Evidence that multiple risk factors for coronary artery disease exist in persons with abnormal glucose tolerance

Zavaroni, Ivana; Dall'Aglio, E; Bonora, Enzo; Alip, Orsola; Passeri, M; Reaven, Gerald M.

doi:10.1016/0002-9343(87)90887-4

Cited by 72 publications

(19 citation statements)

References 34 publications

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“…35 If insulin resistance and NIDDM show familial aggregation as has been proposed, 36 -37 one would expect that subjects with a family history of diabetes are particularly susceptible to abnormalities in the cardiovascular risk factors that are mediated by insulin resistance. Of the known cardiovascular risk factors, high VLDL triglyceride and low HDL cholesterol levels have been shown to be associated with not only hyperinsulinemia 38 - 41 (as demonstrated in this study; Table 3) but also insulin resistance as measured by the euglycemic clamp technique in normoglycemic subjects 42 - 44 and subjects with abnormal glucose tolerance. 44 Furthermore, the elevation of blood pressure levels has been shown to be related to impaired insulin-mediated glucose uptake in both nondiabetic 45 and diabetic 46 subjects.…”

Section: Discussionsupporting

confidence: 60%

Early abnormalities in coronary heart disease risk factors in relatives of subjects with non-insulin-dependent diabetes.

Sarlund

Pyörälà

Penttilä

et al. 1992

Arterioscler Thromb

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Coronary heart disease risk factor levels were studied in 184 first-degree relatives (sisters and brothers) of non-insulin-dependent diabetic subjects (124 relatives with normoglycemia, 34 relatives with impaired glucose tolerance [IGT], and 26 relatives with non-insulin-dependent diabetes mellitus [NIDDM]) and in 215 relatives of nondiabetic subjects (194 relatives with normoglycemia and 21 relatives with IGT). Subjects with IGT exhibited the highest insulin responses to an oral glucose load. Systolic blood pressure was significantly higher; serum high density lipoprotein cholesterol level was significantly lower; and total, low density lipoprotein, and very low density lipoprotein triglyceride levels were higher in the relatives with a family history of diabetes who had IGT or NIDDM than in the normoglycemic relatives without a family history of diabetes. These abnormal changes were not seen in normoglycemic relatives or relatives with IGT who had no family history of NIDDM. Thus, in relatives of diabetics, abnormal glucose tolerance seems to induce changes in cardiovascular heart disease risk factor levels that are similar to those observed in NIDDM. Therefore, a family history of diabetes adds substantially to the risk for atherosclerosis, particularly in subjects with IGT. ( 1 At the time of diagnosis, the existence of atherosclerotic manifestations is already widespread, and furthermore, the prevalence of coronary heart disease shows virtually no correlation with the duration of NIDDM. Although the etiology of this excess risk is largely unexplained, many cardiovascular risk factors are abnormally high in patients with NIDDM. In particular, these factors include hypertension or elevated blood pressure levels, hyperinsulinemia, high serum total and very low density lipoprotein (VLDL) triglyceride levels, and low serum high density lipoprotein (HDL) cholesterol and apolipoprotein A-I levels. 2 -11 It is widely accepted that frank clinical NIDDM is preceded by a long prediabetic stage.12 Impaired glucose tolerance (IGT), which can be assessed by an oral glucose tolerance test, is a widely accepted entity of the prediabetic stage. It is commonly believed that IGT represents a transitional stage between normal and diabetic glucose tolerance. Moreover, IGT is also a risk factor for cardiovascular disease, either by itself or as a consequence of its presumed precursor relation to diabetes.113 " 16 IGT is not, however, a homogeneous condi-

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Section: Discussionsupporting

confidence: 60%

Early abnormalities in coronary heart disease risk factors in relatives of subjects with non-insulin-dependent diabetes.

Sarlund

Pyörälà

Penttilä

et al. 1992

Arterioscler Thromb

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“…Ganda et al 24 reported an elevated level of total triglycerides and lower level of HDL cholesterol level in 65 subjects with IGT compared to corresponding controls. Zavaroni et al 25 reported an elevated total cholesterol and triglyceride level in 50 subjects with IGT compared with 50 normoglycemic controls matched for gender, age, and the degree of obesity, but no difference in HDL cholesterol. In the study of Falko et al, 26 the only lipid or lipoprotein abnormality was elevated LDL cholesterol level in men with IGT compared to corresponding controls.…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic hyperglycemia is associated with lipid and lipoprotein changes favoring atherosclerosis.

