Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of type II diabetes should not only concentrate on blood glucose levels but also should take symptoms like insulin resistance, hyperinsulinemia, low HDL-cholesterol, high VLDL, and systemic hypertension into consideration. These symptoms are well described by the metabolic syndrome and are known to be risk factors of macroangiopathy. In obese type II diabetic patients weight loss by caloric restriction is the most essential therapeutic step. Retarding intestinal carbohydrate uptake glucosidase-inhibitors are able to lower postprandial blood glucose levels without stimulating insulin secretion. The biguanide metformin is suitable to diminish peripheral insulin resistance, gluconeogenesis, and intestinal glucose absorption on cellular mechanisms others than betacytotropic effects. In non obese type II diabetic patients sulfonylureas are advantageous because of meal related stimulation of endogenous insulin which runs the physiological way with first pass through the liver. Therefore, sulfonylurea treatment should be continued when secondary failure indicates the need for exogenous insulin. In accordance with the course of type II diabetes in secondary failure insulin should be added to sulfonylureas in as small amounts as possible to ameliorate poor metabolic control. Thus iatrogenic hyperinsulinemia and resulting insulin resistance can be largely avoided. If there is any long term benefit when different oral antidiabetic agents are administered together with insulin has to be evaluated in further clinical studies.
 ...
PMID:[Combination therapy of oral antidiabetic drugs with insulin]. 847 36

Numerous surveys have shown that in industrial countries diabetic subjects develop hypertension more frequently than non-diabetic persons. In fact, three typical hypertension forms in these patients can be discerned: essential, renal, and isolated systolic hypertension. In type 2-diabetes (NIDDM) hypertension can be seen in close association with obesity, glucose intolerance, lipid changes, and insulin resistance within the framework of the metabolic syndrome. The increased incidence of hypertension in type 1-diabetes (IDDM) is a result of development of diabetic nephropathy. In the elderly type 2-diabetics particularly frequently isolated systolic hypertension is present which reflects increased arterial stiffness and loss of vascular distensibility. In hypertension progression of both macrovascular disease and microangiopathy is increased whereby interaction of hyperglycemia and hypertension seems to be the main risk factor. In most hypertensive diabetic patients drugs will be necessary to lower blood pressure in a therapeutical range. There are several effective substances available which should be prescribed individually according to the needs and accompanying conditions in these patients.
 ...
PMID:[Hypertension and diabetes mellitus]. 847 40

Major cardiovascular risk factors, such as hypertension, hyperlipidemia, and diabetes, often cluster in the same individuals. It has been claimed that obesity, hyperinsulinemia, insulin resistance, and a deranged intracellular handling of ions have pathogenetic importance in the development of this metabolic syndrome. However, a decrease in peripheral blood flow is another factor found in all the different facets of this syndrome. An increased peripheral resistance and a rarefaction of skeletal vessels are often seen in hypertensive subjects. Also, the insulin resistance so commonly seen in hypertension may be a consequence of a decreased blood flow because insulin resistance is associated with a decreased capillarization in skeletal muscle. Furthermore, the activity of skeletal muscle lipoprotein lipase, the key enzyme involved in the removal of triglycerides from the circulation, is known to be related to skeletal muscle vascularization. Because enhanced sympathetic activity has been associated with vascular hypertrophy and rarefaction of vascularization, overactivity in this part of the autonomic nervous system may lead to structural changes that will decrease the blood flow in peripheral tissues and thereby induce the metabolic syndrome of cardiovascular risk factors, particularly in individuals who, for genetic reasons, have decreased capillarization at the onset.
 ...
PMID:Decreased peripheral blood flow in the pathogenesis of the metabolic syndrome comprising hypertension, hyperlipidemia, and hyperinsulinemia. 848 Jun 20

In the modern therapeutic approach to hypertension, the aspect of "metabolic side effects" is receiving ever more attention. This is the result of the recognition that high blood pressure forms part of a metabolic syndrome known as syndrome X, the components of which are variously influenced by different antihypertensive agents. Of particular importance seems to be the response of an underlying insulin resistance, since resulting hyperinsulinemia has been shown to be a separate risk factor. Negative metabolic influences on this syndrome may be a reason for inadequate prevention of coronary heart disease, as has been observed under conventional treatment despite effective lowering of blood pressure over many years. The spectrum of relevant antihypertensive drugs contains only few "metabolically neutral" or "metabolically positive" classes of substances, so that particular importance must be attached to ACE-inhibitors for use in patients with a "metabolic risk"; the most thoroughly studied of such inhibitors is captopril. In order to increase the responder rate to about 90%, a combination with low-dose hydrochlorothiazide can be recommended; the negative effect of the thiazide on insulin sensitivity is balanced by the positive effects of captopril. The great practicability of the single dose form of administration, the synergism of the individual substances, and "metabolic neutrality", together with the high level of tolerability underscore the advantage of this combination treatment.
 ...
PMID:[Treatment of hypertension with consideration of metabolism. A challenge for current therapy of essential hypertension]. 851 26

