bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-Life Investigation of Effectiveness and Tolerability of Hydroxychloroquine in Type 2 Diabetes Mellitus Patients in India
Authors: CHAWLA MANOJ S. , CHAWLA PURVI M. , GUPTA PAYAL
Published: June 2018

Aim: With the increasing incidence of type 2 diabetes mellitus (T2DM) in India (approximately 72 million affected), there is a growing concern and a need for newer, durable and cheaper therapies. Hydroxychloroquine (HCQ), a common anti-malarial also prescribed in rheumatic disease is associated with increased insulin sensitivity and improved glucose tolerance in these patients, with/without diabetes. As a speciality care provider, we initiated an enquiry into the effectiveness and tolerability of HCQ in T2DM patients, uncontrolled on metformin and sulfonylurea (SU) by undertaking this open-label, prospective study at our center.

Methods: A total of 15 T2DM patients, aged between 43-59 years and unresponsive to metformin and SU were included and prescribed an add-on therapy of HCQ at 400 mg once daily for 24 weeks. Change in glycemic and lipid parameters was evaluated at 0, 12 and 24 weeks.

Results: At the end of 24 weeks, there were clinically relevant decreases of 18% and 0.88% in mean fasting plasma glucose and HbA1c, respectively. The total cholesterol, triglycerides, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol decreased by 13.24%, 19.7%, 13.31% and 26.94% respectively, considered clinically meaningful with no patients discontinuing due to any adverse effects.

Discussion: Patients of T2DM, uncontrolled on metformin and SU, often require a third drug/insulin for further treatment management. These results clearly demonstrate the benefits and tolerability of HCQ in Indian T2DM patients over 24 weeks with glycemic and lipid advantages. Although the sample size of the study was small, the encouraging results pave way for larger and longer duration, studies with HCQ.

Conclusion: Based on this investigator-initiated prospective study, HCQ offers a safe, efficacious and cheaper alternative to T2DM patients, when uncontrolled on metformin and SU, particularly in limited resource countries, including India.

Disclosure

M.S. Chawla: Speaker's Bureau; Self; IPCA Laboratories, Eli Lilly and Company, Novo Nordisk A/S, MSD Pharmaceutical Pvt. Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. Speaker's Bureau; Spouse/Partner; Sanofi. P.M. Chawla: Speaker's Bureau; Self; Sanofi. Speaker's Bureau; Spouse/Partner; Eli Lilly and Company, IPCA LABORATORIES, Novo Nordisk A/S, MSD PHARMACEUTICALS PVT. LTD., Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. P. Gupta: None.
Improvements in Blood Pressure (BP) and Markers of Arterial Stiffness with Canagliflozin (CANA) in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program
Authors: TOWNSEND RAYMOND , DHARMALINGAM MALA , GENOVESE STEFANO , STEELE ANDREW , ARENAS JOSE L. , SLEE APRIL , FABBRINI ELISA , MAHAFFEY KENNETH W.
Published: June 2018

The CANVAS Program demonstrated a reduced risk of cardiovascular (CV) and renal outcomes with the SGLT2 inhibitor CANA vs. placebo (PBO) in adults with T2DM and established CV disease or ≥2 CV risk factors (N = 10,142; mean age, 63.3 y; systolic BP [SBP], 136.6 mmHg; diastolic BP [DBP], 77.7 mmHg). This analysis assessed the effects of CANA on BP, pulse, and markers of arterial stiffness including pulse pressure (PP = SBP-DBP) and double product (DP = pulse × SBP). CANA lowered SBP and DBP compared with PBO over the CANVAS Program (mean differences of -3.93 mmHg [95% CI: -4.30, -3.56]) and -1.39 mmHg [95% CI: -1.61, -1.17]; both P <0.001). There were no meaningful differences in pulse over 104 weeks; a ∼0.5 bpm reduction in pulse was seen with CANA at Week 26, which remained stable over time, while pulse with PBO was similar to baseline over 104 weeks. CANA provided reductions in PP and DP compared with PBO (Figure). There was an initial reduction in PP that increased over time with CANA, but remained lower compared with PBO. CANA also provided an initial reduction in DP that was sustained over time. Thus we observed favorable effects of CANA on BP, pulse, and markers of arterial stiffness in patients with T2DM with CV risk factors or established CV disease, which may contribute to the beneficial effects of CANA on CV outcomes.

Disclosure

R. Townsend: None. M. Dharmalingam: None. S. Genovese: Speaker's Bureau; Self; Abbott Diabetes Care, AstraZeneca, Boehringer Ingelheim, Bruno Farmaceutici, Bristol-Myers Squibb, Eli Lilly, Janssen, Lifescan, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Takeda. Consultant; Self; Abbott Diabetes Care, AstraZeneca, Boehringer Ingelheim, Bruno Farmaceutici, Bristol-Myers Squibb, Eli Lilly, Janssen, Lifescan, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Takeda. Research Support; Self; Novartis AG. A. Steele: Speaker's Bureau; Self; Amgen, AZ, Bayer, BI, Lilly, Jansen, Merck, Pfizer, Otsuka, Valeant. Advisory Panel; Self; Amgen, BI/Lilly, Jansen, Otsuka, Shire. J.L. Arenas: None. A. Slee: Other Relationship; Self; Janssen Scientific Affairs, LLC. E. Fabbrini: Employee; Self; Janssen Research & Development. K.W. Mahaffey: Research Support; Self; Afferent, Amgen, AstraZeneca, Daiichi, Ferring, Google (Verily), Janssen, Medtronic, Merck, Novartis, Sanofi, and St. Jude. Consultant; Self; Ablynx, AstraZeneca, BAROnova, Bio2 Medical, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiometabolic Health Congress, Cubist, Eli Lilly, Elsevier, Epson, GlaxoSmithKline, Janssen, Merck, Mt. Sinai, Radiometer, Springer Publishing, The Medicines Company, Theravance, Vindico, and WebMD. Stock/Shareholder; Self; BioPrint Fitness.
The Effect of Saxagliptin on Adipose Tissue Inflammation in Overweight and Obese Nondiabetic Subjects
Authors: KOSKA JURAJ , OSREDKAR TRACY , KAREN D'SOUZA , SINHA SANDEEP , MEYER CHRISTIAN , REAVEN PETER
Published: June 2018

