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Semin Vasc Med 2002; 2(1): 067-074
DOI: 10.1055/s-2002-23097
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Diabetes and Atherothrombotic Disease: Linked through Inflammation?

Russell P. Tracy
  • Department of Pathology and Biochemistry, College of Medicine, University of Vermont, Colchester, Vermont
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Publication History

Publication Date:
25 March 2002 (online)

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ABSTRACT

Inflammation has been accepted as a key pathobiological mechanism in the development of cardiovascular disease, and acceptance is likely on its way for diabetes as well. Inflammation provides a linking mechanism between these two disorders, allowing them to influence each other in a wide variety of ways. Interventions aimed broadly at inflammation are likely to influence both diseases, and pathway-specific interventions may prove useful as well. The role of genetic variation remains poorly understood.

KEYWORD

Diabetes - insulin resistance - obesity - inflammation - thrombosis

REFERENCES

  • 1 Ross R. Atherosclerosis-an inflammatory disease.  N Engl J Med . 1999;  340 115-126
    CrossrefPubMedSearch in Google Scholar
  • 2 Virchow R. Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre. Berlin 1858
    Search in Google Scholar
  • 3 Ross R. The pathogenesis of atherosclerosis-an update.  N Engl J Med . 1986;  314 488-500
    CrossrefPubMedSearch in Google Scholar
  • 4 Meade T, Brozovic M, Chakrabarti R. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study.  Lancet . 1986;  2 533-537
    PubMedSearch in Google Scholar
  • 5 Kannel W, Wolf P, Castelli W, D'Agostino R. Fibrinogen and risk of cardiovascular disease: the Framingham study.  JAMA . 1987;  258 1183-1186
    CrossrefPubMedSearch in Google Scholar
  • 6 Stone M, Thorp J. Plasma fibrinogen-a major coronary risk factor.  J R Coll Gen Pract . 1985;  35 565-569
    PubMedSearch in Google Scholar
  • 7 Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction.  N Engl J Med . 1984;  311 501-505
    CrossrefPubMedSearch in Google Scholar
  • 8 Yarnell J, Baker I, Sweetnam P. Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease.  Circulation . 1991;  83 836-844
    PubMedSearch in Google Scholar
  • 9 Tracy R P, Arnold A M, Ettinger W, Fried L, Meilahn E, Savage P. The relationship of fibrinogen and factors VII and VIII to incident cardiovascular disease and death in the elderly: results from the Cardiovascular Health Study.  Arterioscler Thromb Vasc Biol . 1999;  19 1776-1783
    CrossrefPubMedSearch in Google Scholar
  • 10 Folsom A R, Wu K K, Rosamond W D, Sharrett A R, Chambless L E. Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study.  Circulation . 1997;  96 1102-1108
    CrossrefPubMedSearch in Google Scholar
  • 11 Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies.  JAMA . 1998;  279 1477-1482
    CrossrefPubMedSearch in Google Scholar
  • 12 Kuller L, Eichner J, Orchard T, Grandits G, McCallum L, Tracy R, for the MRFIT Research Group. The relation between serum albumin levels and risk of coronary heart disease in the Multiple Risk Factor Intervention Trial.  Am J Epidemiol . 1991;  134 1266-1277
    PubMedSearch in Google Scholar
  • 13 Koenig W, Sund M, Frohlich M. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men.  Circulation . 1999;  99 237-242
    CrossrefPubMedSearch in Google Scholar
  • 14 Liuzzo G, Biasucci L, Gallimore J. The prognostic value of C-reactive protein and serum amyloid. A protein in severe unstable angina.  N Engl J Med . 1994;  331 417-424
    CrossrefPubMedSearch in Google Scholar
  • 15 Bataille R, Klein B. C-reactive protein levels as a direct indicator of interleukin-6 levels in humans in vivo [letter].  Arthritis Rheum . 1992;  35 982-984
    PubMedSearch in Google Scholar
  • 16 Thompson S, Kienast J, Pyke S, Haverkate F, van de Loo J. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris.  N Engl J Med . 1995;  332 635-641
