bluuebunny/crossref_metadata_2025 huggingface dataset:
1412-P: Racial Differences of Incident Diabetes Postpartum in Women with a History of Gestational Diabetes
Authors: SHEN YUN , HOU LIFANG , LIU HUIKUN , WANG LEISHEN , LENG JUNHONG , LI WEIQIN , HU GANG
Published: June 2019

The aim of the present study was to investigate the race-specific association between a history of GDM and incidence of type 2 diabetes and evaluate how the risk changed over different years after delivery. We performed two large cohorts - the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with African Americans and whites in the U.S. (188 GDM and 1625 non-GDM women), and the Tianjin GDM Observational Study with Chinese in China (1263 GDM and 705 non-GDM women). The multivariate cox regression model was used to assess the risk of incident diabetes postpartum between women with and without GDM. During a mean follow-up of 13.9 years, 419 women developed type 2 diabetes. After adjustment for multiple confounding factors, Chinese women with GDM had a higher risk of incident diabetes within 5 years postpartum than African Americans with GDM compared with Chinese and African Americans without GDM (Hazard ratio 71.5 in Chinese vs. 11.0 in African Americans). When the risk of incident diabetes was analyzed within 10 years, white women with GDM seemed to have a higher hazard ratio than African American and Chinese women with GDM compared with women without GDM of different race. In comparison to African American women without GDM, different racial women with GDM showed an increased risk of type 2 diabetes within 10 years postpartum, however, white women without GDM had a decreased risk of type 2 diabetes. The largest increased risk of type 2 diabetes over 10 years postpartum appeared in Chinese women with GDM (Hazard ratio 23.9), followed by African American women with GDM (Hazard ratio 4.92), and the smallest was seen in white women with GDM (Hazard ratio 3.57). Chinese women with a history of GDM had the highest risk of incident diabetes postpartum. The different genetic backgrounds and other risk factors among different races might contribute to the racial differences in the incidence of diabetes postpartum among women with GDM.

Disclosure

Y. Shen: None. L. Hou: None. H. Liu: None. L. Wang: None. J. Leng: None. W. Li: None. G. Hu: None.

Funding

Tianjin Women’s and Children’s Health Center; Tianjin Public Health Bureau; European Foundation for the Study of Diabetes/Chinese Diabetes Society; Lilly Program for Collaborative Research between China and Europe; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100790 to G.H.); National Institute of General Medical Sciences (U54GM104940 to G.H.)
1428-P: Longitudinal Changes in Glucose during Pregnancy in Women with Gestational Diabetes Risk Factors
Authors: MILANA A BOCHKUR DRATVER , JAMES KAITLYN , ARENAS JULIANA , CAYFORD MELODY , CALLAHAN MICHAEL J. , TANGREN JESSICA S. , BERNSTEIN SARAH N. , HIVERT MARIE-FRANCE , POWE CAMILLE E.
Published: June 2019

Background: It is unclear what diagnostic criteria for hyperglycemia should be applied in early pregnancy; some suggest applying criteria used outside of pregnancy, while others suggest applying gestational diabetes mellitus (GDM) criteria. Prior studies have reported inconsistent changes in glucose levels across pregnancy.

Methods: We recruited women with at least 1 risk factor for GDM. We performed 75-gram oral glucose tolerance tests on 40 non-pregnant (NP) women and serially on 71 pregnant women [completed visits: 71 at 10-14 (mean 12.8) weeks gestation (V1), 46 at 24-28 (mean 26.8) weeks gestation (V2), 32 at 6 weeks-6 months postpartum (V3)]. We tested for differences in glucose levels between the NP and pregnant women at V1, V2, and V3 using linear regression, with adjustment for age and family history of diabetes. We tested for longitudinal differences in glucose levels across pregnancy and postpartum (V1, V2, and V3) using mixed effects models.

Results: Fasting glucose was lower in pregnant compared to NP women by 5.0 mg/dl at V1 (P=0.01) and 5.7 mg/dl at V2 (P=0.01). Fasting glucose was lower by 2.8 mg/dl at both V1 and at V2 compared to postpartum values (V1 vs. V3, P=0.04; V2 vs. V3, P<0.05). Post-load glucose at V1 did not differ from V3 or NP women. At V2, 30 minutes and 1 hour post-load glucose levels were higher in comparison to both V3 and NP levels (30 minutes: V2 vs. V3 9.7 mg/dL P=0.02, V2 vs. NP 12.0 mg/dL P=0.04; 1 hour: V2 vs. V3 13.0 mg/dl P=0.04, V2 vs.NP 21.1 mg/dL P=0.02). Two-hour post-load glucose did not differ between V2 and NP or V3 levels (P>0.3 for all comparisons). There were no differences between V3 and NP glucose levels (P>0.1 for all comparisons).

Conclusion: We confirmed reduced fasting glucose in pregnant women, with stability from the late 1st trimester through the early 3rd trimester. In contrast, early post-load glucose values increased in late pregnancy. This implies that establishing pregnancy- and gestational age- specific diagnostic criteria for hyperglycemia is imperative.

