bluuebunny/crossref_metadata_2025_split huggingface dataset:
No Increased Risk of Breast Cancer in Patients Exposed to Insulin Glargine Compared with Human NPH Insulin
Authors: BOYLE PETER , WU CHUNTAO , SHARMA KRISTEN , LIN STEPHEN L. , JUHAERI JUHAERI 
Published: June 2018

The objective of this study was to compare the risks of breast cancer in women treated with insulin glargine and NPH using claims data. The MarketScan and Clinformatics databases were used to identify patients prescribed glargine or NPH in the study periods of January 2007 to March 2016 and July 20to June 2016, respectively. The risks of breast cancer in patients prescribed glargine relative to NPH were compared using three approaches: (1) on-treatment, (2) intent-to-treat and (3) time-dependent analysis. The overall and follow-up period stratified adjusted hazard ratios (aHRs) for breast cancer for glargine compared to NPH were obtained using Cox proportional hazards modelling controlling for potential confounders.In the MarketScan database, 75,422 glargine and 21,491 NPH patients were identified, of which 42,491 glargine and 7,826 NPH patients were new users. Using the Clinformatics database, 65,648 glargine and 16,194 NPH patients were identified, including 47,118 and 10,560 new users, respectively. The overall aHRs for breast cancer for glargine compared to NPH ranged from 0.90 (95% CI: 0.76-1.07) in the time-dependent analysis for all users in the Clinformatics database to 1.30 (95% CI: 0.76-2.25) in the on-treatment analysis for new users in the MarketScan database. In the MarketScan database, the aHRs stratified by the follow-up period (&lt; 1, 1 - &lt; 3, 3 - &lt; 5 and ≥ 5 Years) ranged from 0.67 to 1.63. In the Clinformatics database the corresponding aHRs ranged from 0.85 to 1.40. All 95% confidence intervals (CIs) included the null value of 1. These findings suggest that the risk of breast cancer in patients prescribed glargine was not different from that in NPH patients.
In conclusion, the risks of breast cancer were not different between patients prescribed glargine and NPH. Additionally, no association between glargine and breast cancer was observed with follow-up longer than 5 years.

Disclosure
P. Boyle: Other Relationship; Self; Sanofi. C. Wu: Employee; Self; Sanofi. K. Sharma: Employee; Spouse/Partner; Sanofi US. S.L. Lin: Employee; Self; Sanofi. Employee; Spouse/Partner; Bristol-Myers Squibb Company. J. Juhaeri: Employee; Self; Sanofi. Other Relationship; Spouse/Partner; Sanofi.
Metformin and Risk of Hepatocellular Carcinoma in Taiwanese Patients with Type 2 Diabetes
Authors: TSENG CHIN-HSIAO 
Published: June 2018

Background: Whether metformin may reduce hepatocellular carcinoma (HCC) risk requires confirmation.
Methods: Newly diagnosed type 2 diabetes patients during 1999-20with 2 or more prescriptions of antidiabetic drugs were enrolled from the Taiwan’s National Health Insurance. A total of 173917 ever users and 21900 never users of metformin were identified (unmatched cohort). A 1:1 matched-pairs cohort of 21900 ever users and 21900 never users based on propensity score was created. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using PS. Additionally, the interactions with aspirin and statin were evaluated.
Results: In the unmatched cohort, 619 never users and 2642 ever users developed HCC, with respective incidence of 668.0 and 330.7 per 100,000 person-years and overall hazard ratio of 0.49 (95% confidence interval: 0.45-0.54). The hazard ratio for the first (&lt;25.7 months), second (25.7-56.9 months) and third (&gt;56.9 months) tertile of cumulative duration of metformin therapy was 0.89 (0.81-0.98), 0.50 (0.46-0.56) and 0.23 (0.21-0.26), respectively. Analyses in the matched cohort showed an overall hazard ratio of 0.69 (0.62-0.78) and the hazard ratio for the respective tertile was 1.28 (1.10-1.50), 0.68 (0.57-0.82) and 0.35 (0.29-0.44). A significant interaction with metformin was observed for aspirin and statin.
Conclusions: Metformin is associated with a reduced risk of HCC in a dose-response pattern. Users of both metformin and aspirin or statin have the lowest risk.

