bluuebunny/crossref_metadata_2025_split huggingface dataset:
404-P: Metformin Treatment Rescues Alterations of Insulin-Sensitive Glucose Transporters in the Lung of Insulin-Resistant Mice
Authors: CAMPOLO ALLISON , MARIA ZAHRA , HINSDALE MYRON , LIU LIN , LACOMBE VERONIQUE 
Published: June 2019

Obesity and hyperglycemia have recently been identified as independent risk factors for the development of respiratory infections. Although the lung is a major organ to utilize glucose, the regulation of glucose transport in the healthy and diabetic lung has received little attention. We hypothesized that metformin would rescue diabetes-induced alterations of glucose transport in the lung. To test this hypothesis, we induced an insulin-resistant diabetic mouse model by feeding a high-fat diet for 16 weeks (n=10/group). A subset of mice was treated with metformin for 8 weeks. Protein content of class I glucose transporters (GLUTs -1, -2, -3, -4) and class III GLUTs (-8, -10, -12) was quantified by Western blotting in whole lung homogenates. Cell surface GLUTs were quantified using the biotinylated photolabeling technique. Glucose concentration in bronchoalveolar lavage (BAL) fluid was measured spectrophotometrically. After feeding a high-fat diet, mice became obese, mildly hyperglycemic, hyperinsulinemic, and insulin tolerant. Total protein content of GLUT4 and GLUT12 was significantly decreased in the lung of the insulin-resistant (IR) group (P &lt;0.05). Following metformin treatment, protein content of GLUT4, but not GLUT12, was rescued in the lung of the treated IR mice (P &lt;0.05). Cell-surface protein content of GLUT4 and GLUT8 was significantly decreased in the lung of IR mice, which was rescued in the treated group (P&lt;0.05). IR mice demonstrated a trend towards a higher glucose concentration in the BAL fluid (P &lt; 0.1). These novel findings suggest that 1) regulation of glucose transport is altered in the lung during obesity and hyperglycemia, potentially increasing the risk for pulmonary infection, and 2) metformin treatment rescues GLUT alterations in the lung of IR mice. Insights gained from this study could lead to the identification of significant metabolic therapeutic targets for diabetic patients affected by concurrent respiratory infections.

Disclosure
A. Campolo: None. Z. Maria: None. M. Hinsdale: None. L. Liu: None. V. Lacombe: None.

Funding
Harold Hamm Diabetes Center; National Institutes of Health
422-P: Long-Term Incidence of Cardiovascular Disease across the Natural History of Type 2 Diabetes
Authors: AN JAEJIN , NICHOLS GREGORY A. , QIAN LEI , WEI RONG , HARRISON TERESA , MUNIS MERCEDES A. , LI ZHUOXIN , WEISS TRACEY , IGLAY KRISTY , RAJPATHAK SWAPNIL , REYNOLDS KRISTI 
Published: June 2019

The elevated risk of cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM) is well established, however, development of these comorbidities from T2DM diagnosis over an extended time period has not been adequately studied. We estimated the cumulative incidence of CVD in T2DM over the course of 15 years in a large U.S. integrated healthcare delivery system. The study population included adult T2DM patients diagnosed between 1/1/2003 and 12/31/2014 based on validated algorithms using the electronic health record (EHR). Patients were followed from 6 months after their T2DM diagnosis date through 6/30/2018. Patient demographics, CVD risk factors, medical history, and medication use were ascertained from the EHR. The cumulative incidence of myocardial infarction (MI), heart failure (HF) and all-cause mortality was estimated separately at 2, 5, 10, 13 and 15 years among the patients who did not have a prior history of each condition (at-risk population) using the Kaplan-Meier method. We identified 135,199 patients newly diagnosed with T2DM. Mean (SD) age was 58 (13) years, 48% were female, 36% were white, 35% Hispanic, 12% black, and 12% Asian. Median follow-up was 6 years. At baseline, 1.3% had MI and 3.5% had HF. By 15 years following T2DM diagnosis, 30.0% of the cohort died, 7.6% had MI and 11.5% HF. The 2-, 5-, 10-, 13-, and 15-year cumulative incidence among the population-at-risk are shown in the Table.

