LDL and HDL lipoprotein subfractions in multiple sclerosis patients with decreased insulin sensitivity

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Objectives. Increased metabolic and cardiovascular morbidity has been reported in multiple sclerosis (MS) patients. Previously, we have found decreased insulin sensitivity and hyperinsulinemia in a group of newly diagnosed MS patients. We hypothesize that these features may be associated with an altered lipid profile and low, intermediate, or high density lipoprotein (LDL, IDL, HDL) subclasses accelerating atherosclerosis and thus contributing to the cardiovascular risk increase in these patients.

Subjects and methods. In a group of 19 newly diagnosed untreated MS patients with previously found hyperinsulinemia and insulin resistance and a matched group of 19 healthy controls, the lipoprotein subclasses profile was determined. Polyacrylamide gel electrophoresis was used to separate and measure the LDL (large LDL and small dense LDL), HDL (large, intermediate and small), and IDL (A, B and C) subclasses with the Lipoprint© System (Quantimetrix Corporation, Redondo Beach, CA, USA).

Results. No difference was found either in the conventional lipid or lipoprotein subclasses profile between the MS patients and healthy controls. We found an inverse association between the level of IDL-B with fasting insulin (r=–0.504, p=0.032), the insulin resistance estimated by homeo-static model assessment – insulin resistance (HOMA-IR) (r=–0.498, p=0.035), insulin response expressed as area under the curve (AUC; r=–0.519, p=0.027), and area above the baseline (AAB; r=–0.476, p=0.045) and positive association with insulin sensitivity estimated by insulin sensitivity index (ISI) Matsuda (r=0.470, 0.048) in MS patients, but not in healthy controls suggesting the first signs in lipoprotein subclasses profile change.

Conclusions. Our data indicate that changes in lipoprotein profile and subclasses are preceded by insulin resistance and hyperinsulinemia in patients with newly diagnosed MS.

Asztalos BF, Cupples LA, Demissie S, Horvath KV, Cox CE, Batista MC, Schaefer EJ. High-density lipoprotein sub-population profile and coronary heart disease prevalence in male participants of the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 24, 2181–2187, 2004.

Boyer JF, Gourraud PA, Cantagrel A, Davignon JL, Constantin A. Traditional cardiovascular risk factors in rheumatoid arthritis: A meta-analysis. Joint Bone Spine 78, 179–183, 2011.

Cederholm J, Wibell L. Insulin release and peripheral sensitivity at the oral glucose tolerance test. Diabetes Res Clin Pract 10, 167–175, 1990.

Feingold KR, Grunfeld C. Introduction to Lipids and Lipoproteins. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000, 2018.

Fellows K, Uher T, Browne RW, Weinstock-Guttman B, Horakova D, Posova H, Vaneckova M, Seidl Z, Krasensky J, Tyblova M, Havrdova E, Zivadinov R, Ramanathan M. Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients. J Lipid Res 56, 2010–2018, 2015.

Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, Hutto A, Pugh K, Jenkins AJ, Klein RL, Liao Y. Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 52, 453–462, 2003.

Giubilei F, Antonini G, Di Legge S, Sormani MP, Pantano P, Antonini R, Sepe-Monti M, Caramia F, Pozzilli C. Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis. Acta Neurol Scand 106, 109–112, 2002.

Guerrero-Garcia JJ, Carrera-Quintanar L, Lopez-Roa RI, Marquez-Aguirre AL, Rojas-Mayorquin AE, Ortuno-Sahagun D. Multiple Sclerosis and Obesity: Possible Roles of Adipokines. Mediators Inflamm 2016: Article ID: 4036232, 2016.

Haffner SM, American Diabetes Association. Management of Dyslipidemia in Adults With Diabetes. Diabetes Care 26, s83–s86, 2003.

Ito K, Yoshida H, Yanai H, Kurosawa H, Sato R, Manita D, Hirowatari Y, Tada N. Relevance of intermediate-density lipoprotein cholesterol to Framingham risk score of coronary heart disease in middle-aged men with increased non-HDL cholesterol. Int J Cardiol 168, 3853–3858, 2013.

Jorissen W, Wouters E, Bogie JF, Vanmierlo T, Noben JP, Sviridov D, Hellings N, Somers V, Valcke R, Vanwijmeersch B, Stinissen P, Mulder MT, Remaley AT, Hendriks JJ. Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL. Sci Rep 7, 43410, 2017.

Jorissen W, Vanmierlo T, Wens I, Somers V, Van Wijmeersch B, Bogie JF, Remaley AT, Eijnde BO, Hendriks JJA. Twelve Weeks of Medium-Intensity Exercise Therapy Affects the Lipoprotein Profile of Multiple Sclerosis Patients. Int J Mol Sci 19, E193, 2018.

