bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Metabolomics Reveal Novel Metabolites in Early Pregnancy in Association with Gestational Diabetes Risk
Authors: ZHANG CUILIN , ANNE FENG YEN-CHEN , FIEHN OLIVER , TSAI MICHAEL Y. , ZHU YEYI , ALBERT PAUL , LIANG LIMING
Published: June 2018

Although metabolomics may shed light on the pathophysiology of glucose metabolism in pregnancy, systematic studies on their roles in the development of gestational diabetes (GDM) are sparse. We aimed to prospectively investigated metabolomics (both targeted and non-targeted) and GDM risk in a matched case-control study of 107 GDM and 214 non-GDM women in a multi-racial cohort. GDM diagnosis was based on Carpenter and Coustan Criteria. Twenty-two amino acids were quantified using plasma collected at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39. In addition, 331 primary metabolites were quantified by GC-TOF-MS as a part of our non-targeted approach. Adjusted odds ratios (aORs) of GDM related to metabolites (in quartiles (Q)) were estimated using conditional logistic regression after adjusting for major GDM risk factors including BMI. The present report focuses on findings using blood samples in early pregnancy 10-14GW. Alanine in GW 10-14were higher in GDM women than controls (mean: 30.5 vs. 27.6 umol/dl) and were positively related to GDM risk; aORs across increasing Qs were 1.00, 1.69, 2.86, 3.05, (P for trend =0.020). By contrast, asparigine and glycine were significantly lower in GDM women, and were inversely related to GDM risk; aORs across increasing Qs were 1.00, 0.92, 0.74, and 0.48 (P for trend = 0.045) for asparagine and 1.00, 0.42, 0.36, and 0.24 (P <0.001) for glycine. In addition, among primary metabolites from the non-targeted approach, isocitric acid levels were positively related to GDM risk; aORs across increasing Qs were 1.00, 1.30, 1.04, 2.32 (P for trend = 0.002). Furthermore, two unknown metabolites were strongly and inversely associated with GDM risk (aORs were 1.00, 0.52, 0.18, 0.11, and 1.00, 0.33, 0.12, 0.respectively; both P < 10-4).

Conclusion: Our study revealed several novel metabolites that may be implicated in the early pathogenesis of GDM, which might provide new etiological insight into the development of GDM.

Disclosure

C. Zhang: None. Y. Feng: None. O. Fiehn: None. M.Y. Tsai: None. Y. Zhu: None. P. Albert: None. L. Liang: None.
Association between Dementia and Glycemic Control in Elderly Patients
Authors: YASUDA TAKUMA , MURO SEIJI , FUJITA HARUKA , FUJIMURA MASAKI , HATOKO TOMONOBU , MORI EISAKU , YONEMITSU SHIN
Published: June 2018

Background: The goals of glycemic control based on their cognitive function are recommended for elderly patients. However, the recommendation of the glycemic control is different among the associations. That is, IDF and the Japan Diabetes Society set lower limit of HbA1c and ADA doesn’t. Moreover, there is not a clear course of treatments for elderly diabetics with dementia.

Methods: We retrospectively assessed the correlation between blood glucose management and cognitive function of 616 outpatients aged 65 years or older who visited our hospital from March 14 to April 30, 2017. HbA1c, blood glucose level, and therapeutic agents were obtained from medical records. Cognitive function was evaluated with Dementia Assessment Sheet for Community-based Integrated Care System 21-items (DASC-21), which the Japan Diabetes Society and the Japan Geriatrics Society approve. The patients were allocated to three categories based on cognitive function (normal function: I, mild dementia: II, moderate and severe dementia: III), and two categories based on therapeutic agents (not using insulin, SU, or glinide: A, using insulin, SU, and/or glinide: B).

Results: The numbers of the patients in IA, IB, IIA, IIB, IIIA, and IIIB were 138, 362, 11, 66, 7, and 32, respectively. The proportion of the patients whose HbA1c were below the lower limit was significantly higher in IIIB than that in IIB (43.8% vs. 19.7%, p <0.05). The proportion of the patients who underwent hypoglycemia (blood glucose <70 mg/dl) within recent 1 month was significantly higher in IIIB than that in IIB (28.1% vs. 18.2%, p <0.05). In IIIB, there were more hypoglycemic events in the patients whose HbA1c were above the lower limit than the patients whose HbA1c were below the lower limit (38.9% vs. 14.3%, p <0.05).

Conclusions: This study shows that progression of cognitive impairment increases the risk of hypoglycemia. Moreover, this result suggests that the risk of hypoglycemia shouldn’t be evaluated only with HbA1c for elderly patients with dementia.

Disclosure

T. Yasuda: None. S. Muro: None. H. Fujita: None. M. Fujimura: None. T. Hatoko: None. E. Mori: None. S. Yonemitsu: None.
Readmission and Comprehension of Diabetes Education at Discharge (ReCoDED Study)
Authors: SWAMI JANYA , DONIHI AMY , SIMINERIO LINDA M. , FRENCH ESRA KARSLIOGLU , DELISI KRISTIN , HLASNIK DEBORAH S. , PATEL NEETI , PINKHASOVA DIANA , RUBIN DANIEL J. , KORYTKOWSKI MARY T.
Published: June 2018

Diabetes (DM) is a major contributor to risk for hospital readmission. The Diabetes Early Readmission Risk Indicator (DERRI) is a predictor of 30-day readmission in patients with DM that may allow early identification and intervention for high-risk patients. A limitation to DERRI is the absence of DM-specific factors as contributors to this risk. To address this, we investigated HbA1c, glycemic measures and variability (GV), changes in DM therapy at discharge, and patient responses to a novel post-discharge questionnaire directed at Patient Comprehension (PC) of instructions provided for home DM management. Non-critically ill adult patients with DM were contacted by phone within 48 hours of hospital discharge to complete the PC Questionnaire. To date, 70 subjects (type 1 n=9, type 2 n=53, pancreatogenic DM n=8) (mean age 57.2 ± 12.8 years, BMI 31 ± 8.8 kg/m2, 56% men, 71% Caucasian, HbA1c 8.6 ± 2.0%, DM duration 19 ± 12 years, mean BG prior to discharge (210 ± 49 mg/dL), GV (66 ± 35 mg/dl) have been recruited. Of 41 subjects completing the PC questionnaire, those reporting that discharge instructions for home DM management were not provided had lower PC scores (70.6% vs. 81.5%, p=0.025) and more readmissions (OR 5.6, p=0.04) than those reporting that instructions were given. Among the 60 subjects with one-month post-discharge data, 22 patients (37%) reporting ≥1 readmission had higher DERRI scores than those without readmissions (26% vs. 20%, p=0.023). HbA1c, GV and changes in DM treatment regimens were not associated with readmission.

