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Insulin resistance, haemostatic factors and cardiovascular risk
Joseph D Mills
Academic Unit of Molecular Vascular Medicine, G Floor, Martin Wing, Leeds General Infirmary, Leeds, LS1 3EX, UK, j.d.mills{at}leeds.ac.uk
Peter J Grant
Increased insulin resistance, which is present in the majority of type 2 diabetics patients, is associated with other metabolic and pro-coagulant cardiovascular risk factors and may account for the accelerated atherosclerosis and increased thrombotic potential observed in these patients. In individuals with normoglycaemia or impaired glucose tolerance (IGT), hyperinsulinaemia (a marker of insulin resistance) is associated with a similar clustering of risk factors and is predictive of cardiovascular events. The origins of insulin resistance are not well understood but data from families, twins and extended pedigrees suggest significant genetic and environmental contributions. The clustering of atherogenic traits begins in childhood, carries through to adult life and may result from the multiple effects of individual genes (pleiotropy) and environmental influences. Important environmental determinants of insulin resistance may occur before birth and, in conjunction with subsequent diet and exercise habits which result in obesity, lead to increased insulin resistance and cardiovascular risk. Therefore, primary prevention should centre around lifestyle changes which increase insulin sensitivity, maintain normoglycaemia and ameliorate atherothrombotic risk factor clustering.
Key Words: insulin resistance haemostatic factors cardiovascular disease pleiotropy environmental factors.
References
- Haffner SM, Lehto S., Ronnemaa T. et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229-34.[Abstract/Free Full Text]
- Petersen S., Rayner M., Press V. Coronary Heart Disease Statistics: British Heart Foundation Statistics Database 2000. British Heart Foundation; 2000.
- Reaven GM Role of insulin resistance in human disease. Diabetes 1988;37:1595-607.[Abstract]
- Ukkola O., Bouchard C. Clustering of metabolic abnormalities in obese individuals: the role of genetic factors. Ann Med 2001;33:79-90.[Web of Science][Medline]
[Order article via Infotrieve]
- Yudkin JS, Kumari M., Humphries SE et al. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 2000;148:209-14.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Hollenbeck C., Reaven GM Variations in insulin-stimulated glucose uptake in healthy individuals with normal glucose tolerance. J Clin Endocrinol Metab 1987;64:1169-73.[Abstract/Free Full Text]
- Zavaroni I., Bonora E., Pagliara M. et al. Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance. N Engl J Med 1989;320:702-6.[Abstract]
- Laakso M. How good a marker is insulin level for insulin resistance? Am J Epidemiol 1993;137:959-65.[Abstract/Free Full Text]
- Ducimetière P., Eschwege E., Papoz L. et al. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 1989;19:205-10.[CrossRef]
- Despres JP, Lamarche B., Mauriege P. et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996;334: 952-7.[Abstract/Free Full Text]
- Pyorala M., Miettinen H., Laakso M. et al. Hyperinsulinemia predicts coronary heart disease risk in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study. Circulation 1998;98:398-404.[Abstract/Free Full Text]
- Lempiainen P., Mykkanen L., Pyorala K. et al. Insulin resistance syndrome predicts coronary heart disease events in elderly nondiabetic men. Circulation 1999;100:123-8.[Abstract/Free Full Text]
- Uusitupa MI, Niskanen LK, Siitonen O. et al. 5-year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level, and abnormalities in lipoprotein composition in non-insulin-dependent diabetic and nondiabetic subjects. Circulation 1990;82:27-36.[Abstract/Free Full Text]
- Pyorala M., Miettinen H., Laakso M. et al. Hyperinsulinemia and the risk of stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study. Stroke 1998;29:1860-6.[Abstract/Free Full Text]
- Ferrara A., Barrett-Connor EL, Edelstein SL Hyperinsulinemia does not increase the risk of fatal cardiovascular disease in elderly men or women without diabetes: the Rancho Bernardo Study, 1984-1991. Am J Epidemiol 1994;140:857-69.[Abstract/Free Full Text]
