Vnitr Lek 2008, 54(11):1045-1053

Relationship between familial combined hyperlipidemia and insulin resistance

D. Jackuliaková*, H. Vaverková, D. Karásek
III. interní klinika Lékařské fakulty UP a FN Olomouc, přednosta prof. MUDr. Vlastimil Ščudla, CSc.

Background and aims:
Familial combined hyperlipidemia is the most frequent hereditary dyslipidemia, usually associated with insulin resistance. Recently, the diagnostic criteria of familial combined hyperlipidemia were redefined: There should be at least two 1st degree hyperlipidemic relatives with both triglycerides ≥ 1.5 mmol.L-1 and apolipoprotein B ≥ 1.20 g L-1. The aim of this study was to evaluate the relationship between this lipoprotein phenotype and the presence of insulin resistance and to assess the presence of metabolic syndrome.

Methods:
Lipid parameters and parameters associated with insulin resistance were determined in 90 subjects of families with familial combined hyperlipidemia and 38 controls. The members of affected families were further divided into the hyperlipidemic and normolipidemic group.

Results:
The hyperlipidemic group showed only significantly higher fasting proinsulin levels [HL 17,4 ± 1.5 vs NL 12.8 ± 1.4 (p = 0.030); and vs CO 11.1 ± 1.4 (p = 0.003)] in comparison with the normolipidemic and control groups. Differences in fasting insulin [HL 9.40 ± 0.78 vs NL 7.78 ± 0.71 (p = NS); and vs CO 7.30 ± 0.76 (p = NS)], C-peptide [HL 2.56 ± 0.19 vs NL 2.27 ± 0.17 (p = NS); and vs CO 2.07 ± 0.18 (p = NS)], and HOMA [HL 2.16 ± 0.21 vs NL 1.84 ± 0.20 (p = NS); and vs CO 1.69 ± 0.21 (p = NS)] did not reach statistical significance. On the contrary, the members of families with familial combined hyperlipidemia with the presence of metabolic syndrome (NCEP-ATP III) had significantly higher fasting insulin [FCH with MS 12.74 ± 1.42 vs HL without MS 9.21 ± 0.92 (p = 0.030); and vs NL without MS 6.75 ± 0.80 (p = 0.001)], and proinsulin levels [FCH with MS 25.28 vs HL without MS 15.69 ± 1.75 (p = 0.002); and vs NL without MS 11.20 ± 1.51 (p = 0.0001)], and HOMA index [FCH with MS 3.03 ± 0.39 vs HL without MS 2.13 ± 0.25 (p = 0.042); and vs. NL without MS 1.56 ± 0.22 (p = 0.003)] in comparison with their relatives without metabolic syndrome and controls.

Conclusion:
The presence of the metabolic syndrome could detect the most insulin resistant subjects in families with familial combined hyperlipidemia who are at increased risk of cardiovascular disease.

Keywords: familial combined hyperlipidemia; insulin resistance; metabolic syndrome

Received: June 23, 2008; Accepted: August 4, 2008; Published: November 1, 2008  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Jackuliaková D, Vaverková H, Karásek D. Relationship between familial combined hyperlipidemia and insulin resistance. Vnitr Lek. 2008;54(11):1045-1053.
Download citation

