bluuebunny/crossref_metadata_2025_split huggingface dataset:
1642-P: Glucose Control among Diabetes Cases Selected from a Representative National Survey in Brazil
Authors: DOS REIS RODRIGO C.P. , DUNCAN BRUCE B. , SCHMIDT MARIA I. 
Published: June 2019

Background: A target of an HbA1c &lt;7% is frequently the cornerstone of clinical guidelines for the care of diabetes globally. Yet, nationally representative NHANES surveys indicate that only 50 to 60% of those with diabetes meet this target. Our aim was to evaluate glucose control when assessed by HbA1c in a national sample of Brazilian adults with diabetes.
Methods: A sub-sample of adults (18 years or older) of the representative Brazilian National Health Survey (2014-2015) was randomly selected for the collection of biological samples. Of these, 8952 (52%) individuals provided samples, and 8541 (50%) have HbA1c results. HbA1c was measured at a NDPG-certified central laboratory. Diabetes was defined by self-report of a physician diagnosis. Given the complex sampling used to select participants and the response rate obtained, we used the rake method of post-stratification survey weights, calculated according to sex, age, and education, to estimate national rates.
Results: Among the 8541 adults, 573 (5.87%; 95% CI: 5.41%-6.33%) reported having received a previous diagnosis of diabetes outside of pregnancy. Of these, only 55.2% (51.1%-59.4%) had HbA1c less than 7%, and 69.5% (65.7%-73.4%) less than the more flexible HbA1c target of 8%. On the other hand, 19.8% (16.5%-23.1%) had HbA1c ≥9.0%, indicating very poor glucose control. Though small sample size limited statistical testing, we found no differences across socio-demographic characteristics except for educational achievement, those of lesser education more frequently presenting worse glucose control (p=0.004).
Conclusion: Our results, showing a glucose control similar to that observed in representative U.S. surveys, highlight the large fraction of cases with very poor control. New strategies are needed to improve glucose control in the entire population of persons living with diabetes.

Disclosure
R.C.P. dos Reis: None. B.B. Duncan: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company. M.I. Schmidt: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company.
1651-P: Diabetes Incidence among Medicare Beneficiaries, 2001-2014
Authors: ANDES LINDA J. , LI YANFENG , SRINIVASAN MEERA , ROLKA DEBORAH B. , GREGG EDWARD 
Published: June 2019

Diabetes mellitus affects more than 12% of the U.S. adult population and has doubled in prevalence between 1990 and 2010. Older adults are particularly affected by the increasing prevalence, which doubles roughly every decade of life and then peaks in the mid-60s at more than 25%. However, there was no change in prevalence or incidence nationally between 2009 and 2012 based on data from the National Health Interview Survey. Increasing prevalence rates are due in part to a higher incidence among adults aged 65 and older. However, these estimates are based on survey research with relatively small numbers of geriatric adults. Administrative data sets built from Medicare claims contain millions of cases, affording an opportunity to explore both trends over time and heterogeneity within the geriatric population. Although most older adults in the U.S. are enrolled in Medicare, claims are only available for those beneficiaries who are enrolled in Fee-for-Service (FFS or Parts A and B). Because beneficiaries can switch between FFS and Medicare Advantage plans, the criteria for identifying prevalent and incident cases of diabetes in FFS claims must be defined carefully. To ensure we had all claims for our study population, we included the 50.4 million Medicare FFS beneficiaries (mean age 68.9 y) who were enrolled for all 60 months of each five-year window centered on index years 2001-2014. We identified prevalent cases as those with either one inpatient or two outpatient diabetes claims within two years. Incident cases were required to have a two year “clean” period with no diabetes diagnostic code. The overall national prevalence of diabetes among Medicare FFS beneficiaries increased from 23.3% in 2001 to a high of 32.2% in 2012, and then remained level through 2014. The overall incidence rate increased from 3.4% in 2001 to a high of 4.1% in 2006-7, then decreased to 3.2% in 2014. Diabetes prevalence and incidence varied considerably across states and were higher among blacks, Hispanics and Asians than among whites.

