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"Obesity, Dyslipidemia and Inflammation"Dr. Robert H. Eckel (biography)
English - 2004-10-23 - 43 minutes
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 | (41 slides) |
Summary :
In this presentation Dr. Eckel discusses various pathways involved in the genesis of metabolic syndrome and options for the treatment of obesity, dyslipidemia and inflammation.
The metabolic syndrome is thought of as a disorder of insulin resistance, which in turn is related to high free fatty acid levels. Beyond the components listed in the NCEP ATP III definition of the metabolic syndrome, associated features include smoking (1) increased apoB (2), small dense LDL and HDL (3), oxidized LDL (4), hyperuricemia (5), microalbuminuria (6), end-organ diseases (7, 8), increased fibrinogen and PAI-1 (9), increased serum viscosity (10) increased asymmetric dimethylarginine (11) increased homocysteine (12) decreased adiponectin (13) increased proinflammatory cytokines and high-sensitivity C-reactive protein (hs-CRP) (14).
Hs-CRP levels increase with the number of metabolic syndrome characteristics present (15), and are related to body mass index, fat mass, visceral adiposity and waist girth (16). CRP concentrations are also elevated in obese, insulin-resistant individuals (17).
Recent studies show that adipose macrophage numbers increase in obesity (18), and that chronic inflammation in fat plays a role in the development of obesity-related insulin resistance (19). Adipose tissue has various functions associated with either visceral or subcutaneous fat ( 20-25 ).
Dr. Eckel concludes his talk with a discussion of therapeutic options for targeting obesity, dyslipidemia and inflammation, such as weight reduction and the use of lipid-lowering agents (26,27) and insulin sensitizers (28-31).
Copyright © 2004 E-MedHosting.com Inc.
Learning objectives :
After viewing this presentation the participant will be able to discuss
- The prevalence of obesity in the U.S. and projected diabetes rates globally
- The dependence of hs-CRP levels on body fat distribution and insulin sensitivity
- The importance of chronic inflammation in fat in the development of obesity-related insulin resistance
- How hs-CRP levels relate to the metabolic syndrome
- Therapeutic options for obesity, dyslipidemia and inflammation
Bibliographic references :
1. Dzien A, Dzien-Bischinger C, Hoppichler F, Lechleitner M.The metabolic syndrome as a link between smoking and cardiovascular diseaseDiabetes Obes Metab. 2004 Mar;6(2):127-32.
2. Ken Williams MS, Allan D. Sniderman MD, Naveed Sattar MD, Ralph D’Agostino Jr PhD, Lynne E. Wagenknecht PhD, and Steven M. Haffner MDComparison of the Associations of Apolipoprotein B and Low-Density Lipoprotein Cholesterol With Other Cardiovascular Risk Factors in the Insulin Resistance Atherosclerosis Study (IRAS)Circulation 2003;108:2312.
3. W. Timothy Garvey, Soonho Kwon, Deyi Zheng, Sara Shaughnessy, Penny Wallace, Amy Hutto, Kimberly Pugh, Alicia J. Jenkins, Richard L. Klein, and Youlian LiaoEffects of Insulin Resistance and Type 2 Diabetes on Lipoprotein Subclass Particle Size and Concentration Determined by Nuclear Magnetic Resonance Diabetes 52:453-462, 2003
4. V. Sigurdardottir, B. Fagerberg & J. HultheCirculating oxidized low-density lipoprotein (LDL) is associated with risk factors of the metabolic syndrome and LDL size in clinically healthy 58-year-old men (AIR study)Journal of Internal Medicine. Volume 252 Issue 5 Page 440 - November 2002.
5. Mercedes R. Carnethon, Stephen P. Fortmann, Latha Palaniappan, Bruce B. Duncan, Maria I. Schmidt and Lloyd E. Chambless.Risk Factors for Progression to Incident Hyperinsulinemia: The Atherosclerosis Risk in Communities Study, 1987–1998 Am J Epidemiol 2003; 158:1058-1067.
6. Latha Palaniappan, Mercedes Carnethon and Stephen P. FortmannAssociation between microalbuminuria and the metabolic syndrome: NHANES IIIAmerican Journal of Hypertension. Volume 16, Issue 11 , November 2003, Pages 952-958.
7. Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, Hui JM, Fung C, Karim R, Lin R, Samarasinghe D, Liddle C, Weltman M, George J. NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome.
Hepatology. 2002 Feb;35(2):373-9.
8. Apridonidze T, Essah PA, Iuorno MJ, Nestler JE.
Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome.
J Clin Endocrinol Metab. 2004 Dec 28.
9. Pamela A. Sakkinen, Patricia Wahl, Mary Cushman, Michael R. Lewis and Russell P. TracyClustering of Procoagulation, Inflammation, and Fibrinolysis Variables with Metabolic Factors in Insulin Resistance Syndrome American Journal of Epidemiology Vol. 152, No. 10 : 897-907.
10. Hoieggen A, Fossum E, Moan A, Enger E, Kjeldsen SE.Whole-blood viscosity and the insulin-resistance syndrome.J Hypertens. 1998 Feb;16(2):203-10.
11. Stuhlinger MC, Abbasi F, Chu JW, Lamendola C, McLaughlin TL, Cooke JP, Reaven GM, Tsao PS.
Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor.JAMA. 2002 Mar 20;287(11):1420-6.
12. James B. Meigs, MD, MPH, Paul F. Jacques, PHD, Jacob Selhub, PHD, Daniel E. Singer, MD, David M. Nathan, MD, Nader Rifai, PHD, Ralph B. D’Agostino, Sr., PHD and Peter W.F. Wilson, MDFasting Plasma Homocysteine Levels in the Insulin Resistance Syndrome: The Framingham Offspring Study Diabetes Care 24:1403-1410, 2001.
