bluuebunny/crossref_metadata_2025_split huggingface dataset:
224-LB: Celiac Disease Prevalence and Screening Practices in Adults with Type 1 Diabetes
Authors: SLOANE JASON , PORNEALA BIANCA , WEXLER DEBORAH J. 
Published: June 2019

There is a well-established association between type 1 diabetes mellitus (T1D) and celiac disease (CD) with CD conferring an increased risk of lower bone mineral density (BMD), depression, and overall mortality. The prevalence of CD in the general population is estimated at 1%, while the prevalence of CD in the T1D population has been estimated to be 2.4-16.4%. There are no CD screening guidelines for screening adult patients with T1D. We aimed to determine the prevalence and characteristics of T1D patients with and without CD, and screened and unscreened patients. We analyzed data from 1,001 people with T1DM from a large single center T1D population. Chart review confirmed CD status and screening with serum antibody or duodenal biopsy since 2010. The prevalence of CD was 4%. Of adults with T1D, 39% had evidence of serologic screening for CD, and 58% of diagnoses were found through screening since 2010. The average age of people with T1D and prevalent CD was 40.7 years, which was younger than unscreened patients (mean age 47.9 years, P&lt;0.006). Unscreened patients had significantly higher BMI (mean BMI 27.5 kg/m2) than those who screened negative (mean BMI 26.2) (p&lt;0.0001). Unscreened patients and those with CD had similar A1C, LDL, and microalbumin suggesting that it may be challenging to risk stratify by clinical characteristics, and that there may be undiagnosed CD in the unscreened population.

Disclosure
J. Sloane: None. B. Porneala: None. D.J. Wexler: Other Relationship; Spouse/Partner; APOLO1BIO.
224-OR: Diurnal Pattern of Insulin Action and Beta-Cell Function in Health and Type 2 Diabetes
Authors: ROMERES DAVIDE , SCHIAVON MICHELE , COBELLI CLAUDIO , MAN CHIARA DALLA , BASU ANANDA , BASU RITA 
Published: June 2019

We have previously reported differences in insulin sensitivity (SI) between T1D and nondiabetic (ND) subjects throughout the day. To explore differences in the diurnal pattern of SI, beta-cell responsivity to glucose (Φ) and disposition index (DI) between type 2 diabetes (T2D) and ND subjects, we present novel preliminary data from 5 ND (BMI 26.6±1.8 kg/m2, age 62.6±4.8 years, Mean±SE) and 5 T2D subjects (BMI 33.6±2.4 kg/m2, age 60.0±6.0 years, HbA1c 55±11 mmol/mol). Studies were conducted in the Clinical Research Unit. Subjects ingested identical mixed meals (75 g carbs, 55% carbohydrate, 15% protein, 30% fat) at either breakfast (B), lunch (L) or dinner (D) in randomized Latin Square order on three consecutive days. Plasma glucose (G), insulin (I) and C-peptide (C) concentrations were frequently sampled. Oral glucose and C-peptide minimal models were applied to estimate SI, Φ and DI. Differences among B, L and D and between ND and T2D were assessed by two-way ANOVA (a p-value &lt;0.05 was considered statistically significant). The emerging patterns suggest that SI, Φ and DI were lower in T2D than ND (Figure 1) subjects throughout the day. While SI steadily decreased in T2D, it was variable in ND subjects as the day progressed. DI was significantly lower in T2D at dinner than at Breakfast. The data to date indicate that the diurnal patterns of insulin action and beta cell function differ between ND and T2D subjects through the day.

Disclosure
D. Romeres: None. M. Schiavon: None. C. Cobelli: None. C. Dalla Man: None. A. Basu: Research Support; Spouse/Partner; AstraZeneca. R. Basu: Other Relationship; Self; AstraZeneca.

