{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:29:54Z","timestamp":1791145794116,"version":"4.1.0"},"reference-count":38,"publisher":"American Diabetes Association","issue":"11","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":4033,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,11,1]]},"abstract":"<jats:p>The objective of this research is to gain a greater understanding of the cause of fasting and postprandial hyperglycemia in people with type 2 diabetes. Endogenous glucose production is excessive before eating and fails to appropriately suppress after eating in people with type 2 diabetes. This is due in part to impaired insulin-induced suppression of endogenous glucose production, which is observed early in the evolution of type 2 diabetes. Increased rates of gluconeogenesis and perhaps glycogenolysis contribute to hepatic insulin resistance. Insulin-induced stimulation of hepatic glucose uptake and hepatic glycogen synthesis are reduced in people with type 2 diabetes primarily due to decreased uptake of extracellular glucose presumably because of inadequate activation of hepatic glucokinase. Delayed insulin secretion results in higher peak glucose concentrations particularly when suppression of glucagon is impaired, whereas insulin resistance prolongs the duration of hyperglycemia, which can be marked when both hepatic and extra-hepatic insulin resistance are present.<\/jats:p>\n               <jats:p>The premise of these studies, as well as those performed by many other investigators, is that an understanding of the pathogenesis of type 2 diabetes will enable the development of targeted therapies that are directed toward correcting specific metabolic defects in a given individual. I, as well as many other investigators, believe that such therapies are likely to be more effective and to have a lower risk than would occur if everyone were treated the same regardless of the underlying cause of their hyperglycemia. While we do not yet have sufficient knowledge to truly individualize therapy, in my opinion this approach will be the norm in the not too distant future.<\/jats:p>","DOI":"10.2337\/db10-1032","type":"journal-article","created":{"date-parts":[[2010,8,13]],"date-time":"2010-08-13T02:04:15Z","timestamp":1281665055000},"page":"2697-2707","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":316,"title":["Pathogenesis of Fasting and Postprandial Hyperglycemia in Type 2 Diabetes: Implications for Therapy"],"prefix":"10.2337","volume":"59","author":[{"given":"Robert A.","family":"Rizza","sequence":"first","affiliation":[{"name":"From the Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2010,8,12]]},"reference":[{"key":"2022031210423197200_B1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2337\/diab.40.1.73","article-title":"Contribution to postprandial hyperglycemia and effect on initial splanchnic glucose clearance of hepatic glucose cycling in glucose-intolerant or NIDDM patients","volume":"40","author":"Butler","year":"1991","journal-title":"Diabetes"},{"key":"2022031210423197200_B2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0002-9343(83)90258-9","article-title":"Insulin secretion and action in noninsulin-dependent diabetes mellitus","volume":"30","author":"Reaven","year":"1983","journal-title":"Am J Med"},{"key":"2022031210423197200_B3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1056\/NEJM197007162830301","article-title":"Abnormal alpha-cell function in diabetes: response to carbohydrate and protein ingestion","volume":"283","author":"M\u00fcller","year":"1970","journal-title":"N Engl J Med"},{"key":"2022031210423197200_B4","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1001\/jama.1975.03260150029015","article-title":"Abnormal pancreatic glucagon secretion and postprandial hyperglycemia in diabetes mellitus","volume":"234","author":"Gerich","year":"1975","journal-title":"JAMA"},{"key":"2022031210423197200_B5","doi-asserted-by":"crossref","first-page":"867","DOI":"10.2337\/diab.15.12.867","article-title":"Plasma insulin responses to glucose and tolbutamide of normal weight and obese diabetic and nondiabetic subjects","volume":"15","author":"Perley","year":"1966","journal-title":"Diabetes"},{"key":"2022031210423197200_B6","doi-asserted-by":"crossref","first-page":"166","DOI":"10.2337\/diab.40.2.166","article-title":"Banting lecture 1990: \u03b2-cells in type II diabetes mellitus","volume":"40","author":"Porte","year":"1991","journal-title":"Diabetes"},{"key":"2022031210423197200_B7","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2337\/diab.35.4.379","article-title":"The limitations to and valid use of C-peptide as a marker of the secretion of insulin","volume":"35","author":"Polonsky","year":"1986","journal-title":"Diabetes"},{"key":"2022031210423197200_B8","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s00125-006-0566-z","article-title":"Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus","volume":"50","author":"Knop","year":"2007","journal-title":"Diabetologia"},{"key":"2022031210423197200_B9","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1056\/NEJM199209033271007","article-title":"Carbohydrate