bluuebunny/crossref_metadata_2025_split huggingface dataset:
1604-P: Glucose Intolerance Modifies the Association between Diastolic Blood Pressure Variability and All-Cause Mortality
Authors: VISARIA AAYUSH , DHARAMDASANI TINA , LO DAVID , WICKRAMASINGHE KAVINDYA , MALHOTRA RAJ 
Published: June 2020

Purpose: There is growing literature on the association between blood pressure variability (BPV) and mortality. We sought to determine whether the association between BPV and all-cause mortality was modified by glucose intolerance (GI).
Methods: A total of 12,256 non-pregnant adults from the National Health and Nutrition Examination Surveys-III (1988-1994) were linked to the National Death Index through 2015. The primary predictors were systolic and diastolic BPV, defined as the standard deviation of 3-6 BP readings taken consecutively. Systolic and diastolic BPV were categorized into quintiles (&lt;3, 3-8, 9-12, 13-15, &gt;15 mmHg). We used Cox proportional hazards modeling to assess the risk of all-cause mortality, adjusting for confounders (age, sex, race/ethnicity, mean BP, BMI, lipids, kidney and liver function, c-reactive protein) and the survey design. Analyses were stratified by GI status (yes/no), defined as either a fasting glucose ≥100 mg/dl, HbA1c ≥5.7%, or diabetes medication use.
Results: Of the 12,256 participants, 28% had GI. The mean follow-up time was 22.1 years, with a total 3,632 deaths (2,096 [46%] among GI and 1,536 [20%] among non-GI) from all causes. Among those with GI, the highest quintile of diastolic BPV had 60% higher risk of mortality relative to the lowest quintile (unadjusted HR [95% CI] = 1.51 [1.04, 2.23], adjusted HR = 1.60 [1.12, 2.28]). This association did not exist among those without GI (unadjusted HR [95% CI] = 0.87 [0.60, 1.26], adjusted HR = 0.80 [0.58, 1.10]). Those in the highest quintile of systolic BPV had an insignificant increase in risk of all-cause mortality among both GI and non-GI participants (GI: adjusted HR = 1.41 [0.98, 2.01], non-GI: adjusted HR = 1.09 [0.78, 1.51], interaction p=0.34).
Conclusion: Only those with GI had a significant positive association between diastolic BPV and all-cause mortality. GI may play a role in modifying this association through changes in vascular autonomic regulation due to autonomic neuropathy.

Disclosure
A. Visaria: None. T. Dharamdasani: None. D. Lo: None. K. Wickramasinghe: None. R. Malhotra: None.
1606-P: Effect of Changes in Dark/Light Cycle on Physiological Homeostasis as a Confounding Prelude to Diabetes in Fischer 334 Animal Model
Authors: SUBRAMANIAN BALANEHRU , RAMAKRISHNAN GANAPATHY , TAMILMARAN PANNERSELVAM , SUNDARAKRISHNAN BALAKRISHNAN , SESHADRI KRISHNA 
Published: June 2020

Understanding the role of modern life-style driven disruption in circadian rhythm can advance appropriate management of the shift in physiological homeostasis that may lead to groups of diseases such as diabetes. This study was carried out to determine the effect of light period changes on this possible shift using Fischer 344 rat model. Animals were split into 3 groups of 6 Males and 6 Females each: G I for normal light period (6 am to 6 pm); G II for reversed light period (6 pm to 6 am on alternate weeks); G III was G I with additional 8 h light period (6 pm to 2 am on alternate days). Daily feed, water intake and weekly body weight was recorded. Elevated plus maze for anxiety was done on day 21. On day 22, blood glucose, cholesterol, triglycerides and ACTH were measured. Histopathology of pancreas was done. Results showed no statistical difference in body weights of both sexes in G II and III. However, females in G III had 7% higher body weight than G I. Feed intake increased by 39.7% in both sexes in G III compared to G II. Water intake decreased by 7.2% in G II and 3.4% in G III compared to G I indicating change in normal physiology. G III showed increased blood glucose (38.4%), cholesterol (34.2%), and triglycerides (77.8%). In G III males ACTH was elevated by 38.9% while the same effect was seen in G II females (27.1%). Open arm behavior analysis decreased was by 24.9% in G III compared to G I indicating animals in a state of anxiety. G I Pancreas showed normal islets of Langerhans; G II with swollen acinar cells with vacuoles in few; G III with additional cellular degeneration of islets of Langerhans. Study indicates less adaptation capacity of Fisher 344 rats to disruption in light period as evidenced (p value &lt;0.05) by changes in ACTH, blood chemistry, cellular morphology and behavioral pattern suggesting a shift in physiological homeostasis that may lead to group of diseases such as diabetes. Further investigation is underway to ascertain associated beta cell function and molecular changes.