Laakso

Barrett‐Connor

1989

Arteriosclerosis

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We studied llpid and lipoprotein concentrations and their relationships to Insulin level in 994 men and 1246 women ages 50 to 91 years In the upper middle-class community of Rancho Bernardo In southern California. Altogether, 593 men and 741 women had normal glucose tolerance, 240 men and 348 women, impaired glucose tolerance (IGT), 104 men and 117 women, newly diagnosed nonlnsullndependent diabetes (NIDDM), and 57 men and 40 women, previously diagnosed NIDDM. In women but not men, total cholesterol and low density lipoprotein were significantly higher In those with newly diagnosed NIDDM, compared to subjects with normal glucose tolerance. In both men and women, high density lipoprotein (HDL) cholesterol was significantly lower, and total trlglycerlde significantly higher, In subjects with IGT and NIDDM compared to those with normal glucose tolerance; these differences persisted after adjusting for age, body mass index, smoking, alcohol Intake, and exercise level. Multiple linear-regression analyses showed that fasting Insulin (but not 2-hour Insulin) was significantly associated with low HDL cholesterol and high total trlglycerldes Independently from other variables (age, body mass index, waist/hip ratio, alcohol Intake, smoking, exercise, and 2-hour glucose). Overall, these results show that asymptomatic hyperglycemia (IGT, newly diagnosed NIDDM) Is associated with llpid and lipoprotein changes favoring atherosclerosis and that fasting hyperinsullnemla (Insulin resistance) is the most Important factor associated with these llpid and lipoprotein abnormalities. (Arteriosclerosis 9:665-672, September/October 1989)

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“…In both syndromes, an increase in cardiovascular mortality is noted [1,43,44]. In fact, two studies examining noncushingoid patients with central adiposity who resemble Syndrome X, found an activation of the hypothalamic-pituitary adrenal axis, with elevated urinary cortisol excretion [45,46].…”

Section: Discussionmentioning

confidence: 99%

Carbohydrate and Lipid Metabolism in Endogenous Hypercortisolism: Shared Features with Metabolic Syndrome X and NIDDM.

et al. 1996

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Abstract.Carbohydrate and lipid metabolism was cross-sectionally assessed in 16 patients with endogenous hypercortisolism (endogenous Cushing syndrome). Five patients (31%) had fasting glucose levels over 6.6 mmol/l and a HbAic over 7.5%. Six patients (38%) had diabetes mellitus based on an abnormal 75 g oral glucose tolerance test (OGTT) and two additional patients (13%) had impaired glucose tolerance based on an OGTT. Compared to obese individuals, patients with Cushing syndrome had an elevated glucose but no elevated insulin response to the OGTT. Regression analysis showed positive correlations between 24-h urinary free cortisol (UFC) and fasting blood glucose (P<0.0005), UFC and OGTT glucose area under the curve (AUC) (P<0.01), and UFC and HbAlc (P<0.005). UFC levels were negatively correlated (P<0.05) with OGTT insulin AUC and insulin/glucose ratios. Eleven (69%) patients required anti-hypertensive therapy for blood pressure control. Total cholesterol and triglycerides were elevated in patients with Cushing syndrome compared to obese controls, while LDL and HDL cholesterol, and Lp(a) were similar in the two groups. We conclude that impaired glucose tolerance and/or diabetes in patients with endogenous Cushing syndrome is due to the hyperglycemic effects of cortisol with relative insulinopenia.Thus, Cushing syndrome shares features with both the Metabolic Syndrome X and NIDDM, including impaired glucose uptake, hyperlipidemia and hypertension.However, in Cushing syndrome, a relative insulinopenia occurs, while in Metabolic Syndrome X and NIDDM, insulin excess is observed. In Cushing syndrome, as the hypercortisolemia exacerbates, insulinopenia becomes more paramount, suggesting that cortisol exerts a direct or indirect "toxic" effect on the fl -cell .

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Evidence that multiple risk factors for coronary artery disease exist in persons with abnormal glucose tolerance

Cited by 72 publications

References 34 publications

Early abnormalities in coronary heart disease risk factors in relatives of subjects with non-insulin-dependent diabetes.

Early abnormalities in coronary heart disease risk factors in relatives of subjects with non-insulin-dependent diabetes.

Asymptomatic hyperglycemia is associated with lipid and lipoprotein changes favoring atherosclerosis.

Carbohydrate and Lipid Metabolism in Endogenous Hypercortisolism: Shared Features with Metabolic Syndrome X and NIDDM.

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