bluuebunny/crossref_metadata_2025_split huggingface dataset:
1119-P: Efficacy and Safety of Sitagliptin (SITA) Compared with Dapagliflozin (DAPA) in People ≥65 Years Old with T2D
Authors: RAJI ANNASWAMY , XU ZHI JIN , LAM RAYMOND L. , KAUFMAN KEITH D. , ENGEL SAMUEL S. 
Published: June 2019

In the U.S., ~45% of patients with T2D are ≥65 years old, of whom ~50% have mild renal insufficiency (eGFR ≥60 and &lt;90 mL/min/1.73 m2). Older people may respond to AHA treatment differently from younger people, and assessments focused on the older population are desirable. We conducted a post hoc analysis of the cohort of patients ≥65 years who participated in a 24-week randomized, double-blind clinical trial (NCT02532855) of the efficacy and safety of SITA 100 mg qd vs. DAPA 10 mg qd in people with mild renal insufficiency while on MET ± SU; the primary efficacy endpoint was change in A1C at Week 24, analyzed with an LDA model.
Treatment groups were well-balanced at baseline (mean A1C [%] = 7.7/7.7, mean eGFR [mL/min/1.73 m2] = 79/76 for SITA/DAPA). At Week 24, LS mean reduction from baseline A1C was greater with SITA compared with DAPA (Table). With SITA treatment, 41% of participants were at A1C goal of &lt;7.0% compared to 28% with DAPA (Table). The SITA group had greater reductions in post-prandial glucose endpoints, and the DAPA group had greater reductions in FPG (Table). Treatments were generally well tolerated; there were significantly fewer drug-related AEs with SITA than with DAPA, but AE profiles were otherwise similar.

Disclosure
A. Raji: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. Z. Xu: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. R.L. Lam: Employee; Self; Merck & Co., Inc. K.D. Kaufman: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc.

Funding
Merck & Co., Inc.
112-OR: Critical Role of Tyrosine Kinase 2 (TYK2) in Human Pancreatic Differentiation
Authors: CHANDRA VIKASH , IBRAHIM HAZEM , BALBOA DIEGO , OTONKOSKI TIMO 
Published: June 2019

Type 1 diabetes (T1D) is caused by the autoimmune destruction of pancreatic beta cells. Genome wide association and fine mapping studies to identify causal variants predicted several loci in the human genome that are associated with T1D risk. One such candidate gene is a member of the JAK (Janus Kinase) family of tyrosine kinases, TYK2, which plays a critical role in intracellular signaling stimulated by cytokines through STATs. Loss-of-function variants of TYK2 are associated with protection against T1D. In line with this, silencing of TYK2 in beta cells attenuated inflammatory signaling pathways and apoptosis. To study the role of TYK2 in human beta-cell development, we now generated TYK2- knockout (KO) human iPSC lines using CRISPR-Cas9 genome editing and induced them to differentiate to pancreatic endocrine lineage. Our results suggest that absence of TYK2 does not compromise the pluripotency or the early pancreatic endoderm differentiation potential of iPSC. However, in the later stages of differentiation, the mRNA levels of key pancreatic TFs (PDX1(55±17%, p=0.03), NGN3(65±13%, p=0.008)), RFX6(58±14%, p=0.014), NKX6.1(39±19%, p=0.114) and NKX2.2(68±7%, p=0.0008)) were significantly reduced in the TYK2-KO cells. In the final stages of controlled induction to endocrine lineage TYK2-KO lines expressed lower levels of INS(53±9%, p=0.004), GCG(70±10.5%, p=0.002) and SST(62±8.6%, p=0.002) compared to control lines (mean ± SEM of 3 independent experiments). Furthermore immunostaining for INS, GCG and SST confirmed a lower number of endocrine hormone positive cells in TYK2-KO lines. In contrast to the wild type controls, the TYK2-KO iPSC-derived pancreatic cells displayed no activation of STAT1 and STAT2 and showed impaired STAT3 activation in response to IFNαor stimulation by polyinosinic-polycitidilic acid treatment, a viral infection mimetic. The present study suggests that TYK2 plays an important early role in pancreatic endocrine differentiation.

