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)

About 10 years ago the WHO defined obesity as a separate disease whereas in Austria until now it is often regarded as a cosmetical problem only. Many diseases like those of joints and spine are correlated to the body weight and the body mass index (BMI), but macrovascular events (cardiovascular and cerebrovascular) and early death are closer associated with the waist to hip ratio (WHR), indicating an abdominal, android fat distribution. This fat distribution tends toward higher insulin levels, dys- and hyperlipidemia and disturbances in glucose metabolism which can in part explain these associations in the light of the metabolic syndrome. In conclusion, there is no healthy overweight, but not all overweight patients share the same risk.
 ...
PMID:[Effect of fat distribution on risk]. 987 86

The aim of the study was 1) to establish the prevalence of GAD antibodies (GADab) in a population-based study of type 2 diabetes in western Finland, 2) to genetically and phenotypically characterize this subgroup, and 3) to provide a definition for latent autoimmune diabetes in adults (LADA). The prevalence of GADab was 9.3% among 1,122 type 2 diabetic patients, 3.6% among 558 impaired glucose tolerance (IGT) subjects, and 4.4% among 383 nondiabetic control subjects. Islet antigen 2 antibodies (IA2ab) or islet cell antibodies were detected in only 0.5% of the GADab- patients. The GADab+ patients had lower fasting C-peptide concentrations (median [interquartile range]: 0.46 [0.45] vs. 0.62 [0.44] nmol/l, P = 0.0002) and lower insulin response to oral glucose compared with GADab- patients. With respect to features of the metabolic syndrome, the GADab+ patients had lower systolic (140 [29.1] vs. 148 [26.0] mmHg, P = 0.009) and diastolic (79.2 [17.6] vs. 81.0 [13.1] mmHg, P = 0.030) blood pressure values, as well as lower triglyceride concentrations (1.40 [1.18] vs. 1.75 [1.25] mmol/l, P = 0.003). GADab+ men had a lower waist-to-hip ratio compared with GADab- patients. Compared with GADab- patients and control subjects, the GADab+ patients had an increased frequency HLA-DQB1*0201/0302 (13 vs. 4%; P = 0.002) and other genotypes containing the *0302 allele (22 vs. 12%; P = 0.010). However, the frequency of these high-risk genotypes was significantly lower in GADab+ type 2 patients than in type 1 diabetes of young or adult onset (0201/0302 or 0302/X: 36 vs. 66 vs. 64%, P < 0.001). The GADab+ type 2 group did not differ from control subjects with respect to genotypes containing the protective DQB1-alleles *0602 or *0603, nor with respect to the type 1 high-risk genotype in the IDDM1 (Hph1 +/+). We conclude that GADab+ patients differ from both GADab- type 2 diabetic patients and type 1 diabetic patients with respect to beta-cell function, features of the metabolic syndrome, and type 1 diabetes susceptibility genes. Further, we propose that LADA be defined as GADab positivity (>5 relative units) in patients older than 35 years at onset of type 2 diabetes.
 ...
PMID:Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. 989 37

