Glucose Tolerance and Insulin Response in Atherosclerosis

Sloan, James M.; Mackay, J. S.; Sheridan, B.

doi:10.1136/bmj.4.5735.586

Cited by 32 publications

(9 citation statements)

References 8 publications

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“…Previously, subjects with lower-extremity arterial disease were shown to have elevated insulin levels following an oral glucose challenge. 15,16 Results from the current study were consistent with the findings from the Cardiovascular Health Study, another population-based cohort study of the elderly. In the Cardiovascular Health Study, fasting insulin level was inversely associated with the ABI index, after adjustment for age and sex, but did not exhibit an independent association in multivariate analysis wherein multiple CVD risk factors, including diabetes and HDL cholesterol, were included.…”

Section: Discussionsupporting

confidence: 87%

Hyperinsulinemia and Cardiovascular Disease in Elderly Men

Burchfiel

Sharp

Curb

et al. 1998

ATVB

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Abstract-Hyperinsulinemia has been associated with cardiovascular disease (CVD), but whether this relation is independent of other CVD risk factors is uncertain. Most studies have focused on coronary heart disease (CHD), but few have included peripheral vascular disease (PVD) and stroke. Moreover, evidence in elderly and minority populations is limited. Between 1991 and 1993, 3562 elderly (71 to 93 years) Japanese-American men from the Honolulu Heart Program were examined and had fasting insulin levels measured. Hyperinsulinemia, defined as a fasting insulin Ն95th percentile among nonobese men with normal glucose tolerance and no diabetic history or medication use, was observed in 22% of the population. Subjects with hyperinsulinemia had a more adverse CVD risk factor profile and had higher age-adjusted prevalences of CHD, angina, PVD, thromboembolic stroke, and hemorrhagic stroke compared with those without hyperinsulinemia. Age-adjusted fasting insulin levels but not 2-hour levels were also significantly elevated (PϽ.01) in those with prevalent CVD compared with those without. In logistic regression analyses, adjustment for multiple CVD risk factors attenuated the relations of hyperinsulinemia with CHD, angina, and PVD to nonsignificant levels, whereas those involving thromboembolic and hemorrhagic stroke were strengthened and remained significant (odds ratiosϭ2.27 and 7.53, 95% confidence intervalsϭ1.25 to 4.13 and 1.65 to 34.25, respectively). When multivariate analyses were restricted to nondiabetic subjects, associations were slightly weaker and in general nonsignificant. Nondiabetic men with thromboembolic stroke were twice as likely to have hyperinsulinemia as those who were stroke-free, although this association was of borderline significance (odds ratioϭ1.99, 95% confidence intervalϭ0.95 to 4.17, Pϭ.069). In subjects with elevated total cholesterol levels, somewhat stronger associations were observed for PVD and stroke but not for CHD. 1-3 More recent investigations, 4-6 but not all, 7 suggest that the association may not be independent of other known CVD risk factors. Some of the discordant findings may be due to the fact that these early studies did not take into account HDL cholesterol levels. 7-9Whether hyperinsulinemia is associated with CVD has not been widely studied in the elderly nor in subsets of the population who might be at increased risk. For example, relatively low levels of total and LDL cholesterol could account for the paradoxically low rates of CHD despite a high prevalence of glucose intolerance in some populations. 10 -12 Moreover, although associations of insulin with CHD have been examined in a number of studies, those involving stroke 13 and PVD 14 -16 have been assessed infrequently. The purpose of this investigation was to assess the association of hyperinsulinemia with several clinical and subclinical manifestations of CVD in elderly subjects. A recent examination of the entire Honolulu Heart Program cohort between 1991 and 1993 provided the opportunity to examine these r...

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Section: Discussionsupporting

confidence: 87%

Hyperinsulinemia and Cardiovascular Disease in Elderly Men

Burchfiel

Sharp

Curb

et al. 1998

ATVB

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“…A high incidence of this type of glucose-insulin-defect has been reported in patients with peripheral vascular disease (4,14,28), stroke (3), hypertension (29), obesity (14), and impotence (S. Deutsch, personal communication) and suggests that an elevation in E/T and perhaps hyperestrogenemia may be operative in these disorders. Administration of estrogen appears to increase the likelihood of stroke in patients who have already had one (30) and may produce hypertension in women (31).…”

Section: Discussionmentioning

confidence: 97%

Relationship between serum sex hormones and glucose, insulin and lipid abnormalities in men with myocardial infarction.

