Understanding Production Drivers and Challenges in Converting a Vertical to Horizontal Oil Play Utilizing Single Well Modeling

Abstract The recent growth in horizontal well technology has resulted in existing oil and gas vertical development plays to be evaluated for horizontal well applicability. As operators attmept to evaluate the criteria for converting from vertical well plays to horizontal well plays, sound data gathering and modeling become crucial to understand how completion strategies needs to be modified for improved production, without utilizing an expensive trial and error methodology. The Powder River basin contains a variety of producing shales and sands currently being explored for vialibility (i.e. Niobrara, Frontier, etc). In this study, reservoir and fracture properties are estimated based on hydraulic fracture modeling, rate-transient analysis techniques and production history matching to calibrate log data measurements. The challenges associated with calibration and modeling measurements from petrophysical and rock mechanics models are compared with hydraulic fracture and production modeling results to understand the direction of optimization and future basin growth. Past experiences are typically the basis for design and implementation of developing a new drilling and completion program. Interpretation of the hydraulic fracture behavior is often inferred from simple diagnostics, and as production ensues the repeatability for success or failure is often attributed to modifying the hydraulic fracturing program or geological influences, which is subject to inconsistency and qualitative introspection. Within this study a single well modeling approach is utilized to understand fracture geometry, correlate this with production history matching results, and distinguish production attribution from hydraulic fracture characteristics or reservoir properties. Exercising this workflow addresses challenges affiliated with modeling fracture propagation and production matching and the gap associated with horizontal well development in existing vertical plays.</jats:p

An Integrated Single-Well Approach to Evaluating Completion Effectiveness and Reservoir Properties in the Wind Dancer Field

Abstract Accelerating the learning curve in a fluvial tight-gas development program can be achieved by understanding the impact of reservoir quality and completion properties on well productivity. Too often completion changes are made over a small sample (statistical) wherein numerous parameters (proppant volumes/type, gel-loading, etc) are changed without clear accountability of the variation in local geology and reservoir quality. This complicates basic production analysis techniques and can be a costly practice to determine the direction in which optimization should proceed. Various proppants, fluid types and design schedules were analyzed to quantify the impact of these designs on productive fracture half-lengths and conductivity. Calibrated fracture propagation models were also utilized to relate these productive properties (fracture length, conductivity and permeability) to stress profile, gel-loading and proppant types via fracture propagation models. The development of calibrated mechanical properties, petrophysical models and understanding of current hydraulic fracture and reservoir properties thus enabled redesigning of future completions and the analysis of these completions. This paper demonstrates the application of appropriate fracture propagation models, rate-transient analysis and production history matching techniques to understand the direction in which completion design changes must move to increase productivity.</jats:p

246-OR: Contribution of Plasma Glucose and Hormones to the Acute Compensatory Rise in Endogenous Glucose Production (EGP) during Glucosuria in T2D Patients

Aim: To examine the role of plasma glucose (GLU), insulin (INS) and glucagon (GG) changes in EGP stimulation during glucosuria (UGE) following SGLT2i administration. Methods: Using tracer (3-3H-glucose), 30 T2D patients (Age=55±1y, BMI=32.2±0.7kg/m2, FPG=140±6mg/dl, A1c=7.3±0.1%) received three 300-min procedures at 2-weeks intervals: (I) control clamp (CON) with no glucose/hormone infusions; (II) pancreatic clamp (PAN) with somatostatin (0.75mg/h), basal replacement of insulin (0.1mU/kg.min) and glucagon (0.3ng/kg.min); (III) isoglycemic clamp (ISO) with variable dextrose infusion to maintain GLU equal to baseline. Prior to start of each clamp subjects received placebo (PCB, n=10) or dapagliflozin 10mg (DAPA, n=20). Results: After DAPA (CON), INS decreased (-7±1µU/ml) while GG increased (+10±1pg/ml) (both p&amp;lt;0.05 vs. PCB). Despite UGE of 0.48mg/kg.min, GLU decline was modest (-31±1) due to a “paradoxical” rise in EGP after DAPA. During PAN with DAPA and PCB, INS and GG were unchanged from baseline, and EGP stimulation in DAPA compared to PCB still increased, yet GLU decline was modest (-28.4±3.0). During ISO, EGP decreased markedly with DAPA as well as PCB despite similar plasma GG and INS concentrations. Conclusion: DAPA-induced glucosuria stimulation of EGP cannot be entirely explained by the rise in plasma glucagon or decline in plasma insulin. Disclosure M. Alatrach: None. C. Agyin: None. N. Laichuthai: None. J.M. Adams: None. M. Abdul-Ghani: None. C.L. Triplitt: Consultant; Self; Abbott. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. E. Cersosimo: None. </jats:sec

