bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cis-Vaccenic Acid Is Associated with Lower HOMA-IR and Incident T2D in Participants from the MESA Cohort
Authors: WEIR NATALIE L. , JOHNSON LISA , GUAN WEIHUA , STEFFEN BRIAN , DJOUSSE LUC , MUKAMAL KENNETH J. , TSAI MICHAEL Y. 
Published: June 2018

The de novo lipogenesis pathway may play a key role in metabolic regulation. The omega-7 monounsaturated fatty acid cis-vaccenic acid (VA) is an endogenous downstream product of this pathway, and in vitro studies have suggested that it may downregulate gluconeogenesis and liver fat accumulation. However, it has been inconsistently shown to be associated with lower risk of type 2 diabetes (T2D). Previous studies have been in primarily homogeneous cohorts with few studies examining its effects on insulin resistance. Therefore, we aimed to evaluate if VA is associated with HOMA-IR and risk of incident T2D in 5,889 participants of the Multi-Ethnic Study of Atherosclerosis (MESA).
Phosphoplipid fatty acid profiles were determined by GC-FID. A multivariable linear regression model adjusted for age, sex, BMI, education status, smoking, ever used alcohol, and race/ethnicity was used to determine associations between baseline VA levels (quartiles) and HOMA-IR; a Cox proportional hazards model estimated risk of incident T2D over a median 12 year follow-up (n cases=663).
Individuals in the three upper quartiles of VA had a significantly lower log HOMA-IR compared to those in the reference quartile (Q1) (coefficient, [p-value]): Q2: -0.13 [p&lt;0.001]; Q3: -0.22 [p&lt;0.001]; Q4: -0.32 [p&lt;0.001]. Race stratified analysis showed similar results for all four races. Risk of incident T2D significantly decreased with increasing levels of VA (Hazard Ratio, [p-value]): Q1: referent; Q2: 0.98 [p&gt;0.05]; Q3: 0.72 [p&lt;0.01]; Q4: 0.48 [p&lt;0.001]. Race stratification showed similar results for Chinese, black, and hispanic but not white participants. Test for interaction shows the difference between Chinese and whites is statistically significant (p&lt;0.001).
In a multi-racial cohort, VA demonstrated graded associations with lower insulin resistance and risk of diabetes. More studies are needed to elucidate the roles of VA and the de novo lipogenesis pathway in glycemic regulation.

Disclosure
N.L. Weir: None. L. Johnson: None. W. Guan: None. B. Steffen: None. L. Djousse: None. K.J. Mukamal: None. M.Y. Tsai: None.
Type 2 Diabetes Mellitus and Renal Impairment in Real-World with Large Outpatient Electronic Medical Records—Antihyperglycemic Medication Dose Adjustment
Authors: HONG SANG MO , PARK CHEOL-YOUNG 
Published: June 2018

Objective: To estimate the level of inappropriate dosing of DPP-4 inhibitors, and to assess the level of emergency room visits, hypoglycemia, and mortality according to inappropriate dosing of DPP-4 inhibitors in type 2 diabetes (T2DM) patients with renal impairment(RI).
Research Design and Methods: Retrospective database analysis using the National Health Insurance Service Database and the General Health Examination Database in Korea. Patients aged ≥ 40 years with evidence of T2DM (ICD-9-CM codes from E10.x-E14.x) January 1, 2009 to December 31, 2015. Renal impairment defined with estimated with the Modification of Diet in Renal Disease [MDRD] GFR equation. To estimate the level of inappropriate dosing of DPP-4 inhibitors in RI was according to daily prescribed dose. And The incidence of emergency room visits, hypoglycemia, and mortality were assessed using the hazard ratios (HRs) estimated with logistic regression model.
Results: In our study, we analysis 161,760 patients with T2DM and RI. Among them DPP-4 inhibitors were prescribed to 44232 patients (27.3%). DPP-4 inhibitor prescribed 21.44% in GFR&lt;30 and 32.28% in 30≤GFR&lt;50. In observation period, percentages of inappropriate dosing of DPP-4 inhibitors in T2DM with RI was 31.9%. The age and sex adjusted HR with 95% confidence interval (CI) for appropriate dosing of DPP-4 inhibitors compared with inappropriate dosing of DPP-4 inhibitors was 0.871(0.842,0.9) for emergency room visits, 0.819(0.748,0.898) for sever hypoglycemia, and 0.775(0.717,0.839) for mortality.
Conclusions: Renal impairment is common but often undetected in patients with T2DM. In Korea, one of three patients with T2DM and RI received inappropriate doses, and they were associated with high risk of emergency room visits and sever hypoglycemia, and higher mortality. Further analyses to understand the clinical and economic consequences of these findings are needed.