- Orchard TJ, Eichner J., Kuller LH et al. Insulin as a predictor of coronary heart disease: interaction with apolipoprotein E phenotype. A report from the Multiple Risk Factor Intervention Trial. Ann Epidemiol 1994;4:40-5.[Medline]
[Order article via Infotrieve]
- Folsom AR, Szklo M., Stevens J. et al. A prospective study of coronary heart disease in relation to fasting insulin, glucose, and diabetes. The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 1997;20:935-42.[Abstract]
- Ruige JB, Assendelft WJ, Dekker JM et al. Insulin and risk of cardiovascular disease: a meta-analysis. Circulation 1998;97:996-1001.[Abstract/Free Full Text]
- Haffner SM, Stern MP, Hazuda HP et al. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA 1990;263:2893-8.[Abstract/Free Full Text]
- U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes 1995;44:1249-58.[Abstract]
- Haffner SM, Mykkanen L., Festa A. et al. Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state. Circulation 2000;101:975-80.[Abstract/Free Full Text]
- Edelstein SL, Knowler WC, Bain RP et al. Predictors of progression from impaired glucose tolerance to NIDDM: an analysis of six prospective studies. Diabetes 1997;46:701-10.[Abstract]
- Zavaroni I., Dall'Aglio E., Bonora E. et al. Evidence that multiple risk factors for coronary artery disease exist in persons with abnormal glucose tolerance. Am J Med 1987;83:609-12.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Fontbonne A., Charles MA, Thibult N. et al. Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15-year follow-up. Diabetologia 1991;34:356-61.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Fuller JH, Shipley MJ, Rose G. et al. Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study. Br Med J (Clin Res Ed) 1983;287:867-70.[Medline]
[Order article via Infotrieve]
- Donahue RP, Abbott RD, Reed DM et al. Postchallenge glucose concentration and coronary heart disease in men of Japanese ancestry. Honolulu Heart Program. Diabetes 1987;36:689-92.[Abstract]
- Jarrett RJ, McCartney P., Keen H. The Bedford survey: ten year mortality rates in newly diagnosed diabetics, borderline diabetics and normoglycaemic controls and risk indices for coronary heart disease in borderline diabetics. Diabetologia 1982;22:79-84.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Fujishima M., Kiyohara Y., Kato I. et al. Diabetes and cardiovascular disease in a prospective population survey in Japan: The Hisayama Study. Diabetes 1996;45(suppl 3):S14-S16.
- Temelkova-Kurktschiev T., Koehler C., Schaper F. et al. Relationship between fasting plasma glucose, atherosclerosis risk factors and carotid intima media thickness in non-diabetic individuals. Diabetologia 1998;41:706-12.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Balkau B., Shipley M., Jarrett RJ et al. High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men. 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study. Diabetes Care 1998;21:360-7.[Abstract]
- Gerstein HC, Yusuf S. Dysglycaemia and risk of cardiovascular disease. Lancet 1996;347:949-50.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Potter van Loon BJ, Kluft C., Radder JK et al. The cardiovascular risk factor plasminogen activator inhibitor type 1 is related to insulin resistance. Metabolism 1993;42:945-9.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Nilsson TK, Boman K., Bjerle P. et al. von Willebrand factor and fibrinolytic variables are differently affected in the insulin resistance syndrome. J Intern Med 1994;235:419-23.[Web of Science][Medline]
[Order article via Infotrieve]
- Carter AM, Catto AJ, Grant PJ Determinants of tPA antigen and associations with coronary artery disease and acute cerebrovascular disease. Thromb Haemost 1998;80:632-6.[Web of Science][Medline]
[Order article via Infotrieve]
- Meigs JB, Mittleman MA, Nathan DM et al. Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. JAMA 2000;283:221-8.[Abstract/Free Full Text]
- Mansfield MW, Stickland MH, Grant PJ PAI-1 concentrations in first-degree relatives of patients with non-insulin-dependent diabetes: metabolic and genetic associations. Thromb Haemost 1997;77:357-61.[Web of Science][Medline]
[Order article via Infotrieve]