Funding
National Institutes of Health (R01029953)
2245-PUB: The Epidemiology and Diagnosis of Diabetic Cardiovascular Autonomic Neuropathy: A Multicenter Clinical Study
Authors: PAN QI , GUO LIXIN , WANG XIAOXIA , ZHANG LINA , XIAN TONGZHANG , MAN FULI , LIU LI 
Published: June 2019

Objective: To evaluate the risk factors of cardiovascular autonomic neuropathy(CAN) in Chinese diabetic patients, estimate the optimal CAN diagnostic method to different diabetics, assess CAN prevalence in our dataset.
Methods: 2, 048 subjects randomly sampled from 13 hospitals were available for data analysis, including 73 type 1 diabetes mellitus (T1DM) and 1, 975 type 2 diabetes mellitus (T2DM). The general data of patients were collected and sympathetic and parasympathetic function tests were executed to CAN preliminary diagnosis. The final CAN diagnosis was based on Ewing's test in which heart rate variation (HRV values were evaluated through deep-breathing (DB), lying-to-standing (LS), Valsalva (V) tests and systolic blood pressure (SBP) variation values was evaluated through LS.
Results: 1) In T1DM group, 61.64% patients were diagnosed with CAN; baseline data and clinical data of CAN group had no difference with those of none-CAN group (P&gt;0.05);while in T2DM group, 62.58% patients were diagnosed with CAN; there were significant differences between CAN and none-CAN group in age, course of the disease, use of metformin, course of metformin treatment, retinopathy and hypertension history (P&lt;0.05). 2) Among various symptoms in CAN group, most frequent symptoms were weakness (28.65%), dizziness (23.42%), frequent urination (19.59%), upper body sweating (18.35%) and enuresisnocturna (15.93%). 3) Course of disease and age were independent risk factors for CAN in T1DM and T2DM, respectively. 4) For T1DM, the optimal CAN diagnostic method was Vtest+LStes (sensitivity=97.62% , AUC=0.887); while for T2DM, DBtest had the highest sensitivity (83.62%) and Vtest+DBtest had the maximal AUC (0.856).
Conclusion: The prevalence of diabetes with CAN was up to 63%.The course of disease and age are independent risk factors of CAN in TIDM and T2DM, respectively. Furthermore, Vtest+LStest and Vtest+DBtest were the optimal CAN diagnostic method for T1DM and T2DM, respectively.

Disclosure
Q. Pan: None. L. Guo: None. X. Wang: None. L. Zhang: None. T. Xian: None. F. Man: None. L. Liu: None.
2259-PUB: Improving the Quality of Life of T1DM Patients in a Community: A KT1DP Initiative
Authors: KESAVADEV JOTHYDEV , SABOO BANSHI D. , SHANKAR ARUN , DAVID ASHWIN , WARRIER ROHIT , AJAI NEETHU A. , SANAL GEETHU , THAMPIRAJ KAVITHA , RAMACHANDRAN LAKSHMY , KRISHNAN GOPIKA , JOTHYDEV SUNITHA 
Published: June 2019

Overall quality of life including longevity is poor among T1DM except for a very few being treated at specialty centers. A trained team for customized education can help improve outcomes. KT1DP Sweet Stars has been conducting a series of workshops partnering with patient organizations. A situational assessment was made during the first session in a community. Patients/parents were administered with ViDa1 questionnaire. n=58, 50% males, age=13.0±4.3y, duration=4.1±3.0y, HbA1c=10.3±2.3%. ViDa1 measures 4 HRQoL dimensions-interference of diabetes with life, self-care, wellbeing and concern about the disease. Interference scores varied significantly w.r.t. healthcare sector consulted (public vs. private; 33.9±8.8 vs. 29.3±7.3; p=0.024) and disease duration (&lt;5 vs. ≥5y; 34.9±9.0 vs. 30.6±8.7; p= 0.047); higher scores indicating greater interference. No other scores varied significantly w.r.t. disease duration, age, gender, HbA1c and healthcare sector. Many were concerned about future complications, 62.07%; unsatisfied with glucose control, 50%; concerned about and afraid of hypoglycemia, 65.51% and 49.15%; and felt diabetes makes life stressful, 55.17%. 93.75% appreciated the educational initiative in improving their perspectives and T1DM management skills. Customized and continuing training programs targeting key areas of failure are expected to improve outcomes and quality of life in T1DM.