1136-P: Glucose Kinetics during Oral Glucose Challenge following Administration of Exenatide and Dapagliflozin Alone and in Combination in Type 2 Diabetes

Aim: To examine the effect of SGLT2i on endogenous glucose production (EGP), tissue glucose disappearance (Rd), and urinary glucose excretion (UGE) following glucose ingestion. Study Design: 28 type 2 diabetes [T2D] patients (Age= 51±2 y; BMI=31.2±0.7; A1C=7.9±0.2%) received 8-hour 3-3H-glucose infusion after an overnight fast. Previously shown, EGP suppression by dapagliflozin (DAPA) compared to placebo (PCB) (Δ=-0.02±0.02 vs. -0.45±0.03, p&amp;lt;0.01 mg/kg.min) was impaired. On a separate day, subjects were randomized to receive 5-hour double-isotope (IV 3-[3H]-glucose and oral [14C]-glucose) OGTT (75-g) preceded by PCB, DAPA 10 mg, EXEN 5 µg, or DAPA+EXEN. Oral [RaO], EGP, Total and Tissue Rd, and UGE were calculated. Results: During 0-300-min, RaO was 65 g in DAPA, 59 g in PCB, 46 g in EXEN, and 48 g in DAPA+EXEN. UGE was 31±4 g in DAPA and 30±4 g in DAPA+EXEN, but only 3±1 g in EXEN and 10±3 g in PCB (p&amp;lt;0.001 vs. DAPA and DAPA+EXEN). Conclusion: The post-OGTT rise in PG was significantly reduced after DAPA+EXEN vs. each drug alone. This resulted from lower oral glucose appearance with greater UGE. During the OGTT, EGP suppression with DAPA (Δ = -0.8±0.1 mg/kg.min) was less than with PCB, EXEN, and DAPA/EXEN (p&amp;lt;0.05-0.01), while EGP suppression with DAPA/EXEN was similar to PCB but required a higher rise in insulin (p&amp;lt;0.05). Tissue glucose clearance was unchanged by any therapy. Disclosure M. Alatrach: None. C. Agyin: None. N. Laichuthai: None. O. Lavrynenko: None. J.M. Adams: None. M. Abdul-Ghani: None. C.L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Xeris Pharmaceuticals, Inc. R.A. DeFronzo: None. E. Cersosimo: None. </jats:sec

1070-P: Bromocriptine-QR (BQR) Ameliorates a Pro-oxidative Stress/Proinflammatory (POS/PI) Monocyte Phenotype in Poorly Controlled T2DM Subjects