Disclosure
L.J. Andes: None. Y. Li: None. M. Srinivasan: None. D.B. Rolka: None. E. Gregg: None.
1664-P: Does “Healthy Diabetes” Exist? Long-Term Survival in Diabetes Heart Study Participants
Authors: BOWDEN DONALD W. , XU JIANZHAO , FREEDMAN BARRY I. , PALMER NICHOLETTE , HSU FANG-CHI 
Published: June 2019

The Diabetes Heart Study, initiated in 1997, includes examination and follow-up of 1221 European Americans, 85% with type 2 diabetes (T2D). Baseline examination included extensive medical history, laboratory measures, and CT-imaging for coronary artery calcium (CAC). Through 2016, 451 participants had died. CVD-attributable deaths occurred over an age range of 39-93 years. In high-risk participants with T2D and CAC&gt;1000, 52% died after mean 14.9 year follow-up; however, many are still alive. 64% of surviving T2D participants lived with diabetes for &gt;20 years and 16.4% (31 male, 46 female) &gt;30 years. Among deceased individuals, the average duration of diabetes was 20.8 years. Comparing long-term T2D-survivors to deceased, difference in CAC, a powerful predictor of mortality, was not significant (P=0.85) with mean CAC in survivors (male=4730, female=1147) and deceased (male=4085, female=1220). Conventional clinical measures did not differ significantly (glucose, HbA1c, BP; P&gt;0.05) or were modestly different (cholesterol P=0.033; LDL P=0.035). There was a difference in the use of statins at baseline: 53% in survivors, 41% in deceased (P=0.05) and C-reactive protein (P=0.04). The strongest individual trait difference was in duration of T2D at baseline (P&lt;0.0001) but mean T2D-duration at baseline in survivors was 20 vs. 12.5 years in deceased). Thus, a significant number of individuals with T2D have long-term survival even in the presence of a significant burden of subclinical CVD, but conventional clinical measures provide little Insight. Research into the characteristics of long-term survivors with T2D may prove beneficial to all T2D patients.

Disclosure
D.W. Bowden: None. J. Xu: None. B.I. Freedman: Consultant; Self; AstraZeneca, Ionis Pharmaceuticals, Inc. N. Palmer: None. F. Hsu: None.

Funding
National Institutes of Health
1669-P: Proinsulin: C-Peptide Ratios in Relatives of Persons with Type 1 Diabetes
Authors: TRIOLO TAYLOR M. , PYLE LAURA , SELIGOVA SONA , YU LIPING , SIMMONS KIMBER , GOTTLIEB PETER , EVANS-MOLINA CARMELLA , STECK ANDREA 
Published: June 2019

Biomarkers are needed to characterize heterogeneity within populations at risk for type 1 diabetes (T1D). The ratio of proinsulin to C-peptide (PI:C ratio), a biomarker of beta cell dysfunction, has been associated with progression to T1D, but relationships between PI:C ratios and autoantibody (Ab) type and number have not been explored. We sought to characterize PI:C ratios in multiple islet Ab positive, single Ab positive and Ab negative relatives of individuals with T1D.
We measured PI:C ratios and Abs with both electrochemiluminescence (ECL) assays (ECL-IAA, ECL-GADA and ECL-IA2)and radio-binding (RBA) assays (mIAA, GADA, IA2A and ZnT8A) in 98 relatives of persons with T1D followed in the Pathway to Prevention Study at the Barbara Davis Center. Of these subjects, 31 were multiple Ab positive, 37 were single Ab positive and 22 were Ab negative at the most recent visit. Eight subjects progressed to T1D over a mean follow-up of 5.5±3.6 years. In cross-sectional analyses, there were no significant differences in PI:C ratios between T1D and/or multiple Ab positive subjects (4.16±4.06) compared to single Ab positive subjects (4.08±4.34) and negative Ab subjects (3.72±3.78) (p=0.92) overall or after adjusting for age, sex and BMI. Higher PI:C ratios were associated with ECL-IA2A (p=0.03) and ECL-IAA (p=0.03) levels, but not with mIAA, GADA, ECL-GADA, IA2A nor ZnT8A levels. In mixed-effects longitudinal models, the trajectories of PI:C ratio over time were not significantly different between the 4 groups, overall or after adjusting for sex, age, and BMI.
In conclusion, higher PI:C ratios were associated with ECL-IAA and ECL-IA2A levels, which have previously been associated with progression to T1D.

Disclosure
T.M. Triolo: None. L. Pyle: None. S. Seligova: None. L. Yu: None. K. Simmons: None. P. Gottlieb: Consultant; Self; Bristol-Myers Squibb Company, Eli Lilly and Company, Kamada, Tolerion, Inc. Research Support; Self; Intrexon, Janssen Pharmaceuticals, Inc., Mercia/NovaImmune, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc. Stock/Shareholder; Self; IM Therapeutics. Other Relationship; Self; Viacyte, Inc. C. Evans-Molina: None. A. Steck: None.