- Juhan-Vague I., Pyke SDM, Alessi MC et al. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. Circulation 1996;94:2057-63.[Abstract/Free Full Text]
- Kohler HP, Grant PJ Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med 2000;342:1792-801.[Free Full Text]
- Chandler WL, Alessi MC, Aillaud MF et al. Clearance of Tissue Plasminogen Activator (TPA) and TPA/Plasminogen Activator Inhibitor Type 1 (PAI-1) Complex. Circulation 1997;96:761-8.[Abstract/Free Full Text]
- Steins MB, Padro T., Li CX et al. Overexpression of tissue-type plasminogen activator in atherosclerotic human coronary arteries. Atherosclerosis 1999;145:173-80.[CrossRef][Medline]
[Order article via Infotrieve]
- Haverkate F., Thompson SG, Duckert F. Haemostasis factors in angina pectoris; relation to gender, age and acute-phase reaction. Results of the ECAT Angina Pectoris Study Group. Thromb Haemost 1995;73:561-7.[Web of Science][Medline]
[Order article via Infotrieve]
- Meade TW, Mellows S., Brozovic M. et al. Haemostatic function and ischaemic heart disease: Principal Results of the Northwick Park Heart Study. Lancet 1986;2:533-7.[Web of Science][Medline]
[Order article via Infotrieve]
- Heinrich J., Balleisen L., Schulte H. et al. Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM Study in Healthy Men. Arterioscler Thromb Vasc Biol 1994;14:54-9.[Abstract/Free Full Text]
- Folsom AR, Wu KK, Rosamond WD et al. Prospective study of hemostatic factors and incidence of coronary heart disease. The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1997;96:1102-8.[Abstract/Free Full Text]
- Meade TW, Ruddock V., Stirling Y. et al. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993;342:1076-9.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Heywood DM, Mansfield MW, Grant PJ Factor VII gene polymorphisms, factor VII:C levels and features of insulin resistance in non-insulin dependent diabetes mellitus. Thromb Haemost 1996;75:401-6.[Web of Science][Medline]
[Order article via Infotrieve]
- Mansfield MW, Heywood DM, Grant PJ Circulating levels of factor VII, fibrinogen, and von Willebrand factor and features of insulin resistance in first-degree relatives of patients with NIDDM. Circulation 1996;94:2171-6.[Abstract/Free Full Text]
- Zitoun D., Bara L., Basdevant A. et al. Levels of factor VIIc associated with decreased tissue factor pathway inhibitor and increased plasminogen activator inhibitor-1 in dyslipidemias. Arterioscler Thromb Vasc Biol 1996;16:77-81.[Abstract/Free Full Text]
- Humphries SE, Lane A., Green FR et al. Factor VII coagulant activity and antigen levels in healthy men are determined by interaction between factor VII genotype and plasma triglyceride concentration. Arterioscler Thromb 1994;14:193-8.[Abstract/Free Full Text]
- Ernst E., Resch KL Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. Ann Intern Med 1993;118:956-63.[Abstract/Free Full Text]
- Ganda OP, Arkin CF Hyperfibrinogenemia. An important risk factor for vascular complications in diabetes. Diabetes Care 1992;15:1245-50.[Abstract]
- Landin K., Stigendal L., Eriksson E. et al. Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1. Metabolism 1990;39:1044-8.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Festa A., D'Agostino R., Howard G. et al. Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study. Kidney Int 2000;58:1703-10.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Yudkin JS Abnormalities of coagulation and fibrinolysis in insulin resistance. Evidence for a common antecedent? Diabetes Care 1999;22 (suppl 3):C25-C30.[Web of Science][Medline]
[Order article via Infotrieve]
- Miller GJ, Esnouf MP, Burgess AI et al. Risk of coronary heart disease and activation of factor XII in middle-aged men. Arterioscler Thromb Vasc Biol 1997;17:2103-6.[Abstract/Free Full Text]
- Kohler HP, Carter AM, Stickland MH et al. Levels of activated FXII in survivors of myocardial infarction-- association with circulating risk factors and extent of coronary artery disease. Thromb Haemost 1998;79:14-8.[Web of Science][Medline]
[Order article via Infotrieve]
- Haffner SM, Stern MP, Hazuda HP et al. Increased insulin concentrations in nondiabetic offspring of diabetic parents. N Engl J Med 1988;319:1297-301.[Abstract]