Disclosure
S. Hong: None. C. Park: None.
Twenty-Year Secular Trend of Diabetes Comorbidities in the United States, 1997-2016
Authors: SUN DIANJIANYI , ZHOU TAO , LI XIANG , HEIANZA YORIKO , SHANG XIAOYUN , FONSECA VIVIAN , QI LU 
Published: June 2018

Diabetes affected over 30 million U.S. adults in 2015, and its comorbidities remained among the leading causes of premature death and reduced quality of life. However, little is known about the secular trend of diabetes comorbidities in the last 20 years. Sample-weighted prevalence of twelve common comorbidities of diabetes was estimated using data from 52,842 adults aged ≥18 years who had diabetes in the National Health Interview Survey from 1997 through 2016, with age-standardized to the 2000 U.S. population. We ranked the prevalence [% (SE)] of twelve diabetes comorbidities, and the top five were hypertension [53.7(3.1)], arthritis [33.2(3.1)], asthma [17.2(2.9)], coronary heart disease [CHD: 14.4(2.3)]), and chronic obstructive pulmonary disease [COPD: 9.1(2.3)]. From 1997 to 2016, the estimated prevalence (%) of diabetes comorbidities including hypertension (47.8 to 59.7), asthma (13.2 to 21.0), cancer (7.6 to 10.4), and liver cirrhosis (3.0 to 4.1) continuingly increased (P&lt;0.05), while CHD (15.4 to 13.4), COPD (10.1 to 8.0), and hepatitis (5.5 to 2.9) declined (P&lt;0.05). Such trends were similar among subgroups stratified by gender or by race. In the past two decades, along with continuing increase of diabetes, the rates of its comorbidities including hypertension, asthma, cancer, and liver cirrhosis showed increasing trends, whereas the rates of CHD, COPD, and hepatitis exhibited decreasing trends in the U.S. adults.

Disclosure
D. Sun: None. T. Zhou: None. X. Li: None. Y. Heianza: None. X. Shang: None. V. Fonseca: Consultant; Self; Abbott. Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Eli Lilly and Company. Stock/Shareholder; Self; Amgen Inc.. Consultant; Self; Asahi Kasei Corporation, AstraZeneca, Novo Nordisk Inc., ADOCIA, Intarcia Therapeutics, Inc., Sanofi-Aventis. L. Qi: None.
Causes of Mortality in Patients with Type 2 Diabetes, 2009-2014
Authors: MENEY CARRON , COLLIER ANDREW , HAIR MARIO D. , CAMERON LYALL , BISAMBAR CHAD , ILYAS JUNAID 
Published: June 2018

Aims: To determine the cause of death of people with type 2 diabetes in Ayrshire and Arran between 2009 and 2014 compared to the national mortality rate.
Methods: The primary cause of death (as noted on the death certificates) of 2116 patients with type 2 diabetes between the years 2009 and 2014 were collated. The causes of death were clustered into nine categories- heart disease, stroke, infection, renal failure, respiratory disorders, cancer, mental health, decompensated diabetes and other. The total rates were then compared to national rates using Standardised Mortality Ratio (SMR) and then individually due to heart disease, cerebrovascular disease and cancer.
Results: The most common cause of death in the cohort was cancer (27.8%) followed by heart disease (24.1%). SMR for type 2 diabetes was 145 (95% CI 139,152; p&lt;0.01) and was greater than 100 in all age bands. The SMR was higher in the younger age bands: SMR 35-44 years 330 (95% CI 180,553), SMR 45-55 years 232 (95% CI 177, 299) and SMR 55-64 years 188 (95% CI 163,216) (p values all &lt;0.01). The SMR was consistently higher for females particularly in the younger age groups. SMR for heart disease was significantly greater than 100 for both genders in all age bands under 85 years and was consistently higher for females. There was no difference in mortality causes related to duration of diabetes (&lt;5 years, 5-10years, 10-15 years, &gt;15 years). SMR for strokes was elevated in the 55-74 age range with no significant gender difference. Cancer deaths in males was not significantly elevated (SMR 109) but it was elevated in females (120, 95% CI 104,137) (p&lt;0.05).
Conclusions: The all-cause mortality for patients with type 2 diabetes was consistently higher across all age brackets. The greatest differences were noted in females with heart disease aged less than 65.

