Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.6 (CAD)
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In this article we have focused on the evolving pattern of nutritional management of the person with diabetes. Before the advent of insulin in 1922, it was sufficient to identify a meal plan that would keep people alive until they could be rescued from mortality due to diabetic ketoacidosis (the major killer of the era) by pharmacologic means. Now, the life expectancy of people with diabetes is close to that of the general population and focus has turned to combating the new threats of macrovascular disease and kidney failure. Over recent years the susceptibility of NIDDM patients to macrovascular events has been established and the twofold increase in risk of a heart attack in diabetic men is outshadowed by the four- to fivefold risk in diabetic women and the 13- to 17-fold greater risk in diabetics under the age of 30 years compared with their nondiabetic counterparts. The mechanism behind the susceptibility to macrovascular disease has generated a veritable plethora of investigations focusing on the atherogenic profile of diabetic dyslipidemia. Hyperinsulinemia, insulin resistance, and overtreatment of the diabetic with insulin have been claimed as contributors to the development of premature atherosclerosis. The hallmark of the diabetic dyslipidemia is the tendency to elevated VLDL triglyceride levels and the closely linked reduction in HDL cholesterol. Although there is some controversy on the relationship between triglyceride levels and the incidence of CAD, there is no doubt that HDL is an independent risk factor. It can now be safely said that elevated triglycerides are a risk factor in women and that in men elevated triglycerides constitute a risk factor if accompanied by a reduced HDL level. For these reasons, any approach to nutritional management of the diabetic must attempt not only to normalize glycemia but to make every effort to reduce the atherogenic profile. In the accompanying algorithm (Fig. 4), we consider the risk factors conducive to a reduction in life expectancy and offer a meal plan that is appropriate for the individual with diabetes. For the 80% of NIDDM patients who are obese, a diet with a reduction of 500 to 1000 kcal is in order and this may be achieved by a periodic VLCD. We examined carefully the controversy related to yo-yo dieting and support the notion that its effects in humans are not all that harmful. Ingestion of simple sugars in the high carbohydrate diet has negative effects both on carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The good, the bad, and the ugly in diabetic diets. 131 32

BACKGROUND--Thirty-five percent of type I-diabetic patients are dead of coronary artery disease by age 55 years, and the risk of death is increased eightfold to 15-fold in patients with nephropathy. However, the prevalence of coronary artery disease with respect to age is unknown and few risk factors have been identified. METHODS--One hundred ten insulin-dependent diabetic patients underwent routine pretransplant coronary angiography and cardiac risk factor assessment. Angiograms were evaluated by two angiographers for presence or absence of coronary artery disease (CAD, defined as one or more coronary artery stenoses of 50% or greater in diameter, and no CAD, defined as no stenosis of 25% or greater in diameter, respectively). Prevalence of CAD by age was determined, and associated risk factors were defined. RESULTS--Fifty-two of 110 patients had CAD. Coronary artery disease prevalence increased significantly with age; 13 of 16 patients older than 45 years of age had CAD. For patients 35 years of age or younger, associated risk factors included a family history of premature myocardial infarction, higher hemoglobin A1c level, hypertension for more than 5 years, lower high-density lipoprotein level, and smoking for more than 5 pack-years. For patients between 35 and 45 years of age, associated risk factors included number of years of diabetes, higher hemoglobin A1c levels, and smoking more than 5 pack-years. CONCLUSIONS--In type I-diabetic patients with nephropathy, CAD prevalence increased significantly with age and was found in the majority of patients older than 45 years of age. Coronary artery disease risk factors operative in the general population were significantly associated with CAD in this high-risk group. In addition, a role for hyperglycemia in accelerated atherogenesis was supported by the association of both higher hemoglobin A1c levels and number of years of diabetes with CAD.
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PMID:Prevalence of, and risk factors for, angiographically determined coronary artery disease in type I-diabetic patients with nephropathy. 145 56

