is a competing risk).

Methods: UKPDS participants with Homeostasis Model Assessment v2 Insulin Resistance (HOMA2_IR) values (derived from paired fasting plasma glucose and insulin measures) were used in multivariable Cox model and Kaplan Meier survival curves to evaluate a possible association between HOMA2_IR and HF/ACM or HF alone, adjusting for potential confounders (variables with a univariate association (P<0.1) and a multivariable P value <0.05 were retained in the full model).

Results: Of 5102 UKPDS participants, 4344 had the data required. They were mean (SD) age 52.5 (8.7) years, HbA1c 7.2 (1.8) %, body mass index 28.8 (5.5) kg/m2, with median (IQR) HOMA2_IR 1.6 (1.1-2.2). Over median 16.4 years the composite endpoint occurred in 1974 (45.4%) participants (235 HF, 1897 death first events) with a 27% greater risk for those with HOMA2_IR ≥1.6 (compared with <1.6), and a 55% greater risk for HF (Table).

Conclusion: Insulin resistant patients with newly-diagnosed T2D were more likely to develop HF or die than those who were more insulin sensitive.

Disclosure

M. Wamil: None. R.L. Coleman: None. A. Adler: None. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc. R.R. Holman: Advisory Panel; Self; Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp.

Funding

Oxfordshire Health Services Research Committee (1239)
1419-P: Lower Medium and Total HDL Particle Concentrations May Contribute to CVD Risk in Type 1 Diabetes
Authors: COSTACOU TINA , VAISAR TOMAS , JU JINGHUI , BORNFELDT KARIN , ORCHARD TREVOR J. , HEINECKE JAY
Published: June 2020

Although it has long been proposed that HDL is dysfunctional in type 1 diabetes (T1D), this hypothesis has not been formally tested in large cohorts using validated functional and biochemical HDL metrics. We therefore determined whether HDL particle concentration (HDL-P) and function differed between 187 middle-aged adults with childhood-onset T1D (mean age 51 years, T1D duration 43 years, 53% women) and 200 individuals with normal glucose tolerance (NGT) of similar age and sex distribution. HDL-P was assessed by calibrated ion mobility analysis. HDL function, i.e., serum HDL cholesterol efflux capacity, was quantified in J774 cells using a validated assay. Separate stepwise linear regression models were constructed for each HDL metric, allowing for T1D status and potential confounding factors, including HDL cholesterol (HDL-C). The presence of significant effect modification by sex was evaluated. After adjustment, the concentrations of total (T-HDL-P; β=-0.44, p=0.09) and medium-sized (M-HDL-P; β=-0.84, p<0.0001) HDL particles were lower in the T1D compared with the NGT group. In contrast, T1D status was not significantly associated with small (S-HDL-P) and large-sized (L-HDL-P) HDL-P. A significant sex by T1D status interaction term was observed for M-HDL-P (p=0.03), indicating that women had higher M-HDL-P only in NGT; M-HDL-P did not differ by sex in T1D. Moreover, a marginally significant sex by T1D status interaction was observed for L-HDL (p=0.08), suggesting that women had higher L-HDL-P only in T1D. Unexpectedly, serum HDL cholesterol efflux capacity was higher in the T1D compared with the NGT group (β=0.29, p<0.0001).

In conclusion, lower levels of T-HDL-P and M-HDL-P in T1D may explain in part the higher cardiovascular risk in T1D, as these metrics were recently shown to be associated with protection from vascular complications. The lack of a difference in M-HDL-P by sex in T1D may contribute to the loss of cardioprotection associated with female sex.

Disclosure

T. Costacou: None. T. Vaisar: Consultant; Self; AstraZeneca. J. Ju: None. K. Bornfeldt: None. T.J. Orchard: None. J. Heinecke: None.

