Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus.
BACKGROUND
Oxidative stress plays an important role in the pathophysiology of diabetes mellitus. The aim of this study was to evaluate the formation of cholesterol oxides (ChOx) as biomarkers of oxidative stress in subjects with impaired glucose tolerance (IGT) and diabetes.


METHODS
Blood plasma levels of cholesterol oxidation products were determined in the following groups: type 1 diabetes mellitus (DM1), type 2 diabetes (DM2), impaired glucose tolerance (IGT), children without diabetes (C1) and adults without diabetes (C2). The serum levels of cholest-5-ene-3alpha,7alpha-diol (7alpha-hydroxycholesterol, 7alpha-OH), cholest-5-ene-3beta,7beta-diol (7beta-hydroxycholesterol, 7beta-OH), 3beta-hydroxycholest-5-7-one (7-ketocholesterol, 7-K), 5alpha-cholestane-3beta,5,6beta-triol (cholestanetriol), 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol (cholesterol-5alpha,6alpha-epoxide,), 5,6beta-epoxy-5beta-cholestan-3beta-ol (cholesterol-5beta,6beta-epoxide) and cholest-5-eno-3beta,25-diol (25-hydroxycholesterol, 25-OH) (trivial name and abbreviations indicated in parentheses) were quantified by gas chromatography using flame ionization detection.


RESULTS
The levels of total ChOx were elevated in the DM1 and DM2 groups compared to age-matched subjects without diabetes (p < 0.05). The concentrations of 7beta-hydroxycholesterol, cholesterol-alpha-epoxide and cholesterol-beta-epoxide were higher in the blood plasma of subjects in the DM2 group than in the blood plasma of subjects in the C2 and IGT groups (p < 0.05). Treatment of type 2 diabetic patients with oral hypoglycemic drugs associated with insulin resulted in lower concentrations of nitrotyrosine in the blood plasma without significant changes in the concentrations of glucose and glycated hemoglobin. Moreover, combination with statins in both treatments decreased the concentrations of ChOx.


CONCLUSIONS
ChOx are suitable biomarkers of oxidative stress and may be useful in clinical studies to follow drug effects on lipid oxidative modifications in diabetic patients.
Ferderbar
S
S
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Pereira
E C
EC
Apolinário
E
E
Bertolami
M C
MC
Faludi
A
A
Monte
O
O
Calliari
L E
LE
Sales
J E
JE
Gagliardi
A R
AR
Xavier
H T
HT
Abdalla
D S P
DS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers; D002648:Child; D002777:Cholestanols / Q000097:blood; D002784:Cholesterol / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007653:Ketocholesterols / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D002777:Cholestanols; D006888:Hydroxycholesterols; D007004:Hypoglycemic Agents; D007328:Insulin; D007653:Ketocholesterols; C000474:cholestane-3,5,6-triol; C002415:cholesterol alpha-oxide; C011724:cholest-5-en-3 beta,7 alpha-diol; C007997:25-hydroxycholesterol; D002784:Cholesterol; C003001:7-ketocholesterol