Disclosure
V. Chandra: None. H. Ibrahim: None. D. Balboa: None. T. Otonkoski: None.
1124-P: Beneficial Changes in Glycemic Control in Patients with Hypogonadism and Type 2 Diabetes (T2DM) Receiving Long-Term Treatment with Injectable Testosterone Undecanoate (TU): Ten-Year Data from a Registry
Authors: SAAD FARID , HAIDER KARIM S. , HAIDER AHMAD 
Published: June 2019

Background: Men with T2DM have a high prevalence of hypogonadism.
Methods: In a registry of 823 men with hypogonadism, 324 men (39%) had T2DM. 152 received TU 1000 mg/12 weeks (T-group), 172 opted against treatment (CTRL). Changes over time between groups were compared by mixed effects model for repeated measures with random effect for intercept and fixed effects for time, group and their interaction. Changes were adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the two groups.
Results: Mean follow-up 7.9±2.4, age: 62.8±5.1 years. T-group: baseline HbA1c: 9.1±1.2%. HbA1c progressively decreased by 2.7±0.3% at 10 years. CTRL: baseline HbA1c: 7.8±0.7%. HbA1c increased by 2.9±0.3%. Estimated adjusted difference between groups: 5.6% (p&lt;0.0001 for all). Fasting glucose (mmol/L) decreased in T-group by 1.7±0.2 and increased in CTRL by 1.6±0.2, difference between groups: 3.2 (p&lt;0.0001 for all). Fasting insulin (µU/mL) decreased in T-group by 17.4±0.4 and increased in CTRL by 10.7±1.1, difference between groups: 28.1 (p&lt;0.0001 for all). In the T-group, baseline HOMA-IR was 10.2±2.1. HOMA-IR progressively decreased by 6.9±0.2 at 10 years. CTRL: baseline HOMA-IR: 7.5±1.3. HOMA-IR increased by 7.6±0.5. Difference between groups: 14.5 (p&lt;0.0001 for all). In the T-group, 92 men (60.5%) received insulin at baseline at a mean dose of 36.5±12.2 U/d and 66 in CTRL at a mean dose of 30.8±6.0 U/d. The dose requirement in the T-group declined by 17.7±1.0 U/d and increased in CTRL by 17.7±1.0 U/d. Difference between groups: 35.3 U/d (p&lt;0.0001 for all). In CTRL, 20 patients were started on insulin during the observation time.
Conclusions: Long-term testosterone therapy with TU in men with hypogonadism and T2DM progressively improved glycemic control which worsened in untreated hypogonadal controls.

Disclosure
F. Saad: Employee; Self; Bayer AG. Stock/Shareholder; Self; AbbVie Inc., Amgen Inc., Bayer AG. K.S. Haider: Speaker's Bureau; Self; Bayer AG. A. Haider: Research Support; Self; Bayer AG. Speaker's Bureau; Self; Bayer AG.

Funding
Bayer AG
1135-P: Real-World Effectiveness of a Blood Sugar Monitor and Companion Digital Therapeutic Combination in Improving Blood Glucose Levels among People with Diabetes in India
Authors: CHAWLA RAJEEV , KRISHNAKUMAR ARJUN , KHATRY VARSHA , SHAH ABHISHEK , JOSHI SHILPA , SHAIKH SHEHLA SAJID , LATHIA TEJAL , THACKER HEMANT , SAMUDRA KIRTI , MATTOO VINOD 
Published: June 2019

