bluuebunny/crossref_metadata_2025 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<0.001]; Q3: -0.22 [p<0.001]; Q4: -0.32 [p<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>0.05]; Q3: 0.72 [p<0.01]; Q4: 0.48 [p<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<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<30 and 32.28% in 30≤GFR<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<0.05), while CHD (15.4 to 13.4), COPD (10.1 to 8.0), and hepatitis (5.5 to 2.9) declined (P<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<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 <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 (<5 years, 5-10years, 10-15 years, >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<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, >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<0.01]; Q3: -0.[p<0.01]; Q4: -0.10 [p<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<0.01]; Q3: 0.62 [p<0.001]; Q4: 0.58 [p<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 (<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<.0001), UM systolic blood pressure (SBP) (HR 1.03 p<.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<.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<.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<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<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.
Protection from Severe Periodontal Disease among People with Type 1 Diabetes with Duration of 50 Years or Longer
Authors: SHINJO TAKANORI , ISHIKADO ATSUSHI , HASTURK HATICE , TINSLEY LIANE J. , POBER DAVID M. , WU I-HSIEN , VAN DYKE THOMAS E. , GENCO ROBERT J. , KING GEORGE L.
Published: June 2018

Periodontal disease (PD) is more common and severe in people with diabetes than the general population. The presence of severe PD is correlated with decreased survival, since it can potentially affect glycemic control and severity of complications in people with diabetes. We have reported that Medalists (people with T1DM of 50 years or longer duration) may have endogenous protective factors for the development of diabetic nephropathy (DN) and retinopathy (DR). This study assessed the prevalence of PD in the Medalist cohort and correlated it to the known risk factors of PD and diabetic complications. Severity of PD was defined in a subset (n=170) of Medalists with comparable characteristics of the whole cohort, according to the AAP criteria. The prevalence of severe PD was dramatically decreased in Medalists (13.5%) compared with other studies of people with diabetes of similar age, approximately 33%. Clinical parameters, such as male gender, chronological age, age at diagnosis, and total insulin dose were correlated positively with severity of PD (p=0.04, 0.01, 0.03, and 0.02, respectively), while duration of disease, hemoglobin A1c, BMI, and lipid profiles did not exhibit any correlation. Interestingly, detectible plasma C-peptide levels correlated inversely with severity of PD (p=0.04). Systemic inflammatory markers, such as plasma IL-6, clearly correlated positively with the severity of PD (p=0.01). Serum antibody titer against Porphyromonas gingivalis (Pg), a known pathogen of PD, trended with severity of PD (p=0.08). Amongst the various complications, only the prevalence of CVD correlated positively with severity of PD (p=0.02). These results suggest that Medalists are protected from severe PD even with hyperglycemia. The endogenous protective factors for PD could be similar to those for CVD, possibly related to endogenously produced insulin to neutralize the chronic inflammation caused by residual infection with Pg in the gingival tissues.

Disclosure

T. Shinjo: None. A. Ishikado: Employee; Self; Sunstar Inc.. Employee; Spouse/Partner; Sunstar Inc.. H. Hasturk: None. L.J. Tinsley: None. D.M. Pober: None. I. Wu: None. T.E. Van Dyke: None. R.J. Genco: None. G.L. King: Research Support; Self; Sanofi-Aventis.
Using Google Cloud and Predictive Analytics to Promote Influenza Vaccination among People with Diabetes
Authors: LISKA JAN , GUPTA AASHIMA , THOMSON ANGUS , SAMSON SANDRINE I. , MILLS HENRY G. , GREENBERG MICHAEL E. , KAMKOLKAR MILIND , BEAL ANNE C. , BEAUDIN MARYSE
Published: June 2018

Background: Although influenza vaccination is recommended for people with type 1 and 2 diabetes, uptake is suboptimal, often leading to complications and hospitalizations. Vaccine acceptance is influenced by several psychosocial and behavioral factors, including one’s knowledge of flu and vaccination beliefs. We used novel data sources to understand predictors of vaccination adherence among countries and subpopulations.

Methods: We used VaxiTrends, a proprietary dataset, to identify variables influencing vaccine uptake among adults in the U.S., China, France, Mexico, and U.K. We combined the data with NHI Interview Survey results, which offer insights into health behaviors of Americans with diabetes. This information was aggregated with data from Google’s FluTrend, which signals flu incidence, and Google Trends Application Programming Interface, which tracks search keyword popularity by location and date in a de-identified fashion. Cluster analyses indicated factors most positively and negatively associated with acceptance and adherence.