Disclosure
J. An: Research Support; Self; Merck & Co., Inc. G.A. Nichols: Research Support; Self; Amarin Corporation, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Scientific Affairs, LLC., Merck Sharp & Dohme Corp. L. Qian: None. R. Wei: None. T. Harrison: None. M.A. Munis: None. Z. Li: None. T. Weiss: Employee; Self; Merck & Co., Inc. K. Iglay: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. S. Rajpathak: None. K. Reynolds: Research Support; Self; Amarin Corporation, Amgen Inc., Merck Sharp & Dohme Corp., Novartis AG.
424-P: HDL miR-181c as a Novel Biomarker for Diabetic Vascular Complications in Australian Aboriginal People
Authors: MORRISON KAITLIN R. , BURSILL CHRISTINA , SOLLY EMMA , SHEMESH TOMER , NICHOLLS STEPHEN , BROWN ALEX D. , TAN JOANNE T.M. 
Published: June 2019

Diabetes is a major burden on Australia’s Indigenous population, with high rates of disease and vascular complications. Diabetic vascular complications are associated with impaired ischemia-driven angiogenesis. MicroRNAs (miRNAs) are known to regulate angiogenesis. We have recently identified a novel anti-angiogenic role for miR-181c. High-density lipoproteins (HDL) are associated with reduced rates of diabetic complications and serve as carriers of miRNAs in the circulation. HDL miRNA profiles differ in disease states. We sought to determine if circulating miR-181c levels reflect the severity of diabetic complications in Australian Aboriginal people. HDL was isolated from plasma samples of Australian Aboriginal participants with or without diabetes and associated complications living in regional South Australia; and a cohort of non-Indigenous participants without diabetes. We found that HDL miR-181c levels were strikingly elevated in the group of Aboriginal people with diabetic complications. However, plasma miR-181c levels were overall lower in Australian Aboriginal participants compared to the non-Indigenous group. Angiogenic capacity of isolated HDL was assessed in vitro using the Matrigel tubulogenesis assay. Under high glucose (25 mM) conditions, cells treated with HDL from the group of Aboriginal people with diabetic complications had a reduced capacity to form tubules and had lower mRNA levels of the hypoxia angiogenic transcription factor HIF-1α compared to all other groups. This attenuation of pro-angiogenic capacity may be attributed to the concurrent increase in cellular miR-181c levels.
In conclusion, HDL from Aboriginal people with diabetic complications had reduced angiogenic capacity, highlighting its impaired function in the diabetic state and is potentially linked to the increased levels of the anti-angiogenic miRNA miR-181c. HDL miR-181c may be a novel biomarker for the extent of diabetic complications in Australian Aboriginal people.

Disclosure
K.R. Morrison: None. C. Bursill: None. E. Solly: None. T. Shemesh: None. S. Nicholls: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Cerenis, CSL Behring, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Omthera, Pfizer Inc., Resverlogix Corp., Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; Amgen Inc., AstraZeneca, Athernova, Cerenis, Eli Lilly and Company, InfraReDx, Novartis Pharmaceuticals Corporation, Resverlogix Corp., Sanofi. A.D. Brown: None. J.T.M. Tan: None.
439-P: Assessing the Relationship between Asthma and Cardiovascular Disease Risk in Type 2 Diabetes Using Revised Risk Estimates
Authors: BURGE MARK R. , ALDRETE KARISSA L. , EHRHART MARK , MURRAY-KREZAN CRISTINA 
Published: June 2019