In summary, these results demonstrate that PC of discharge instructions may be a novel mediator of readmission risk and may add an additional measure of risk for hospital readmission.

Disclosure

J. Swami: None. A. Donihi: None. E. Karslioglu French: None. K. Delisi: None. D.S. Hlasnik: None. N. Patel: None. D. Pinkhasova: None. D.J. Rubin: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. M.T. Korytkowski: Advisory Panel; Self; Novo Nordisk Inc.. Other Relationship; Self; JAEB Center For Health Research.
Metformin and Lifestyle Interventions in DPP Do Not Have Long-Term Effects on Bone Density or Falls
Authors: SCHWARTZ ANN V. , PAN QING , ARODA VANITA , CRANDALL JILL P. , KRISKA ANDREA , PIROMALLI CHRISTOPHER S. , TEMPROSA MARINELLA , FLOREZ HERMES ,   DPP RESEARCH GROUP
Published: June 2018

Randomization to lifestyle intervention (ILS) or metformin (MET) in the Diabetes Prevention Program (DPP) resulted in weight loss and reduced progression to diabetes. The long term effects of these interventions on bone mineral density (BMD) and falls, both associated with weight loss, are not known. We determined if ILS or MET was associated with prevalence of osteoporosis, osteopenia or history of falls in the DPP Outcome Study (DPPOS).

During DPP, 3234 participants at high risk for diabetes were randomized to ILS, MET or PLB; 2779 continued in DPPOS and were offered modified group ILS.

During DPPOS, ILS was offered additional lifestyle reinforcement semi-annually and MET received unmasked metformin. This analysis includes 1384 DPPOS participants who had dual-energy X-ray absorptiometry hip scans at year 12 (Y12). Osteoporosis was defined as femoral neck BMD T-score ≤-2.5 and osteopenia as -2.5<T-score≤-1. Participants were asked at Y12 if they had a fall in the previous year. Outcomes were compared across the 3 treatment groups using Pearson’s chi- squared test. Associations between treatment and outcomes were assessed with logistic regression.

Mean age at Y12 was 66.5 (±9.5) years. Mean time since DPP baseline was 15.6 (±0.7) years. Weight loss (DPP baseline to DPPOS Y12) did not differ across treatment groups (-4.4 kg ILS; -3.5 kg MET; -3.1 kg PLB; p=0.114). There were no differences across groups in the prevalence of osteoporosis in men (1.4% ILS, 1.3% MET, 0.7% PLB; p=0.836) or women (2.9% ILS, 2.9% MET, 3.1% PLB; p=0.983). Prevalence of osteopenia was also similar across groups. Prevalence of history of falls was similar across groups in men (16.0% ILS, 16.4% MET, 16.0% PLB; p=0.995) and women (25.7% ILS, 21.3% MET, 21.6% PLB; p=0.342). Prevalence of osteoporosis, osteopenia or history of falls did not differ between ILS or MET and PLB in men or women.

In a cohort at high risk of diabetes, lifestyle intervention or metformin did not have long-term effects on bone density or falls.

Disclosure

A.V. Schwartz: None. Q. Pan: None. V. Aroda: Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc., AstraZeneca, Calibra Medical, Eisai Inc., Sanofi. Consultant; Self; Sanofi. Research Support; Self; Theracos, Inc.. Employee; Spouse/Partner; Merck & Co., Inc.. Other Relationship; Self; American Diabetes Association. Consultant; Self; ADOCIA. J.P. Crandall: None. A. Kriska: None. C.S. Piromalli: None. M. Temprosa: Other Relationship; Self; Merck KGaA. H. Florez: Advisory Panel; Self; Sanofi. D. Research Group: None.
Joint Associations of Diabetes and Sarcopenia on All-Cause Mortality among U.S. Older Adults
Authors: XIA JIN , SONG YIQING
Published: June 2018

Background: Recent studies have shown that sarcopenia defined as the loss of muscle mass and/or strength was associated with diabetes and independently predicted all-cause mortality in older adults; however, it is unclear whether sarcopenia and diabetes synergistically affect all-cause mortality.

Methods: We aimed to prospectively examine joint associations of sarcopenia (defined by either low muscle mass (LMM), low muscle strength (LMS), or both) and diabetes on all-cause mortality in a nationally representative sample of U.S. adults, including 4,449 participants aged 50 years and older from NHANES 1999-2002 with linked mortality data. Weighted multivariable logistic regression models were adjusted for age, sex, race, BMI, smoking, alcohol use, education, leisure time physical activity, sedentary time, and comorbid diseases.

Results: Overall, we had 971 with diabetes and 921 with sarcopenia defined by LMM (ALM/BMI), 762 with LMS, 207 with sarcopenia defined by both LMM (ALM/BMI) and LMS. The prevalence of sarcopenia was higher in diabetic than nondiabetic individuals (23.7% vs. 14.6% for LMM, 15.8% vs. 13.8% for LMS, and 4.0% vs. 3.5% for both LMM and LMS). In the joint analyses, diabetic individuals had increased risk of all-cause mortality than those without diabetes or LMM, whether they had LMM (OR=2.79; 95% CI: 1.56-4.98) or not (OR=1.40; 95% CI: 1.02-1.92) (P for joint effect=0.001). LMS was associated with higher risk of all-cause mortality among both diabetic (OR=4.10; 95% CI: 1.59-10.55) and nondiabetic individuals (OR=2.39; 95% CI: 1.77-3.23) (P for joint effect<0.0001). Compared to those without diabetes or sarcopenia (both LMM and LMS), all-cause mortality risk was higher among individuals with sarcopenia alone (OR=1.78; 95% CI: 1.15-2.75) (P for joint effect=0.011).