Inflammation plays a crucial role in early stages of both insulin resistance and atherosclerosis development. Preclinical evidence suggests an important role for DPP-4 in the regulation of adipose tissue (AT) inflammation. The present study tests the hypothesis that DPP-4 inhibition by saxagliptin reduces adipose tissue inflammation independent of changes in glucose metabolism. Forty-four overweight or obese individuals without diabetes were randomized to receive once daily saxagliptin (5 mg) or matching placebo (2:1 randomization) for 6 weeks. Adipose tissue biopsies, 4 hour fat-enriched meal challenge tests, and endothelial function measurement were performed at baseline and at the end of each treatment. Forty-two participants completed the study (27 saxagliptin/15 placebo). There were no group differences in the AT expression of inflammation-related genes (MCP-1, CD36, CD68, IL-6, IL-8, TxNIP and adiponectin) and protein pathway activation (ERK, JNK and NFκB). Secretion of IL-8 from adipose tissue explants was reduced after saxagliptin compared to placebo (median fold-baseline 0.8 saxagliptin vs. 2.3 placebo, p=0.01) and there was also a trend for reduced IL-6 release (0.7 vs. 1.5, p=0.06). After the high-fat meal, plasma glucose was slightly lower after saxagliptin (4 hour AUC, 0.96 vs. 1.0, p=0.04) while insulin and triglycerides were similar between the two groups. There were no treatment differences in endothelial function.

In conclusion, reduced AT secretion of IL-8 and IL-6 (trend) in obese nondiabetic subjects suggests saxagliptin may directly reduce AT inflammation. However, this effect was relatively modest, with many other indicators of tissue inflammation remaining unchanged. The reduction in AT inflammation did not appear sufficiently potent to influence postprandial metabolism or endothelial function.

Disclosure

J. Koska: None. T. Osredkar: None. K. D'Souza: None. S. Sinha: None. C. Meyer: Employee; Self; Merck & Co., Inc. P. Reaven: Research Support; Self; AstraZeneca, Amgen Inc., Bristol-Myers Squibb Company.
Effect of Metformin on Lymphoid Cancer Cells
Authors: AHMADI NEEKI , SEN SABYASACHI
Published: June 2018

Metformin is a commonly prescribed drug for metabolic disorders particularly in type 2 diabetes. In addition to Metformin’s established antidiabetic effect it has a potential for use as an anti-cancer medication, via mitochondrial complex inhibition.

Methods: In order to determine what effect Metformin could have on a common cancer such as lymphoma at a cellular level, we performed a 14 day experiment on the effect of 3 different doses of Metformin (0mM, 0.025mM, 0.25mM) on two different lymphoid cell lines, Jurkat and Jeko. Metformin at 0.025mM, is considered physiological. Cells in culture were collected on Days 3, 7, 10, and 14 and RT-PCR targeted gene expression was carried out focusing on mitochondrial and apoptosis related genes such as cytochrome oxidases (COX2 and 4), nuclear respiratory factor (NRF1), apoptosis gene (P53) and other mitochondrial genes such as PGC1A, SOD2, and TFAM.

Results: Jeko cells showed initial significant mitochondrial gene suppression with Metformin. The suppression in mRNA gene expression however appear to reverse by day 7. By Day 10 there is a uniform up-regulation in mRNA expressions and the effects stabilized by day 14. Our Jurkat cells showed less consistent mRNA level changes, though the pattern was similar.

In summary, Jeko cells, upon initial exposure to Metformin, show a decrease in mitochondrial biogenesis and increased apoptosis. This initial suppression seems to be replaced by over-expression of mitochondrial genes over a period of time and its effects stabilizes by day 10 of exposure. This phenomenon appears to be shown in both cell lines. We plan to corroborate our gene expression findings with Sea-Horse cell respiration studies.

Conclusion: We believe that Metformin initially causes cancer cell damage, however with time the cells are able to escape that phenomenon by up-regulating mitochondrial genes particularly at physiological doses. In order for Metformin to be an effective pro-apoptotic agent in a cancer scenario, brief pulses of supra-physiological doses may be more effective.

Disclosure

N. Ahmadi: None. S. Sen: None.
Success of Interactive, Case-Based Education on Improving Physician Clinical Competence
Authors: LARKIN AMY , HANLEY KELLY L. , HEALY COLLEEN S. , LE ANNE
Published: June 2018

We sought to determine if interactive, case-based online continuing medical education (CME) could improve the clinical competence of primary care physicians (PCPs) and diabetologists/endocrinologists (D/Es) regarding clinical application of guidelines and individualized diabetes management. A 3-question case-based and 1-question confidence linked pre-/post-assessment study design and McNemar’s chi-squared test were used. P values are shown as a measure of significance. The activity launched May 3, 2017, and data collected through June 6, 2017. PCPs (N=473) demonstrated a lower baseline knowledge level compared to D/Es (N=198) as shown by the following baseline data: 35% of PCPs compared to 61% of D/Es corrently individualized treatment for a patient with T2D and HF.22% of PCPs compared to 37% of D/Es correctly individualized treatment for a patient with newly diagnosed T2D and multiple comorbidities. Significant overall improvements (P < .05) were seen: 26% more D/Es and 36% more PCPs correctly individualized the T2D treatment regimen of a patient with comorbid HF.15% more D/Es and 11% more PCPs addressed the importance of lifestyle modification in a patient with newly diagnosed T2D.47% more D/Es and 49% more PCPs correctly individualized pharmacotherapy intensification in a patient with T2D.20% of D/Es and 32% of PCPs reported an increase in confidence initiating or intensifying treatment in patients with T2D. This study demonstrates the success of interactive, case-based education on improving clinical competence of D/Es and PCPs related to management of T2D. PCPs were found to have lower baseline knowledge and competence compared to D/Es, which is not surprising given the level of specialization in both groups. PCPs may need more foundational education related to guidelines and T2D management than D/Es.

