Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition.

E Dimitriadis, M Griffin, D Owens, A Johnson, P Collins, G H Tomkin
Author Information
  1. E Dimitriadis: Department of Clinical Medicine, Trinity College, Dublin, Republic of Ireland.

Abstract

The increased risk of atherosclerotic disease in diabetic subjects may be due to enhanced foam cell formation following an increased susceptibility of low density lipoprotein to oxidative modification. This study has compared fatty acid content and lipoprotein oxidisability in 10 non-insulin-dependent diabetic subjects with that in 10 control subjects. Both groups were normocholesterolaemic and the diabetic subjects had higher triglyceride levels (2.2 +/- 0.4 vs 1.2 +/- 0.2 mmol/l, p < 0.05). The fatty acid composition was compared in low density lipoprotein following Folch extraction, separation by thin layer chromatography (for the lipid classes) and analysis by gas liquid chromatography. Low density lipoprotein oxidisability was assessed by conjugated diene and thiobarbituric acid reacting substance formation in the presence of copper ions. The esterified/free cholesterol ratio was higher in the low density lipoprotein from patients compared to control subjects (2.9 +/- 0.1 vs 1.9 +/- 0.3, p < 0.05). Linoleic acid in the cholesteryl ester fraction of the lipoprotein was higher in the patients than in the control subjects (48.2 +/- 2.2% vs 42.4 +/- 3.4%, p < 0.05) as was the total quantity of linoleic acid in the cholesteryl ester fraction (317.8 +/- 68.0 vs 213.2 +/- 28.0 micrograms/mg protein, p < 0.05) and in the low-density lipoprotein as a whole (443.2 +/- 70.0 vs 340.2 +/- 28.2 micrograms/mg protein, p < 0.05). Lipoprotein oxidisability was also increased in the diabetic group with increased formation of thiobarbituric acid reacting substances (35.6 +/- 7.2 vs 22.3 +/- 3.5 nmol/mg protein, p < 0.05, increased total diene formation (502 +/- 60 vs 400 +/- 30 nmol/mg protein, p < 0.05) and increased rate of diene formation (7.2 +/- 0.6 vs 5.1 +/- 0.9 nmol diene.mg protein-1.min-1, p < 0.05). This study indicates that low-density lipoprotein from diabetic subjects is more susceptible to oxidation. This could, in vivo, accelerate foam-cell formation thereby increasing atherosclerotic risk in diabetic subjects.