Disclosure

M.A. Bochkur Dratver: None. K. James: None. J. Arenas: None. M. Cayford: None. M.J. Callahan: None. J.S. Tangren: None. S.N. Bernstein: None. M. Hivert: None. C.E. Powe: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K23DK113218); Robert Wood Johnson Foundation; Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD094150)
1429-P: A Review of Prepregnancy Care and Pregnancy Outcomes in Pregestational Diabetes—Are Prior Improvements in Pregnancy Preparation and Outcomes Maintained for Women with Pregestational Diabetes?
Authors: NEWMAN CHRISTINE , CARMODY LOUISE , EGAN AOIFE M. , OWENS LISA A. , DUNNE FIDELMA
Published: June 2019

Women with pre-existing diabetes (T1DM/T2DM) face increased risk in pregnancy. Optimising glycaemic control, folic acid use and smoking cessation are all advised to improve outcomes. Maintaining these goals can be difficult. We retrospectively analysed data from sites across our Atlantic DIP network from 2015-17 and compared outcomes to data 2010-14 to see if prior improvements were maintained. Data was collected on pre-pregnancy care (PPC), glycaemic targets and neonatal outcomes. In total 98 women attended; 76 (78%)/22 (22%) with T1DM and T2DM respectively. Booking maternal BMI reduced but a fall in PPC attendance lead to lower folic acid use, greater teratogenic medication use and static smoking rates. Trimester 1 HbA1C was suboptimal in T1DM but patients subsequently reached target. HbA1C improved throughout pregnancy for T2DM and was at target (Table 1). Between the two time periods outcomes were unchanged for miscarriage, shoulder dystocia, NICU admission, macrosomia, LGA, SGA and birth weight. We recorded no stillbirths or congenital malformations. Improvements occurred in prematurity (<003C34w) and neonatal hypoglycaemia.

It is reassuring to record maintenance/improvement in neonatal outcomes but ongoing education on the importance of PPC and novel ways to reach patients are required.

Disclosure

C. Newman: Speaker's Bureau; Self; Sanofi. L. Carmody: None. A.M. Egan: None. L.A. Owens: None. F. Dunne: None.
1431-P: Intuitive Eating in Pregnancy Is Associated with BMI, Fasting Glucose, and A1c at One-Year Postpartum in Women with GDM: A Cohort Study
Authors: QUANSAH DAN YEDU , GROSS JUSTINE , GILBERT LEAH , HORSCH ANTJE , PUDER JARDENA J.
Published: June 2019

In women with GDM, there is a need to investigate novel lifestyle approaches to reduce the risk of future diabetes. Intuitive eating (IE) is an adaptive eating behavior where individuals accurately interpret and adhere to instinctive feedback regarding the required amount and timing of food. We evaluated the associations between IE during and after pregnancy with BMI, fasting glucose and A1c at 1-year postpartum (PP) in 117 women with GDM and in high-risk GDM subgroups with PP prediabetes or overweight/obesity. Women with GDM who consented and completed the “Eating for Physical rather than Emotional Reasons (EPR)” and “Reliance on Hunger and Satiety cues (RHSC)” subscales of the validated Intuitive Eating Scale-2 questionnaire during the first GDM clinic visit at 24-32 weeks of gestation and at 1-year PP were included. Participants mean age was 33.21±5.37 years, weight and BMI before pregnancy and at 1-year PP were 69.46±13.99kg, 25.82±4.69kg/m2 and 72.79±16.22kg, 27.06±5.54kg/m2 respectively, and the prevalence of prediabetes at 1-year PP was 46.2%. EPR at the first GDM visit predicted lower BMI (β=-0.219, p=0.017) and fasting glucose (β=-0.229, p=0.014) at 1-year PP, while associations were not significant for RHSC. At 1-year PP, EPR and RHSC were inversely associated with BMI (β=-0.243 to -0.337, both p≤ 0.012), whereas EPR was inversely associated with A1c and fasting glucose (β=-0.216 to -0.222, both p=0.018). In the subgroup of women with prediabetes, EPR and RHSC at the first GDM visit predicted lower fasting glucose at 1-year PP, while in the overweight/obese subgroup this was only significant for EPR (all p≤0.02). At 1-year PP however, both EPR and RHSC were inversely associated with BMI in women with prediabetes and with fasting glucose in overweight/obese women (all p≤0.03). No associations were found in low-risk GDM subgroups. Higher adherence to IE could represent a novel approach for PP BMI and glycemic control in women with previous GDM.

Disclosure

D.Y. Quansah: None. J. Gross: None. L. Gilbert: None. A. Horsch: None. J.J. Puder: None.

Funding

Swiss National Science Foundation; Lausanne Integrative Metabolism and Nutrition Alliance
144-OR: Ultra Rapid Lispro (URLi) Improves Postprandial Glucose (PPG) Control vs. Humalog (Lispro) in T1D: PRONTO-T1D Study
Authors: KLAFF LESLIE J. , CAO DACHUANG , DELLVA MARY A. , TOBIAN JANET , MIURA JUNNOSUKE , DAHL DOMINIK , BUE-VALLESKEY JULIANA M.
Published: June 2019

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. This phase 3, 26-week trial evaluated the efficacy and safety of URLi vs. lispro in 1222 adults with T1D. The primary endpoint was A1C change from baseline after 26 weeks of treatment, with multiplicity adjusted objectives for PPG excursions (PPGE) after test meal. After an 8-week lead-in to optimize basal insulin glargine or degludec, patients were randomized to double-blind URLi (n=451) or lispro (n=442) given at the start of the meal, or open-label URLi (n=329) given 20 minutes after the meal (URLi +20).

A1C was reduced for URLi and lispro and non-inferiority (NI) was shown: estimated treatment difference (ETD) -0.08 [-0.16; 0.00] p=0.06 (Figure). NI for URLi +20 vs. lispro was also shown: ETD +0.13 [0.04; 0.22] p=0.003. URLi was superior to lispro in controlling 1- and 2-h PPGE during the test meal (Figure).

No significant differences were seen between URLi vs. lispro in rate or incidence of severe hypoglycemia; overall daily or postprandial hypoglycemia (<54 mg/dL) ≤4 h after meals, but URLi had a 37% lower hypoglycemia rate in the period >4 h, (p=0.013). Overall, the incidence of treatment-emergent adverse events was similar between groups.

URLi was efficacious with a similar safety profile to lispro and, when given at start of the meal, provided superior PPG control vs. lispro.