Although estradiol (E2) is considered primarily for its role in reproduction, it can exert numerous physiological actions on a variety of tissues. However, there are several difficulties in isolating these actions and determining its impact for in vivo situations. Despite the limitations, it does appear that E2 can alter, under certain conditions, resting and acute exercise metabolism and blood glucose regulation. Specifically, E2 can increase lipid availability and utilization and decrease gluconeogenesis and glycogenolysis. Development of glucose intolerance as a result of insulin insensitivity has also been documented. The mechanisms of E2 may be through direct alterations in key enzyme activity and membrane permeability or indirectly via changes in insulin:glucagon, cortisol, hGH, and catecholamine levels or sensitivity. Future research should focus on understanding the effects of exercise and diet on chronic E2 status and the resulting impact for a variety of conditions that include reproductive and skeletal integrity and predisposing metabolic risk factors for CAD and diabetes. In order to make meaningful correlations between E2 levels and physiological measurements such as bone mineral content, lipid profiles, glucose intolerance, etc., there needs to be a standard guideline for determining and defining one's "estrogen status." Finally, in order to identify underlying mechanisms, an understanding of and appreciation for the interrelationships among the numerous compositional, metabolic, and (neuro)endocrine factors involved is needed. A general model is presented, along with specific applications, to study these interactions.
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PMID:Metabolic actions of estradiol: significance for acute and chronic exercise responses. 219 50

We have previously reported the existence of an association between endogenous male sex hormone and lipoprotein levels in elderly men confined to a nursing home. In a further attempt to elucidate the significance of the association mentioned, we studied the relationship existing in that population between serum testosterone and fasting insulin levels, and between fasting insulin level and lipoprotein pattern. The data were analysed by means of stepwise multiple regression analyses. Serum testosterone and fasting insulin were found to be strongly correlated; this is consistent with the notion that androgen secretion affects directly circulating insulin level. But no independent relationship was demonstrable between fasting insulin and the three lipid-lipoprotein categories studied, namely total serum cholesterol, triglyceride and HDL-cholesterol, suggesting that in this particular population, the effect of male sex hormones upon lipoproteins is not mediated through insulin. Together, these various observations support the belief that androgen secretion affects significantly CAD risk factor levels in elderly men.
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PMID:Relationships between serum testosterone, fasting insulin and lipoprotein levels among elderly men. 264 12

Left ventricular function was assessed by means of radionuclide ventriculography in 42 patients with long-standing (13 +/- 5 yrs) insulin-dependent diabetes mellitus and in eleven healthy age matched control subjects. Only diabetics were included in the study without diabetes related cardiac risk factors such as hypertension and CAD in order to evaluate diabetes specific changes of cardiac function. No differences were seen between diabetics and controls concerning heart rate and functional parameters of left ventricle in systole and diastole. The rapid filling period was not prolonged. According to our radionuclide data there is no evidence of diabetes related impairment of ventricular function in young patients with long-standing type-1-diabetes mellitus.
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PMID:[Stress testing of long-term type I diabetic patients with radionuclide ventriculography]. 273 79

Based on the data reviewed, it is necessary to conclude that diabetes is associated with profound changes in HDL metabolism. However, once we go beyond this simple generalization, it is apparent that the relationship between diabetes and HDL metabolism is not a simple one. A good deal of the complication evolves from the fact that IDDM and NIDDM seem to affect HDL metabolism quite differently, with the only apparent similarity the fact that plasma HDL-cholesterol concentration can be low in untreated patients with either IDDM or NIDDM. Thus, in patients with IDDM the primary event seems to be related to the insulin-deficient state, which results in a decrease in HDL turnover rate and resultant decline in plasma HDL-cholesterol concentration. In contrast, HDL turnover appears to be accelerated, not reduced in patients with NIDDM, and the low plasma HDL-cholesterol concentration is a consequence of the increased turnover rate. In addition, patients with NIDDM are not absolutely insulin deficient, and available evidence suggests that the higher the plasma insulin level, the lower the plasma HDL-cholesterol concentration in these patients. The differences noted above in the effect of IDDM and NIDDM on HDL metabolism are of great interest, and, unfortunately, not very well understood. There is, however, one additional difference, which may be of paramount clinical importance. For reasons not totally clear, plasma HDL-cholesterol concentrations in patients with IDDM treated with insulin are not lower than normal, and even tend to be higher than these values in a nondiabetic population. Possibly as a result of this phenomenon, there is no evidence that changes in plasma HDL-cholesterol concentration play a role in the development of macrovascular complications in IDDM. Although it is apparent from the considerations discussed in this review that a great deal more needs to be learned about the effect of insulin deficiency on HDL metabolism, changes in HDL metabolism do not appear to be clinically important in patients with IDDM. Unfortunately, this does not appear to be the situation in patients with NIDDM. Plasma HDL-cholesterol concentrations are lower than normal in patients with NIDDM, and this finding seems to be related to increased morbidity and mortality from CAD. Furthermore, there is no form of anti-diabetic treatment, irrespective of how effective it has been in achieving glycemic control, that has been shown to substantially increase plasma HDL-cholesterol level. Indeed, it has been difficult to demonstrate a consistent effect of any therapeutic approach on plasma HDL-cholesterol concentration.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:HDL metabolism in diabetes. 330 Dec 37

