Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to examine characteristics associated with the insulin metabolic syndrome, including insulin resistance, abnormal glucose tolerance, dyslipidemia, obesity, and elevated blood pressure, among women who have experienced gestational diabetes. 39 nondiabetic, young (20-42 years), postpartum (3-18 months) white women were recruited from obstetrical clinics. Twenty-one women had a history of gestational diabetes; 18 had uncomplicated pregnancies. Multivariate analyses revealed a significant difference between groups in insulin resistance (M, measured by euglycemic clamp) and insulin levels (from an oral glucose tolerance test), with insulin resistance showing a statistically stronger difference than insulin levels. Groups also differed significantly when compared on a set of variables associated with insulin metabolic syndrome: glucose tolerance, triglycerides, blood pressure, and body-mass index. Using insulin resistance as a covariate eliminated these group differences, suggesting that insulin resistance is the key factor underlying insulin metabolic syndrome. The higher risk of later developing type 2 diabetes and hypertension in women who have a history of gestational diabetes is explicable by their poorer profile on variables associated with insulin metabolic syndrome, and appears to be attributable to insulin resistance. Thus, insulin resistance appears to distinguish young women at risk for cardiovascular disease.
 ...
PMID:History of gestational diabetes, insulin resistance and coronary risk. 1061 62

Recent epidemiological data have reaffirmed that elevated plasma triglyceride and low HDL-cholesterol levels are important risk factors for atherosclerotic vascular disease. The rationale for the clinical use of fibric acid derivatives, which are designed to correct this metabolic nexus, is now on firmer ground. The mechanism of action of fibrates on lipoprotein metabolism has recently been elucidated at the molecular level and involves the activation of peroxisome proliferator-activated receptor-alpha 1 in the liver, with the net effect of improving the plasma transport rates of several lipoproteins. Other potential anti-atherothrombotic effects include the inhibition of coagulation and enhancement of fibrinolysis, as well as the inhibition of inflammatory mediators involved in atherogenesis. These consequences probably underpin the favourable effects of fibrates seen in recent angiographic and clinical trials. Two important clinical trials on the effect of gemfibrozil (Veterans Administration-HDL-Cholesterol Intervention Trial) and bezafibrate (Bezafibrate Infarction Prevention Study) have recently been completed in subjects with elevated triglyceride, low HDL and normal or near-normal LDL-cholesterol levels. The results testify to the efficacy of these agents in decreasing the incidence of cardiovascular events, particularly in patients with multiple risk factors and plasma triglyceride levels of over 2.2 mmol/l. The findings of these trials are compared with the statin-based Air Force/Texas Coronary Atherosclerosis Prevention Study, with a recommendation that future studies in appropriately selected patients should examine the synergistic effect of the fibrate/statin combination. The absolute risk reduction in the incidence of coronary events in the Veterans Administration-HDL-Cholesterol Intervention Trial compares favourably with the statin trials. The therapeutic aspects of the efficacy and safety of fibrates are reviewed. Besides primary mixed hyperlipidaemias, particular indications for the clinical use of fibrates include type 2 diabetes, the metabolic syndrome and renal insufficiency. The St Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention Study has suggested that fibrates may decrease the incidence of coronary events in type 2 diabetes, but this hypothesis will be more extensively tested in the Diabetes Atherosclerosis Intervention Study, Fenofibrate in Event Lowering in Diabetes Study and Lipids in Diabetes Study projects. Although significant new knowledge has accrued over the past few years concerning the fundamental and clinical aspects of fibrates, the success of these agents in clinical practice depends on the availability of methods for assessing cardiovascular risk as well as on treatment guidelines, which as presently designed and recommended may be inaccurate and suboptimal.
 ...
PMID:Fibrates, dyslipoproteinaemia and cardiovascular disease. 1068 50

The widely propagated morbidity and mortality risks of obesity appear somewhat exaggerated, except for morbid obesity (BMI > 40 kg/m2) and for high risk obese subgroups concerning diabetes mellitus, hypertension, metabolic syndrome and obstructive sleep apnea syndrome. Non-medical reasons represent a major component of the social pressure that is presently experienced by obese persons in our society. Weight reduction represents the primary therapeutic approach in overweight patients with type 2 diabetes, hypertension, metabolic syndrome and obstructive sleep apnea, and it may be recommended in high-risk individuals for primary prevention of these diseases. Massive obesity is associated with excess mortality, especially in younger, physically inactive men with upper-body-segment obesity. It is widely assumed that weight reduction will lead to a reduction of excess mortality in these individuals; so far, however, there is no proof for this assumption. Non-medicamentous conservative therapeutic approaches to weight reduction have the advantage of safety, even though their long-term efficacy is generally disappointing. There are no randomized, controlled trials to prove a reduction of morbidity or mortality risks and of therapeutic safety for pharmacological, invasive or surgical methods to treat obesity.
 ...
PMID:[Perspectives and limits in treatment of obesity]. 1073 79

