Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Abnormal distribution of VLDL subfractions in Type 1 (insulin-dependent) diabetic patients: could plasma lipase activities play a role?


Very low density lipoproteins (VLDL) have an abnormal lipid composition in Type 1 (insulin-dependent) diabetic patients. Since VLDL represent a heterogeneous lipoprotein class, this might be due either to a shift in the distribution or to an abnormal composition of VLDL subclasses or both. In order to investigate these possibilities and to evaluate possible pathogenetic mechanisms, lipid composition (non-esterified and esterified cholesterol, triglycerides, phospholipids) of four VLDL subfractions of decreasing size (A: Svedberg flotation unit [Sf]>400, B: Sf, 175–400, C: Sf 100–175, D: Sf 20–100), isolated by density gradient preparative ultracentrifugation, and plasma post-heparin lipolytic activity (lipoprotein lipase and hepatic lipase) were evaluated in 13 male normolipidaemic insulin-dependent diabetic patients in good glycaemic control (HbA1c 6.9±0.5%) (mean±SEM) and 9 male control subjects matched for age, body mass index and plasma lipid values. Compared to control subjects, diabetic patients showed a reduced total lipid concentration of VLDL of intermediate size (B and C) reaching statistical significance only for VLDL C (0.16±0.02 vs 0.24±0.03 mmol/l; p <0.05). Expressing each VLDL subfraction as percent of the total VLDL lipid concentration, a significant decrease in particles of intermediate size (C) (20.5±1.6 vs 27.9±1.5%; p <0.005) was present, which was compensated by an increase in the smallest ones (D) (50.5±2.7 vs 37.4±3.1%; p <0.05). VLDL of smaller size were also the only particles with an abnormal composition consisting of a significant increase in esterified cholesterol (12.2±0.8 vs 8.7±1.2%, p <0.01). Post-heparin hepatic lipase activity was significantly reduced in diabetic patients as compared to control subjects (232.9±27.9 vs 332±42.3 mU/ml; p <0.05) while post-heparin lipoprotein lipase activity was similar in the two groups. Furthermore, hepatic lipase activity was inversely related to the percentage of smaller VLDL (D)(r=−0.72; p <0.01) in diabetic patients and this relationship was independent of changes in intermediate VLDL (VLDL C). In conclusion the data suggest that Type 1 diabetic patients, although normolipidaemic and in good blood glucose control, show a shift in the distribution of VLDL subclasses toward VLDL of a smaller size which also have an abnormal composition. The different distribution of VLDL subfractions seems to be related to a reduced hepatic lipase activity.


  1. 1.

    Howard BV (1987) Lipoprotein metabolism in diabetes mellitus. J Lipid Res 28: 613–628

  2. 2.

    Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 14: 915–924

  3. 3.

    Austin MA (1991) Plasma triglyceride and coronary heart disease. Arteriosclerosis Thrombosis 11: 2–14

  4. 4.

    Haffner SM (1991) Compositional changes in lipoproteins of subjects with non-insulin-dependent diabetes mellitus. J Lab Clin Med 118: 109–110

  5. 5.

    Suzuki N, Oikawa S, Hori S et al. (1989) Appearance of multidisperse low density lipoprotein and altered lipoprotein composition in non-insulin-dependent diabetes with type II a hyperlipoproteinemia. Metabolism 38: 224–229

  6. 6.

    Bagdade JD, Helve E, Taskinen MR (1991) Effects of continuous insulin infusion therapy on lipoprotein surface and core lipid composition in insulin-dependent diabetes mellitus. Metabolism 40: 445–449

  7. 7.

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

  8. 8.

    Rivellese A, Riccardi G, Romano G et al. (1988) Presence of very low density lipoprotein compositional abnormalities in type 1 (insulin-dependent) diabetic patients; effects of blood glucose optimisation. Diabetologia 31: 884–888

  9. 9.

    Rivellese AA, Romano G, Patti L, Annuzzi G, Riccardi G (1992) Persistent lipoprotein composition-abnormalities in long term well controlled insulin dependent diabetic patients. Diabetes Nutr Metab 5: 99–105

  10. 10.

    Lippel KI, Gianturco S, Fogelman A et al. (1987) Lipoprotein heterogeneity workshop. Arteriosclerosis 7: 315–323

  11. 11.

    Eisenberg S (1987) Intravascular metabolism and conversion of lipoproteins. In: Olsson AG (ed) Atherosclerosis biology and clinical science. Churchill Livingston, London, pp 261–268

  12. 12.

    Home PD, Capaldo B, Burrin JM, Worth R, Alberti KGMM (1982) A cross-over comparison of continuous subcutaneous infusion (CSII) against multiple insulin injection in insulin dependent diabetic subjects: improved control with CSII. Diabetes Care 5: 466–471

  13. 13.

    WHO Expert Committee on Diabetes Mellitus (1980) Second report. Tech Rep Ser 646, World Health Organization, Geneva

  14. 14.

