Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: a prospective randomized clinical trial using magnetic resonance imaging and spectroscopy

Aim To conduct a prospective randomized trial to investigate the effect of glucagon‐like peptide‐1 (GLP‐1) analogues on ectopic fat stores. Methods A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treat...

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Published inDiabetes, obesity & metabolism Vol. 18; no. 9; pp. 882 - 891
Main Authors Dutour, A., Abdesselam, I., Ancel, P., Kober, F., Mrad, G., Darmon, P., Ronsin, O., Pradel, V., Lesavre, N., Martin, J. C., Jacquier, A., Lefur, Y., Bernard, M., Gaborit, B.
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.09.2016
Wiley Subscription Services, Inc
Wiley
Subjects
Adiponectin
Adipose tissue
Adipose Tissue - diagnostic imaging
Adipose Tissue - metabolism
Body fat
Body mass index
Body weight loss
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Endocrinology and metabolism
epicardial adipose tissue
Fatty liver
Fatty Liver - complications
Fatty Liver - diagnostic imaging
Fatty Liver - metabolism
Female
Glucagon
glucagon-like peptide 1 receptor agonist
Glycated Hemoglobin A - metabolism
Heart - diagnostic imaging
Hemoglobin
hepatic triglyceride content
Human health and pathology
Humans
Hypoglycemic Agents - therapeutic use
Insulin resistance
Life Sciences
Liver - diagnostic imaging
Liver - metabolism
Magnetic Resonance Imaging
Magnetic resonance spectroscopy
Male
Middle Aged
myocardial triglyceride content
Myocardium - metabolism
NMR
Nuclear magnetic resonance
Obesity
Obesity - complications
Obesity - metabolism
Pancreas - diagnostic imaging
Pancreas - metabolism
pancreatic triglyceride content
Patients
Peptides - therapeutic use
Pericardium - diagnostic imaging
Pericardium - metabolism
Population studies
Postprandial Period
Proton Magnetic Resonance Spectroscopy
Spectrum analysis
Steatosis
Treatment Outcome
Triglycerides - metabolism
type 2 diabetes
Venoms - therapeutic use
magnetic resonance imaging
type 2 diabetes
hepatic triglyceride content
pancreatic triglyceride content
epicardial adipose tissue
myocardial triglyceride content
proton magnetic resonance spectroscopy
glucagon-like peptide 1 receptor agonist
obesity
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Abstract Aim To conduct a prospective randomized trial to investigate the effect of glucagon‐like peptide‐1 (GLP‐1) analogues on ectopic fat stores. Methods A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue (EAT), myocardial triglyceride content (MTGC), hepatic triglyceride content (HTGC) and pancreatic triglyceride content (PTGC) were assessed 45 min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26 weeks of treatment. Results The study population had a mean glycated haemoglobin (HbA1c) level of 7.5 ± 0.2% and a mean body mass index of 36.1 ± 1.1 kg/m2. Ninety five percent had hepatic steatosis at baseline (HTGC ≥ 5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (−0.7 ± 0.3% vs. −0.7 ± 0.4%; p = 0.29), whereas significant weight loss was observed only in the exenatide group (−5.5 ± 1.2 kg vs. −0.2 ± 0.8 kg; p = 0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (−8.8 ± 2.1%) and HTGC (−23.8 ± 9.5%), compared with the reference treatment (EAT: −1.2 ± 1.6%, p = 0.003; HTGC: +12.5 ± 9.6%, p = 0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r = 0.47, p = 0.03, and r = 0.50, p = 0.018, respectively). Conclusion Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.
AbstractList Aim To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores. Methods A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue (EAT), myocardial triglyceride content (MTGC), hepatic triglyceride content (HTGC) and pancreatic triglyceride content (PTGC) were assessed 45min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26weeks of treatment. Results The study population had a mean glycated haemoglobin (HbA1c) level of 7.5 plus or minus 0.2% and a mean body mass index of 36.1 plus or minus 1.1kg/m super(2). Ninety fivepercent had hepatic steatosis at baseline (HTGC greater than or equal to 5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (-0.7 plus or minus 0.3% vs. -0.7 plus or minus 0.4%; p=0.29), whereas significant weight loss was observed only in the exenatide group (-5.5 plus or minus 1.2kg vs. -0.2 plus or minus 0.8kg; p=0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (-8.8 plus or minus 2.1%) and HTGC (-23.8 plus or minus 9.5%), compared with the reference treatment (EAT: -1.2 plus or minus 1.6%, p=0.003; HTGC: +12.5 plus or minus 9.6%, p=0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r=0.47, p=0.03, and r=0.50, p=0.018, respectively). Conclusion Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.