metabolism in non-insulin-dependent diabetes mellitus","volume":"327","author":"Dinneen","year":"1992","journal-title":"N Engl J Med"},{"key":"2022031210423197200_B10","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1172\/JCI112467","article-title":"Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus: role of hepatic and extrahepatic tissues","volume":"77","author":"Firth","year":"1986","journal-title":"J Clin Invest"},{"key":"2022031210423197200_B11","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1152\/ajplegacy.1974.227.6.1314","article-title":"Interaction of insulin and glucose in the control of hepatic glucose balance","volume":"227","author":"Bergman","year":"1974","journal-title":"Am J Physiol"},{"key":"2022031210423197200_B12","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/0026-0495(78)90213-5","article-title":"Relationship between the plasma glucose level and glucose uptake in the conscious dog","volume":"27","author":"Cherrington","year":"1978","journal-title":"Metabolism"},{"key":"2022031210423197200_B13","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/0026-0495(91)90194-2","article-title":"Effects of small changes in glucagon on glucose production during a euglycemic, hyperinsulinemic clamp","volume":"40","author":"Myers","year":"1991","journal-title":"Metabolism"},{"key":"2022031210423197200_B14","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2337\/diab.32.1.35","article-title":"Regulation of splanchnic and peripheral glucose uptake by insulin and hyperglycemia in man","volume":"32","author":"DeFronzo","year":"1983","journal-title":"Diabetes"},{"key":"2022031210423197200_B15","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.2337\/diabetes.53.8.2042","article-title":"Insulin dose-response curves for stimulation of splanchnic glucose uptake and suppression of endogenous glucose production differ in nondiabetic humans and are abnormal in people with type 2 diabetes","volume":"53","author":"Basu","year":"2004","journal-title":"Diabetes"},{"key":"2022031210423197200_B16","doi-asserted-by":"crossref","first-page":"272","DOI":"10.2337\/diabetes.49.2.272","article-title":"Effects of type 2 diabetes on the ability of insulin and glucose to regulate splanchnic and muscle glucose metabolism: evidence for a defect in hepatic glucokinase activity","volume":"49","author":"Basu","year":"2000","journal-title":"Diabetes"},{"key":"2022031210423197200_B17","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/0026-0495(91)90019-S","article-title":"Quantitation of glycogen\/glucose-1-P cycling in liver","volume":"40","author":"Wajngot","year":"1991","journal-title":"Metabolism"},{"key":"2022031210423197200_B18","first-page":"21925","article-title":"Glucokinase: structural analysis of a protein involved in susceptibility to diabetes","volume":"269","author":"Pilkis","year":"1994","journal-title":"J BiolChem"},{"key":"2022031210423197200_B19","doi-asserted-by":"crossref","first-page":"31833","DOI":"10.1074\/jbc.274.45.31833","article-title":"Glucokinase overexpression restores glucose utilization and storage in cultured hepatocytes from male Zucker diabetic fatty rats","volume":"274","author":"Seoane","year":"1999","journal-title":"J Biol Chem"},{"key":"2022031210423197200_B20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1055\/s-2007-979899","article-title":"Liver glucokinase: decreased activity in patients with type II diabetes","volume":"27","author":"Caro","year":"1995","journal-title":"Horm Metab Res"},{"key":"2022031210423197200_B21","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1172\/JCI118974","article-title":"Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2) subjects","volume":"98","author":"Velho","year":"1996","journal-title":"J Clin Invest"},{"key":"2022031210423197200_B22","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1172\/JCI111533","article-title":"Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects","volume":"74","author":"Bogardus","year":"1984","journal-title":"J Clin Invest"},{"key":"2022031210423197200_B23","doi-asserted-by":"crossref","first-page":"810","DOI":"10.2337\/diabetes.50.4.810","article-title":"Effects of free fatty acids on gluconeogenesis and autoregulation of glucose production in type 2 diabetes","volume":"50","author":"Boden","year":"2001","journal-title":"Diabetes"},{"key":"2022031210423197200_B24","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1475-097X.1994.tb00383.x","article-title":"Overnight glucose metabolism in obese non-insulin-dependent diabetic patients and in healthy lean individuals","volume":"14","author":"Tappy","year":"1994","journal-title":"Clin Physiol"},{"key":"2022031210423197200_B25","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1172\/JCI115997","article-title":"Increased rate of gluconeogenesis in type II diabetes mellitus: a 13C nuclear magnetic resonance study","volume":"90","author":"Magnusson","year":"1992","journal-title":"J Clin