Purpose: Type 2 diabetes (T2D) and asthma are independent risk factors for cardiovascular disease (CVD), but CVD risk is reduced in individuals with T2D + Asthma compared to those with T2D alone when using the 2013 ACC/AHA CVD Risk Score. Because these guidelines may overestimate CVD risk by up to 20%, revised risk equations have recently been proposed. We hypothesize that using these revised risk score equations will not alter the relationship between asthma, T2D, and CVD Risk Score.
Methods: Data were extracted from Electronic Health Record using ICD-9/10 codes. Patients with both T2D and Asthma (n=603) were identified and compared to a group of matched patients with T2D Alone (n=603). Estimates of the 10-year risk of a major CVD event were derived using generalized linear models.
Results: As shown in the Table, 10 year CVD risk was significantly increased in the T2D Alone group compared to the T2D + Asthma group using both the 2013 ACC/AHA CVD Risk Score estimates and the revised 2018 CVD Risk Score estimates. CVD risk is approximately 2% higher in both groups using the newer estimates.
Conclusions: In this matched, case controlled retrospective study, Asthma conferred a protective effect against CVD risk over the next 10 years for patients with co-morbid T2D. This result was initially demonstrated with the 2013 ACC/AHA Risk Score estimates and confirmed with the 2018 revised Risk Score estimates.

Disclosure
M.R. Burge: None. K.L. Aldrete: None. M. Ehrhart: None. C. Murray-Krezan: None.

Funding
National Institutes of Health
453-P: Metabolic Syndrome Severity Score, All-Cause Mortality, and Incident Vascular Events in Type 2 Diabetes: A 13-Year, Single-Centre, Follow-Up Study
Authors: GAROFOLO MONIA , GUALDANI ELISA , LUCCHESI DANIELA , GIUSTI LAURA , SANCHO-BORNEZ VERONICA , DANIELE GIUSEPPE , MICCOLI ROBERTO , FRANCESCONI PAOLO , PENNO GIUSEPPE , PRATO STEFANO DEL 
Published: June 2019

Metabolic Syndrome (MetS) is associated with CV events in T2DM. We assessed over a 13-years follow-up the association between a “MetS severity score”, derived from WC, sBP, HDL and triglycerides (courtesy Dr. Mark DeBoer) and both all-cause death and incident CV events in 986 T2DM. Compared to lowest quartile, Q2-4 showed a steeply worsening CV risk profile. A total of 230 deaths occurred over 12.9±2.7 years (23.3%; 18.0 x 1000 PYs). Death rate was J-shaped: Q1 22.4%; Q2 18.2%; Q3 25.9% and Q4 26.8% (p=0.090). Electing arbitrarily Q2 as reference, and after adjustment for confounders and, finally, for parameters of MetS score, HRs (95% CI) vs. Q2 for death were: Q1 1.46 (0.97-2.19; p=0.070), Q3 1.61 (1.09-2.38; p=0.016) and Q4 1.82 (1.20-2.75, p=0.005). Over 11.3±4.4 years, 276 major CV events occurred in 972 T2DM (28.4%; 25.2 x 1000 PYs); adjusted HRs vs. Q1 were: Q2 1.34 (0.93-1.93; p=0.117), Q3 1.99 (1.40-2.82, p&lt;0.0001) and Q4 2.37 (1.66-3.39, p&lt;0.0001). Over 11.8±4.0 years, 184 coronary events occurred (18.9%; 16.03 x 1000 PYs); adjusted HRs vs. Q1 were: Q2 1.79 (1.12-2.84; p=0.015), Q3 2.27 (1.44-3.60, p&lt;0.0001) and Q4 2.99 (1.88-4.74, p&lt;0.0001). Over 12.7±3.1 years, 84 heart failure occurred (8.6%; 6.78 x 1000 PYs); HRs vs. Q1 were: Q2 2.23 (1.01-4.90; p=0.046), Q3 3.38 (1.56-7.31, p=0.002) and Q4 4.60 (2.16-9.82, p&lt;0.0001). Finally, over 12.8±3.1 years, 71 ESRD occurred (7.3%; 5.72 x 1000 PYs); HRs vs. Q1 were: Q2 1.27 (0.57-2.82; p=0.558), Q3 2.12 (1.01-4.45, p=0.048) and Q4 2.16 (1.01-4.65, p=0.048). Further correction for MetS score components excluded MetS score as an independent covariate of outcomes other than death. With the limitations imposed by sample size and the strenght of long-term observation, we suggest that in T2DM MetS score predicts all-cause mortality indipendent of main risk factors and of each component of MetS. MetS score was associated with CV outcomes and ESRD, but these associations were attenuated after adjustment for its components.

