Download PDF
Exp Clin Endocrinol Diabetes 2015; 123(04): 232-239
DOI: 10.1055/s-0034-1396863
Article
© Georg Thieme Verlag KG Stuttgart · New York

Effects of Glycemic Control upon Serum Lipids and Lipid Transfers to HDL in Patients with Type 2 Diabetes Mellitus: Novel Findings in Unesterified Cholesterol Status

O. G. Laverdy
1   Lipid Metabolism Laboratory, Heart Institute (INCOR) of the Medical School Hospital of São Paulo University, São Paulo, Brazil
2   Endocrinology and Metabolism Department, Medical School Hospital of São Paulo University, São Paulo, Brazil
,
W. A. Hueb
3   Department of Atherosclerosis, Heart Institute (INCOR) of the Medical School Hospital of São Paulo University, São Paulo, Brazil
,
M.C. O. Sprandel
1   Lipid Metabolism Laboratory, Heart Institute (INCOR) of the Medical School Hospital of São Paulo University, São Paulo, Brazil
,
R. Kalil-Filho
3   Department of Atherosclerosis, Heart Institute (INCOR) of the Medical School Hospital of São Paulo University, São Paulo, Brazil
,
R. C. Maranhão
1   Lipid Metabolism Laboratory, Heart Institute (INCOR) of the Medical School Hospital of São Paulo University, São Paulo, Brazil
4   Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
› Author Affiliations
Further Information

Publication History

received 12 May 2014
first decision 09 October 2014

accepted 10 December 2014

Publication Date:
06 February 2015 (online)

Also available at
    Permissions and Reprints

Abstract

Objective: Investigate the relations of glycemic levels with plasma lipids and in vitro lipid transfers to HDL in patients with type 2 diabetes mellitus.

Materials and Methods: 143 patients with type 2 diabetes not taking anti-lipidemic drugs were separated into 2 groups: group A included 62 patients with glycated hemoglobin (HbA1c)≤6.5% (48 mmol/mol) and group B 81 patients with HbA1c>6.5%. In vitro transfer of lipids was determined by 1 h incubation of a donor nanoemulsion containing radioactively labeled unesterified and esterified cholesterol, phospholipids and triglycerides with whole plasma followed by chemical precipitation and radioactive counting in the supernatant (HDL).

Results: LDL and HDL cholesterol were similar in Group A and B, but group B had higher triglycerides (2.31±1.30 vs. 1.58±0.61 mmol/l, P<0.0001) and total and non-HDL unesterified cholesterol (36.3±7.8 vs. 33.9±5.9 mmol/l, P<0,05; 30.6±7.9 vs. 27.6±6.2 mmol/l, P<0,05; respectively) than group A and a non-significant trend to increased apolipoprotein B (103±20 vs. 97±20 mg/dl, P=0.08). 36 patients with the highest, ≥8.0% (64 mmol/mol), HbA1c also showed non-significant trend of elevated non-esterified fatty acids (NEFA) compared to 37 with lowest, ≤6.0% (42 mmol/mol), HbA1c (P=0.08). Patients with higher NEFA had higher triglycerides than those with lower NEFA levels (P<0.01).Transfers of all lipids from nanoemulsion to HDL and lipid composition of HDL were equal in both groups.

Conclusions: For the first time it was shown that in addition to triglycerides, unesterified cholesterol is also a marker of poor glycemic control. In vitro HDL lipid transfers, an important aspect of HDL metabolism, were not related with the glycemic control.