Disclosure
B. Subramanian: None. G. Ramakrishnan: None. P. Tamilmaran: None. B. Sundarakrishnan: None. K. Seshadri: None.

Funding
Primer Academy of Medical Sciences (PAMS-CAReTS-SBV)
1607-P: Real-World Evidence of the Impact of Obesity on Residual Teeth in the Japanese Population
Authors: HAYASHI MAYU , MORINO KATSUTARO , HARADA KAYO , ISHIKAWA MIKI , MIYAZAWA ITSUKO , TAKAKO YASUDA , ISHIKADO ATSUSHI , MAEGAWA HIROSHI 
Published: June 2020

Previous studies have shown that diabetes and obesity increase the severity of periodontal disease—a well-known risk factor for tooth loss. However, the effect of obesity on tooth loss has not yet been fully characterized. Thus, we investigated the association between obesity and residual teeth (number and sites) using a large database of the Japanese population. We used the MinaCare database, composed of data from Japanese health insurance claims and health check-ups in 2015 to select 233,517 subjects from 706,150 based on the availability of BMI, HbA1c, teeth, and smoking information. Obesity was defined as BMI ≥25.0. The number of residual teeth at every age group was correlated with 4 BMI subsets (&lt;18.5, 18.5-24.9, 25.0-30.0, &gt;30.0). The unadjusted and adjusted odds ratios (ORs) for fewer than 24 residual teeth were estimated using logistic regression models. The number of residual teeth decreased with age (p for trend&lt;0.001). Groups with higher BMIs had fewer residual teeth at all ages over 40s (p for trend&lt;0.001). The number of residual teeth in the lowest vs. highest BMI groups in the 50s and 60s were 26.0 ± 3.2 vs. 25.2 ± 3.9 and 24.0 ± 5.0 vs. 23.3± 5.1, respectively. The negative effects of obesity on residual teeth were dominant in the right mandibular first molar. Additionally, smoking enhanced the effect of obesity. The OR for fewer than 24 residual teeth in obese people was 1.47 (95% CI: 1.43-1.52). Although diabetes (defined as HbA1c ≥6.5%) is an independent factor, the OR for fewer than 24 residual teeth in obese people after adjustment with sex, age, smoking status, and diabetes was 1.35 (95% CI: 1.31-1.40). Thus, obesity is an independent risk factor for tooth loss in the Japanese population, suggesting the importance of weight management to maintain oral health in obese people. Further studies are necessary to confirm our findings, due to limitations in our study such as data-availability from only the subject’s dental visit and the exclusion of full dentures and a small number of residual teeth.

Disclosure
M. Hayashi: Employee; Self; Sunstar Group. K. Morino: None. K. Harada: Employee; Self; Sunstar Group. M. Ishikawa: None. I. Miyazawa: None. A. Ishikado: Employee; Self; Sunstar Group. Employee; Spouse/Partner; Sunstar Group. H. Maegawa: Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Sanofi K.K., Takeda Pharmaceutical Company Limited.
1612-P: Liver Enzyme Is Associated with Future Remission from Impaired Fasting Glucose to Normal Fasting Glucose: The Kansai Healthcare Study
Authors: SHIBATA IZUMI , SATO KYOKO K. , SHIBATA MIKIKO , KOH HIDEO , UEHARA SHINICHIRO , OUE KEIKO , KAMBE HIROSHI , MORIMOTO MICHIO , HAYASHI TOMOSHIGE 
Published: June 2020