Disclosure

A. Larkin: None. K.L. Hanley: None. C.S. Healy: None. A. Le: None.
Empagliflozin Exhibits Therapeutic Effect in Preclinical Model of Liver Disease (NASH)
Authors: MAYOUX ERIC , KLEIN THOMAS , MARK MICHAEL
Published: June 2018

Nonalcoholic steatohepatitis (NASH) and diabetes are common conditions that coexist and drive adverse outcomes. Empagliflozin (empa), a sodium-glucose co-transporter-2 inhibitor (SGLT2i), has achieved a 38% reduction in the cardiovascular (CV) and all-cause mortality in type 2 diabetes patients with high CV risks. In preclinical models, SGLT2 inhibitors have been reported to increase insulin sensitivity, decrease body weight and reduce markers of oxidative stress and inflammation in tissues. Therefore, we investigated the effect of empa in a mouse model of NASH and hyperglycemia. Neonatal male mice (2 days after birth) were injected subcutaneously with streptozotocin and then were fed with a HFD from 4 weeks of age. Then from 6 to 8 weeks of age, mice were treated by oral gavage with vehicle, empa (10 mg/kg) in comparison to telmisartan (telmi, 15 mg/kg) as positive control. A group of mice, under normal diet and without STZ injection were used also as normal controls. NAS, (Histological NAFLD Scoring) evaluating fat deposition, inflammation and ballooning as well as mRNA expression for inflammation markers were performed. Blood glucose level was significantly increased in the vehicle group (525 mg/dL,) compared to the normal group (50 mg/dL). Empa significantly decreased the blood glucose (261 mg/dL) while telmi did not (429.4 mg/dL). NAS was significantly increased in the vehicle (4.1) compared to the normal control (0.0) groups and significantly decreased in telmi (1.4) and empa (1.4 ± 1.0) groups compared to the vehicle group. Telmi but also empa reduced collagen deposition and ameliorated the fat deposition. This was accompanied by a significant reduction of hepatic TNFα mRNA (1.7, 2.8 for telmi and empa, respectively compared to vehicle group (5.7). These features may qualify empagliflozin for the therapy of NASH and raise interest to evaluate further the potential of the combination of these two approved drugs, with different modes of action in the treatment of liver diseases.

Disclosure

E. Mayoux: None. T. Klein: Employee; Self; Boehringer Ingelheim GmbH. M. Mark: Employee; Self; Boehringer Ingelheim GmbH.
Effect of a Controlled-Release Mitochondrial Protonophore (CRMP) on Healthspan and Lifespan in Mice
Authors: GOEDEKE LEIGH , CAMPOREZ JOAO PAULO , NASIRI ALI , WANG YONGLIANG , ZHANG XIAN-MAN , SHULMAN GERALD I.
Published: June 2018

Caloric restriction without malnutrition (CR) is the most robust and reproducible way to extend lifespan and delay the onset of age-related diseases, such as hepatic steatosis, insulin resistance and type 2 diabetes (T2D). Unfortunately, the strict dietary regime necessary to achieve the beneficial effects of CR limits the use of this treatment to retard aging and disease in humans and new therapies are required. In this regard, our lab has recently developed a new class of therapeutic agents that are designed to safely promote liver-targeted mitochondrial uncoupling with a wide-therapeutic index. Our second-generation compound in this class is controlled-release mitochondrial protonophore (CRMP) that is functionally liver-targeted and promotes oxidation of hepatic triglycerides by promoting a subtle sustained increase in hepatic mitochondrial inefficiency. While we have previously demonstrated that this agent safely reverses hypertriglyceridemia, fatty liver, and hepatic inflammation/fibrosis in young-adult diet-induced rodent models of obesity, its effects on healthspan and lifespan remain to be determined. Here, we evaluated the impact of CRMP on hepatic steatosis and insulin action in aged 74-week-old male C57BL/6J mice fed a high-fat diet (HFD; 45% fat) for 12 weeks. Specifically, we demonstrate that CRMP treatment significantly reduced liver triglycerides, diacylglycerols, and transaminase levels independently of changes in body weight, whole-body energy expenditure or food intake. Additionally, long-term CRMP treatment reduced fasting plasma glucose concentrations (P <0.05) and improved whole-body insulin responsiveness, as reflected by a marked increase in the glucose infusion rate required to maintain euglycemia during a hyperinsulinemic-euglycemic clamp. Taken together, these studies provide important proof-of-concept data to support the use of liver-targeted mitochondrial uncouplers to promote healthy aging.

Disclosure

L. Goedeke: None. J. Camporez: None. A. Nasiri: None. Y. Wang: None. X. Zhang: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc.. Research Support; Self; Gilead Sciences, Inc..
Compound C Inhibits NLRP3 Inflammasome through an AMPK-Independent Mechanism
Authors: WANG FANG , YANG WENJUN , WANG LINGHAO , LIU YUXING , MO ZHAOHUI
Published: June 2018

It has been demonstrated that NLRP3 inflammasome is a key contributor to obesity-related insulin resistance and type 2 diabetes (T2D), which are characterized with chronic, low-grade inflammation. Adenosine monophosphate-activated protein kinase (AMPK) is a principle intracellular energy sensor, which prevents the production of proinflammatory cytokines and has beneficial effects on the protection against T2D. Comound C, an inhibitor of AMPK, has been demonstrated to be not only an inhibitor of AMPK, but also has some actions independent of AMPK inhibition. We unexpectedly found 25uM compound C considerably inhibited IL-1βand IL-18 secretion when THP-1 cells were stimulated with 100ng/ml LPS plus 0.5mM palmitic acid (PA) (P < 0.01). In order to address the underlying mechanism, we examined whether compound C affected NLRP3 inflammasome, a multiprotein complex which controls the processing and production of IL-1β and IL-18. Contrary to our expectations, compound C significantly inhibited NLRP3 inflammasome activation (P < 0.05). Additionally, this effect was reproduced in AMPK siRNA transfected THP-1 cells, indicating that compound C exerts this function through an AMPK-independent mechanism. Mechanistically, we found compound C significantly suppresses mitochondria generated reactive oxygen species (ROS), which is required for NLRP3 inflammasome activation.

