Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationships between metabolic disorders and cardiovascular diseases are very strong. Hypercholesterolaemia and diabetes mellitus, for instance, are well-known risk factors. The multifaceted metabolic syndrome or syndrome X, originally described by Reaven in 1988, comprises several abnormalities which are associated to insulin resistance and compensatory hyperinsulinaemia. Syndrome X results in an increased vascular risk by at least two mechanisms. On the one hand, it favours atherosclerosis and is associated to angiographic lesions, especially in the coronary arteries. On the other hand, it is associated to endothelial dysfunction which may contribute to myocardial ischaemia even in presence of angiographically normal arteries, a phenomenon named also syndrome X by the cardiologists. Thus, metabolic syndrome X and cardiological syndrome X are very close and syndrome X may be considered as a crossing between metabolic disorders and cardiovascular diseases.
 ...
PMID:[Syndrome X, at the crossroads of metabolic and cardiovascular diseases]. 955 80

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of troglitazone are reviewed. Troglitazone is the first oral thiazolidinedione approved for use in treating non-insulin-dependent diabetes mellitus (NIDDM). The drug's mechanism of action has not been fully elucidated. Troglitazone acts as an insulin sensitizer. Cell-line and animal models indicate that troglitazone may decrease hepatic glucose output by decreasing the rate of gluconeogenesis in the liver or by increasing glycolysis. Troglitazone is rapidly absorbed after oral administration, with peak concentration occurring in two to three hours. Food increases absorption by 30-85%. The drug is extensively metabolized in the liver. Troglitazone has been shown to be efficacious in treating NIDDM, both as monotherapy and in combination with oral sulfonylureas. Patients who are obese or who have high fasting plasma insulin levels may derive the greatest benefit. Patients with impaired glucose tolerance, syndrome X, polycystic ovary syndrome, gestational diabetes, or Werner's syndrome may also benefit from troglitazone. Adverse effects, including hematologic abnormalities, liver toxicity, and hypoglycemia, have been rare in published trials; no life-threatening effects have been reported thus far. The recommended initial dosage is 200 mg once daily with meals, with an increase to 400 mg daily if satisfactory glycemic control is not achieved after two to four weeks. The average wholesale price is $348 for 100 200-mg tablets and $534 for 100 400-mg tablets. Troglitazone may be an effective agent for treating NIDDM, especially in patients who are obese or who have high fasting plasma insulin levels.
 ...
PMID:Troglitazone: an antidiabetic agent. 958 50

The sympathoadrenal system plays an important role in the regulation of metabolic and cardiovascular activity. With respect to carbohydrate metabolism, specifically, catecholamines affect both insulin secretion and insulin action. Alterations in sympathoadrenal system function have been suggested to contribute to the constellation of disorders referred to as syndrome X (obesity, hypertension, NIDDM, and dyslipoproteinemia). The origin of any such abnormalities in sympathoadrenal function is unknown. The sympathoadrenal system, like other parts of the mammalian nervous system, is susceptible to environmental influences during development. Although these neurological alterations in rats are particularly prominent during the postpartum period, they are also apparent during intrauterine life. Moreover, the effects of these early environmental factors last well into adulthood and may represent permanent alterations in sympathetic nervous system behavior. Although the impact of maternal diabetes on sympathetic neural development has not been examined extensively, limited data available indicate that maternal diabetes may affect sympathetic nervous system development in the offspring. Although the full impact of maternal diabetes on neurological development in the offspring is unknown, given the myriad effects of the sympathoadrenal system on mammalian physiology, lasting changes in autonomic nervous system function may have potentially profound consequences for metabolic and cardiovascular regulation in adulthood.
Diabetes Care 1998 Aug
PMID:Effects of fetal and neonatal environment on sympathetic nervous system development. 970 44

Insulin resistance of skeletal muscle is fundamental to both syndrome X and its frequent sequel, type II diabetes. In these disorders, excessive exposure of muscle to free fatty acids (FFAs) and their metabolic derivatives appears to play a prominent role in the induction of insulin resistance. Recent evidence suggests that activation of novel isoforms of protein kinase C (PKC) by diacylglycerol may mediate at least part of the adverse impact of FFAs on muscle insulin sensitivity. Vitamin E and fish oil omega-3s, by promoting the activity of diacylglycerol kinase and inhibiting that of phosphatidate phosphohydrolase, should reduce diacylglycerol levels, thus accounting for their documented favorable impact on insulin sensitivity. Thiazolidinediones such as troglitazone, on the other hand, appear to intervene in the signaling pathway whereby PKC down-regulates insulin function. The insulin-sensitizing activity of chromium picolinate may be attributable, at least in part, to increased expression of insulin receptors. In combination with lifestyle modifications which reduce FFA exposure--weight loss, very-low-fat eating, excessive training--these measures can be expected to work in a complementary way to promote increased numbers of insulin receptors that are more functionally competent. As these measures appear to be safe and well-tolerated, they may have utility for the prevention of diabetes as well as its therapy. When they do not prove sufficient to achieve optimal glycemic control, excessive hepatic glucose output and impaired cell response to glucose can be addressed with metformin and sulfonylureas, respectively. The prospects for a rational medical management of type II diabetes, obviating the need for injectible insulin, have never been brighter.
 ...
PMID:Complementary measures for promoting insulin sensitivity in skeletal muscle. 1005 64