Iodine-123 beta-methyl iodophenylpentadecanoic acid (BMIPP) has been used for evaluating myocardial fatty acid metabolism in vivo. The whole body BMIPP imaging was acquired in 26 patients (11 with HCM, 11 with CAD and 4 with DCM) to calculate % uptake in the myocardium and to correlate its uptake with biochemical data, including blood sugar (BS), nonesterified fatty acid (NEFA) and insulin in the blood. BMIPP was administered at rest with overnight fasting state, and the anterior and posterior whole body imaging was performed one hour later. The background corrected whole myocardial counts were calculated to obtain %BMIPP uptake. In addition, the heart to mediastinum count ratio (H/M ratio) was calculated from the mean counts in the heart and the upper mediastinum in the anterior view. The %BMIPP uptake was 3.70 +/- 1.22% and H/M ratio was 2.30 +/- 0.23. The patients with DCM showed higher %BMIPP uptake values (DCM = 5.58 +/- 0.67% vs. CAD = 3.09 +/- 0.97% and HCM = 3.63 +/- 0.86%, both p < 0.01), but similar values of H/M ratio with other patients (DCM = 2.43 +/- 0.20, CAD = 2.22 +/- 0.25 and HCM = 2.32 +/- 0.20). Although the biochemical data varied at the time of the tracer administration, they were not significantly correlated with the %BMIPP uptake or H/M ratio. However, there was a significant correlation between %BMIPP uptake and H/M ratio with the correlation coefficient of 0.80 (p < 0.001). We conclude that the myocardial uptake of BMIPP is not influenced by the plasma substrate level under the fasting state.
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PMID:[Myocardial uptake ratio of iodine-123 labeled beta-methyl iodophenylpentadecanoic acid (123I-BMIPP) in relation to the concentration of the substrates of energy]. 767 68

In order to evaluate whether Lp(a), a lipoprotein that is potentially thrombogenic and atherogenic, is a potential risk factor for CAD in non-insulin-dependent diabetes (NIDDM), we compared the Lp(a) and its distribution in 145 NIDDM patients with that in 94 healthy control subjects. Furthermore, we studied the effect of insulin treatment on serum Lp(a) in 108 patients with NIDDM. Male and female NIDDM patients had similar Lp(a) concentrations to healthy controls (median value 167 mg L-1, range 15-1550 mg L-1 vs. 157 mg L-1, range 15-919 mg L-1, NS and 92, range 15-1190 mg L-1 vs. 103 mg L-1, range 15-842 mg L-1, NS). Also, the cumulative distribution of Lp(a) did not differ between the NIDDM patients and healthy subjects. Insulin treatment increased Lp(a) in diabetics with a Lp(a) concentration of less than 300 mg L-1, but this effect was not related to the concomitant improvement in metabolic control (mean change (+/- SEM) of HbA1c from 9.80 +/- 0.15 to 8.00 +/- 0.12; P < 0.001). In subjects with elevated Lp(a) concentrations (> 300 mg L-1) the Lp(a) concentration was unaffected by insulin, despite a similar improvement in glycaemic control. These results suggest that insulin may modulate the concentration of Lp(a).
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PMID:Effect of insulin treatment on serum lipoprotein(a) in non-insulin-dependent diabetes. 778 67