Background: The glycaemic control among people with diabetes in India is very poor. This study evaluated the effectiveness an iPDM (integrated personalised self-management) in changing health behavior to improve blood glucose levels.
Methods: We used data from 883 participants (Average = 45.41 years; 72.71% male) who were using Accu-Chek® Active in conjunction with Wellthy Care™ digital therapeutic (WC DTx). The participants had to log the blood sugar values into the app manually. The WC DTx, developed in lines with AADE7 and RSSDI guidelines, includes skill-development through self-management education, and real time feedback and coaching through artificial intelligence (AI).
Results: The users were on the combination of the Accu-Chek® Active blood sugar monitor and its companion WC DTx for an average of 30.87 days. There was a significant difference between the mean first and last logged fasting blood sugar (FBS) (149.33 mg/dl vs. 132.83 mg/dl, p = 0.0013) and random blood sugar (202.20 mg/dl vs. 169.79 mg/dl, p = 0.004) values. The average per-user app interaction was 8.12 instances. A total of 2184 blood glucose measurements were logged with an average of 2.29 measurements per user. There was a step-wise decrease in FBS as the app engagement increased. The lowest tertile of app engagers reduced their FBS by 20.99 mg/dl (p=0.086), the middle tertile of app engagers reduced their FBS 23.98 mg/dl (p=0.038), and those in the highest tertile of app engagers reduced their FBS by 25.36 mg/dl (p=0.016). The reduction in random blood sugar in the highest level of app engagers was significant (p=0.04) than the reduction in the lowest (p=0.144) and middle tertile (0.296) of app engagers.
Conclusion: iPDM using Accu-Chek® Active along with Wellthy Care™ as a companion therapeutic, can help people with diabetes in India to improve self-management skills and overall blood sugar levels.

Disclosure
R. Chawla: None. A. Krishnakumar: Employee; Self; Wellthy Therapeutics. V. Khatry: Employee; Self; Roche Diabetes Care. A. Shah: Stock/Shareholder; Self; Wellthy Therapeutics. S. Joshi: None. S.S. Shaikh: None. T. Lathia: None. H. Thacker: None. K. Samudra: None. V. Mattoo: Consultant; Self; Wellthy Therapeutics.
114-LB: GX-G6, a Novel Long-Acting Glucagon-Like Peptide Receptor Agonist: Result of Phase I Study in Healthy Volunteers
Authors: BYUN MISUN , SEO CHINAM , WOO JUNGWON , SUNG YOUNGCHUL 
Published: June 2019

GLP-1 receptor agonists are widely used in T2DM. GX-G6 is a hyFcTM fused long acting GLP-1, and is a proposed alternative to other GLP-1 agents. In this phase I, randomized, double-blind, placebo-controlled, single ascending dose study, 8 subjects randomly received GX-G6 or its matching placebo in a 6:2 ratio, in each of 6 cohorts at 0.01, 0.02, 0.04, 0.08, 0.16 and 0.24 mg/kg. Primary endpoint was safety and tolerability. Pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity were also assessed. GX-G6 was well tolerated, and no subject experienced hypoglycemia. Decreased appetite was the most common treatment-emergent adverse event which resolved spontaneously without treatment. GX-G6 was rapidly absorbed and its average terminal half-life ranged 62-92 hours. AUC0-t and Cmax increased in dose-proportional manner. No dose dependency in plasma glucose level was observed in healthy subject setting. However, in the OGTT, tendency of decrease in glucose concentration compared to placebo was demonstrated at 0.5 hours. No subjects developed antibodies against GX-G6. Single SC doses of GX-G6 were safe and well-tolerated in a dose range of 0.01 to 0.24 mg/kg in healthy subjects. Dose dependent and durable PK profile and OGTT results show potentials of GX-G6 to be both weekly and twice-monthly treatment for T2DM. [Clinicaltrials.gov: NCT03651466].

Disclosure
M. Byun: None. J. Woo: None. Y. Sung: None.
117-OR: Carvedilol Prevents Impairment of the Counterregulatory Response in Recurrently Hypoglycemic Diabetic Rats
Authors: FARHAT RAWAD , CHAN OWEN , SU GONG , VAN VLIET ELIANE DE SANTANA 
Published: June 2019

It has been suggested that repeated activation of the adrenergic system during antecedent episodes of hypoglycemia may contribute to the development of counterregulatory failure. We previously showed that treatment with the non-specific β-blocker, carvedilol, can prevent counterregulatory failure in nondiabetic, recurrently hypoglycemic rats. The current study investigated whether carvedilol, can be used to prevent the development of counterregulatory failure in recurrently hypoglycemic diabetic rats. Sprague-Dawley rats were made diabetic with a single injection of streptozotocin (STZ; 60mg/kg; I.P.) One week after the induction of diabetes, carvedilol (4.5mg/kg QID; IP) treatment was started and continued for one week in one subgroup of STZ-diabetic rats. The remaining animals received a saline injection as controls. Three days later, the animals received either 3 bouts of insulin-induced hypoglycemia (RH) over the course of 3 days or they received 3 saline injections. On day 14, the animals underwent a hyperinsulinemic-hypoglycemic clamp to assess the counterregulatory hormone responses. Compared to hypoglycemia-naïve STZ Controls, glucose infusion rates were more than doubled in the STZ+RH animals (P&lt;0.001) and this was associated with an ∼50% reduction in the epinephrine response to hypoglycemia. Treatment of STZ+RH animals with carvedilol improved the epinephrine responses to hypoglycemia. Of note, RH did not further diminish the glucagon response in STZ-diabetic rats. Our data suggests that carvedilol may be useful to prevent impairments in the counterregulatory response during recurring episodes of hypoglycemia in diabetic animals.