Key words

glycated hemoglobin - diabetic dyslipidemia - lipoproteins metabolism
 

  • References

  • 1 Taskinen MR. Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 2003; 46: 733-749
    CrossrefPubMedGoogle Scholar
  • 2 Vergès B. Abnormal hepatic apolipoprotein B metabolism in type 2 diabetes. Atherosclerosis 2010; 211: 353-360
    CrossrefPubMedGoogle Scholar
  • 3 Grundy SM, Benjamin IJ, Burke GL et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 1999; 100: 1134-1146
    CrossrefPubMedGoogle Scholar
  • 4 Brunzell JD, Davidson M, Furberg CD et al. Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care 2008; 31: 811-822
    CrossrefPubMedGoogle Scholar
  • 5 Kontush A, Chapman MJ. Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 2006; 58: 342-374
    CrossrefPubMedGoogle Scholar
  • 6 Khan HA, Sobki SH, Khan SA. Association between glycaemic control and serum lipids profile in type 2 diabetic patients: HbA1c predicts dyslipidaemia. Clin Exp Med 2007; 7: 24-29
    CrossrefPubMedGoogle Scholar
  • 7 Ahmad Khan H. Clinical significance of HbA1c as a marker of circulating lipids in male and female type 2 diabetic patients. Acta Diabetol 2007; 44: 193-200
    CrossrefPubMedGoogle Scholar
  • 8 Sánchez-Quesada JL, Vinagre I, Juan-Franco ED et al. Effect of improving glycemic control in patients with type 2 diabetes mellitus on low-density lipoprotein size, electronegative low-density lipoprotein and lipoprotein-associated phospholipase A2 distribution. Am J Cardiol 2012; 110: 67-71
    CrossrefPubMedGoogle Scholar
  • 9 Ray KK, Seshasai SR, Wijesuriya S et al. Effect ofintensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomized controlled trials. Lancet 2009; 373: 1765-1772
    CrossrefPubMedGoogle Scholar
  • 10 Kelly TN, Bazzano LA, Fonseca VA et al. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med 2009; 151: 394-403
    CrossrefPubMedGoogle Scholar
  • 11 Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomized controlled trials. BMJ 2011; 343: d4169
    CrossrefPubMedGoogle Scholar
  • 12 Lo Prete AC, Dina CH, Azevedo CH et al. In vitro simultaneous transfer of lipids to HDL in coronary artery disease and in statin treatment. Lipids 2009; 44: 917-924
    CrossrefPubMedGoogle Scholar
  • 13 Maranhão RC, Roland IA, Hirata MH. Effects of Triton WR 1339 and heparin on the transfer of surface lipids from triglyceride-rich emulsions to high density lipoproteins in rats. Lipids 1990; 25: 701-705
    CrossrefPubMedGoogle Scholar
  • 14 American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care 2008; 31: 55-60
    PubMedGoogle Scholar
  • 15 Handelsman Y, Mechanick JI, Blonde L et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract 2011; 17: 1-53
    PubMedGoogle Scholar
  • 16 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; 18: 499-502
    CrossrefPubMedGoogle Scholar
  • 17 Lima E, Maranhão RC. Rapid simple laser-light scattering method for HDL particle size in whole plasma. Clin Chem 2004; 50: 1086-1091
    CrossrefPubMedGoogle Scholar
  • 18 Gaziano JM, Hennekens CH, O’Donnell CJ et al. Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation 1997; 96: 2520-2525
    CrossrefPubMedGoogle Scholar
  • 19 Malmström R, Packard CJ, Caslake M et al. Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. Diabetologia 1997; 40: 454-462
    CrossrefPubMedGoogle Scholar
  • 20 Morita S, Shimajiri Y, Sakagashira S et al. Effect of exposure to non-esterified fatty acid on progressive deterioration of insulin secretion in patients with Type 2 diabetes: a long-term follow-upstudy. Diabet Med 2012; 29: 980-985
    CrossrefPubMedGoogle Scholar
  • 21 Bittolo Bon G, Cazzolato G, Avogaro P. Lipids, lipoproteins and apolipoproteins in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus. Acta Diabetol Lat 1984; 21: 315-324
    CrossrefPubMedGoogle Scholar
  • 22 Abraira C, Colwell JA, Nuttall FQ et al. Veterans Affairs Cooperative Study on glycemic control and complications in type II diabetes (VACSDM). Results of the feasibility trial. Veterans Affairs Cooperative Study in Type II Diabetes. Diabetes Care 1995; 18: 1113-1123