    CrossrefPubMedSearch in Google Scholar
  • 17 Kuller L, Tracy R, Shaten J, Meilahn E, for the MRFIT Research Group. Relationship of C-reactive protein and coronary heart disease in the MRFIT nested case-control study.  Am J Epidemiol . 1996;  144 537-547
    PubMedSearch in Google Scholar
  • 18 Tracy R, Lemaitre R, Psaty B. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health Study and the Rural Health Promotion Project.  Arterioscler Thromb Vasc Biol . 1997;  17 1121-1127
    PubMedSearch in Google Scholar
  • 19 Cushman M, Arnold A, Kuller L. C-reactive protein and risks of myocardial infarction, stroke and death in an elderly cohort [abstract].  Circulation . 1999;  98 1108
    PubMedSearch in Google Scholar
  • 20 Ridker P, Cushman M, Stampfer M, Tracy R, Hennekens C. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.  N Engl J Med . 1997;  336 973-979
    CrossrefPubMedSearch in Google Scholar
  • 21 Ridker P M, Buring J E, Shih J, Matias M, Hennekens C H. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women.  Circulation . 1998;  98 731-733
    CrossrefPubMedSearch in Google Scholar
  • 22 Ridker P M, Glynn R J, Hennekens C H. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction.  Circulation . 1998;  97 2007-2011
    CrossrefPubMedSearch in Google Scholar
  • 23 Mendall M A, Patel P, Ballam L, Strachan D, Northfield T C. C-reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study.  BMJ . 1996;  312 1061-1065
    PubMedSearch in Google Scholar
  • 24 Tracy R, Macy E, Bovill E. Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects.  Arterioscler Thromb Vasc Biol . 1997;  17 2167-2176
    PubMedSearch in Google Scholar
  • 25 Yudkin J S, Stehouwer C D, Emeis J J, Coppack S W. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue?.  Arterioscler Thromb Vasc Biol . 1999;  19 972-978
    CrossrefPubMedSearch in Google Scholar
  • 26 Aggawal B, Puri R, eds.. Human Cytokines: Their Role in Disease and Therapy Cambridge, MA: Blackwell Science 1995
  • 27 Levi M, ten Cate H, van der Poll T, van Deventer J. Pathogenesis of disseminated intravascular coagulation in sepsis.  JAMA . 1993;  270 975-979
    CrossrefPubMedSearch in Google Scholar
  • 28 Esmon C, Taylor F, Snow T. Inflammation and coagulation: linked processes potentially regulated through a common pathway mediated by protein C.  Thromb Haemostas . 1991;  66 160-165
    PubMedSearch in Google Scholar
  • 29 Tracy R. Atherosclerosis, thrombosis and inflammation: a question of linkage.  Fibrinolysis and Proteolysis . 1997;  11 (suppl 1) 137-142
    PubMedSearch in Google Scholar
  • 30 Festa A, D'Agostino Jr R, Howard G, Mykkanen L, Tracy R P, Haffner S M. Chronic subclinical inflammation as part of the insulin resistance syndrome: The Insulin Resistance Atherosclerosis Study (IRAS).  Circulation . 2000;  102 42-47
    CrossrefPubMedSearch in Google Scholar
  • 31 Ridker P M, Rifai N, Stampfer M J, Hennekens C H. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men.  Circulation . 2000;  101 1767-1772
    CrossrefPubMedSearch in Google Scholar
  • 32 Harris T B, Ferrucci L, Tracy R P. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly.  Am J Med . 1999;  106 506-512
    CrossrefPubMedSearch in Google Scholar
  • 33 Ridker P M, Hennekens C H, Buring J E, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.  N Engl J Med . 2000;  342 836-843
    CrossrefPubMedSearch in Google Scholar
  • 34 Ernst E, Resch K. Fibrinogen as a cardiovascular risk factor: A meta-analysis and review of the literature.  Ann Intern Med . 1993;  118 956-963
    PubMedSearch in Google Scholar
  • 35 Tracy R P. Inflammation in cardiovascular disease: cart, horse, or both?.  Circulation . 1998;  97 2000-2002
    PubMedSearch in Google Scholar
  • 36 Melnick S L, Shahar E, Folsom A R. Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis. Atherosclerosis Risk in Communities (ARIC) Study Investigators.  Am J Med . 1993;  95 499-504
    CrossrefPubMedSearch in Google Scholar