Conclusions: Our results suggest that LMS was independently and strongly associated with elevated risk of all-cause mortality, with additional risk synergistically with diabetes among U.S. older adults.

Disclosure

J. Xia: None. Y. Song: None.
Secular Trend for Cancer Incidence in Type 2 Diabetic Patients and the Association between Type 2 Diabetic Patients and Cancer between 2004 and 2014
Authors: GUO QI , XU HUILIN , XU DONGLI
Published: June 2018

Background: Type 2 diabetes mellitus (T2DM) has been suggested to increase the risk of cancers. The aim of this study was to evaluate the secular trend for cancer incidence in T2DM patients in Minhang District of Shanghai and the incidence rate ratios from cancer between T2DM patients and the general population between 2004 and 2014.

Methods: All T2DM patients were enrolled from the standardized management system based on local electronic information system in Minhang District of Shanghai, China. Newly-diagnosed cancer cases were identified by record-linkage with the Shanghai Cancer Registry. The incidence rates (per 100,000) from cancer according to age for the T2DM patients for each year between 2004 and 2014 were calculated. Age-specific incidence from cancer for T2DM patients and their Standardized incidence ratios (SIR) and 95% confidence interval (CI) compared with the general population were estimated.

Results: A total of 2593 T2DM patients (1317 male and 1276 female) aged ≥40 years were included. A trend for an increase in the annual rate was observed for all age groups. The incidence (per 1000, 000) from cancer was 997.17 in male and 829.57 in female, with age-standardized rate (ASR) being 207.12 and 218.57, respectively. The incidence from cancer showed an upward trend with age compared with the general population, except the age of 40- and 45- year in female T2DM patients. The incidence from cancer was 588.16 at ages of 40- years, and 548.79 at ages of 45- years in female. Compared with the general population, an increased risk was observed in female patients, with SIRs being 2.15 (95% CI: 1.13-3.17) at ages of 40- years and 1.49 (95% CI: 1.05-1.93) at ages of 45- years.

Conclusions: We identified a secular trend of an increase in the rate of cancer incidence in the T2DM patients by ages. Our results suggested that a higher risk of cancer incidence in female T2DM patients at age of 40- and 45-years compared with the general population.

Disclosure

Q. Guo: None. H. Xu: None. D. Xu: None.
The Burden of Aging with Diabetes and the Impact of Cognitive Decline
Authors: SMALLS BRITTANY L. , BARDACH SHOSHANA H. , SCHOENBERG NANCY
Published: June 2018

Objective: T2DM effects approximately 25% of older adults and prevalence of cognitive decline (CD) increases with age. Furthermore, some research suggests that individuals living with these conditions find it difficult to manage their health. The goal of this study was to use the 2015 BRFSS to assess the difference in disease burden experienced by older adults with T2DM and with or without CD.

Research Design and Methods: Older adults with T2DM were assessed for CD based on self-reported affirmative responses to the Cognitive Decline questions. Disease burden was assessed using Healthy Days—Health Related Quality of Life questions. Logistic regression was used to determine the likelihood of disease burden based on cognitive status. Differences in reported days of disease burden between those with and without CD using pairwise comparison of marginal linear predictions. An alpha level of .05 was used.

Results: The sample reported an average of 3 chronic conditions in addition to T2DM. Compared to those without CD, those with CD had a 57% increased likelihood of experiencing poor physical health, were 2.7x as likely to report poor mental health, and had a 97% increased likelihood of reporting poor physical or mental health impeded usual activities, including self-care. There was also a significant difference in the number of days of disease burden reported by those with cognitive decline for poor physical (+6.1 days) and mental health (+5.2 days) and the number of days that poor physical or mental health interfered with usual activities (+4.8 days).

Conclusion: As the population ages, it is imperative to understand how CD influences disease burden and ability to perform T2DM-related self-care activities. Future research is needed to understand, along with cognitive decline, how geriatric syndromes and other chronic conditions contribute to disease burden in older adults. Also, additional research is needed to identify potential social determinants that may be unique to older adults with T2DM.

Disclosure

B.L. Smalls: None. S.H. Bardach: None. N. Schoenberg: None.
NOD1 Mediates Insulin Resistance in Response to Circulating Free Fatty Acids
Authors: RIVERS SYDNEY L. , YEUNG LUCY SHU NGA , CHAN KENNY L. , MORI YUSAKU , PHILPOTT DANA , KLIP AMIRA , GIACCA ADRIA
Published: June 2018

Insulin resistance (IR) in type 2 diabetes (T2D) is associated with chronic low-grade inflammation. We have shown that nucleotide binding oligomerization domain (NOD)1, an intracellular pattern recognition receptor for bacterial wall peptidoglycans, is a factor linking the innate immune system to the development of high fat diet-induced IR. Although high fat diet may result in NOD1 activation via increased intestinal absorption of bacterial products, NOD1 has also been shown to be activated by saturated fatty acids in intestinal cells and adipocytes. We hypothesize that NOD1 plays a role in IR caused by chronic high levels of circulating free fatty acids (FFA) as found in obesity and T2D. Wild type (WT) and NOD1-/- mice were infused with ethylpalmitate (resulting in raised circulating palmitate) or ethanol vehicle as a control, for 48 hours to model prolonged elevation of circulating FFA in vivo. Hyperinsulinemic-euglycemic clamp with tracer methodology was then used to assess peripheral and hepatic insulin sensitivity. WT mice treated with ethylpalmitate had decreased peripheral and hepatic insulin sensitivity expressed as stimulation of glucose utilization (Control= 123%±30 and Ethylpalmitate= 25%±25, p<.05) and suppression of glucose production (Control= 51%±10 and Ethylpamitate= 22%±2, p<.05). NOD1-/- mice were protected from palmitate induced IR, showing no difference in stimulation of glucose utilization (Control= 289%±27 and Ethylpalmitate= 352%±64) and suppression of glucose production (Control= 63%±16 and Ethylpalmitate= 95%±25) with or without palmitate. Thus, our data provide compelling evidence that NOD1 activation via elevated plasma FFA contributes to the development of peripheral and hepatic IR.