Disclosure
C. Meney: None. A. Collier: None. M.D. Hair: None. L. Cameron: None. C. Bisambar: None. J. Ilyas: None.
Incidence and Prevalence of Bile Duct and Gallbladder Disease in Patients with Diabetes in the U.S.
Authors: ALI AYAD K. , ADETUNJI OMOLARA R. 
Published: June 2018

The epidemiology of Bile duct and gallbladder disease (BDGD) in patients with diabetes mellitus (DM) is not well characterized. Records of patients enrolled in U.S. Truven Health MarketScan database between 2015-2016 were analyzed to estimate the incidence and prevalence rates of BDGD among patients with DM. Rates were stratified by age, gender, and DM type (T1D and T2D), and compared to general population. Diagnosis and procedure codes for cholelithiasis, cholecystitis, cholangitis, and other biliary disorders (excluding neoplasms, congenital, and pregnancy disorders) were used to define BDGD.
During the analysis year, &gt;4 million patients with DM were identified, of which only 78,067 were documented as T1D and 1,747,161 as T2D. In general, incidence and prevalence rates of BDGD increased with age and female gender in all populations; however, males with T2D had higher incidence rates (Table). Compared to general population, incidence (per 1,000 person-years) and prevalence rates of BDGD were 3-times higher in patients with DM (incidence, 82.7 v 27.4; prevalence, 10.3% v 3.4%), with T2D having 4-times the incidence and 3-times the prevalence of that in T1D (incidence, 186.8 vs. 44.2; prevalence, 13% vs. 4.4%).
Patients with DM, particularly T2D, are at high risk for BDGD, and clinicians should consider these disorders as potential comorbidities during DM management.

Disclosure
A.K. Ali: Employee; Self; Eli Lilly and Company. O.R. Adetunji: None.
Epigenetic and Metabolic Changes in Skeletal Muscle Underlying the Improvement of Insulin Sensitivity after Bariatric Surgery in Humans
Authors: GANCHEVA SOFIYA , OUNI MERIEM , KOLIAKI CHRYSI , JELENIK TOMAS , MARKGRAF DANIEL F. , SZENDROEDI JULIA , SCHLENSAK MATTHIAS , SCHUERMANN ANNETTE , RODEN MICHAEL 
Published: June 2018

Weight loss-induced improvement in insulin sensitivity (IS) has been related to enhanced muscle energy metabolism. Thus, we hypothesized that weight loss due to bariatric surgery may induce epigenomic changes, which in turn modify mitochondrial function and intracellular lipids. We previously reported that IS fails to improve at 2 weeks (2 w), but then continuously increases until 52 weeks (52 w) after surgery. Now, we monitored muscle mitochondrial function and lipid intermediates in 49 obese humans (OBE; 40±10 years, BMI 51±7 kg/m2) before and for 52 w after bariatric surgery. Genome-wide gene expression and DNA methylation were analyzed in a subgroup of 16 OBE. Initial weight loss increases muscle oxidative capacity by 11% at 2 w, but transient elevation of certain muscle diacylglycerols resulting from unrestrained adipose lipolysis prevents from rapid improvement in IS. At 52 w, both mitochondrial function and intracellular lipids are comparable to lean humans. Acute alterations in expression of 1287 genes involved primarily in mitochondrial function, transcriptional regulation, protein transport, fatty acid metabolism and inflammatory processes, but not changes in DNA methylation, underlie the transient upregulation of mitochondrial function and lipolysis. At 52 w, 1091CpGs are differentially methylated, which relates to improved IS. Specifically, epigenetic alterations at 52 w in FTO gene, encoding an α-ketoglutarate dependent dioxygenase, and TOMM7 gene, encoding a translocase of the outer mitochondrial membrane, contribute to reprogramming transient changes in mRNA expression at 2 w.
In conclusion, initial metabolic changes after weight loss induce epigenetic modification of genes involved in muscle energy metabolism, which in turn leads to long-term beneficial changes in gene expression.

