Skip to main content
SpringerLink
Log in

Marine lipids normalize cholesteryl ester transfer in IDDM

  • Originals
  • Published:
Diabetologia Aims and scope Submit manuscript

Summary

Patients with insulin-dependent diabetes mellitus (IDDM) have a pathological increase in cholesteryl ester transfer (CET) that enriches the apolipoprotein B-containing lipoproteins with cholesteryl ester and increases their atherogenicity. Since we have shown earlier that omega-3 (n-3) fatty acids present in marine lipids normalize both CET and lipoprotein composition in non-diabetic patients with hypercholesterolaemia, we sought to determine whether the same beneficial effects could be achieved in nine normolipidaemic (triglycerides 1.10; cholesterol 4.94, high density lipoprotein 1.10 mmol/l) IDDM patients (fructosamine 424±156; normal 174–286 Μmol/l) treated for 2 months with n-3 fatty acids (4.6 g/day). Before treatment, CET measured by both mass and isotopic assays was abnormally accelerated (p<0.001). While marine lipids modestly decreased triglyceride levels (−14%; p<0.05), CET fell dramatically in all subjects (mass assay: −97% at 1 h; isotopic assay: −58%; p<0.001) to below control levels with no change in glycaemic control (fructosamine 408±103 Μmol/l). The mass of cholesteryl ester transfer protein paradoxically increased significantly (pre-treatment: 2.04±0.86 vs post-treatment 2.48±0.97 Μg/ml; p<0.05). Since it is believed that accelerated CET promotes the formation of atherogenic cholesteryl ester-enriched apo B-containing lipoproteins, the capacity of marine lipids to reverse this functional abnormality without altering glycaemic control suggests that these agents may have an adjunctive role to play in the nutritional therapy of IDDM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

IDDM:

Insulin-dependent diabetes mellitus

NIDDM:

non-insulin-dependent diabetes mellitus

CET:

cholesteryl ester transfer

CETP:

cholesteryl ester transfer protein

HDL:

high density lipoprotein

LpL:

lipoprotein lipase

apo B:

apolipoprotein B

n-3 fatty acids:

omega-3 fatty acids

References

  1. Eskimo diets and diseases (1983) (Editorial) Lancet I: 1139–1141

  2. Arthaud JB (1970) Cause of death in 339 Alaskan natives as determined by autopsy. Arch Pathol Lab Med 90: 433–438

    Google Scholar 

  3. Leaf A, Weber PC (1988) Cardiovascular effects of n-3 fatty acids. N Engl J Med 318: 549–557

    PubMed  Google Scholar 

  4. Colwell JA, Lopes-Virella MF, Halushka PV (1981) Pathogenesis of atherosclerosis in diabetes mellitus. Diabetes Care 4: 121–133

    PubMed  Google Scholar 

  5. Bagdade JD, Subbaiah PV, Ritter MC (1991) Accelerated cholesteryl ester transfer in patients with insulin dependent diabetes mellitus. Eur J Clin Invest 21: 161–167

    PubMed  Google Scholar 

  6. Bagdade JD, Subbaiah PV (1989) Abnormal high-density lipoprotein composition in women with insulin dependent diabetes. J Lab Clin Med 113: 235–240

    PubMed  Google Scholar 

  7. Bagdade JD, Subbaiah PV (1989) Whole-plasma and high-density lipoprotein subfraction surface lipid composition in IDDM men. Diabetes 38: 1226–1230

    PubMed  Google Scholar 

  8. Mahley RW (1982) Atherogenic hyperlipoproteinemia: the cellular and molecular biology of plasma lipoproteins altered by dietary fat and cholesterol. Med Clin North Am 66: 375–402

    PubMed  Google Scholar 

  9. Bagdade JD, Ritter MC, Davidson M, Subbaiah PV (1992) Effects of marine lipids on lipoprotein composition and cholesteryl ester transfer in patients with hypercholesterolemia. Arterioscler Thromb 12: 1146–1152

    PubMed  Google Scholar 

  10. Bagdade JD, Subbaiah PV, Ritter MC (1991) Accelerated cholesteryl ester transfer in plasma of patients with hypercholesterolemia. J Clin Invest 87: 1259–1265

    PubMed  Google Scholar 

  11. Gibson JC, Rubenstein A, Brown WV (1984) Precipitation of apoE-containing lipoproteins by precipitation reagents for apolipoprotein B. Clin Chem 30: 1784–1788

    PubMed  Google Scholar 

  12. Quig DW, Zilversmit DB (1988) Plasma lipid transfer activity in rabbits: effects of dietary hyperlipidemias. Atherosclerosis 70: 263–271

    PubMed  Google Scholar 

  13. Marcel YL, McPherson R, Hogue M, et al. (1990) Distribution and concentration of cholesteryl ester transfer protein in plasma of normolipidemic subjects. J Clin Invest 85: 10–17

    PubMed  Google Scholar 

  14. Kasim SE, Stern B, Khilnani S, McLin P, Baciorowski S, Jen K-LC Jen (1988) Effects of omega-3 fish oils on lipid metabolism, glycemic control and blood pressure in type II diabetic patients. J Clin Endo Metab 67: 1–5