Disclosure
M. Garofolo: None. E. Gualdani: None. D. Lucchesi: None. L. Giusti: None. V. Sancho-Bornez: None. G. Daniele: None. R. Miccoli: None. P. Francesconi: None. G. Penno: 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.
46-LB: Improvement of Ischemic Lesions of Lower Limbs in Diabetic Mice by Liraglutide
Authors: CHAO ZHENG 
Published: June 2019

Diabetic foot is a common reason of foot ulcer and amputation. Studies found GLP-1 receptor agonist (GLP-1RA) enhances the angiogenesis of endothelial progenitor cells (EPCs) on ischemic lower limbs in diabetic mice. But the cause is unclear. The blood perfusion and capillary density are observed in diabetic mice after the treat of GLP-1RA by establishing a model of ischemic hind limb. Primary EPCs being isolated and cultured we observed the number of peripheral EPCs the NO stimulated by GLP-1RA. The results that GLP-1RA enhance blood perfusion and capillary density of ischemic hind limbs.
Conclusion, High glucose decrease the expression of GLP-1R in EPCs and angiogenesis and migration of EPCs while the remedy of GLP-1RA Reverse this phenomenon.(A)The LDPI index were significantly higher in the liralutide group than that in the Vehicle group (N=8-10 per group).**:p&lt;0.01, ***:p&lt;0.001. (B) Quantitative analysis of (A). (C) The angiogenesis ability of EPCs was evaluated using a Matrigel-like structure formation assay. (D)Quantitative analysis of (C). the high glucose significantly impaired the angiogenic ability of EPCs, while GLP-1RA. Reverse this phenomenon, and this improvement showed a dose effect.**:p&lt;0.01. (N=3-4 per group)(E). The results that high glucose significantly impaired the migration ability of EPCs, while GLP-1RA Reverse this phenomenon. **: p&lt;0.01.(N=4 per group) (F) Quantitative analysis of (E).

Disclosure
Z. Chao: None.
463-P: Linagliptin Ameliorated Heart Damage Associated with the Suppression of Necroptosis in Type 1 Diabetic Mice
Authors: HIRAI TARO , TAKAGAKI YUTA , KANASAKI KEIZO , KOYA DAISUKE 
Published: June 2019

Background: In diabetic patients, the incident of heart failure is two to five times greater when compared to that of general population. The influence of DPP-4 inhibitor on the heart failure and cardiac damage in diabetes is not completely elucidated yet. Therefore, to understand the pathobiology of heart damage in diabetes and the influence of DPP-4 inhibitor is emerged as significant. Necroptosis, recently identified as programmed cell death, had shown to be involved in heart damage of ischemic heart disease model. Here we found that intervention with DPP-4 inhibitor linagliptin (LINA) ameliorated heart damage in diabetic mice associated with the suppression of necroptosis.
Method: We utilized streptozotocin-induced diabetic CD-1 mice (STZ:200mg/kg). At 20 weeks after the onset of diabetes, diabetic mice were treated with LINA (STZ+LINA) for 4 weeks.
Result: Blood pressure, blood glucose, body and heart weights were not different between STZ and STZ+LINA. Ultrasonic Echocardiography analysis revealed that LVDd and LVDs were significantly decreased in STZ and STZ+LINA compared with control. STZ-induced diabetic CD-1 mice exhibited perivascular fibrosis evaluated by picrosirius red staining and strong immunoreactivity for DPP-4 expression in cardiac interstitium; STZ+LINA exhibited suppression of DPP-4 and amelioration of heart fibrosis. Diabetic CD-1 mice exhibited deficiency in myocardial stripe structure and endothelial damage in electron microscopy; LINA normalized all. When necroptosis was evaluated by associated kinases, RIP3 and MLKL, diabetic CD-1 mice were exhibited a strong RIP3 and MLKL mRNA and protein expression levels in myocyte; LINA suppressed RIP3 and MLKL levels in myocyte.
Conclusion: These results indicated that LINA restored cardiac structure associated with suppression of necroptosis in type 1 diabetic mice.

