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Ralph defronzo

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https://www.readbyqxmd.com/read/27871675/glucagon-like-peptide-1-and-the-central-peripheral-nervous-system-crosstalk-in-diabetes
#1
REVIEW
Giovanna Muscogiuri, Ralph A DeFronzo, Amalia Gastaldelli, Jens J Holst
Glucagon-like peptide-1 (GLP-1) is released in response to meals and exerts important roles in the maintenance of normal glucose homeostasis. GLP-1 is also important in the regulation of neurologic and cognitive functions. These actions are mediated via neurons in the nucleus of the solitary tract that project to multiple regions expressing GLP-1 receptors (GLP-1Rs). Treatment with GLP-1R agonists (GLP-1-RAs) reduces ischemia-induced hyperactivity, oxidative stress, neuronal damage and apoptosis, cerebral infarct volume, and neurologic damage, after cerebral ischemia, in experimental models...
October 27, 2016: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/27639082/exenatide-improves-both-hepatic-and-adipose-tissue-insulin-resistance-a-dynamic-pet-study
#2
Amalia Gastaldelli, Melania Gaggini, Giuseppe Daniele, Demetrio Ciociaro, Eugenio Cersosimo, Devjit Tripathy, Curtis Triplitt, Peter Fox, Nicolas Musi, Ralph DeFronzo, Patricia Iozzo
: GLP-1 receptor agonists (GLP-1-RAs) act on multiple tissues, in addition to the pancreas. Recent studies suggest that GLP-1-RAs act on liver and adipose tissue to reduce insulin resistance (IR). Thus, we evaluated the acute effects of exenatide (EX) on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake. 15 male subjects (age=56±8 y, BMI=29±1 kg/m(2) , A1c=5.7±0.1%) were studied on two occasions, with a double blind subcutaneous injection of exenatide (5 mcg) or placebo (PLC) 30 min before a 75-gram oral glucose tolerance test (OGTT)...
September 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27624579/islet-amyloid-polypeptide-response-to-maximal-hyperglycemia-and-arginine-is-altered-in-impaired-glucose-tolerance-and-type-2-diabetes-mellitus
#3
Rodolfo Guardado-Mendoza, Alberto O Chávez, Lilia M Jiménez-Ceja, Andrea Hansis-Diarte, Ralph A DeFronzo, Franco Folli, Devjit Tripathy
AIMS: Pancreatic islet amyloid deposition is a characteristic feature of type 2 diabetes mellitus (T2DM). Islet amyloid polypeptide (IAPP) is co-secreted with insulin, but its secretion profile and relationship to insulin and C-peptide in response to glucose and non-glucose stimuli has not been clearly defined. METHODS: Forty subjects (13 NGT, 12 IGT and 15 T2DM) participated in an OGTT and two-step hyperglycemic (225 and 400 mg/dl) clamp (80 min/step) followed by an IV arginine bolus...
September 13, 2016: Acta Diabetologica
https://www.readbyqxmd.com/read/27585671/pioglitazone-is-equally-effective-for-diabetes-prevention-in-older-versus-younger-adults-with-impaired-glucose-tolerance
#4
Sara E Espinoza, Chen-Pin Wang, Devjit Tripathy, Stephen C Clement, Dawn C Schwenke, Mary Ann Banerji, George A Bray, Thomas A Buchanan, Robert R Henry, Abbas E Kitabchi, Sunder Mudaliar, Frankie B Stentz, Peter D Reaven, Ralph A DeFronzo, Nicolas Musi
To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA...
September 1, 2016: Age (2005-)
https://www.readbyqxmd.com/read/27561923/dapagliflozin-enhances-fat-oxidation-and-ketone-production-in-patients-with-type-2-diabetes
#5
Giuseppe Daniele, Juan Xiong, Carolina Solis-Herrera, Aurora Merovci, Roy Eldor, Devjit Tripathy, Ralph A DeFronzo, Luke Norton, Muhammad Abdul-Ghani
OBJECTIVE: Insulin resistance is associated with mitochondrial dysfunction and decreased ATP synthesis. Treatment of individuals with type 2 diabetes mellitus (T2DM) with sodium-glucose transporter 2 inhibitors (SGLT2i) improves insulin sensitivity. However, recent reports have demonstrated development of ketoacidosis in subjects with T2DM treated with SGLT2i. The current study examined the effect of improved insulin sensitivity with dapagliflozin on 1) mitochondrial ATP synthesis and 2) substrate oxidation rates and ketone production...
