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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rationale for the use of exercise in the treatment of type II (non-insulin-dependent) diabetes and its special implications for Blacks are reviewed herein. When performed on a regular basis, exercise may improve glycemic control and improve several risk factors for coronary heart disease including hypertriglyceridemia, hypertension, and hyperinsulinemia. In addition, it may be a useful adjunct to diet in producing weight loss. The metabolic benefits of exercise in part appear to be related to its ability to enhance insulin sensitivity. Benefits are short lived after discontinuing exercise. Because of problems with compliance and concurrent medical problems, many patients with type II diabetes are not good candidates for an exercise-diet program. For this reason, the optimum target population may be people at risk for type II diabetes and premature atherosclerosis. Such a population might include the offspring of patients with these disorders and individuals with impaired glucose tolerance, hyperinsulinemia, gestational diabetes, and/or an android pattern of fat distribution. Type II diabetes is more common in Blacks than in the general population. In most instances, it is associated with cardiovascular risk factors benefited by exercise. Despite this, there are no available studies regarding the effects of regular exercise in Blacks with type II diabetes or those at risk for it.
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PMID:Exercise in therapy and prevention of type II diabetes. Implications for blacks. 226 37

In a long-term longitudinal study of gestational diabetes mellitus in Black women, risk factors that were identified were age, obesity, a family history of diabetes, and the presence of hypertension. Poor predictors were a history of a previous large-for-date infant, parity, and age at first pregnancy. The prevalence of smooth muscle and nuclear autoantibodies was higher in gestational diabetic subjects. Gestational diabetic subjects who required insulin for glycemic control were more obese, had a lower frequency of the Bf-F phenotype and a higher frequency of the Bf-F1 phenotype, and had a lower frequency of the type 2 allele at the polymorphic locus adjacent to the insulin gene. Restriction-fragment-length polymorphisms flanking the insulin and apolipoprotein A-I and C-III genes, although not associated with gestational diabetes mellitus, may be associated with hyperlipidemia and subsequent atherosclerosis.
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PMID:Risk factors for gestational diabetes in black population. 226 42

Of the various types of diabetes mellitus, non-insulin-dependent diabetes (NIDDM) is by far the most common and is increasing rapidly in many populations around the world. It is a heterogeneous disorder, characterized by a genetic predisposition and interaction between insulin resistance and decreased pancreatic beta-cell function. There is a strong association between the presence of obesity and low levels of physical exercise and the development of NIDDM. However, NIDDM may also develop in lean individuals and the incidence increases significantly with increasing age. A diagnosis of impaired glucose tolerance or gestational diabetes is a strong predictor for future development of NIDDM and should signal appropriate interventions to prevent or delay the progression to NIDDM. NIDDM is frequently associated with other conditions such as hypertension, hypertriglyceridemia and decreased high-density lipoprotein which are additional risk factors for atherosclerosis and cardiovascular disease. The 'insulin resistance syndrome', which includes obesity, NIDDM, hypertension, hyperinsulinemia and dyslipidemia is a major and increasing cause of morbidity and mortality in many populations. In addition, people with NIDDM and poor glycemic control may develop severe microvascular complications of diabetes, including retinopathy, nephropathy and neuropathy. Appropriate diet, weight control and increased physical activity will increase insulin sensitivity in insulin resistant patients and are effective treatments for patients with NIDDM or may prevent the development of NIDDM in susceptible individuals. If these measures are unsuccessful, then oral hypoglycemic agents or insulin therapy may be required.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:NIDDM--the devastating disease. 852 17

Plasma fibrinogen concentration has been shown to be a predictor of major cardiovascular events. Information on plasma fibrinogen amongst Chinese has been scanty. We examined the relationships between plasma fibrinogen concentration and cardiovascular risk factors in 988 chinese subjects who underwent 75 g oral glucose tolerance test for screening for glucose intolerance. The study involved a selected sample with subjects who had an history of gestational diabetes, delivery of big babies (birth weight > or = 4 kg), equivocal plasma glucose concentrations and subjects who were family members of diabetic patients. This was mainly a non-smoking (96.6%), non-drinking (98%) and non-exercising (99%) population of which 87% (n = 855) were female. Among the 988 subjects (age +/- S.D. 36.8 +/- 10.2, range 16-79 years), plasma fibrinogen concentration ranged from 1.40 to 9.90 g/l with a mean of 3.26 +/- 0.93 g/l. On stratification of the subjects into 4 quartiles based on plasma fibrinogen concentrations, we found that increased plasma fibrinogen was associated with older age, higher body mass index (BMI), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose (PG), prevalence of diabetes, glycated haemoglobin (HbA1c) and triglyceride (TG) level. After adjustment for age and sex, increased plasma fibrinogen concentration remained associated with higher BMI, systolic BP, 2 h PG and TG level. On multivariate analysis using age, BMI, BP, TG, HbA1c and PG as independent variables, plasma fibrinogen was independently related to plasma TG concentration and HbA1c. With 1 S.D. change in TG concentration and HbA1c, there were 3.7 and 5.2% changes in plasma fibrinogen concentration respectively. These findings emphasize the close relationships between plasma fibrinogen and cardiovascular risk factors, in particular abnormal lipid and glucose metabolism.
Atherosclerosis 1997 Jun
PMID:Plasma fibrinogen concentration in a Chinese population. 919 74