Results: Our analysis indicates that targeted interventions focussing on country-specific drivers of flu vaccination adherence among subpopulations of people with diabetes could lead to an increase in vaccination rates of up to 5%. In France, Mexico and U.K., relationships with HCPs were most predictive of vaccination adherence, while in the U.S., reminders and strategies addressing affordability concerns were key predictors. In China, encouragement from relatives, convenient options for receiving vaccinations and education to counter fear of flu vaccination may have the greatest impact. Within countries,we found some patient subgroups were more amenable to vaccination than others.

Conclusion: By identifying country-specific behavioral drivers of flu vaccination and most receptive subgroups, we can design more tailored interventions to increase uptake.

Disclosure

J. Liska: Employee; Self; Sanofi. A. Gupta: None. A. Thomson: Employee; Self; Sanofi Pasteur. S.I. Samson: Employee; Self; Sanofi Pasteur. H.G. Mills: Employee; Self; Sanofi. M.E. Greenberg: Stock/Shareholder; Self; Merck & Co., Inc.. Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi, GlaxoSmithKline plc., Pfizer Inc.. M. Kamkolkar: None. A.C. Beal: Employee; Self; Sanofi. Board Member; Self; AcademyHealth. M. Beaudin: Employee; Self; Sanofi.
Betatrophin Predicts Cardiovascular Events Independently from the Presence of Type 2 Diabetes and Coronary Artery Disease
Authors: LEIHERER ANDREAS , MUENDLEIN AXEL , GEIGER KATHRIN , SAELY CHRISTOPH H. , BRANDTNER EVA-MARIA , EBNER JANINE , LARCHER BARBARA , MADER ARTHUR , FRAUNBERGER PETER , DREXEL HEINZ
Published: June 2018

Betatrophin, also known as ANGPTL8 or lipasin is a nutritionally-regulated protein secreted by the liver and adipose tissue. It is associated with type 2 diabetes mellitus (T2DM) and lipid metabolism. Whether betatrophin is associated with the risk for cardiovascular events is unknown and is addressed in the present study. We measured betatrophin in 553 patients undergoing coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD) and prospectively recorded cardiovascular events in these patients during a follow-up period of up to 8 years. During follow-up, 301 cardiovascular events occurred. The incidence of cardiovascular events was significantly higher in patients with T2DM (n=161) than in those who did not have diabetes (47.2% vs. 34.4%; p=0.005). Betatrophin was significantly and inversely associated with cardiovascular events both univariately (HR 0.64 [95% CI 0.47-0.87], p=0.004) and after full adjustment including T2DM and baseline CAD (HR 0.55 [95% CI 0.40-0.76], p<0.001). The inclusion of betatrophin to a basic prediction model for the cardiovascular event risk significantly increased model performance (NRI=0.188, p<0.01).

In conclusion, this study for the first time shows that betatrophin predicts cardiovascular events independently from conventional risk factors including the presence of T2DM.

Disclosure

A. Leiherer: None. A. Muendlein: None. K. Geiger: None. C.H. Saely: None. E. Brandtner: None. J. Ebner: None. B. Larcher: None. A. Mader: None. P. Fraunberger: None. H. Drexel: None.
Vitamin D, Prediabetes, and Diabetes—Bidirectional Mendelian Randomization Analysis
Authors: WANG NINGJIAN , ZHAO LI , CHEN CHI , CHEN YI , LU YINGLI
Published: June 2018

Background: Vitamin D deficiency is associated with diabetes in many observational studies. However, the causality between them has not been established. We used bi-directional mendelian randomization (MR) analysis to explore the causal relationship between 25-hydroxyvitamin D [25(OH)D] and glycemic status and indices.

Methods: Participants were included from a survey in East China from 2014-2016 (10,338 and 10,655 participants having diabetes and vitamin D related genotyping information). We calculated weighted genetic risk scores (GRS) as the instrumental variables for 25(OH)D concentration and diabetes based on related single nucleotide polymorphisms. Fasting plasma glucose and HbA1c were measured. Diagnosis of diabetes and prediabetes was based on American Diabetes Association criteria.