November 2016: Diabetes Care
https://www.readbyqxmd.com/read/27489336/discordance-between-central-brain-and-pancreatic-action-of-exenatide-in-lean-and-obese-subjects
#6
Roy Eldor, Giuseppe Daniele, Claudia Huerta, Mariam Al-Atrash, John Adams, Ralph DeFronzo, Timothy Duong, John Lancaster, Mahmoud Zirie, Amin Jayyousi, Muhammad Abdul-Ghani
OBJECTIVE: This study examined the effect of exenatide on brain activity measured by functional (f)MRI and on insulin secretion in lean and obese normal-glucose-tolerant individuals. RESEARCH DESIGN AND METHODS: The brain fMRI signal in response to high-calorie-content food pictures was measured with and without intravenous exenatide infusion in 10 lean and 10 obese healthy volunteers. Insulin secretion was measured with a two-step (+100 and +200 mg/dL) hyperglycemic clamp with exenatide and with saline infusion...
October 2016: Diabetes Care
https://www.readbyqxmd.com/read/27440828/positioning-sglt2-inhibitors-incretin-based-therapies-in-the-treatment-algorithm
#7
REVIEW
John P H Wilding, Surya Panicker Rajeev, Ralph A DeFronzo
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the most recent addition to the therapeutic options available for the treatment of type 2 diabetes and became available after the introduction of incretin-based therapies, dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These agents have potential advantages with regard to their weight loss-promoting effect, low risk of hypoglycemia, reduction in blood pressure, and reduction in cardiovascular events in high-risk patients (with empagliflozin)...
August 2016: Diabetes Care
https://www.readbyqxmd.com/read/27398621/the-genetic-architecture-of-type-2-diabetes
#8
Christian Fuchsberger, Jason Flannick, Tanya M Teslovich, Anubha Mahajan, Vineeta Agarwala, Kyle J Gaulton, Clement Ma, Pierre Fontanillas, Loukas Moutsianas, Davis J McCarthy, Manuel A Rivas, John R B Perry, Xueling Sim, Thomas W Blackwell, Neil R Robertson, N William Rayner, Pablo Cingolani, Adam E Locke, Juan Fernandez Tajes, Heather M Highland, Josee Dupuis, Peter S Chines, Cecilia M Lindgren, Christopher Hartl, Anne U Jackson, Han Chen, Jeroen R Huyghe, Martijn van de Bunt, Richard D Pearson, Ashish Kumar, Martina Müller-Nurasyid, Niels Grarup, Heather M Stringham, Eric R Gamazon, Jaehoon Lee, Yuhui Chen, Robert A Scott, Jennifer E Below, Peng Chen, Jinyan Huang, Min Jin Go, Michael L Stitzel, Dorota Pasko, Stephen C J Parker, Tibor V Varga, Todd Green, Nicola L Beer, Aaron G Day-Williams, Teresa Ferreira, Tasha Fingerlin, Momoko Horikoshi, Cheng Hu, Iksoo Huh, Mohammad Kamran Ikram, Bong-Jo Kim, Yongkang Kim, Young Jin Kim, Min-Seok Kwon, Juyoung Lee, Selyeong Lee, Keng-Han Lin, Taylor J Maxwell, Yoshihiko Nagai, Xu Wang, Ryan P Welch, Joon Yoon, Weihua Zhang, Nir Barzilai, Benjamin F Voight, Bok-Ghee Han, Christopher P Jenkinson, Teemu Kuulasmaa, Johanna Kuusisto, Alisa Manning, Maggie C Y Ng, Nicholette D Palmer, Beverley Balkau, Alena Stancáková, Hanna E Abboud, Heiner Boeing, Vilmantas Giedraitis, Dorairaj Prabhakaran, Omri Gottesman, James Scott, Jason Carey, Phoenix Kwan, George Grant, Joshua D Smith, Benjamin M Neale, Shaun Purcell, Adam S Butterworth, Joanna M M Howson, Heung Man Lee, Yingchang Lu, Soo-Heon Kwak, Wei Zhao, John Danesh, Vincent K L Lam, Kyong Soo Park, Danish Saleheen, Wing