In conclusion, we demonstrate for the first time that, compound C significantly inhibited NLRP3 inflammasome in an AMPK-independent manner, suggesting NLRP3 inflammasome is to be the novel target of compound C. And we inferred that compound C inhibit NLRP3 inflammasome may through the suppression of mitochondrial ROS production. These findings offer unique insight into compound C as a novel pharmacological agent with significant therapeutic potential in NLRP3 inflammasome-related disorders including obesity, insulin resistance and T2D. Further studies are needed to identify the effect of compound C on these diseases in vitro.

Disclosure

F. Wang: None. W. Yang: None. L. Wang: None. Y. Liu: None. Z. Mo: None.
The Effect of Metformin and Dapagliflozin on Epicardial Adipose Tissue in Prediabetes and Type 2 Diabetic Patients
Authors: AL-TALABANY SHAWEEN , WEIR-MCCALL JONATHAN , MOHAN MOHAPRADEEP , SINGH JAGDEEP S. , MORDI IFY , GANDY STEPHEN J. , KHAN FAISEL , CHOY ANNAMARIA , HOUSTON JOHN G. , PEARSON EWAN , GEORGE JACOB , STRUTHERS ALLAN D. , LANG CHIM C.
Published: June 2018

Background: Epicardial adipose tissue (EAT) is an emerging cardio-metabolic risk factor that has been shown to correlate with adverse cardiovascular outcomes through potential local and systemic effects. Consequently, EAT has been proposed as a therapeutic target. The biguanide, metformin, and Sodium-glucose Cotransporter-2 inhibitors have been reported to improve cardiovascular outcomes. We have investigated the effects of both metformin and dapagliflozin, on EAT in patients with prediabetes and type 2 diabetes respectively.

Methods: EAT area measurements were performed blindly on cine 4 chamber views during the end diastolic phase of the cardiac cycle at baseline and at the end of study treatment using CMR scans in patients that participated in two randomized double-blinded placebo controlled trials: (1) MET-REMODEL (ClinicalTrials.gov. NCT02226510) (n=68 patients, mean age 65 ± 8 y; mean BMI 31.9 ± 3.6 kg/m²) with prediabetes and /or insulin resistance who received either metformin (2g /day) or placebo for 12 months and (2) REFORM (ClinicalTrial.gov NCT02397421) (n=56 patients, mean age 67 ± 7 y; mean BMI 32.5± 5.3 kg/m²) with chronic heart failure and type 2 diabetes who received either dapagliflozin (10mg/day) or placebo for 12 months respectively.

Results: Metformin treatment in the METREMODEL trial reduced body weight significantly by 4.2kgs (p=0.001).but did not reduce EAT area (metformin -0.1 ± 3.8 cm² vs. placebo -0.5 ± 2.9 cm² p= 0.7). In the REFORM trial, dapagliflozin reduced body weight significantly by -1.9 kg (p= 0.054) with no significant reduction in EAT area (dapagliflozin -1.00 ± 3.6 cm² vs. placebo -0.7 ± 3.1 p=0.8).

Conclusion: In prediabetes and type 2 diabetes, we found that metformin and dapagliflozin treatment resulted in significant weight loss but had no significant effect on EAT. Our findings suggest that the reported cardiovascular benefits of these two diabetic therapies are not likely to be mediated by effects on EAT.

Disclosure

S. Al-Talabany: None. J. Weir-McCall: None. M. Mohan: None. J.S. Singh: None. I. Mordi: None. S.J. Gandy: None. F. Khan: None. A. Choy: None. J.G. Houston: None. E. Pearson: Speaker's Bureau; Self; Eli Lilly and Company. J. George: None. A.D. Struthers: Research Support; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca. C.C. Lang: None.
Physician Feedback on the Quality of Diabetes Care—An Important Strategy with Moderate Impact
Authors: ZAREI PARMIDA , HAM SANDRA A. , NATHAN AVIVA , SEPULVEDA LUISA , SARGIS ROBERT M. , QUINN MICHAEL T. , HUANG ELBERT , LAITEERAPONG NEDA
Published: June 2018

Background: Physicians often receive feedback on their quality of diabetes care. However, it is unclear what performance measures (e.g., blood pressure targets) are used in this feedback, whether these measures correspond with diabetes care guideline recommendations, and whether feedback affects their clinical practice.

Methods: In 2016, we mailed a national survey to 1,200 U.S. primary care physicians and endocrinologists. We excluded physicians who did not provide longitudinal care to patients with type 2 diabetes (adjusted response rate, 41% (N=356)). Physicians were asked to report whether they received feedback on their quality of diabetes care, the hemoglobin A1c (A1C), cholesterol, and blood pressure (BP) goals they were encouraged to reach, and the usual A1C, cholesterol, and BP goals they recommend to their patients.

Results: In total, 56% of physicians reported receiving feedback. Among those who received feedback, the most frequent goals were an A1C<7.0% (51%), LDL<100 mg/dL (58%), and BP<130/80 mmHg (37%). In clinical practice, physicians frequently used goals that did not correspond with performance measure goals (A1C, 53%; cholesterol, 51%; systolic BP, 45%; diastolic BP, 47%). Only 22% of physicians reported that receiving feedback on their quality of diabetes care affected their treatment decisions “most of the time”/“almost always,” compared to 40% and 38% reporting “sometimes” and “never”/“rarely,” respectively.