The prevalence of coronary artery (CAD) disease in the Indian urban population is comparable to British population. Dietary intakes, antioxidant vitamins, prevalence of risk factors and CAD, were studied in a random sample of 152 adult urban subjects between 26-65 years of age (80 males, 72 females) from Peerzada street, Moradabad and compared with Indian immigrants to U.K. and a British comparison group. There was no significant relation with vitamin A. Smoking and diabetes were the confounding factors. Plasma antioxidant vitamin C (21.6 +/- 3.3 vs 42.5 +/- 4.5 mumol/L), vitamin E (15.2 +/- 2.8 vs 21.4 +/- 3.2 mumol/L) and beta-carotene (0.33 +/- 0.6 vs 0.55 +/- 0.08 mumol/L) were significantly lowered and lipid peroxides higher (2.82 +/- 0.22 vs 1.3 +/- 0.20 nmol/ml) in patients with CAD compared to subjects without any risk factors. The relation between low plasma level of vitamin C and E levels and carotene remained independently and inversely related after adjustment for smoking, diabetes and other risk factors. Regression analysis showed that after adjustment. Odd's ratio for carotene (1.82, 95% C.I. 0.50 to 3.72), vitamin C (2.23, 95% C.I. 1.14 to 5.26) and vitamin E (2.35, 95% C.I. 1.29 to 5.30) were significantly related to CAD. Underlying these changes, dietary intake of vitamin A, E, C and beta-carotene was significantly less in patients with CAD. Vitamin C and beta-carotene intake were less in smokers and diabetes. Compared with British population, the Indian urbans consumed less total and saturated fat and cholesterol and more polyunsaturated fat and complex carbohydrates. The plasma total and low density lipoprotein cholesterol levels were less in Indian urbans compared to Britons and so were mean body weight, body mass index and waist-hip ratio. Plasma insulin levels were comparable. The fatty acid composition of the diet, blood lipids, central obesity and insulin levels do not appear to account for high rates of CAD among Indians. The findings suggest that urban population in India may benefit from eating diets rich in antioxidant vitamin C, E and beta-carotene.
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PMID:Diet, antioxidant vitamins, oxidative stress and risk of coronary artery disease: the Peerzada Prospective Study. 783 64

The present study was designed to evaluate the potential role of plasma cholesteryl ester transfer protein (CETP) activity in the regulation of high-density lipoprotein (HDL) subclasses in non-insulin-dependent diabetes mellitus (NIDDM). We studied 45 men with NIDDM and angiographically defined coronary artery disease ([CAD] DM+CAD+, aged 54.4 +/- 6.1 years, mean +/- SD); 47 nondiabetic men with similarly proven CAD (DM-CAD+, aged 54.9 +/- 6.6 years; 43 men with NIDDM but no CAD (DM+CAD-, aged 55.2 +/- 7.3 years); and 29 nondiabetic men without CAD (DM-CAD-, aged 53.2 +/- 5.3 years). The groups were matched for age and body mass index (BMI). Plasma CETP activity was determined by measuring the ability of the plasma sample to transfer esterified cholesterol from exogenous 14C-cholesteryl ester-labeled low-density lipoprotein (LDL) to exogenous HDL. Plasma lipoproteins were separated by ultracentrifugation. The concentration of HDL cholesterol was reduced in the DM+CAD+ group as compared with the DM-CAD- group (P < .01). This change was due to a decrease of both HDL2 cholesterol (P < .05) and HDL3 cholesterol (P < .001). There was a clear-cut decrease in HDL3 cholesterol in the DM-CAD+ (P < .01) and DM+CAD- (P < .05) groups as compared with the DM-CAD- group. Plasma CETP activity was lower in the DM+CAD- group (1.06 +/- 0.24 arbitrary units [AU]) than in the DM-CAD- group (1.19 +/- 0.26 AU, P < .05). In the DM+CAD+ group, the mean of CETP activities was 1.09 AU.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma cholesteryl ester transfer protein activity in non-insulin-dependent diabetic patients with and without coronary artery disease. 799 Jul 2


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