Yee So, Claudia H T Tam, Uzma Afzal, David Aguilar, Rector Arya, Tin Aung, Edmund Chan, Carmen Navarro, Ching-Yu Cheng, Domenico Palli, Adolfo Correa, Joanne E Curran, Denis Rybin, Vidya S Farook, Sharon P Fowler, Barry I Freedman, Michael Griswold, Daniel Esten Hale, Pamela J Hicks, Chiea-Chuen Khor, Satish Kumar, Benjamin Lehne, Dorothée Thuillier, Wei Yen Lim, Jianjun Liu, Yvonne T van der Schouw, Marie Loh, Solomon K Musani, Sobha Puppala, William R Scott, Loïc Yengo, Sian-Tsung Tan, Herman A Taylor, Farook Thameem, Gregory Wilson, Tien Yin Wong, Pål Rasmus Njølstad, Jonathan C Levy, Massimo Mangino, Lori L Bonnycastle, Thomas Schwarzmayr, João Fadista, Gabriela L Surdulescu, Christian Herder, Christopher J Groves, Thomas Wieland, Jette Bork-Jensen, Ivan Brandslund, Cramer Christensen, Heikki A Koistinen, Alex S F Doney, Leena Kinnunen, Tõnu Esko, Andrew J Farmer, Liisa Hakaste, Dylan Hodgkiss, Jasmina Kravic, Valeriya Lyssenko, Mette Hollensted, Marit E Jørgensen, Torben Jørgensen, Claes Ladenvall, Johanne Marie Justesen, Annemari Käräjämäki, Jennifer Kriebel, Wolfgang Rathmann, Lars Lannfelt, Torsten Lauritzen, Narisu Narisu, Allan Linneberg, Olle Melander, Lili Milani, Matt Neville, Marju Orho-Melander, Lu Qi, Qibin Qi, Michael Roden, Olov Rolandsson, Amy Swift, Anders H Rosengren, Kathleen Stirrups, Andrew R Wood, Evelin Mihailov, Christine Blancher, Mauricio O Carneiro, Jared Maguire, Ryan Poplin, Khalid Shakir, Timothy Fennell, Mark DePristo, Martin Hrabé de Angelis, Panos Deloukas, Anette P Gjesing, Goo Jun, Peter Nilsson, Jacquelyn Murphy, Robert Onofrio, Barbara Thorand, Torben Hansen, Christa Meisinger, Frank B Hu, Bo Isomaa, Fredrik Karpe, Liming Liang, Annette Peters, Cornelia Huth, Stephen P O'Rahilly, Colin N A Palmer, Oluf Pedersen, Rainer Rauramaa, Jaakko Tuomilehto, Veikko Salomaa, Richard M Watanabe, Ann-Christine Syvänen, Richard N Bergman, Dwaipayan Bharadwaj, Erwin P Bottinger, Yoon Shin Cho, Giriraj R Chandak, Juliana C N Chan, Kee Seng Chia, Mark J Daly, Shah B Ebrahim, Claudia Langenberg, Paul Elliott, Kathleen A Jablonski, Donna M Lehman, Weiping Jia, Ronald C W Ma, Toni I Pollin, Manjinder Sandhu, Nikhil Tandon, Philippe Froguel, Inês Barroso, Yik Ying Teo, Eleftheria Zeggini, Ruth J F Loos, Kerrin S Small, Janina S Ried, Ralph A DeFronzo, Harald Grallert, Benjamin Glaser, Andres Metspalu, Nicholas J Wareham, Mark Walker, Eric Banks, Christian Gieger, Erik Ingelsson, Hae Kyung Im, Thomas Illig, Paul W Franks, Gemma Buck, Joseph Trakalo, David Buck, Inga Prokopenko, Reedik Mägi, Lars Lind, Yossi Farjoun, Katharine R Owen, Anna L Gloyn, Konstantin Strauch, Tiinamaija Tuomi, Jaspal Singh Kooner, Jong-Young Lee, Taesung Park, Peter Donnelly, Andrew D Morris, Andrew T Hattersley, Donald W Bowden, Francis S Collins, Gil Atzmon, John C Chambers, Timothy D Spector, Markku Laakso, Tim M Strom, Graeme I Bell, John Blangero, Ravindranath Duggirala, E Shyong Tai, Gilean McVean, Craig L Hanis, James G Wilson, Mark Seielstad, Timothy M Frayling, James B Meigs, Nancy J Cox, Rob Sladek, Eric S Lander, Stacey Gabriel, Noël P Burtt, Karen L Mohlke, Thomas Meitinger, Leif Groop, Goncalo Abecasis, Jose C Florez, Laura J Scott, Andrew P Morris, Hyun Min Kang, Michael Boehnke, David Altshuler, Mark I McCarthy
The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups...