Conclusions: Many U.S. physicians are being measured on their quality of diabetes care using performance measures that are inconsistent with diabetes care guidelines and national quality standards. Further, many physicians may not be strongly influenced by diabetes performance measurement. These discrepancies suggest that the impact of physician feedback on quality of diabetes care may be limited.

Disclosure

P. Zarei: None. S.A. Ham: None. A. Nathan: None. L. Sepulveda: None. R.M. Sargis: Advisory Panel; Self; CVS/Caremark. M.T. Quinn: None. E. Huang: None. N. Laiteerapong: None.
Cost as the Main Driver of T2D Treatment Patterns—Lessons from Real-World Data and Physician Focus Groups
Authors: WU SZE-JUNG , RAVAL AMIT D. , STEPHENSON JUDITH J. , PENG XIAOMEI , WEISMAN HARRY , FARIES DOUGLAS E.
Published: June 2018

This two-phased study consists of a decision tree model built from real-world claims data to determine factors related to physician choice of 2nd line therapy for type 2 diabetes (T2D) patients after metformin, followed by a physician focus group study to validate results of the data-driven approach. We identified 58patients in the U.S. who initiated sulfonylurea (SU), DPP-4 inhibitor, GLP-1-RA, or insulin after metformin during 2012-2014 from the HealthCore Integrated Research Database. Claims-derived factors, such as demographics, clinical characteristics, and prior healthcare utilization and costs, were selected from a classification and regression tree (CART) model that minimized classification errors. Of factors most predictive of 2nd line drug assignment, patients’ cost sharing for antidiabetic drugs (Relative Importance, RI=1) was 3 times more important than HbA1c level (RI=0.3), and 10 times more important than age, comorbidity, and kidney status (GFR) (RI=0.1). SU was most likely to be assigned to patients with lowest drug spending, moderate HbA1c control, abnormal kidney function, or no comorbid conditions. Similar themes were identified from the four physician focus groups (consisting of 8 endocrinologists and 10 PCPs in NYC and LA) and supported the findings. This study identified a gap in diabetes care where patients often receive SU due to lack of access to other treatment options.

Disclosure

S. Wu: None. A.D. Raval: None. J.J. Stephenson: None. X. Peng: Employee; Self; Eli Lilly and Company. H. Weisman: Employee; Self; Anthem, Inc. D.E. Faries: Employee; Self; Eli Lilly and Company.
Embedding Diabetes Expertise within Primary Care
Authors: CLORE JOHN N. , THURBY-HAY LINDA
Published: June 2018

Efficient delivery of care within the primary care setting is critical to address the needs of the vast majority of individuals living with diabetes. And yet, as diabetes care has become more complex, primary care providers often find themselves insufficiently prepared and capacity for referral to subspecialty care is lacking. We have designed and implemented a novel program within primary care practices in a large healthcare system. Practices were engaged in a model whereby an interprofessional diabetes team was embedded for 6 months. The team was composed of an endocrinologist, CNS, PharmD and RD. The practices were oriented to the program and questions and concerns addressed. All diabetes metrics were pended as a part of the rooming process. Patient-centered care was delivered in one-on-one visits with the entire team as well as in shared medical appointments. Providers and staff were provided didactic and experiential instruction in practical strategies to diabetes care to ensure that diabetes self-management training (DSMT) was available within the practice once the 6 month program was completed.

Results: 157 patients with type 2 diabetes participated in the initial program. Age (58.4±11.8 years), gender (82F/75M), and HbA1c (9.8±2.0%) characterized the selected population. 40 individuals did not return for a second visit so data were analyzed for those completing at least 2 visits. Over the course of the program, HbA1c fell from 10.3±0.02 to 8.2±0.01%*; adherence to diabetes metrics increased for foot exams (31.2 to 98.1% *), microalbumin (61.1 to 87.2%*) and eye exams (25.5 to 47.1%*, * p<0.01 all comparisons) . All patients were returned to their primary care provider for long term care after completion of the program or once target HbA1c (<7.0%) had been achieved.

Conclusion: Embedding an interprofessional diabetes team within a primary care setting 1) significantly improves HbA1c and overall diabetes care; 2) provides sustainable DSMT services for primary care providers; and 3) focuses greater attention on diabetes.

Disclosure

J.N. Clore: None. L. Thurby-Hay: None.
Characterization of Patients Requiring High-Dose Insulin Infusion for the Management of Hyperglycemia
Authors: FELEKE AFOMIA A. , FULLER RACHAEL C. , ISMAIL REEM , CADIZ MEGAN
Published: June 2018

There are several validated insulin infusion protocols to help guide intravenous (IV) insulin dose titrations. However, when continued upward titration of insulin infusion is required to achieve glycemic control, little is known to guide how high the infusion rate can be increased without compromising safety and improving efficacy. The purpose of this study was to characterize patients requiring high-dose insulin infusions (rates >20 units/hour) for the management of hyperglycemia and determine the incidence at our institution. A retrospective chart review of all patients aged 18 years or older who received IV insulin infusion between 01/01/2016 and 07/31/2017 at Beaumont Hospital, MI resulted in 82 patients (2.9%) who received high-dose insulin infusion for the management of hyperglycemia. Average age was 62 years old and majority were Caucasian males. Most patients had hyperglycemia associated with risk factors such as: history of type 2 diabetes (71%), obesity (median body mass index (BMI) was 33.9 kg/m2), critical illness (89%), many were surgical patients (>50%), and a large proportion received vasopressors (79%) and corticosteroids (36%). The highest infusion rate observed was 80 units/hour, with a median infusion rate of 6.5 units/hour. Hypoglycemia (BG ≤ 70 mg/dl) was reported in 29% of patients and 11% had recurrent hypoglycemic episodes. Our findings suggest that the overall need for high-dose insulin infusion rates is very low. However, the incidence of hypoglycemia in these patients was substantially high and therefore concerning. Insulin is a high-alert medication requiring implementation of appropriate safety measures to prevent errors and careful investigation is warranted when used in high-doses. We recommend an insulin infusion “time-out” to assess the infusion site, the IV line and insulin bag before exceeding 20 units/hour. Furthermore, institutional policies for soft- and hard-maximum infusion parameters should be established to conserve use.

