Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin
| Autor: | Lindsay B. Harrison, Keith Mcleod Hulsey, Ivan E. Dimitrov, Daniella F. Pinho, Jeremy T. Warshauer, Xilong Li, Takeshi Yokoo, Laurentiu M. Pop, Beverley Adams-Huet, Adam W. Jaster, Anna Vanderheiden, Ivan Pedrosa, Robert E. Lenkinski, Qing Yuan, Ildiko Lingvay |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry 030209 endocrinology & metabolism Context (language use) Type 2 diabetes Biochemistry Glucagon 03 medical and health sciences 0302 clinical medicine Endocrinology Insulin resistance Double-Blind Method Internal medicine Diabetes mellitus Insulin Secretion medicine Humans Hypoglycemic Agents Insulin Glycated Hemoglobin business.industry Liraglutide Biochemistry (medical) Glucagon secretion Middle Aged medicine.disease Magnetic Resonance Imaging Adipose Tissue Diabetes Mellitus Type 2 030211 gastroenterology & hepatology Female Insulin Resistance business medicine.drug |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 101(4) |
| ISSN: | 1945-7197 |
| Popis: | Context: The mechanisms of action of incretin mimetics in patients with long-standing type 2 diabetes (T2D) and high insulin requirements have not been studied. Objective: To evaluate changes in β-cell function, glucagon secretion, and fat distribution after addition of liraglutide to high-dose insulin. Design: A single-center, randomized, double-blind, placebo-controlled trial. Setting: University of Texas Southwestern and Parkland Memorial Hospital clinics. Patients: Seventy-one patients with long-standing (median, 17 years) T2D requiring high-dose insulin treatment (>1.5 U/kg/d; average, 2.2 ± 0.9 U/kg/d). Intervention: Patients were randomized to liraglutide 1.8 mg/d or matching placebo for 6 months. Main Outcome Measures: We measured changes in insulin and glucagon secretion using a 4-hour mixed-meal challenge test. Magnetic resonance-based techniques were used to estimate sc and visceral fat in the abdomen and ectopic fat in the liver and pancreas. Results: Glycosylated hemoglobin improved significantly with liraglutide treatment, with an end-of-trial estimated treatment difference between groups of −0.9% (95% confidence interval, −1.5, −0.4%) (P = .002). Insulin secretion improved in the liraglutide group vs placebo, as measured by the area under the curve of C-peptide (P = .002) and the area under the curves ratio of C-peptide to glucose (P = .003). Insulin sensitivity (Matsuda index) and glucagon secretion did not change significantly between groups. Liver fat and sc fat decreased in the liraglutide group vs placebo (P = .0006 and P = .01, respectively), whereas neither visceral nor pancreatic fat changed significantly. Conclusions: Treatment with liraglutide significantly improved insulin secretion, even in patients with long-standing T2D requiring high-dose insulin treatment. Liraglutide also decreased liver and sc fat, but it did not alter glucagon secretion. |
| Databáze: | OpenAIRE |
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