This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Toft-Nielsen, M.-B. Articles by Holst, J. J. Search for Related Content PubMed PubMed Citation Articles by Toft-Nielsen, M.-B. Articles by Holst, J. J.

Determinants of the Effectiveness of Glucagon-Like Peptide-1 in Type 2 Diabetes

Department of Endocrinology (M.-B.T.-N., S.M.), Hvidovre Hospital, University of Copenhagen, DK-2650 Hvidovre, Denmark; and Department of Medical Physiology (M.-B.T.-N., J.J.H.), the Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark

Address all correspondence and requests for reprints to: Prof. Jens Juul Holst, Department of Medical Physiology, The Panum Institute, Blegdamsvej 3, DK- 2200 Copenhagen NV, Denmark. E-mail: holst{at}mfi

Abstract

GLP-1 lowers blood glucose in fasting type 2 diabetic patients. To clarify the relation of the effect of GLP-1 to obesity, blood glucose, ß-cell function, and insulin sensitivity, GLP-1 (1.2 pmol/kg·min) was infused iv for 4–6 h into 50 fasting type 2 diabetic patients with a wide range of age, body mass index, HbA1c, and fasting plasma glucose. The effectiveness of GLP-1 was evaluated by calculation of a glucose disappearance constant for each individual (Kg, linear slope of log-transformed plasma glucose), and by the lowest stable glucose level (Nadir plasma glucose) obtained during the infusion. Grouped according to fasting plasma glucose (<10, 10–15, >15 mmol/liter), Kg values were 0.45 ± 0.03, 0.38 ± 0.04, and 0.28 ± 0.04%/min (P = 0.005), and Nadir plasma glucose values were 4.7 ± 0.1 (3.9–5.9), 5.8 ± 0.4 (4.3–8.4), and 8.7 ± 1.4 (6.2–18.7) mmol/liter (P = 0.0003). Nonresponders were not identified. Multiple regression analysis with Kg or Nadir plasma glucose as the dependent parameter and body mass index, age, gender, diabetes duration, and significantly correlated parameters (in multiple regression for Kg: fasting plasma glucose, fasting nonesterified fatty acid, dipeptidyl peptidase activity, peak insulin, and the logarithm of ß-cell function; and for Nadir plasma glucose: fasting plasma glucose, fasting nonesterified fatty acid, dipeptidyl peptidase activity, glucagon decrement, F-GLP-1 total, logarithm of ß-cell function, and Kg) as independent parameters resulted in fasting plasma glucose as the only significant predictor of Kg, and fasting plasma glucose and Kg as predictors of Nadir plasma glucose. Kg and Nadir plasma glucose were neither influenced by treatment nor by neuropathy per se. In conclusion, GLP-1 lowers plasma glucose in type 2 diabetes regardless of severity, but glucose elimination is faster and obtained glycemic level lower in patients with the lower fasting plasma glucose. Not all patients can be expected to reach normoglycemia.

This article has been cited by other articles:

				A. L. PETERS Patient and treatment perspectives: Revisiting the link between type 2 diabetes, weight gain, and cardiovascular risk Cleveland Clinic Journal of Medicine, December 1, 2009; 76(Suppl_5): S20 - S27. [Abstract] [Full Text] [PDF]

				A. A. Palladino, S. Sayed, L. E. Levitt Katz, P. R. Gallagher, and D. D. De Leon Increased Glucagon-Like Peptide-1 Secretion and Postprandial Hypoglycemia in Children after Nissen Fundoplication J. Clin. Endocrinol. Metab., January 1, 2009; 94(1): 39 - 44. [Abstract] [Full Text] [PDF]

				J. J. Holst The Physiology of Glucagon-like Peptide 1 Physiol Rev, October 1, 2007; 87(4): 1409 - 1439. [Abstract] [Full Text] [PDF]

				T. P. Vahl, M. Tauchi, T. S. Durler, E. E. Elfers, T. M. Fernandes, R. D. Bitner, K. S. Ellis, S. C. Woods, R. J. Seeley, J. P. Herman, et al. Glucagon-Like Peptide-1 (GLP-1) Receptors Expressed on Nerve Terminals in the Portal Vein Mediate the Effects of Endogenous GLP-1 on Glucose Tolerance in Rats Endocrinology, October 1, 2007; 148(10): 4965 - 4973. [Abstract] [Full Text] [PDF]

				F. K. Knop, T. Vilsboll, S. Larsen, P. V. Hojberg, A. Volund, S. Madsbad, J. J. Holst, and T. Krarup Increased postprandial responses of GLP-1 and GIP in patients with chronic pancreatitis and steatorrhea following pancreatic enzyme substitution Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E324 - E330. [Abstract] [Full Text] [PDF]

				J. J. Holst and C. Orskov The Incretin Approach for Diabetes Treatment: Modulation of Islet Hormone Release by GLP-1 Agonism Diabetes, December 1, 2004; 53(suppl_3): S197 - S204. [Abstract] [Full Text] [PDF]

				D. A. D'Alessio and T. P. Vahl Glucagon-like peptide 1: evolution of an incretin into a treatment for diabetes Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E882 - E890. [Abstract] [Full Text] [PDF]

				G. S. Meneilly, N. Greig, H. Tildesley, J. F. Habener, J. M. Egan, and D. Elahi Effects of 3 Months of Continuous Subcutaneous Administration of Glucagon-Like Peptide 1 in Elderly Patients With Type 2 Diabetes Diabetes Care, October 1, 2003; 26(10): 2835 - 2841. [Abstract] [Full Text] [PDF]

				S. Quddusi, T. P. Vahl, K. Hanson, R. L. Prigeon, and D. A. D'Alessio Differential Effects of Acute and Extended Infusions of Glucagon-Like Peptide-1 on First- and Second-Phase Insulin Secretion in Diabetic and Nondiabetic Humans Diabetes Care, March 1, 2003; 26(3): 791 - 798. [Abstract] [Full Text] [PDF]