    CrossrefPubMedGoogle Scholar
  • 23 Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol 1998; 81 (Suppl. 01) 7B-12B
    CrossrefPubMedGoogle Scholar
  • 24 Sarwar N, Danesh J, Eiriksdottir G et al. Triglycerides and the risk of coronary heart disease:10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 2007; 115: 450-458
    CrossrefPubMedGoogle Scholar
  • 25 Sposito AC, Ventura LI, Vinagre CG et al. Delayed intravascular catabolism of chylomicron-like emulsions is an independent predictor of coronary artery disease. Atherosclerosis 2004; 176: 397-403
    CrossrefPubMedGoogle Scholar
  • 26 Santos RD, Hueb W, Oliveira AA et al. Plasma kinetics of a cholesterol-rich emulsion in subjects with or without coronary artery disease. J Lipid Res 2003; 44: 464-469
    CrossrefPubMedGoogle Scholar
  • 27 Nakhjavani M, Esteghamati A, Esfahanian F et al. HbA1c negatively correlates with LCAT activity in type 2 diabetes. Diabetes Res Clin Pract 2008; 81: 38-41
    CrossrefPubMedGoogle Scholar
  • 28 Schernthaner G, Kostner GM, Dieplinger H et al. Apolipoproteins (A-I, A-II, B), Lp(a) lipoprotein and lecithin: cholesterol acyltransferase activity in diabetes mellitus. Atherosclerosis 1983; 49: 277-293
    CrossrefPubMedGoogle Scholar
  • 29 Wang J, Stančáková A, Soininen P et al. Lipoprotein subclass profiles in individuals with varying degrees of glucose tolerance: a population-based study of 9399 Finnish men. J Intern Med 2012; 272: 562-572
    CrossrefPubMedGoogle Scholar
  • 30 Beylot M, Garcia I, Temori SA et al. Serum lipids in diabetes mellitus. Relation to equilibration and microangiopathy. Diabete Metab 1983; 9: 199-203
    PubMedGoogle Scholar
  • 31 Hollenbeck CB, Chen YD, Greenfield MS et al. Reduced plasma high density lipoprotein-cholesterol concentrations need not increase when hyperglycemia is controlled with insulin in non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1986; 62: 605-608
    CrossrefPubMedGoogle Scholar
  • 32 Gatti A, Maranghi M, Bacci S et al. Poor glycemic control is an independent risk factor for low HDL cholesterol in patients with type 2 diabetes. Diabetes Care 2009; 32: 1550-1552
    CrossrefPubMedGoogle Scholar
  • 33 Nobecourt E, Davies MJ, Brown BE et al. The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin:cholesterol acyl transferase. Diabetologia 2007; 50: 643-653
    CrossrefPubMedGoogle Scholar
  • 34 Oliveira CP, Maranhao RC, Bertato MP et al. 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 2012; 11: 65
    CrossrefPubMedGoogle Scholar
  • 35 Rocha MP, Maranhão RC, Seydell TM et al. Metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density lipoprotein in young obese and normal-weight patients with polycystic ovary syndrome. Fertil Steril 2010; 93: 1948-1956
    CrossrefPubMedGoogle Scholar
  • 36 Borggreve SE, De Vries R, Dullaart RP. Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin:cholesterolacyltransferase and lipid transfer proteins. Eur J Clin Invest 2003; 33: 1051-1069
    CrossrefPubMedGoogle Scholar
  • 37 Maranhão RC, Freitas FR, Strunz CM et al. Lipid transfer to HDL are predictors of precocious clinical coronary heart disease. Clin Chim Acta 2012; 413: 502-505
    CrossrefPubMedGoogle Scholar
  • 38 Sprandel MC, Hueb W, Casella-Filho A et al. Lipid transfer to high density lipoproteins in type 2 diabetic patients with and without coronary artery disease. J Am Coll Cardiol 2012; 59: E1623
    CrossrefPubMedGoogle Scholar
  • 39 Quig DW, Zilversmit DB. Plasma lipid transfer activities. Annu Rev Nutr 1990; 10: 169-193
    CrossrefPubMedGoogle Scholar
  • 40 Feitosa-Filho GS, SeydellTde M, Feitosa AC et al. Lipid transfer to HDL in type-2 diabetic patients: associations with microalbuminuria, statin, and insulin. Arq Bras Cardiol 2009; 92: 94-106
    PubMedGoogle Scholar
  • 41 Nathan DM, Buse JB, Davidson MB et al. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2006; 29: 1963-1972
    CrossrefPubMedGoogle Scholar
  • 42 Taskinen MR, Kuusi T, Helve E et al. Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin-dependent diabetes. Arteriosclerosis 1988; 8: 168-177
    CrossrefPubMedGoogle Scholar