Recent evidence is reviewed indicating increased oxidative damage in Type 1 and Type 2 diabetes mellitus as well as deficits in antioxidant defence enzymes and vitamins. Mechanisms are considered whereby hyperglycaemia can increase oxidative stress, and change the redox potential of glutathione and whereby reactive oxygen species can cause hyperglycaemia. It is argued that oxygen, antioxidant defences, and cellular redox status should now be regarded as central players in diabetes and the metabolic syndrome.
 ...
PMID:Radicals and oxidative stress in diabetes. 1078 20

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance, and is now considered as one of the commonest liver diseases in western countries. It is frequently associated with severe obesity, especially abdominal adiposity, and is intimately related to various clinical and biological markers of the insulin resistance syndrome. Especially, both the prevalence and the severity of liver steatosis are related to male sex, body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. A substantial weight loss following gastroplasty is accompanied by a marked reduction in the prevalence and the severity of the various biological abnormalities of the metabolic syndrome and, concomitantly, by an important regression of liver steatosis in most obese patients. However, in some patients, this rapid and drastic weight loss may result in a mild increase in inflammatory lesions (hepatitis), despite the regression of steatosis, which might result from the rapid mobilization of fatty acids or cytokines from adipose tissue, especially visceral fat. The intimate relationship between NASH and obesity leads to the concept that NASH may be considered as another disease of affluence, as is the insulin resistance syndrome and perhaps being part of it.
 ...
PMID:Non-alcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss. 1080 23

Previous epidemiological studies have demonstrated relationships between individual nutrients and glucose intolerance and type 2 diabetes, but the association with the overall pattern of dietary intake has not previously been described. In order to characterize this association, 802 subjects aged 40-65 years were randomly selected from a population-based sampling frame and underwent a 75 g oral glucose-tolerance test. Principal component analysis was used to identify four dietary patterns explaining 31.7% of the dietary variation in the study cohort. These dietary patterns were associated with other lifestyle factors including socio-economic group, smoking, alcohol intake and physical activity. Component 1 was characterized by a healthy balanced diet with a frequent intake of raw and salad vegetables, fruits in both summer and winter, fish, pasta and rice and low intake of fried foods, sausages, fried fish, and potatoes. This component was negatively correlated with central obesity, fasting plasma glucose, 120 min non-esterified fatty acid and triacylglycerol, and positively correlated with HDL-cholesterol. It therefore appears to be protective for the metabolic syndrome. Component 1 was negatively associated with the risk of having undiagnosed diabetes, and this association was independent of age, sex, smoking and obesity. The findings support the hypothesis that dietary patterns are associated with other lifestyle factors and with glucose intolerance and other features of the metabolic syndrome. The results provide further evidence for the recommendation of a healthy balanced diet as one of the main components of chronic disease prevention.
 ...
PMID:A cross-sectional study of dietary patterns with glucose intolerance and other features of the metabolic syndrome. 1088 14

The metabolic syndrome represents a vicious cycle whereby insulin resistance leads to compensatory hyperinsulinaemia, which maintains normal plasma glucose but may exacerbate insulin resistance. Excess insulin secretion may eventually reduce beta-cell function due to amyloid deposition, leading to raised blood glucose and further deterioration of beta-cell function and insulin sensitivity via glucose toxicity. Reducing postprandial glucose and insulin responses may be a way to interrupt this process, but there is disagreement about the dietary approach to achieve this. Glucose and insulin responses are determined primarily by the amount of carbohydrate consumed and its rate of absorption. Slowly absorbed, low glycaemic-index (GI) foods are associated with increased HDL cholesterol and reduced risk of type 2 diabetes. There is some evidence that low-GI foods improve insulin sensitivity in humans, although studies using established techniques (glucose clamp or frequently sampled intravenous glucose tolerance test) have not been done. Low carbohydrate diets have been suggested to be beneficial in the treatment of the metabolic syndrome because of reduced postprandial insulin. However, they may increase fasting glucose and impair oral glucose tolerance--effects which define carbohydrate intolerance. The effects of low carbohydrate diets on insulin sensitivity depend on what is used to replace the dietary carbohydrate, and the nature of the subjects studied. Dietary carbohydrates may affect insulin action, at least in part, via alterations in plasma free fatty acids. In normal subjects a high-carbohydrate/low-GI breakfast meal reduced free fatty acids by reducing the undershoot of plasma glucose, whereas low-carbohydrate breakfasts increased postprandial free fatty acids. It is unknown if these effects occur in insulin-resistant or diabetic subjects. Thus further work needs to be done before a firm conclusion can be drawn as to the optimal amount and type of dietary carbohydrate for the treatment of the metabolic syndrome.
 ...
PMID:Dietary carbohydrates and insulin action in humans. 1088 99