Funding

National Institutes of Health (HL130153, DK34818)
142-LB: Very Low Dose SGLT2 Inhibition Is as Effective as Angiotensin II Receptor Blockage for Cardiac and Renal Fibrosis in High Salt 5/6 Nephrectomized Rats
Authors: ZENG SHUFEI , HASAN AHMED A. , DELIC DENIS , XIONG YINGQUAN , CHU CHANG , YIN LIANGHONG , FRANKENREITER SANDRA , KRÄMER BERNHARD , KLEIN THOMAS , HOCHER BERTHOLD
Published: June 2020

SGLT2 inhibition has beneficial effects on cardiovascular and renal endpoints but the lowest effective dose is unknown. Effects of the SGLT2 inhibitor, empagliflozin (EMPA) were evaluated in nondiabetic, 5/6 nephrectomy (5/6 Nx) rats. Rats were treated for 8 weeks: Sham + normal diet + placebo (PBO); 5/6Nx + 2% high salt diet (HSD) + PBO; 5/6Nx + HSD + EMPA 1.2 mg/kg/day); 5/6Nx + HSD + telmisartan (5 mg/kg/day); 5/6Nx + HSD + linagliptin (3 mg/kg/day). EMPA increased urinary glucose excretion at dosages eight times lower than currently used low doses. 5/6Nx HSD rats treated with EMPA showed significantly (-29.95/-25.00 mmHg, p<0.001) lower blood pressure (BP) and significantly reduced renal (-33.67%; p<0.05) and cardiac (- 34.85%; p<0.05) fibrosis vs. PBO. Effects of EMPA on BP and renal and cardiac fibrosis were comparable to telmisartan (BP: -31.89/-24.24 mmHg, p<0.001; renal fibrosis -43.96%; p<0.01; cardiac fibrosis: -36.37%; p<0.01) and effects on fibrosis were comparable to linagliptin (renal fibrosis -41.54%; p<0.05; cardiac fibrosis: -50.01%; p<0.001). Many genes were differentially regulated among groups, e.g., transferrin receptor (Trfc), A-kinase anchor protein 1 (Akap1) and mitogen-activated protein kinase 9 (Mapk9) were affected by EMPA and telmisartan while Caspase 1 (Casp1) gene expression was altered by EMPA only in the heart. In the kidney, both EMPA and linagliptin led to differential regulation of pleckstrin homology domain-containing family A member 1 (Plekha1), while only EMPA resulted in differential expression of prostaglandin E synthase (Ptges) and G protein-coupled receptor, class C, group 5, member A (Gprc5a) gene expression. Very low dose EMPA was almost as effective as standard dosages of telmisartan or linagliptin in counteracting BP increase and cardiac and renal fibrosis. The underlying mechanism involves regulation of genes involved in cardiac and renal fibrosis.

Disclosure

S. Zeng: None. A.A. Hasan: Research Support; Self; Boehringer Ingelheim International GmbH. D. Delic: None. Y. Xiong: None. C. Chu: None. L. Yin: None. S. Frankenreiter: Employee; Self; Boehringer Ingelheim Pharma GmbH & Co. KG. Other Relationship; Self; Evotec International GmbH. B. Krämer: Advisory Panel; Self; Boehringer Ingelheim International GmbH. T. Klein: Employee; Self; Boehringer Ingelheim International GmbH. B. Hocher: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.

Funding

Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance
1420-P: Trends in Cardiovascular and Economic Outcomes of Patients Hospitalized for Stroke and Diabetes in the U.S.: Data from the National Inpatient Sample (2005-2014)
Authors: TABBALAT AYA , DARGHAM SOHA R. , ELSHAZLY MOHAMED B. , KHALIL CHARBEL ABI
Published: June 2020

Background: As the prevalence of diabetes is increasing worldwide, our aim is to assess the recent cardiovascular and economic trend in outcomes of patients with stroke and diabetes in the U.S.

Methods: Data from the National Inpatient Sample was analyzed between 2005 to 2014. We studied: In-hospital mortality, length of stay (LoS) and overall hospital charges in patients hospitalized for stroke, >18 years of age and known to have diabetes.