BM 17.0744 (2,2-dichloro-12-(p-chlorophenyl)-dodecanoic acid) is a substance from a group of omega-substituted alkyl carboxylic acids with the general formula, ring-spacer-carboxylic acid. With BM 17.0744-a compound structurally unrelated to thiazolidinediones--antihyperglycemic and antihyperinsulinemic potency has been demonstrated in various animal models of type II diabetes. The antidiabetic effect is independent of the genetic background of the disease, gender, and animal species. The 24-hour blood glucose profile was dose- and time-dependently improved in ob/ob mice after a single and fourth oral administration of 0.3, 1, and 3 mg/kg/d. A dose-dependent reduction of hyperglycemia (10%, 15%, 28%, and 66%) was found in db/db mice after the fifth oral administration of 3, 10, 30, and 100 mg/kg/d. Hyperinsulinemia was reduced dose-dependently in yellow KK mice by 1%, 24%, 34%, and 66% after the fifth oral administration of 0.3, 1, 3, and 10 mg/kg/d. Overall glucose metabolism was predominantly higher in euglycemic-hyperinsulinemic clamp studies in obese fa/fa rats pretreated for 14 days with 10 mg/kg/d BM 17.0744. The data in diabetic and insulin-resistant animals suggest an improvement of insulin action that is supported by enhancement of insulin effects in vitro. There is no evidence of a risk for hypoglycemia in diabetic and metabolically healthy animals. Triglyceride (TG) and cholesterol were reduced in the serum of metabolically healthy rats, as well as serum lipids in db/db mice, which suggests this effect is independent of amelioration of the diabetic status. Lipid-lowering effects in diabetic and healthy animals show an additional property of BM 17.0744. Because of its antidiabetic and lipid-lowering potency, the substance is of great interest in treating the metabolic syndrome. Lipid decreases in rats are associated with a dose-dependent increase in carnitine acetyltransferase activity in the liver to about 100-fold (12.5 mg/kg/d). This together with hepatomegaly in small rodents may indicate peroxisomal proliferation, a phenomenon considered species-specific. Its relevance for humans is well documented for other classes of compounds including fibrates. Specific side effects of insulin sensitizers of the thiazolidinedione type, such as an increase in body weight and heart weight, could not be observed after 4-week oral application of BM 17.0744 in rats. In general, BM 17.0744 was well tolerated in the pharmacological dose range in all species tested.
 ...
PMID:BM 17.0744: a structurally new antidiabetic compound with insulin-sensitizing and lipid-lowering activity. 992 Jan 42

Family studies point to an important genetic element in the genesis of type 2 diabetes. A variety of metabolic abnormalities have been documented in offspring of patients with type 2 diabetes. It has not been shown, however, at what age reduced insulin sensitivity is demonstrable using the sensitive the euglycemic clamp technique. To address this issue we screened 425 consecutive type 2 diabetic patients and examined all available (n = 48) normotensive, normoglycemic, non-smoking offspring (mean age 31.4+/-0.9 years) and compared them to 22 healthy offspring of non-diabetic parents (controls). The two groups were of similar age and BMI. Measurements in offspring and controls included baseline IRI, tissue glucose uptake (TGU, using euglycemic hyperinsulinemic clamp technique), and 24 hour ambulatory blood pressure (ABP). TGU was significantly (p < 0.001) lower in offspring of diabetic parents (338.8+/-19.9 (mol/kg/min) when compared to controls (516.6+/-22.2 micromol/kg/min). 24 h systolic ABP was significantly higher (p < 0.02) in propositi compared to controls (121.2+/-2.2 mm Hg and 113.8+/-1.7 mm Hg, respectively). No difference in triglycerides concentration was found. A borderline negative correlation was observed, however, between triglyceride levels and TGU (R = -0.48, p < 0.001). TGU was not related to the presence or absence of diabetic nephropathy in the parents. We conclude: Insulin resistance and various facets of the metabolic syndrome are demonstrable even at age 30 years in young non-obese, normotensive offspring of patients with type 2 diabetes. These disturbances are not related to the presence of microvascular complications in parents.
 ...
PMID:Reduced insulin-mediated glucose uptake by euglycemic clamp in offspring of patients with type 2 diabetes. 1007 26

The aim of the study was to assess the total prevalence of obesity, non-insulin-dependent diabetes mellitus (NIDDM), hypertension, hypertriglyceridemia, hypercholesterolemia and central fat distribution, in a population-based survey. Two-hundred and ten individuals from the community were selected by random digit dialing. Obesity was defined as a body mass index > or = 25 kg/m2, central distribution of fat if the waist-to-hip ratio > 0.80 in women and 1.0 in men, diabetes was diagnosed if fasting plasma glucose levels > or = 140 mg/dl and/or currently under treatment, hypertension was defined as a systolic blood pressure > or = 140 mm Hg and/or diastolic blood pressure > 90 mm Hg and/or currently taking antihypertensive medications, hypertriglyceridemia was defined as a fasting serum triglyceride concentration > or = 200 mg/kg and hypercholesterolemia as a fasting serum cholesterol level > or = 200 mg/dl and/or currently taking specific medication. Prevalence rates of obesity, NIDDM, hypertension, hypertriglyceridemia, hypercholesterolemia and central fat distribution were 54.3%, 8.0%, 60.0%, 13.9%, 67.0% and 46.7% respectively. The prevalence of each of these conditions in its isolated form was 2.8% for obesity, 0.0% for diabetes, 3.8% for hypertension, 0.5% for hypertriglyceridaemia, 12.0% for hypercholesterolemia and 0.1% for the central fat distribution pattern. The large differences in prevalence between isolated and combined forms in the six disorders analyzed indicate a great overlap between these cardiovascular risk factors, and give epidemiologic support to a proposed metabolic syndrome.
 ...
PMID:[The clustering of cardiovascular risk factors in the urban population of Porto]. 1019 77