There is good evidence that central (visceral) adiposity is important in the development of the insulin resistance or metabolic syndrome (obesity, hyperinsulinemia, dyslipidemia, glucose intolerance, hypertension, and coronary heart disease). It is proposed that some non-Caucasian populations are especially susceptible to development of this syndrome, and that lifestyle changes may play important etiologic roles. We postulate that this is due to the presence in these populations of a genetic predisposition to weight gain, perhaps related to a "thrifty" genotype, leading to the concentration of weight gain in visceral fat depots, when there is exposure to conditions associated with westernization.
 ...
PMID:Susceptibility to development of central adiposity among populations. 858 74

Obesity is a multifactorial heterogenous condition. The location of excess fat on the body determines the risk of morbidity and mortality for significant disease. Visceral, or intraabdominal, fat is the fat depot most highly associated with illness and death from cardiocerebrovascular disease and diabetes. Visceral fat is also associated with a quartet of metabolic disturbances. Referred to as the metabolic syndrome, these abnormalities include hypertension, hyperlipidemia, hyperinsulinemia, and insulin resistance. The metabolic syndrome is also present in Cushing's syndrome, which is characterized by primary hypercortisolism as well as profound visceral adiposity and obesity. The interrelationship between hyperactivation or hypersensitivity of the stress axis and disease can be elucidated by an understanding of the effect of excess glucocorticoids upon energy storage and metabolism. The complex interactions of the stress axis upon the growth and reproductive axes, as well as upon the adipose tissue, suggest that chronic stress, whether psychological and/or physical, exerts an intense effect upon body composition, which, in turn, significantly affects the longevity and survival of the organism.
 ...
PMID:Hypercortisolism and obesity. 859 40

Insulin resistance is part of a metabolic syndrome that also includes non-insulin-dependent diabetes mellitus, dyslipidemia, obesity, and hypertension. It has been hypothesized that insulin resistance represents the primary physiological defect underlying this syndrome. Since insulin resistance is at least partially genetically determined, we hypothesized that genes influencing insulin resistance would have pleiotropic effects on a number of other traits, including triglyceride (TG) and HDL cholesterol levels, body mass index (BMI) and body fat distribution, and blood pressure levels. To investigate this hypothesis, we analyzed data obtained from individuals in 41 families enrolled in the San Antonio Family Heart Study. Statistical methods that take advantage of the relatedness among individuals were used to differentiate between genetic and nongenetic (ie, environmental) contributions to phenotypic variation between traits. Serum levels of fasting and 2-hour insulin (measured in 767 and 743 nondiabetic family members, respectively) were used as a measure of insulin resistance. The genetic correlations were high between insulin levels (both fasting and 2-hour) and each of the following: BMI, HDL level, waist-to-hip ratio, and subscapular-to-triceps ratio, indicating that the same gene, or set of genes, influences each pair of traits. In contrast, the genetic correlations of insulin levels with systolic and diastolic blood pressures were low. We have previously shown that a single diallelic locus accounts for 31% of the phenotypic variation in 2-hour insulin levels in this population. We conducted a bivariate segregation analysis to see if the common genetic effects on insulin and these other traits could be attributable to this single locus. These results indicated a significant effect of the 2-hour insulin locus on fasting insulin levels (P = .02) and BMI (P = .05), with the "high" insulin allele associated with higher levels of fasting insulin but lower levels of BMI. There was no detectable effect of this locus on HDL level, TG level, subscapular-to-triceps ratio, or blood pressure. Overall, these results suggest that a common set of genes influencing insulin levels also influences other insulin resistance syndrome-related traits, although for the most part this pleiotropy is not attributable to the 2-hour insulin level major locus.
 ...
PMID:Genetic analysis of the IRS. Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures. 862 Mar 44

