Salsalate-induced changes in lipid, lipoprotein, and apoprotein concentrations in overweight or obese, insulin-resistant, nondiabetic individuals.
OBJECTIVE
Although salsalate administration consistently lowers plasma triglyceride concentrations in patients with type II diabetes, prediabetes, and/or insulin resistance, changes in low-density lipoprotein cholesterol (LDL-C) concentrations have been inconsistent; varying from no change to a significant increase. To evaluate the clinical relevance of this discordance in more detail, we directly measured LDL-C and obtained a comprehensive assessment of changes in lipid, lipoprotein, and apoprotein concentrations associated with salsalate use in insulin-resistant individuals, overweight or obese, but without diabetes, using vertical auto profile method.


METHODS
A single-blind, randomized, placebo-controlled study was performed in volunteers who were overweight or obese, without diabetes, and insulin resistant on the basis of their steady-state plasma glucose concentration during an insulin suppression test. Participants were randomized 2:1 to receive salsalate 3.5 g/d (n = 27) or placebo (n = 14) for 4 weeks. Comprehensive lipid, lipoprotein, and apoprotein analysis by vertical auto profile was obtained after an overnight fast, before and after study intervention.


RESULTS
There was no change in directly measured LDL-C concentration in salsalate-treated individuals. However, salsalate administration was associated with various changes considered to decrease atherogenicity; including decreases in triglyceride and total very low-density lipoprotein cholesterol (VLDL-C) concentrations, a shift from small denser LDL lipoproteins toward larger, more buoyant LDL particles, decreases in VLDL(1+2)-C and LDL(4)-C, and nonsignificant decreases in non-high-density lipoprotein cholesterol and apolipoprotein B. No significant changes occurred in the placebo-treated group.


CONCLUSIONS
Atherogenicity of the lipid, lipoprotein, and apoprotein profile of insulin-resistant individuals who were overweight or obese improved significantly in association with salsalate treatment. The clinical importance of this finding awaits further study.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: dariel@stanford.edu.
Danit
D
Ariel
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Sun H
SH
Kim
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Alice
A
Liu
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Fahim
F
Abbasi
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Cindy A
CA
Lamendola
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Kaylene
K
Grove
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Vanessa
V
Tomasso
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Gerald M
GM
Reaven
D001059:Apoproteins / Q000097:blood*; D050197:Atherosclerosis / Q000097:blood; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D012459:Salicylates / Q000494:pharmacology*
D001059:Apoproteins; D008074:Lipoproteins; D012459:Salicylates; C014182:salicylsalicylic acid
Cardiovascular disease risk; Insulin resistance; Lipid and/or lipoprotein abnormalities; Prediabetes; Salsalate