13. Johannes Hulthe, Lillemor Mattsson Hultén and Björn FagerbergLow adipocyte-derived plasma protein adiponectin concentrations are associated with the metabolic syndrome and small dense low-density lipoprotein particles: Atherosclerosis and insulin resistance study
Metabolism. December 2003 Volume 52 Number 12.
14. Urpu Salmenniemi, MD; Eija Ruotsalainen, MD; Jussi Pihlajamäki, MD; Ilkka Vauhkonen, MD; Sakari Kainulainen, MD; Kari Punnonen, MD; Esko Vanninen, MD; Markku Laakso, MD Multiple Abnormalities in Glucose and Energy Metabolism and Coordinated Changes in Levels of Adiponectin, Cytokines, and Adhesion Molecules in Subjects With Metabolic Syndrome Circulation. 2004;110:3842-3848.
15. Andreas Festa, MD; Ralph D’Agostino, Jr, PhD; George Howard, DrPH; Leena Mykkänen, MD, PhD; Russell P. Tracy, PhD; Steven M. Haffner, MD.Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome Circulation. 2000;102:42.
16. Isabelle Lemieux; Agnès Pascot; Denis Prud’homme; Natalie Alméras; Peter Bogaty; André Nadeau; Jean Bergeron; Jean-Pierre Després. Elevated C-Reactive Protein: Another Component of the Atherothrombotic Profile of Abdominal Obesity Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:961.
17. Tracey McLaughlin, MD; Fahim Abbasi, MD; Cindy Lamendola, RN, MSN; Lynn Liang, PhD; Gerald Reaven, MD; Patricia Schaaf, MS, RD; Peter Reaven, MD.Differentiation Between Obesity and Insulin Resistance in the Association With C-Reactive Protein Circulation. 2002;106:2908.
18. Stuart P. Weisberg, Daniel McCann, Manisha Desai, Michael Rosenbaum, Rudolph L. Leibel and Anthony W. Ferrante, Jr.Obesity is associated with macrophage accumulation in adipose tissue J. Clin. Invest. 112:1796-1808 (2003).
19. Haiyan Xu, Glenn T. Barnes, Qing Yang, Guo Tan, Daseng Yang, Chieh J. Chou, Jason Sole, Andrew Nichols, Jeffrey S. Ross, Louis A. Tartaglia and Hong Chen.Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance J. Clin. Invest. 112:1821-1830 (2003).
20. J Bolinder, L Kager, J Ostman and P Arner. Differences at the receptor and postreceptor levels between human omental and subcutaneous adipose tissue in the action of insulin on lipolysisDiabetes. 183; Vol 32, Issue 2 117-123.
21. CT Montague, JB Prins, L Sanders, JE Digby and S O'Rahilly
Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distributionDiabetes. 1997; Vol 46, Issue 3 342-347.
22. Arner P.Catecholamine-induced lipolysis in obesity.Int J Obes Relat Metab Disord. 1999 Feb;23 Suppl 1:10-3.
23. Mavri A, Alessi MC, Bastelica D, Geel-Georgelin O, Fina F, Sentocnik JT, Stegnar M, Juhan-Vague I.
Subcutaneous abdominal, but not femoral fat expression of plasminogen activator inhibitor-1 (PAI-1) is related to plasma PAI-1 levels and insulin resistance and decreases after weight loss.Diabetologia. 2001 Nov;44(11):2025-31.
24. Giacchetti G, Faloia E, Mariniello B, Sardu C, Gatti C, Camilloni MA, Guerrieri M, Mantero F.
Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects.Am J Hypertens. 2002 May;15(5):381-8.
25. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW.
Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans.
Endocrinology. 2004 May;145(5):2273-82.
26. Julie K. Plenge, MD; Teri L. Hernandez, RN, BSN; Kathleen M. Weil, RN, MSS; Paul Poirier, MD; Gary K. Grunwald, PhD; Santica M. Marcovina, PhD; Robert H. Eckel, MD Simvastatin Lowers C-Reactive Protein Within 14 Days: An Effect Independent of Low-Density Lipoprotein Cholesterol Reduction Circulation. 2002;106:1447.
27. I. Jialal, MD, PhD; D. Stein, MD; D. Balis, MD; S. M. Grundy, MD, PhD; B. Adams-Huet, MS; S. Devaraj, PhD Effect of Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitor Therapy on High Sensitive C-Reactive Protein LevelsCirculation. 2001;103:1933.
28. Chiquette E, Ramirez G, Defronzo R.
A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors.
Arch Intern Med. 2004 Oct 25;164(19):2097-104.
29. Boden G, Cheung P, Mozzoli M, Fried SK.
Effect of thiazolidinediones on glucose and fatty acid metabolism in patients with type 2 diabetes.
Metabolism. 2003 Jun;52(6):753-9.
30. Willa A. Hsueh; Dennis Bruemmer Peroxisome Proliferator-Activated Receptor (gamma): Implications for Cardiovascular DiseaseHypertension. 2004;43:297.
31. Tontonoz P, Nagy L.
Regulation of macrophage gene expression by peroxisome-proliferator-activated receptor gamma: implications for cardiovascular disease.Curr Opin Lipidol. 1999 Dec;10(6):485-90.
32. Paul M Ridker, MD; Julie E. Buring, ScD; Nancy R. Cook, ScD; Nader Rifai, PhD C-Reactive Protein, the Metabolic Syndrome, and Risk of Incident Cardiovascular Events Circulation 2003;107: 391-7.
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