Disclosure
J. Kesavadev: None. B.D. Saboo: None. A. Shankar: None. A. David: None. R. Warrier: None. N.A. Ajai: None. G. Sanal: None. K. Thampiraj: None. L. Ramachandran: None. G. Krishnan: None. S. Jothydev: None.
2269-PUB: Early Attrition from a Randomized Lifestyle Modification Protocol
Authors: REVERE CATHY , SMITH A. GORDON , KLUDING PATRICIA , MARCUS ROBIN L. , DIMACHKIE MAZEN , VIVANCO FELIX , FOSTER-PALMER STORMY C. , HAUER PETER E. , APERGHIS ADRIENNE B. , PASNOOR MAMATHA , STONEBRAKER ANGELA , HAWKS ALEXIS N. , HERBELIN LAURA , SINGLETON J. ROBINSON 
Published: June 2019

Assigned exercise and other lifestyle modification can alter the natural history of diabetic neuropathy, but adherence to lifestyle change protocols poses a challenge in a clinical trial setting. In particular, the commitment for participants to begin engagement with the assigned intervention is a critical juncture. The Activity for DiAbetic neuroPaThy (ADAPT) trial is an NIDDK sponsored two-center single blinded protocol that randomizes type 2 diabetic neuropathy patients for 18 months to either brief lifestyle counseling or a combination of monitored exercise, diet counseling and actigraphy driven anti-sedentary behavioral modification. 103 participants have consented, screened, and been found eligible for ADAPT. Of these, 20 dropped from the trial during baseline evaluation (n=3), randomization (n=1), or before the first intervention visit or 3-month follow-up (n=16). Of the 83 who have reached 3-month follow-up, only 7 participants have dropped from the study. The pattern of early attrition has differed at the two sites. At one site, early attrition was essentially equal between assigned groups. The second site 9 of those randomized to intervention and one assigned to control dropped before 3 months. At the second site, protocol changes to improve “hand-off” from the assessment to intervention coordinators, and marked reduction in time from randomization to first intervention visit has improved retention. Structured counseling to set expectations, reduce performance anxiety, and address disappointment with assignment to the less intensive arm has improved initial retention at both sites. Once familiar with the intervention process, most participants will continue with behavioral modification. Clinical trials utilizing patient-motivated lifestyle modification protocols should seek to minimize physical barriers to initial engagement, and focus counseling and motivational effort on the critical early trial period during which participants commit internally to the intervention process.

Disclosure
C. Revere: None. A. Smith: Consultant; Self; Alexion Pharmaceuticals, Inc., Disarm, Regenesis. P. Kluding: None. R.L. Marcus: None. M. Dimachkie: Research Support; Self; Viromed. F. Vivanco: None. S.C. Foster-Palmer: None. P.E. Hauer: None. A.B. Aperghis: None. M. Pasnoor: Advisory Panel; Self; Alexion Pharmaceuticals, Inc., Terumo BCT. Consultant; Self; Momenta Pharmaceuticals. A. Stonebraker: None. A.N. Hawks: None. L. Herbelin: None. J. Singleton: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases; National Center for Advancing Translational Sciences
227-OR: Novel Method of Assessing Hypothalamic KATP Channel Activation in Humans Using Magnetic Resonance Imaging (MRI)
Authors: SHARMA SHIKSHA , ALEKSIC SANDRA , MAGINLEY ROGER , YIMAGOU ERIC LONTCHI , UPADHYAY LAXMI , BHANSALI SHOBHIT , SANDU OANA , BRANCH CRAIG A. , HAWKINS MEREDITH 
Published: June 2019