- Chen W., Srinivasan SR, Elkasabany A. et al. The association of cardiovascular risk factor clustering related to insulin resistance syndrome (Syndrome X) between young parents and their offspring: the Bogalusa Heart Study. Atherosclerosis 1999;145:197-205.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Bao W., Srinivasan SR, Wattigney WA et al. Persistence of multiple cardiovascular risk clustering related to syndrome X from childhood to young adulthood. The Bogalusa Heart Study. Arch Intern Med 1994;154:1842-7.[Abstract/Free Full Text]
- Bao W., Srinivasan SR, Berenson GS Persistent elevation of plasma insulin levels is associated with increased cardiovascular risk in children and young adults. The Bogalusa Heart Study. Circulation 1996;93:54-9.[Abstract/Free Full Text]
- Mayer EJ, Newman B., Austin MA et al. Genetic and environmental influences on insulin levels and the insulin resistance syndrome: an analysis of women twins. Am J Epidemiol 1996;143:323-32.[Abstract/Free Full Text]
- Narkiewicz K., Chrostowska M., Kuchta G. et al. Genetic influences on insulinemia in normotensive twins. Am J Hypertens 1997;10:467-70.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Mitchell BD, Kammerer CM, Blangero J. et al. Genetic and environmental contributions to cardiovascular risk factors in Mexican Americans. The San Antonio Family Heart Study. Circulation 1996;94:2159-70.[Abstract/Free Full Text]
- de Lange M., Snieder H., Ariëns RAS et al. The genetics of haemostasis: a twin study. Lancet 2001;357:101-5.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Souto JC, Almasy L., Borrell M. et al. Genetic determinants of hemostasis phenotypes in Spanish families. Circulation 2000;101:1546-51.[Abstract/Free Full Text]
- Mitchell BD, Kammerer CM, Mahaney MC et al. Genetic analysis of the IRS. Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures. Arterioscler Thromb Vasc Biol 1996;16:281-8.[Abstract/Free Full Text]
- Hong Y., Pedersen NL, Brismar K. et al. Genetic and environmental architecture of the features of the insulin-resistance syndrome. Am J Hum Genet 1997;60:143-52.[Web of Science][Medline]
[Order article via Infotrieve]
- Ravelli AC, van der Meulen JH, Michels RP et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet 1998;351:173-7.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Mayer-Davis EJ, D'Agostino R., Jr., Karter AJ et al. Intensity and amount of physical activity in relation to insulin sensitivity: the Insulin Resistance Atherosclerosis Study. JAMA 1998;279:669-74.[Abstract/Free Full Text]
- Lithell HO, McKeigue PM, Berglund L. et al. Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50-60 years. BMJ 1996;312:406-10.[Abstract/Free Full Text]
- Shimokata H., Muller DC, Andres R. Studies in the distribution of body fat. III. Effects of cigarette smoking. JAMA 1989;261:1169-73.[Abstract/Free Full Text]
- Frati AC, Iniestra F., Ariza CR Acute effect of cigarette smoking on glucose tolerance and other cardiovascular risk factors. Diabetes Care 1996;19:112-8.[Abstract]
- Facchini FS, Hollenbeck CB, Jeppesen J. et al. Insulin resistance and cigarette smoking. Lancet 1992;339:1128-30.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Eliasson B., Attvall S., Taskinen MR et al. Smoking cessation improves insulin sensitivity in healthy middle-aged men. Eur J Clin Invest 1997;27:450-6.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Dallosso HM, James WP The role of smoking in the regulation of energy balance. Int J Obes 1984;8:365-75.[Web of Science][Medline]
[Order article via Infotrieve]
- Grant PJ The effects of high and medium dose metformin therapy on cardiovascular risk factors in patients with type II diabetes. Diabetes Care 1996;19:64-6.[Abstract]
- Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854-65.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Bailey CJ The Diabetes Prevention Program: headline results. Br J Diabetes Vasc Dis 2001;1:62-4.[Abstract/Free Full Text]
- Tuomilehto J., Lindstrom J., Eriksson JG et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343-50.[Abstract/Free Full Text]
The British Journal of Diabetes & Vascular Disease, Vol. 2, No. 1,
19-26 (2002)
DOI: 10.1177/14746514020020011301

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