Disclosure
S. Gancheva: None. M. Ouni: None. C. Koliaki: None. T. Jelenik: None. D.F. Markgraf: None. J. Szendroedi: None. M. Schlensak: None. A. Schuermann: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi.
Omega-6 Eicosadienoic Acid Is Associated with Lower HOMA-IR and Incident T2D in Participants from the MESA Cohort
Authors: WEIR NATALIE L. , GUAN WEIHUA , STEFFEN BRIAN , STEFFEN LYN M. , KARGER AMY B. , TSAI MICHAEL Y. 
Published: June 2018

Linoleic acid (LA) and related omega-6 fatty acids have been implicated in contributing to metabolic dysfunction. However, there is some evidence to support that certain omega-6 fatty acids, such as eicosadienoic acid (EDA), may play a beneficial role in inflammation. Although, studies have inconsistently shown EDA to be inversely associated with insulin resistance and type 2 diabetes (T2D). The present study evaluated associations of EDA with log HOMA-IR and risk of incident T2D in 5,889 participants of the Multi-Ethnic Study of Atherosclerosis (MESA).
Phospholipid fatty acid profiles were determined by GC-FID. A multivariable linear regression model adjusted for age, sex, BMI, education status, smoking status, ever used alcohol, and race/ethnicity was used to determine associations between baseline EDA levels (quartiles) and log HOMA-IR; a Cox proportional hazards model estimated risk of incident T2D over a median 12 year follow-up.
Individuals in the three upper quartiles of EDA had a significantly lower log HOMA-IR compared to those in the reference quartile (Q1) (coefficient, [p-value]): Q2: -0.[p&lt;0.01]; Q3: -0.[p&lt;0.01]; Q4: -0.10 [p&lt;0.001]. Race-stratified analyses showed similar results across all races. Risk of incident T2D was significantly lower across successive quartiles of EDA (Hazard Ratio, [p-value]): Q1: referent; Q2: 0.76 [p&lt;0.01]; Q3: 0.62 [p&lt;0.001]; Q4: 0.58 [p&lt;0.001]. After race stratification, all four races showed lower risk of incident T2D but the association was only significant in Blacks; however, the interaction test for race was not significant.
We hypothesize that upregulation of EDA synthesis through preferential elongation of linoleic acid may be associated with increased insulin sensitivity leading to lowered risk for T2D. Further in vitro and in vivo studies are required to elucidate the role of EDA in mitigating insulin resistance and lowered risk of diabetes and the associated states of inflammation.

Disclosure
N.L. Weir: None. W. Guan: None. B. Steffen: None. L.M. Steffen: None. A.B. Karger: Research Support; Self; Siemens. M.Y. Tsai: None.
Risk Factors Differ by First Manifestation of Cardiovascular Disease (CVD) in Type 1 Diabetes (T1D)
Authors: MILLER RACHEL G. , ORCHARD TREVOR J. 
Published: June 2018

CVD is a major contributor to T1D morbidity and mortality but presents in a variety of first manifestations. Thus we aimed to assess risk factors for 3 CVD manifestations in a T1D cohort: 1) major atherosclerotic cardiovascular event (MACE, i.e., CVD death, myocardial infarction (MI), stroke), 2) coronary revascularization, no prior MI (REV), 3) soft CVD (SOFT, i.e., ischemic ECG or angina). Data are from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, an ongoing, prospective cohort study of childhood-onset (&lt;17 years) T1D diagnosed 1950-80 with 25 years of follow-up (n=658, 49% women, mean age 27, T1D duration 18 years at 1986-88 baseline). Follow-up exams occurred biennially for the first 10 years and at 18 and 25 years. MACE and REV were ascertained by death certificate adjudication or self-report, confirmed with medical records. Angina was determined by EDC physician history and ischemia by Minnesota coded ECGs. Prevalent CVD cases (n=54) were excluded. Those experiencing each manifestation were compared to participants not developing any CVD over follow-up. Baseline (BL), time varying updated mean (UM) and time varying most recent (MR) risk factors were assessed in Cox models (HRs per unit). CVD first manifested as n=107 MACE, n=38 REV, and n=91 SOFT. In T1D duration-adjusted multivariable models, MACE was predicted by MR ln (albumin excretion rate (AER)) (HR 1.3 p&lt;.0001), UM systolic blood pressure (SBP) (HR 1.03 p&lt;.0001), BL smoking (HR 1.9 p=0.003), UM LDLc (HR 1.01 p=0.03) and UM HbA1c (HR 1.2 p=0.03). REV was predicted by BL LDLc (HR 1.03, p&lt;.0001), BL estimated glomerular filtration rate (HR 0.98 p=0.002) and MR HbA1c (HR 1.3 p=0.03). SOFT was predicted by MR SBP (HR 1.03 p&lt;.0001), UM ln(triglycerides) (HR 1.8 p=0.01), MR HbA1c (HR 1.2 p=0.01) and MR ln(AER) (HR 1.2 p=0.02). HbA1c was consistently, but modestly, associated with all CVD manifestations. Additionally, BP and AER are important predictors of MACE and SOFT, while REV is most strongly predicted by BL LDLc.