Disclosure

L.J. Klaff: Research Support; Self; Abbott, Ascensia Diabetes Care, Cnoga Medical, Gan & Lee Pharmaceuticals, Lilly Diabetes, Medtronic MiniMed, Inc., Novo Nordisk Inc., REMD Biotherapeutics, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. D. Cao: Employee; Self; Eli Lilly and Company. M.A. Dellva: Employee; Self; Eli Lilly and Company. J. Tobian: Employee; Self; Eli Lilly and Company. J. Miura: None. D. Dahl: None. J.M. Bue-Valleskey: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
1440-P: Does HbA1c Impact Survival in the Newly Diagnosed Elderly Aged 75 Years and Over?
Authors: MCGILL MARGARET , MOLYNEAUX LYNDA M. , CONSTANTINO MARIA I. , TWIGG STEPHEN M. , MIDDLETON TIMOTHY , WU TED , WONG JENCIA
Published: June 2019

Clinical practice guidelines recommend screening for diabetes after the age of 45 years, but without an upper age limit. An ageing population has resulted in increasing numbers of older people being diagnosed. Previous reports indicate a J-shaped relationship between HbA1c and mortality in older populations with largely longstanding diabetes. However, whether these mortality relationships hold true in the newly diagnosed elderly remains uncertain, as do appropriate glycaemic targets. We aimed to study the relationship between HbA1c and mortality in newly diagnosed elderly aged ≥ 75 years. Records from the RPA Diabetes Clinical Database from 1988 to 2015, linked with the Australian National Death Index to establish all cause, IHD and cancer mortality outcomes were examined. 376 subjects were studied; median diabetes duration at first visit was 0.8 years (IQR 0.2-2.4), with mean age at diagnosis 78.7±3.1 years, 48% male and 53% Angloceltic. Data were stratified by updated HbA1c% NGSP Units categories (< 6; 6.1-7.0; 7.1-8.0; 8.1-9.0 and >9) with a median of 1.8±1.5 measures. Over a median observation period of 6.0 (IQR 2.8-10.4) years there were 237 deaths (17% from cancer, 38.9% from IHD). Using Kaplan-Meier survival analysis for all-cause mortality, no differences in survival between the HbA1c categories were seen (logrank p=0.8). Cox regression was used to examine the relationship between all-cause mortality and updated HbA1c categories after accounting for age or duration at first visit, gender and ethnicity. No significant differences nor observable trends in RR were seen using the HbA1c 6.1-7% group as reference. Prior albuminuria, stroke history and lipid status also had no impact on this relationship. Examination of IHD and cancer-related deaths similarly showed no relationship with HbA1c in this population. Whilst current guidelines recommend a general HbA1c target of 7% to 8% in the elderly we did not demonstrate a survival benefit for any HbA1c level in these newly diagnosed over 75 years of age.

Disclosure

M. McGill: None. L.M. Molyneaux: None. M.I. Constantino: None. S.M. Twigg: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Board Member; Self; AstraZeneca. Research Support; Self; Abbott. Speaker's Bureau; Self; Abbott, AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. T. Middleton: Other Relationship; Self; AstraZeneca. T. Wu: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. J. Wong: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; AstraZeneca, Lilly Diabetes.
1441-P: Correlation of Serum Osteocalcin Levels and Relative Skeletal Muscle Index and Hyperglycaemia in a Cohort of Middle-Aged and Elderly Individuals
Authors: XU YITING , MA XIAOJING , SHEN YUN , GU CHENGCHENG , TANG JUNLING , BAO YUQIAN
Published: June 2019

Aims: Osteocalcin is involved in energy metabolism and is sufficient to prevent age-related muscle loss. The aim of the present study was to investigate the association of serum osteocalcin levels with muscle mass and the role of metabolic factors in this association.

Methods: A total of 1742 middle-aged and elderly subjects (median age: 61.2 years; interquartile range: 56.9-65.3 years) were enrolled from Shanghai communities, including 775 men and 967 postmenopausal women. Serum osteocalcin levels were measured by an electrochemical immunoluminescence assay. An automatic bioelectric impedance analyser (BIA) was used to measure body compositions. Relative skeletal muscle index (SMI) was calculated using the BIA equation from Janssen et al.

Results: SMI was significantly higher in men than in postmenopausal women (37.30% [35.14%-39.63%] versus 27.72% [25.99%-29.66%], P < 0.001). Increasing SMI was associated with decreases in the frequency of overweight/obesity, central obesity, dyslipidaemia, elevated blood pressure, and hyperglycaemia (all P < 0.001). Serum osteocalcin levels were positively correlated with SMI in both men and women, regardless of treatment as a categorical or continuous variable (all P < 0.001). However, after accounting for confounding variables, the relationship remained only in men with hyperglycaemia (standardized β = 0.068, P = 0.024). Among men with isolated impaired glucose tolerance, the odds ratio of increased SMI was 2.861 in the fourth osteocalcin quartile compared with the lowest (P = 0.046). Multiple stepwise regression revealed that each standard deviation (SD) increase of serum osteocalcin levels resulted in an increase of 0.131 SD in SMI (P = 0.024).

Conclusion: In men with hyperglycaemia, especially in those with isolated impaired glucose tolerance, serum osteocalcin levels were positively correlated to SMI. However, no association was detected in postmenopausal women.

