Atherosclerosis
Volume 195, Issue 1 , Pages e181-e190 , November 2007

Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: Relation to liver, muscle and regional body fat content

  • E. Louise Thomas

      Affiliations

    • The Robert Steiner MR Unit, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    • Corresponding Author InformationCorresponding author at: Robert Steiner MR Unit, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK. Tel.: +44 20 8383 3772; fax: +44 20 8383 3038.
    • ,
  • Elizabeth Potter

      Affiliations

    • Lipid Clinic and Clinical Research Facility, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    • ,
  • Isabella Tosi

      Affiliations

    • Lipid Clinic and Clinical Research Facility, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    • ,
  • Julie Fitzpatrick

      Affiliations

    • The Robert Steiner MR Unit, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    • ,
  • Gavin Hamilton

      Affiliations

    • The Robert Steiner MR Unit, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    • ,
  • Vian Amber

      Affiliations

    • Division of Investigative Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    • ,
  • Robert Hughes

      Affiliations

    • Department of Cardiology, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    • ,
  • Christopher North

      Affiliations

    • Department of Medicine, University College London, University College Hospitals, London, UK
    • ,
  • Paul Holvoet

      Affiliations

    • Department of Cardiovascular Diseases, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium
    • ,
  • Mary Seed

      Affiliations

    • Lipid Clinic, Charing Cross Hospital, London, UK
    • ,
  • D. John Betteridge

      Affiliations

    • Department of Medicine, University College London, University College Hospitals, London, UK
    • ,
  • Jimmy D. Bell

      Affiliations

    • The Robert Steiner MR Unit, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    • ,
  • Rossi P. Naoumova

      Affiliations

    • Lipid Clinic and Clinical Research Facility, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK

Received 12 January 2007 ,Revised 9 March 2007 ,Accepted 23 March 2007.