References

  1. Goldstein JL, Hazzard WR, Schrott HG. Hyperlipidemia in coronary heart disease. I. Lipid levels in 500 survivors of myocardial infarction. J Clin Invest 1973; 52: 1533-1543. Go to original source... Go to PubMed...
  2. Goldstein JL, Schrott HG, Hazzard WR. Hyperlipidemia in coronary heart disease. II: Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest 1973; 52:1544-1568. Go to original source... Go to PubMed...
  3. Goldstein JL, Schrott HG, Hazzard WR. Hyperlipidemia in coronary heart disease. III: Evaluation of lipoprotein phenotypes of 156 genetically defined survivors of myocardial infarction. J Clin Invest 1973; 52: 1569-1577. Go to original source... Go to PubMed...
  4. Veerkamp MJ, de Graaf J, Hendriks JCM et al. Nomogram to diagnose familial combined hyperlipidemia on the basis of results of a 5-year follow-up study. Circulation 2004; 109: 2980-2985. Go to original source... Go to PubMed...
  5. Hopkins PN, Heis G, Ellison RC et al. Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia. Circulation 2003; 108: 519-523. Go to original source... Go to PubMed...
  6. Ayyobi AF, McGladdery SH, McNeely MJ et al. Small, dense LDL and elevated apolipoprotein B are the common characteristics for the three major lipid phenotypes of familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol 2003; 23: 1289-1294. Go to original source... Go to PubMed...
  7. Brunzel JD, Albers JJ, Chait A et al. Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia. J Lipid Res 1983; 24: 147-155. Go to original source...
  8. Delawi D, Meijssen S, Cabezas S. Intra-individual variations of fasting plasma lipids, apolipoproteins and postprandial lipemia in familial combined hyperlipidemia controls. Clinica Chimica Acta 2003; 328: 139-145. Go to original source... Go to PubMed...
  9. Karjalainen L, Pihlajamäki J, Karhapää P et al. Impaired insulin-stimulated glucose oxidation and free fatty acid suppression in patients with familial combined hyperlipidemia: A precursor defect for dyslipidemia? Arterioscler Thromb Vasc Biol 1998; 18: 1548-1553. Go to original source... Go to PubMed...
  10. Keulen ETP, Kruijshoop M, Schaper NC et al. Increased intima-media thickness in familial combined hyperlipidemia associated with apolipoprotein B. Arterioscler Thromb Vasc Biol 2002; 22: 283-288. Go to original source... Go to PubMed...
  11. Pischon T, Girman CJ, Sacks FM et al. Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation 2005; 112: 3375-3383. Go to original source... Go to PubMed...
  12. Porkka KVK, Nuotio I, Pajukanta P et al. Phenotype expression in familial combined hyperlipidemia. Atherosclerosis 1997; 133: 245-253. Go to original source... Go to PubMed...
  13. Veerkamp MJ, de Graaf J, Bredie SJH et al. Diagnosis of familial combined hyperlipidemia based on lipid phenotype expression in 32 families. Arterioscler Thromb Vasc Biol 2002; 22: 274-282. Go to original source... Go to PubMed...
  14. Venkatesan S, Cullen P, Pacy P et al. Stable isotopes show a direct relation between VLDL apoB overproduction and serum triglyceride levels and indicate a metabolically and biochemically coherent basis for familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol 1993; 13: 1110-1118. Go to original source... Go to PubMed...
  15. Soro A, Jauhianinen M, Ehnholm C et al. Determinants of low HDL levels in familial combined hyperlipidemia. J Lipid Res 2003; 44: 1536-1544. Go to original source... Go to PubMed...
  16. Georgieva AM, van Greevenbroek MMJ, Krauss RM et al. Subclasses of low-density lipoprotein and very low-density lipoprotein in familial combined hyperlipidemia: Relationship to multiple lipoprotein phenotype. Arterioscler Thromb Vasc Biol 2004; 24: 744-749. Go to original source... Go to PubMed...
  17. Vakkilainen J, Jauhiainen M, Ylitalo K et al. LDL particle size in familial combined hyperlipidemia: Effects of serum lipids, lipoproetin-modifying enzymes, and lipid transfer proteins. J Lipid Res 2002; 43: 598-603. Go to original source...