Hypothalamic KATP channels play an important role in regulating metabolism: activation of these channels with diazoxide (DZX) reduces endogenous glucose production (EGP) in rodents. When insulin is maintained at basal levels, oral DZX similarly suppresses EGP in humans (JCI 121:4916, 2011). Given the need to directly examine central regulation of EGP in humans, we developed a novel non-invasive measure of hypothalamic KATP channel activation.
Since cerebral blood flow (CBF) and neuronal activity are coupled, we mapped hypothalamic neuronal activity using pseudo-continuous arterial spin labeling (pCASL) to measure CBF using 3 Tesla MRI with high resolution 3-dimensional (3D) acquisition and published analyses approaches (MRM 73: 102, 2015). The hypothalamus was extracted from each 3D map (3x3x3mm) using a hypothalamus region-of-interest (ROI) mask delineated upon the Johns Hopkins Template. To directly assess hypothalamic KATP channel activity using pCASL, we examined the time dependent effects of DZX (6mg/kg) vs. placebo in a randomized, double blinded fashion. Eight healthy nondiabetic individuals (42±4 yr, BMI 24±1 kg/m2, 7M) underwent a baseline scan, with repeat scans at 2.5 and 5 hours following DZX or placebo. This time course was determined based on previous observations that DZX appearance in rat CSF precedes EGP suppression, which is maximal at ∼6 hours in rats and humans.
DZX induced an ∼11% drop in hypothalamic CBF, from 59.5±2.5 to 53.0±3.1 ml/100g/min at 2.5 hours (p=0.06), returning to baseline at 5 hours (57.7±2.7 ml/100g/min, p=0.3). Following placebo there was no change in CBF (p=0.8 by repeated measures ANOVA). No change in CBF was observed in other brain regions (e.g., cerebral cortex, thalamus, or hippocampus).
In conclusion, pCASL provides a novel image-based measure of hypothalamic response to KATP channel activation in vivo, and can thus be used to examine the metabolic significance of hypothalamic KATP channel activation in humans.

Disclosure
S. Sharma: None. S. Aleksic: None. R. Maginley: None. E. Lontchi Yimagou: None. L. Upadhyay: None. S. Bhansali: None. O. Sandu: None. C.A. Branch: None. M. Hawkins: Other Relationship; Self; Novo Nordisk Inc.

Funding
National Institutes of Health (R01DK069861); Albert Einstein College of Medicine
2276-PUB: A Palatable, Novel Whey Protein Shot Attenuates Postprandial Glycemia in Lean and Centrally Obese Adult Males
Authors: SMITH KIERAN , TAYLOR GUY S. , OKWOSE NDUKA , ALLERTON DEAN M. , BRUNSGAARD LISE HOEJ , STEVENSON EMMA J. , WEST DANIEL J. 
Published: June 2019

Background: Consuming large doses of whey protein (WP) ∼30 minutes before high-glycemic load meals reduces postprandial glycemia (PPG). However, it is unclear if this effect is retained at smaller doses of WP, ingested at realistic times before typical meals. Moreover, as central obesity is associated with elevated PPG, WP may offer benefit in improving PPG within such individuals. We examined the PPG responses to breakfast following consumption of a small WP shot in centrally obese and lean males.
Methods: In a randomized-crossover design, 7 lean (BMI 24.3±1.5; waist circumference 79.3±7.1 cm; waist/hip ratio [WHR] 0.83±0.04) and 9 centrally obese (34.6±1.9; 112.8±10.2 cm; 0.97±0.1) age-matched, adult males performed two 240 minutes mixed-meal tests, 7d apart. After an overnight fast, participants consumed either a 100ml ready-to-drink WP shot (15g Protein) or 100ml water (CON) 10 minutes before a typical breakfast meal. Interval blood samples were collected for the measurement of plasma glucose. Data (mean±SD) were analyzed by a mixed-design ANOVA and Pearson’s correlation with significance accepted as p≤0.05.
Results: WP reduced early PPG AUC0-60min by 22±9.3% and 13.1±10% in lean and obese males, respectively, vs. CON (p&lt;0.01). Obese males had greater AUC0-60min following WP vs. lean (p=0.02) with no differences after CON (p=0.62). Total trial glucose AUC0-240min was comparable between conditions in both groups (p&gt;0.05). WP reduced peak PPG vs. CON (lean: -26.5±7% [p&lt;0.001]; obese: -16.4±9.8% [p&lt;0.01]) with a tendency for more marked reductions within lean males (p=0.052). Central obesity (WHR) was associated with greater increases in glucose from fasting values, despite WP consumption (r=0.7; p&lt;0.01).
Conclusion: Consuming a palatable, ready-to-drink WP shot before breakfast attenuates early elevations in PPG and reduces hyperglycemia in lean and centrally obese males. Central obesity predicts the glucose lowering effect of WP and may limit its application in this group.