Disclosure

S.L. Rivers: None. L. Yeung: None. K.L. Chan: None. Y. Mori: None. D. Philpott: None. A. Klip: None. A. Giacca: None.
Association between Diabetes Mellitus and Urinary Incontinence in Elderly Patients
Authors: VU HUYEN T.
Published: June 2018

Background and Aim: Urinary incontinence (UI) has been known as a problem associated with diabetes, especially in elderly. The aging process and geriatric syndromes contribute to the incidence of UI. The aim of the study was to assess UI and related factors in elderly diabetic patients.

Materials and Methods: We conducted a cross-sectional study on 322 diabetic patients aged ≥ 60 years, who were admitted to the National Geriatric Hospital from December 2016 to December 2017. The 3 Incontinence Questions (3IQ) was used to identify the prevalence of UI and its classification. Information on socio-demography, medical history, glycaemic control [fasting plasma glucose (FPG) and HbA1c], co-morbidities (Charlson index), polypharmacy, and cognitive impairment were assessed to investigate the relationship of diabetes mellitus and UI.

Results: Three hundred twenty two patients were recruited. Age of subjects was ranging between 60 and 96 years old (average age: 74.8 ± 8.28 years). The prevalence of UI among patients with diabetes was 65.2%. The prevalence of urge, stress, overflow and mixed incontinence were 36.7%, 36.2%, 17.6% and 9.5%, respectively. Advanced age and overweight status were associated with UI (p<0.05). The level of FPG and HbA1c among the incontinence diabetic patients were significantly higher than those in the continence diabetic patients (p<0.05). Multiple logistic regressions revealed risk factors for UI including: age > 70 years old (OR: 1.7, 95% CI: 1.1-2.7, p<0.05); history of pelvic surgery (OR:4.5, 95% CI: 1.6-12.8, p<0.05); long duration of diabetes (OR:2.8, 95% CI:1.6-4.9, p<0.001); Charlson index (OR: 2.7, 95% CI: 1.7-4.3, p<0.001); polypharmacy (OR: 2.9, 95% CI: 1.4-5.7, p<0.05); cognitive impairment (OR:40.5, 95% CI: 5.0-329.9, p=0.001).

Conclusion: Advanced age, long duration of diabetes, the level of FPG and HbA1c, comorbidities, polypharmacy and cognitive impairment were associated with increased risk of urinary incontinence in elderly diabetic patients.

Disclosure

H.T. Vu: None.
Acute Increase in Creatinine after Starting ACE Inhibitor and Vascular Events and Premature Death in Patients with Type 2 Diabetes—The ADVANCE Trial
Authors: OHKUMA TOSHIAKI , JUN MIN , WOODWARD MARK , CHALMERS JOHN , PERKOVIC VLADO , RODGERS ANTHONY
Published: June 2018

Background: An acute increase in serum creatinine (AICr) after starting ACE inhibitor is frequently observed, and consideration of discontinuation has been recommended if creatinine values increased 30% or more. However, the long term effect of continuation or discontinuation of that therapy is unclear.

Objective: To examine the association of AICr after starting a fixed combination of perindopril-indapamide and its continuation or discontinuation, with clinical outcomes using data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.

Research Design and Methods: A total of 11,140 diabetes patients were randomly assigned to a fixed combination of perindopril-indapamide or placebo after a 6-week active run-in period. These analyses included 11,066 patients with 2 measurements of serum creatinine, before and during the active run-in period (3 weeks apart). AICr was determined using these 2 measurements, classified into 4 groups: <10%, 10-19%, 20-29%, and ≥30%.

Results: AICr after starting perindopril-indapamide in the run-in period was subsequently associated with an increased risk of a composite of major macrovascular events, new or worsening nephropathy, all-cause mortality, in both randomized groups (P for trend <0.for each). However, a consistent benefit of randomized treatment for the outcome was observed across subgroups defined by AICr, with no heterogeneity in the magnitude of the effects (P for heterogeneity = 0.94). Similar results were observed for major macrovascular events alone, new or worsening nephropathy alone, and all-cause mortality alone.

Conclusions: AICr after starting ACE inhibitor was associated with an increased risk of clinical outcomes, irrespective of continuation or discontinuation of the therapy. However, randomized treatment effects are consistent and beneficial across subgroups defined by AICr.

Disclosure

T. Ohkuma: None. M. Jun: None. M. Woodward: None. J. Chalmers: Research Support; Self; Servier. Other Relationship; Self; Servier. V. Perkovic: Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Consultant; Self; AbbVie Inc.. Advisory Panel; Self; Janssen Global Services, LLC.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novartis Pharmaceuticals Corporation, AstraZeneca, Gilead Sciences, Inc.. Consultant; Self; Servier. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company. A. Rodgers: Other Relationship; Self; George Health Enterprises.
Increased Cardiovascular Risk in Patients with Diabetes, Statin-Controlled LDL Cholesterol, and Residual Hypertriglyceridemia
Authors: NICHOLS GREGORY , PHILIP SEPHY , GRANOWITZ CRAIG B. , REYNOLDS KRISTI , FAZIO SERGIO
Published: June 2018