Disclosure
T. Hirai: None. Y. Takagaki: None. K. Kanasaki: Other Relationship; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanofi, Taisho Toyama Pharmaceutical. D. Koya: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Astellas Pharma Inc., Astellas Pharma Inc., AstraZeneca, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Taisho Pharmaceutical Co., Ltd.

Funding
Japan Society for the Promotion of Science
472-P: Associations between Ankle Brachial Index, Diabetes, and Sleep Apnea: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Database
Authors: ALSHEHRI MOHAMMED M. , ALQAHTANI ABDULFATTAH S. , ALENAZI AQEEL M. , ALOTHMAN SHAIMA , ALDHAHI MONIRA , GRAY COREY M. , ALQAHTANI BADER , KLUDING PATRICIA 
Published: June 2019

Introduction: Sleep apnea and diabetes mellitus (DM) negatively impact cardiovascular health. One important indicator of cardiovascular health is the Ankle-Brachial Index (ABI). Either low (LABI) or high (HABI) are signs of peripheral vascular impairment. Impaired vascular health and DM, together, might provoke sleep apnea; however, information regarding these relationships is limited. Therefore, this study aimed to investigate the association between ABI, DM status, and severity of sleep apnea in people of Hispanic/Latino descent.
Methods: A cross sectional analysis from a multi-center epidemiologic study, HCHS/SOL‎, was utilized, including 8,378 participants (mean age 45.92?±?13.96, female = 49%, mean BMI=30.06?±?5.55). The sample was divided into 6 groups based on ADA guidelines (no-DM or DM) and ABI categories (LABI, normal ABI, or HABI). A linear regression was used to determine the strength of association between groups to predict the severity of sleep apnea, measured by the Apnea-Hypopnea Index (AHI). A Kruskal-Wallis H test was used for AHI comparisons between groups. Significance level was set at 0.01.
Results: There were significant differences between groups for mean AHI (P&lt;0.001; no-DM+normal ABI= 19.28±16.57, DM+normal ABI = 26.85?±?21.87, no-DM+LABI = 17.63?±?18.22, DM?+LABI = 26.31?±?21.62, no-DM?+HABI = 27.12?±?19.82, and DM?+HABI = 33.0?±?22.01). Linear regression ?showed that DM and HABI was significantly associated with severe sleep apnea (β= 5.7, p=0.007) after controlling for age, waist-hip ratio, and Statin medication.
Conclusion: ?These data suggest that ?people with DM and HABI were more likely to have severe apnea compared to the other groups. People with DM, HABI, and severe sleep apnea might be at higher risk of cardiovascular complications. Thus, further research is required to elucidate the appropriate intervention to combat the high level of Peripheral artery disease.

Disclosure
M.M. Alshehri: None. A.S. Alqahtani: None. A.M. Alenazi: None. S. Alothman: None. M. Aldhahi: None. C.M. Gray: None. B. Alqahtani: None. P. Kluding: None.
478-P: Accelerating Atherosclerosis by Autoimmune Process in Nonobese Diabetic Mice Made ApoE Deficient by CRISPR/Cas9 Gene Editing
Authors: PARK KYOUNGMIN , LI QIAN , WANG HAIYAN , ST-LOUIS RONALD , YOKOMIZO HISASHI , MADDALONI ERNESTO , SHINJO TAKANORI , FU JIALIN , WU I-HSIEN , KISSLER STEPHAN , KING GEORGE L. 
Published: June 2019