Relationships between cardiovascular risk factors, body composition, and tissue distributions were examined in 10 Indian and 10 Swedish males matched by age, height, and weight. The body was divided into 29 compartments by means of a multiscan computed tomography (CT) technique. Fasting glucose, insulin, and triglycerides (TG) were higher in Indians than in Swedes. During the oral glucose tolerance test (OGTT), the glucose area was similar in both groups, whereas the insulin area was 80% larger in Indians. Adipose tissue (AT) and skin volumes were larger and remaining lean tissues were smaller in Indians. Indians had proportionally less muscle and more skeleton in the legs, but no ethnic difference could be demonstrated with respect to AT distribution. The visceral AT to total AT volume ratio was positively related to insulin and TG, and with higher risk factors for Indians at any given ratio. TG and glucose were negatively related to the leg muscle to total muscle volume ratio, and this ratio was smaller in Indians. It is concluded that the metabolic disturbances of Indians are not necessarily dependent on a preponderance of visceral AT, and also that an upper-body muscle distribution-recognized as a new phenotypic companion to the metabolic syndrome-is statistically related to cardiovascular risk factors.
 ...
PMID:Computed tomography-determined body composition in relation to cardiovascular risk factors in Indian and matched Swedish males. 862 9

NIDDM and the metabolic syndrome are characterized by a low serum, HDL cholesterol content and a high triglyceride level, whereas total and LDL cholesterol concentrations are not necessarily elevated. Variable results have been reported on cholesterol absorption, elimination, and synthesis in NIDDM, but no studies are available on subjects within the normal range of blood glucose. From serum samples collected in 1985 from 203 nondiabetic men aged 51-66 years, we examined lipids, cholesterol precursors (reflecting cholesterol synthesis), and plant sterols and cholestanol (reflecting cholesterol absorption) in relation to fasting blood glucose. The findings prompted us (in 1993) to further examine 11 men from the highest and lowest glucose thirds of 203 nondiabetic men by additional dietary, serum, and fecal analyses for absorption, elimination, and synthesis of cholesterol and insulin sensitivity. In 1985, blood glucose was significantly related to LDL apolipoprotein B (P = 0.05) but not to LDL cholesterol (P = 0.19). Significantly higher serum lathosterol and desmosterol-to-cholesterol proportions and lower plant sterol and cholestanol proportions in the highest rather than the lowest glucose thirds suggested that the subjects with high normal blood glucose had decreased absorption and enhanced synthesis of cholesterol. In 1993, men with the lowest glucose versus those with the highest glucose had a lower waist-to-hip ratio, plasma HbA1c, fasting and postload insulin and glucose values, and a higher insulin sensitivity index. In agreement with the 1985 non-cholesterol sterol data, direct analyses of cholesterol metabolism showed further higher cholesterol absorption efficiency (P = 0.03) and serum plant sterol and cholestanol proportions (P < 0.001). Despite a slightly lower dietary cholesterol intake, cholesterol synthesis (P = 0.02) and serum lathosterol (P < 0.01) and desmosterol (P < 0.01) proportions were lowest in men with the lowest glucose third. We conclude that noncholesterol sterols in serum exhibits a long-lasting correlation with blood glucose level in a nondiabetic male population. Low intestinal absorption and high synthesis of cholesterol characterize men with high normal blood glucose. Differences in cholesterol metabolism could be due to underlying insulin effects associated with obesity-like fat distribution and may thus imply novel aspects in the metabolic interrelation between insulin and cholesterol in humans.
 ...
PMID:Associations of fasting blood glucose with cholesterol absorption and synthesis in nondiabetic middle-aged men. 863 49

Clustering of elevated triglycerides, decreased high-density lipoprotein cholesterol (HDL-C), hyperuricemia, diabetes, and hypertension has been related to insulin resistance/high insulin levels and central and/or overall obesity. The extent to which these abnormalities cluster and whether hyperinsulinemia, central adiposity, and overall obesity each independently associate with this clustering were evaluated in 14,481 US whites and African-Americans 45 to 64 years of age. With the exception of hypertension, abnormalities rarely existed in isolated form. Clustering greatly exceeded chance association (P < .001). Although this clustering was greater in relative terms (ratio of observed to expected cluster frequency) in the lean and less centrally obese, it was greater in absolute terms (observed minus expected cluster frequency as a percent of total population) in the more centrally and more generally obese. The greatest excesses were found for clusters that included both hypertriglyceridemia and low HDL-C. Multiple logistic regression models showed strong and independent graded relationships of clusters with quintiles of fasting insulin (fifth quintile odds ratio, 10 to 54, P < .001) and to a lesser degree with quintiles of the waist to hip ratio (2.2 to 5.4, P < .001 for most) and of body mass index (1.6 to 4.5, P < .05 for most). In conclusion, all abnormalities cluster in excess of that predicted by chance, with clusters showing remarkable and graded independent associations with fasting hyperinsulinemia and to a lesser extent with central and overall obesity. Thus, a metabolic syndrome occurs in both lean and obese middle-aged US adults.
 ...
PMID:Clustering of dyslipidemia, hyperuricemia, diabetes, and hypertension and its association with fasting insulin and central and overall obesity in a general population. Atherosclerosis Risk in Communities Study Investigators. 863 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>