High triglyceride (TG) levels are common in type 2 diabetes (T2D). We evaluated T2D patients at high risk for CV events who had statin-controlled LDL cholesterol (LDLc) to determine whether the presence of high TG levels contribute to residual CV risk. We combined data from the Southern California and Northwest regions of Kaiser Permanente to identify adults on statin therapy with LDLc 40-100 mg/dL, no other lipid therapies, and with T2D and a prior diagnosis of myocardial infarction, ischemic stroke, peripheral artery disease or at least one other CV risk factor. Patients were grouped into high (200-499 mg/dL, n=5,542) or normal (<150 mg/dL, n=22,411) TGs in 2010 and followed them through December 2016 to compare the adjusted incidence rates and rate ratios of first non-fatal MI, non-fatal stroke, unstable angina, coronary revascularization, death, and their composite. Models were adjusted for demographic and clinical characteristics using generalized linear models with Poisson errors. Over mean follow-up of 5 years, patients with high TG were at increased risk of CV outcomes (Table). High TG levels independently increase CV risk in T2D patients with statin-controlled LDLc. The ongoing CV outcome trial, REDUCE-IT, will determine if high dose pure prescription eicosapentaenoic acid reduces CV risk among statin users with persistently high TG levels, including T2D patients.

Disclosure

G. Nichols: Research Support; Self; Boehringer Ingelheim GmbH, Amarin Corporation, Janssen Pharmaceuticals, Inc., Sanofi. S. Philip: Stock/Shareholder; Self; Amarin Corporation. Employee; Self; Amarin Corporation. C.B. Granowitz: Employee; Self; Amarin Corporation. K. Reynolds: Research Support; Self; Amarin Corporation, Novartis Pharmaceuticals Corporation, Amgen Inc., CSL Behring. S. Fazio: Consultant; Self; Amarin Corporation, Akcea Therapeutics, Amgen Inc., Kowa Pharmaceuticals America, Inc..
Impact of Prior Coronary Artery Disease (CAD) and Glucose Tolerance Status (GTS) on Incident CAD in Japanese Men
Authors: KITAZAWA MASARU , FUJIHARA KAZUYA , HARADA MAYUKO , ISHIZAWA MASAHIRO , YAMAMOTO MASAHIKO , KANEKO MASANORI , OSAWA TAEKO , YAMADA TAKAHO , MATSUBAYASHI YASUHIRO , SONE HIROHITO
Published: June 2018

Despite a decade of historical debate and the recent rebuttal regarding “diabetes mellitus (DM) as a CAD risk equivalent”, few studies have evaluated the impact of prediabetes (preDM) separately. Thus, it is still possible that the impact of DM has been underestimated unless preDM is excluded from the nondiabetic category and independently assessed along with normal glucose tolerance (NGT) and DM. To clarify the independent risk of NGT, preDM and DM with and without prior CAD for incident CAD, we analyzed data using a nationwide claim-based database that included 138,162 men (NGT 78,230; preDM 45,610; DM 14,322) aged 18-72 y in Japan. Multivariate Cox analysis showed that the impact of preDM on CAD was modest compared to DM even with prior CAD (Model 1, Table) whereas prior CAD confers a 5-8-fold excess risk for CAD regardless of GTS (Model 2, Table). The hazard ratio (HR) of CAD in NGT individuals with prior CAD was much higher than in DM individuals without prior CAD (HR 3.08(95% CI 2.08-4.54)). The HR in those with both DM and prior CAD was 15.7(11.8-21.0) compared to NGT without prior CAD.

In conclusion, DM alone is not prior CAD risk-equivalent even if the influence of preDM is eliminated. Prior CAD confers a far higher risk for subsequent CAD regardless of GTS. Necessity of intense intervention for the secondary prevention of CAD is implied considering the enormously high risk in those with both DM and prior CAD.

Disclosure

M. Kitazawa: None. K. Fujihara: None. M. Harada: None. M. Ishizawa: None. M. Yamamoto: None. M. Kaneko: None. T. Osawa: None. T. Yamada: None. Y. Matsubayashi: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..
Sex Differences in Coronary Artery Disease Patients With and in Those Without Type 2 Diabetes
Authors: SAELY CHRISTOPH H. , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN DANIELA , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ
Published: June 2018

Life-term cardiovascular risk is high also in women, and women with coronary artery disease (CAD) or with type 2 diabetes (T2DM) are at a particularly high risk. In this prospective cohort study, we addressed sex differences in CAD patients with as well in those without T2DM. We recorded cardiovascular events in an unselected consecutive series of 1472 patients with angiographically proven CAD over 7.5±2.9 years. T2DM prevelance was similar in men (n=1060) and women (27.3 vs. 30.1%; p=0.277). Among nondiabetic CAD patients women were older than men (68±9 vs. 63±11 years; p<0.001), had higher LDL cholesterol (138±42 vs. 130±38 mg/dl; p=0.022) and HDL cholesterol (63±16 vs. 51±14 mg/dl; p<0.001) and a lower prevelance of smoking (35.5 vs. 69.6%; p<0.001) and of prior myocardial infarction (20.6 vs. 31.2%; p=0.001). Among those with T2DM, women also were older (69±9 vs. 64±10 years; p<0.001), had higher HDL cholesterol (53±14 vs. 46±13 mg/dl; p<0.001) and a lower prevalence of smoking (28.6 vs. 80.1%; p<0.001); further among those with T2DM the prevelance of hypertension (79.9 vs. 70.7%; p=0.049) and of statin use (66.9 vs. 48.3%; p<0.001) was higher in women. Prospectively, sex did not predict cardiovascular events in CAD patients without nor in those with T2DM, with adjusted hazard ratios of 0.96 [0.73-1.26]; p=0.757 and 0.82 [0.55-1.22]; p=0.329, respectively. We conclude that baseline risk factors both among CAD patients without and among those with T2DM differ between women and men, whereas irrespective of diabetes status sex does not affect the incidence of future cardiovascular events in this population.

