bluuebunny/crossref_metadata_2025_split huggingface dataset:
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&lt;0.001). The inclusion of betatrophin to a basic prediction model for the cardiovascular event risk significantly increased model performance (NRI=0.188, p&lt;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&lt;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&lt;0.0001) and in-patient admission costs (p=0.02), specifically related to CVD (p&lt;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&lt;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=&lt;0.001). Diabetics had a higher rate of hypertension compared to nondiabetics (57% vs. 20%, p&lt;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..