Invest"},{"key":"2022031210423197200_B26","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/s001250100589","article-title":"Production and metabolic clearance of glucose under basal conditions in type II (non-insulin-dependent) diabetes mellitus","volume":"44","author":"Radziuk","year":"2001","journal-title":"Diabetologia"},{"key":"2022031210423197200_B27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0026-0495(88)90023-6","article-title":"Quantification of the relative impairment in actions of insulin on hepatic glucose production and peripheral glucose uptake in non-insulin-dependent diabetes mellitus","volume":"37","author":"Campbell","year":"1988","journal-title":"Metabolism"},{"key":"2022031210423197200_B28","doi-asserted-by":"crossref","first-page":"E55","DOI":"10.1152\/ajpendo.00549.2003","article-title":"Both fasting glucose production and disappearance are abnormal in people with \u201cmild\u201d and \u201csevere\u201d type 2 diabetes","volume":"287","author":"Basu","year":"2004","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2022031210423197200_B29","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.2337\/db06-1776","article-title":"Contribution of hepatic and extrahepatic insulin resistance to the pathogenesis of impaired fasting glucose: role of increased rates of gluconeogenesis","volume":"56","author":"Bock","year":"2007","journal-title":"Diabetes"},{"key":"2022031210423197200_B30","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1172\/JCI118803","article-title":"Contributions of gluconeogenesis to glucose production in the fasted state","volume":"98","author":"Landau","year":"1996","journal-title":"J Clin Invest"},{"key":"2022031210423197200_B31","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2337\/db07-0694","article-title":"Evidence that processes other than gluconeogenesis may influence the ratio of deuterium on the fifth and third carbons of glucose: implications for the use of 2H2O to measure gluconeogenesis in humans","volume":"57","author":"Bock","year":"2008","journal-title":"Diabetes"},{"key":"2022031210423197200_B32","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.2337\/db08-1300","article-title":"Additional evidence that transaldolase exchange, isotope discrimination during the triose-isomerase reaction, or both occur in humans: effects of type 2 diabetes","volume":"58","author":"Basu","year":"2009","journal-title":"Diabetes"},{"key":"2022031210423197200_B33","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1172\/JCI579","article-title":"Mechanism by which glucose and insulin inhibit net hepatic glycogenolysis in humans","volume":"101","author":"Petersen","year":"1998","journal-title":"J Clin Invest"},{"key":"2022031210423197200_B34","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1172\/JCI118678","article-title":"Effects of a change in the pattern of insulin delivery on carbohydrate tolerance in diabetic and nondiabetic humans in the presence of differing degrees of insulin resistance","volume":"97","author":"Basu","year":"1996","journal-title":"J Clin Invest"},{"key":"2022031210423197200_B35","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1210\/jcem-41-6-1178","article-title":"Normalization of fasting hyperglucagonemia and excessive glucagon responses to intravenous arginine in human diabetes mellitus by prolonged infusion of insulin","volume":"41","author":"Gerich","year":"1975","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031210423197200_B36","doi-asserted-by":"crossref","first-page":"E283","DOI":"10.1152\/ajpendo.1999.277.2.E283","article-title":"Impact of lack of suppression of glucagon on glucose tolerance in humans","volume":"277","author":"Shah","year":"1999","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2022031210423197200_B37","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.2337\/diabetes.54.7.1942","article-title":"Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis as well as gluconeogenesis","volume":"54","author":"Basu","year":"2005","journal-title":"Diabetes"},{"key":"2022031210423197200_B38","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.2337\/diabetes.50.6.1351","article-title":"Type 2 diabetes impairs splanchnic uptake of glucose but does not alter intestinal glucose absorption during enteral glucose feeding: additional evidence for a defect in hepatic glucokinase activity","volume":"50","author":"Basu","year":"2001","journal-title":"Diabetes"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/59\/11\/2697\/396338\/zdb01110002697.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/59\/11\/2697\/396338\/zdb01110002697.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:24:16Z","timestamp":1667406256000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/59\/11\/2697\/16191\/Pathogenesis-of-Fasting-and-Postprandial"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8,12]]},"references-count":38,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2010,8,12]]},"published-print":{"date-parts":[[2010,11,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db10-1032","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,8,12]]}}}