Background: Elevated sympathetic tone stimulates a POS/PI leucocyte phenotype that promotes cardiovascular disease (CVD) and augments postprandial hyperglycemia in T2D. BQR, a sympatholytic dopamine agonist for treatment of T2DM, improves postprandial dysglycemia and reduces CVD events. Aim: To examine the effect of BQR on POS/PI phenotype of blood monocytes in T2DM. Study Design: 15 T2DM subjects treated with a GLP-1 RA received BQR (3.2 mg/day) for 16 weeks. Endothelial function was measured by post-occlusion hyperemia. Blood monocytes were isolated and expression (PCR) of the following genes was quantitated: (i) master antioxidant gene regulators that increase in response to systemic oxidative stress (OS) (oxidation resistance gene 1 [OXR1] and nuclear factor erythroid 2 like 2 [NRF2]); (ii) genes known to induce a proinflammatory profile in T2DM (toll like receptor 2 [TLR2], nuclear factor kappa B p65 [NFkBp65], and L-selectin, a surface adhesion protein that stimulates transendothelial migration and PI biochemistry); (iii) glucocorticoid receptor [GCR] that produces a PI environment. Results: BQR significantly improved HbA1c (-0.6%; baseline HbA1c=8.3%), postprandial hyperglycemia (by 22%) and endothelial dysfunction (by 36%). BQR reduced OS response gene transcript levels of OXR1 and NRF2 by 30% (P&amp;lt;0.03) and of PI genes TLR2, NFkBp65, GCR, and L-selectin by 40, 33, 26, and 32% respectively (P&amp;lt;0.05). Plasma levels of OS markers (TBARS and nitrotyrosine) and PI cytokines (MCP1 and IL-18) also were significantly reduced (p&amp;lt;0.01-0.05) by BQR. Conclusion: BQR reduces postprandial dysglycemia, improves endothelial function, and improves multiple aspects of the POS/PI state in T2DM, providing a potential mechanism for BQR’s cardiovascular protective effect. Disclosure M. Ezrokhi: Employee; Self; VeroScience LLC. A. Cincotta: Employee; Self; VeroScience LLC. E. Cersosimo: None. J.M. Adams: None. M. Alatrach: None. C. Agyin: None. C.L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Xeris Pharmaceuticals, Inc. N. Cominos: Employee; Self; VeroScience LLC. R.A. DeFronzo: None. </jats:sec

352-OR: Combination Therapy with Dapagliflozin plus Exenatide on Endogenous Glucose Production: A Mechanism of Action Study

Aim: To examine the mechanisms with which GLP-1 RA plus SGLT2i improve glycaemia versus each agent as monotherapy. Study Design: 21 T2D patients (Age= 51±2; BMI=31.2±0.7; A1C=7.9±0.2%, FPG= 172±8; mean PG OGTT [0-5h] =249±8) received 5-hour double tracer (3-3H-glucose IV/1-14C-glucose orally) OGTT and then were randomized to dapagliflozin (DAPA) 10 mg/d, exenatide (EXEN) 2 mg/wk, dapagliflozin plus exenatide (DAPA/EXEN) for 4 months. Results: Combination DAPA/EXEN therapy produced a completely additive effect to reduce HbA1c and near additive effect to decrease FPG and mean PG during OGTT. The additive effect of DAPA/EXEN resulted from: (1) decreased basal EGP; (2) increased urinary glucose excretion (UGE); (3) decreased rate of oral glucose appearance (RaO); (4) enhanced insulin secretion; (5) increased tissue glucose clearance. Of note, exenatide could not overcome the impaired suppression of EGP by dapagliflozin. Disclosure M. Alatrach: None. C. Agyin: None. J.M. Adams: None. O. Lavrynenko: None. N. Laichuthai: None. E. Cersosimo: None. C.L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Xeris Pharmaceuticals, Inc. A. Gastaldelli: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Inventiva Pharma, Novo Nordisk Inc. M. Abdul-Ghani: None. R.A. DeFronzo: None. </jats:sec

Modeling the impacts of projected climate change on wheat crop suitability in semi-arid regions using the AHP-based weighted climatic suitability index and CMIP6

L

1166-P: Bromocriptine-QR (BQR) Therapy Reduces Elevated Sympathetic Nervous System Activity (SNSA) and Oxidative Stress (OS) in Type 2 Diabetes (T2D) Subjects whose Dysglycemia Is Poorly Controlled on GLP-1 Receptor Agonist (GLP-1RA)