  • 37 Howell T H, Ridker P M, Ajani U A, Hennekens C H, Christen W G. Periodontal disease and risk of subsequent cardiovascular disease in U.S  male physicians. J Am Coll Cardiol . 2001;  37 445-450
    PubMedSearch in Google Scholar
  • 38 Folsom A R, Nieto F J, Sorlie P, Chambless L E, Graham D Y. Helicobacter pylori seropositivity and coronary heart disease incidence. Atherosclerosis Risk In Communities (ARIC) Study Investigators.  Circulation . 1998;  98 845-850
    PubMedSearch in Google Scholar
  • 39 Davidson M, Kuo C C, Middaugh J P. Confirmed previous infection with Chlamydia pneumoniae (TWAR) and its presence in early coronary atherosclerosis.  Circulation . 1998;  98 628-633
    PubMedSearch in Google Scholar
  • 40 Nieto F. Infections and atherosclerosis: new clues from an old hypothesis?.  Am J Epidemiol . 1998;  148 937-948
    PubMedSearch in Google Scholar
  • 41 Nieto F J, Folsom A R, Sorlie P D, Grayston J T, Wang S P, Chambless L E. Chlamydia pneumoniae infection and incident coronary heart disease: the Atherosclerosis Risk in Communities Study.  Am J Epidemiol . 1999;  150 149-156
    PubMedSearch in Google Scholar
  • 42 Tracy R P. Inflammation markers and coronary heart disease.  Curr Opin Lipidol . 1999;  10 435-441
    CrossrefPubMedSearch in Google Scholar
  • 43 Tracy R, Bovill E, Yanez D, for the CHS Investigators. Fibrinogen and factor VIII, but not factor VII, are associated with measures of subclinical cardiovascular disease in the elderly: results from the Cardiovascular Health Study.  Arterioscler Thromb Vasc Biol . 1995;  15 1269-1279
    PubMedSearch in Google Scholar
  • 44 Lagrand W K, Visser C A, Hermens W T. C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon?.  Circulation . 1999;  100 96-102
    PubMedSearch in Google Scholar
  • 45 Cermak J, Key N, Bach R, Balla J, Jacob H, Vercellotti G. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor.  Blood . 1993;  82 513-520
    PubMedSearch in Google Scholar
  • 46 Pasceri V, Willerson J T, Yeh E T. Direct proinflammatory effect of C-reactive protein on human endothelial cells.  Circulation . 2000;  102 2165-2168
    CrossrefPubMedSearch in Google Scholar
  • 47 Ridker P M, Rifai N, Pfeffer M A. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators.  Circulation . 1998;  98 839-844
    PubMedSearch in Google Scholar
  • 48 Ridker P M, Rifai N, Pfeffer M A, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators.  Circulation . 1999;  100 230-235
    PubMedSearch in Google Scholar
  • 49 Ridker P M, Rifai N, Clearfield M. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.  N Engl J Med . 2001;  344 1959-1965
    CrossrefPubMedSearch in Google Scholar
  • 50 Cushman M, Meilahn E N, Psaty B M, Kuller L H, Dobs A S, Tracy R P. Hormone replacement therapy, inflammation, and hemostasis in elderly women.  Arterioscler Thromb Vasc Biol . 1999;  19 893-899
    PubMedSearch in Google Scholar
  • 51 Cushman M, Legault C, Barrett-Connor E. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study.  Circulation . 1999;  100 717-722
    CrossrefPubMedSearch in Google Scholar
  • 52 Walsh B W, Paul S, Wild R A. The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial.  J Clin Endocrinol Metab . 2000;  85 214-218
    CrossrefPubMedSearch in Google Scholar
  • 53 Cushman M, Costantino J P, Tracy R P. Tamoxifen and cardiac risk factors in healthy women: suggestion of an anti-inflammatory effect.  Arterioscler Thromb Vasc Biol . 2001;  21 255-261
    PubMedSearch in Google Scholar
  • 54 de Maat P M, Kastelein J J, Jukema J W. -455G/A polymorphism of the beta-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: proposed role for an acute-phase reaction pattern of fibrinogen. REGRESS group.  Arterioscler Thromb Vasc Biol . 1998;  18 265-271
    PubMedSearch in Google Scholar
  • 55 Schmidt H, Schmidt R, Niederkorn K. Beta-fibrinogen gene polymorphism (C148T) is associated with carotid atherosclerosis: results of the Austrian Stroke Prevention Study.  Arterioscler Thromb Vasc Biol . 1998;  18 487-492
    PubMedSearch in Google Scholar