Results: The prevalence of diabetes gradually increased from 28.2% to 35.5% in all patients hospitalized for stroke (p trend<0.001) between 2005 and 2014. In those patients with diabetes, mean (SD) age slightly decreased from 70 (13) years to 69 (13) years (p trend <0.001). Interestingly, hospitalization for stroke increased from 17.4 to 20.0/100 000 U.S. adults (p trend <0.001). However, in-hospital age-adjusted mortality decreased from 4.64% to 3.73% (p trend <0.001). Age-adjusted mortality of hemorrhagic strokes - which represent only a small proportion of all strokes- decreased from 28.1% to 23.1%, that of ischemic strokes decreased from 3.23% to 2.48% (p trend <0.01 for both) whereas that of TIA was almost stable and lower than 0.2%. As expected, total charges of hospital stay almost doubled as they went up from 15,970 to 31,018 USD/stay (adjusted for inflation). Nevertheless, median (IQR) LoS slightly decreased from 4 (2-6) to 3 (2-6) days (p trend <0.05).

Conclusion: Our preliminary data show that the prevalence of diabetes in patients hospitalized for stroke is gradually increasing. Moreover, hospitalization for stroke is also increasing. Nevertheless, in-hospital mortality is on a descending slope, which comes at a price of an almost 2-fold increase in hospital charges from 2005 to 2014.

Disclosure

A. Tabbalat: None. S.R. Dargham: None. M.B. Elshazly: Stock/Shareholder; Self; Ember Medical. C. Abi Khalil: None.
1424-P: Generalizability of Glucagon-Like Peptide-1 Receptor Agonist Cardiovascular Outcome Trials to the Type 2 Diabetes Population in China
Authors: CAI XIAOLING , ZHANG LIN , WU HAIYA , HUO LI , MA XIAO , CAO HAIJUN , JI LINONG
Published: June 2020

Introduction: A number of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been evaluated in cardiovascular outcome trials (CVOTs). In this study, we aim to examine the generalizability of results from GLP-1 RAs CVOTs among Chinese type 2 diabetes (T2D) population.

Methods: Patients enrolled or eligible for inclusion in four GLP-1RAs CVOTs (EXSCEL, LEADER, REWIND and SUSTAIN-6) were examined in reference to 3B (Blood Glucose, Blood Pressure and Blood Lipid) population, a nationally representative population of T2D patients in China (n=25,411). We descriptively compared key baseline characteristics of the populations in each trial to those in 3B population. We also estimated the proportions of patients in 3B population who would have met the six key inclusion and exclusion (I/E) criteria (age, HbA1c, BMI, eGFR, CVD history and antidiabetic medication) in each trial.

Results: The REWIND population most closely matched 3B population in sex, diabetes duration, HbA1c, DBP, LDL, CVD history and prior MI. The EXSCEL most matched in age, BMI and SBP, while the SUSTAIN-6 most matched in eGFR (Table 1). Based on I/E criteria, 31.10% of the 3B population were eligible for enrolment in REWIND, versus 15.04% in SUSTAIN-6, 12.97% in LEADER, and 11.30% in EXSCEL.

Conclusions: Among the four CVOTs, REWIND has the most generalizable eligibility to the Chinese T2D population.

Disclosure

X. Cai: None. L. Zhang: Employee; Self; Eli Lilly and Company. H. Wu: None. L. Huo: Employee; Self; Eli Lilly and Company. X. Ma: None. H. Cao: None. L. Ji: None.
1426-P: Utilization of Glucose-Lowering Drugs in Patients with T2DM and Established CVD in the U.S.
Authors: GANZ MICHAEL L. , USTYUGOVA ANASTASIA V. , SAWALHI-LECKENBY NICOLA , SOUZA SABRINA DE , GAO RAN , HOMSY DIANA , GUNNARSSON ERIK , ZHANG LU , DESAI NIHAR
Published: June 2020

Background: People with T2DM have increased risks of CV morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce risks of CV events, but the degree to which they are used in clinical practice remains unknown. Our objectives were to describe glucose-lowering drug utilization in U.S. patients with T2DM and established CVD (eCVD) in 2014-18.

Methods: Annual drug use by adults (≥ 18 years) with T2DM and eCVD (during the same 12-months) was determined from the MarketScan claims database.