References 

  1. Goldstein JL, Schrott HG, Hazzard WR, Bierman EL, Motulsky AG. 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
  2. Hopkins PN, Heiss G, Ellison RC, et al. Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia: a case–control comparison from the National Heart, Lung, and Blood Institute Family Heart Study. Circulation. 2003;108:519–523
  3. Aitman TJ, Godsland IF, Farren B, et al. Defects of insulin action on fatty acid and carbohydrate metabolism in familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 1997;17:748–754
  4. McNeely MJ, Edwards KL, Marcovina SM, et al. Lipoprotein and apolipoprotein abnormalities in familial combined hyperlipidemia: a 20-year prospective study. Atherosclerosis. 2001;159:471–481
  5. 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
  6. Shoulders CC, Jones EL, Naoumova RP. Genetics of familial combined hyperlipidemia and risk of coronary heart disease. Hum Mol Genet. 2004;13(Spec no. 1):R149–R160
  7. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med. 2004;351:1106–1118
  8. Betteridge DJ, Verges B. Long-term effects on lipids and lipoproteins of pioglitazone versus gliclazide addition to metformin and pioglitazone versus metformin addition to sulphonylurea in the treatment of type 2 diabetes. Diabetologia. 2005;48:2477–2481
  9. Winkler K, Konrad T, Fullert S, et al. Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. Diabetes Care. 2003;26:2588–2594
  10. Kelly IE, Han TS, Walsh K, Lean ME. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care. 1999;22:288–293
  11. Miyazaki Y, Mahankali A, Matsuda M, et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2002;87:2784–2791
  12. Bajaj M, Suraamornkul S, Piper P, et al. Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients. J Clin Endocrinol Metab. 2004;89:200–206
  13. Rasouli N, Raue U, Miles LM, et al. Pioglitazone improves insulin sensitivity through reduction in muscle lipid and redistribution of lipid into adipose tissue. Am J Physiol Endocrinol Metab. 2005;288:E930–E934
  14. Naoumova RP, Bonney SA, Eichenbaum-Voline S, et al. Confirmed locus on chromosome 11p and candidate loci on 6q and 8p for the triglyceride and cholesterol traits of combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 2003;23:2070–2077
  15. Kreymann B, Williams G, Ghatei MA, Bloom SR. Glucagon-like peptide-1 7–36: a physiological incretin in man. Lancet. 1987;2:1300–1304
  16. Holvoet P, Macy E, Landeloos M, et al. Analytical performance and diagnostic accuracy of immunometric assays for the measurement of circulating oxidized LDL. Clin Chem. 2006;52:760–764
  17. Rajala U, Laakso M, Paivansalo M, et al. Low insulin sensitivity measured by both quantitative insulin sensitivity check index and homeostasis model assessment method as a risk factor of increased intima-media thickness of the carotid artery. J Clin Endocrinol Metab. 2002;87:5092–5097
  18. Boizel R, Benhamou PY, Lardy B, et al. Ratio of triglycerides to HDL cholesterol is an indicator of LDL particle size in patients with type 2 diabetes and normal HDL cholesterol levels. Diabetes Care. 2000;23:1679–1685
  19. Holvoet P, Kritchevsky SB, Tracy RP, et al. The metabolic syndrome, circulating oxidized LDL, and risk of myocardial infarction in well-functioning elderly people in the health, aging, and body composition cohort. Diabetes. 2004;53:1068–1073
  20. Thomas EL, Hamilton G, Patel N, et al. Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study. Gut. 2005;54:122–127
  21. Rico-Sanz J, Thomas EL, Jenkinson G, et al. Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by (1)H MRS. J Appl Physiol. 1999;87:2068–2072
  22. Thomas EL, Saeed N, Hajnal JV, et al. Magnetic resonance imaging of total body fat. J Appl Physiol. 1998;85:1778–1785
  23. Promrat K, Lutchman G, Uwaifo GI, et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology. 2004;39:188–196
  24. Arioglu E, Duncan-Morin J, Sebring N, et al. Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. Ann Intern Med. 2000;133:263–274
  25. Carreon-Torres E, Juarez-Meavepena M, Cardoso-Saldana G, et al. Pioglitazone increases the fractional catabolic and production rates of high-density lipoproteins apo AI in the New Zealand White Rabbit. Atherosclerosis. 2005;181:233–240
  26. Sakamoto J, Kimura H, Moriyama S, et al. Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone. Biochem Biophys Res Commun. 2000;278:704–711
  27. Lamarche B, Lemieux I, Despres JP. The small, dense LDL phenotype and the risk of coronary heart disease: epidemiology, patho-physiology and therapeutic aspects. Diabetes Metab. 1999;25:199–211
  28. Gaziano JM, Hennekens CH, O’Donnell CJ, Breslow JL, Buring JE. Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation. 1997;96:2520–2525
  29. Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2005;28:1547–1554
  30. Mazzone T, Meyer PM, Feinstein SB, et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA. 2006;296:2572–2581
  31. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279–1289
  32. Thompson GR, Morrell J, Wilson P. Dyslipidemia in clinical practice. 2nd ed.. Oxon: Informa UK Ltd.; 2006;
  33. Trujillo ME, Scherer PE. Adipose tissue-derived factors: impact on health and disease. Endocr Rev. 2006;
  34. Sharma AM, Staels B. Peroxisome proliferator-activated receptor gamma and adipose tissue—understanding obesity-related changes in regulation of lipid and glucose metabolism. J Clin Endocrinol Metab. 2007;92:386–395
  35. Cnop M, Havel PJ, Utzschneider KM, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia. 2003;46:459–469
  36. Yu JG, Javorschi S, Hevener AL, et al. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes. 2002;51:2968–2974
  37. Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007;92:1023–1033
  38. Rodenburg J, Vissers MN, Wiegman A, et al. Oxidized low-density lipoprotein in children with familial hypercholesterolemia and unaffected siblings: effect of pravastatin. J Am Coll Cardiol. 2006;47:1803–1810
  39. van den Akker JM, Bredie SJ, Diepenveen SH, et al. Atorvastatin and simvastatin in patients on hemodialysis: effects on lipoproteins C-reactive protein and in vivo oxidized LDL. J Nephrol. 2003;16:238–244
  40. Abbink EJ, De GJ, De Haan JH, et al. Effects of pioglitazone in familial combined hyperlipidaemia. J Intern Med. 2006;259:107–116
  41. Smith SR, De JL, Volaufova J, et al. Effect of pioglitazone on body composition and energy expenditure: a randomized controlled trial. Metabolism. 2005;54:24–32
  42. Hirose H, Kawai T, Yamamoto Y, et al. Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes. Metabolism. 2002;51:314–317
  43. Basu A, Jensen MD, McCann F, et al. Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes. Diabetes Care. 2006;29:510–514
  44. Pruchnic R, Katsiaras A, He J, et al. Exercise training increases intramyocellular lipid and oxidative capacity in older adults. Am J Physiol Endocrinol Metab. 2004;287:E857–E862
  45. Tamura Y, Tanaka Y, Sato F, et al. Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2005;90:3191–3196
  46. Frost GS, Goff LM, Hamilton G, et al. Carbohydrate-induced manipulation of insulin sensitivity independently of intramyocellular lipids. Br J Nutr. 2003;89:365–375
  47. Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006;355:2297–2307

☆ This work was supported in part by the J. Coller Foundation.

PII: S0021-9150(07)00206-7

doi: 10.1016/j.atherosclerosis.2007.03.043

Atherosclerosis
Volume 195, Issue 1 , Pages e181-e190 , November 2007

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