  • 55a Humphries S E, Luong L A, Ogg M S, Hawe E, Miller G C. The interleukin-6-174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men.  Eur Heart J . 2001;  22 2243-2252
    CrossrefPubMedSearch in Google Scholar
  • 56 Ogg M, Tracy R, Luong L. The -174 G/C interleukin-6 polymorphism is associated with increased levels of inflammation markers and increased blood pressure [abstract].  Circulation . 2000;  101 712
    PubMedSearch in Google Scholar
  • 57 Huber S A, Sakkinen P, Conze D, Hardin N, Tracy R. Interleukin-6 exacerbates early atherosclerosis in mice.  Arterioscler Thromb Vasc Biol . 1999;  19 2364-1367
    PubMedSearch in Google Scholar
  • 58 Huber S A, Sakkinen P, David C, Newell M K, Tracy R P. T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia.  Circulation . 2001;  103 2610-2616
    PubMedSearch in Google Scholar
  • 59 Schmidt M I, Duncan B B, Sharrett A R. Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study.  Lancet . 1999;  353 1649-1652
    CrossrefPubMedSearch in Google Scholar
  • 60 Festa A, D'Agostino Jr R, Tracy R, Haffner S. Elevated levels of acute phase proteins predict the development of type 2 diabetes mellitus-The Insulin Resistance Atherosclerosis Study (IRAS) [abstract].  Diabetes . 2000;  49 (suppl 1) A24
    PubMedSearch in Google Scholar
  • 61 Sakkinen P A, Wahl P, Cushman M, Lewis M R, Tracy R P. Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome.  Am J Epidemiol . 2000;  152 897-907
    CrossrefPubMedSearch in Google Scholar
  • 62 Meigs J, D'Agostino R, Wilson P, Cupples L, Nathan D, Singer D. Risk variable clustering in the insulin resistance syndrome. The Framingham Offspring Study.  Diabetes . 1997;  46 1594-1600
    PubMedSearch in Google Scholar
  • 63 Edwards K L, Austin M A, Newman B, Mayer E, Krauss R M, Selby J V. Multivariate analysis of the insulin resistance syndrome in women.  Arterioscler Thromb Vasc Biol . 1994;  14 1940-1945
    PubMedSearch in Google Scholar
  • 64 Tracy R, Losito R, Howard P, Cushman M, Bovill E. The association of plasma lipids and vitamin K-dependent coagulation factors. In: Bray G, Ryan D, eds. Nutrition, Genetics and Heart Disease Baton Rouge, LA: LSU Pr 1996: 29-49
    Search in Google Scholar
  • 65 Hoffman C, Lawson W, Miller R, Hultin M. Correlation of vitamin K-dependent clotting factors with cholesterol and triglycerides in healthy young adults.  Arterioscler Thromb Vasc Biol . 1994;  14 1737-1740
    CrossrefPubMedSearch in Google Scholar
  • 66 Alessi M, Peiretti F, Morange P, Henry M, Nalbone G, Juhan-Vague I. Production of plasminogen activator inhibitor-1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease.  Diabetes . 1997;  46 860-867
    CrossrefPubMedSearch in Google Scholar
  • 67 Kluft C, Verheijen J, Jie A. The postoperative fibrinolytic shutdown: a rapidly reverting acute phase pattern for the fast actimg inhibitor of tissue-type plasminogen activator after trauma.  Scand J Clin Lab Invest . 1985;  45 605-610
    CrossrefPubMedSearch in Google Scholar
  • 68 Vague P, Juhan-Vague I, Aillaud M. Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects.  Metabolism . 1986;  35 250-253
    CrossrefPubMedSearch in Google Scholar
  • 69 Alessi M, Juhan-Vague I, Kooistra T, Declerck P, Collen D. Insulin stimulates the synthesis of plasminogen activator inhibitor-1 by the human hepatocellular cell line HepG2.  Thromb Haemostas . 1988;  60 491-494
    PubMedSearch in Google Scholar
  • 70 Kooistra T, Bosma P, Tons H, van den Berg A, Meyer P, Princen H. Plasminogen activator inhibitor-1: biosynthesis and mRNA level are increased by insulin in cultured human hepatocytes.  Thromb Haemostas . 1989;  62 723-728
    PubMedSearch in Google Scholar
  • 71 Grant P, Kruithof E, Felley C, Felber J, Bachmann F. Short-term infusions of insulin, triacylglycerol and glucose do not cause acute increases in plasminogen activator inhibitor-1 concentrations in man.  Clin Sci . 1990;  79 513-516
    CrossrefPubMedSearch in Google Scholar
  • 72 Sobel B E. Increased plasminogen activator inhibitor-1 and vasculopathy. A reconcilable paradox [editorial].  Circulation . 1999;  99 2496-2498