  18. Ascaso JF, Real JT, Merchante A et al. Lipoprotein phenotype and insulin resistance in familial combined hyperlipidemia. Metabolism 2000; 49: 1627-1631. Go to original source... Go to PubMed...
  19. Pihlajamaki J, Karjalainen L, Karhapaa L et al. Impaired free fatty acid suppression during hyperinsulinemia is a characteristic finding in familial combined hyperlipidemia, but insulin resistance is observed only in hypertriglyceridemic patients. Arterioscler Thromb Vasc Biol 2000; 20: 164-170. Go to original source... Go to PubMed...
  20. van der Kallen CJ, Voors-Pette C, de Bruin TWA. Abdominal obesity and expression of familial combined hyperlipidemia. Obes Res 2004; 12: 2054-2061. Go to original source... Go to PubMed...
  21. Veerkamp MJ, de Graaf MJ, Stalenhoef AFH. Role of insulin resistance in familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol 2005; 25:1026-1031. Go to original source... Go to PubMed...
  22. Cabezas MC, de Bruin TWA, de Valk HW et al. Impaired fatty acid metabolism in familial combined hyperlipidemia. A mechanism associating hepatic apolipoprotein B overproduction and insulin resistance. J Clin Invest 1993; 92: 160-168. Go to original source... Go to PubMed...
  23. van der Kallen CJH, Voors-Pette C, Bouwman CG et al. Evidence of insulin resistant lipid metabolism in adipose tissue in familial combined hyperlipidemia, but not type 2 diabetes mellitus. Atherosclerosis 2002; 164: 337-346. Go to original source... Go to PubMed...
  24. Purnell JQ, Kahn SE, Schwartz RS et al. Relationship of Insulin Sensitivity and ApoB Levels to Intra-abdominal Fat in Subjects With Familial Combined Hyperlipidemia. Arterioscler Thromb Vasc Biol 2001; 24: 744-749. Go to original source... Go to PubMed...
  25. Walldius G, Jungner I. Apolipoprotein B and apolipoprotein A-I: risk indicators of coronary heart disease and targets for lipid-modifying therapy. J Intern Med 2004; 255: 188-205. Go to original source... Go to PubMed...
  26. Janus ED, Nicoll AM, Turner PR et al. Kinetic bases of the primary hyperlipidaemias: studies of apolipoprotein B turnover in genetically defined subjects. Eur J Clin Invest 1980; 10: 161-172. Go to original source... Go to PubMed...
  27. Demacker PN, Veerkamp MJ, Bredie SJ et al. Comparison of the measurement of lipids and lipoproteins versus assay of apolipoprotein B for estimation of coronary heart disease risk: a study in familial combined hyperlipidemia. Atherosclerosis 2000; 153: 483-490. Go to original source... Go to PubMed...
  28. Sniderman AD, Cabezas MC, Ribalta J et al. A proposal to redifine familial combined hyperlipidaemia - Third workshop on FCHL held in Barcelona from 2 to 5 may 2001, during the Scientific Sessions of the European Society for Clinical Investigation. Eur J C Invest 2002; 32: 71-73. Go to original source... Go to PubMed...
  29. de Graaf J, van der Vleuten G, Stalenhoef AF. Diagnostic criteria in relation to the pathogenesis of familial combined hyperlipidemia. Semin Vasc Med 2004; 4: 229-240. Go to original source... Go to PubMed...
  30. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 6: 499-502. Go to original source...
  31. Pischon T, Girman CJ, Sacks FM et al. Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation, 2005; 112: 3375-3383. Go to original source... Go to PubMed...
  32. Jiang R, Schulze MB, Li T et al. Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes. Diabetes Care 2004; 27: 1991-1997. Go to original source... Go to PubMed...
  33. Dobiášová M, Frohlich J. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER/HDL). Clin Biochem 2001; 34: 583-588. Go to original source... Go to PubMed...
  34. Dobiášová M. Ahterogenic index of plasma (log (triglycerides/HDL-cholesterol): theoretical and practical implications. Clin Chem 2004; 50: 1113-1115. Go to original source... Go to PubMed...
  35. Matthews DR, Hosker JP, Rudenski AS et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419. Go to original source... Go to PubMed...