Disclosure
R. Farhat: None. O. Chan: Research Support; Self; Zucara Therapeutics Inc. G. Su: None. E. De Santana Van Vliet: None.

Funding
JDRF; National Institutes of Health
1183-P: A Crossover Randomized Controlled Trial Using Dialbetics: Smartphone-Based Self-Management System for Lifestyle-Related Disease Management
Authors: MIYAKE KANA , WAKI KAYO , OHE KAZUHIKO 
Published: June 2019

Objective: We evaluated the clinical effects of mHealth system in self-management among subjects at risk of developing diabetes.
Method: DialBetics comprises three modules. (1) Data transmission: patients’ data—blood glucose, blood pressure, body weight, and pedometer counts—are measured at home and sent by smartphone to the server. (2) Evaluation: data are evaluated following the Japan Diabetes Society guideline’s targeted values; DialBetics determines if each reading satisfies the values, then sends the results back to each smartphone. (3) Communication: (a) the patient’s text messages about meals and exercise are sent to the server; (2) processed advice on lifestyle modification. A crossover randomized controlled trial—for six months—was conducted.
Results: The 122 subjects were classified into two groups: 61 in the group A that used the system in the first three months, and 61 in the group B that used the system the latter three months (age, respectively, 46.5±7.2 vs. 46.7±7.1 years). After three month, BMI, abdominal fat area (AFA), and waist circumference (WC) were significantly improved in the group A compared with the group B. At the end of the study, the data of both groups equally improved (Fig. 1).
Conclusions: DialBetics seems effective in improving self-management of subjects who are at risk of developing diabetes.

Disclosure
K. Miyake: Research Support; Self; NTT DOCOMO, INC. K. Waki: Consultant; Self; Nihon Chouzai Co.,Ltd. Research Support; Spouse/Partner; Boehringer Ingelheim Pharmaceuticals, Inc., MSD K.K., Novo Nordisk Inc. Research Support; Self; NTT DOCOMO, INC. K. Ohe: None.

Funding
Daiwa Securities Group Inc.; NTT Docomo Inc.
1187-P: The Novel Biguanide NT1195 Is an Oral Antidiabetes Drug for Patients with Kidney Disease
Authors: BATCHELOR KENNETH W. , LIVINGSTON JAMES N. , BROWN KATHLEEN K. , KAVANAGH KYLIE , COBB JEFFERY E. 
Published: June 2019

Metformin, the most prescribed drug for T2D, has significant deficiencies in potency, pharmacokinetics (PK) and safety, especially in patients with kidney disease. Despite these deficiencies no improvements have been made to the biguanide (BIG) drug class. Novel BIGs with greater efficacy and without the risk of lactic acidosis are needed for T2D in patients with impaired renal function. A library of novel BIGs was screened for functional activity against a panel of organic cation transporters (OCTs). This OCT activity profile has allowed us to select BIGs with increased potency, improved PK properties and reduced elimination in urine. NT1195 was identified from this library and examined in more detail. This BIG is 5-10x more potent in mouse OGTT than metformin and is potent in the db:db mouse model, lowering plasma glucose after 8 days of dosing when metformin did not. NT1195 is more effective at elevating GLP-1 levels and inhibited gastric emptying in mice, where metformin did not. Improved potency alone is not sufficient to create the next generation of BIG therapeutics; it is also important to improve drug safety and to reduce the risk of lactic acidosis. Detailed PK studies in mice show that NT1195 has a 28.5h half-life (metformin = 1.97h), high levels of exposure (6x &gt;metformin) and renal clearance that is 50x less than metformin. This latter finding suggests an increase in the safety of NT1195 in patients with impaired renal function, since we anticipate that NT1195 will be cleared by non-renal processes and that drug levels will not be affected by kidney disease. PK studies in cynomolgus monkeys provide similar findings for NT1195 with good exposure and a long half-life after oral administration. Also, NT1195 was found to increases glucose disposal in an IVGTT in insulin resistant monkeys. Safety studies are underway that will prepare NT1195 for a micro-dose study in T2D patients with and without kidney disease.