Disclosure

Y. Xu: None. X. Ma: None. Y. Shen: None. C. Gu: None. J. Tang: None. Y. Bao: None.
1449-P: Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Diabetes: The Study of Women's Health Across the Nation (SWAN)
Authors: HEDDERSON MONIQUE M. , LEE CATHERINE , CAPRA ANGELA , LEE JENNIFER , CHANG PO-YIN , GOLD ELLEN , WAETJEN ELAINE , HABEL LAUREL A. , EL KHOUDARY SAMAR R.
Published: June 2019

Low circulating levels of sex hormone-binding globulin (SHBG), a putative marker of androgenicity, have been associated with poor glucose control in studies conducted primarily among post-menopausal women. However, the relation of long-term changes in endogenous SHBG to risk of type 2 diabetes (T2DM) in women during and after the menopause transition is unclear. We aimed to assess the longitudinal associations between SHBG levels and risk of developing T2DM among such women. We included 3,060 participants in the Study of Women’s Health Across the Nation (SWAN) who were free of diabetes at baseline. SWAN is a longitudinal cohort study with up to 17 years of follow-up. SHBG levels were measured at 13 visits. Participants reported diagnosed diabetes status at all visits, and fasting glucose was measured at 8 follow-up visits. T2DM was defined based on self-report or fasting glucose levels. Women averaged 46 (SD=3) years of age at baseline. 311 women developed T2DM during follow-up. We used complementary log-log-based discrete time survival models anchored at baseline to estimate associations of longitudinal SHBG with incident T2DM. A 5-unit (nM) increase in time-varying SHBG was associated with a hazard ratio (HR) of 0.86 (95% CI 0.82, 0.90), for T2DM, after controlling for race-ethnicity, age, cycle day of blood draw, site, time-varying body mass index (BMI), testosterone, and baseline SHBG level. After adjusting for covariates, women in the lowest ((-92.0 - -1.1 nM/year) vs. highest quartile (0.7 - 42.1 nM/year) for time-invariant average rate of change per year in SHBG levels) had a HR of 5.18 (95% CI: 3.55,7.56). No association was observed for other quartiles in rate of change of SHBG with developing T2DM. Women with low levels of SHBG and/or decreases in SHBG levels were at increased risk to develop T2DM. Clinicians should be aware that declining levels of SHBG in mid-life women is strongly associated with developing T2DM, independent known T2DM risk factors.

Disclosure

M.M. Hedderson: None. C. Lee: None. A. Capra: None. J. Lee: None. P. Chang: None. E. Gold: None. E. Waetjen: None. L.A. Habel: None. S.R. El Khoudary: None.

Funding

National Institutes of Health
145-LB: Phase 1/2 Safety and Proof of Biological Activity Study of AT-001, an Aldose Reductase Inhibitor in Development for Diabetic Cardiomyopathy
Authors: SHENDELMAN SHOSHANA , PERFETTI RICCARDO
Published: June 2019

Hyperactivation of the polyol pathway (PP) contributes to development of diabetic complications. Aldose reductase (AR) is the rate-controlling enzyme in PP that catalyzes NADPH-dependent reduction of glucose to sorbitol. In hyperglycemic and ischemic conditions, PP activation causes intracellular sorbitol accumulation leading to osmotic stress, cell death and diabetic complications. We developed AT-001 based on further characterization of AR and structural changes within the active site of AR following enzymatic activation to design molecular AR inhibitors with enhanced specificity, affinity and selectivity compared with previous AR inhibitors that failed to inhibit redox-activated AR and were associated with off-target effects and/or lack of efficacy. AT-001 safety, pharmacokinetics (PK) and efficacy were assessed in a phase 1/2 study comprised of single oral ascending doses (SAD, n=8 per group) of 5, 10, 20 and 40 mg/kg once daily (QD) and multiple doses (MAD) of placebo (Pbo) or AT-001 5, 20, 40 mg/kg QD or 20 mg/kg twice daily (BID) for 7 d. Subjects with type 2 diabetes, age 18-75 and HbA1c 5.0-8.5% were allocated to each dose cohort (n=8 AT-001, n=2 Pbo). AT-001 was well-tolerated with no drug-related AEs or changes in liver or renal function up to the highest dose tested. Mean half-life (T1/2) and time of maximum concentration (Tmax) ranged from 1.7-3h and 1.75-3h, respectively in both SAD and day 1 MAD with no accumulation at day 7. AR inhibition was confirmed by significant dose-dependent reductions in whole blood sorbitol in SAD and MAD up to approximately -50% change from baseline in SAD and days 1 and 7 of MAD vs. a -3% change in Pbo (p<0.05 for all doses vs. Pbo). Maximum inhibition occurred between 2-4 h. Conclusions: greater selectivity and affinity of AT-001 for AR may endow acceptable safety. These findings support further investigation of the therapeutic potential of AT-001 in subjects with diabetes complications.

Disclosure

S. Shendelman: Stock/Shareholder; Self; Applied Therapeutics Inc. Other Relationship; Self; Applied Therapeutics Inc. R. Perfetti: Employee; Self; Applied Therapeutics Inc., Sanofi. Stock/Shareholder; Self; Applied Therapeutics Inc., Sanofi.
1451-P: The Association of Metformin with Mortality in Frail Older Veterans with Diabetes
Authors: MILYANI RANEEM , APARICIO-UGARRIZA RAQUEL , GUERRA JULIANA FERRI , SALGUERO DOUGLAS , MOHAMMED YAQUB NADEEM , VALENCIA WILLY , FLOREZ HERMES , RUIZ JORGE G.
Published: June 2019