Funding
American Diabetes Association (1-14-CD-17 to A.S.)
168-LB: Burden of Cardiovascular Comorbidity in U.S. Adults with T1D
Authors: EDELMAN STEVEN V. , ZHOU FANG L. , PREBLICK RON , VERMA SUMIT , PARANJAPE SACHIN A. , DAVIES MICHAEL J. , JOISH VIJAY N. 
Published: June 2019

Around 75% of adults with T1D do not achieve glycemic control, putting them at risk of macrovascular complications. This observational study evaluated prevalence of CVD and cardiovascular risk factors (CVRF) in T1D and the economic impact on U.S. payers. Adults with T1D were identified using previously published criteria and a large health plan claims dataset. Descriptive and multivariate analyses were performed to compare economic outcomes between those with/without CVD/CVRF. A total of 12687 adults with T1D met the study criteria; prevalence of CVD and CVRF were 23% and 42%, respectively. Patients with CVD/CVRF had significantly (P&lt;0.05) greater healthcare utilization compared with those without CVD/CVRF. Percentage of hospitalized patients (CVD: 11%; CVRF: 27%; none: 8%) and mean number of outpatient physician visits (CVD: 8.1±7.6; CVRF: 5.0±5.1; none: 3.5±3.6) were higher among CVD comorbid patients vs. those without comorbidity. Significantly higher overall costs, as well as higher inpatient, outpatient, ED, and prescription costs, were observed for the CVD and CVRF cohorts vs. the No CVD/CVRF cohort (Figure). The results were consistent for all-cause and diabetes-related parameters after adjusting for confounding factors. Over 1 in 5 adults with T1D have CVD and 2 in 5 have a CVRF, with higher healthcare expenditures vs. those without. Better management of CVD in T1D could significantly reduce the economic burden and improve patient outcomes.

Disclosure
S.V. Edelman: Advisory Panel; Self; BrightSight, InPen, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Board Member; Self; Senseonics. Speaker’s Bureau; Self; AstraZeneca, Lilly Diabetes, MannKind Corporation, Merck Foundation, Sanofi-Aventis. F.L. Zhou: Employee; Spouse/Partner; Lexicon Pharmaceuticals, Inc. Employee; Self; Sanofi. Stock/Shareholder; Spouse/Partner; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Sanofi. R. Preblick: Employee; Self; Sanofi-Aventis. S. Verma: None. S.A. Paranjape: Employee; Self; Sanofi US. M.J. Davies: Employee; Self; Lexicon Pharmaceuticals, Inc. V.N. Joish: Employee; Self; Lexicon Pharmaceuticals, Inc.

Funding
Sanofi US
1683-P: Analysis of Type 1 Diabetes Genetic Risk Score Shows 1 in 8 People with Clinically Diagnosed Adult-Onset T1D Are Misdiagnosed, and Presenting Features at Diagnosis Do Not Identify Those Misdiagnosed
Authors: PATEL KASHYAP A. , THOMAS NICHOLAS , WEEDON MICHAEL N. , WALKEY HELEN C. , KAUR AKAAL , WILLIAMS ALISTAIR J. , MISRA SHIVANI , OLIVER NICK , JOHNSTON DESMOND G. , HATTERSLEY ANDREW T. ,   ADDRESS-2 CONSORTIUM
Published: June 2019

Aims: Accurate initial diagnosis of adult-onset type 1 diabetes (T1D) is important. We aimed to estimate the rate of misdiagnosis in clinically-diagnosed adult T1D. We also assessed the utility of Islet autoantibodies and presenting features to identify misdiagnosed-T1D.
Methods: We used a T1D-genetic risk score (T1D-GRS) to estimate misdiagnosed-T1D in 1112 white-Europeans adults clinically-diagnosed with T1D (age diagnosis &gt;18y) from the ADDRESS-2 study. We used 1924 gold-standard T2D as a non-T1D control. All patients were recruited &lt;6m from diagnosis and insulin treated. We assessed clinical features and autoantibodies (GADA, IA-2A, ZNT8A) in misdiagnosed and true-T1D.
Results: People with one (n=309), two (n=285) or three (n=300) autoantibodies had a similar T1D-GRS suggesting people with ≥1 antibody positive had true-T1D (mean GRS 0.270 vs. 0.269 vs. 0.273, p=0.13). People without antibody had T1D-GRS (0.243, n=218) between true-T1D (0.271, n=894, ≥1ab+ve) and T2D (0.229, n=1924, p&lt;0.0001) suggesting presence of non-T1D in antibody negative group. The estimated proportion of non-T1D in antibody negative group was 67% (n=146/218) which was 13% of the whole cohort (95% CI 11-15%). Misdiagnosis was higher in people diagnosed 30-75y (21%) vs. 18-30y (6%, p&lt;0.001). Misdiagnosed-T1D and true-T1D had similar rates of polyuria (91% vs. 95%), weight loss (85% vs. 88%) and DKA (38% vs. 43%) (all p&gt;0.05). Misdiagnosed-T1D were more likely to be male (81% vs. 59%), older (40y vs. 32y), had higher BMI (28 vs. 24) and HbA1c (105 vs. 91 mmol/mol) compared to true-T1D (all p&lt;0.001).
Conclusion: Initial misdiagnosis of T1D is common in people diagnosed &gt;30y (21%). When clinically-diagnosed with T1D at diagnosis, negative islet autoantibodies but not severe hyperglycaemia/DKA identify misdiagnosed people.

