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Plasma Lipids, Lipoprotein Metabolism and HDL Lipid Transfers are Equally Altered in Metabolic Syndrome and in Type 2 Diabetes

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Lipids

Abstract

Metabolic syndrome (MetS) refers to states of insulin resistance that predispose to development of cardiovascular disease and type 2 diabetes (T2DM). The aim was to investigate whether plasma lipids and lipid metabolism differ in MetS patients compared to those with T2DM with poor glycemic control (glycated hemoglobin > 7.0). Eighteen patients with T2DM, 18 with MetS and 14 controls, paired for age (40–70 years) and body mass index (BMI), were studied. Plasma lipids and the kinetics of a triacylglycerol-rich emulsion labeled with [3H]-triolein ([3H]-TAG) and [14C]-cholesteryl esters ([14C]-CE) injected intravenously followed by one-hour blood sampling were determined. Lipid transfers from an artificial nanoemulsion donor to high-density lipoprotien (HDL) were assayed in vitro. Low-density lipoprotein (LDL) and HDL cholesterol (mg/dl) were not different in T2DM (128 ± 7; 42 ± 7) and MetS (142 ± 6; 39 ± 3), but triacylglycerols were even higher in MetS (215 ± 13) than in T2DM (161 ±11, p < 0.05). Fractional clearance rate (FCR, in min1) of [3H]-TAG and [14C]-CE were equal in T2DM (0.008 ± 0.018; 0.005 ± 0.024) and MetS (0.010 ± 0.016; 0.006 ± 0.013), and both were reduced compared to controls. The transfer of non-esterified cholesterol, phospholipids and triacylglycerols to HDL was higher in MetS and T2DM than in controls (p < 0.01). Cholesteryl ester transfer and HDL size were equal in all groups. Results imply that MetS is equal to poorly controlled T2DM concerning the disturbances of plasma lipid metabolism examined here, and suggest that there are different thresholds for the insulin action on glucose and lipids. These findings highlight the magnitude of the lipid disturbances in MetS, and may have implications in the prevention of cardiovascular diseases.

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Abbreviations

ATP-III:

Adult Treatment Panel III criteria

IDF:

International Diabetes Federation

CAD:

Coronary artery disease

T2DM:

Type 2 diabetes

MetS:

Metabolic syndrome

HbA1c:

Glycated hemoglobin

HDL:

High-density lipoprotein

LDL:

Low-density lipoprotein

VLDL:

Very low density lipoprotein

Apo:

Apolipoprotein

PLTP:

Phospholipid transfer protein

CETP:

Cholesteryl ester transfer protein

[14C]-CE [14C]:

Cholesteryl esters

[3H]-TAG [3H]:

Triolein

FCR:

Fractional clearance rate

FFA:

Unesterified fatty acids

TAG:

Triacylglycerol(s)

References

  1. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third report of the National Education (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel iii) final report. Circulation 106(25):3143–3421

    Google Scholar 

  2. Alberti KG, Zimmet P, Shaw J (2006) Metabolic syndrome a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med 23:469–480. doi:10.1111/j.1464-5491.2006.01858.x

    Article  CAS  PubMed  Google Scholar 

  3. Wallace TM, Matthews DR (2002) The assessment of insulin resistance in man. Diabet Med 19:527–534. doi:10.1046/j.1464-5491.2002.00745.x

    Article  CAS  PubMed  Google Scholar 

  4. Monzillo LU, Hamdy O (2003) Evaluation of insulin sensitivity in clinical practice and in research settings. Nutr Rev 61:397–412. doi:10.1301/nr.2003.dec.397-412

    Article  PubMed  Google Scholar 

  5. Ford ES (2005) Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 28:1769–1778

    Article  PubMed  Google Scholar 

  6. Alexander CM, Landsman PB, Teutsch SM, Haffner SM (2003) Third National Health and Nutrition Examination Survey (NHANES III); National Cholesterol Education Program (NCEP).NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 52:1210–1214

    Article  CAS  PubMed  Google Scholar 

  7. Ginsberg HN, Huang LS (2000) The insulin resistance syndrome: impact on lipoprotein metabolism and atherothrombosis. J Cardiovasc Risk 7:325–333

    CAS  PubMed  Google Scholar 

  8. Maranhão RC, Feres MC, Martins MT et al (1996) Plasma kinetics of a chylomicron- like emulsion in patients with coronary artery disease. Atherosclerosis 126:15–21

    Article  PubMed  Google Scholar 

  9. Maranhão RC, Roland IA, Hirata MH (1990) Effects of Triton WR-1339 and heparin on the transfer of surface lipids from triglyceride-rich emulsions to high-density lipoprotein in rats. Lipids 25:701–705