    Google Scholar 

  15. Schectman G, Kaul S, Kissebah AH (1989) Heterogeneity of low density lipoprotein responses to fish-oil supplementation in hypertriglyceridemic subjects. Arteriosclerosis 9: 345–354

    PubMed  Google Scholar 

  16. Connor WE, Prince MJ, Ullmann D, Riddle M, Hatcher L, Smith FE, Wilson D (1993) The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. Ann NY Acad Sci 683: 337–342

    PubMed  Google Scholar 

  17. Parks JS (1993) The effect of dietary n-3 fatty acids on the atherogenic properties of low density lipoproteins (LDL) and atherosclerosis in nonhuman primates. In: Yasugi T, Nakamura H, Soma M (eds) Adv polyunsaturated fatty acid research. Excerpta Medica, Amsterdam B. V., pp 141–145

    Google Scholar 

  18. Bagdade JD, Buchanan WE, Levy RL, Subbaiah PV, Ritter MC (1990) Effects of omega-3 fish oils on plasma lipids, lipoprotein composition, and post-heparin lipoprotein lipase in women with insulin dependent diabetes. Diabetes 39: 426–431

    PubMed  Google Scholar 

  19. Nestel PJ, Connor WE, Reardon MF, Connor S, Wong S, Boston R (1984) Suppression by diets rich in fish oil of very low density lipoprotein production in man. J Clin Invest 74: 82–89

    PubMed  Google Scholar 

  20. Tall AR (1993) Plasma cholesteryl ester transfer protein. J Lip Res 34: 1255–1274

    Google Scholar 

  21. Dullaart RPF, Groener JEM, Dikkaschei LD, Erkelens DW, Doorenbos H (1989) Increased cholesteryl ester transfer activity in complicated type 1 (insulin-dependent) diabetes mellitus — its relationship with serum lipids. Diabetologia 32: 14–19

    PubMed  Google Scholar 

  22. Bagdade JD, Lane JT, Subbaiah PV, Otto ME, Ritter MC (1993) Accelerated cholesteryl ester transfer in noninsulin dependent diabetes mellitus. Atherosclerosis 104: 69–77

    PubMed  Google Scholar 

  23. Tall A, Granot E, Brochia R et al. (1987) Accelerated cholesteryl ester transfer in dyslipidemic plasma. Role of cholesteryl ester transfer protein. J Clin Invest 79: 1217–1225

    PubMed  Google Scholar 

  24. Mann GJ, Yen FT, Grant AM, Bihain BE (1991) Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia. J Clin Invest 88: 2059–2066

    PubMed  Google Scholar 

  25. Inazu A, Brown ML, Hesler CB et al. (1990) Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med 323: 1234–1238

    PubMed  Google Scholar 

  26. Tall AR (1986) Plasma lipid transfer proteins. J Lipid Res 27: 361–367

    PubMed  Google Scholar 

  27. Marotti KR, Castle CK, Boyle TP et al. (1993) Severe atherosclerosis in transgenic mice expressing simian cholesteryl ester transfer protein. Nature 364: 73–75

    Article  PubMed  Google Scholar 

  28. Quinet E, Tall A, Rudel L (1991) Plasma lipid transfer protein as a determinant of the atherogenicity of monkey plasma lipoproteins. J Clin Invest 87: 1559–1566

    PubMed  Google Scholar 

  29. Eckel RH (1989) Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic disease. N Engl J Med 320: 1060–1068

    PubMed  Google Scholar 

  30. Bagdade JD, Dunn FL, Eckel R, Ritter MC (1994) Intraperitoneal insulin therapy corrects abnormalities in cholesteryl ester transfer and lipoprotein lipase in insulin-dependent diabetes mellitus. Arterioscler Thromb 14: 1933–1939

    PubMed  Google Scholar 

  31. Tall AR, Sammett D, Granot E (1986) Mechanisms of enhanced cholesteryl ester transfer from high density lipoproteins to apo B-containing lipoproteins during alimentary lipemia. J Clin Invest 77: 1163–1172

    PubMed  Google Scholar 

  32. Brown G, Albers JJ, Fisher LD, Schaffer SM et al. (1990) Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein-B. N Engl J Med 323: 1289–1298

    PubMed  Google Scholar 

  33. Harris W (1989) Fish oils and plasma lipid and lipoprotein metabolism in humans. A critical review. J Lipid Res 30: 785–801

    PubMed  Google Scholar 

  34. Morton RE, Steinbrunner JV (1993) Determination of lipid transfer inhibitory protein activity in human lipoprotein-deficient plasma. Arterioscler Thromb 13: 1843–1851

    PubMed  Google Scholar 

  35. Swenson TL (1992) Transfer proteins in reverse cholesterol transport. Current Opinion in Lipidology 3: 67–74

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rush Medical College, Chicago, Illinois, USA

    J. D. Bagdade, M. Ritter & P. V. Subbaiah

Authors
  1. J. D. Bagdade
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Ritter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. V. Subbaiah
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bagdade, J.D., Ritter, M. & Subbaiah, P.V. Marine lipids normalize cholesteryl ester transfer in IDDM. Diabetologia 39, 487–491 (1996). https://doi.org/10.1007/BF00400682

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00400682

Keywords

Search

Navigation