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The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study

Aim/hypothesis Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action i... Full description

Journal Title: Diabetologia 2008-12-23, Vol.52 (3), p.385-393
Main Author: Koska, J
Other Authors: Ortega, E , Bunt, J. C , Gasser, A , Impson, J , Hanson, R. L , Forbes, J , de Courten, B , Krakoff, J
Format: Electronic Article Electronic Article
Language: English
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Publisher: Berlin/Heidelberg: Springer-Verlag
ID: ISSN: 0012-186X
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title: The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study
format: Article
creator:
  • Koska, J
  • Ortega, E
  • Bunt, J. C
  • Gasser, A
  • Impson, J
  • Hanson, R. L
  • Forbes, J
  • de Courten, B
  • Krakoff, J
subjects:
  • Adiponectin - blood
  • Adolescent
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
  • Article
  • Biological and medical sciences
  • Blood Glucose - drug effects
  • Blood Glucose - metabolism
  • Body Mass Index
  • C-Reactive Protein - metabolism
  • Clinical science
  • Clinical trials
  • Cytokines
  • Dextrose
  • Diabetes
  • Diabetes. Impaired glucose tolerance
  • Double-Blind Method
  • Endocrine pancreas. Apud cells (diseases)
  • Endocrinology
  • Endocrinopathies
  • Etiopathogenesis. Screening. Investigations. Target tissue resistance
  • Fatty Acids, Nonesterified - blood
  • Female
  • Glucose
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Glucose tolerance tests
  • Human
  • Human Physiology
  • Humans
  • Hyperinsulinism
  • Insulin
  • Insulin - blood
  • Insulin - pharmacology
  • Insulin - physiology
  • Insulin resistance
  • Insulin sensitivity and resistance
  • Internal Medicine
  • Male
  • Medical sciences
  • Medicine
  • Medicine & Public Health
  • Metabolic Diseases
  • Metabolism
  • Middle Aged
  • Obesity - blood
  • Obesity - drug therapy
  • Placebos
  • Prediction and prevention of type 2 diabetes
  • Salicylates - therapeutic use
  • Salsalate
  • Sample Size
  • Young Adult
ispartof: Diabetologia, 2008-12-23, Vol.52 (3), p.385-393
description: Aim/hypothesis Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals. Methods The study was a randomised, double-blind, placebo-controlled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI ≥ 30 kg/m 2 . The intervention was salsalate (3 g/day, n  = 28) or identical placebo ( n  = 26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal ( R d ) by euglycaemic–hyperinsulinaemic clamp (insulin infusion rate 40 mU m −2 min −1 ) and glucose tolerance by 75 g OGTT. Results The study was completed by 47 participants, of which 40 were analysed (salsalate n  = 22, placebo n  = 18). Salsalate treatment resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83 [0.28] vs 5.11 [0.33] mmol/l, p  = 0.001) and glucose AUC during the OGTT ( p  = 0.01), and in increased R d (20 [8] vs 18 [6] µmol [kg estimated metabolic body size] −1 min −1 , p  = 0.002), while there was no significant change in these variables with placebo ( p  > 0.3 for all). The effect of salsalate on R d disappeared ( p  = 0.9) after normalising to increased insulin concentrations (701 [285] vs 535 [201] pmol/l, p  
language: eng
source:
identifier: ISSN: 0012-186X
fulltext: no_fulltext
issn:
  • 0012-186X
  • 1432-0428
url: Link