Results: The MR-derived odds ratios of genetically determined 25(OH)D for risk of diabetes and prediabetes was 0.985 (95% CI 0.940, 1.032) and 0.982 (95% CI 0.948, 1.016), respectively. The MR-derived estimates for fasting plasma glucose and HbA1c were also not significant. Conversely, the MR-derived regression coefficients of genetically determined diabetes and prediabetes for 25(OH)D was 0.448 (95% CI -0.395, 1.291) and 1.303 (95% CI -1.210, 3.816).

Conclusion: Our results support the conclusion that there is no causal association between vitamin D and diabetes and prediabetes using a bi-directional MR approach in a Chinese population. MR studies using 1,25-dihydroxyvitamin D and large intervention trials are needed to further validate the findings.

Disclosure

N. Wang: None. L. Zhao: None. C. Chen: None. Y. Chen: None. Y. Lu: None.
Insulin Therapy and Breast Cancer Risk
Authors: PIZOT CECILE , DRAGOMIR MIRUNA , BOYLE PETER , AUTIER PHILIPPE
Published: June 2018

Some observational studies have suggested an association between insulin therapy and cancer risk. Using a meta-analytical approach, the risk of breast cancer in diabetic patients treated with insulin was compared to the risk in diabetic patients treated with a non-insulin therapy (NIT). A systematic literature search was conducted in the PubMed database from inception to October 2017. Studies with a prospective design including nested case-control and case-cohort studies were selected. Summary relative risks (SRR) of breast cancer associated with the use of any type of insulin therapy compared to NIT were computed using a random-effect model. Three sub-analyses were carried out: one according to the adoption of a new-user design (i.e., including only new users of a drug) vs. a prevalent user design (i.e., including both new and past users of a drug); one according to the type of comparator (specific NIT vs. any type of NITs); and one according to the type of diabetes. A total of 12 studies, representing 1,392,040 diabetics and 15,430 breast cancer cases, were included in the analysis. Overall, the SRR of breast cancer associated with insulin use was 0.97 (95% CI: 0.87, 1.08) with a high degree of heterogeneity between studies (I²=60%, p<0.01) and no evidence for publication bias. In all three sub-analyses, the SRR remained close to 1.0 and statistically non-significant. The heterogeneity was reduced in studies restricted to T2DM patients, in studies with a new-user design and in studies with a specific NIT used as comparator (I²=0%, 21% and 0%, respectively). Heterogeneity was increased in studies using a prevalent user design and in studies with a no/never use as comparator (I²=70% and 73%, respectively). This meta-analysis showed no evidence for an association between breast cancer occurrence and insulin therapy prescription history when the comparators are other NITs. The marked differences in heterogeneity indicate that studies with a new-user design or with a specific NIT as comparator are probably less affected by confounding and biases.

Disclosure

C. Pizot: None. M. Dragomir: None. P. Boyle: Other Relationship; Self; Sanofi. P. Autier: Other Relationship; Self; Sanofi.
Thiazolidinediones and Reduced Risk of Incident Bacterial Abscess in Adults with Type 2 Diabetes—A Population-Based Cohort Study
Authors: CHANG CHIA-HSUIN , WANG JIUN-LING , DONG YAA-HUI , KO WEN-CHIEN , WU LI-CHIU , CHUANG LEE-MING , CHEN PAU-CHUNG
Published: June 2018

Objective: Previous research has suggested that peroxisome proliferator-activated receptor-gamma (PPAR-γ) may play an important role in immunomodulation. We examined whether PPAR-γ agonists (thiazolidinediones) were associated with the incidence of bacterial abscess among patients with type 2 diabetes.

Research Design and Methods: This retrospective cohort study included 46,986 propensity-matched patients diagnosed with type 2 diabetes between 2000 and 2010. We compared the incidence of bacterial abscess and the incidences of two subclasses: liver and non-liver abscesses, between groups treated with either metformin plus a thiazolidinedione (M+T, N=7831) or metformin plus a sulfonylurea (M+S, N=39,155). Data were retrieved from a population-based Taiwanese database. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox proportional hazard regression models.