Results: We identified 345,340 (2014) to 227,418 (half year 2018) patients with T2DM and eCVD; hypertension and ischemic heart disease were the most prevalent eCVDs. About 55-60% of patients used any type of glucose lowering drug. Although the use of GLP-1 RA and SGLT2i increased 6.2 and 9.5 percentage points respectively across 2014-18, the use of dipeptidyl peptidase-4 inhibitors (DPP-4i) decreased by 3.7 points and use of other glucose lowering drugs decreased by 10.8 points. Patients who used GLP-1 RA and SGLT2i were 8 years younger than users of DPP-4i or other glucose lowering drugs. SGLT2i users had the lowest prevalence of chronic heart failure and chronic kidney disease.

Conclusion: Despite recent increases, GLP 1-RA and SGLT2i are significantly underused among patients with T2DM and eCVD in the MarketScan claims database.

Disclosure

M.L. Ganz: None. A.V. Ustyugova: Employee; Self; Boehringer Ingelheim International GmbH. N. Sawalhi-Leckenby: None. S. de Souza: None. R. Gao: None. D. Homsy: None. E. Gunnarsson: None. L. Zhang: None. N. Desai: None.
1427-P: Higher Prevalence of Heart Failure and Length of Stay in Hospitalized Type 2 Diabetics with Atrial Fibrillation
Authors: ALKHAYRU ALI , TAPPUNI BASSMAN , KASEER BELAL , BRANDT DOMINIQUE M. , GHAZI FREIDOON , WINNER MARSHALL W. , SHEMISA KAMAL
Published: June 2020

Background: Cardiovascular (CV) disease is a major cause of morbidity in patients with type 2 diabetes mellitus (DM2). DM2 patients often experience Atrial Fibrillation (AF) with aggravated CV morbidity and mortality. We investigated the clinical risk factors in patients with DM2 hospitalized with AF with rapid ventricular response (RVR).

Methods: A retrospective study was conducted using a community hospital EMR database from 2013-2018. Adults with admission codes for AF with RVR were included in the study, and were stratified based on the presence or absence of DM2. Patient characteristics, and clinical outcomes were compared.

Results: Among 1643 patients with AF with RVR, 501 (30.5%) had DM2. Median (IQR) age for DM2 patients compared to controls was 72(64, 79) vs. 73(62, 83), P=0.12, 54.5% vs. 54.6% were female P=0.98, had coronary artery disease [39.5% vs. 25.3% (P<.0001)], heart failure (HF) [68.5% vs. 51.8 % (P<.0001)], hypertension [88% vs. 67.7% (P< 0.0001)]. length of stay (LOS), 3(2,6) days vs. 2(1,4) days, (P<.0001)] LOS was higher for DM2 patients with HF with 4(2,6) vs. 3(2,5) (p <.0001).

Conclusion: Among patients hospitalized for AF with RVR, DM2 patients had a higher prevalence of cardiovascular disease and longer LOS. A higher prevalence of HF may be a contributing factor to longer LOS. Understanding the risk of HF in patients with DM2 and AF is needed to address clinical outcomes in the future.

Disclosure

A. Alkhayru: None. B. Tappuni: None. B. Kaseer: None. D.M. Brandt: None. F. Ghazi: Speaker’s Bureau; Self; AstraZeneca K.K., Boston Scientific, Janssen Pharmaceuticals, Inc. M.W. Winner: None. K. Shemisa: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Pfizer Inc.
143-OR: All-Cause Mortality over 16 Years in Look AHEAD
Authors: WING RENA R. , CLARK JEANNE , GREGG EDWARD W. , KRITCHEVSKY STEPHEN B. , LEWIS CORA E. , PI-SUNYER XAVIER , REBOUSSIN DAVID M. , WADDEN THOMAS A. , WAGENKNECHT LYNNE E. , YANOVSKI SUSAN Z. ,   THE LOOK AHEAD GROUP
Published: June 2020