Disclosure
K. Smith: None. G.S. Taylor: None. N. Okwose: None. D.M. Allerton: None. L.H. Brunsgaard: Employee; Self; Arla Foods Ingredients. E.J. Stevenson: None. D.J. West: Research Support; Self; Arla Foods Ingredients, Dexcom, Inc.

Funding
Arla Foods Ingredients Group P/S
23-OR: The Effect of 14-Day Atorvastatin Treatment on Postprandial Glucose Metabolism in Healthy Males—A Link to Why Statin Therapy Increases the Risk of Type 2 Diabetes?
Authors: THOMASEN MARTIN L. , SONNE DAVID P. , KÅRHUS MARTIN L. , BRØNDEN ANDREAS , STAELS BART , HOLST JENS J. , VILSBØLL TINA , KNOP FILIP K. 
Published: June 2019

Background and Aim: Statins are LDL cholesterol-lowering drugs that are highly effective in the prevention of cardiovascular disease and death. Recently, it has become known that statin therapy increases the risk of type 2 diabetes, but the mechanism behind this phenomenon remains obscure. We evaluated the gluco-metabolic effects of statin therapy in healthy male individuals.
Methods: In a placebo-controlled, double-blinded, randomized, cross-over study, we investigated the effect of 14 days of treatment with atorvastatin (40 mg once-daily for one week and 80 mg once-daily the second week) on fasting and postprandial concentrations of glucose, gluco-regulatory hormones and bile acid profiles in 15 healthy male individuals (age 25.6±3.8 years; BMI 24.7±2.8 kg/m2; glycated hemoglobin A1c 4.8±0.2% (mean±SD)). Four-hour mixed meal tests were performed following each of the two 14-day treatment periods with placebo or atorvastatin, respectively.
Results: Treatment with atorvastatin did not affect postprandial plasma glucose or insulin concentrations, but basal as well as postprandial concentrations of glucagon were increased compared to placebo. Postprandial plasma concentrations of the gut-derived incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 were increased after atorvastatin treatment compared to placebo. Also, postprandial concentrations of taurine-conjugated primary bile acids increased, whereas glycine-conjugated secondary bile acids decreased.
Conclusion: In healthy male individuals, 14 days of atorvastatin treatment did not affect postprandial glucose tolerance or insulin concentrations. Fasting and postprandial glucagon concentrations were increased by atorvastatin treatment, which may point to hyperglucagonemia as a possible link between statin treatment and type 2 diabetes.

Disclosure
M.L. Thomasen: None. D.P. Sonne: None. M.L. Kårhus: None. A. Brønden: Other Relationship; Self; AstraZeneca. B. Staels: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. T. Vilsbøll: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S.

Funding
Augustinus Fonden
2347-PUB: Relationship between Aging and Effects of SGLT2 Inhibitors on Glucose and Lipid Metabolisms and Hepatic Function in Japanese Patients with Type 2 Diabetes
Authors: KUSUNOKI MASATAKA , NATSUME YUKIE , OSHIDA YOSHIHARU , MIYATA TETSURO 
Published: June 2019

SGLT2 inhibitors (SGLT2is) have been found to improve blood glucose, HbA1c and triglyceride levels and also hepatic dysfunction in patients with type 2 diabetes. However, scarcely any studies have examined whether there are differences in the effects of SGLT2is according to patient age. In this study, we stratified the patients into 3 groups according to the age and investigated whether age influences the effects of SGLT2is on glucose and lipid metabolisms and hepatic function in these patients.
The patients were stratified into the following 3 age groups: &lt;50, 50 to 64, and ≥65 years. Five SGLT2is were administered for 6 months at the following doses: 2.5 mg/day luseogliflozin, 5 mg/day dapagliflozin, 20 mg/day tofogliflozin, 10 mg/day empagliflozin, and 100 mg/day canagliflozin. Blood samples were collected before and after the treatment to measure biochemical parameters.
Significant decreases, compared to the baseline, of HbA1c, serum glucose and insulin, and HOMA-R were observed after the treatment with the SGLT2is in the &lt;64 years age groups, but not the ≥65 years age group. With regard to the effects on lipid metabolism, increase in serum HDL cholesterol and decrease in LDL cholesterol/HDL cholesterol ratio were observed in the ≥65 years age group. In addition, hepatic function parameters improved significantly in the &lt;64 years age groups, but to a lesser degree in the ≥65 years age group. The effects on BMI were not affected.
The results revealed that some effects of SGLT2is were affected by aging. The SGLT2is improved glucose metabolism in the patients aged &lt;64 years, but this effect was weaker in those aged ≥65 years. However, the SGLT2is led to a more anti-atherogenic serum lipid profile in patients aged ≥65 years than in those aged &lt;65 years. In addition, it appears that the hepatic function-improving effect of SGLT2is decreases with age, especially in patients aged ≥65 years. The effects of SGLT2 inhibitors on BMI were not affected.