Prediabetes is a key risk for type 2 diabetes and its remission to normal glucose regulation has been shown to prevent or delay the onset of diabetes. However, which factors play roles in remission is not fully understood. We prospectively examined the relationships between liver enzymes at baseline and future remission from impaired fasting glucose (IFG) to normal fasting glucose (NFG). We included 3334 middle-aged Japanese men with IFG and not taking diabetic medications at baseline. They were followed for up to 11 years. IFG was defined as fasting plasma glucose level 100-125 mg/dL and HbA1c &lt;6.5%. Remission to NFG was defined as fasting plasma glucose level &lt;100 mg/dL detected two times consecutively at the annual checkup. Those who had developed diabetes before they achieved remission to NFG were not counted as remission. Cox proportional hazard models were used to estimate hazard ratios (HRs) for achieving remission to NFG. Alanine transaminase (ALT) and aspartate transaminase (AST) were divided into the following quartiles: 5-19, 20-26, 27-37, and ≥38 IU/L for ALT; 11-19, 20-23, 24-29, and ≥30 IU/L for AST. A total of 1224 subjects remitted to NFG during 19780 person-years. Incidence rates per 1000 person-years for quartiles 1, 2, 3, and 4 of ALT/AST were 81/65, 62/67, 56/60, and 49/56, respectively. In a multiple-adjusted model that included age, fasting plasma glucose, body mass index, smoking status, regular physical exercise, alcohol consumption, and family history of diabetes, HRs of future remission to NFG for quartiles 2, 3, and 4 of ALT were 0.84 (95% CI, 0.72-0.99), 0.84 (0.72-0.99), and 0.82 (0.69-0.97), respectively, compared to quartile 1. In the same model except AST was substituted for ALT, HRs of those for quartiles 2, 3, and 4 of AST were 1.04 (0.89-1.22), 1.02 (0.87-1.20), and 1.02 (0.87-1.21), respectively, compared to quartile 1.
In conclusion, elevated ALT was inversely associated with future remission from IFG to NFG, but AST was not.

Disclosure
I. Shibata: None. K.K. Sato: None. M. Shibata: None. H. Koh: None. S. Uehara: None. K. Oue: None. H. Kambe: None. M. Morimoto: None. T. Hayashi: None.
1613-P: The Veterans Administration Diabetes Risk Cohort: Profile and Diabetes Incidence
Authors: KANCHI RANIA , THORPE LORNA , LOPEZ PRISCILLA M. , ELBEL BRIAN , MERCADO CARLA , SIEGEL KAREN R. , AVRAMOVIC SANJA , ALEMI FARROKH , SCHWARTZ MARK D. 
Published: June 2020

Background: The Veterans Administration (VA) cares for over 8 million U.S. veterans annually, approximately 20% of whom have prevalent diabetes. To foster research and intervention opportunities, we developed the VA Diabetes Risk (VADR) Cohort using the VA electronic health record, a national cohort of diabetes-free U.S. veterans receiving primary care at the VA since January 1, 2008. This cohort provides important opportunities to study community-level risk factors for diabetes, such as attributes of the food environment, via geospatial linkage to residence information. We describe here the cohort profile and diabetes incidence by sub-group.
Methods: To be eligible, diabetes-free patients had to have at least 2 primary care visits at least 30 days apart prior to enrollment. Diabetes incidence was defined as having ≥2 inpatient or outpatient encounters with diabetes ICD-9/10 codes, any prescription of diabetes medicine, or one encounter with diabetes ICD-9/10 codes and ≥2 hemoglobin A1C ≥6.5%. The incidence of diabetes was calculated as the number of new cases diagnosed per 1000 person-years (PY) through December 31, 2018. Demographic and comorbidities data were abstracted using diagnostic codes, labs, prescriptions, and vital signs.
Results: The VADR cohort consisted of 6.17 million veterans, the majority of whom were male (91.7%) and non-Hispanic (NH) white (75.7%). Nearly half were above 60 years of age at enrollment (48.8%). The diabetes incidence rate was 27.0 per 1000 PY, increasing with age from 13.3 per 1000 PY among adults &lt;45 years old to 41.8 per 1000 PY among those 65 years and older. Incidence was higher among men than women (34.6 vs. 18.6 per 1000 PY) and higher among NH black patients compared to NH white patients (38 vs. 31.7 per 1000 PY).
Conclusions: The VADR cohort provides a novel infrastructure for examination of community-level risk factors for diabetes among veterans, and facilitates assessment of the impact of national or regional strategies to prevent or manage diabetes in veterans.