Diabetes (DM) is associated with an accelerated aging that promotes frailty, a state of vulnerability to stressors resulting in higher morbidity, mortality and healthcare utilization. Data from the UKPDS showed that metformin may lead to lower risk of overall mortality in middle aged adults with type 2 DM (T2D) but the evidence is less clear in frail older adults. The aim of this study was to determine whether metformin is associated with reduced mortality in frail older Veterans. This is a retrospective cohort study of 393 Veterans 65 years and older with DM, who were identified as frail through calculation of a 44-item frailty index (FI≥.21) on January 2016-August 2017 and followed until October 2018. The FI was constructed as a proportion of all potential variables (demographics, comorbidities, medications, laboratory tests, and ADLs) at the time of the screening. At the end of follow-up, we aggregated data on mortality of those Veterans with frailty and compared those who were taking metformin (n=164, 41.7%) versus those who were not taking that medication (n=229, 58.3%). After adjusting for age, race, ethnicity, BMI, DM complications, level of glycemic control, use of insulin or sulfonylureas and comorbidities, the association of metformin with mortality was determined using a multivariate Cox regression model. Patients were 56.3% white, 76.9% non-Hispanic, 98.7% male, mean age was 73.14 (SD=7.31) years. Over a median follow-up period of 593 days (IQR=179), 62 deaths occurred (n=15, in those taking metformin vs. n=47 in those not taking it). After adjusting for covariates, frail Veterans taking metformin had a lower risk for mortality, adjusted hazard ratio (HR) .466 (95% CI: .255-.849), p=.013 than those not taking the drug. These results suggest that metformin may reduce all-cause mortality in frail older adults with diabetes. Further studies may be needed to assess the impact of metformin on quality of life and potential benefits on specific morbidity and mortality in this high-risk population.

Disclosure

R. Milyani: None. R. Aparicio-Ugarriza: None. J. Ferri Guerra: None. D. Salguero: None. Y. Mohammed: None. W. Valencia: None. H. Florez: None. J.G. Ruiz: None.

Funding

Miami VA Healthcare System Geriatric Research Education and Clinical Center
1455-P: Evaluating Opportunities for Deprescribing in the Elderly and Extreme Elderly with Diabetes
Authors: SHARP SABRINA A. , OVERLAND JANE , MCGILL MARGARET , MOLYNEAUX LYNDA M. , WU TED , TWIGG STEPHEN M. , WONG JENCIA
Published: June 2019

Individualised approaches to diabetes management are essential so that an optimal balance is realised between the risk and benefits of treatment. In the elderly (E, 75-84 years) and extreme elderly (EE, ≥ 85 years) treatment adjustment is the cornerstone of management, in order to provide medicines that deliver efficacy, and to de-prescribe agents to limit iatrogenic adverse effects. To assess the opportunity to de-prescribe and better target prescribing, we performed a retrospective audit of 1,806 patients (E, n=1,649; EE, n=157). Data are presented as E and EE respectively. The majority had T2DM (99.1%), with long duration (median, IQR 13.9, 7.4-21.7; 17.5, 10.3-25.1 years); and were overweight (mean ± SD BMI 28.7 ± 5.4; 27.0 ± 4.5 kg/m2). Over 50% used polypharmacy for glycaemic control; 37.9% and 40.8% used insulin +/- tablets. 39.4% of E and 33.3% of EE achieved an HbA1c of <7.0%, with HbA1c 7.5 ±1.4% and 7.8 ± 1.6% (mean± SD NGSP units). Over half (55.8%) of the EE group with an HbA1c <7.0% were treated with insulin and/or sulphonyureas, whereas only 38.2% of E were treated with these agents (p=0.01). While reported severe hypoglycaemia was uncommon (1.5% E and 2.8% EE), 35% of EE patients using insulin and/or sulphonyureas experienced hypoglycaemia. Metformin had appropriately been ceased in all but 7 of the 63 patients with an eGFR < 30 ml/min/1.73m2. While lipid profiles were favourable (HDL: 1.3 ± 0.4 mmol/L; LDL: 2.3 ± 0.9 mmol/L, Trig: 1.5, IQR: 1.1-2.1 mmol/L and HDL: 1.3 ± 0.3 mmol/L; LDL: 2.3 ± 1.0 mmol/L, Trig: 1.5, IQR: 1.0-2.1 mmol/L), lipid lowering therapy was used less frequently in EE (51.0%) versus E (62.6%) (p=0.004). Only 1 in 2 patients with known macrovascular disease were on anti-platelet treatment. This data demonstrates the potential over treatment of glycaemia in the EE specifically in hypoglycaemia inducing agents, highlighting the need to consider de-prescribing. Conversely, under-utilisation of evidence-based medication to address macrovascular risk is also evident.

Disclosure

S.A. Sharp: None. J. Overland: None. M. McGill: None. L.M. Molyneaux: None. T. Wu: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. S.M. Twigg: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Board Member; Self; AstraZeneca. Research Support; Self; Abbott. Speaker's Bureau; Self; Abbott, AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. J. Wong: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; AstraZeneca, Lilly Diabetes.
1463-P: LEADER Eligibility and Preventable Cardiovascular Events in the U.S. Population: An Analysis of the National Health and Nutrition Examination Survey
Authors: WONG NATHAN D. , FAN WENJUN , TONG COREY A.
Published: June 2019

Background: The LEADER trial showed in persons with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) or at high CVD risk the efficacy of liraglutide in reducing CVD events. We projected the impact of applying the LEADER trial results on reducing CVD events in U.S. adults with T2DM.

Methods: We identified U.S. adults eligible for LEADER from available inclusion criteria in the U.S. NHANES Survey. We estimated the number of primary (CVD death, myocardial infarction and stroke) and secondary CVD and microvascular events based on LEADER published event rates in the liraglutide and placebo groups, the difference being the number of preventable events.

Results: Among 29,629 adults aged >18 years (representing 231.9 million [M]), 4,672 (27.3 M) were identified with T2DM; 1,299 (7.2M) had an HbA1c of >7% and were aged >50 years, of which 595 (3.3M) had CVD or chronic kidney disease and 205 (0.9M) were aged >60 years with microalbuminuria or proteinuria for a total of 800 (4.2 M) who fit LEADER eligible criteria. Other criteria such as carotid or peripheral arterial disease or left ventricular hypertrophy were not available. From LEADER primary endpoint event rates of 13.0% and 14.9% over 3.8-year follow-up in the liraglutide and placebo groups, respectively, we estimated 551,420 and 632,012 events would occur, respectively, for a total of 80,592 (21,209/yr) preventable CVD events. Estimated preventable expanded composite outcomes were 101,800 (29,691/yr), myocardial infarctions 42,417 (12,725/yr), microvascular events 55,142 (12,725/yr), nephropathy occurrences 63,625 (19,967/yr), and all-cause 59,384 (16,967/yr) and CVD 55,142 (16,967/yr) deaths.