Results: During a median follow-up of 4.5 years, the adjusted rate of incident bacterial abscess was lower with M+T than with M+S treatment (1.89 vs. 3.15 per 1000 person-years). M+T was associated with a reduced risk of bacterial abscess (adjusted HRs: 0.58, 95% CI: 0.42-0.80 for bacterial abscess; 0.54, 95% CI: 0.28-1.07 for liver abscess; and 0.59, 95% CI: 0.41-0.85 for non-liver abscess). The results did not change materially, after accounting for unmeasured confounding factors and differential censoring between the two treatment groups. Rosiglitazone and pioglitazone, in combination with metformin, produced similar reductions in risk for all abscess outcomes.

Conclusions: We found that M+T had a substantial protective effect in reducing the incidence of bacterial abscesses. These findings merit further investigation.

Disclosure

C. Chang: None. J. Wang: None. Y. Dong: None. W. Ko: None. L. Wu: None. L. Chuang: None. P. Chen: None.
Quarterly HbA1c Surveillance in Children with Islet Antibodies (IA) Accurately Predicts Type 1 Diabetes (T1D) Timing
Authors: KILLIAN MICHAEL , VEHIK KENDRA , LITTLE RANDIE R. , LARSSON HELENA ELDING , HALLER MICHAEL J. , REWERS MARIAN , SHE JINXIONG , TOPPARI JORMA , AKOLKAR BERNA , KRISCHER JEFFREY , HAGOPIAN WILLIAM ,   TEDDY STUDY GROUP
Published: June 2018

IA sensitively predict future T1D, but onset often occurs many years after seroconversion. Early diagnosis results in less DKA and milder initial disease, especially in young children. Using the international TEDDY cohort, we asked if quarterly HbA1c testing could predict T1D among pre-pubertal subjects with ≥1 persistent IA (GADA, IA2A, IAA). Mean(SD) age at seroconversion and T1D onset was 43(29) and 73(22) months respectively. Of 8,504 HLA high risk children, 456 had persistent confirmed IA, had undergone at least 3 quarterly HbA1c tests in the prior 12 months, and were not on diabetes drugs or diets. Of these, 104 progressed to T1D and 352 did not. Subjects were split into training (292 total, 62 progressors) and test (164 total, 40 progressors) datasets with similar characteristics. The optimal maximum HbA1c cutpoint within 1 year pre-onset to predict T1D, by ROC analysis, was similar in training and test datasets (p=0.66). For both, HbA1c ≥5.6% gave the best Youden index. Other factors significant for T1D risk in the training dataset included age at HbA1c test, month of HbA1c test, continent and IA2A titer, but not gender, family history, HLA type, seroconversion age, IAA titer nor T1D-related SNP genotypes. Adjusted for significant factors, the optimal HbA1c cutpoint of ≥5.6% for quarterly testing was 91% sensitive, 91% specific, 73% PPV and 98% NPV to predict T1D within 1 year in children with HLA and IA risk. The final predictive model fit both training and test data similarly (p=0.28). Median(SD) time from first HbA1c ≥5.6% to diagnosis was 8.6(4.5) months, enabling monitoring and education for earlier treatment. Quarterly HbA1c surveillance is cost-effective and clinically accessible. A hierarchical plan for pediatric T1D prediction is proposed comprising initial genetic screening, then IA surveillance of those at genetic risk, then HbA1c surveillance of those with IA, and finally close glycemic surveillance of those with HbA1c ≥5.6% to ascertain metabolic onset.

Disclosure

M. Killian: None. K. Vehik: None. R.R. Little: None. H. Elding Larsson: None. M.J. Haller: None. M. Rewers: None. J. She: None. J. Toppari: None. B. Akolkar: None. J. Krischer: None. W. Hagopian: None.
A Cost Analysis of Intensified vs. Conventional Multifactorial Therapy of Patients with Type 2 Diabetes—The Steno 2 Study
Authors: GAEDE JOACHIM , OELLGAARD JENS , IBSEN RIKKE , GÆDE PETER , NOERTOFT EMIL , KJELLBERG JAKOB , PEDERSEN OLUF
Published: June 2018

Introduction: Follow-up at 21.2 years after the initiation of the Steno-2 study, demonstrated that intensified multifactorial intervention increases median life-span with 7.9 years and delays incident cardiovascular disease (CVD) with a median of 8.1 years compared to conventional multifactorial intervention. Here we aimed to analyse the direct medical costs in the two original treatment groups during 21.2 years of follow-up.