Disclosure
R. Kanchi: None. L. Thorpe: None. P.M. Lopez: None. B. Elbel: None. C. Mercado: None. K.R. Siegel: None. S. Avramovic: None. F. Alemi: None. M.D. Schwartz: None.
1616-P: Stimulated ß-Cell Response Is Unaltered in Adult Autoantibody (AB) Negative Relatives of Individuals with Type 1 Diabetes (T1D)
Authors: NEYMAN ANNA , MOORS KELLY , EVANS-MOLINA CARMELLA , DIMEGLIO LINDA , MIRMIRA RAGHAVENDRA , MATHER KIEREN J. , HANNON TAMARA S. , SIMS EMILY K. 
Published: June 2020

Emerging evidence suggests intrinsic β cell dysfunction contributes to T1D development. However, it is unclear whether defects in β cell response are evident in individuals at genetic risk for T1D without detectable islet autoimmunity. To explore this, we performed mixed meal tolerance tests (MMTTs) and hyperglycemic clamps to measure stimulated β cell response in 2 groups: Islet Ab negative 1st-degree adult relatives of persons with T1D (FDR-) and normoglycemic, age, sex, and BMI-matched controls without T1D family history. Median and IQR values for 1st phase responses, including C-peptide15min-0 (MMTT) and C-peptide incremental AUC (iAUC)0-10min (clamp), and 2nd phase responses, including C-peptide iAUC0-120min (MMTT) and average C-peptide (C-peptideavg) during the steady state (clamp), were compared using paired t-tests or Wilcoxon tests.
MMTTs and clamps were performed in 15 euglycemic (A1c&lt;5.7%) FDR- and control pairs (34.3yrs ±7.7; 20% male; BMI 25.6kg/m2 ±4.4). There were no differences in 1st phase or 2nd phase-stimulated responses. For the FDR- vs. control group, C-peptide15min-0 was 1.2ng/mL (0.9,1.9) vs. 1.62(1.1,2.2), p=0.62, C-peptide iAUC0-10min was 22.6ng/mL*min (19.4-51.6) vs. 24.4 (19.3-31), p=0.72, and C-peptide iAUC0-120min was 404 (369.3,435.5) vs. 383.3 (291.2,558), p=&gt;0.99, C-peptideavg steady state was 12 (10.8-18.9) vs. 11.5 (8.9-14.5), p=0.98.
In this small cohort, no significant differences between stimulated 1st or 2nd phase responses were detected between FDR- and matched controls, suggesting that FDR- relatives may not have a defect in stimulated β cell response. Nondiabetic relatives are heterogeneous in their risk of autoimmunity; this could explain a lack of between-group differences. At-risk pediatric cohorts, which have increased risks of developing autoimmunity, could be more likely to show a difference in β cell response. Ongoing investigations will define β cell function in relatives with detectable Abs.

Disclosure
A. Neyman: None. K. Moors: None. C. Evans-Molina: Consultant; Self; Bristol-Myers Squibb. L. DiMeglio: None. R. Mirmira: Advisory Panel; Self; Hibercell, Sigilon Therapeutics, Veralox Therapeutics. Employee; Spouse/Partner; Eli Lilly and Company. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. T.S. Hannon: None. E.K. Sims: None.