Disclosure

A.A. Feleke: None. R.C. Fuller: None. R. Ismail: None. M. Cadiz: None.
Old but (Unfortunately) Not Forgotten—The Alarming Use of Outdated Sulfonylureas (InHypo-DM Study)
Authors: AU NATALIE H. , RATZKI-LEEWING ALEXANDRIA , RYAN BRIDGET L. , MEQUANINT SELAM , BLACK JASON E. , REICHERT SONJA M. , BROWN JUDITH B. , HARRIS STEWART
Published: June 2018

While sulfonylureas (SUs) are known to induce hypoglycemia, their low cost and ease-of-use has made them a mainstay therapy for T2DM. Second-generation SUs (SGSUs), compared to first-generation SUs (FGSUs), have been successful at reducing these events. Pragmatic evidence substantiating this association remains limited; this study leverages data from the population-based InHypo-DM study to describe the real-world patterns of SU use and impact on hypoglycemia incidence in Canada. A validated questionnaire (InHypo-DMPQ) was administered online to a nationwide panel consisting of adults with SU-treated T2DM. Questions related to respondents’ past hypoglycemia events, as well as socio-demographic and clinical traits. Negative binomial regression (NBR) was used to test the effect of SU type (FGSUs (chlorpropamide/tolbutamide) vs. SGSUs (glyburide/gliclazide/glimepiride)) on the annual rate of any hypoglycemia. A directed acyclic graph was constructed to identify the adjustment set. Of the 255 adults with SU-treated T2DM (56% male, mean age: 53.1 (SD: 14.4) years), 10.6% were on FGSUs (chlorpropamide: 7.5%, tolbutamide: 3.1%) and 89.5% on SGSUs (glyburide: 27.5%, gliclazide: 54.9%, glimepiride: 7.1%). Annualized crude event frequencies revealed that those on FGSUs, vs. SGSUs, were 1.57 times as likely to have ≥1 event; this group also experienced an average of 2.70 more events/person-year. Based on the NBR, FGSUs vs. SGSUs was associated with a 2.76 (95% CI: 1.07-7.11, p=0.035) factor increase in the rate of hypoglycemia, adjusting for drug coverage, T2DM duration, income, and clinician type. These results confirm that FGSUs induce a dangerous, real-world risk for hypoglycemia. It exposes a worrying trend for the continued use of outdated SUs for T2DM, despite the availability of safer alternatives in Canada. Our study serves as a pressing call-to-action to ensure that clinicians provide the safest and most effective therapeutic management for patients with T2DM.

Disclosure

N.H. Au: None. A. Ratzki-Leewing: None. B.L. Ryan: None. S. Mequanint: None. J.E. Black: None. S.M. Reichert: Other Relationship; Self; Novo Nordisk Inc., Sanofi, Abbott, AstraZeneca. Advisory Panel; Self; Servier. Speaker's Bureau; Self; Eli Lilly and Company. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Merck & Co., Inc., Janssen Pharmaceuticals, Inc.. J.B. Brown: None. S. Harris: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, Merck, AstraZeneca, Amgen Inc., Lilly/Boehringer Ingelheim, Abbott, Janssen. Consultant; Self; Novo Nordisk A/S, Sanofi, Merck, AstraZeneca, Lilly/Boehringer Ingelheim, Abbott, Janssen. Research Support; Self; Novo Nordisk A/S, Sanofi, Merck, Abbott, AstraZeneca, Janssen. Other Relationship; Self; CIHR, CDA, The Lawson Foundation.
Risk Factors for Hospital Readmission following Implementation of a Diabetic Ketoacidosis (DKA) Power Plan
Authors: KARAJGIKAR NEHA , DONIHI AMY , SALATA ROSE A. , CODARIO RONALD , ACHARYA RUNA , MANROA POOJA , KORYTKOWSKI MARY T.
Published: June 2018

Patients admitted to the hospital with DKA are at high-risk for readmission. We have previously demonstrated that implementation of a DKA PowerPlan (PP) that guides IV insulin dosing following acute management and transition to SC insulin reduces the frequency of recurrent DKA and rebound hyperglycemia during the index hospitalization. The purpose of this study was to determine whether the DKA PP reduces all cause and diabetes-related (recurrent DKA, hyperglycemia, hypoglycemia) hospital readmissions at 30 days and 1 year following an index hospitalization, as well to examine the contribution of high risk co-morbidities (psychiatric illness and/or history of alcohol/polysubstance abuse) associated with readmission risk in this group of patients. Retrospective chart review was performed for patients admitted with primary diagnosis of DKA prior to (pre-PP, n=60) and following DKA PP implementation (Post-PP, n=60). The groups were similar in age (Pre- vs. Post-PP: 38 ± 13.5 vs. 40 ± 16.6), BMI (26 ± 6.7 vs. 27 ± 7 kg/m2), gender (%Male: 38% vs. 48%), HbA1c (11.7 ± 2.4 vs. 11.3 ± 2.9%), admission BG (560 vs. 615 mg/dl) and anion gap (AG) (27.6 vs. 27.4), but differed in the prevalence of comorbidities which were higher in the pre-PP group (58 vs. 40%, p = 0.045). All cause readmissions were similar at 30 days (Pre vs. Post-PP: 1.4 ± 0.8 vs. 1.2 ± 0.4) but were lower at 1 year in the post-PP group (5.2 ± 4.7 vs. 3.5 ± 2.7, p = 0.07). Patients with co-morbidities in the post-PP group had lower all-cause (p = 0.023) but not diabetes related readmissions at 1 year, compared to patients with co-morbidities in the pre-PP group.

In summary, these findings suggest that a DKA PP may be associated with a reduction in all cause hospital readmission in high risk patients with underlying psychiatric or substance abuse disorders. These results emphasize the need to identify and address patient specific factors that contribute to readmission in this high risk group.