The increased risk of premature atherosclerosis in noninsulin-dependent diabetes mellitus (NIDDM) might be related in part to augmented expression of endothelial adhesion molecules (AMs). So far it is, however, unknown whether increased circulating (c) AMs in NIDDM are only a consequence of this disease or also involved in its sequelae. To determine the presence of cAMs in a population at increased risk for subsequent development of NIDDM, we analyzed fasting and postprandial [oral glucose tolerance test (OGTT): 100 g] serum concentrations of circulating E-selectin, vascular cell adhesion molecule-1 (cVCAM-1), and intercellular adhesion molecule-1 (cICAM-1) in pregnant women with either gestational diabetes (GDM) or normal glucose tolerance (NT) before and after delivery vs. nonpregnant healthy women (C). During pregnancy cE-selectin and cVCAM-1 were elevated in both GDM and NT vs. nonpregnant females (P < 0.01 vs. C). Following delivery, all GDM females regained normal glucose tolerance according to OGTT criteria, but showed slightly higher postprandial [area under the curve (AUC)180 min] glycemia and HbA1c values than nonpregnant healthy women (P < 0.05), indicating persisting subtle abnormalities in carbohydrate metabolism. cE-selectin and cVCAM-1 remained increased in GDM (P < 0.01 vs.C) after delivery, but fell to normal in NT (P < 0.05 before vs. after delivery). Furthermore, a correlation was seen in GDM females between cE-selectin and HbA1c (P < 0.005), fasting glucose (P < 0.01), and insulin (P < 0.05) as well as postprandial (AUC180 min) glucose and insulin concentrations (P < 0.05) during OGTTs, both before and after delivery. ICAM-1, however, did not differ significantly between groups. In summary, GDM is characterized by persistently raised levels of cE-selectin and cVCAM-1 12 weeks after delivery. Whether these persistent elevations of cE-selectin and cVCAM-1 reflect early vascular injury or represent a risk factor for atherosclerosis in women at increased risk for NIDDM remains to be determined.
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PMID:Persistent elevation and metabolic dependence of circulating E-selectin after delivery in women with gestational diabetes mellitus. 939 24

The TRoglitazone In the Prevention Of Diabetes (TRIPOD) trial is a single-center, randomized, placebo-controlled, double-masked study. The primary aim of the TRIPOD trial is to test the hypothesis that chronic administration of troglitazone to nondiabetic women with prior gestational diabetes mellitus (GDM) will improve whole-body insulin sensitivity and reduce the incidence of non-insulin-dependent diabetes (NIDDM). Because troglitazone is already known to lower blood glucose concentrations in persons who have developed NIDDM, an additional aim of the project will be to determine whether early intervention with troglitazone will achieve better final glycemic control than can be achieved by later intervention. In addition, since troglitazone treatment is expected to improve insulin sensitivity and may prevent or delay a decline in glucose tolerance, we also plan to determine whether long-term troglitazone treatment alters the development or progression of atherosclerosis. In this article we describe the experiment's design, the study's endpoints and methods for determining those endpoints, methods for assessing quality of life, and proposed methods for statistical analyses. The unique two-phase study design of the TRIPOD trial will permit testing not only of the biological question about reversal of insulin resistance and prevention of diabetes, but also of the clinical question about whether early intervention is superior to late intervention. Results from this trial will have an important impact on the monitoring and treatment of patients at high risk for NIDDM.
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PMID:TRIPOD (TRoglitazone In the Prevention Of Diabetes): a randomized, placebo-controlled trial of troglitazone in women with prior gestational diabetes mellitus. 955 Dec 85

Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same compound or an OC containing EE and DSG we found similar changes in triglycerides and total cholesterol, but increased levels of HDL-cholesterol and unchanged LDL-cholesterol concentrations. In the women with IDDM there was a negative correlation between daily insulin requirement and HDL-cholesterol before and during treatment, but no other statistically significant correlation between estimates of glycaemic control and lipids and lipoproteins were observed. In the non-diabetic women, changes in the haemostatic system included an increase in the procoagulant factors fibrinogen and Factor VIIc; the concentration of active t-PA increased, mainly because of decreased inhibition by PAI-1. The ratio between molecular markers of the activity of the coagulation system and the efficacy of fibrinolysis was unchanged. This was also found in the women with IDDM, who showed evidence of increased fibrin formation and an attenuated fibrinolytic response during treatment. The regulation of the t-PA/PAI system was studied in non-diabetic women in order to elucidate if the effects of OCs are caused by a direct effect on synthesis or clearance of these variables or if they are secondary to changed insulin sensitivity, as described in individuals with atherosclerosis. We found no indications that insulin resistance is involved in the regulation of t-PA and PAI-1 antigen levels, neither before nor during intake of OCs. We showed, however, that the decreased t-PA antigen concentration observed in OC users is caused by reduced synthesis outside the splanchnic circulation. The studies indicate that low-dose OCs containing newer gonane progestogens are able to induce insulin resistance and to impair glucose tolerance. Lipoproteins were not adversely influenced by the OCs neither in the diabetic nor the non-diabetic women; on the contrary, there was a tendency towards increased plasma levels of HDL-cholesterol and decreased LDL-cholesterol which are associated with a decreased risk of atherosclerosis. The changes observed within the haemostatic system were in accordance with a maintained balance between coagulation and fibrinolysis although the rate of fibrin formation may be increased in the women with IDDM. Irrespective of OC use, the interrelationships between metabolic systems in young non-diabetic women are different from those reported in individuals with atherosclerosis or insulin resistance. The effects of OCs on the t-PA/PAI system seem to be mediated by a direct effect on the vessel wall and not by changes in the hepatic clearance. The present findings were obtained in diabetic women without vascular complications, so the conclusion that women with IDDM can use OCs without metabolic alterations of known clinical significance is therefore restricted to those without evidence of diseased vessels. When evaluating the results obtained in the non-diabetic women, it should be remembered that women with recognised risk factors were excluded. The results may therefore be of limited value when evaluating the risk of arterial thrombosis in predisposed populations. In healthy individuals, the present integrated evaluation of biochemical markers does not indicate an increased risk of arterial thrombosis during use of low-dose OCs containing newer gonane progestogens; thus, the findings are in accordance with the recent epidemiological studies on these compounds. The application of relevant biochemical markers facilitate the understanding of the non-reproductive effects of sex steroids which have increasing importance because of their expanding use, not only as contraceptives, but also in the treatment of benign gynaecological disorders, as hormone replacement therapy and as prophylactic agents against specific degenerative conditions. Moreover, they may prove to be helpful in the future identification of women, who have increased susceptibility to the metabolic effects of sex steroids due to genetic predisposition.
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PMID:Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus. 1189 23

Many studies show that low-dose OCs have little adverse effect on carbohydrate metabolism and are safe for healthy women, women with a history of gestational diabetes, and women with insulin-dependent diabetes to use. In fact, large epidemiologic studies indicate that OCs, even the high-dose OCs (=or 50 mcg) for long periods, do not increase the risk of diabetes. There is some evidence indicating that OC use does not heighten the progression of diabetic retinopathy, nephropathy, or cardiovascular complications among women with insulin-dependent diabetes. There is no significant difference in carbohydrate metabolism among the different OC formulations. One must carefully consider the risk:benefit ratio of OC use in diabetic women since pregnancy has serious consequences for both mother and fetus. Cardiovascular complications in OC users do not originate from atherogenesis. The androgenic properties of the progestin in low-dose OCs and their effect on lipids are inconsequential for later development of coronary atherogenesis. The estrogen in OCs may protect against atherosclerosis, particularly among women at high risk of atherosclerosis. Former OC users are not at an increased risk of coronary heart disease, stroke, or other heart disease. Lipid changes in OC users tend to remain within the normal range and return to pretreatment values during the pill-free week. All OCs suppress gonadotropins and subsequent ovarian androgen production. They partially suppress androgen production by the adrenals as well. This suppression from two fronts outweighs any androgenic action of the progestin alone. Further, androgenic action probably cannot overpower the estrogen effect. The dose of levonorgestrel used in OCs is too low to express androgenic effects. Since OCs suppress androgen production, all OCs tend to improve acne. OCs reduce free testosterone and increase sex hormone binding globulin levels.
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PMID:Metabolic effects of oral contraceptives: fact vs. fiction. 1232 11