Whether intentional weight loss reduces mortality in overweight/obese individuals with diabetes is unclear. Look AHEAD, a randomized trial of intensive lifestyle intervention (ILI) and diabetes support and education (DSE) (control) in 5145 individuals with overweight/obesity and type 2 diabetes, is ideal for examining this due to large sample, extended follow-up, excellent retention, and sustained difference in weight loss (y1: 8.6% ILI; 0.7% DSE; y10: 6.1% ILI; 3.9% DSE). After 10 years of intervention, participants had 6-month calls and biennial visits. The primary outcome for the current phase is all-cause mortality from randomization to 16 years. Data were analyzed with proportional hazards regression stratified by clinical site; significance was based on the likelihood ratio. All-cause mortality was 9% lower in ILI compared to DSE, not a statistically significant difference (Fig 1). Deaths by arm were: ILI 496/2570 and DSE 530/2575. Interactions of treatment with prespecified subgroups (sex, CVD history, age) were not significant. In post-hoc analyses, ILI participants who lost >10% at 1year had an 18% reduced risk (HR=.82, CI 0.68,0.97) and ILI participants who gained or lost <2% had a 29% higher risk (HR=1.29, CI 1.01,1.67) relative to all DSE. The difference in mortality between ILI and DSE was not statistically significant. Post-hoc analyses suggest an association between magnitude of weight change and all-cause mortality in ILI.

Disclosure

R.R. Wing: None. J. Clark: None. E.W. Gregg: None. S.B. Kritchevsky: None. C.E. Lewis: None. D.M. Reboussin: None. T.A. Wadden: Board Member; Self; Novo Nordisk Inc., Weight Watchers International, Inc. L.E. Wagenknecht: None. S.Z. Yanovski: None.

Funding

National Institutes of Health
1442-P: Validity of the American Diabetes Association Diabetes Risk Test in a Low-Income African-American Population
Authors: CHIMA CHARLES C. , ANIKPEZIE NNABUCHI , WADE BREANNA C. , PONGETTI LAUREN S. , POWELL THOMAS , BEECH BETTINA
Published: June 2020

Objective: The use of self-reported data to assess diabetes risk in the general population is a key component of the National Diabetes Prevention Program. The American Diabetes Association Diabetes Risk Test (ADADRT) is a popular tool used for this purpose, yet there is paucity of data on its validity in real-world clinical settings. We assessed the performance of ADADRT in identifying undiagnosed prediabetes or diabetes at a Federally Qualified Health Center serving predominantly African Americans.

Methods: The ADADRT was administered to participants without pre-existing diagnosis of prediabetes or diabetes and standard validation measures were calculated using HbA1c as the gold standard. Findings are reported for participants who self-identified as being Black or African American (n = 151).

Results: HbA1c identified 25.8% of the sample as having prediabetes or diabetes. At the recommended cutoff for ADADRT (i.e., score ≥5) the following measures were observed: proportion of high-risk persons 47.7%, sensitivity 74.4%, specificity 61.6%, positive predictive value 40.3%, negative predictive value 87.3%, Youden Index 36, and area under the receiver-operating characteristic curve 0.68.

Conclusion: ADADRT reasonably identifies low income African Americans with high diabetes risk. Findings are comparable to the precursor to ADADRT as validated with nationally representative data.

Disclosure

C.C. Chima: None. N. Anikpezie: None. B.C. Wade: None. L.S. Pongetti: None. T. Powell: None. B. Beech: None.
1445-P: Metabolic Syndrome Subtypes Point to Distinct Origins of Glucose Intolerance
Authors: LUKOSE CHRISTY , CAMPBELL ERIN , CISTOLA DAVID P.
Published: June 2020

Introduction: Metabolic syndrome (MetS) is a risk factor for type 2 diabetes and cardiovascular disease. The underlying pathophysiology encompasses insulin resistance (IR), abdominal obesity, ectopic lipid deposition and glucose intolerance. However, individual subjects may exhibit distinct MetS subtypes.

Hypothesis and Aim: We hypothesized that MetS has IR and non-IR subtypes. The specific aim was to identify and compare these subtypes, in human subjects without diabetes, using data from the 2015-2016 U.S. National Health and Nutrition Examination Survey.