Disclosure
K.A. Patel: None. N. Thomas: None. M.N. Weedon: None. H.C. Walkey: None. A. Kaur: None. A.J. Williams: None. S. Misra: None. N. Oliver: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Self; Dexcom, Inc., Sanofi. D.G. Johnston: None. A.T. Hattersley: None.

Funding
Diabetes UK; JDRF; Diabetes Research & Wellness Foundation
169-LB: A Randomized Encouragement Trial to Increase Mail Order Pharmacy Use and Medication Adherence
Authors: SCHMITTDIEL JULIE , TRINACTY CONNIE M. , WHARAM J. FRANK , DURU O. KENRIK , NEUGEBAUER ROMAIN , BROWN SUSAN D. , ROSS-DEGNAN DENNIS , KARTER ANDREW J. , DYER WENDY T. , RAMACHANDRAN BHARATHI 
Published: June 2019

Medication non-adherence is a major contributor to poor diabetes outcomes. Observational studies show positive associations between mail order pharmacy (MOP) use and adherence, and suggest that mail order is cost-saving to patients. However, no prospective trials have examined the effect of encouraging MOP use on medication adherence. We conducted a randomized encouragement trial in 2017 in three health plans: Kaiser Permanente (KP) Northern California, KP Hawaii, and Harvard Pilgrim Health Care (HPHC). Patients were eligible if they had diabetes, poor adherence (Proportion of Days Covered &lt;80%) to at least one class of cardiometabolic medications, and had not used MOP in the prior 12 months. Patients were randomized to receive either no intervention (controls) or outreach encouraging MOP use consisting of a mailed letter, secure email message, and automated telephone call outlining the potential benefits of MOP use for diabetes patients; HPHC intervention patients received the letter only. We compared the percentages of patients in both arms that began using mail order and that became adherent to cardiometabolic medication classes during the 12-month follow-up. A total of 63,012 patients were included: mean age was 60; 45% were female; 41% were non-Hispanic white; 12% were black; 25% were Hispanic/Latino, and 22% were Asian/Native Hawaiian/Pacific Islander. During follow-up, 12% of intervention patients used the mail order pharmacy vs. 10% of controls (p&lt;.001); the percent of cardiometabolic medications delivered via mail was 42% vs. 39% (p&lt;.01). Metformin adherence improved in the intervention group relative to controls at the two KP sites (52% vs. 49%, p&lt;.01). This randomized trial shows that simple outreach to encourage MOP use modestly improved its use, and improved adherence to a key class of diabetes medications in some settings. Clinicians and health systems should consider such low-cost interventions to actively promote MOP among diabetes patients.

Disclosure
J. Schmittdiel: None. C.M. Trinacty: None. J. Wharam: None. O. Duru: Advisory Panel; Self; Healthwise. R. Neugebauer: None. S.D. Brown: None. D. Ross-Degnan: None. A.J. Karter: None. W.T. Dyer: None. B. Ramachandran: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases
1704-P: SIRT1 rs7896005 SNP and Incidence of Major Vascular Events in Type 2 Diabetes: A 13-Year, Single-Centre, Follow-Up Study
Authors: PENNO GIUSEPPE , GAROFOLO MONIA , GUALDANI ELISA , LUCCHESI DANIELA , GIUSTI LAURA , SANCHO-BORNEZ VERONICA , DARDANO ANGELA , FRANCESCONI PAOLO , PRATO STEFANO DEL 
Published: June 2019