Aim To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores. Methods A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue (EAT), myocardial triglyceride content (MTGC), hepatic triglyceride content (HTGC) and pancreatic triglyceride content (PTGC) were assessed 45min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26weeks of treatment. Results The study population had a mean glycated haemoglobin (HbA1c) level of 7.5±0.2% and a mean body mass index of 36.1±1.1kg/m2. Ninety fivepercent had hepatic steatosis at baseline (HTGC≥5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (-0.7±0.3% vs. -0.7±0.4%; p=0.29), whereas significant weight loss was observed only in the exenatide group (-5.5±1.2kg vs. -0.2±0.8kg; p=0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (-8.8±2.1%) and HTGC (-23.8±9.5%), compared with the reference treatment (EAT: -1.2±1.6%, p=0.003; HTGC: +12.5±9.6%, p=0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r=0.47, p=0.03, and r=0.50, p=0.018, respectively). Conclusion Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.
Aim To conduct a prospective randomized trial to investigate the effect of glucagon‐like peptide‐1 (GLP‐1) analogues on ectopic fat stores. Methods A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue (EAT), myocardial triglyceride content (MTGC), hepatic triglyceride content (HTGC) and pancreatic triglyceride content (PTGC) were assessed 45 min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26 weeks of treatment. Results The study population had a mean glycated haemoglobin (HbA1c) level of 7.5 ± 0.2% and a mean body mass index of 36.1 ± 1.1 kg/m2. Ninety five percent had hepatic steatosis at baseline (HTGC ≥ 5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (−0.7 ± 0.3% vs. −0.7 ± 0.4%; p = 0.29), whereas significant weight loss was observed only in the exenatide group (−5.5 ± 1.2 kg vs. −0.2 ± 0.8 kg; p = 0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (−8.8 ± 2.1%) and HTGC (−23.8 ± 9.5%), compared with the reference treatment (EAT: −1.2 ± 1.6%, p = 0.003; HTGC: +12.5 ± 9.6%, p = 0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r = 0.47, p = 0.03, and r = 0.50, p = 0.018, respectively). Conclusion Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.
To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores. A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue (EAT), myocardial triglyceride content (MTGC), hepatic triglyceride content (HTGC) and pancreatic triglyceride content (PTGC) were assessed 45 min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26 weeks of treatment. The study population had a mean glycated haemoglobin (HbA1c) level of 7.5 ± 0.2% and a mean body mass index of 36.1 ± 1.1 kg/m(2) . Ninety five percent had hepatic steatosis at baseline (HTGC ≥ 5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (-0.7 ± 0.3% vs. -0.7 ± 0.4%; p = 0.29), whereas significant weight loss was observed only in the exenatide group (-5.5 ± 1.2 kg vs. -0.2 ± 0.8 kg; p = 0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (-8.8 ± 2.1%) and HTGC (-23.8 ± 9.5%), compared with the reference treatment (EAT: -1.2 ± 1.6%, p = 0.003; HTGC: +12.5 ± 9.6%, p = 0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r = 0.47, p = 0.03, and r = 0.50, p = 0.018, respectively). Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.
AimTo conduct a prospective randomized trial to investigate the effect of glucagon‐like peptide‐1 (GLP‐1) analogues on ectopic fat stores.MethodsA total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue (EAT), myocardial triglyceride content (MTGC), hepatic triglyceride content (HTGC) and pancreatic triglyceride content (PTGC) were assessed 45 min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26 weeks of treatment.ResultsThe study population had a mean glycated haemoglobin (HbA1c) level of 7.5 ± 0.2% and a mean body mass index of 36.1 ± 1.1 kg/m2. Ninety five percent had hepatic steatosis at baseline (HTGC ≥ 5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (−0.7 ± 0.3% vs. −0.7 ± 0.4%; p = 0.29), whereas significant weight loss was observed only in the exenatide group (−5.5 ± 1.2 kg vs. −0.2 ± 0.8 kg; p = 0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (−8.8 ± 2.1%) and HTGC (−23.8 ± 9.5%), compared with the reference treatment (EAT: −1.2 ± 1.6%, p = 0.003; HTGC: +12.5 ± 9.6%, p = 0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r = 0.47, p = 0.03, and r = 0.50, p = 0.018, respectively).ConclusionOur data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.
AIM: To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores. METHODS: A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue (EAT), myocardial triglyceride content (MTGC), hepatic triglyceride content (HTGC) and pancreatic triglyceride content (PTGC) were assessed 45 min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26 weeks of treatment. RESULTS: The study population had a mean glycated haemoglobin (HbA1c) level of 7.5 ± 0.2% and a mean body mass index of 36.1 ± 1.1 kg/m(2) . Ninety five percent had hepatic steatosis at baseline (HTGC ≥ 5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (-0.7 ± 0.3% vs. -0.7 ± 0.4%; p = 0.29), whereas significant weight loss was observed only in the exenatide group (-5.5 ± 1.2 kg vs. -0.2 ± 0.8 kg; p = 0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (-8.8 ± 2.1%) and HTGC (-23.8 ± 9.5%), compared with the reference treatment (EAT: -1.2 ± 1.6%, p = 0.003; HTGC: +12.5 ± 9.6%, p = 0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r = 0.47, p = 0.03, and r = 0.50, p = 0.018, respectively). CONCLUSION: Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.