Methods: In 1993, 160 Danish patients with type 2 diabetes and microalbuminuria were randomised to receive either conventional or intensified and target-driven multifactorial intervention for 7.8 years. Information on direct health costs was gathered from health registers and any difference of costs in the two groups was assessed by non-parametric bootstrap t-test analysis.

Results: Intensified treatment was on average more expensive regarding drug prescriptions, but less expensive in primary health sector services (both p<0.0001) and in-patient admission costs (p=0.02), specifically related to CVD (p<0.0001) during the entire follow-up period. There was no significant difference in total costs between the intensified treatment group, $13.0M and the conventional treatment group, $12.3M (p=0.19). When further assessing the cost per patient year there was no significant difference between the intensified group, $9,648, and the conventional treatment group, $10,681 (p=0.13).

Conclusion: Over an average follow-up of 21.2 years we found no significant increase in total costs or in costs per person year associated with intensified multipronged treatment for 7.8 years when compared to conventional multipronged treatment. Considering the substantial gain of years of life and health benefits achieved with intensified treatment we conclude that intensified multifaceted intervention in high-risk patients with type 2 diabetes is highly cost-effective in a Danish health care setting.

Disclosure

J. Gaede: None. J. Oellgaard: None. R. Ibsen: None. P. Gæde: None. E. Noertoft: Employee; Self; Novo Nordisk A/S. J. Kjellberg: None. O. Pedersen: None.
The Prevalence and Impact of Diabetes Mellitus among Undocumented Immigrants in an Indigent Care Program in Riverside, California
Authors: LEE HAYLEY , ZAKHARY BISHOY L. , FIREK MATTHEW A. , LANGE HEIDI , GOMEZ CLAUDIN A. , FIREK ANTHONY
Published: June 2018

Background: Acculturated undocumented immigrants (UI) in the U.S. with sedentary lifestyle and poor eating habits are at risk for diabetes mellitus (DM). UI also face adverse social, economic, and psychological stressors that may lead to poor clinical outcomes. No study to date has assessed DM prevalence and clinical outcomes among UI.

Methods: Riverside University Health System, a county health system, provides medical care for indigent patients including UI. Of 8,466 UI receiving indigent care as of March, 2017, 500 UI were randomly selected to assess DM prevalence and clinical outcomes.

Results: The mean age was 46.2 with more females (59%) accessing medical care. Over 95% were Hispanics and 74% were born in Mexico. Most were married and only 11% worked full time. A majority of UI never smoked (67%), and only 18% consumed alcohol. The prevalence of DM was 27%, and diabetics were older than nondiabetics (52.2 vs. 43.9, p<0.001) with comparable BMIs (29.9 vs. 28.9, p=0.12). The mean hemoglobin A1c was 8.3 and insulin and oral anti-hyperglycemic medication use was 8% and 19%, respectively. The total clinic visits among diabetics was 19 compared to 13 in nondiabetics (p=0.018) while total emergency department visits were comparable between two groups (2 vs. 2, p=0.100). The use of prescription medications was higher in diabetics than nondiabetics (7 vs. 4, p=<0.001). Diabetics had a higher rate of hypertension compared to nondiabetics (57% vs. 20%, p<0.001), but other clinical conditions were similar [congestive heart failure (1% vs. 3%), cancer (4% vs. 3%), depression (6% vs. 3%), chronic kidney disease (7% vs. 3%)].

Conclusions: The prevalence of DM among UI is high with poor glycemic control. Diabetics had more clinic visits than nondiabetics and were taking more prescription medications. Despite high prevalence of DM, diabetes-related complication and comorbidity rates were low, which may be due to medical care access through the indigent care program.