Treatment of arterial hypertension is known to reduce cardiovascular morbidity and mortality and has a positive effect against stroke, where benefit is strongly linked to reduction in blood pressure per se. The protective effects against coronary heart disease (CHD) have also been significant but numerically less impressive than the effect against stroke. It is conceivable that this due to the fact that not just blood pressure, but also a number of metabolic variables need to be considered in this context. The insight that hypertension is often just one of the components of the so-called metabolic syndrome suggests that a modern antihypertensive drug should not only lower blood pressure; to exert optimal cardioprotective properties it should also have a neutral or even positive metabolic profile as regards its effects on lipids, glucose and insulin in order to achieve a better protection against CHD. Against this background the centrally acting selective imidazoline receptor (I1) agonist moxonidine is of considerable interest. Moxonidine has been shown to improve glucose tolerance in man, probably by two different mechanisms, i.e. by augmenting insulin sensitivity in peripheral tissues and by enhancing glucose-stimulated insulin release from the pancreas. By employing a therapeutic intervention against hypertension that not only lowers elevated arterial pressure but also positively affects some of the frequently occurring concomitant metabolic disturbances, it appears that today's standard of antihypertensive therapy may be surpassed in tomorrow's perspective.
 ...
PMID:Therapy of hypertension and metabolic syndrome: today's standard and tomorrow's perspectives. 1032 50

The metabolic syndrome consists of a cluster of metabolic disorders, many of which promote the development of atherosclerosis and increase the risk of cardiovascular disease events. Insulin resistance may lie at the heart of the metabolic syndrome. Elevated serum triglycerides commonly associate with insulin resistance and represent a valuable clinical marker of the metabolic syndrome. Abdominal obesity is a clinical marker for insulin resistance. The metabolic syndrome manifests 4 categories of abnormality: atherogenic dyslipidemia (elevated triglycerides, increased small low-density lipoproteins, and decreased high-density lipoproteins), increased blood pressure, elevated plasma glucose, and a prothrombotic state. Various therapeutic approaches for the patient with the metabolic syndrome should be implemented to decrease the risk of cardiovascular disease events. These interventions include decreasing obesity, increasing physical activity, and managing dyslipidemia; the latter may require the use of pharmacotherapy with cholesterol-lowering and triglyceride-lowering drugs.
 ...
PMID:Hypertriglyceridemia, insulin resistance, and the metabolic syndrome. 1035 72

The author presents a review on candidate genes of proteins involved in the metabolism of glucose, lipids and other metabolites (glucose carriers, insulin receptors, proinsulin, glucokinase, amyline, glycogen synthase). One of the main causes of enhanced atherogenesis in patients with type II diabetes (NIDDM) are marked genetically conditioned deviations of the lipid, lipoprotein and apolipoprotein metabolism. In the metabolic dyshomeostasis of multiple metabolic syndrome participate in the process of atherogenesis also: isoforms of apolipoprotein E4, isoforms of apolipoprotein A-IV-1/1, hyperuricaemia, raised levels of the plasminogen activator inhibitor 1 (PAI-1), hyperfibrinogenaemia, hyperhomocysteinaemia and other metabolites (cytokines, endothelin etc.). Patients with a greated genetic sensitivity manifest diabetes sooner and more intensely and die at a younger age in particular from cardiovascular disease, but also on account of a higher incidence of tumours diseases.
 ...
PMID:[Genetic predisposition in multiple metabolic syndrome. Part 2. Candidate genes in type II diabetes mellitus]. 1037 88