Disclosure
C. Tseng: None.
Effect of Vitamin D Supplementation on Glucose Metabolism Biomarkers—A Meta-analysis of Randomized Controlled Trials
Authors: PIZOT CECILE , MULLIE PATRICK , MACACU ALINA , DRAGOMIR MIRUNA , BOYLE PETER , AUTIER PHILIPPE 
Published: June 2018

Observational studies have linked higher serum concentrations of 25(OH)D with a reduced risk of diabetes. In order to assess the effect of vitaminD supplementation (VDS) on glucose metabolism biomarkers, a systematic review with meta-analysis of randomized-controlled trials (RCTs) was undertaken. RCTs published until February 2017 conducted in adults were selected if they examined the effect of VDS on glycosylated haemoglobin (HbA1c), fasting glucose (FG), fasting insulin (FI), or HOMA-IR. For each biomarker, summary mean differences (MDs) between intervention and placebo groups were computed using a random-effect model. A total of 48 (n=5,100 subjects), 80 (n=9,565), 58 (n=7,841), and 57 (n=7,763) RCTs were selected for the analyses on HbA1c, FG, FI and HOMA-IR, respectively, with a majority of studies conducted in Europe and the Middle-East. The summary MDs (95% confidence intervals) were: -0.06% (−0.12, 0.00) for HbA1c, -0.12 mmol/L (-0.20, -0.05) for FG, -8.53 pmol/L (-13.17, -3.90) for FI, and −0.35 (-0.54, -0.15) for HOMA-IR. High heterogeneity between studies was observed for all biomarkers (I² &gt; 70%) and no evidence for publication bias was noted. Important differences appeared between countries. In the Middle-East, the results were -0.25 (−0.42, -0.08) for FG, -17.74 (-26.36, -9.11) for FI and -0.71 (-1.09, -0.32) for HOMA-IR, with high heterogeneity (I²=76%, 79%, 79% respectively). In Europe, the results were 0.01 (-0.06, 0.07) for FG, −0.59 (-6.86, 5.68) for FI and -0.04 (-0.19, 0.10) for HOMA-IR, with lower heterogeneity (I²=21%, 48%, 0% respectively). In studies with high dose of vitamin D (≥ 100 µg/d) and subjects with baseline 25(OH)D ≤ 20 ng/mL, the summary MDs for HB1Ac and FG were -0.09% (-0.24, 0.07) and -0.mmol/l (-0.16, 0.06). The influence of VDS on glucose metabolism biomarkers seems to be marginal. The reasons underlying the heterogeneity of results across countries is unknown but differences in the conduct of RCTs cannot be excluded.

Disclosure
C. Pizot: None. P. Mullie: None. A. Macacu: None. M. Dragomir: None. P. Boyle: Other Relationship; Self; Sanofi. P. Autier: Other Relationship; Self; Sanofi.
Both Diabetes Duration and Cumulative Hyperglycemic Exposure Promote Myocardial Fibrosis and Increase Coronary Microvascular Resistance Evaluated by Comprehensive Myocardial CT Perfusion
Authors: CHOU SHENGPU , HARAGUCHI MIKIKO , FUJINO YUSUKE , TOMIZAWA NOBUO , NOJO TAKESHI , NAKAMURA SUNAO 
Published: June 2018

Background: Diabetes cardiomyopathy is raising attention recently, however, there is few clinical study to evaluate changes in the early stage before clinical signs appear. The present study investigated the risk of diabetes duration and cumulative hyperglycemic exposure (CHE) to myocardial extracellular volume (ECV), a marker of myocardial fibrosis, and coronary microvascular resistance (CMVR) assessed by dynamic myocardial CT perfusion (DMCTP).
Material and Methods: We assessed 192 patients who had undergone DMCTP from April 2016 to October 2017. Patients with significant coronary stenosis and previous stent intervention were excluded. ECV of myocardium was calculated from CT delay enhancement subtraction image. CMVR was derived from the diastolic pressure gradient divided by myocardial blood flow. We defined HbA1c debt as sum of elevated HbA1c in recent 10 years as the indicator of CHE. The impacts of diabetes duration and HbA1c debt to ECV and CMVR were analyzed by multivariable analysis.
Results: Diabetic patients showed significant increase of ECV (30.4±4.4% vs. 25.9±3.8%, p &lt;0.05) and CMVR (32.2±22.6 vs. 18.6±7.0, p &lt;0.01) compared with those without diabetes. Diabetes duration was positively related to ECV (r=0.313) and CMVR (r=0.411) respectively. A positive correlation also existed between HbA1c debt and ECV (r=0.373), and CMVR (r=0.442) respectively. Grouping patients in relation to diabetes duration presented that longer duration elevated ECV and CMVR significantly (p&lt;0.01). Elevation of HbA1c debt was also related to increase of ECV and CMVR (p&lt;0.01).
Conclusion: Diabetes induces myocardial fibrosis and increases microvascular resistance since the very early stage. Both longer diabetes duration and CHE are risk factors to the progression of microcirculatory disorders, suggesting that good glycemic control is warranted to reduce risk of diabetes cardiomyopathy.