Methods: The inclusion criterion was ages ≥ 12, and the exclusion criteria were diabetes, pregnancy, fasting < 8 h or TG ≥ 885 mg/dL. The 2,325 subjects were categorized into four groups: no MetS and no hyperinsulinemia (NN; n=1,149), no MetS with hyperinsulinemia (NY; 497), MetS without hyperinsulinemia (YN; 249), and MetS with hyperinsulinemia (YY; 430); insulin cut point 11.25 µIU/mL. Parameter distributions were compared using non-parametric Kruskal-Wallis and Steel-Dwass tests, and 95% CI.

Results: Compared with YY, the YN subtype had significantly higher median age, blood pressure, HDL and smoking frequency, and lower waist circumference, TG and hs-CRP. Despite a large difference in median HOMA-IR for YY (2.33; 95% CI 2.26, 2.40) vs. YN (1.07; 95% CI 1.04, 1.14), the median fasting glucose and HbA1c were statistically identical for YY and YN. Most subjects in the YN group had impaired fasting glucose (median 104.7 mg/dL; 95% CI 103.2, 106.0). By contrast, median fasting glucose for the NN and NY groups were 95.8 (95% CI: 95.2, 96.3) and 97.6 mg/dL (95% CI: 96.8, 98.5), respectively.

Conclusion: In subjects without diabetes, the YN subtype of metabolic syndrome is characterized by glucose intolerance without insulin resistance. Thus, diabetes risk for YN subjects must arise from a loss of beta-cell function by IR-independent mechanisms. Therapeutic strategies designed to improve insulin sensitivity are unlikely to be effective in the YN subtype.

Disclosure

C. Lukose: None. E. Campbell: None. D.P. Cistola: None.

Funding

National Institutes of Health (R21HL143030)
145-LB: Improving Continuous Glucose Monitoring (CGM) Use across Ten National Centers: Results from the T1D Exchange Quality Improvement Collaborative (T1DX-QI)
Authors: EBEKOZIEN OSAGIE , RIOLES NICOLE , DESALVO DANIEL , GALLAGHER KATHRYN , LEE JOYCE M. , MCDONOUGH RYAN , OBRYNBA KATHRYN , PRAHALAD PRIYA , THOMAS SARAH , WEINSTOCK RUTH S. , CORATHERS SARAH
Published: June 2020

Many studies have demonstrated the clinical benefit of continuous glucose monitoring (CGM) in type 1 diabetes (T1D). Although favorable insurance policy changes have gradually increased the access of CGM nationally, widespread uptake has been slow. The T1DX-QI is a national type 1 diabetes learning collaborative coordinated by the T1D Exchange in Boston, MA.

This work describes how 10 diabetes centers in the T1DX-QI used QI principles including the Plan - Do - Study - Act (PDSA) cycles to test and expand different interventions to increase CGM use in their respective centers. Successful efforts include the redesign of relevant workflows, assessing and removing barriers to adoption, developing CGM patient education classes, and advocating for state Medicaid coverage of CGM. The centers piloted these changes in 12 - 26 year olds with T1D.

The coordinating center used statistical process control charts to evaluate the effectiveness of the interventions (Figure 1). Eight of 10 participating centers improved CGM use significantly. There was a 12% improvement from over 20 months across the entire cohort of centers (range 7-34%).

This demonstrates that by using QI principles to test interventions and cross-learning, the T1D community can increase use of CGM devices.

Figure 1.

Disclosure

O. Ebekozien: None. N. Rioles: None. D. DeSalvo: Consultant; Self; Dexcom, Inc., Insulet Corporation. K. Gallagher: None. J.M. Lee: Advisory Panel; Self; Goodrx. Consultant; Self; T1D Exchange. Research Support; Self; Lenovo. R. McDonough: None. K. Obrynba: None. P. Prahalad: None. S. Thomas: None. R.S. Weinstock: Board Member; Self; JDRF. Consultant; Self; Insulogic LLC. Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Jaeb Center for Health Research, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. S. Corathers: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
1452-P: High-Altitude Polycythemia Is an Independent Risk Factor for Type 2 Diabetes
Authors: REN QIAN , LV XUEMEI , ZHOU LINGLI , LUO YINGYING , YANG LIHUI , JI LINONG
Published: June 2020

Background: According to previous researches, there were several risk factors of type 2 diabetes, including age, overweight or obesity, hypertension, dyslipidemia etc. However, it is not clear whether there are specific diabetes related risk factors in high altitude areas due to the unique low oxygen and low atmospheric pressure environment.