Disclosure

N. Karajgikar: None. A. Donihi: None. R.A. Salata: None. R. Codario: None. R. Acharya: None. P. Manroa: None. M.T. Korytkowski: Advisory Panel; Self; Novo Nordisk Inc.. Other Relationship; Self; JAEB Center For Health Research.
Patient-Reported Outcome Labeling for Antidiabetic Agents Approved in the United States, 2011–2017
Authors: ZETTLER MARJORIE E. , SANDOVAL RENATO
Published: June 2018

Background: Patient-reported outcomes (PROs), defined as any report on the status of a patient’s health condition that comes directly from the patient without interpretation by any other party, have been the subject of increased focus during drug development. The U.S. FDA issued final guidance on the use of PRO measures to support labeling claims in 2009, as a means of integrating patients’ experience. Diabetes is a chronic condition requiring patient self-management. Achieving optimal glycemic control necessitates patient engagement and commitment to treatment adherence. Given the significant patient burden, data regarding quality of life (QoL) and treatment satisfaction may be important to patients and clinicians in considering treatment options. This paper evaluates the incorporation of PROs into labeling for antidiabetic agents approved by the FDA between 2011 and 2017.

Methods: The FDA’s Novel New Drug Summaries (2011-2017) were reviewed to identify antidiabetic agents. Drug approval packages and product labels were accessed via the Drugs@FDA database and analyzed for PRO endpoints, measures, and labeling claims. Clinical trial designs were ascertained via the ClinicalTrials.gov website.

Results: Of 250 novel drugs approved by the FDA between 2011 and 2017, 11 (4.4%) were for antidiabetic indications. None of the 11 incorporated PROs in their labeling. However, 5 of the 11 (45.5%) collected QoL or treatment satisfaction data as a secondary or tertiary endpoint in at least 1 of the trials supporting approval. Measures included the EQ-5D, SF-36, and the Diabetes Treatment Satisfaction Questionnaire.

Conclusions: Although nearly half of all antidiabetic agents approved in the past 7 years assessed PROs during drug development, none acquired PRO label claims. As diabetes can have a significant impact on patients’ day-to-day functioning and QoL, failure to integrate PROs into labeling may represent a missed opportunity for patients, clinicians, and industry sponsors.

Disclosure

M.E. Zettler: None. R. Sandoval: None.
Optimization of Blood Pressure Control, Metabolic Parameters, and Target Organs Protection with Perindopril + Indapamide Fixed Combination in Hypertensive Patients with Obesity and Prediabetes
Authors: NEDOGODA SERGEY V. , BARYKINA IRINA , SALASYUK ALLA , SMIRNOVA VIKTORIA O. , POPOVA EKATERINA
Published: June 2018

The study objective was to evaluate the ability of the fixed combination (FC) of perindopril + indapamide (P+I) to reduce insulin resistance and low intensive noninfectious inflammation as well as to improve arterial elasticity in patients with hypertension, obesity and prediabetes on previous successful antihypertensive therapy with losartan + hydrochlorothiazide (L+HTZ) 100/12.5 mg. A 12-week open-label study included 50 patients (age 54.8 ± 6.6 years, body mass index (BMI) 32.5 ± 3.2 kg/m2). All patients underwent a 24-hour ambulatory blood pressure monitoring, applanation tonometry (assessment of augmentation index (AI), central blood pressure (CBP)), pulse wave velocity (PWV) measurement and laboratory investigations (lipid profile, fasting glucose, the homeostatic model assessment (HOMA) index, homocysteine, leptin, adiponectin, high-sensitive C-reactive protein (hsCRP)).

Results: The switch of patients from L+HTZ to a FC of P+I resulted in an additional decrease in systolic BP and diastolic BP by 3.9% and 5.4%, respectively (p <0.05). Significant decrease in the BP load and variability was observed. PWV, AI, central SBP, vascular age decreased by 2.2%, 9.4%, 2.1% and 6.0% (p <0.05 for all). Fasting glycemia, insulinemia, and HOMA index decreased by 4.9%, 6.0% and 10.3% (p <0.05 for all). Triglycerides (TG) decreased by 13.5% (p<0.05) and high density lipoproteins (HDL) increased by 9.6% (p <0.05). Leptin and hsCRP levels decreased by 14.4% and 11.0%, adiponectin increased by 9.9% (p <0.05 for all). Clinically significant results were obtained in weight and BMI reduction on 6,0% and 1,2%.

Conclusions: FC of P+I is superior to the L+HTZ in BP control, improvement of arterial elasticity and promotes a decrease in BMI, suppression of insulin-resistance and low intensive noninfectious inflammation in patients with hypertension, associated obesity and prediabetes.

Disclosure

S.V. Nedogoda: None. I. Barykina: None. A. Salasyuk: None. V.O. Smirnova: None. E. Popova: None.
Different Sampling and Modeling Strategies Affect Analyses of Readmission Risk among Diabetes Patients
Authors: ZHAO HUAQING , TANNER SAMUEL , GOLDEN SHERITA , FISHER SUSAN G. , RUBIN DANIEL J.
Published: June 2018

Readmissions are an undesirable outcome for which hospitals are being held accountable. Despite a growing literature, there is little consensus on the optimal method of sampling hospitalizations for calculating readmission rate and modeling methods for analyzing risk factors.

We compared 2 sampling and 3 multivariable predictive modeling strategies in a retrospective cohort of adult patients with diabetes discharged from an academic medical center between 2004 and 2012. Diabetes was defined by ICD-9-CM code 250 or documentation of taking a diabetes-specific medication. The outcome for all models was all-cause readmission within 30 days of discharge (30d readmission). Models were built on 46 sociodemographic, clinical and administrative variables.

With sampling only the first discharge per patient (N=17,284), the 30d readmission rate was 10.2% vs. 20.3% for all discharges per patient (N=44,203). Model performance varied by sampling and modeling strategy. Logistic regression (LR) without generalized estimating equations (GEE) using all discharges had the highest overall performance.