Conclusion: We show many CVD events (including myocardial infarctions, CVD and total deaths, as well as microvascular complications) in U.S. adults with DM could be prevented from liraglutide therapy highlighting the need for interventions with proven cardioprotective effects.

Disclosure

N.D. Wong: Advisory Panel; Self; Novartis Pharmaceuticals Corporation. Consultant; Self; Akcea Therapeutics, AstraZeneca. Research Support; Self; Amarin Corporation, Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. W. Fan: None. C.A. Tong: None.

Funding

Novo Nordisk
1486-P: Longitudinal Interrelationships of Adiposity-Associated Biomarkers in Women
Authors: BADEN MEGU , HU FRANK , HUANG TIANYI
Published: June 2019

Background: Most prior studies on associations of adiposity-associated biomarkers are cross-sectional. Understanding their longitudinal interrelationships may provide mechanistic insights into biologic pathways that lead to cardiometabolic diseases.

Methods: We included 850 healthy women in the Nurses’ Health Study II (mean age: 45y) who provided two blood samples in 1996-1999 and 2010-2011 and measured plasma concentrations of adiponectin (ADPN), leptin, soluble leptin receptor, insulin, retinol binding protein-4, high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6). All biomarkers were log2-transformed. Spearman partial correlations were used to examine cross-sectional biomarker associations at baseline and follow-up. Multivariable general linear models were used to evaluate associations of each biomarker change over 13 years with (1) concurrent changes in other biomarkers (change-change) and (2) baseline levels of other biomarkers (baseline-change).

Results: In cross-sectional analyses, most biomarkers were correlated after multivariable adjustment including BMI (p<0.05) both at baseline and follow-up, with the strongest associations observed between leptin/insulin and hsCRP/IL-6. There were similar associations in the change-change analysis with multivariable adjustment including weight change. However, only two associations were consistently present in the baseline-change analysis after multivariable adjustment including baseline BMI. Every doubling in baseline hsCRP was associated with 3.1% leptin change (p=0.01), whereas every doubling in baseline ADPN was associated with -9.2% insulin change (p=0.01). Notably, baseline insulin was not associated with other biomarker changes.

Conclusions: While most adiposity-associated biomarkers were interrelated both cross-sectionally and longitudinally, our results suggest that baseline hsCRP and ADPN were strong predictors for long-term changes in leptin and insulin, respectively.

Disclosure

M. Baden: Other Relationship; Self; Manpei Suzuki Diabetes Foundation. F. Hu: None. T. Huang: None.

Funding

National Institutes of Health; Manpei Suzuki Diabetes Foundation
1490-P: Using Longitudinal Modeling to Find One-Hour Glucose Alternatives to Two-Hour Glucose for Prediction and Diagnosis of Glucose Tolerance
Authors: HA JOON , CHUNG STEPHANIE T. , SUMNER ANNE E. , BERGMAN MICHAEL , BOGARDUS CLIFTON , SHERMAN ARTHUR
Published: June 2019

One-hour glucose (1h-PG) during an oral glucose tolerance test (OGTT) is an emerging biomarker for diagnosis and prediction of prediabetes (preDM) and type 2 diabetes (T2D). Our objectives were to: (1) use a longitudinal mathematical model to predict the pattern of glucose rise in 1h-PG and 2h-PG concentration with time and (2) test our predictions in a longitudinal cohort of 52 Pima Indians (baseline age, 26.5±5.8 years; BMI, 36.6±5.8 kg/m2) who were followed for 7.2±3.5 years. Model simulations suggested that the 1h-PG would pass the threshold of 155 mg/dl before the 2h-PG passed the threshold of 140 mg/dl for most individuals, and that the time difference could be as much as several years, depending on the balance of impairments in insulin resistance and early-phase insulin secretion. Using the longitudinal data set, we estimated the times of crossing the 1h-PG and 2h-PG thresholds by fitting a linear mixed effect model to trajectories of individual participants. Participants had a median of 6 (range 3-11) separate OGTTs, 1.7±0.8 years apart. For most participants (48/52), 1h-PG of 155 mg/dl was observed before 2h-PG reached 140 mg/dl (time difference, 1.9±2.0 years). Using the linear fits we also estimated that the average 1h-PG value would be 217 mg/dl (12.0 mmol/L) when 2h-PG reached 200 mg/dl (11.1 mmol/L). Overall, the times of crossing the 1h-PG threshold of 155 mg/dl and the 2h-PG threshold of 140 mg/dl were correlated, but 1h-PG crossed earlier, thus providing an earlier indication of future hyperglycemia. Additionally, since 1h-PG and 2h-PG rise together during the progression from preDM to T2DM, a 1h-PG of 217 mg/dl could be an alternative marker to the 2h-PG of 200 mg/dl for the diagnosis of T2D.