Disclosure

C.H. Saely: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin: None. B. Larcher: None. A. Mader: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None.
Comparative Cardiovascular Effectiveness of SGLT2 Inhibitors vs. Liraglutide in Routine Care
Authors: PATORNO ELISABETTA , EVERETT BRENDAN M. , SCHNEEWEISS SEBASTIAN , GLYNN ROBERT J. , LIU JUN , KIM SEOYOUNG C.
Published: June 2018

Both SGLT2 inhibitors (canagliflozin and empagliflozin) and liraglutide have shown cardiovascular (CV) benefits in CV outcome trials. Whether these agents are associated with differential CV effects in routine care remains unexplored. In a large commercial U.S. health insurance database (4/2013-9/2015), we assessed the comparative CV risk of SGLT2 inhibitors (SGLT2i) vs. liraglutide in patients with type 2 diabetes. We used 1:1 propensity score (PS) matching to balance over 100 baseline characteristics. We estimated the hazard ratio (HR) of a combined CV outcome (hospitalization for myocardial infarction (MI) or stroke) and heart failure hospitalization (HHF). Secondary outcomes included an expanded combined CV outcome (hospitalization for MI, stroke, unstable angina, or coronary revascularization) and individual MI or stroke hospitalization. Over 30 months, SGLT2i initiators had no significant difference in the risk of the combined CV outcome (HR= 1.01 [95% CI 0.76-1.34]) or other secondary CV outcomes, but had an approximately 30% decrease in the risk of HHF (HR= 0.68 [0.52-0.88]), compared with liraglutide (Table). Subgroup analyses in patients with and without baseline CV disease produced largely consistent results.

In conclusion, this study rules out large differences in atherosclerotic CV risk between SGLT2i and liraglutide, but supports larger benefits of SGLT2i vs. liraglutide for HHF.

Disclosure

E. Patorno: Research Support; Self; National Institute on Aging. Other Relationship; Self; Boehringer Ingelheim GmbH, GlaxoSmithKline plc. B.M. Everett: Research Support; Self; Roche Diagnostics Corporation, Novartis Pharmaceuticals Corporation. Consultant; Self; Roche Diagnostics Corporation, Abbott Laboratories, Novartis Pharmaceuticals Corporation, U.S. Food and Drug Administration, UpToDate. Other Relationship; Self; American College of Cardiology. S. Schneeweiss: Consultant; Self; WHISCON, LLC. Other Relationship; Self; Aetion, Inc.. Research Support; Self; Genentech, Inc., Bayer AG, Boehringer Ingelheim GmbH, U.S. Food and Drug Administration, Patient-Centered Outcomes Research Institute. R.J. Glynn: Research Support; Self; Pfizer Inc., Novartis AG, Kowa Pharmaceuticals America, Inc.. J. Liu: None. S.C. Kim: None.
Epigenetic Link between Statin Use and Diabetes
Authors: OCHOA-ROSALES CAROLINA , PORTILLA-FERNANDEZ ELIANA , WILSON RORY , NANO JANA , GHANBARI MOHSEN , RUEDA-OCHOA OSCAR L. , LEHTIMÄKI TERHO , GAO XU , LEHNE BENJAMIN , VOORTMAN TRUDY , FRANCO OSCAR , MUKA TAULANT
Published: June 2018

Current evidence associates statin use with increased risk of type 2 diabetes (T2D). Mechanism are unclear. Statins may impact DNA methylation, a key regulator in gene expression. We conducted an epigenome-wide association study among 8313 Europeans (7163 never users and 1150 current statin users) from 7 cohorts to assess the association of statin use and DNA methylation in blood. After replication we found genome-wide associations of methylation sites annotated to DHCR24 (cg17901584, cg10177197), SC4MOL (cg05119988), and ABCG1 (cg06500161, cg27243685), which are involved in cholesterol, insulin and lipoprotein lipase pathways. Cg06500161 hypermethylation was related to decreased ABCG1 expression in two probes (P = 5 x 10-12 and 9 x 10-13), lower high density lipoprotein cholesterol (HDL, P = 0.002) and higher triglycerides (P = 1 x 10-4). Mendelian Randomization suggested that HDL and triglycerides might be a consequence of cg06500161 rather than a cause. Lower methylation of cg17901584 was associated with higher insulin (P = 0.006). Prevalent T2D was related to all sites except cg27243685 (P from 6 x 10-10 to 9 x 10-4). Only cg06500161 independently predicted incident T2D (P = 6 x 10-7), implicating that ABCG1 may be a causal factor for T2D as suggested by Mendelian Randomization (Figure 1). Our study is the first to provide evidence of DNA methylation as potential mechanism by which statin use can lead to adverse metabolic alterations and subsequently T2D.

Disclosure

C. Ochoa-Rosales: None. E. Portilla-Fernandez: None. R. Wilson: None. J. Nano: None. M. Ghanbari: None. O.L. Rueda-Ochoa: None. T. Lehtimäki: None. X. Gao: None. B. Lehne: None. T. Voortman: None. O. Franco: None. T. Muka: Employee; Self; Novo Nordisk A/S.
Screening Patients for Diabetes in a Large, National Clinical Database
Authors: STEMPNIEWICZ NIKITA , CUDDEBACK JOHN K. , RATTELMAN CORI R. , CIEMINS ELIZABETH L.
Published: June 2018

Objective: To characterize diabetes screening patterns among eligible patients per ADA Standards of Medical Care in Diabetes using a large, geographically diverse clinical dataset.

Study Design: Retrospective descriptive analysis conducted in a clinical database containing over 25 million patient records. Population Studied: A total of 5.1 million patients aged 18-75 in 23 health care organizations (HCOs) with at least one outpatient visit in the study period (7/2016-6/2017), no prior diagnosis of diabetes mellitus, and no prior diabetes medication prescriptions (except metformin).