August 4, 2016: Nature
https://www.readbyqxmd.com/read/27389083/prediabetes-and-risk-of-diabetes-and-associated-complications-impaired-fasting-glucose-versus-impaired-glucose-tolerance-does-it-matter
#9
Muhammad Abdul-Ghani, Ralph A DeFronzo, Amin Jayyousi
PURPOSE OF REVIEW: The purpose of this review is to summarize the distinct metabolic and pathophysiologic phenotype of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and the subsequent clinical implications with regard to future type 2 diabetes mellitus (T2DM) and cardiovascular risk. RECENT FINDINGS: Both IFG and IGT manifest the two core defects of T2DM, that is, insulin resistance and β-cell dysfunction. However, the site of insulin resistance and shape of β-cell dysfunction differ...
July 6, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/27311500/corrigendum-to-metformin-associated-lactic-acidosis-current-perspectives-on-causes-and-risk-metabolism-65-2016-20-29
#10
Ralph DeFronzo, G Alexander Fleming, Kim Chen, Thomas A Bicsak
No abstract text is available yet for this article.
September 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27216492/once-daily-delayed-release-metformin-lowers-plasma-glucose-and-enhances-fasting-and-postprandial-glp-1-and-pyy-results-from-two-randomised-trials
#11
Ralph A DeFronzo, John B Buse, Terri Kim, Colleen Burns, Sharon Skare, Alain Baron, Mark Fineman
AIMS/HYPOTHESIS: Delayed-release metformin (Metformin DR) was developed to maximise gut-based mechanisms of metformin action by targeting the drug to the ileum. Metformin DR was evaluated in two studies. Study 1 compared the bioavailability and effects on circulating glucose and gut hormones (glucagon-like peptide-1, peptide YY) of Metformin DR dosed twice-daily to twice-daily immediate-release metformin (Metformin IR). Study 2 compared the bioavailability and glycaemic effects of Metformin DR dosages of 1,000 mg once-daily in the morning, 1,000 mg once-daily in the evening, and 500 mg twice-daily...
August 2016: Diabetologia
https://www.readbyqxmd.com/read/27208375/sglt2-inhibitors-and-cardiovascular-risk-lessons-learned-from-the-empa-reg-outcome-study
#12
Muhammad Abdul-Ghani, Stefano Del Prato, Robert Chilton, Ralph A DeFronzo
Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD) risk. Thus, novel strategies to reduce CVD risk in T2DM patients are needed. The recently published BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) study demonstrated that in T2DM patients with high CVD risk empagliflozin reduced the primary major adverse cardiac event end point (CV death, nonfatal myocardial infarction, nonfatal stroke) by 14%...
May 2016: Diabetes Care
https://www.readbyqxmd.com/read/27114903/transcriptomics-in-type-2-diabetes-bridging-the-gap-between-genotype-and-phenotype
#13
Christopher P Jenkinson, Harald H H Göring, Rector Arya, John Blangero, Ravindranath Duggirala, Ralph A DeFronzo
Type 2 diabetes (T2D) is a common, multifactorial disease that is influenced by genetic and environmental factors and their interactions. However, common variants identified by genome wide association studies (GWAS) explain only about 10% of the total trait variance for T2D and less than 5% of the variance for obesity, indicating that a large proportion of heritability is still unexplained. The transcriptomic approach described here uses quantitative gene expression and disease-related physiological data (deep phenotyping) to measure the direct correlation between the expression of specific genes and physiological traits...