Disclosure
S. Chou: None. M. Haraguchi: None. Y. Fujino: None. N. Tomizawa: None. T. Nojo: None. S. Nakamura: None.
Impacts of the Kumamoto Earthquake 2016 on Glycemic Control in Diabetic Patients
Authors: KONDO TATSUYA , MIYAKAWA NOBUKAZU , MOTOSHIMA HIROYUKI , ISHII NORIO , IGATA MOTOYUKI , YOSHINAGA KAYO , KUKIDOME DAISUKE , SENOKUCHI TAKAFUMI , KAWASHIMA JUNJI , MATSUMURA TAKESHI , ARAKI EIICHI 
Published: June 2018

In April 14th and 16th, 2016, Kumamoto area was severely damaged by massive M7 class earthquakes. To examine the effects of these earthquakes on glycemic control and stress factors in diabetic outpatients regularly cared in diabetic clinic of Kumamoto University Hospital, sequential HbA1c, glycated albumin, other biochemical parameters, life style associated questionnaire and Impact of Event Scale-Revised (IES-R) scores were analyzed. A total of 557 patients were enrolled and data were collected from 13 months before to 13 months after the earthquakes. In patients with type 1 diabetes (T1D) or specific types of diabetes due to other causes, glycemic control was not altered during the observational period. This glycemic stability in T1D may result from self-management of insulin doses (increase in 7% and decrease in 20% of patients). In patients with type 2 diabetes (T2D), HbA1c was decreased by 0.11% (from 7.33% to 7.22%) at 1-2 months after the earthquakes compared to that before the earthquakes, and increased at 3-4, 6-7 and 12-13 months after the earthquakes. The reduction of HbA1c at after 1-2 months in T2D was associated with “quick restoration of life-lines” and “sufficiency of sleep.” The glycemic deterioration at after 3-4 months was related to “shortage of antidiabetic agents” and “insufficient amount of food”, and at after 12-13 months that was connected to “large-scale partial destruction of houses” and “changes in working environments.” IES-R, representing disaster associated stress levels were positively correlated with “age”, “delayed restoration of life-lines”, “self-managements of antidiabetic agents” and “increased amount of activity”, and negatively associated with “early restoration of life-lines” and “sufficiency of sleep.” Thus, the glycemic control, associated factors and stress levels are altered in chronological order. Post-disaster diabetic medical care must consider these corresponding points in accordance with the time period.

Disclosure
T. Kondo: None. N. Miyakawa: None. H. Motoshima: None. N. Ishii: None. M. Igata: None. K. Yoshinaga: None. D. Kukidome: None. T. Senokuchi: None. J. Kawashima: None. T. Matsumura: None. E. Araki: Speaker's Bureau; Self; Astellas Pharma US, Inc., MSD K.K., Kowa Pharmaceuticals America, Inc., Sanofi, Novo Nordisk Inc.. Research Support; Self; Astellas Pharma US, Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Takeda Pharmaceuticals U.S.A., Inc., Daiichi Sankyo Company, Limited, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk Inc., Sanofi, Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co..
Impact of Early Intensification with Sitagliptin on Glycemic Goal Attainment among Patients with Metformin Monotherapy Failure
Authors: EJZYKOWICZ FLAVIA , LIU JINAN , ENGEL SAMUEL S. , RAJPATHAK SWAPNIL 
Published: June 2018