Disclosure

H. Lee: None. B.L. Zakhary: None. M.A. Firek: None. H. Lange: None. C.A. Gomez: None. A. Firek: None.
Distance from Glycemic Target at the Time of Add-On Initiation in Patients with Type 2 Diabetes (T2D) Failing Metformin Monotherapy in the United States
Authors: FERNANDES GAIL , HANNACHI HAKIMA , LIU JINAN , WANG TONGTONG , MCNEILL ANN MARIE , FU ALEX Z. , RAJPATHAK SWAPNIL
Published: June 2018

While it is known that a substantial proportion of U.S. patients with T2D are not at glycemic target, the distance to glycemic target has not been adequately characterized, especially at the time of add-on initiation. The objective of the study was to quantify the distance from an HbA1c target of 7% among patients failing metformin monotherapy at the time of treatment intensification with an add-on agent. This retrospective study using Quintiles Electronic Medical Record database included patients with diagnosed T2DM on metformin monotherapy between Jan 2012- Dec 2014 (index date), with at least 12 months of continuous enrollment pre-index date, documented HbA1c ≥7% and prescribed an add-on agent. Patients with type 1 diabetes, pregnancy/gestational diabetes or other secondary diabetes were excluded. Distance from glycemic target was calculated as the median difference of HbA1c from target of 7% at the time of add-on initiation was reported. A total of 22,239 T2DM patients met the study criteria; mean age of 58.3 years, 51.2% were female, 10.8% of patients had a history of microvascular complications; 5.1% had a history of macrovascular complications. Median difference from HbA1c target was 1.3%, with 23.7% (n=5261) of patients between 1 to 2%, and 35.5% (n=7897) greater than 2% from HbA1c target of 7%. In a sensitivity analysis that excluded patients for whom HbA1c target higher than 7% may be more appropriate (older patients ≥75 years, those with chronic diabetes complications or history of hypoglycemia; n = 5195) this distance to goal was still as high as 1.4%. In these patients, where a target of 8% may be more appropriate, 27.0% were ≥1% away from the target at the time of intensification. In this study, we found more than half of the metformin monotherapy patients were at least 1% away from glycemic target of 7% at the time of add-on initiation.

Disclosure

G. Fernandes: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; Janssen Research & Development. Stock/Shareholder; Self; Merck & Co., Inc.. Stock/Shareholder; Spouse/Partner; Janssen Research & Development. H. Hannachi: Employee; Self; Merck & Co., Inc. J. Liu: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; Anthem, Inc.. Employee; Self; Janssen Scientific Affairs, LLC. T. Wang: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc.. Employee; Spouse/Partner; Janssen Pharmaceuticals, Inc. A. McNeill: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc.. A.Z. Fu: None. S. Rajpathak: Employee; Self; Merck & Co., Inc..
Prediction of Adverse Pregnancy Outcomes among Women with Type 1 Diabetes
Authors: COSTACOU TINA , RUBINSTEIN DEBRA , ORCHARD TREVOR J.
Published: June 2018

Women with type 1 diabetes are at a greater risk for adverse pregnancy outcomes (APO) compared with the general population, though factors relating to the occurrence of APO have not been well studied. We thus assessed predictors of APO among women with type 1 diabetes. Female participants (n=325; mean baseline age 28, duration 19 years) of a prospective cohort of childhood onset type 1 diabetes were selected for study. Among 320 with pregnancy data available, all pregnancies occurred after study entry (1986-88) for 61 (mean baseline age 21 and duration 14 years). APO were defined as tubal/ectopic pregnancies, spontaneous or induced abortions and stillbirths. Follow-up time was calculated as time in years from study entry to the date of the first adverse pregnancy outcome or date of last live birth for those with normal pregnancies. During 25 years of follow-up, 28 (45.9%) had at least one APO. With the exception of a greater number of total pregnancies in those with an APO (p=0.03), no other univariate differences were observed. In multivariable Cox models, a greater number of pregnancies (HR=1.49, p=0.03), log albumin excretion rate (HR=1.27, p=0.03) and proliferative retinopathy (HR=5.04, p=0.003) predicted APO. In multiple linear regression analyses, the number of pregnancies (β=0.58, p<0.0001) and the presence of proliferative retinopathy (β=0.75, p=0.01) directly predicted number of APO. In analyses excluding induced abortions from the outcome definition (19 adverse events (31.1%)), glomerular filtration rate was the only predictor of any APO (HR=0.98, p=0.08). A greater number of pregnancies (β=0.48, p<0.0001), non-HDL cholesterol (β=0.006, p=0.04), white blood cell count (β=-0.10, p=0.05) and proliferative retinopathy (β=0.74, p=0.02) predicted number of APO. Among women with type 1 diabetes, the presence of microvascular complications relates to both the occurrence and the number of subsequent adverse pregnancy outcomes.

Disclosure

T. Costacou: None. D. Rubinstein: None. T.J. Orchard: None.