Elevated SNSA induces dysglycemia by enhancing adipose lipolysis and stimulating hepatic glucose production. It also promotes cardiovascular disease (CVD) by multiple mechanisms including augmenting systemic and vascular reactive oxygen and nitrogen species (ROS, RNS) generation. Elevated plasma prolactin (subclinical hyperprolactinemia) has also been associated with systemic inflammation, which can potentiate dysglycemia and CVD. BQR, the only dopamine agonist approved for treatment of T2D, improves postprandial dysglycemia and reduces CVD events. To evaluate mechanisms for the glucose lowering and CVD protective effects of BQR, we evaluated BQR’s effect on plasma markers of SNSA and ROS/RNS and plasma prolactin and leptin from a mechanistic study in which BQR added to 15 T2D subjects (HbA1c 8.3%) treated with a GLP-1 RA significantly improved HbA1c (-0.6%), postprandial hyperglycemia (by 22%) and endothelial dysfunction (by 36%). Plasma norepinephrine (NE), normetanephrine (NM), TBAR (a marker of systemic OS), nitrotyrosine (NT, a marker of systemic oxidative/nitrosative stress), prolactin and leptin were measured at baseline and after 4 months of BQR add-on therapy (3.2 mg/day). Plasma NE, NM, TBAR, NT and prolactin levels were elevated at baseline and decreased significantly with BQR [NE by 33% (2.95 to 1.95 ng/mL, p &amp;lt;0.0005); NM by 22% (56.5 to 44.3 pg/ml, p&amp;lt;0.018); TBAR by 10% (10.2 to 9.2 μM, p=0.04); NT by 13% (214 to 187 nM, p&amp;lt;0.02); prolactin by 42% (13.0 to 7.6 ng/ml, p&amp;lt;0.012)]. Plasma leptin, unchanged in the whole group, decreased 23% (35.7 to 27.5 ng/mL, p=0.038) in subjects with elevated leptin (&amp;gt;20 ng/dl, N=7) at baseline. Conclusion: Bromocriptine-QR is the only T2D therapy known to simultaneously reduce elevated plasma NE, NM, prolactin and OS and such actions may be important for the drug’s glucose lowering and CVD protective effects. Disclosure B. Chamarthi: Employee; Self; VeroScience LLC. E. Cersosimo: None. J.M. Adams: None. M. Alatrach: None. C. Agyin: None. C.L. Triplitt: Consultant; Self; Abbott. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc. M. Ezrokhi: Employee; Self; VeroScience LLC. S. Luo: Employee; Self; VeroScience LLC. E. Duvallet: Employee; Self; VeroScience LLC. A.H. Cincotta: Employee; Self; VeroScience LLC. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. </jats:sec

155-LB: The Increase in Endogenous Glucose Production with SGLT2 Inhibition Is Unchanged by Renal Denervation but Highly Correlates to Urinary Glucose Excretion

Background: SGLT2 inhibition causes a “paradoxical” increase in EGP, indicating the presence of a “reno-hepatic axis.” Aim: We measured EGP after SGLT2 inhibition in renal transplant subjects with and without type 2 diabetes to evaluate the role of renal nerves and SNS in mediating this “reno-hepatic axis.” Six T2D (A1c = 7.2±0.1) and 8 non-T2D (A1c = 5.6±0.1) with normal renal function and no history of rejection (prednisone ≤ 5mg/day) received two 6-hr measurements of EGP preceded by dapagliflozin or placebo. Results: Following DAPA in T2D, FPG (143±15 to 112±9 mg/dl, p=0.01) and FPI (14±3 to 11±2, p=0.02) decreased while glucagon increased (45±13 to 54±14 pg/mL, p=0.09) (all p&amp;lt;0.05 vs. placebo); plasma epinephrine and norepi did not change from baseline. Following placebo, EGP decreased (p&amp;lt;0.01) in both T2D and non-DM. In contrast, after DAPA EGP increased (p&amp;lt;0.01) in both T2D (by 0.4±0.1 mg/kg.min) and in non-T2D (by 0.1±0.1 mg/kg.min) compared to placebo. The DAPA-induced increment in EGP production was highly correlated (r = 0.824, p&amp;lt;0.001) with the increment in urinary glucose excretion in all subjects (Figure). Conclusions: (1) Renal denervation in renal transplant patients failed to block the DAPA-mediated stimulation of EGP; (2) DAPA-stimulated rise in EGP is strongly related to the increase in urinary glucose excretion blunting the decline in FPG. Disclosure C. Solis-Herrera: Advisory Panel; Self; Sanofi. M. Alatrach: None. C. Agyin: None. H. Honka: None. R. Patel: None. C.L. Triplitt: Consultant; Self; Abbott. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc. J.M. Adams: None. A. Gastaldelli: Consultant; Self; A. Menarini Diagnostics, Eli Lilly and Company, Genentech, Inc., Gilead Sciences, Inc., Inventiva Pharma. M. Abdul-Ghani: None. E. Cersosimo: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc. </jats:sec