Background: Delay in the intensification of type 2 diabetes (T2DM) treatment after metformin monotherapy failure, or clinical inertia, is often observed among patients with poor glycemic control. Sitagliptin is used frequently as an add-on to metformin monotherapy among patients with T2DM. The objective of the study is to evaluate the association between early treatment intensification with sitagliptin and glycemic goal attainment among patients failing metformin monotherapy.
Methods: This retrospective database study of adult T2DM patients was conducted using the Quintiles Electronic Medical Record (EMR) database. The study population consisted of patients diagnosed with T2DM who failed to achieve A1c level of &lt;7% on metformin monotherapy between January 20and June 2015. The study included two groups (1) those who did not receive treatment intensification within 3 months after metformin failure (non-early group), but were intensified with any oral anti-hyperglycemic agent between 4 and 12 months and (2) those who were intensified with sitagliptin within 3 months (early sitagliptin group). A Cox regression analysis was conducted to evaluate the association between sitagliptin use and A1c goal attainment within 12 months.
Results: We identified 2,852 patients aged ≥18 years with T2DM who failed metformin monotherapy, of which 362 patients were intensified with sitagliptin within 3 months and 2,490 patients were included in the non-early group. A multivariate Cox regression model adjusted for age, gender, BMI, smoking status, baseline A1c, comorbidities, and other nondiabetic medications showed that early sitagliptin therapy resulted in doubling the likelihood of achieving A1c goal attainment (HR 2.12; 95% CI 1.80-2.50) within 12 months compared to non-early group.
Conclusion: Early intensification with sitagliptin results in higher goal achievement levels among patients failing metformin monotherapy failure.

Disclosure
F. Ejzykowicz: Employee; Self; Merck Sharp & Dohme Corp. J. Liu: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; Anthem, Inc.. Employee; Self; Janssen Scientific Affairs, LLC. S.S. Engel: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. S. Rajpathak: Employee; Self; Merck & Co., Inc..
Treatment Patterns in Patients with Newly Diagnosed Type 2 Diabetes in 2015
Authors: WU JIANMIN , XIE JIN , WONG-JACOBOSN SIEW HOONG , HAYNES VIRGINIA S. , ZHAO ZHENXIANG 
Published: June 2018

This study explored the treatment pattern of newly diagnosed type 2 diabetes (T2D) patients in 2015 using the Commercial and Medicare MarketScan databases. Therapy lines were defined in Table 1. A total of 115,091 adult patients with newly diagnosed (Dx) T2D were identified. Of patients who had antidiabetic drug (ADD) claims within a year after first T2D Dx (n = 53,041), about 20% progressed to second line. The average time from initial Dx to first line and from first to second line were 53 and 117 days respectively. The proportion of combination therapy (≥ 2 ADDs) was increased from 12% in first line to 63% in second line. Table 1 captured the top 20 therapies in each line. About 76% of patients started with metformin (MET) as monotherapy or in combination with sulfonylurea (SU). Substantial variation exists in second line therapies with SU leading the top monotherapy (8.7%). A very small number of patients received newer drugs such as dapagliflozin, dulaglutide and empagliflozin. In line with ADA recommendations, the majority of patients initiated MET-based regimens in first line. SUs were widely used in second line. Despite ongoing research and drug development, little has changed in prescribing of ADD, suggesting a need for better understanding of the gaps in diabetes management and/or education on use and benefits of newer drugs. This study most likely underestimated ADD therapy due to lack of prescriptions filled without pharmacy benefits.

Disclosure
J. Wu: None. J. Xie: None. S. Wong-Jacobosn: None. V.S. Haynes: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Z. Zhao: None.
Burden of Hospitalization in Young-Onset Type 2 Diabetes—The Hong Kong Diabetes Register
Authors: KE CALVIN , LAU ERIC S.H. , LUK ANDREA , MA RONALD C. , KONG ALICE P. , CHOW ELAINE , CLARKE PHILIP M. , CHAN JULIANA C. 
Published: June 2018

Objective: Young-onset type 2 diabetes (YOD, defined as age &lt;40 years) is associated with early β-cell failure and poor risk factor control. While YOD incidence is increasing rapidly, its disease burden is poorly understood, resulting in clinical inertia and poor treatment adherence. We examined the burden of hospitalization among Chinese adults with YOD.
Methods: We conducted a prospective cohort study measuring all-cause hospitalization in YOD and usual-onset type 2 diabetes (T2D) among adults aged 20-75 years using the Hong Kong Diabetes Register (2000-2015, n=21,779). We estimated the impacts of YOD and risk factor control on hospitalization rate after T2D diagnosis using negative binomial regression.
Results: YOD hospitalization had a bimodal distribution, with a disproportionate burden of mental illness &lt; age 40 years (35.9% of bed-days; Figure. 1). YOD was associated with a 3-fold increase in hospitalization rate vs. usual-onset T2D (adjusted rate ratio 2.8, 95% confidence interval 2.5-3.2). Intensified risk factor control (A1C&lt;6.2%, blood pressure&lt;120/75, LDL cholesterol&lt;2.0 mmol/L) was associated with a 39.5% reduction in cumulative hospital days.
Conclusions: YOD is associated with substantial excess hospitalization across the adult lifespan. Urgent efforts are required to develop aggressive management strategies, and to address the unrecognized burden of mental illness in YOD.