Disclosure
K.W. Batchelor: None. J.N. Livingston: Consultant; Self; CohBar, Inc. Employee; Self; NovoTarg Therapeutics. K.K. Brown: None. K. Kavanagh: Research Support; Self; Takeda Development Centre Europe Ltd. J.E. Cobb: Consultant; Self; NovaTarg Therapeutics.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases
1218-P: Amlodipine-Related Pedal Edema Resolved by Adding Sodium-Glucose Cotransporter 2 Inhibitor: A Technical Co-prescription for Type 2 Diabetes Mellitus with Hypertension
Authors: GAUTAM ASHISH , AGRAWAL PRABHAT K. , PURSNANI NIKHIL , JAIN APOORVA 
Published: June 2019

Idea for this study was conceived after observation form three cases. Amlodipine, a potent CCB Antihypertensive drug often causes pedal edema secondary to arteriolar dilatation leading to intracapillary hypertension and fluid extravasation. Edema usually do not resolve with diuretics and frequently needed to withdraw amlodipine. Selected subjects were patients having DM2 and hypertension, who developed pedal edema after they were prescribed amlodipine (2.5/5/10mg/d) for hypertension. Total 112 subject (60 study cases and 62 comparators) were enrolled. Patients were randomized one to one between study cases and comparators. Without changing dose of amlodipine cases were given Sodium-glucose co-transporter 2 (SGLT2) inhibitor (Canagliflozin) 100 mg once a day with individualized simultaneous reduction of other OHA’s to avoid hypoglycemia. In comparator group Amlodipine was withdrawn, replacing with other antihypertensive drug not affecting study results. Both groups were followed for 4 weeks with subjective grade of edema and weight recorded before and after study duration. 48 out of 60 study cases, whereas 24 out of 62 comparators showed complete remission of pedal edema. Fisher exact value calculated to be 0.0008 at P&lt; 0.05. Average weight loss in 4 weeks of 60 cases was 3.8 Kg, whereas 1.6 Kg in control (Z-Score is -6.3668. The p-value is 0. The result is significant at p≤ 0.05). Due to development of clinical hypotension, 10 (16.6%) study cases needed dose reduction of amlodipine whereas, 16 (25%) comparators needed another antihypertensive drug for blood pressure control. No major side effects observed during study in both groups except one female who developed polyuria and urogenital infection in study group which resolved with oral antibiotics and antifungal.
A judicious co-prescription of Amlodipine and SGLT2 inhibitor can avoid fluid overload and pedal edema in diabetes mellitus with hypertension.

Disclosure
A. Gautam: None. P.K. Agrawal: None. N. Pursnani: None. A. Jain: None.
1229-P: Dapagliflozin Improves Liver Dysfunction in Parallel with a Decrease in Serum Soluble DPP-4/CD26 Level in Type 2 Diabetic Patients with Nonalcoholic Fatty Liver Disease
Authors: KATO KANAKO , ASO YOSHIMASA , JOJIMA TERUO , IIJIMA TOSHIE , USUI ISAO 
Published: June 2019