Author Darmon, P.
Kober, F.
Ancel, P.
Martin, J. C.
Abdesselam, I.
Dutour, A.
Lesavre, N.
Bernard, M.
Jacquier, A.
Ronsin, O.
Pradel, V.
Lefur, Y.
Gaborit, B.
Mrad, G.
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  fullname: Lesavre, N.
  organization: Aix Marseille Université, Marseille, France
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  email: : Bénédicte Gaborit, Inserm U1062, Inra U1260, Aix Marseille Université, Faculté de Médecine, 27 boulevard Jean Moulin, 13385 Marseille cedex 05, France., benedicte.gaborit@ap-hm.fr
  organization: Inserm U1062, Inra U1260, Faculté de Médecine, 13385, Marseille, France
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27106272$$D View this record in MEDLINE/PubMed
https://hal.science/hal-01478321$$DView record in HAL
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Issue 9
Keywords magnetic resonance imaging
type 2 diabetes
hepatic triglyceride content
pancreatic triglyceride content
epicardial adipose tissue
myocardial triglyceride content
proton magnetic resonance spectroscopy
glucagon-like peptide 1 receptor agonist
obesity
Language English
License http://onlinelibrary.wiley.com/termsAndConditions#vor
2016 John Wiley & Sons Ltd.
Distributed under a Creative Commons Attribution 4.0 International License: http://creativecommons.org/licenses/by/4.0
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Amylin
Figure S1. Discriminant multivariate analysis showing the distribution of patients according to the change of clinical and biological variables between baseline and 26 weeks.Figure S2. Heat map of patients regarding the change of their metabolic data between baseline and 26 weeks.Table S1. Left ventricular function parameters evolution between groups.
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PublicationTitle Diabetes, obesity & metabolism
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2012; 60
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2013; 24
2010; 18
2013; 61
2014; 27
2016; 387
2016; 101
2011; 54
2007; 30
2008; 31
2011; 19
2014; 60
2014; 20
2015; 89
2011; 124
2013; 17
2009; 94
2014; 9
2009; 19
2006; 444
2009; 204
2010; 33
2015; 17
2015; 125
2015; 52
2013; 269
2013; 305
2008; 16
2011; 34
2008; 11
2008; 52
2012; 36
2011; 6
2014; 114
2012; 308
1997; 129
2007; 116
2013; 33
2006; 43
2005; 288
2015; 64
2016; 65
2015
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2012; 7
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Snippet Aim To conduct a prospective randomized trial to investigate the effect of glucagon‐like peptide‐1 (GLP‐1) analogues on ectopic fat stores. Methods A total of...
To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores. A total of 44 obese...
Aim To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores. Methods A total of...
AimTo conduct a prospective randomized trial to investigate the effect of glucagon‐like peptide‐1 (GLP‐1) analogues on ectopic fat stores.MethodsA total of 44...
AIM: To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores. METHODS: A total...
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SubjectTerms Adiponectin
Adipose tissue
Adipose Tissue - diagnostic imaging
Adipose Tissue - metabolism
Body fat
Body mass index
Body weight loss
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Endocrinology and metabolism
epicardial adipose tissue
Fatty liver
Fatty Liver - complications
Fatty Liver - diagnostic imaging
Fatty Liver - metabolism
Female
Glucagon
glucagon-like peptide 1 receptor agonist
Glycated Hemoglobin A - metabolism
Heart - diagnostic imaging
Hemoglobin
hepatic triglyceride content
Human health and pathology
Humans
Hypoglycemic Agents - therapeutic use
Insulin resistance
Life Sciences
Liver - diagnostic imaging
Liver - metabolism
Magnetic Resonance Imaging
Magnetic resonance spectroscopy
Male
Middle Aged
myocardial triglyceride content
Myocardium - metabolism
NMR
Nuclear magnetic resonance
Obesity
Obesity - complications
Obesity - metabolism
Pancreas - diagnostic imaging
Pancreas - metabolism
pancreatic triglyceride content
Patients
Peptides - therapeutic use
Pericardium - diagnostic imaging
Pericardium - metabolism
Population studies
Postprandial Period
Proton Magnetic Resonance Spectroscopy
Spectrum analysis
Steatosis
Treatment Outcome
Triglycerides - metabolism
type 2 diabetes
Venoms - therapeutic use
Title Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: a prospective randomized clinical trial using magnetic resonance imaging and spectroscopy
URI https://api.istex.fr/ark:/67375/WNG-1S742GZD-9/fulltext.pdf
https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fdom.12680
https://www.ncbi.nlm.nih.gov/pubmed/27106272
https://www.proquest.com/docview/1813599931
https://www.proquest.com/docview/3059407008
https://www.proquest.com/docview/1815711331
https://hal.science/hal-01478321
Volume 18
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