Funding
JDRF (2-SRA-2017-498-M-B)
1617-P: Association of High-Affinity Autoantibodies with High-Risk HLA Haplotypes
Authors: TRIOLO TAYLOR M. , PYLE LAURA , YU LIPING , GOTTLIEB PETER , STECK ANDREA 
Published: June 2020

Electrochemiluminescence (ECL) assays are high-affinity autoantibodies (Abs) that are more specific than radiobinding assay (RBA) Abs for the prediction of type 1 diabetes (T1D) in natural history studies screening for risk and progression to T1D. We analyzed 603 subjects from the TrialNet Pathway to Prevention Study who were positive for at least one RBA diabetes related Ab and for whom ECL and HLA data were available. We sought to characterize ECL-GADA and ECL-IAA positivity and levels (z-scores) by HLA genotype and haplotypes. Mean age at initial visit was 19.4 ± 13.7 years; 345 (57.2%) were female and 104 (17.2%) carried the high-risk HLA- DR3/4*0302 genotype. At initial visit 425 (70%) of subjects were positive for either ECL-GADA or ECL-IAA, with 207 (34.3%) ECL-IAA positive subjects and 367 (60.9%) ECL-GADA positive subjects. For subjects with high-risk HLA-DR3/4 genotype (n=104), 80 (76.9%) were positive for ECL-GADA, while 42 (40.4%) were positive for ECL-IAA. ECL and RBA-GADA z-scores were higher in subjects with HLA-DR3 haplotypes, while ECL-IAA (but not RBA-IAA) z-scores were associated with HLA-DR4 haplotypes. Associations of ECL and RIA Abs with high-risk HLA haplotypes are shown in the Table.
In conclusion, ECL and RBA-GADA positivity are associated with both HLA-DR3 and DR4 haplotypes, whereas only ECL-IAA (but not RBA-IAA) positivity and levels are associated with HLA-DR4 haplotype.

Disclosure
T.M. Triolo: None. L. Pyle: None. L. Yu: None. P. Gottlieb: Advisory Panel; Self; Janssen Scientific Affairs, LLC., Tolerion, Inc., Viacyte, Inc. Research Support; Self; Caladrius Biosciences, Inc., Immune Tolerance Network, Janssen Pharmaceuticals, Inc., JDRF, Leona M. and Harry B. Helmsley Charitable Trust, Mercia/Nova Laboratories, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc. Stock/Shareholder; Self; IM Therapeutics. A. Steck: None.

Funding
American Diabetes Association (1-14-CD-17 to A.S.); National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; JDRF
1619-P: Trends in Severe Hypoglycemia and Mortality in Individuals with Type 1 Diabetes
Authors: BAE JAE HYUN , KIM KYOUNG JIN , KIM JI YOON , KIM SIN GON , KIM NAM HOON 
Published: June 2020

Background: Hypoglycemia is one of the major complications in the management of individuals with type 1 diabetes, and severe hypoglycemia increases the risk of mortality.
Objective: To investigate trends and risk factors for severe hypoglycemia and mortality in individuals with type 1 diabetes.
Methods: We evaluated age- and sex-standardized annual incidence rates of severe hypoglycemia requiring hospitalization and mortality in individuals with type 1 diabetes using the Korean National Health Insurance Service Database from 2002 to 2016.
Results: Age- and sex-standardized incidence rates of severe hypoglycemia have increased from 2002 to 2016 in individuals with type 1 diabetes (5.79 per 1,000 in 2002-2004 to 12.57 per 1,000 in 2015-2016, P for trend &lt; 0.0001). Individuals with severe hypoglycemia had significantly lower body weight (64.8 ± 12.4 kg vs. 57.7 ± 9.5 kg; P &lt; 0.0001) and higher proportions of chronic kidney disease (2.5% vs. 5.3%, P = 0.0012) and end-stage renal disease (0.6% vs. 2.0%, P = 0.0071) compared with those without severe hypoglycemia. However, age- and sex-standardized mortality has decreased in both individuals with and without severe hypoglycemia (P for trends &lt; 0.001). The use of new-generation insulin analogs was associated with a lower risk of severe hypoglycemia and mortality.
Conclusion: The incidence rates of severe hypoglycemia have significantly increased, while the mortality has significantly decreased in Korean individuals with type 1 diabetes from 2002 to 2016.