Methods: This study is a population-based, cross-sectional epidemiological survey. The permanent Tibetan residents in Lhasa and Shigatse were enrolled in this study, including 1 urban area (10 communities) and 7 rural areas (48 villages). OGTT, HbA1c, blood lipid and blood cell counts were measured in all the subjects. Diabetes was diagnosed according to the WHO criteria. The diagnostic standard of high altitude polycythemia (HAPC) is the universal Qinghai standard (male hemoglobin ≥ 210g/L, female ≥ 190g/L).

Results: A total of 1401 subjects were enrolled in this study. The average age was 44.3 ± 15.0 years old, 33.3% were male. The prevalence of diabetes in the study population was 3.6% (5.8% among men and 2.6% among women, p=0.003; 4.4% in rural vs. 2.4% in urban areas, p=0.033). The prevalence of diabetes increased with increasing age (1.9%, 4.7%, and 7.1% among persons who were 18 to 44, 45 to 59, and ≥60 years of age, respectively) and with increasing BMI (0, 2.3%, 4.7%, and 11.3% among persons with a BMI of <18.5, 18.5 to 23.9, 24.0 to 27.9, and ≥28.0, respectively). The prevalence of HAPC was 6.4% (6.2% among men and 6.5% among women, p=0.453). The prevalence of diabetes was significantly higher in HAPC group than in non HAPC group (11.2% vs. 3.1%, P<0.001). After quartile grouping of Hb, the prevalence of diabetes was 1.6%, 1.8%, 4.5% and 6.3% respectively (p=0.001). After adjusting for gender, age, BMI, hypertension, hyperuricemia and hypercholesterolemia, logistic regression analysis indicated that HAPC was an independent risk factor for diabetes (or = 3.514, 95% CI 1.606-7.689, P = 0.002).

Conclusion: HAPC is an independent risk factor of type 2 diabetes in Tibet, China.

Disclosure

Q. Ren: None. X. Lv: None. L. Zhou: None. Y. Luo: None. L. Yang: None. L. Ji: None.

Funding

Science and Technology Project of Tibet Autonomous Region (CGZH2017000085); National Key Research and Development Program (2016YFC1304901)
1455-P: Effect of Treatment of Anemia on HbA1c Levels
Authors: PENDELA VENKATA SATISH , VENUGOPAL SHARINI , KUDARAVALLI PUJITHA
Published: June 2020

Introduction: While glucose remains the major determining factor of HbA1C, other conditions like hemolytic anemia, iron/vitamin B 12 deficiency anemia have also been shown to affect HbA1C.

Material and Methods: A prospective study was carried out in a tertiary care center, Kasturba hospital, India over a period of two years, that included patients in the age group of 18 to 70 years with anemia and no proven diabetes. We excluded all patients with diabetes, other forms of anemia, major organ dysfunction, hemoglobin <5 g/dL and pregnancy.

Anemia was treated with iron and/or cobalamin. Hemoglobin was measured every month till normal values were attained. HbA1C was measured at the beginning and at the end of completion of 3 months of treatment. For comparing pre and post therapy HbA1C levels, paired t-testwas used. A p value of <0.01 was considered statistically significant.

Results: We found a significant decrease in HbA1C levels among 70% of the iron deficient group, 72% of the B12 deficiency group and 83% of the dual deficiency group with the treatment of anemia. In our study, as many as 27 (38%) patients were labeled as prediabetic without considering their anemic status.

Conclusion: From the observations made in this study, it is evident that HbA1C could be influenced by the anemic state of an individual. Hence, it is advisable to treat patients with anemia before defining their diabetic status. Larger studies are required to know the degree of impact of anemia on HbA1C.

Disclosure

V. Pendela: None. S. Venugopal: None. P. Kudaravalli: None.