Impaired beta-cell function, incretin effect, and glucagon suppression in patients with type 1 diabetes who have normal fasting glucose

Carla J GreenbaumDavid A D'Alessio


We have recently described a novel phenotype in a group of subjects with type 1 diabetes that is manifested by glucose >11.1 mmol/l 120 min after an oral glucose load, but with normal fasting glucose levels. We now describe the metabolic characteristics of these subjects by comparing parameters of islet hormone secretion and glucose disposal in these subjects to age-matched nondiabetic control subjects. The patients with type 1 diabetes had fasting glucose, insulin, and glucagon values similar to those of control subjects. Additionally, the insulin secretory response to intravenous arginine at euglycemia was similar in the control and diabetic groups (264 +/- 33.5 and 193 +/- 61.3 pmol/l; P = 0.3). However, marked differences in beta-cell function were found in response to hyperglycemia. Specifically, the first-phase insulin response was lower in diabetic subjects (329.1 +/- 39.6 vs. 91.3 +/- 34.1 pmol/l; P < 0.001), as was the slope of glucose potentiation of the insulin response to arginine (102 +/- 18.7 vs. 30.2 +/- 6.1 pmol/l per mmol/l; P = 0.005) and the maximum insulin response to arginine (2,524 +/- 413 vs. 629 +/- 159 pmol/l; P = 0.001). Although plasma levels of glucagon-like peptide (GLP)-1 and gastric inhibitory pep...Continue Reading


Jun 1, 1979·The American Journal of Physiology·R N BergmanClaudio Cobelli
Dec 1, 1990·The Journal of Clinical Endocrinology and Metabolism·S WelchL S Phillips
Jan 1, 1986·Diabetologia·M A NauckW Creutzfeldt
Aug 1, 1986·The Journal of Clinical Endocrinology and Metabolism·M A NauckW Creutzfeldt
Apr 1, 1987·Scandinavian Journal of Clinical and Laboratory Investigation·C Orskov, J J Holst
Aug 1, 1984·Diabetes·S SrikantaGeorge S Eisenbarth
Oct 1, 1984·The Journal of Clinical Investigation·W K WardD Porte
Mar 1, 1994·The Journal of Clinical Investigation·M M ByrneG I Bell
Jan 24, 1998·Metabolism: Clinical and Experimental·J W FrankRobert A Rizza
Aug 13, 1999·The American Journal of Physiology·P ShahRobert A Rizza
Mar 29, 2001·Diabetes·Carla J GreenbaumDisease Prevention Trial of Type I Diabetes Study Group


Jul 7, 2012·Current Diabetes Reports·Claire M Issa, Sami T Azar
Jul 6, 2012·Current Diabetes Reports·Michael R Rickels
Aug 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jingyu DiaoMichael B Wheeler
Dec 22, 2004·Pediatric Research·Sabita UthayaNeena Modi
Jan 2, 2007·Southern Medical Journal·Nasser Mikhail
Apr 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Atsushi SuzukiHideki Taniguchi
Nov 4, 2015·Diabetes·Meera ShahAdrian Vella
Feb 17, 2015·FEBS Open Bio·Tadaho NakamuraKazuhiko Yanai
Mar 11, 2008·Metabolism: Clinical and Experimental·Kevin M KrudysPaolo Vicini
Apr 1, 2014·Immunologic Research·Linda Yip, C Garrison Fathman
Apr 30, 2015·Diabetes, Obesity & Metabolism·P J LefèbvreA J Scheen
Jun 29, 2004·Diabetes Care·Etienne LargerBenjamin Rakotoaminina
Feb 28, 2003·Diabetes·Massimo FedericiRaffaella Buzzetti
Apr 29, 2011·Diabetes·Mark A AtkinsonChristopher J Rhodes
Jan 31, 2006·Diabetes Care·Matthew C Riddle, Daniel J Drucker
Mar 13, 2016·The Lancet. Diabetes & Endocrinology·Christian S FrandsenSten Madsbad
Feb 3, 2007·The Diabetes Educator·Skye Aiko McKennon, R Keith Campbell
Oct 27, 2017·Diabetes, Obesity & Metabolism·Myfanwy C GeyerJennifer J Couper
Mar 10, 2017·Physiological Reviews·T D MüllerM H Tschöp
Jul 12, 2018·Expert Opinion on Pharmacotherapy·Christian S FrandsenJens Juul Holst
Sep 20, 2018·Diabetes, Obesity & Metabolism·Jing W HughesDavid W Piston
Jul 31, 2018·Endocrine Reviews·Karen D CorbinAdvancing Care for Type 1 Diabetes and Obesity Network (ACT1ON)
Aug 8, 2007·The Journal of Clinical Endocrinology and Metabolism·Jennifer Bollyky, Carla J Greenbaum
Aug 5, 2017·Expert Opinion on Drug Delivery·Kathleen H Ang, Jennifer L Sherr
Jan 3, 2020·The Journal of Clinical Investigation·Michael R RickelsT1D Exchange β-Cell Function Study Group
Jan 31, 2007·Endocrine Reviews·Jesper GromadaClaes B Wollheim
Jan 24, 2003·American Journal of Physiology. Endocrinology and Metabolism·Nathalie PamirRaymond A Pederson
Sep 29, 2005·American Journal of Physiology. Endocrinology and Metabolism·Rui TakahashiYoshitomo Oka
Jan 28, 2010·American Journal of Physiology. Endocrinology and Metabolism·Kristine J HareFilip K Knop
May 18, 2011·Physiological Research·M HumlJ Sýkora
Nov 25, 2005·Diabetes·Nicole A SherryKevan C Herold
Oct 19, 2017·The Journal of Clinical Endocrinology and Metabolism·Wei HaoCarla J Greenbaum
Jun 18, 2018·Current Diabetes Reports·Melinda E ChenTamara S Hannon
Sep 9, 2017·Transplantation·Christian SchuetzIPITA YIC Young Investigator Committee
Apr 29, 2008·Arquivos brasileiros de endocrinologia e metabologia·Mônica de A Lima Gabbay

Related Concepts

Islet cell surface antibodies
MKC 253
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Glucagon-Like Peptides
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