Several epidemiological studies link consumption of fibre-rich foods to a reduced risk of type 2 diabetes and CHD. The 'fibre hypothesis' suggested that this was a direct effect of fibre. However, fibre-rich foods contain different types of fibre as well as other potentially beneficial compounds, and many foods naturally high in fibre have low glycaemic and insulinaemic indices, possibly due to food form. The question therefore emerges as to the effect of isolated fibre per se on insulin sensitivity, lipids and other risk factors associated with the metabolic syndrome. Many beneficial effects are seen with pharmacological doses of isolated viscous soluble fibre, including improved insulin sensitivity, decreased LDL-cholesterol levels and decreased clotting factors. Similar effects are seen with low glycaemic-index foods. In contrast, insoluble non-viscous cereal fibre is not seen to act directly on risk factors when taken in refined foods such as in milled flour. Since cereal fibre, the major type of fibre in western diets, does not directly act on the risk factors for the metabolic syndrome, the question remains as to possible mechanisms. Until now, fibre and the nature and processing of the starch and particle size have been seen as the main determinants of the metabolic response to starchy foods. However, fibre-rich foods also have an increased protein-to-carbohydrate ratio. Hence we suggest that the protective effect of fibre may also be due to increased vegetable protein content, which may act directly to reduce clotting factors and oxidized LDL-cholesterol levels.
 ...
PMID:Dietary fibre, lente carbohydrates and the insulin-resistant diseases. 1088 7

The metabolic syndrome represents a complex combination of the symptoms obesity, insulin resistance, dyslipoproteinemia, hypertension, and type 2 diabetes. These components have a heterogeneous genetic basis and appear to be closely linked. Obesity is determined by a polygenic constellation and produces insulin resistance, hypertension and dyslipidemia. In addition, defects in the signal transduction of insulin appear to aggravate the insulin resistance independent of obesity. Type 2 diabetes is produced by a third genetic predisposition and is precipitated by the failure of pancreatic beta-cell to compensate insulin resistance. Because prevalence and course of the diabetes markedly depend on the extent of obesity and insulin resistance, these symptoms of the metabolic syndrome represent crucial targets for preventive and therapeutic strategies.
 ...
PMID:[Insulin resistance and metabolic syndrome]. 1090 Jun 66

Insulin resistance has been described as a possible underlying link for the clustering of Type 2 diabetes mellitus, hypertension, obesity, and dyslipidemia, known as the metabolic syndrome. Mutations within the insulin receptor have been associated with hypertension in some white and Oriental populations. We examined the relationship between the insulin receptor NsiI restriction fragment-length polymorphism (RFLP) and biochemical and anthropometric parameters associated with these disorders in 933 Chinese subjects. Of the 933 subjects, 117 were control subjects and 816 had one or more components of the metabolic syndrome: 59.7% hypertension, 64.6% glucose intolerance, 55.3% dyslipidemia, and 53.3% obesity. The prevalences of the N1 allele and N1N1 genotype were 74.4% and 55.8%, respectively, in the whole population. No differences were observed in the genotype and allele frequency distributions between the control group and the cohorts with glucose intolerance, hypertension, or dyslipidemia alone or in combination. Using one-way ANOVA, there was a weak relationship between the insulin receptor genotypes and diastolic blood pressure (DBP), P = .069. The DBP was significantly higher in subjects carrying the N1N1 genotype in both the total population (80 +/- 13 v 76 +/- 12 mm Hg, P = .038) and subjects with glucose intolerance (80 +/- 12 v 76 +/- 10 mm Hg, P = .048). Using stepwise multiple regression, the insulin receptor NsiI polymorphism was found to be an independent predictor of DBP in this Chinese population, P = .018. Age, gender, and body mass index (BMI) were also included in the analysis and were all significantly associated with diastolic DBP. To conclude, the insulin receptor gene NsiI RFLP is associated with DBP in these Chinese subjects.
 ...
PMID:An insulin receptor gene polymorphism is associated with diastolic blood pressure in Chinese subjects with components of the metabolic syndrome. 1093 64


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