Disclosure
R.G. Miller: None. T.J. Orchard: None.
Insulin Therapy for Insulin Resistant Patients—Harm or Benefit?
Authors: MENDEZ CARLOS E. , EILER CHRISTIAN , WALKER REBEKAH J. , EGEDE LEONARD E. 
Published: June 2018

Insulin therapy has been proven to be effective in the management of type 2 diabetes. However, in patients with known insulin resistance, additional exogenous insulin used to achieve glycemic control may further contribute to the underlying dysmetabolic process resulting in increased complications. We sought to compare clinical outcomes in patients with diabetes and high insulin resistance by insulin use status. Data from NHANES (2001-2010) was used for this study. Of the 52,195 individuals included in the survey, 1,470 were reported to have diabetes with available serum fasting insulin and glucose levels. Of these, 395 were on insulin. Individuals were categorized to have high or low insulin resistance based on HOMA IR being lower or greater than the population median. Outcomes of interest included mortality status, any reported major adverse cardiovascular event (MACE), chronic kidney disease (CKD), and LDL cholesterol levels. Stratified logistic regression were used for all dichotomous variables and survey normal regression was used for LDL. Regressions were adjusted for HbA1c level, demographics, and comorbidities. Results showed that patients with high HOMAIR who were receiving insulin therapy had a significantly greater risk of dying (OR 3.487, p&lt;0.001) and of a MACE (OR 2.756 p=0.003) compared to those not on insulin. The risk of CKD was also increased by taking insulin in the high HOMA IR group. (OR 3.657 p&lt;0.001). In patients with low HOMA IR, receiving insulin did not significantly impact risk for mortality, MACE, or CKD. No significant association was found between patients with high HOMA IR on insulin and LDL levels, however a significant negative correlation was found for LDL levels in the low HOMA IR group on insulin (-14.164 p=0.034).
In conclusion, results of this study suggest that insulin therapy for patients with high insulin resistance may result more harmful than beneficial. Future studies are warranted given the importance of these potential clinical implications.

Disclosure
C.E. Mendez: None. C. Eiler: None. R.J. Walker: None. L.E. Egede: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Advisory Panel; Self; Novo Nordisk Inc..
Diabetes Comorbidity and All-Cause, Cardiovascular, and Cancer Mortality in U.S. Adults
Authors: SUN DIANJIANYI , ZHOU TAO , LI XIANG , HEIANZA YORIKO , SHANG XIAOYUN , FONSECA VIVIAN , QI LU 
Published: June 2018

Type 2 diabetes is one of the most common chronic diseases in the U.S.; however, few studies have comprehensively assessed the relations between its comorbidities and premature death. Prospective analyses were performed linking data from National Health Interview Surveys (1997 to 2009) to National Death Index records (2011) among 366,971 adults. Cox models were used to test the relations of diabetes and eleven comorbidities with all-cause, CVD, or cancer mortality. After a median follow-up of 8.0 years (2.9 million person-years), a total of 38,687 participants had died. Compared with common-conditions-free subjects, we ranked hazard ratios (HR[95% CI]) of eleven diabetic comorbidities, and the top three were chronic kidney disease (CKD: 5.3[4.9-5.7]), liver cirrhosis (5.1[4.6-5.8]), and blindness (4.4[3.8-5.1]) for all-cause mortality. Diabetics with CKD (5.9[5.0-6.9]) and blindness (5.0[3.8-6.5]) were at the highest risk for CVD deaths. Comorbid cancer (4.1[3.6-4.6]), liver cirrhosis (4.1[3.2-5.2]), and hepatitis (2.7[2.1-3.5]) ranked top three for cancer mortality. Diabetes comorbidities may substantially increase the risk of all-cause, CVD, or cancer mortality. Liver disease is more strongly related to cancer mortality, whereas CKD and blindness with CVD. Recognition of these associations may assist with more appropriate and effective screening programs that may help decrease associated mortality.

Disclosure
D. Sun: None. T. Zhou: None. X. Li: None. Y. Heianza: None. X. Shang: None. V. Fonseca: Consultant; Self; Abbott. Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Eli Lilly and Company. Stock/Shareholder; Self; Amgen Inc.. Consultant; Self; Asahi Kasei Corporation, AstraZeneca, Novo Nordisk Inc., ADOCIA, Intarcia Therapeutics, Inc., Sanofi-Aventis. L. Qi: None.