Effects of oral contraceptives (OCs) on glucose metabolism can be considered on 2 levels: production of diabetes or impaired glucose tolerance, and production or aggravation of vascular complications caused by chronic hyperglycemia. Combined OCs can promote development of diabetes in predisposed women. The frequency of impaired glucose tolerance increases and the reversibility of the condition decreases with duration of use. Subjects with impaired glucose tolerance are known to have much higher eventual rates of diabetes than normal subjects. It can be concluded that OC usage in the long run can indirectly increase the incidence of diabetes. It is now accepted that diabetic microangiopathy is related to the degree and duration of hyperglycemia, although a genetic component appears to determine its severity. The possibility that OCs thicken the basal membranes of capillaries, an index of diabetic microangiopathy, cannot be formally ruled out. On the macroangiopathic level, OCs considerably increase the incidence of cardiovascular maladies. The relative risk of death for all cardiovascular diseases taken together is tripled in OC users. The excess mortality is related primarily to increased incidence of myocardial infarcts, cerebral vascular accidents, and pulmonary emboli. 2 kinds of vascular accidents are related to pill use: early venous or arterial accidents of poorly elucidated physiopathology, and arterial accidents after longer use which recall the classic atherosclerotic factors related to chronic hyperglycemia. A study by Whitehall of 18,403 subjects indicated that even slight deterioration of glucose tolerance caused by pills might aggravate vascular risks. All pills produce a state of chronic hyperinsulinemia. Chronic hyperinsulinemia has been incriminated as an atherosclerotic risk factor because of its effects on the arterial walls, including proliferation of smooth muscle fibers and development of fat-filled lesions similar to those of early atherosclerosis. Atherosclerosis is multifactorial, and OCs aggravate most of the factors. Pill-induced hypertension is associated with more serious deterioration of glucose tolerance and more severe hyperlipidemia. Few epidemiologic studies have examined the vascular risks of OCs in a population of diabetic women, but 1 study of 120 insulin-dependent diabetic women using OCs and 136 insulin dependent nonusers found 4 vascular accidents in users under 30 years old and none in nonusers. Deterioration of glucose tolerance in normal women using OCs should be regarded as a sign of increased vascular risk. Glucose tolerance should be determined for all women prior to OC prescription. OCs in any form are contraindicated in cases of a history of gestational diabetes or of diabetes or impaired glucose tolerance appearing with pill use and disappearing on termination of use; in cases of impaired glucose tolerance with a familial or obstetric history of diabetes; and of diabetes or impaired glucose tolerance complicated with angiopathy. Relative contraindications to OC use include diabetes and impaired glucose tolerance in cases where angiopathy is absent. Low-dose pregestin pills may be used in such cases. Effective contraception is necessary for diabetic women. The IUD may be used in well controlled diabetics with careful surveillance for infection.
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PMID:[Oral contraception and carbohydrate metabolism: III--practical implications]. 1234 Dec 42

Although combined oral contraceptives (OCs) do not create a true cardiovascular risk, they may increase the impact of existing vascular risk factors. Pill use disturbs metabolism of lipids and carbohydrates as well as the balance of water and sodium. New combinations with lower doses of steroids have significantly reduced these risks, and the development of new and less androgenic progestins for low dose pills is expected to reduce them further. The diabetogenic effect of OCs has been noted since 1963. Among normal women, the observed modifications in carbohydrate metabolism are minor and temporary, with increases in levels of blood sugar maximal at the beginning of use and normalizing after 12 months. Among women with family histories of diabetes or who have had gestational diabetes, use of combined OCs can entail irreversible deterioration of glucose tolerance or diabetes. The number of women with poor glucose tolerance increases with the duration of pill use. Reversibility of the condition decreases with duration of use. The proportion of women with poor glucose tolerance who develop diabetes is higher than among normal subjects. Women with poor glucose tolerance must be considered at risk of diabetes. Ethinyl estradiol is responsible for the early modification of glucose tolerance, which regresses after about 6 months of use. Hyperinsulinemia is caused by the direct stimulation of progestins on insulin secretion by the pancreas as well as by the development of peripheral resistence to glucose utilization resulting from a decrease of insulin receptors. The effect on insulin resistence is among the most androgenic progestins. Chronic hyperinsulinism represents a classic risk factor for atherosclerosis because of the effects on the arterial wall: proliferation of smooth muscle fibers, inhibition of lipolysis, and development of lesions of the intima analogous to those of atheroma. Estrogen is primarily responsible for the increased blood pressure of pill users, but the development of hypertension is also correlated with the progestin content. Progestins have an antidiuretic effect which contributes to increases in blood pressure when added to the estrogen stimulation of the renin-aldosterone-angiotensin system. Gestodene, a new progestin in the gonane series, is the most powerful synthetic progesterone yet known. Its uniqueness derives from the dissociation between its very powerful antigonadotropic activity even at small doses and its androgenic effects which only appear at considerably higher doses. Most of the metabolic effects of progestins are linked to their degree of androgenicity. Different studies of gestodene tolerance in a triphasic formulation have concluded that it is innocuous. The use of gestodene in a low-dose triphasic formulation may result in a combined OC that does not increase the individual atheromatous risk of the user.
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PMID:[Combined estrogen-progestagen contraception and glucid and water-sodium metabolism]. 1234 1


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