Disclosure

J. Ha: None. S.T. Chung: None. A.E. Sumner: None. M. Bergman: None. C. Bogardus: None. A. Sherman: None.
1500-P: Continuous Glucose Monitoring and Beta-Cell Function in Youth with Cystic Fibrosis
Authors: CHAN CHRISTINE L. , VIGERS TIM B. , PYLE LAURA , ZEITLER PHILIP , NADEAU KRISTEN J.
Published: June 2019

Continuous glucose monitoring (CGM) is frequently used to assess glucose abnormalities in cystic fibrosis (CF) prior to frank diabetes, yet the biological significance of various CGM measures is unclear. Our aim is to identify CGM measures correlated with β-cell function decline in youth with CF. CGM and 2 hour oral glucose tolerance testing (OGTT) were collected in youth with CF and healthy controls (HC). Glucose and insulin were measured at baseline and 30 minutes on OGTT. Insulinogenic index [IGI=(insulin30-insulin0)/(Glucose30-Glucose0)] was used to estimate β-cell function. Eighty-one participants were included in the analysis [15 HC, 13 CF normal glucose tolerance (NGT), 41 CF abnormal glucose tolerance, and 12 CF related diabetes by OGTT]. There were no differences in age (13.6±3.5 years), sex, race, nor BMI z-score among groups. IGI was significantly lower in all CF groups, even CF NGT, compared to HC (p<0.0001). Table 1 presents correlations between CGM measures and IGI. Youth with CF, despite NGT by OGTT, have impairments in insulin secretion. Greater peak glucose, %time >140 mg/dl, and glucose variability (SD and MAGE), but not measures of average nor low glucose, on CGM correlate with declines in β-cell function. Further studies are needed to determine whether these CGM measures predict clinical decline in CF.

Disclosure

C.L. Chan: None. T.B. Vigers: None. L. Pyle: None. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc. K.J. Nadeau: None.

Funding

Cystic Fibrosis Foundation (CHAN16A0, CHAN16GE0); National Institutes of Health (DK094712-04)
1503-P: Seasonal Changes in the Achievement of Guideline Goals for HbA1c, Blood Pressure, and Cholesterol in Patients with Type 2 Diabetes Mellitus: A Nationwide Population-Based Study (ABC Study)
Authors: MATSUTANI DAISUKE , SAKAMOTO MASAYA , MINATO SOICHIRO , TSUJIMOTO YUKI , KAYAMA YOSUKE , UTSUNOMIYA KAZUNORI , NISHIKAWA MASAKO
Published: June 2019

Aim: Precise monthly achievement rates for reaching guideline goals for HbA1c, blood pressure (BP), and cholesterol levels remain unknown. We evaluated achievement rates on a monthly basis in patients with type 2 diabetes mellitus (T2DM) and explored related factors.

Material and Methods: This retrospective study initially analyzed data on 104,601 patients with T2DM throughout Japan (38 medical clinics). Patients whose HbA1c, BP, and low-density lipoprotein (LDL)-cholesterol were measured ≥12 times during a 2-year period were included. We evaluated monthly achievement rates. Achieved goals were defined as HbA1c <7%, BP <130/80 mmHg, and LDL-cholesterol <100 mg/dL. Achievement of all goals was expressed as the "all ABC achievement."

Results: A total of 4,678 patients were analyzed. The achievement rates of all ABC, HbA1c, BP, and LDL-cholesterol exhibited seasonal variations with the lowest rates in winter, with those for systolic BP (SBP) being particularly low (all ABC, summer 15.6%, winter 9.6%; HbA1c, 53.1%, 48.9%; SBP, 56.6%, 40.9%; LDL-cholesterol, 50.8%, 47.2%). In the multiple logistic regression analysis, in winter, BMI ≥25 kg/m2 (BMI 25-30 kg/m2, odds ratio 0.45 [0.29-0.70], p < 0.001; BMI ≥30 kg/m2, 0.35 [0.22-0.57], p < 0.001) and diabetes duration ≥10 years (0.53 [0.37-0.76], p < 0.001) were independently related to lower achievement rates for HbA1c, and age ≥65 years (0.47 [95% CI 0.34-0.63], p < 0.001) was independently related to decreased achievement rates for SBP. Insulin and sulfonylurea use were independently associated with the decreased all ABC achievement rates in both summer and winter.

Conclusion: This study showed that in patients with T2DM, the achievement rates for blood glucose, BP, and lipid goal levels varied seasonally. Seasonal variations in the all ABC achievement rate should be considered when managing T2DM in ordinary clinical practices.

Disclosure

D. Matsutani: None. M. Sakamoto: None. S. Minato: None. Y. Tsujimoto: None. Y. Kayama: None. K. Utsunomiya: None. M. Nishikawa: None.
1509-P: Development of Self-Assessable Diabetes Risk Score: A 10-Year Prospective Cohort Study
Authors: OH TAE JUNG , MOON JAE HOON , CHOI SUNGHEE , LIM SOO , CHO YOUNG MIN , PARK KYONG SOO , CHO NAM H. , CHUL JANG HAK
Published: June 2019

Self-awareness of diabetes is the first step to prevent this non-curable disease. Therefore, it is important to develop diabetes risk scores which can be easily calculated by general people. We developed self-assessable diabetes risk score using the data of Korean Genome and Epidemiology Study (KoGES). A total of 8,740 subjects without diabetes at baseline were followed-up biannually over 10 years. We assessed the significantly different clinical and non-laboratory variables at baseline between subjects developed diabetes mellitus and those free from diabetes at 10-year follow-up. Each of variables generated a maximum score of 100 in each gender group. Next, the 10-year probability of incident diabetes in each score was calculated. During a median follow-up of 9.7 years, 22.7% of subjects progressed to diabetes. The self-assessable diabetes risk scores included age, living location, smoking history, hypertension, family history of diabetes and waist circumference. The developed risk score yielded acceptable discrimination for incident diabetes in both male (AUC 0.661) and female (AUC 0.691). If the subject had a score more than 50, the probability of 10-year incident diabetes would be 43.4% and 36.1% in male and female, respectively.

In conclusion, our newly developed self-assessable diabetes risk score is easily applicable to people without diabetes to predict their future risk of diabetes by themselves without laboratory tests. This model would be helpful to make a diabetes prevention program and to identify high risk subjects who should undergo laboratory tests more frequently. Further studies will be needed to validate the model and to test its feasibility in real clinical settings.