  36. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285: 19.
  37. Cífková R, Škodová Z, Lánská V et al. Longitudinal trends of total and HDL cholesterol in a representative population sample in the Czech Republic. Vnitř Lék 2000; 46: 501-505.
  38. Vaverková H, Weinbergová O, Horčička V et al. Familial combined hyperlipidemia. Part I. Lipid values and the lipoprotein pattern. Acta Univ Palacki Olomuc, Fac Med 1986; 113: 193-216. Go to PubMed...
  39. Ascaso JF, Sales J, Merchante A et al. Influence of obesity on plasma lipoproteins, glycaemia and insulinaemia in patients with familial combined hyperlipidaemia. Int J Obes 1997; 21: 360-366. Go to original source... Go to PubMed...
  40. Ascaso JF, Merchante A, Lorente RI et al. A study of insulin resistance using the minimal model in nondiabetic familial combined hyperlipidemic patients. Metabolism 1998; 47: 508-513. Go to original source... Go to PubMed...
  41. Ascaso JF, de Graaf J, Stalenhoef AFH. Role of insulin resistance in familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol 2005; 25: 1026-1031. Go to original source... Go to PubMed...
  42. Martinez-Hervás S, Real JT, Priego A et al. Familial combined hyperlipidemia, metabolic syndrome and cardiovascular disease. Rev Esp Cardiol 2006; 59: 1195-1198. Go to original source...
  43. Skoumas J, Papadimitriou L, Pitsavos C et al. Metabolic syndrome prevalence and characteristics in Greek adults with familial combined hyperlipidemia. Metabolism 2007; 56: 135-141. Go to original source... Go to PubMed...
  44. Van der Vleuten GM, van Tits LJH, den Heijer M et al. Decreased adiponectin levels in familial combined hyperlipidemia patients contribute to the atherogenic lipid profile. Journal of Lipid Research 2005; 46: 2398-2404. Go to original source... Go to PubMed...
  45. Mills JD, Mansfield MW, Grant PJ. Tissue plasminogen activator, fibrin D-dimer, and insulin resistance in the relatives of patients with premature coronary artery disease. Arterioscler Thromb Vasc Biol 2002; 22: 704-709. Go to original source... Go to PubMed...
  46. Jeng JR, Sheu WH, Jeng CY et al. Impaired fibrinolysis and insulin resistance in patients with hypertension. Am J Hypertens 1996; 9: 484-490. Go to original source... Go to PubMed...
  47. Georgieva AM, Cate HT, Keulen ET et al. Prothrombotic markers in familial combined hyperlipidemia: evidence of endothelial cell activation and relation to metabolic syndrome. Atherosclerosis 2004; 175: 345-351. Go to original source... Go to PubMed...
  48. Andersen P. Hypercoagulability and reduced fibrinolysis in hyperlipidemia: relationship to the metabolic cardiovascular syndromee. J Cardiovasc Pharmacol 1992; 20 (Suppl 8): 29-31. Go to original source...
  49. Hamsten A, Wiman B, de Faire U et al. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-1563. Go to original source... Go to PubMed...
  50. Kaba NK, Francis CW, Moss AJ et al. Effects of lipids and lipid-lowering therapy on hemostatic factors in patients with myocardial infarction. Thromb Haemost 2004; 2: 718-725. Go to original source... Go to PubMed...
  51. Karásek D, Vaverková H, Halenka M et al. Endothelial haemostatic markers in members of families with familial combined hyperlipidemia. Thromb Res 2008 [Epub ahead of print]. Go to original source...
  52. Jansson JH, Olofsson BO, Nilsson TK. Predictive value of tissue plasminogen activator mass concentration on long-term mortality in patients with coronary artery disease. A 7-year follow-up. Circulation 1993; 88: 2030-2034. Go to original source... Go to PubMed...
  53. Lindahl B, Asplund K, Eliasson M et al. Insulin resistance syndrome and fibrinolytic activity: the Northern Sweden MONICA study. Int J Epidemiol 1996; 25: 291-299. Go to original source... Go to PubMed...
  54. Souček M. Úvod do problematiky metabolického syndromu. Vnitř Lék 2005; 51: 48-52.




Vnitřní lékařství

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.