It is unclear whether the role of insulin resistance in the development of atherosclerotic cardiovascular disease is similar in populations in which the incidence of atherosclerotic diseases significantly differs from that in Western countries. The aim of this study was to determine the relationship between insulin resistance and the development of cardiovascular disease in the Japanese population. We conducted 75 g-oral glucose tolerance tests (OGTTs) on 1,928 inhabitants of two towns in Hokkaido, Japan. Subjects using anti-hypertensive agents and known diabetic patients were excluded from the study. Data from the remaining 1,227 subjects (540 males and 687 females; mean age 56.0±10.8 years) were used for the analysis, and 1,051 subjects were seen in a follow-up care setting for a period of 8 years. The presence of insulin resistance was defined according to the guidelines reported our previous study: insulin levels of 64.0 mU/l or higher 2 h after the 75 g-OGTT. The insulin-resistant (IR) group had several risk factors such as hypertension, diabetes, treated or untreated hypercholesterolemia, hypertriglyceridemia, low high-density-lipoprotein (HDL) cholesterol levels, and obesity. During the follow-up period of 8 years, the incidence of coronary artery disease, which was adjusted for age, body mass index, sex, systolic blood pressure, fasting plasma glucose, total cholesterol, triglyceride, and HDL cholesterol was significantly (3.2 times) higher in the IR group than in the insulin non-resistant group. The results suggested that insulin resistance is an independent risk factor for coronary artery disease in Japanese subjects, as has also been demonstrated in the case of individuals in Europe and USA.
Juhan-Vague I, Thompson SG, Jespersen J : Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris. The ECAT Angina Pectoris Study Group. Arterioscler Thromb 1993; 13: 1865–1873.
Suzuki M, Shinozaki K, Harano Y, et al: Insulin resistance as an independent risk factor for carotid wall thickening. Hypertension 1996; 28: 593–598.
Wingard DL, Barrett-Connor EL, Ferrara A : Is insulin really a heart disease risk factor. Diabetes Care 1995; 18: 1299–1304.
Jarrett RJ : Is insulin atherogenic? Diabetologia 1988; 31: 71–75.
Stout RW : Insulin and atheroma. 20-yr perspective. Diabetes Care 1990; 13: 631–654.
Reaven GM, Laws A : Insulin resistance, compensatory hyperinsulinaemia, and coronary heart disease. Diabetologia 1994; 37: 948–952.
Ruige JB, Assendelft WJ, Dekker JM, Kostense PJ, Heine RJ, Bouter LM : Insulin and risk of cardiovascular disease: a meta-analysis. Circulation 1998; 97: 996–1001.
Nelson RG, Sievers ML, Bennett PH, et al: Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non-insulin-dependent diabetes. Circulation 1990; 81: 987–995.
Saitoh S, Tanaka S, Iimura O, et al: Glucose tolerance, obesity, and hypertension: epidemiological study in Hokkaido, Japan. Ann N Y Acad Sci 1993; 676: 342–344.
Oimatsu H, Saitoh S, Ura N, Shimamoto K : A practical index for evaluation of insulin resistance. J Jpn Diabetes Soc 2000; 43: 205–213.
Matsuzawa Y : The new diagnostic criteria of obesity. J Jpn Soc Study Obesity 2000; 6: 18–28.
The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997; 157: 2413–2446.
American Diabetes Association : Clinical practice recommendations 1997. Diabetes Care 1997; 20 ( Suppl 1): S1–S70.
Investigating Committee of Guideline for Diagnosis and Treatment of Hyperlipidemias, Japan Atherosclerosis Society : Guideline for Diagnosis and Treatment of Hyperlipidemias in Adults. Tokyo, Japan Atherosclerosis Society, 1997.
Zavaroni I, Bonora E, Passeri M, et al: Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance. N Engl J Med 1989; 320: 702–706.
Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP : Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes 1992; 41: 715–722.
Howard G, O'Leary DH, Bergman R, et al: Insulin sensitivity and atherosclerosis. Circulation 1996; 93: 1809–1817.
Tanaka Y, Atsumi Y, Kawamori R, et al: Usefulness of revised fasting plasma glucose criterion and characteristics of the insulin response to an oral glucose load in newly diagnosed Japanese diabetic subjects. Diabetes Care 1998; 21: 1133–1137.
Pyorala M, Miettinen H, Halonen P, Laakso M, Pyorala K : Insulin resistance syndrome predicts the risk of coronary heart disease and stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study. Arterioscler Thromb Vasc Biol 2000; 20: 538–544.
Shinozaki K, Naritomi H, Harano Y, et al: Role of insulin resistance associated with compensatory hyperinsulinemia in ischemic stroke. Stroke 1996; 27: 37–43.
Hirose H, Saito I, Kawabe H, Saruta T : Insulin resistance and hypertension: seven-year follow-up study in middle-aged Japanese men (the KEIO study). Hypertens Res 2003; 26: 795–800.
Sugaya T, Yasu T, Saito M, et al: Effect of atrial septal aneurysm on risk of cerebrovascular events in Japanese patients. Int J Cardiol 2004; 93: 253–256.
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Fujiwara, T., Saitoh, S., Takagi, S. et al. Development and Progression of Atherosclerotic Disease in Relation to Insulin Resistance and Hyperinsulinemia. Hypertens Res 28, 665–670 (2005) doi:10.1291/hypres.28.665
- insulin resistance
- cardiovascular disease
- risk factors
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