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titleThe effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study
creatorKoska, J ; Ortega, E ; Bunt, J. C ; Gasser, A ; Impson, J ; Hanson, R. L ; Forbes, J ; de Courten, B ; Krakoff, J
creatorcontribKoska, J ; Ortega, E ; Bunt, J. C ; Gasser, A ; Impson, J ; Hanson, R. L ; Forbes, J ; de Courten, B ; Krakoff, J
descriptionAim/hypothesis Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals. Methods The study was a randomised, double-blind, placebo-controlled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI ≥ 30 kg/m 2 . The intervention was salsalate (3 g/day, n  = 28) or identical placebo ( n  = 26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal ( R d ) by euglycaemic–hyperinsulinaemic clamp (insulin infusion rate 40 mU m −2 min −1 ) and glucose tolerance by 75 g OGTT. Results The study was completed by 47 participants, of which 40 were analysed (salsalate n  = 22, placebo n  = 18). Salsalate treatment resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83 [0.28] vs 5.11 [0.33] mmol/l, p  = 0.001) and glucose AUC during the OGTT ( p  = 0.01), and in increased R d (20 [8] vs 18 [6] µmol [kg estimated metabolic body size] −1 min −1 , p  = 0.002), while there was no significant change in these variables with placebo ( p  > 0.3 for all). The effect of salsalate on R d disappeared ( p  = 0.9) after normalising to increased insulin concentrations (701 [285] vs 535 [201] pmol/l, p  < 0.0001) measured during the clamp. No side effects of salsalate were observed during the study. Conclusions/interpretation The glucose-lowering potential of salicylates appears to be due to effects on insulin concentration rather than improved insulin action. Salicylate-based compounds may be useful for the treatment and prevention of type 2 diabetes. Trial registration: ClinicalTrials.gov NCT 00339833. Funding: Intramural research programme of the NIDDK/NIH/DHHS.
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languageeng
publisherBerlin/Heidelberg: Springer-Verlag
subjectAdiponectin - blood ; Adolescent ; Adult ; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; Article ; Biological and medical sciences ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Body Mass Index ; C-Reactive Protein - metabolism ; Clinical science ; Clinical trials ; Cytokines ; Dextrose ; Diabetes ; Diabetes. Impaired glucose tolerance ; Double-Blind Method ; Endocrine pancreas. Apud cells (diseases) ; Endocrinology ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Fatty Acids, Nonesterified - blood ; Female ; Glucose ; Glucose Clamp Technique ; Glucose Tolerance Test ; Glucose tolerance tests ; Human ; Human Physiology ; Humans ; Hyperinsulinism ; Insulin ; Insulin - blood ; Insulin - pharmacology ; Insulin - physiology ; Insulin resistance ; Insulin sensitivity and resistance ; Internal Medicine ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolism ; Middle Aged ; Obesity - blood ; Obesity - drug therapy ; Placebos ; Prediction and prevention of type 2 diabetes ; Salicylates - therapeutic use ; Salsalate ; Sample Size ; Young Adult
ispartofDiabetologia, 2008-12-23, Vol.52 (3), p.385-393
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descriptionAim/hypothesis Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals. Methods The study was a randomised, double-blind, placebo-controlled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI ≥ 30 kg/m 2 . The intervention was salsalate (3 g/day, n  = 28) or identical placebo ( n  = 26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal ( R d ) by euglycaemic–hyperinsulinaemic clamp (insulin infusion rate 40 mU m −2 min −1 ) and glucose tolerance by 75 g OGTT. Results The study was completed by 47 participants, of which 40 were analysed (salsalate n  = 22, placebo n  = 18). Salsalate treatment resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83 [0.28] vs 5.11 [0.33] mmol/l, p  = 0.001) and glucose AUC during the OGTT ( p  = 0.01), and in increased R d (20 [8] vs 18 [6] µmol [kg estimated metabolic body size] −1 min −1 , p  = 0.002), while there was no significant change in these variables with placebo ( p  > 0.3 for all). The effect of salsalate on R d disappeared ( p  = 0.9) after normalising to increased insulin concentrations (701 [285] vs 535 [201] pmol/l, p  < 0.0001) measured during the clamp. No side effects of salsalate were observed during the study. Conclusions/interpretation The glucose-lowering potential of salicylates appears to be due to effects on insulin concentration rather than improved insulin action. Salicylate-based compounds may be useful for the treatment and prevention of type 2 diabetes. Trial registration: ClinicalTrials.gov NCT 00339833. Funding: Intramural research programme of the NIDDK/NIH/DHHS.
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17Endocrine pancreas. Apud cells (diseases)
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20Etiopathogenesis. Screening. Investigations. Target tissue resistance
21Fatty Acids, Nonesterified - blood
22Female
23Glucose
24Glucose Clamp Technique
25Glucose Tolerance Test
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31Insulin
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37Internal Medicine
38Male
39Medical sciences
40Medicine
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42Metabolic Diseases
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45Obesity - blood
46Obesity - drug therapy
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abstractAim/hypothesis Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals. Methods The study was a randomised, double-blind, placebo-controlled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI ≥ 30 kg/m 2 . The intervention was salsalate (3 g/day, n  = 28) or identical placebo ( n  = 26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal ( R d ) by euglycaemic–hyperinsulinaemic clamp (insulin infusion rate 40 mU m −2 min −1 ) and glucose tolerance by 75 g OGTT. Results The study was completed by 47 participants, of which 40 were analysed (salsalate n  = 22, placebo n  = 18). Salsalate treatment resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83 [0.28] vs 5.11 [0.33] mmol/l, p  = 0.001) and glucose AUC during the OGTT ( p  = 0.01), and in increased R d (20 [8] vs 18 [6] µmol [kg estimated metabolic body size] −1 min −1 , p  = 0.002), while there was no significant change in these variables with placebo ( p  > 0.3 for all). The effect of salsalate on R d disappeared ( p  = 0.9) after normalising to increased insulin concentrations (701 [285] vs 535 [201] pmol/l, p  < 0.0001) measured during the clamp. No side effects of salsalate were observed during the study. Conclusions/interpretation The glucose-lowering potential of salicylates appears to be due to effects on insulin concentration rather than improved insulin action. Salicylate-based compounds may be useful for the treatment and prevention of type 2 diabetes. Trial registration: ClinicalTrials.gov NCT 00339833. Funding: Intramural research programme of the NIDDK/NIH/DHHS.
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