June 2016: Genomics Data
https://www.readbyqxmd.com/read/27082665/american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-position-statement-on-the-association-of-sglt-2-inhibitors-and-diabetic-ketoacidosis
#14
Yehuda Handelsman, Robert R Henry, Zachary T Bloomgarden, Sam Dagogo-Jack, Ralph A DeFronzo, Daniel Einhorn, Ele Ferrannini, Vivian A Fonseca, Alan J Garber, George Grunberger, Derek LeRoith, Guillermo E Umpierrez, Matthew R Weir
AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology DKA = diabetic ketoacidosis EMA = European Medicines Agency FDA = U.S. Food and Drug Administration SGLT-2 = sodium glucosecotransporter 2 T1D = type 1 diabetes T2D = type 2 diabetes.
June 2016: Endocrine Practice
https://www.readbyqxmd.com/read/26982008/diabetes-incidence-and-glucose-tolerance-after-termination-of-pioglitazone-therapy-results-from-act-now
#15
Devjit Tripathy, Dawn C Schwenke, MaryAnn Banerji, George A Bray, Thomas A Buchanan, Stephen C Clement, Robert R Henry, Abbas E Kitabchi, Sunder Mudaliar, Robert E Ratner, Frankie B Stentz, Nicolas Musi, Peter D Reaven, Ralph A DeFronzo
CONTEXT: Thiazolidinediones have proven efficacy in preventing diabetes in high-risk individuals. However, the effect of thiazolidinediones on glucose tolerance after cessation of therapy is unclear. OBJECTIVE: To examine the effect of pioglitazone (PIO) on incidence of diabetes after discontinuing therapy in ACT NOW. Design, Settings and Patients: Two-hundred ninety-three subjects (placebo [PLAC], n = 138; PIO, n = 152) completed a median followup of 11.7 mo after study medication was stopped...
May 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/26919068/revitalization-of-pioglitazone-the-optimum-agent-to-be-combined-with-a-sodium-glucose-co-transporter-2-inhibitor
#16
R A DeFronzo, R Chilton, L Norton, G Clarke, R E J Ryder, M Abdul-Ghani
The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events (MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction (MI) and stroke, in patients with high-risk type 2 diabetes (T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death...
May 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/26773926/metformin-associated-lactic-acidosis-current-perspectives-on-causes-and-risk
#17
REVIEW
Ralph DeFronzo, G Alexander Fleming, Kim Chen, Thomas A Bicsak
Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e...
February 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/26765576/effect-of-dapagliflozin-with-and-without-acipimox-on-insulin-sensitivity-and-insulin-secretion-in-t2dm-males
#18
Aurora Merovci, Muhammad Abdul-Ghani, Andrea Mari, Carolina Solis-Herrera, Juan Xiong, Giuseppe Daniele, Devjit Tripathy, Ralph A DeFronzo
AIM: To investigate the effect of lowering the plasma glucose and free fatty acid (FFA) concentrations with dapagliflozin and acipimox, respectively, on insulin sensitivity and insulin secretion in T2DM individuals. METHODS: Fourteen male T2DM patients received an oral glucose tolerance test and euglycemic hyperinsulinemic clamp at baseline and were treated for 3 weeks with dapagliflozin (10 mg per day). During week 3, acipimox (250 mg four times per day) treatment was added to dapagliflozin...
March 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/26583910/empagliflozin-and-linagliptin-combination-therapy-for-treatment-of-patients-with-type-2-diabetes-mellitus
#19
REVIEW
C Triplitt, C Solis-Herrera, E Cersosimo, M Abdul-Ghani, Ralph A Defronzo
INTRODUCTION: Many patients with type 2 diabetes mellitus (T2DM) fail to achieve the desired A1c goal because the antidiabetic medications used do not correct the underlying pathophysiologic abnormalities and monotherapy is not sufficiently potent to reduce the A1c to the 6.5 - 7.0% range. Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in T2DM. We examine combination therapy with linagliptin plus empagliflozin as a therapeutic approach for the treatment of inadequately controlled T2DM patients...
2015: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/26541076/the-empa-reg-study-what-has-it-told-us-a-diabetologist-s-perspective
#20
EDITORIAL
Ralph A DeFronzo
No abstract text is available yet for this article.
January 2016: Journal of Diabetes and its Complications
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