Phillips¹

1977

Proc. Natl. Acad. Sci. U.S.A.

106

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Fifteen patients who had had a myocardial infarction before the age of 43 were compared with thirteen age-matched normal subjects. Twelve of the patients and three of the controls had a delayed glucose and insulin peak in the glucose tolerance test. Curves with delayed peaks defin larger mean glucose and insulin areas than normal curves. When the measurements of the four patients with the largest areas under the glucose tolerance curve were separated, significant correlations were observed in the remaining patients and controls.The ratio in serum of the concentrations of estradiol-17j# to testosterone (E/) correlated with serum glucose area (r = +0.69, P < 0.001), insulin area (r = +0.80, P < 0.001), and the ratio of insulin area to glucose area (I/G) (r = +0.64, P < 0.005) in the glucose tolerance test. Serum cholesterol concentration correlated with E/T, insulin area, and I/G, and serum triglyceride concentration correlated with glucose area, I/G, and serum cholesterol concentration. The hypothesis is presented (i) that in men who have had a myocardial infarction, an abnormality in glucose tolerance and insulin response and elevation in serum cholesterol and triglyceride concentrations are all part of the same defect (glucose-insulin-lipid defect), (ii) that this glucose-insulin-lipid defect when glucose intolerance is present is the "mild diabetes" commonly associated with myocardial infarction but is based on a mechanism different from that of classical diabetes, (iii) that this glucose-insulin-lipid defect is secondary to an elevation in E/T, and (iv) that an alteration in the sex hormone milieu is the major predisposing factor for myocardial infarction.An abnormality in glucose tolerance, insulin response, serum lipid or lipoprotein concentrations, or some combination of these has been reported to occur in 80-96% of patients with coronary heart disease (1-7). In a previous study (8), a high incidence of hyperestrogenemia was observed in men under 44 years of age with myocardial infarction. The present report describes further investigations carried out on the patients and normal subjects of that study in order to determine whether the hyperestrogenemia was related to the glucose, insulin, and lipid abnormalities. The results of these investigations show a high level of correlation between the degrees of the glucose and insulin defects and the ratio of the weight concentrations in serum of estradiol-17fl to testosterone (E/T). The degree of the glucose-insulin defect was also found to correlate with the serum cholesterol and triglyceride concentrations, suggesting that an elevation in the concentrations of these lipids is part of the same defect (glucose-insulin-lipid defect). These observations raise the possibility that this glucose-insulin-lipid defect is secondary to an elevation in E/T and that a disturbance in the relationships of serum sex hormones is the major predisposing factor for myocardial infarction in men.

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“…Nowever, incan insulin and glucosc, 1 1 1 after t h e oral glucose load, were highcr in eases than in controls (1 1 1 insulin, 73.6 mlJ/l in cases, 59.8 m1J/1 in controls; P 20.05; 1 1 1 glucose, 8.9 nilJ/I in cases, 8.1 mU/I in controls; I-'< 0.05). Whcn the total study population was split by sex, 1 1 1 insulin was significantly highcr in mcn than in women (men 72.8 mtJ/l, women 59.4 mtJ/I; P IO.05).…”

Section: Univariate Analysis Of Risk Factorsmentioning

confidence: 79%

“…I n particular, tlie association between insulin and the dcvclopment of pcriphcral arterial disease in tlie non-diabetic general population is unltnown. 'livo small studies indicated that non-diabetic men with athcrosclcrotic disease of the lower limbs had higher plasma insulin levcls than healthy controls [7,8], but the studies did not consider the influence of other cardiovascular risk factors. In this respect, hyperinsulinaemia is known to b e associated with liypcrtriglyceridaemia, low levels of high-density lipoprotein ( H D L ) cholesterol, and hypertension [9].…”

Section: Introductionmentioning

confidence: 98%