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      Relation between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects. Results from a cross-sectional study in Malmö, Sweden.

      Diabetic Medicine
      Aged, Blood Pressure, Carotid Arteries, pathology, ultrasonography, Carotid Stenosis, epidemiology, surgery, Cross-Sectional Studies, Diabetes Mellitus, physiopathology, Diabetic Angiopathies, Female, Humans, Insulin, blood, Insulin Resistance, Male, Middle Aged, Sweden, Tunica Intima, Tunica Media

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          Abstract

          To assess whether there is an association between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects free from symptomatic cardiovascular disease. A cross-sectional population-based study in Malmö, Sweden, of 4,816 (40% men) subjects, born 1926-1945. The prevalence of insulin resistance was established by the homeostasis model assessment (HOMA) and defined as values above the 75th percentile. Criteria issued by the European Group for the Study of Insulin Resistance (EGIR) were used for the definition of the insulin resistance syndrome. Common carotid artery intima-media thickness (IMT) and carotid stenosis (> 15%) were measured by B-mode ultrasonography. Age and sex-adjusted common carotid IMT among subjects with the insulin resistance syndrome (12.7%) and controls was 0.812 mm, respectively, 0.778 mm (P < 0.001). The prevalence of stenosis in the two groups was 22.9 and 19.2% (P = 0.040). Insulin resistance per se was after adjustment for age and sex associated with increased IMT (0.780 mm vs. 0.754 mm, P < 0.001). This association disappeared, however, when other factors included in the insulin resistance syndrome were taken into account. Fasting serum insulin covaries with a number of factors and conditions known to influence the development of atherosclerosis. It is concluded that the association between insulin resistance, as assessed by the HOMA method in non-diabetic subjects, and atherosclerosis is explained by its covariance with established risk factors for cardiovascular disease of which hypertension seems to be the most significant.

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          Most cited references34

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          Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993.

          Few studies have determined whether greater carotid artery intima-media thickness (IMT) in asymptomatic individuals is associated prospectively with increased risk of coronary heart disease (CHD). In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measurements at six sites of the carotid arteries using B-mode ultrasound. The authors assessed its relation to CHD incidence over 4-7 years of follow-up (1987-1993) in four US communities (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland) from samples of 7,289 women and 5,552 men aged 45-64 years who were free of clinical CHD at baseline. There were 96 incident events for women and 194 for men. In sex-specific Cox proportional hazards models adjusted only for age, race, and center, the hazard rate ratio comparing extreme mean IMT (> or = 1 mm) to not extreme (< 1 mm) was 5.07 for women (95% confidence interval 3.08-8.36) and 1.85 for men (95% confidence interval 1.28-2.69). The relation was graded (monotonic), and models with cubic splines indicated significant nonlinearity. The strength of the association was reduced by including major CHD risk factors, but remained elevated at higher IMT. Up to 1 mm mean IMT, women had lower adjusted annual event rates than did men, but above 1 mm their event rate was closer to that of men. Thus, mean carotid IMT is a noninvasive predictor of future CHD incidence.
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            Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study.

            Noninvasive assessment of intima-media thickness (IMT) is widely used in observational studies and trials as an intermediate or proxy end point for cardiovascular disease. However, data showing that IMT predicts cardiovascular disease are limited. We studied whether common carotid IMT is related to future stroke and myocardial infarction. We used a nested case-control approach among 7983 subjects aged > or =55 years participating in the Rotterdam Study. At baseline (March 1990 through July 1993), ultrasound images of the common carotid artery were stored on videotape. Determination of incident myocardial infarction and stroke was predominantly based on hospital discharge records. Analysis (logistic regression) was based on 98 myocardial infarctions and 95 strokes that were registered before December 31, 1994. IMT was measured from videotape for all case subjects and a sample of 1373 subjects who remained free from myocardial infarction and stroke during follow-up. The mean duration of follow-up was 2.7 years. Results were adjusted for age and sex. Stroke risk increased gradually with increasing IMT. The odds ratio for stroke per standard deviation increase (0.163 mm) was 1.41 (95% CI, 1.25 to 1.82). For myocardial infarction, an odds ratio of 1.43 (95% CI, 1.16 to 1.78) was found. When subjects with a previous myocardial infarction or stroke were excluded, odds ratios were 1.57 (95% CI, 1.27 to 1.94) for stroke and 1.51 (95% CI, 1.18 to 1.92) for myocardial infarction. Additional adjustment for several cardiovascular risk factors attenuated these associations: 1.34 (95% CI, 1.08 to 1.67) and 1.25 (95% CI, 0.98 to 1.58), respectively. The present study, based on a short follow-up period, provides evidence that an increased common carotid IMT is associated with future cerebrovascular and cardiovascular events.
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              Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging.

              A study in vitro of specimens of human aortic and common carotid arteries was carried out to determine the feasibility of direct measurement (i.e., not from residual lumen) of arterial wall thickness with B mode real-time imaging. Measurements in vivo by the same technique were also obtained from common carotid arteries of 10 young normal male subjects. Aortic samples were classified as class A (relatively normal) or class B (with one or more atherosclerotic plaques). In all class A and 85% of class B arterial samples a characteristic B mode image composed of two parallel echogenic lines separated by a hypoechoic space was found. The distance between the two lines (B mode image of intimal + medial thickness) was measured and correlated with the thickness of different combinations of tunicae evaluated by gross and microscopic examination. On the basis of these findings and the results of dissection experiments on the intima and adventitia we concluded that results of B mode imaging of intimal + medial thickness did not differ significantly from the intimal + medial thickness measured on pathologic examination. With respect to the accuracy of measurements obtained by B mode imaging as compared with pathologic findings, we found an error of less than 20% for measurements in 77% of normal and pathologic aortic walls. In addition, no significant difference was found between B mode-determined intimal + medial thickness in the common carotid arteries evaluated in vitro and that determined by this method in vivo in young subjects, indicating that B mode imaging represents a useful approach for the measurement of intimal + medial thickness of human arteries in vivo.
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