Joshi PH, Khokhar AA, Massaro JM, Lirette ST, Griswold ME, Martin SS, Blaha MJ, Kulkarni KR, Correa A, D’Agostino RB Sr, Jones SR, Toth PP; Lipoprotein Investigators Collaborative (LIC) Study Group. Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Off-spring Cohort Studies. J Am Heart Assoc 5, e002765, 2016.

Kassi E, Pervanidou P, Kaltsas G, Chrousos G. Metabolic syndrome; definitions and controversies. BMC Med 9, 48, 2011.

Krauss RM, PaulT.Williams PT, Brensike J, Detre KM, Lindgren FT, Kelsey SF, Vranizan K, Levy RI. Intermediate-density lipoproteins and progression of coronary artery disease in hypercholesterolaemic men. The Lancet 330, 62–66, 1987.

Krauss RM. Lipids and lipoproteins in patients with type 2 diabetes. Diabetes Care 27, 1496–1504, 2004.

Lee JE, Min SH, Lee DH, Oh TJ, Kim KM, Moon JH, Choi SH, Park KS, Jang HC, Lim S. Comprehensive assessment of lipoprotein subfraction profiles according to glucose metabolism status, and association with insulin resistance in subjects with early-stage impaired glucose metabolism. Int J Cardiol 225, 327–331, 2016.

Mandoj C, Renna R, Plantone D, Sperduti I, Cigliana G, Conti L, Koudriavtseva T. Anti-annexin antibodies, cholesterol levels and disability in multiple sclerosis. Neurosci Lett 606, 156–160, 2015.

Martin SS, Faridi KF, Joshi PH, Blaha MJ, Kulkarni KR, Khokhar AA, Maddox TM, Havranek EP, Toth PP, Tang F, Spertus JA, Jones SR. Remnant Lipoprotein Cholesterol and Mortality After Acute Myocardial Infarction: Further Evidence for a Hypercholesterolemia Paradox From the TRIUMPH Registry. Clin Cardiol 38, 660–667, 2015.

Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22, 1462–1470, 1999.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419, 1985.

Nakamura T, Obata JE, Hirano M, Kitta Y, Fujioka D, Saito Y, Kawabata K, Watanabe K, Watanabe Y, Mishina H, Kugiyama K. Predictive value of remnant lipoprotein for cardiovascular events in patients with coronary artery disease after achievement of LDL-cholesterol goals. Atherosclerosis 218, 163–167, 2011.

Penesova A, Vlcek M, Imrich R, Vernerova L, Marko A, Meskova M, Grunnerova L, Turcani P, Jezova D, Kollar B. Hyperinsulinemia in newly diagnosed patients with multiple sclerosis. Metab Brain Dis 30, 895–901, 2015.

Sicras-Mainar A, Ruiz-Beato E, Navarro-Artieda R, Maurino J. Comorbidity and metabolic syndrome in patients with multiple sclerosis from Asturias and Catalonia, Spain. BMC Neurol 17, 134, 2017.

Srisawasdi P, Vanavanan S, Rochanawutanon M, Kruthkul K, Kotani K, Kroll MH. Small-dense LDL/large-buoyant LDL ratio associates with the metabolic syndrome. Clin Biochem 48, 495–502, 2015.

Steiner G, Schwartz L, Shumak S, Poapst M. The association of increased levels of intermediate-density lipoproteins with smoking and with coronary artery disease. Circulation 75, 124–130, 1987.

Tettey P, Simpson S Jr, Taylor B, Blizzard L, Ponsonby AL, Dwyer T, Kostner K, van der Mei I. An adverse lipid profile is associated with disability and progression in disability, in people with MS. Mult Scler 20, 1737–1744, 2014.

Torres A, Askari AD, Malemud CJ. Cardiovascular disease complications in systemic lupus erythematosus. Biomark Med 3, 239–252, 2009.

Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y. Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev 13, 981–1000, 2014.

Weinstock-Guttman B, Zivadinov R, Mahfooz N, Carl E, Drake A, Schneider J, Teter B, Hussein S, Mehta B, Weiskopf M, Durfee J, Bergsland N, Ramanathan M. Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis. J Neuroinflammation 8, 127, 2011.

Wens I, Dalgas U, Stenager E, Eijnde BO. Risk factors related to cardiovascular diseases and the metabolic syndrome in multiple sclerosis – a systematic review. Mult Scler 19, 1556–1564, 2013.

Journal Information

CiteScore 2018: 1.27

SCImago Journal Rank (SJR) 2018: 0.411
Source Normalized Impact per Paper (SNIP) 2018: 0.441


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