Objective: Serum levels of soluble DPP-4/CD26 are elevated in patients with type 2 diabetes and nonalcoholic fatty disease (NAFLD). Hepatocyte-secreted sDPP-4 induce directly adipose inflammation and insulin resistance in the liver. SGLT2 inhibitors reduce hepatic steatosis by inhibiting hepatic de novo lipogenesis. We investigated effects of dapagliflozin, an SGLT2 inhibitor, on liver dysfunction, hepatic steatosis, and serum levels of sDPP-4 in patients with type 2 diabetes and NAFLD.
Methods: Fifty-seven patients with type 2 diabetes and NAFLD were randomized into a dapagliflozin (5 mg/day) treatment group (n=33) or an active placebo group (n=24) for 24 weeks. Visceral adipose tissue (VAT) volumes were measured using a dual bioelectrical impedance analysis. Hepatic steatosis was evaluated by controlled attenuated parameter (CAP) using a transient elastography.
Results: At baseline, serum sDPP-4 showed positive correlations with AST, ALT, GGT, and HOMA-IR in a total of 57 patients. VAT significantly decreased in the dapagliflozin group, but not in the placebo group. AST, ALT, and GGT showed a significant decrease at 24 weeks in the dapagliflozin group, while they were unchanged in the control group. CAP also significantly decreased in the dapagliflozin group. Although both groups showed a significant reduction in serum sDPP-4 at 24 weeks after treatment, the magnitude of sDPP-4 reduction was greater in the dapagliflozin group. Changes in liver enzymes after dapagliflozin treatment correlated positively with those in serum sDPP-4 levels, but not those in VAT or HbA1c.
Conclusions: An improvement of liver dysfunction was associated with a decrease in serum sDPP-4, but not that in VAT or HbA1c, after treatment with dapagliflozin in these patients, suggesting that reducing serum sDPP-4 by SGLT2 inhibitors may be a therapeutic strategy for treatment of NAFLD/NASH in people with type 2 diabetes.

Disclosure
K. Kato: None. Y. Aso: Research Support; Self; Ono Pharmaceutical Co., Ltd. T. Jojima: None. T. Iijima: None. I. Usui: None.
1263-P: Diabetes Care Network: A Paradigm Shift in Diabetes Care Delivery Utilizing Collaborative Care Pathway
Authors: BANDI ARCHANA , LARSON MEG J. , LUTZ-MCCAIN STACEY J. , SUMMERVILLE ASHLEY M. , LUMLEY BRANDI K. , BOUDREAUX-KELLY MONIQUE Y. 
Published: June 2019

Diabetes Care Network is a telemedicine based collaborative care pathway with team-based approach to improve diabetes care and scale the endocrine expertise. Veterans with poorly controlled type 2 diabetes were identified from electronic database, consultation completed via E-consult, and continuity care collaborated with primary care liaisons. We studied the efficacy and sustainability of our approach in improving diabetes care over 12 months.
Methods: Means (+/-SD), frequencies and percentages were presented, and Spearman correlations were assessed. Statistical significance set at p&lt;0.05. Cohort (n=87) was predominantly white (90.8%) males (97.7%), with a mean age 67.2 (8.9), and had an average of 3.3 co-morbid conditions, 0.7 macro and 1.3 micro-vascular complications. Significant decline in A1C occurred from baseline A1C of 10.2% (1.4), to 8.1% (0.99) at 3 months, 7.6% (0.96) at 6 months, and 7.5 % (0.86) at 12 months (all p&lt;0.0001). Proportion of patients out of 87 who achieved A1C of &lt;8 were 38 (43.6%), 56 (64%), and 56 (64%) and those who achieved A1C &lt;7 were 10 (11.4%), 21(24.1%), and 23 (26.4%) at 3, 6, and 12 months respectively. Non-significant improvements were noted in Weight {229.3 lbs (48.1) to 228.4 lbs (46.9)}, LDL {89.0 mg/dl (36.4) to 79.5 mg/dl (32.5)}, systolic BP {130.5 mmHg (16.1) to 123.9 mmHg (17.5)}, and triglycerides {226.9 mg/dl (195.3) to 159.3 (97.4)}. Compared to 12 months pre-enrollment period, no difference in healthcare utilization (ER visits or admissions) was noted in study period. From baseline to completion, non-significant improvement was noted in the use of anti-platelet agents, ACE/ARB, moderate to high-intensity statins and, in the frequency of Urine micro albumin measurements, annual foot and retinal exams.
Conclusion: A paradigm shift in diabetes care delivery is urgently needed. Use of telehealth technologies based collaborative pathways can scale the endocrine expertise and help attain better care for diabetic patients.

Disclosure
A. Bandi: None. M.J. Larson: None. S.J. Lutz-McCain: None. A.M. Summerville: None. B.K. Lumley: Employee; Spouse/Partner; Quest Diagnostics. M.Y. Boudreaux-Kelly: None.