Postprandial (pp) hyperglycemia--frequently associated with an increase in cardiovascular risk factors--may be damaging for the endothelium. So far, little information exists how glucose, insulin and lipids may affect atherosclerosis in the pp state. Therefore, we evaluated the relationship of pp hyperglycemia, insulin secretion and coronary risk factors to intima-media thickness (IMT) in a non-diabetic risk population. In 403 subjects (147 males, 256 females), aged 40-70 years, in the majority relatives of index cases with type 2 diabetes--a 75 g oral glucose tolerance test was performed together with measurement of insulin fractions, various risk factors and IMT of the common carotid artery. We found a continuous rise of 2h pp insulin fractions along the quintiles of 2h pp plasma glucose. A significant increase of body mass index, waist to hip ratio, triglycerides and decrease of HDL-cholesterol was observed in the top quintile of 2h pp plasma glucose (8.24 > or = pp plasma glucose < 11.1 mmol/l). Albuminuria was significantly enhanced in the 5th quintile. In parallel, IMT was significantly increased in the 5th quintile versus the bottom quintile of 2 h and maximal glucose (range 11.7-15.3 mmol/l) postprandially. After age and sex adjustment pp glucose and C-peptide, total cholesterol, triglycerides and HDL-cholesterol but not fasting plasma glucose were significantly correlated to IMT. In multivariate analysis age, male sex, pp plasma glucose, total and HDL-cholesterol were found to be independent risk factors for increased IMT. In conclusion, our data in a non-diabetic European risk population show that the two top quintiles of pp plasma glucose are associated with a clustering of standard risk factors. Corresponding to this clustering of risk factors IMT was significantly increased in the top quintile of 2 h and maximal pp plasma glucose. These data show that pp hyperglycemia may exert a noxious impact on the arterial wall together with a cluster of anomalies typical for the metabolic syndrome.
 ...
PMID:Postprandial plasma glucose is an independent risk factor for increased carotid intima-media thickness in non-diabetic individuals. 1038 Dec 96

Hyperinsulinemia and impaired insulin action are familial and predictive of Type 2 diabetes onset. Since high levels of insulin are characteristic of our general (venezuelan)hispanic population, the purpose of this investigation was to identify early metabolic defects in a group of healthy first degree relatives of Type 2 diabetic patients. We studied 46 (29 women and 17 men; ages ranging 18-66 y) first degree relatives of Type 2 diabetic patients comparing them with 22 (12 women and 10 men; ages ranging 22-60 y) subjects who had no family history of diabetes. All subjects underwent resting blood pressure and anthropometric measurements; a 75 g oral glucose tolerance test with determination of glucose and insulin and a fasting lipid profile. The relatives of Type 2 diabetic patients had higher tricipital (TC) and subscapular (SC) skinfolds, and elevated DBP in relation to the control group. The skinfolds elevation was more evident in women, while in men the elevation in DBP predominates. None of the relatives had glucose intolerance, however, the glucose-stimulated insulin response was elevated at all points in men as well as in women. No difference was observed in the HOMA values for IR and beta cell function, or in the delta I30/delta G30 ratio. The lipid profile showed a marked elevation in TG levels in men as well as in women, with low HDL-C values in men. No other lipid abnormalities were observed. Correlation analysis revealed strong association between BMI and WHR with skinfolds and several parameters of the carbohydrate metabolism in women, but not in men. IR in women was possitively associated with skinfolds, SBP and lipid parameters and beta cell function with VLDL-C. Adult relatives of Type 2 diabetic venezuelan patients from hispanic origin had, early in their lives, several parameters of the metabolic syndrome as hyperinsulinemia, obesity, dyslipidemia and high blood pressure. These alterations were more prominent in women, group in which the association among BMI, WHR and IR were statistically significant respect to SBP, DBP, basal insulin, insulin/glucose ratio, TG and HDL-C.
 ...
PMID:Women relatives of Hispanic patients with type 2 diabetes are more prone to exhibit metabolic disturbances. 1039 Sep 51


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