Disclosure
M. Kusunoki: Other Relationship; Self; Kaken Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd. Y. Natsume: Other Relationship; Self; Kaken Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd. Y. Oshida: None. T. Miyata: Research Support; Self; Bayer AG, Daiichi Sankyo Company, Limited.
238-LB: Prevalence of GCK-MODY in 92,412 Exomes from an Unselected Clinical Population
Authors: MIRSHAHI UYENLINH L. , GOEHRINGER JESSICA M. , HU YING , WARDEH AMR H. , WILLIAMS JANET , MANNEY CATARINA B. , STAPLES JEFFREY C. , LEADER JOSEPH B. , SHULDINER ALAN R. , POLLIN TONI I. , CAREY DAVID J. 
Published: June 2019

Maturity onset diabetes of the young (MODY) is a monogenic form of diabetes attributed to a highly penetrant variant in one of several genes, including GCK. GCK-MODY rarely requires pharmacotherapy, however, the clinical management of pregnant mothers depends on whether the fetus inherited the GCK variant. The classic GCK-MODY phenotype is young (diagnosed before 25 years), lean (BMI &lt; 25 mg/kg2), with stable, mild hyperglycemia (Hba1c 5.8-7.6%). We hypothesized that strict application of these guidelines has led to under-reporting of GCK-MODY (prevalence 1.1 per 1000). In a cohort of 92,412 individuals from the DiscovEHR study, we identified 252 heterozygous carriers of 88 rare GCK variants (minor allele frequency &lt; 0.02%). None had an existing diagnosis of monogenic diabetes. The median BMI of GCK carriers was 35 mg/kg2, compared to 31 mg/kg2 for nondiabetic noncarriers and 38 mg/kg2 for noncarriers with type 2 diabetes (T2D). Excluding variants with no evidence of hyperglycemia in 50% of the carriers resulted in 70 variants in 213 individuals. GCK-MODY variant carriers had mean HbA1c, fasting blood glucose (FBG), and random glucose measurements that were greater than nondiabetic non-carriers but less than those with T2D. Kaplan-Meier analysis adjusted for left-truncation bias showed that the age at which 50% of GCK-MODY subjects diagnosed with impaired fasting glucose and diabetes is 35 and 55 years, respectively, compared to 60 and 65 years in non-carriers with T2D (p&lt; 2e-16). Within-individual variability of lifetime FBG measurements of GCK-MODY carriers was less than noncarriers with T2D (GCK-MODY, 7.9 ± 2.0 mg/dL; T2D, 17.6 ± 0.03 mg/dl, p &lt;1e-4). The odds ratios [95% confidence intervals] for diabetes in GCK-MODY carriers was 4.0 [3.1 - 5.2], p&lt;0.0001. We estimate a GCK-MODY prevalence of 1 per 508 individuals and 1 per 59 individuals with gestational diabetes. GCK variant carriers in this study had a broader spectrum of clinical characteristics compared to the classic GCK phenotype.

Disclosure
U.L. Mirshahi: None. J.M. Goehringer: None. Y. Hu: None. A.H. Wardeh: None. J. Williams: None. C.B. Manney: None. J.C. Staples: Employee; Self; Regeneron Pharmaceuticals. J.B. Leader: None. A.R. Shuldiner: Employee; Self; Regeneron Pharmaceuticals. Stock/Shareholder; Self; Rhythm Pharmaceuticals, Inc. T.I. Pollin: Other Relationship; Self; Regeneron Genetics Center. D.J. Carey: None.