References

  1. Anal Biochem. 1978 Jun 15;87(1):206-10 [PMID: 98070]
  2. Diabet Med. 1994 Jan-Feb;11(1):85-91 [PMID: 8181259]
  3. Am J Med. 1993 Apr;94(4):350-6 [PMID: 8475928]
  4. Atherosclerosis. 1993 Aug;102(1):63-7 [PMID: 8257453]
  5. J Lipid Res. 1987 May;28(5):495-509 [PMID: 3598395]
  6. J Am Diet Assoc. 1993 Mar;93(3):276-83 [PMID: 8382712]
  7. Klin Wochenschr. 1985 Aug 16;63(16):765-8 [PMID: 4046501]
  8. Biochim Biophys Acta. 1995 Feb 9;1254(3):250-6 [PMID: 7857965]
  9. Arterioscler Thromb. 1993 May;13(5):712-9 [PMID: 8485123]
  10. Atherosclerosis. 1994 Jul;108(1):103-10 [PMID: 7980703]
  11. Anal Biochem. 1991 Oct;198(1):184-90 [PMID: 1838668]
  12. Metabolism. 1990 Dec;39(12):1285-91 [PMID: 2246969]
  13. Diabetologia. 1988 Aug;31(8):576-84 [PMID: 3065111]
  14. Arterioscler Thromb. 1992 Dec;12(12):1496-502 [PMID: 1450181]
  15. Clin Chim Acta. 1988 Feb 15;171(2-3):293-303 [PMID: 3286062]
  16. J Am Geriatr Soc. 1991 Jun;39(6):571-4 [PMID: 2037746]
  17. Metabolism. 1991 Feb;40(2):175-80 [PMID: 1988775]
  18. Diabetologia. 1984 Feb;26(2):134-7 [PMID: 6425101]
  19. Free Radic Res Commun. 1989;6(1):67-75 [PMID: 2722022]
  20. Lancet. 1994 Jun 18;343(8912):1528-30 [PMID: 7911870]
  21. Diabetes. 1992 Oct;41 Suppl 2:61-6 [PMID: 1526338]
  22. Atherosclerosis. 1989 Oct;79(2-3):245-52 [PMID: 2597232]
  23. Adv Exp Med Biol. 1991;285:353-65 [PMID: 1858567]
  24. J Lipid Res. 1990 Jun;31(6):1043-50 [PMID: 2373954]
  25. Diabetes. 1990 Nov;39(11):1420-4 [PMID: 2227114]
  26. Methods Enzymol. 1978;52:302-10 [PMID: 672633]
  27. Atherosclerosis. 1992 Apr;93(3):189-99 [PMID: 1590824]
  28. J Clin Invest. 1993 Feb;91(2):668-76 [PMID: 8432867]
  29. Diabet Med. 1987 Sep-Oct;4(5):452-6 [PMID: 2959437]
  30. Arterioscler Thromb. 1992 Apr;12(4):529-33 [PMID: 1558840]
  31. Am J Clin Nutr. 1991 Oct;54(4):701-6 [PMID: 1897476]
  32. Free Radic Biol Med. 1992 Oct;13(4):341-90 [PMID: 1398217]
  33. Diabete Metab. 1992 Jul-Aug;18(4):264-71 [PMID: 1459313]
  34. Diabetes Res Clin Pract. 1992 Nov;18(2):89-98 [PMID: 1478157]
  35. J Biol Chem. 1957 May;226(1):497-509 [PMID: 13428781]
  36. J Biol Chem. 1987 Mar 15;262(8):3603-8 [PMID: 3102491]
  37. Diabet Med. 1991 Oct;8(8):752-8 [PMID: 1838067]
  38. J Biol Chem. 1989 Feb 15;264(5):2599-604 [PMID: 2914924]
  39. J Clin Invest. 1955 Sep;34(9):1345-53 [PMID: 13252080]
  40. Biochem Soc Trans. 1994 Feb;22(1):34S [PMID: 8206256]
  41. Diabetologia. 1988 Feb;31(2):126-7 [PMID: 3360222]
  42. Biochem Pharmacol. 1992 Mar 3;43(5):995-1000 [PMID: 1554398]

MeSH Term

Aged
Case-Control Studies
Diabetes Mellitus, Type 2
Fatty Acids
Female
Humans
Lipoproteins, LDL
Male
Middle Aged
Oxidation-Reduction
Triglycerides

Chemicals

Fatty Acids
Lipoproteins, LDL
Triglycerides

Word Cloud

Created with Highcharts 10.0.00+/-2lipoproteinsubjectsvsp<05acidincreaseddiabeticformationdensity1diene3proteinlowcomparedfattyoxidisabilitycontrolhigher9low-densityriskatheroscleroticfollowingstudy104compositionchromatographythiobarbituricreactingpatientscholesterylesterfractiontotal28micrograms/mg675nmol/mgdiseasemaydueenhancedfoamcellsusceptibilityoxidativemodificationcontentnon-insulin-dependentgroupsnormocholesterolaemictriglyceridelevelsmmol/lFolchextractionseparationthinlayerlipidclassesanalysisgasliquidLowassessedconjugatedsubstancepresencecopperionsesterified/freecholesterolratioLinoleic482%424%quantitylinoleic317868213whole44370340Lipoproteinalsogroupsubstances35225026040030ratenmolmgprotein-1min-1indicatessusceptibleoxidationvivoacceleratefoam-celltherebyincreasingOxidationNIDDM:relationship

Similar Articles

Cited By