Combination GLP-1 and Insulin Treatment Fails to Alter Myocardial Fuel Selection vs. Insulin Alone in Type 2 Diabetes
| Autor: | Adam G. Goodwill, LaTonya Hamilton, Niral A. Patel, Wendy Territo, Gary D. Hutchins, Mark A. Green, Robert V. Considine, Kieren J. Mather, Johnathan D. Tune, Carla J. Mathias |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty endocrine system diseases Endocrinology Diabetes and Metabolism medicine.medical_treatment Glucose uptake Clinical Biochemistry Context (language use) Type 2 diabetes 030204 cardiovascular system & hematology Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology Insulin Detemir Coronary Circulation Diabetes mellitus Internal medicine medicine Humans Hypoglycemic Agents 030212 general & internal medicine Clinical Research Articles Insulin detemir business.industry Liraglutide Myocardium Insulin Biochemistry (medical) nutritional and metabolic diseases Heart Middle Aged medicine.disease Metformin Treatment Outcome Diabetes Mellitus Type 2 Drug Therapy Combination Female business medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 103:3456-3465 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2018-00712 |
| Popis: | Context It is unclear if effects of glucagon-like peptide-1 (GLP-1) and clinically available GLP-1 agonists on the heart occur at clinical doses in humans, possibly contributing to reduced cardiovascular disease risk. Objective To determine whether liraglutide, at clinical dosing, augments myocardial glucose uptake (MGU) alone or combined with insulin compared with insulin alone in metformin-treated type 2 diabetes mellitus (T2D). Design In a randomized clinical trial of patients with T2D treated with metformin plus oral agents or basal insulin, myocardial fuel use was compared after 3 months of treatment with insulin detemir, liraglutide, or combination detemir plus liraglutide added to background metformin. Main Outcome Measures Myocardial blood flow (MBF), fuel selection, and rates of fuel use were evaluated using positron emission tomography, powered to demonstrate large effects. Results MBF was greater in the insulin-treated groups [median (25th, 75th percentile): detemir, 0.64 mL/g/min (0.50, 0.69); liraglutide, 0.52 mL/g/min (0.46, 0.58); detemir plus liraglutide, 0.75 mL/g/min (0.55, 0.77); P = 0.035 comparing three groups, P = 0.01 comparing detemir groups to liraglutide alone]. There were no evident differences among groups in MGU [detemir, 0.040 µmol/g/min (0.013, 0.049); liraglutide, 0.055 µmol/g/min (0.019, 0.105); detemir plus liraglutide, 0.037 µmol/g/min (0.009, 0.046); P = 0.68 comparing three groups]. There were no treatment-group differences in measures of myocardial fatty acid uptake or handling, and no differences in total oxidation rate. Conclusion These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection. |
| Databáze: | OpenAIRE |
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