Disclosure

T. Oh: None. J. Moon: None. S. Choi: None. S. Lim: None. Y. Cho: Consultant; Self; Hanmi Pharm. Co., Ltd. Research Support; Self; AstraZeneca, Sanofi-Aventis. K. Park: None. N.H. Cho: None. H. Jang: None.

Funding

Korea Centers for Disease Control & Prevention
1521-P: An Efficacy Evaluation on Prediabetes Management Using a Machine Learning-Based Risk Stratification Approach
Authors: ZOU XIANTONG , ZHU ZHANXING , LUO YINGYING , LI YUFENG , ZHOU XIANGHAI , JI LINONG
Published: June 2019

The progression of prediabetes towards diabetes was heterogeneous, suggesting a demand for individualized management. We aim to investigate whether stratifying participants with prediabetes according to their progression risk could affect the response to interventions. We developed a 1-year diabetes progression risk evaluating model with a panel of diabetes risk factors using a machine learning method (i.e., Bagging algorithm with 300 decision trees) in prediabetes participants in Pinggu Study (a prospective population-based survey in suburban Beijing, n=622). The model training phase was conducted on 2/3 randomly selected participants and the validation phase was conducted on other 1/3. This model successfully predicted the 1-year progression of prediabetes participants in Pinggu study (internal ROC AUC 1.000, external ROC AUC 0.883). In Beijing Prediabetes Reversion Program (BPRP, a multi-central RCT to evaluate the efficacy of lifestyle and/or pioglitazone on prediabetes reversion, n=1897), subjects were divided into tertiles as high, medium and low risk groups according to their progression probability predicted by the model. Pioglitazone plus intensive lifestyle significantly increased reversion and reduced diabetes progression only in high risk group. This study suggests personalized treatment on prediabetes according to their progression risk is necessary.

Disclosure

X. Zou: None. Z. Zhu: None. Y. Luo: None. Y. Li: None. X. Zhou: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi.

Funding

The Major Chronic Non-Communicable Disease Prevention and Control Research of China; Beijing Science and Technology Committee; National Natural Science Foundation of China
1525-P: Increasing Trend in Dyslipidaemia among the Urban and Rural Populations in Tamil Nadu, Southern India, the STRiDE-I Study
Authors: NANDITHA ARUN , RAGHAVAN ARUN , SUSAIRAJ PRISCILLA , SATHEESH KRISHNAMOORTHY , SIMON MARY , VINITHA RAMACHANDRAN , SNEHALATHA CHAMUKUTTAN , RAMACHANDRAN AMBADY
Published: June 2019

Two cross-sectional epidemiological surveys were done in 2006 (Ramachandran A et al, Diabetes Care 2008) and 2016 (Nanditha A et al, Diabetes Care 2019, in press) in the same locations in men and women aged ≥ 20 years. We analyzed the increasing trend in dyslipidaemia among populations of varied levels of urbanization and socio-economic development in a 10 year period. Anthropometric measurements, clinical history, blood glucose and fasting serum lipid parameters were measured. The cut-off value suggested by the World Health Organization for Asian Indians for obesity was used. Prevalence of dyslipidaemia was calculated using the National Cholesterol Education Program criteria (NCEP Executive Summary, JAMA 2001). Prevalence of anthropometric and lipid abnormalities in 2006 and 2016 are shown in the Table. The total number screened were 7066 in 2006 and 9848 in 2016. Significant increases (p<0.0001) in the prevalence of generalized obesity and abdominal obesity were observed in the urban and even among the rural populations. Total cholesterol, triglycerides, HDLc, LDLc, and non-HDLc showed significant increase in all three areas except for HDLc in the town. The increasing prevalence of diabetes, prediabetes and abdominal obesity, noted in the primary study, could have been the major determinant for the rising trend in dyslipidaemia in these populations.

Disclosure

A. Nanditha: None. A. Raghavan: None. P. Susairaj: None. K. Satheesh: None. M. Simon: None. R. Vinitha: None. C. Snehalatha: None. A. Ramachandran: None.
1542-P: Diabetes Care Goal Achievement over 1999-2016 Was Similar in Rural and Urban America
Authors: MERCADO CARLA , BULLARD KAI M. , ALI MOHAMMED K. , IMPERATORE GIUSEPPINA , SAYDAH SHARON , GREGG EDWARD
Published: June 2019

Although it is hypothesized that rural American adults with diabetes (DM) have poorer control of ABCS risk factors [glycohemoglobin (A1c), Blood pressure (BP), Cholesterol, and Smoking], there are no empiric data comparing diabetes care in rural versus urban areas. We examined rural and urban differences in proportions of U.S. adults with DM achieving A1c <8.0%, BP <140/90 mmHg, non-HDL cholesterol <160 mg/dL, and current non-smoker, separately and combined. We analyzed data from 5,534 participants aged ≥18 years with diagnosed DM in the NHANES during 1999-2016. About 20% of U.S. adults with diagnosed DM reside in rural areas. ABCS goal achievement changes from 1999-2004 to 2011-2016 varied by urban/rural areas (see Table). Current non-smoker prevalence increased only for rural areas by 17 percentage points. Non-HDL cholesterol goal achievement increased by 17 percentage points in both rural and urban areas. In urban areas, achievement in BP and all ABCS goals increased by 8 and 15 percentage points, respectively. Although no significant difference was noted in achieving A1c goal from 1999-2004 to 2011-2016 in rural or urban areas, between 2005-2010 to 2011-2016, there was a decrease in A1c goal achievement in rural setting by 11 percentage points. Achievement of ABCS goals has generally improved among U.S. adults with DM, with about 1/3 of U.S. adults with DM achieving all four ABCS goals, regardless of rural/urban status.

Disclosure

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