Disclosure
C. Ke: None. E.S.H. Lau: None. A. Luk: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Sanofi. R.C. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd. A.P. Kong: Research Support; Self; AstraZeneca. E. Chow: Research Support; Self; Sanofi. P.M. Clarke: None. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck & Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp & Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company.
Prevalence of Prediabetes and Undiagnosed Diabetes among Adults Aged 18 to 70 Years in France—The CONSTANCES Cohort
Authors: FUENTES SONSOLES , FOSSE-EDORH SANDRINE , REGNAULT NOLWENN , GOLDBERG MARCEL , COSSON EMMANUEL 
Published: June 2018

Introduction: This study aimed to update the prevalence of different diabetes stages in France among adults aged 18 to 70 years according to gender, age and socioeconomic status.
Methods: The CONSTANCES cohort is a randomly selected representative sample of French adults. In 2013, 16,340 participants were recruited. Based on data from self-administered questionnaires, medical examination (including fasting plasma glucose (FPG) measurement) and data from the French National Insurance System (antidiabetic drugs consumption and hospitalization), three stages were defined: prediabetes (WHO definition), diagnosed and undiagnosed (FPG ≥ 126 mg/dL) diabetes. Weighted prevalence of each stage was estimated for all population and by gender, age and education. Confidence intervals were calculated using logit transformation.
Results: In 2013, the prevalence of prediabetes, undiagnosed diabetes and diagnosed diabetes was 7.4%, 1.9% and 3.9%, respectively. All these rates were higher in males, increased steadily with age while decreasing with education (Figure).
Discussion: Our results show that the prevalence of prediabetes and unknown diabetes are still very high in developed countries, like France. They highlight the need to increase primary prevention, and to reinforce secondary prevention of diabetes, especially through promotion of screening in population at risk.

Disclosure
S. Fuentes: None. S. Fosse-Edorh: None. N. Regnault: None. M. Goldberg: None. E. Cosson: Consultant; Self; Lilly France. Board Member; Self; Novartis France. Consultant; Self; Roche Diagnostics France. Board Member; Self; Ascensia Diabetes Care. Consultant; Self; Bezins France. Board Member; Self; MSD France.
Impact of Diabetes on Colorectal Cancer Screening Rates in U.S. Adults
Authors: CAMPBELL JENNIFER A. , WALKER REBEKAH J. , EILER CHRISTIAN , EGEDE LEONARD E. 
Published: June 2018

Background: Individuals with diabetes have an increased risk for colorectal cancer, however routine diabetes care visits may increase colorectal screening rates. The aim of this study is to examine whether diabetes diagnosis influences screening completion in U.S. adults.
Methods: This study used data from 464,664 adults completing the 2014 BRFSS national survey. Logistic regression models tested the likelihood of colorectal screening by diabetes status, and whether diabetes quality of care indicators predicted colorectal screening among diabetes patients. A stratified analysis examined predictors of screening by demographic status for diabetes/nondiabetes patients.
Result: Of the population, 13.1% reported having diabetes and of these, 67% reported completing colorectal screening. Diabetes status, accounting for demographic variables, predicted blood stool screening in the last year (OR 1.09), colonoscopy (OR 1.17), and any colorectal screening technique (OR 1.08). For diabetes patients, non-Hispanic black patients were significantly more likely to receive any type of screening (OR 1.18), as well as women (OR 1.15). Diabetes patients reporting an HbA1c check (OR 1.49), having their eyes checked (OR 1.52), and receiving diabetes education (OR 1.37) were significantly more likely to have completed any screening technique, whereas primary care visits did not predict screening.
Conclusions: Patients with diabetes are more likely to complete colorectal screening compared to patients without diabetes. Non-Hispanic blacks and women with diabetes were significantly more likely to complete any screening, whereas this was not the case in patients with no diabetes. Quality of care indicators and receiving diabetes education significantly predicted screening completion compared to having a physician visit alone. Colorectal screening interventions incorporating patient engagement may be warranted for both the diabetes and general population.

Disclosure
J.A. Campbell: None. R.J. Walker: None. C. Eiler: None. L.E. Egede: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Advisory Panel; Self; Novo Nordisk Inc..