Sex differences in coronary mortality among diabetics in Evans County, Georgia

Heyden, S; Heiss, Gerardo; Bartel, Alan G.; Hames, Curtis G.

doi:10.1016/0021-9681(80)90021-1

Cited by 112 publications

(57 citation statements)

References 8 publications

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“…Moreover, it has been reported recently that in diabetic women, coronary artery calcification, a measure of atherosclerotic plaque burden, is greatly increased and the gender difference is lost (36). Because little of this can be explained by known coronary risk factors, the observed increase in lipid ROOH along with the decrease in TRAP and uric acid levels in diabetic women compared with diabetic men could play an important role in the development of the atherosclerotic plaque and may represent one of the pathophysiological explanations for the higher cardiovascular risk of diabetic versus nondiabetic women (3)(4)(5)(6)37).…”

Section: Results -As Shown Inmentioning

confidence: 99%

“…Diabetes reduces the gender protection against vascular disease in premenopausal women, and in diabetic women, the coronary heart disease (CHD) mortality rate is significantly higher than in nondiabetic women (3)(4)(5). Moreover, several studies show that diabetes increases cardiovascular risk to a greater extent in women than in men (6,7). There is currently great interest in the potential role of increased oxidative stress in the development of diabetic complications (8,9).…”

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confidence: 99%

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Early Increase of Oxidative Stress and Reduced Antioxidant Defenses in Patients With Uncomplicated Type 1 Diabetes

et al. 2002

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OBJECTIVE -Diabetes increases the risk of coronary heart disease (CHD) to a greater extent in women than in men. We investigated whether type 1 diabetic patients with short duration of disease and without complications have an altered oxidative status and whether there are differences between men and women.RESEARCH DESIGN AND METHODS -We investigated oxidative status in 29 control subjects and 37 patients with uncomplicated type 1 diabetes with duration of 6 Ϯ 3 years.RESULTS -Compared with control subjects, type 1 diabetic patients had lower total plasma antioxidant capacity (TRAP) (720.3 Ϯ 111.2 vs. 972.5 Ϯ 97.7 mol/l in men, P Ͻ 0.001; 579.8 Ϯ 95.4 vs. 930.1 Ϯ 84.2 in women, P Ͻ 0.001), higher lipid hydroperoxide (ROOH) levels (6.4 Ϯ 2.2 vs. 2.0 Ϯ 0.7 mol/l in men, P Ͻ 0.001; 8.1 Ϯ 1.9 vs. 2.2 Ϯ 0.6 in women, P Ͻ 0.001), higher total conjugated diene (CD) levels (0.037 Ϯ 0.003 vs. 0.033 Ϯ 0.002 A.U. in men, P Ͻ 0.001), lower 246-nm CD levels (0.0032.Ϯ 0.0010 vs. 0.0070 Ϯ 0.0012 A.U. in men, P Ͻ 0.001; 0.0022 Ϯ 0.0011 vs. 0.0072 Ϯ 0.0014 A.U. in women, P Ͻ 0.001), and higher 232-nm CD levels (0.0348 Ϯ 0.0041 vs. 0.0257 Ϯ 0.0022 A.U. in men, P Ͻ 0.001; 0.0346 Ϯ 0.0031 vs. 0.0246 Ϯ 0.0074 A.U. in women, P Ͻ 0.001). Compared with diabetic men, diabetic women had lower TRAP (P Ͻ 0.01), higher ROOH levels (P Ͻ 0.01), and lower 246-nm CD levels (P Ͻ 0.05). Plasma concentration of uric acid was significantly lower in patients with type 1 diabetes than in control subjects (3.3 Ϯ 0.3 vs. 4.3 Ϯ 0.2 mg/dl; P ϭ 0.009) with a significant difference between women and men with type 1 diabetes (2.6 Ϯ 0.3 vs. 3.9 Ϯ 0.3, respectively; P ϭ 0.009).CONCLUSIONS -Our findings suggest that reduced antioxidant activity and increased oxidative stress occur early after the diagnosis of type 1 diabetes, especially in women, and this might explain, at least in part, the increased susceptibility of diabetic women to cardiovascular complications.

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Section: Results -As Shown Inmentioning

confidence: 99%

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confidence: 99%

Early Increase of Oxidative Stress and Reduced Antioxidant Defenses in Patients With Uncomplicated Type 1 Diabetes

et al. 2002

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“…None separated the insulin-treated from the rest, but in each population, most subjects were not receiving insulin. In the Evans County study (USA) [17], 4.5-year CHD mortality rates when standardised for age, systolic blood pressure, serum cholesterol and triglyceride levels, body mass and smoking habit were not increased in diabetic men but were increased in diabetic women. This suggests a specific effect of diabetes only in females, but as there were only seven CHD deaths (four men, three women) any conclusion must be tentative.…”

Section: Effect Of Risk Factors In Diabetic Subjectsmentioning

confidence: 96%

Type 2 (non-insulin-dependent) diabetes mellitus and coronary heart disease ? chicken, egg or neither?