Principal Findings: Among 5.1 million patients, 74% were eligible for screening and 55% were screened according to guidelines. Adequate screening ranged from 47%-76% across 23 HCOs. Adults 65 and older were most likely to be adequately screened (61%; P < .01). Least likely to be screened were patients with low-income insurance types (P < .01); non-white race (P < .01) or lower education by zip code (P < .01). Of 1.7 million patients screened, 2.8% and 36.5% had evidence of diabetes and prediabetes, respectively. Diabetes/prediabetes was identified in 30% of patients aged 35-44 and 48% of patients 65 and older. Patients with lower education were less likely to be adequately screened, but yielded greater rates of diabetes/prediabetes, 47% to 39% from least to most educated (P < .01). More African Americans (46%) screened positive for diabetes/prediabetes compared to other race/ethnicities (42%) (P < .01).

Conclusions: Screening practices vary greatly, mostly within and across HCOs. Patients least likely to be adequately screened were often those with highest yields of diabetes/prediabetes. The identification of inadequately screened, low-income, lower education, or race/ethnic minority populations may facilitate targeted efforts to decrease disparities in screening practices. Identification of organizations with the highest net yield may also provide insight into strategies for efficient screening practices.

Disclosure

N. Stempniewicz: None. J.K. Cuddeback: Research Support; Self; Novo Nordisk Inc.. Other Relationship; Self; Johnson & Johnson Diabetes Institute, LLC., Merck & Co., Inc., Sanofi US, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. C.R. Rattelman: None. E.L. Ciemins: None.
Heterogeneity between Pharmacoepidemiological Studies Using the Clinical Practice Research Datalink (CPRD)
Authors: KOECHLIN ALICE , BOYLE PETER , AUTIER PHILIPPE
Published: June 2018

The CPRD has been collecting medical data among UK patients since 1987. Many studies on the risk of cancer associated with prescription of antidiabetic drugs have used the CRPD database. The objective was to compare methods and results of studies on the same exposure and outcome combination based on the CPRD.A systematic Pubmed search of articles on diabetes and cancer based on the CPRD was performed. Articles were grouped into common exposure and outcome combinations. Methods and results were compared, especially in case of diverging results between studies, with a focus on study design and statistical methods. Forty-six studies were identified. Five of them studied colorectal cancer (CRC) occurrence in diabetic patients prescribed with metformin. All studies consistently found no significant increased or decreased CRC risk associated with metformin prescription. Five studies examined the risk of bladder cancer in relation to pioglitazone prescription. Two studies found a significantly increased risk of bladder cancer, one based on the analysis of the full dataset and one based on a nested case-control design using conventional matching procedures. The three other studies found no association, all of which used propensity score matched cohort design. Four studies investigated the risk of breast cancer among insulin glargine users. The three studies that included diabetic subjects who were prescribed glargine or another insulin therapy for the first time (i.e., the new user design) found no association. The study that included past and new users of glargine and of another insulin found a significantly increased risk. Despite the use of the same data source, studies on the same exposure and outcome may arrive at markedly different conclusions. Studies using propensity scores for matching subjects or including past users in cohorts may obtain results substantially different than studies using conventional statistical approaches.

Disclosure

A. Koechlin: None. P. Boyle: Other Relationship; Self; Sanofi. P. Autier: Other Relationship; Self; Sanofi.
The Role of NT-proBNP as a Biomarker in Evaluating Residual Cardiovascular Risk in 200 Type 2 DM Patients Optimized for Conventional CV Risk Markers over Two Years
Authors: GUPTA VISHAL , TELI VAISHALI
Published: June 2018

Methodology: Two hundred T2DM patients who were on standard glucose lowering agents and who may be on lipid and blood pressure lowering agents were optimised for conventional CV risk markers and followed for a period of 2 years. We evaluated CV risk using markers like BMI, HbA1c, Systolic blood pressure (SBP), diastolic BP (DBP), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), non-HDL cholesterol, cholesterol remnant, highly sensitive CRP (hsCRP), serum creatinine, eGFR and urine microalbumin/creatinine ratio (UACR). At the end of 2 years, N-terminal pro-b type natriuretic peptide (NTpro-BNP) was measured to assess its role as a residual CV risk marker. T2DM patients with recent history (<1 years) of revascularization or any major surgery were excluded. Data was analysed using SPSS version 20 and represented as Mean + 2SD with 95% confidence interval, paired t test was used and p value of 0.was considered significant.

Results: Baseline characteristics were: 101(50.5%) males and 99 (49.5%) females, mean age was 61.63 ± 9.84 years, mean age since diagnosis 11.89 ± 7.3y and mean BMI 30.53 ± 5.7 kg/m2. There was an overall significant reduction from baseline to 2 years in HbA1c (7.61 ± 1.7 to 6.8 ± 1.05; p-<0.001), TC (142.55 ± 42.79 to 134.88 ± 40.56, p-0.01), LDL (79.79 ± 35.98 to 70.37 ± 30.69, p-<0.001), TG (133.31 ± 74.27 to 121.68 ± 74.11, p-0.018), Serum creatinine (0.97 ± 0.29 to 0.93 ± 0.26, p-<0.001), UACR (91.43 ± 34.4 to 56.49 ± 16.74), hsCRP (7.02 ± 2.77 to 4.1 ± 1.85, p-0.001). There was no significant change observed with respect to BMI, SBP, DBP, HDL and eGFR from baseline to 2 years. The mean NTpro-BNP at the end of 2 years was 166.33 ± 23.6.

Conclusion: In the present study, inspite of reduction in various CV risk markers over a period of 2 years, mean NTpro-BNP level remained high. Hence, this may suggest the role of NT pro BNP to be of additional value as a CV risk assessment tool in T2DM patients.

Disclosure

V. Gupta: None. V. Teli: None.
Validation of FINDRISC with Latin American Abdominal Perimeter Cutting Points for Risk of Dysglycemia in Workers of a Peruvian National Hospital
Authors: YOVERA MARLON , DAMAS LUCY , TICSE RAY W.
Published: June 2018

Introduction: Diabetes screening questionnaires such as FINDRISC need to be evaluated in the target population taking into account their own characteristics.

