Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance

• Published in: Diabetes (New York, N.Y.) Vol. 57; no. 3; pp. 678 - 687
• Main Authors: Vollmer, Kirsten, Holst, Jens J., Baller, Birgit, Ellrichmann, Mark, Nauck, Michael A., Schmidt, Wolfgang E., Meier, Juris J.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.2008
• Subjects: Aged; Biological and medical sciences; Blood Glucose - metabolism; Defects; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Experiments; Fatty Acids, Nonesterified - blood; Fatty Acids, Nonesterified - metabolism; Female; Gastric Inhibitory Polypeptide - metabolism; Genetic aspects; Glucagon; Glucagon - blood; Glucagon - metabolism; Glucagon-Like Peptide 1 - metabolism; Glucose; Glucose - metabolism; Glucose Intolerance - blood; Glucose Tolerance Test; Glucose tolerance tests; Health aspects; Homeostasis; Humans; Incretins - metabolism; Insulin; Male; Medical sciences; Middle Aged; Pathogenesis; Polypeptides; Research design; Triglycerides - blood; Triglycerides - metabolism; Type 2 diabetes; Germany; Endocrinopathy; Human; Tolerance; Incretin; Glucose; Diabetes mellitus
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db07-1124

Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance Kirsten Vollmer 1 , Jens J. Holst 2 , Birgit Baller 1 , Mark Ellrichmann 1 , Michael A. Nauck 3 , Wolfgang E. Schmidt 1 and Juris J. Meier 1 1 Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Germany 2 Department of Medical Physiology, The Panum-Institute, University of Copenhagen, Denmark 3 Diabeteszentrum Bad Lauterberg, Germany Address correspondence and reprint requests to Dr. Juris J. Meier, Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791 Bochum, Germany. E-mail: juris.meier{at}rub.de Abstract OBJECTIVE— Defects in glucagon-like peptide 1 (GLP-1) secretion have been reported in some patients with type 2 diabetes after meal ingestion. We addressed the following questions: 1 ) Is the quantitative impairment in GLP-1 levels different after mixed meal or isolated glucose ingestion? 2 ) Which endogenous factors are associated with the concentrations of GLP-1? In particular, do elevated fasting glucose or glucagon levels diminish GLP-1 responses? RESEARCH DESIGN AND METHODS— Seventeen patients with mild type 2 diabetes, 17 subjects with impaired glucose tolerance, and 14 matched control subjects participated in an oral glucose tolerance test (75 g) and a mixed meal challenge (820 kcal), both carried out over 240 min on separate occasions. Plasma levels of glucose, insulin, C-peptide, glucagon, triglycerides, free fatty acids (FFAs), gastric inhibitory polypeptide (GIP), and GLP-1 were determined. RESULTS— GIP and GLP-1 levels increased significantly in both experiments ( P < 0.0001). In patients with type 2 diabetes, the initial GIP response was exaggerated compared with control subjects after mixed meal ( P < 0.001) but not after oral glucose ingestion ( P = 0.98). GLP-1 levels were similar in all three groups in both experiments. GIP responses were 186 ± 17% higher after mixed meal ingestion than after the oral glucose load ( P < 0.0001), whereas GLP-1 levels were similar in both experiments. There was a strong negative association between fasting glucagon and integrated FFA levels and subsequent GLP-1 concentrations. In contrast, fasting FFA and integrated glucagon levels after glucose or meal ingestion and female sex were positively related to GLP-1 concentrations. Incretin levels were unrelated to measures of glucose control or insulin secretion. CONCLUSIONS— Deteriorations in glucose homeostasis can develop in the absence of any impairment in GIP or GLP-1 levels. This suggests that the defects in GLP-1 concentrations previously described in patients with long-standing type 2 diabetes are likely secondary to other hormonal and metabolic alterations, such as hyperglucagonemia. GIP and GLP-1 concentrations appear to be regulated by different factors and are independent of each other. AUC, area under the curve DPP-4, dipeptidyl peptidase IV FFA, free fatty acid GIP, gastric inhibitory polypeptide GLP-1, glucagon-like peptide 1 HOMA, homeostasis model assessment IGT, impaired glucose tolerance Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on December 2007. DOI: 10.2337/db07-1124. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received August 10, 2007. Accepted November 20, 2007. DIABETES