Although metabolic risk factors that accelerate atherosclerosis are shared between people with type 1 (T1D) and 2 (T2D) diabetes, it remains unknown whether autoimmunity in T1D contribute to cardiovascular pathologies, which have been reported for other autoimmune diseases. In order to determine the role of autoimmunity with and without overt diabetes, we generated ApoE deficient NOD (ApoE-/--NOD) mice by CRISPR/Cas9 gene editing. The ApoE-/- NOD mice spontaneously developed autoimmune diabetes and atherosclerosis. We also generated congenic ApoE-/--NOD mice that do not carry a protective MHC class II allele (CongNOD), and these mice are prone to atherosclerosis but do not develop insulitis or diabetes to control for the effects of the NOD background independently of autoimmunity. ApoE deficiency in NOD mice was ascertained by PCR and DNA sequencing in both ApoE-/--NOD mice and ApoE-/--CongNOD mice The ApoE protein expression levels in the liver and plasma of ApoE-/--NOD mice was also confirmed by immunoblot analysis and ELISA. Female and male ApoE-/--NOD mice exhibited diabetes frequencies (blood glucoses &gt;500 mg/dL) of 70% and 25%, respectively. Histological analysis of pancreatic islets sections by H&E staining showed peri-insulitis (25%) and insulitis (75%), similar rates as hyperglycemia in NOD mice. Nondiabetic ApoE-/--NOD mice developed more severe atherosclerosis than ApoE-/--CongNOD mice after fed Western diet (6% vs. 1.5% plaque, P&lt;0.01). Preliminary studies showed that greater extent of atherosclerosis was observed in diabetic ApoE-NOD than nondiabetic ApoE-/-NOD mice by 3.2 folds. Total plasma cholesterol (884mg/dL vs. 945mg/dL) and triglyceride (185mg/dL vs. 211mg/dL) levels were high but not significant different between ApoE-/--NOD mice and ApoE-/--CongNOD mice on either a regular diet or WD. These studies indicate that T1D autoimmunity with or without hyperglycemia can exacerbate the development of atherosclerosis.

Disclosure
K. Park: None. Q. Li: None. H. Wang: None. R. St-Louis: None. H. Yokomizo: None. E. Maddaloni: Speaker's Bureau; Self; Merck & Co., Inc., Pikdare. T. Shinjo: None. J. Fu: None. I. Wu: None. S. Kissler: None. G.L. King: Research Support; Self; Sanofi.

Funding
Sanofi-Aventis; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK053105-17)
48-LB: Long-Term A1C Benefit from Using One Drop
Authors: HIRSCH ASHLEY , OSBORN CHANDRA Y. , HEYMAN MARK , HUDDLESTON BRIAN , DACHIS JEFF 
Published: June 2019

One Drop (OD) provides self-care support via an evidence-based mobile app, a Bluetooth-connected glucometer and testing supplies, and in-app coaching from CDEs. The app with coaching is associated with a 0.9 to 1.3% lab hemoglobin (A1c) improvement over 3 months. The full solution is associated with a 1.9% eA1c improvement over 3 months. We enrolled people with diabetes to participate in an IRB-approved study examining OD’s long-term effect on A1c. Adults with lab-verified ≥ 7.0% A1c and no prior OD account participated in a single-group longitudinal study. Participants used OD for an average 7.7 months. Lab A1c was assessed at baseline, 3, and 8 months. Descriptive statistics characterized the sample. Repeated measures ANOVA tested A1c change over time. Bonferroni-corrected post hoc tests examined A1c change between timepoints. Participants (N = 10) were 53 ± 7 years old and half female. Sphericity was assumed (Mauchly’s W = .30, p = .05). A1c significantly changed over time, F(2, 12) = 5.62, p &lt; 0.019, partial eta = .48 (see Figure 1). When adjusted for multiple comparisons, baseline to 3-mo A1c change (MDiff = .64%, p = .10) and 3-mo to 8-mo Alc change trended significant (MDiff = 1.74 %, p = .10). Using OD for up to 8 months is associated with improved A1c. This is the first OD study to observe participants beyond 3 months and collect multiple measures of lab A1c over time. An accumulation of non-experimental and experimental evidence suggests OD improves A1c among people with diabetes.

Disclosure
A. Hirsch: Employee; Self; Informed Data Systems Inc. Research Support; Self; Fitbit, Inc., MannKind Corporation. Stock/Shareholder; Self; Informed Data Systems Inc. C.Y. Osborn: Employee; Self; One Drop. M. Heyman: Consultant; Self; Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Tandem Diabetes Care. Employee; Self; One Drop. B. Huddleston: Employee; Self; One Drop. J. Dachis: Stock/Shareholder; Self; Informed Data Systems Inc.