    Article  PubMed  Google Scholar 

  10. Chan DC, Watts GF, Barrett PH, O’Neill FH, Redgrave TG, Thompson GR (2003) Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome. Clin Sci (Lond) 104(4):383–388

    Article  CAS  Google Scholar 

  11. Chan DC, Watts GF, Barrett PH, Mamo JC, Redgrave TG (2002) Markers of triglyceride-rich lipoprotein remnant metabolism in visceral obesity. Clin Chem 48:278–283

    CAS  PubMed  Google Scholar 

  12. Adeli K, Lewis GF (2008) Intestinal lipoprotein overproduction in insulin-resistant states. Curr Opin Lipidol 19(3):221–228. doi:10.1097/MOL.0b013e3282ffaf82

    Article  CAS  PubMed  Google Scholar 

  13. Nogueira JP, Maraninchi M, Béliard S, Padilla N, Duvillard L, Mancini J, Nicolay A, Xiao C, Vialettes B, Lewis GF, Valéro R (2012) Absence of acute inhibitory effect of insulin on chylomicron production in type 2 diabetes. Arterioscler Thromb Vasc Biol 32:1039–1044. doi:10.1161/ATVBAHA.111.242073

    Article  CAS  PubMed  Google Scholar 

  14. Kontush A, Chapman MJ (2006) Antiatherogenic small, dense HDLguardian angel of the arterial wall? Nat Clin Pract Cardiovasc Med 3:144–153. doi:10.1038/ncpcardio0500

    Article  CAS  PubMed  Google Scholar 

  15. Oliveira CP, Maranhão RC, Bertato MP, Wajchenberg BL, Lerario AC (2012) Removal from the plasma of the free and esterified forms of cholesterol and transfer of lipids to HDL in type 2 diabetes mellitus patients. Lipids Health Dis. 7:11–65. doi:10.1186/1476-511X-11-65

    Google Scholar 

  16. American Diabetes Association (2008) Standards of medical care in diabetes. (Position Statement). Diabetes Care 31:S55–S60

    Article  Google Scholar 

  17. Sposito AC, Santos RD, Amancio RF et al (2003) Atorvastatin enhances the plasma clearance of chylomicron-like emulsions in subjects with atherogenic dyslipidemia: relevance to the in vivo metabolism of triglyceride-rich lipoproteins. Atherosclerosis 166:311–321. doi:10.1016/S0021-9150(02)00334-9

    Article  CAS  PubMed  Google Scholar 

  18. Redgrave TG, Zech LA (1987) A kinetic model of chylomicron core lipid metabolism in rats: the effect of a single meal. J Lipid Res 28:473–482

    CAS  PubMed  Google Scholar 

  19. Marchese SRM, Mesquita CH, Cunha HL (1998) Anacomp program application to calculate 137C transfer rates in marine organisms and dose in man. J Radioanal Nucl Chem 232:233–236

    Article  Google Scholar 

  20. Lo Prete AC, Dina CH, Azevedo CH et al (2009) In vitro simultaneous transfer of lipids to HDL in coronary artery disease and in Statin treatment. Lipids 44:917–924. doi:10.1007/s11745-009-3342-2

    Article  CAS  PubMed  Google Scholar 

  21. Lima ES, Maranhão RC (2004) Rapid, simple laser-light-scattering method for HDL particle sizing in whole plasma. Clin Chem 50:1086–1088. doi:10.1373/clinchem.2004.032383

    Article  CAS  PubMed  Google Scholar 

  22. Jocken JW, Langin D, Smit E et al (2007) Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. J Clin Endocrinol Met 92:2292–2299. doi:10.1210/jc.2006-1318

    Article  CAS  Google Scholar 

  23. Rashid S, Watanabe T, Sakaue T et al (2003) Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity. Clin Biochem 36(6):421–429. doi:10.1016/S0009-9120(03)00078-X

    Article  CAS  PubMed  Google Scholar 

  24. Kontush A, Chapman MJ (2008) Why is HDL functionally deficient in type 2 diabetes? Curr Diab Rep 8:51–59

    Article  CAS  PubMed  Google Scholar 

  25. Cooper AD (1997) Hepatic uptake of chylomicron remnants. J Lipid Res 38:2173–2192

    CAS  PubMed  Google Scholar 

  26. Redgrave TG (2004) Chylomicron metabolism. Biochem Soc Trans 32:79–82

    Article  CAS  PubMed  Google Scholar 

  27. Preiss D, Sattar N (2009) Lipids, lipid modifying agents and cardiovascular risk: a review of the evidence. Clin Endocrinol (Oxf) 70:815–828. doi:10.1111/j.1365-2265.2008.03490.x