    Hatch FT, Lees RS (1968) Practical methods for plasma lipoprotein analysis. In: Paoletti R, Kritchevsky D (eds) Advances in lipid research, vol 6. Academic Press, London, pp 1–68

  15. 15.

    Kostner GM (1976) Enzymatic determination of cholesterol in high density lipoprotein fractions prepared by polyanion precipitation. Clin Chem 22: 695–698

  16. 16.

    Carlson K (1973) Lipoprotein fractionation. J Clin Pathol 26 [Suppl 5]: 32–37

  17. 17.

    Lindgren FT, Jensen LC, Hatch FT (1972) The isolation and quantitative analysis of serum lipoproteins. In: Nelsen GJ (ed) Blood lipids and lipoproteins: quantitation, composition and metabolism. Wiley-Interscience, New York, pp 181–274

  18. 18.

    Redgrave TR, Carlson LA (1979) Changes in plasma very low density and low density lipoprotein content, composition, and size after a fatty meal in normo- and hypertriglyceridemic man. J Lipid Res 20: 217–229

  19. 19.

    Holmquist L (1982) Surface modification of Beckman Ultra-Clear centrifuge tubes for density gradient ultracentrifugation of lipoprotein. J Lipid Res 23: 1249–1250

  20. 20.

    Nilsson-Ehle P, Ekman R (1977) Rapid, simple and specific assays for lipoprotein lipase and hepatic lipase. Artery 3: 194–209

  21. 21.

    Belfrage P, Vaughan M (1969) Simple liquid/liquid partition system for isolation of labeled oleic acid from mixtures with glycerides. J Lipid Res 10: 341–344

  22. 22.

    Staehler F, Gruber W, Stinshoff K, Roeschlau P (1977) Eine praktischgerechte enzymatische Cholesterin-Bestimmung. Med Lab 30: 29–30

  23. 23.

    Siedel J, Schlumberger H, Klose S, Ziegenhorm J, Wahlefeld AW (1981) Improved reagent for enzymatic determination of serum cholesterol. J Clin Chem Clin Biochem 19: 838–839

  24. 24.

    Wahlefeld AW (1974) Triglycerides determination after enzymatic hydrolysis. In: Bergmeyer HU (ed) Methods of enzymatic analysis, 2nd edn, vol 4. Verlag Chemie, Weinheim Academic Press, New York, London, pp 1831–1974

  25. 25.

    Takaiama M, Itoh S, Nagasaki T, Tanimizu I (1977) A new enzymatic method for determination of serum choline containing phospholipids. Clin Chim Acta 79: 93–98

  26. 26.

    Grafnetter D (1977) World Health Organization (WHO) coordinated quality control in the lipid laboratory. Giorn Arterioscl 2: 113–128

  27. 27.

    Davis JE, McDonald JM, Jarrett L (1978) A high-performance liquid chromatography method for haemoglobin A1c. Diabetes 27: 102–107

  28. 28.

    Snedecor GW, Cochran WG (1980) Statistical methods, 7th edn. The Iowa State University Press, Ames

  29. 29.

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

  30. 30.

    James RW, Pometta D (1990) Differences in lipoprotein subtraction composition and distribution between type I diabetic men and control subjects. Diabetes 39: 1158–1164

  31. 31.

    Nicoll A, Lewis B (1980) Evaluation of the roles of lipoprotein lipase and hepatic lipase in lipoprotein metabolism: in vivo and in vitro studies in man. Eur J Clin Invest 10: 487–495

  32. 32.

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

  33. 33.

    Pietri AO, Dunn FL, Raskin P, Grundy SM (1983) The effect of continuous subcutaneous insulin infusion on very-low-density lipoprotein triglyceride metabolism in type 1 diabetes mellitus. Diabetes 32: 75–81

  34. 34.

    Nikkila EA, Harmila P (1978) Serum lipids and lipoprotein in insulin treated diabetes. Diabetes 27: 1078–1086

  35. 35.

    Patti L, Swinburn B, Riccardi G, Rivellese AA, Howard BV (1991) Alterations in very low density lipoprotein subfractions in normotriglyceridemic non-insulin-dependent diabetics. Atherosclerosis 91: 15–23

  36. 36.

    Klein RL, Lyons TJ, Lopes-Virella MF (1989) Interaction of very low-density lipoprotein isolated from type 1 (insulin-dependent) diabetic subjects with human monocyte-derived macrophages. Metabolism 38: 1108–1114

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Patti, L., Romano, G., Di Marino, L. et al. Abnormal distribution of VLDL subfractions in Type 1 (insulin-dependent) diabetic patients: could plasma lipase activities play a role?. Diabetologia 36, 155–160 (1993).

Download citation

Key words

  • Lipoproteins
  • VLDL subfractions
  • diabetes mellitus
  • lipid composition
  • lipolytic enzymes