    PubMedSearch in Google Scholar
  • 73 Iacoviello L, Di Castelnuovo A, De Knijff P. Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction.  N Engl J Med . 1998;  338 79-85
    CrossrefPubMedSearch in Google Scholar
  • 74 Iacoviello L, Burzotta F, Di Castelnuovo A, Zito F, Marchioli R, Donati M B. The 4G/5G polymorphism of PAI-1 promoter gene and the risk of myocardial infarction: a meta-analysis [letter].  Thromb Haemost . 1998;  80 1029-1030
    PubMedSearch in Google Scholar
  • 75 Corral J, Gonzalez-Conejero R, Lozano M, Rivera J, Heras I, Vicente V. The venous thrombosis risk factor 20210 A allele of the prothrombin gene is not a major risk factor for arterial disease.  Br J Haemotol . 1997;  99 304-307
    PubMedSearch in Google Scholar
  • 76 Bertina R, Koeleman B, Koster T. Mutation in blood coagulation factor V associated with resistance to activated protein C.  Nature . 1994;  369 64-67
    CrossrefPubMedSearch in Google Scholar
  • 77 Kalafatis M, Mann K. Factor VLeiden and thrombophilia.  Arterioscler Thromb Vasc Biol . 1997;  17 620-627
    PubMedSearch in Google Scholar
  • 78 Cushman M, Rosendaal F R, Psaty B M. Factor VLeiden is not a risk factor for arterial vascular disease in the elderly: results from the Cardiovascular Health Study.  Thromb Haemost . 1998;  79 912-915
    PubMedSearch in Google Scholar
  • 79 Rosendaal F R, Siscovick D S, Schwartz S M. Factor VLeiden (resistance to activated protein C) increases the risk of myocardial infarction in young women.  Blood . 1997;  89 2817-2821
    PubMedSearch in Google Scholar
  • 80 Sakkinen P A, Cushman M, Psaty B M. Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort.  Thromb Haemost . 1998;  80 134-139
    PubMedSearch in Google Scholar
  • 81 Jacobs J, Tracy R, Gross M. Plasma C-reactive protein and vitamin C are associated with coronary calcification in young adults: The Cardia Study [abstract].  Circulation . 2000;  101 720
    PubMedSearch in Google Scholar
  • 82 Ridker P, Hennekens C, Cerskus A, Stampfer M. Plasma concentration of cross-linked fibrin degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men.  Circulation . 1994;  90 2236-2240
    PubMedSearch in Google Scholar
  • 83 Folsom A R, Aleksic N, Park E, Salomaa V, Juneja H, Wu K K. Prospective study of fibrinolytic factors and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study.  Arterioscler Thromb Vasc Biol . 2001;  21 611-617
    CrossrefPubMedSearch in Google Scholar
  • 84 Lowe G D, Rumley A. Use of fibrinogen and fibrin D-dimer in prediction of arterial thrombotic events.  Thromb Haemost . 1999;  82 667-672
    PubMedSearch in Google Scholar
  • 85 Cushman M, Lemaitre R N, Kuller L H. Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study.  Arterioscler Thromb Vasc Biol . 1999;  19 493-498
    CrossrefPubMedSearch in Google Scholar
  • 86 Kohler H P, Stickland M H, Ossei-Gerning N, Carter A, Mikkola H, Grant P J. Association of a common polymorphism in the factor XIII gene with myocardial infarction.  Thromb Haemost . 1998;  79 8-13
    PubMedSearch in Google Scholar
  • 87 Weiss E J, Bray P F, Tayback M. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis.  N Engl J Med . 1996;  334 1090-1094
    CrossrefPubMedSearch in Google Scholar
  • 88 Ridker P, Hennekens C, Schmitz C, Stampfer M, Lindpaintner K. PI A1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis.  Lancet . 1997;  349 385-388
    CrossrefPubMedSearch in Google Scholar
  • 89 Cheung A T, Ree D, Kolls J K, Fuselier J, Coy D H, Bryer-Ash M. An in vivo model for elucidation of the mechanism of tumor necrosis factor-alpha (TNF-alpha)-induced insulin resistance: evidence for differential regulation of insulin signaling by TNF-alpha.  Endocrinology . 1998;  139 4928-4935
    CrossrefPubMedSearch in Google Scholar
  • 90 Scarim A L, Heitmeier M R, Corbett J A. Irreversible inhibition of metabolic function and islet destruction after a 36-hour exposure to interleukin-1beta.  Endocrinology . 1997;  138 5301-5307
    CrossrefPubMedSearch in Google Scholar