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Glucagon-Like Peptide-1 Receptor Agonist Treatment Prevents Glucocorticoid-Induced Glucose Intolerance and Islet-Cell Dysfunction in Humans

van Raalte, Daniël H ; van Genugten, Renate E ; Linssen, Margot M.L ; Ouwens, D. Margriet ; Diamant, Michaela

Diabetes care, 2011-02, Vol.34 (2), p.412-417 [Periódico revisado por pares]

Alexandria, VA: American Diabetes Association

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Glucagon-Like Peptide-1 Receptor Agonist Treatment Prevents Glucocorticoid-Induced Glucose Intolerance and Islet-Cell Dysfunction in Humans
Autor: van Raalte, Daniël H ; van Genugten, Renate E ; Linssen, Margot M.L ; Ouwens, D. Margriet ; Diamant, Michaela
Assuntos: Adolescent ; Adult ; Apoptosis ; Autoimmune diseases ; Biological and medical sciences ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; C-Peptide - blood ; Clinical medicine ; Corticosteroids ; Cross-Over Studies ; Design ; Dextrose ; Diabetes ; Diabetes. Impaired glucose tolerance ; Disease ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Family medical history ; Glucagon-Like Peptide 1 - agonists ; Glucocorticoids - adverse effects ; Glucose ; Glucose Clamp Technique ; Glucose intolerance ; Glucose Intolerance - chemically induced ; Glucose Intolerance - drug therapy ; Glucose Intolerance - prevention & control ; Humans ; Hyperglycemia ; Hyperglycemia - drug therapy ; Hyperinsulinism - drug therapy ; Hypoglycemic Agents - administration & dosage ; Hypoglycemic Agents - adverse effects ; Insulin Resistance ; Islets of Langerhans - drug effects ; Islets of Langerhans - physiology ; Male ; Medical sciences ; Metabolic diseases ; Metabolism ; Miscellaneous ; Original Research ; Peptides ; Peptides - administration & dosage ; Peptides - adverse effects ; Plasma ; Prednisone - adverse effects ; Prevention ; Public health. Hygiene ; Public health. Hygiene-occupational medicine ; Rheumatoid arthritis ; Shift work ; Studies ; Venoms - administration & dosage ; Venoms - adverse effects ; Young Adult
É parte de: Diabetes care, 2011-02, Vol.34 (2), p.412-417
Descrição: OBJECTIVE: Glucocorticoids (GCs) are regarded as diabetogenic because they impair insulin sensitivity and islet-cell function. This study assessed whether treatment with the glucagon-like peptide receptor agonist (GLP-1 RA) exenatide (EXE) could prevent GC-induced glucose intolerance. RESEARCH DESIGN AND METHODS: A randomized, placebo-controlled, double-blind, crossover study in eight healthy men (age: 23.5 [20.0-28.3] years; BMI: 26.4 [24.3-28.0] kg/m²) was conducted. Participants received three therapeutic regimens for 2 consecutive days: 1) 80 mg of oral prednisolone (PRED) every day (q.d.) and intravenous (IV) EXE infusion (PRED+EXE); 2) 80 mg of oral PRED q.d. and IV saline infusion (PRED+SAL); and 3) oral placebo-PRED q.d. and intravenous saline infusion (PLB+SAL). On day 1, glucose tolerance was assessed during a meal challenge test. On day 2, participants underwent a clamp procedure to measure insulin secretion and insulin sensitivity. RESULTS: PRED+SAL treatment increased postprandial glucose levels (vs. PLB+SAL, P = 0.012), which was prevented by concomitant EXE (vs. PLB+SAL, P = NS). EXE reduced PRED-induced hyperglucagonemia during the meal challenge (P = 0.018) and decreased gastric emptying (vs. PRED+SAL, P = 0.028; vs. PLB+SAL, P = 0.046). PRED+SAL decreased first-phase glucose- and arginine-stimulated C-peptide secretion (vs. PLB+SAL, P = 0.017 and P = 0.05, respectively), whereas PRED+EXE improved first- and second-phase glucose- and arginine-stimulated C-peptide secretion (vs. PLB+SAL; P = 0.017, 0.012, and 0.093, respectively). CONCLUSIONS: The GLP-1 RA EXE prevented PRED-induced glucose intolerance and islet-cell dysfunction in healthy humans. Incretin-based therapies should be explored as a potential strategy to prevent steroid diabetes.
Editor: Alexandria, VA: American Diabetes Association
Idioma: Inglês

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Glucagon-Like Peptide-1 Receptor Agonist Treatment Prevents Glucocorticoid-Induced Glucose Intolerance and Islet-Cell Dysfunction in Humans

van Raalte, Daniël H ; van Genugten, Renate E ; Linssen, Margot M.L ; Ouwens, D. Margriet ; Diamant, Michaela

Alexandria, VA: American Diabetes Association

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