Disclosure
J. Bae: None. K. Kim: None. J. Kim: None. S. Kim: None. N. Kim: None.
1621-P: Period Prevalence of Chronic Kidney Disease and Obesity in Adults with Type 1 Diabetes
Authors: WALLACE AMELIA , CHANG ALEX R. , GRAMS MORGAN , SELVIN ELIZABETH 
Published: June 2020

Introduction: Trends in the prevalence of chronic kidney disease (CKD) and obesity in adults with type 1 diabetes have not been rigorously characterized. We hypothesized that, like the type 2 diabetes population, there have been increases in the prevalence of eGFR &lt;60 ml/min/1.73 m2 (CKD) and body mass index (BMI) &gt;30 kg/m2 (obesity) in the population with type 1 diabetes.
Methods: We conducted a retrospective analysis of 4215 patients in the Geisinger Health System (central Pennsylvania) with type 1 diabetes, defined using the validated Klompas algorithm. We constructed period prevalent cohorts within each calendar year from 2004 to 2018 and estimated the prevalence of CKD and obesity using average values within each calendar year.
Results: The 2004 cohort contained 530 people with type 1 diabetes; the 2018 cohort contained 1485 people. Percent female was 54.0% in 2004 and 50.4% in 2018; average age was 43.9 (SD, 16.1) and 48.1 (SD, 15.9), respectively. The prevalence of CKD was 14.7% in 2004 and 17.4% in 2018 (p-trend = 0.80) (Figure). The prevalence of obesity was 30.0% in 2004 and 38.9% in 2018 (p-trend =0.006). The average BMI was 27.6 (6.0) in 2004 and 29.1 (6.6) in 2018 (p-trend = 0.002). In associations adjusted for demographics, trends were similar.
Conclusions: The prevalence of obesity increased, but there was no change in the prevalence of CKD over the last 15 years among people with type 1 diabetes in a rural health care system.

Disclosure
A. Wallace: None. A.R. Chang: None. M. Grams: Other Relationship; Self; DCI. E. Selvin: None.

Funding
National Heart, Lung, and Blood Institute (T32HL007024)
1623-P: Prevalence and Clinical Determinants of Obesity in Type 1 Diabetes Mellitus
Authors: TSUSHIMA YUMIKO , KASHYAP SANGEETA , ZHOU KEREN 
Published: June 2020

The prevalence of obesity in adults with type 1 diabetes mellitus (T1DM) is rising and is known to increase cardiovascular (CV) risk and mortality. However, the clinical features of adiposity are poorly described and discovery of novel associations may shed light on areas of possible intervention. We performed a retrospective cross-sectional analysis of 625 adults diagnosed with T1DM who were seen in Endocrinology between 2015-2018. These patients were stratified into 5 weight categories (normal weight, overweight, and obesity classes 1-3) then compared across various comorbidities, medication use, and metabolic parameters. Patients had a mean age of 35.2 ± 15.3 years, 53% were female, and &gt;25% had a BMI ≥ 30. HbA1c did not significantly increase with weight. CV risk factors were more prevalent in patients with obesity (p&lt;0.05) (Table 1). The anti-obesity medication, phentermine, was only prescribed in 3/172 patients and antidiabetic agents associated with weight loss were rarely applied to overweight individuals. Obesity combined with T1DM was associated with higher rates of metabolic disturbances and risk factors for CV disease. The sparse use of phentermine suggests suboptimal treatment of obesity in this population. Therefore, increased attention towards optimization of weight management for patients with obesity and T1DM is needed in an effort to reduce the comorbidities seen in this study.

Disclosure
Y. Tsushima: None. S. Kashyap: Other Relationship; Self; GI Dynamics Inc. K. Zhou: None.