Material and Methods: A cross-sectional study of diagnostic tests was carried out. We found Original FINDRISC (OF) and Modified FINDRISC (MF) scores with Latin American abdominal obesity cut-offs (male ≥ 94 cm and female ≥ 90 cm) to determine dysglicemia including impaired fasting glucose (IFT), glucose intolerance (GIT), and diabetes mellitus (DM), according to Oral Glucose Tolerance Test in workers of the María Auxiliadora Hospital. The Area under the ROC Curve (AUROC) of the MF and OF was found. The sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of each MF and OF point were calculated. A PLR> 2 was rated as useful and one greater than 10 as excellent, and an NLR <0.5 was considered useful and <0.1 as excellent.

Results: Of 549 subjects, 77.5% were female, 70% were> 45 years old, 75% had a BMI> 25 and 65.4% abdominal obesity with Latin American criteria. About 15% had some history of hyperglycemia or hypertension and 70% did not exercise or did not eat vegetables daily. Half of them had a family member with diabetes. There was dysglicemia in 17.8%, of which 11.4% had IFT; 3.8% GIT and 2.6% DM. The MF presented greater accuracy than OF (AUROC: 0.71 vs. 0.69, p = 0.007). There were no differences in the curves between women or men.The score 11 obtained a sensitivity and specificity of 78.6% and 53.0% respectively and the score 14 a sensitivity and specificity of 56.1% and 76.7 respectively. A PLR, a value of 14 is rated useful and an excellent 21. On the other hand, one NLR qualifies a score of 11 as useful and 2 as excellent.

Conclusion: MF had greater diagnostic accuracy than OF for dysglycemia. Scores of 14 and 21, confer high and very high risk; on the contrary, scores of 11 and 2, low and very low risk.

Disclosure

M. Yovera: None. L. Damas: None. R.W. Ticse: None.
Effect of Obesity and Exercise on Amino Acid Metabolites in American-Indian Adolescents at Risk for Diabetes
Authors: SHORT KEVIN R. , CHADWICK JENNIFER , TULLIER MARY A. , WOLBERT LISA D. , COLEMAN CHARLOTTE L. , COPELAND KENNETH C.
Published: June 2018

Circulating amino acids (AA) and their metabolites are biomarkers for insulin resistance and future diabetes in adults, but there are few, and conflicting findings in studies of adolescents. We performed amino acid metabolomic profiling in American Indian adolescents to determine whether specific analytes would vary with body composition and insulin sensitivity, and/or be altered in response to exercise training. Boys and girls, 11-18 years who were normal weight (NW, n=36) or obese (Ob, n=58) completed tests of fitness, body composition, and a fasting blood draw. Forty-two of the Ob group were retested after completing 16 weeks of aerobic exercise training. A panel of 42 plasma amino acids and metabolites were measured by UPLC/MS/MS. The Ob group had several risk factors for future diabetes, including higher body fat, lower aerobic fitness, and lower insulin sensitivity (iHOMA2). The Ob group had 16 analytes that were higher and 8 lower than the NW group. Among those that were higher in the Ob group were branched chain AAs (Val, Leu, Ile, +13-17%) and aromatic AAs (His, Phe, Tyr, +15-34%); those AAs were also correlated with body fat (r=0.32 to 0.53) and insulin sensitivity (r=-0.32 to -0.60). The Lys metabolite, α-aminoadipic acid, a predictor of diabetes in adults, was 46% higher in the Ob group and correlated with insulin sensitivity (r=-0.43). β-aminoisobutyric acid, a myokine related to insulin resistance in adults, was 29% lower in the Ob vs. the NW group and correlated with insulin sensitivity (r=0.32). Exercise training resulted in a 10% increase in aerobic fitness, but body composition and insulin sensitivity were unchanged. Only two AAs were changed (His, Cys) after training. These novel findings in adolescents demonstrate that several plasma AAs are altered by obesity and serve as biomarkers of insulin action, but are not altered with this exercise intervention.

Disclosure

K.R. Short: None. J. Chadwick: None. M.A. Tullier: None. L.D. Wolbert: None. C.L. Coleman: None. K.C. Copeland: Other Relationship; Self; Novo Nordisk Inc..
Concordance of Glucose-Based and of HbA1c-Based Diagnoses of Diabetes in Patients with Peripheral Artery Disease—A Comparison between Two Age Groups
Authors: SAELY CHRISTOPH H. , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN DANIELA , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ
Published: June 2018

Concordance between glucose-based and HbA1c-based diagnoses of diabetes differ between populations. Here, we aimed at investigating their concordance in younger and in older patients with peripheral artery disease (PAD). We measured fasting glucose as well as HbA1c and performed 75g oral glucose tolerance tests in 188 consecutive patients, 113 older and 75 younger than 65 years, who had sonographically proven PAD but not previously diagnosed diabetes. Based on glucose values, diabetes was diagnosed with fasting plasma glucose (FPG) ≥126 mg/dl or post-challenge glucose ≥200 mg/dl 2 hours after the oral glucose load; based on HbA1c values diabetes was diagnosed with HbA1c ≥6.5%. Among PAD patients <65 years, 5 had diabetes based on glucose criteria, of whom 3 also had diabetes according to the HbA1c criterion, and 70 did not have diabetes according to glucose criteria, of whom 67 also did not have diabetes using HbA1c criteria; among those ≥65 years, 19 had diabetes based on glucose criteria, of whom 10 also had diabetes according to the HbA1c criterion and 94 did not have diabetes based on glucose criteria, of whom 93 also did not have diabetes according to HbA1c criteria. Concordance of glucose and HbA1c criteria was similar in younger and older PAD patients (93.3% and 91.2%; p=0.589). Applying glucose criteria as a standard, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the HbA1c criterion for PAD patients <65 years were 60.0%, 95.7%, 50.0%, and 97.1%, and for those ≥65 years 52.6%, 98.9%, 90.9%, and 91.2%. We conclude that the concordance of glucose and HbA1c criteria among patients with PAD is high and is similar in older and younger subjects. However, for both age groups the sensitivity of the HbA1c criterion is poor in this patient population.

Disclosure

C.H. Saely: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin: None. B. Larcher: None. A. Mader: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None.