1984

Diabetologia

167

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Summary. Review of the literature yields much evidence against a correlation between duration of non-insulin-dependent diabetes mellitus (Type 2 diabetes) and the degree of coronary atherosclerosis or the risk of clinically evident coronary heart disease (CHD). Furthermore, an increased risk of CHD, similar to that in previously diagnosed diabetic subjects, has been demonstrated in persons with impaired glucose tolerance. These observations suggest that an increased risk of CHD is not a consequence of the development of diabetes (i. e. persistent hyperglycaemia). It is more likely that diabetes develops in individuals who already possess characteristics which increase the risk of CHD in addition to the risk of developing diabetes.

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“…The reason for the observed gender effect is not immediately apparent from this study. However, postmenopausal diabetic women are more at risk for cardiovascular disease, particularly coronary heart disease, an observation that has been well known for many years of uncertain etiology (43)(44)(45)(46)(47)(48). Interestingly, it was reported that the treatment of female rats with estradiol for 1 year attenuated the age-related increase in stiffening, glycoxidation, and permeability in carotid arteries (49).…”

Section: Table I Spearman Correlation Coefficients (R) Of Measured Skmentioning

confidence: 99%

Glucosepane Is a Major Protein Cross-link of the Senescent Human Extracellular Matrix

Sell

Biemel

Reihl

et al. 2005

Journal of Biological Chemistry

185

143

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The extracellular matrix in most tissues is characterized by progressive age-related stiffening and loss of proteolytic digestibility that are accelerated in diabetes and can be duplicated by the nonenzymatic reaction of reducing sugars and extracellular matrix proteins. However, most cross-links of the Maillard reaction described so far are present in quantities too low to account for these changes. Here we have determined in human skin and glomerular basement membrane (GBM) collagen the levels of the recently discovered lysinearginine cross-links derived from glucose, methylglyoxal, glyoxal, and 3-deoxyglucosone, i.e. glucosepane, MODIC, GODIC, and DOGDIC, respectively. Insoluble preparations of skin collagen (n ‫؍‬ 110) and glomerular basement membrane (GBM, n ‫؍‬ 28) were enzymatically digested, and levels were measured by isotope dilution technique using liquid chromatography/mass spectrometry. In skin, all cross-links increased with age (p < 0.0001) except DOGDIC (p ‫؍‬ 0.34). In nondiabetic controls, levels at 90 years were 2000, 30, and 15 pmol/mg for glucosepane, MODIC, and GODIC, respectively. Diabetes, but not renal failure, increased glucosepane to 5000 pmol/mg (p < 0.0001), and for all others, increased it to <60 pmol/mg (p < 0.01). In GBMs, glucosepane reached up to 500 pmol/mg of collagen and was increased in diabetes (p < 0.0001) but not old age. In conclusion, glucosepane is the single major cross-link of the senescent extracellular matrix discovered so far, accounting for up to >120 mole% of triple helical collagen modification in diabetes. Its presence in high quantities may contribute to a number of structural and cell matrix dysfunctions observed in aging and diabetes.Reducing sugars react nonenzymatically with proteins to form adducts and cross-links referred to as advanced glycation end products (1). Their accumulation is particularly high in long-lived proteins, such as lens crystallins and collagen, and results in intra-and intermolecular cross-linking. The latter has been hypothesized to result in an age-and diabetes-related stiffening of collagenous tissues and is believed to play an important role in the etiology of atherosclerosis and cardiovascular disease (3) as well as the loss of elasticity in lungs, joints, and skin (4 -6). These age-related processes are markedly accelerated by diabetes and are associated with morbidity and mortality in diabetic individuals (7,8). In skin, protein crosslinking is associated with an age-related loss of elasticity, increased stiffening, and wrinkling (9). However, this process occurs ubiquitously with age, suggesting a fundamental underlying mechanism.Although most of the age-related changes in the extracellular matrix could be duplicated by incubating reducing sugars with proteins, Eble et al. (10) suggested that the major cross-links are not stable to conventional conditions of acid hydrolysis. Indeed, Biemel et al. (11) recently showed that glucose and sugar-derived dicarbonyl intermediates react with human serum albumin to form various acid...

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Sex differences in coronary mortality among diabetics in Evans County, Georgia

Cited by 112 publications

References 8 publications

Early Increase of Oxidative Stress and Reduced Antioxidant Defenses in Patients With Uncomplicated Type 1 Diabetes

Early Increase of Oxidative Stress and Reduced Antioxidant Defenses in Patients With Uncomplicated Type 1 Diabetes

Type 2 (non-insulin-dependent) diabetes mellitus and coronary heart disease ? chicken, egg or neither?

Glucosepane Is a Major Protein Cross-link of the Senescent Human Extracellular Matrix

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