Genetic variants of SIRT1, in particular the G allele of the rs7896005 SNP, are associated with increased risk for T2DM. We recently reported that this SNP was not associated with all-cause mortality over a 13-year follow-up. We are now exploring the association of this SNP with incidence of major CV events in 917 T2DM (98.6% of the original cohort). Incidence data were obtained by interrogating hospital discharge registers. Genotypes distribution was: AA, n. 83 (9.1%), AG, n. 397 (43.3%), GG, n. 437 (47.7%). MAF was 0.307 and Hardy-Weinberg equilibrium met (chi-square 0.2809, p=0.596). There was no difference across genotypes for major CV risk factors and treatments. Over 11.25±4.40 years, 261 major CV events occurred (28.5%): AA/AG n. 121, 25.2%; GG n. 140, 32.0% (K-M logrank 5.798, p=0.016). After adjustment for age, sex, DD, BMI, HbA1c, A/C ratio, eGFR (CKD-EPI), smoking, hypertension, dyslipidemia, retinopathy, peripheral neuropathy and prior CV events, HR of GG vs. AA/AG was 1.28 (95% CI 1.00-1.65, p=0.047). Over 11.81±4.06 years, 176 coronary events occurred (19.2%): AA/AG n. 77, 16.0%; GG n. 99, 22.7% (K-M logrank 7.093, p=0.008). After adjustment, HR vs. AA/AG was 1.47 (1.09-2.00, p=0.013). A total of 81 (8.8%) hospitalization for heart failure (HF) occurred over a follow-up of 12.75±3.11 years: AA/AG n. 33, 6.9%; GG n. 48, 11.0% (K-M logrank 4.999, p=0.025). After correction, HR vs. AA/AG was 1.54 (0.98-2.42, p=0.063). Finally, over 12.92±2.95 years, 36 peripheral vascular events occurred (3.9%): AA/AG n. 11, 2.3%; GG n. 25, 5.7% (K-M logrank 7.320, p=0.007). After adjustment, HR vs. AA/AG was 2.15 (1.02-4.50, p=0.043). No association was found with cerebrovascular events and ESRD. With the limitations of the relatively small sample size, but the strength of the long-term observation, we suggest that in T2DM rs7896005 A/G SNP of SIRT1 is independently associated with incidence of major CV, coronary and peripheral vascular events and also with hospitalization for heart failure.

Disclosure
G. Penno: None. M. Garofolo: None. E. Gualdani: None. D. Lucchesi: None. L. Giusti: None. V. Sancho-Bornez: None. A. Dardano: None. P. Francesconi: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Board Member; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited.
1706-P: A Promoter Variant of TYK2, a Putative Virus-Induced Susceptibility Gene, Is Associated with Impaired Insulin Secretion and Nonobese Type 2 Diabetes
Authors: MORI HITOE , TAKAHASHI HIROKAZU , MINE KEIICHIRO , INOUE KANAKO , KOJIMA MOTOYASU , KUROKI SHIGETAKA , ONO YASUHIRO , INUZUKA SADATAKA , NAGAFUCHI SEIHO , ANZAI KEIZO 
Published: June 2019

Background: Type 2 diabetes mellitus is typically associated with obesity and insulin resistance. It is well known that viral infection triggers type 1 diabetes, but a potential link with type 2 diabetes has not been fully established. We have reported that a natural mutation in the tyrosine kinase 2 (TYK2) gene, which encodes an interferon receptor signaling molecule, is responsible for encephalomyocarditis (EMC) virus-induced diabetes in mice (Nat Commun 2015). Moreover, a human TYK2 promoter variant (TYK2PV) (NCBI ClinVer ID:440728) is associated with higher risks of not only type 1, but also type 2 diabetes (EBioMedicine 2015). Therefore, we hypothesized that impaired insulin secretion associated with TYK2PV causes type 2 diabetes. Here, we studied the relationships between TYK2PV, and insulin secretion and obesity in patients with type 2 diabetes.
Methods: The presence of TYK2PV was determined using direct sequencing, and insulin secretion was evaluated, in type 2 diabetes patients who were not administering either sulfonylureas or insulin.
Results: Of the 173 patients assessed, 18 (10.4%) were TYK2PV-positive, and their median BMI was significantly lower than those without the variant (25.3 vs. 23.4 kg/m2, p=0.029). Moreover, the HOMA-β (19.1 vs. 30.0, p=0.027) and fasting serum insulin (3.91 vs. 6.16 μIU/mL, p=0.007) were lower in patients with TYK2PV than in those without. Multivariable analysis showed that TYK2PV was significantly associated with fasting insulin &lt;5μIU/ml (odds ratio 4.14, 95% confidence interval 1.404-12.21, p=0.021).
Conclusions: TYK2PV is associated with lower insulin secretion in type 2 diabetes, consistent with it being a virus-induced diabetes susceptibility gene. Therefore, type 2 diabetes patients with TYK2PV should be carefully followed, so that they receive the most appropriate treatment, including insulin.

Disclosure
H. Mori: None. H. Takahashi: None. K. Mine: None. K. Inoue: None. M. Kojima: None. S. Kuroki: None. Y. Ono: None. S. Inuzuka: None. S. Nagafuchi: None. K. Anzai: None.