    Article  CAS  Google Scholar 

  28. Watts GF, Karpe F (2011) Why, when and how should hypertriglyceridemia be treated in the high-risk cardiovascular patient? Expert Rev Cardiovasc Ther 9:987–997. doi:10.1586/erc.11.61

    Article  CAS  PubMed  Google Scholar 

  29. Santos RD, Ventura LI, Spósito AC et al (2001) The effects of gemfibrozil upon the metabolism of chylomicron-like emulsions in patients with endogenous hypertriglyceridemia. Cardiovasc Res 49:456–465. doi:10.1016/S0008-6363(00)00274-1

    Article  CAS  PubMed  Google Scholar 

  30. Sposito AC, Ventura LI, Vinagre CG et al (2004) Delayed intravascular catabolism of chylomicron- like emulsions is an independent predictor of coronary artery disease. Atherosclerosis 176:397–403. doi:10.1016/j.atherosclerosis.2004.05.023

    Article  CAS  PubMed  Google Scholar 

  31. Oram JF, Wolfbauer G, Vaughan AM et al (2003) Phospholipid transfer protein interacts with and stabilizes ATPbinding cassette transporter A1 and enhances cholesterol efflux from cells. J Biol Chem 278:52379–52385. doi:10.1074/jbc.M310695200

    Article  CAS  PubMed  Google Scholar 

  32. Pietzsch J, Fuecker K (2003) Increased cholesteryl ester transfer protein activity in impaired glucose tolerance: relationship to high density lipoprotein metabolism. Croat Med J 44:171–177

    PubMed  Google Scholar 

  33. Masson D, Jiang XC, Lagrost L et al (2009) The role of plasma lipid transfer proteins in lipoprotein metabolism and atherogenesis. J Lipid Res 50:201–206. doi:10.1194/jlr.R800061-JLR200

    Article  Google Scholar 

  34. Watts GF, Barrett PH, Chan DC (2008) HDL metabolism in context: looking on the bright side. Curr Opin Lipidol 19:395–404. doi:10.1097/MOL.0b013e328306596d

    Article  CAS  PubMed  Google Scholar 

  35. Lamarche B, Rashid S, Lewis GF (1999) HDL metabolism in hypertriglyceridemic states: an overview. Clin Chim Acta 286:145–161

    Article  CAS  PubMed  Google Scholar 

  36. Borggreve SE, De Vries R, Dullaart RP (2003) Alterations in high density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin:cholesterol acyltransferase and lipid transfer proteins. Eur J Clin Invest 33:1051–1069

    Article  CAS  PubMed  Google Scholar 

  37. de Vries R, Groen AK, Perton FG, Dallinga-Thie GM, van Wijland MJ, Dikkeschei LD, Wolffenbuttel BH, van Tol A, Dullaart RP (2008) Increased cholesterol efflux from cultured fibroblasts to plasma from hypertriglyceridemic type 2 diabetic patiens: roles of preβ-HDL, phospholipid transfer protein and cholesterol esterification. Atherosclerosis 196(2):733–741. doi:10.1016/j.bbalip.2011.06.013

    Article  PubMed  Google Scholar 

  38. Fryirs MA, Barter PJ, Appavoo M et al (2010) Effects of high-density lipoprotein on pancreatic beta-cell insulin secretion. Arterioscler Thromb Vasc Biol 30(8):1642–1648. doi:10.1161/ATVBAHA.110.207373

    Article  CAS  PubMed  Google Scholar 

  39. Feitosa AC, Feitosa-Filho GS, Freitas FR et al (2013) Lipoprotein metabolism in patients with type 1 diabetes under intensive insulin treatment. Lipids Health Dis 11:12–15. doi:10.1186/1476-511X-12-15

    Google Scholar 

Download references

Acknowledgments

This study was supported by the Research Support Foundation of the State of São Paulo (FAPESP, São Paulo, Brazil) and the Zerbini Foundation, both in São Paulo, Brazil. Dr. Maranhão is a Research Awardee of the National Council for Scientific and Technological Development (CNPq, Brasília, Brazil).

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The authors have nothing to disclose relative to the content of this study.

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Correspondence to Raul C. Maranhão.

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Silva, V.M., Vinagre, C.G.C., Dallan, L.A.O. et al. Plasma Lipids, Lipoprotein Metabolism and HDL Lipid Transfers are Equally Altered in Metabolic Syndrome and in Type 2 Diabetes. Lipids 49, 677–684 (2014). https://doi.org/10.1007/s11745-014-3899-2

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  • DOI: https://doi.org/10.1007/s11745-014-3899-2

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