Sampling only the first discharge per patient underestimates the readmission rate and is associated with misleading measures of model performance. LR without GEE may yield overly optimistic measures of model performance. Because commonly used approaches may produce misleading results, consensus is needed.

Performance of logistic regression models to predict all-cause 30d readmission.Model and Sampling StrategyPerformance Measurement(95% CI)First Discharges without GEEAll Discharges without GEEAll Discharges with GEEAll Discharges with weighted GEEArea Under ROC Curve (C-statistic)0.821 (0.806, 0.835)0.811 (0.803, 0.818)0.803 (0.796, 0.811)0.791 (0.783, 0.798)Correlation Coefficient0.366 (0.345, 0.386)0.450 (0.438, 0.462)0.437 (0.425, 0.449)0.415 (0.403, 0.427)Coefficient of Determination, %14.96 (14.06, 15.86)21.00 (20.39, 21.61)18.40 (17.85, 18.96)15.83 (15.32, 16.34)Brier Score0.080 (0.075, 0.084)0.129 (0.126, 0.132)0.132 (0.128, 0.135)0.135 (0.132, 0.139)GEE=generalized estimating equations with an exchangeable correlation structure

Disclosure

H. Zhao: None. S. Tanner: None. S. Golden: None. S.G. Fisher: None. D.J. Rubin: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc..
Safe Ramadan Fasting Is Possible for Subjects with Poorly Controlled Type 2 Diabetes Mellitus
Authors: CHEE YING JIE , NG SHONDA , KWEK KEVIN J. , ABDUL SHAKOOR SHAIKH ABDUL KADER
Published: June 2018

Background: Poorly controlled diabetic patients (PCDP) are at increased risk during Ramadan fasting. International guidelines caution against Ramadan fasting among PCDP. However, many PCDP fast against medical advice. To our knowledge, no studies have specifically addressed the safety of Ramadan fasting by PCDP and hence, we aimed to study this.

Methods: Adults with type 2 DM attending a tertiary hospital’s Endocrinology clinic, who had fasted for at least 2 weeks in Ramadan, were evaluated. The safety and biochemical parameters were compared between the 2 groups based on pre- Ramadan glycemic control-Group 1 (HbA1c <9%) and group 2 (PCDP, HbA1C ≥ 9%).

Results: We evaluated 139 Ramadan fasts by 113 participant-70 fasts were by PCDP, of which 26 were studied twice (2016 and 2017). The results are summarised below.

Hypoglycemia was more frequent in group 1 compared to PCDP (p = 0.017). However, there was no significant difference in other safety parameters between both groups. None of the PCDP suffered from hyperglycemia related complications.

Conclusion: Most of the PCDP in our cohort were able to fast safely during Ramadan. Our findings need to be confirmed with prospective studies in different ethnic and geographic settings. PCDP with no prior hyperglycemic crisis can fast during Ramadan safely if specific education is offered and may even harness the beneficial effects of Ramadan such as metabolic memory.

CharacteristicsGroup 1 (N = 69; mean HbA1c 7.8%)Group 2 (N = 70; mean HbA1c 10.8%)No. of days fasted (Mean)26.927.7Polydipsia (N)813Hypoglycemia (N)149Hyperglycemia (capillary blood glucose > 16 mmol/L, N)912Need to break fast due to hypoglycemia (N)149Need to break fast due to hyperglycemia (N)00Hyperglycemic crisis/ DM related hospital admissions (N)00Mean HbA1c change (%) pre and post-Ramadan+ 0.18- 0.28

Disclosure

Y. Chee: None. S. Ng: None. K.J. Kwek: None. S. Abdul Shakoor: None.
Awareness of Preconception Care for Women with Type 1 Diabetes—From Family Members' Perspective
Authors: WANG CHAOFAN , LUO SIHUI , ZHENG XUEYING , HU XILING , YAN JINHUA , GUO YAN , XIONG SHANSHAN , YANG DAIZHI , QIU LILING , YAO BIN , WENG JIANPING
Published: June 2018

Background: Preconception care (PCC) can improve pregnancy outcomes in women with type 1 diabetes (T1D). Little was known on current status of PCC in China. We aimed to investigate the current practice and attitude about PCC from the perspective of the patients’ family members.

Method: We conducted in-depth interviews with family members of T1D women. By purposive sampling we included their husbands, parents and parents-in-law. Transcripts of the interviews were coded into themes by 3 researchers via thematic framework method and analyzed in NVIVO 11. The recruitment ended when no new themes emerged.

Results: We interviewed 16 family members of 14 T1D women (10 husbands, 4 mothers, 1 father and 1 mother-in-law) and rendered 9 themes. 1. Knowledge of T1D and PCC: most demonstrated little knowledge of both due to lack of education. 2. Content of PCC: dietary guidance and glycaemic control were most required. 3. Timing of starting PCC: adulthood was most recommended while the rest adolescence. 4. Approach of PCC: internet and on-site consultation were well recognized while tutorials and materials as supplements. 5. Multi-disciplinary cooperation: most suggested that endocrinology professionals take the main responsibility of PCC with other professionals. 6. Attitude on pregnancy: most thought women had the obligation of childbearing while the rest showed respect to the women’s own decision. 7. Concern: worries on complications during pregnancy, inheritance of T1D, social discrimination and economic cost. 8. Doctor-patient communication: most considered the information and consultation time provided by doctors were inadequate. 9. Peer support: peer communication was mainly supported in order to convey experience and confidence while the minority opposed it fearing the spread of negative information.

Conclusions: Family members of T1D women scarcely owned knowledge of PCC and suffered various concerns. Their participation in PCC should be encouraged and mental support should be enhanced.

Disclosure

C. Wang: None. S. Luo: None. X. Zheng: None. X. Hu: None. J. Yan: None. Y. Guo: None. S. Xiong: None. D. Yang: None. L. Qiu: None. B. Yao: None. J. Weng: None.