Syndrome X is used to describe a constellation of factors that lead to coronary heart disease (CHD): hypertension, hyperinsulinemia, impaired glucose tolerance, and an abnormality in lipid metabolism. We investigated the relationship between serum levels of C-peptide immunoreactivity (CPR) and diabetic complications in 256 patients with type-2 diabetes mellitus. The serum level of CPR was measured by radioimmunoassay (RIA). Diabetic patients were divided into 3 groups according to the serum level of CPR as follows: low CPR (n = 19, <0.7 ng/ml), normal CPR (n = 174, 0.7 to 2.2 ng/ml) and high CPR (n = 63, >2.2 ng/ml). The body mass index (BMI) and the serum level of triglycerides were significantly higher in the high CPR group (P < 0.05, respectively) compared with normal CPR group. The prevalence of hypertension was significantly higher in the high CPR group than in the other 2 groups (low CPR: 16%, normal CPR: 28%, high CPR: 38%). The frequency of the number of patients receiving insulin therapy was greater in the low CPR group than in the other 2 groups, (low CPR: 58%, normal CPR: 15%, high CPR: 11%). The serum CPR level was significantly lower in patients with than without proliferative retinopathy or macroalbuminuria. Our conclusion is that the present data suggest that an increased serum level of CPR is associated with obesity, elevated serum triglycerides, and hypertension in patients with type-2 diabetes mellitus. A low CPR level leading to hyperglycemia is associated with the progression of diabetic microangiopathies, such as retinopathy and nephropathy.
Exp Clin Endocrinol Diabetes 1999
PMID:Relation between the serum level of C-peptide and risk factors for coronary heart disease and diabetic microangiopathy in patients with type-2 diabetes mellitus. 1007 54

Insulin resistance is an early and major feature in the development of non-insulin-dependent diabetes mellitus(NIDDM). It is also associated with hyperlipidemia, hypertension, obesity and cardiovascular disease. It is the clustor of the risk factors for atherosclerosis and recognized as 'insulin-resistance syndrome' (Syndrome X). Central (abdominal) obesity is much more strongly associated with insulin resistance than overall obesity. The increase of both the influx of free fatty acid to liver and the production of TNF-alpha in adipose tissue may play an important role in mechanism of insulin resistance associated with central obesity. Calorie restriction and weight loss improve insulin sensitivity in overweight humans. Exercise training also improves insulin sensitivity via increased oxidative enzymes, glucose transporters (GLUT4) and capillarity in muscle as well as by reducing abdominal fat. The new 'glitazones' (thiazolidinediones) is used clinically to improve insulin sensitivity.
 ...
PMID:[Syndrome X]. 1019 44

Plasma leptin levels are elevated in most obese individuals, and obesity is accompanied by a high incidence of cardiovascular disease. Therefore, leptin could be involved in the pathogenesis of cardiovascular disease. In the present study, the role of leptin was explored in the regulation of platelet function. The expression of the long form of the leptin receptor was detected in human platelets. At 50 ng/ml, human leptin induced phosphorylation of several proteins of platelets at the tyrosine residue. Neither leptin at concentrations < or = 100 ng/ml nor ADP at concentrations > or = 1 micromol/l affected platelet aggregation. However, after pretreatment with 100 ng/ml leptin for 5 min, 1 micromol/l ADP caused aggregation. Thus, leptin and ADP acted synergistically. At a concentration of 2 micromol/l, ADP induced platelet aggregation, which was markedly enhanced by 30-100 ng/ml leptin in a concentration-dependent manner. This concentration range corresponds to that of plasma leptin levels in obese individuals. At the lower concentrations (< 10 ng/ml) that are observed in normal individuals, leptin had no effect on platelet aggregation. In conclusion, leptin at high concentrations has the novel function of promoting platelet aggregation, which may be a key coupling factor between obesity and the cardiovascular disease associated with syndrome X and diabetes.
Diabetes 1999 Feb
PMID:Leptin promotes aggregation of human platelets via the long form of its receptor. 1033 26

The purpose of this investigation was to determine the prevalence and correlates of abnormal urinary albumin excretion and to examine the possible additive effects of cardiovascular risk factors on urinary albumin excretion in African Americans with type 2 diabetes mellitus. One hundred fifty-one African-American subjects who met WHO criteria for type 2 diabetes were included in this cross-sectional analysis. Subjects were identified through computerized medical records from a family medicine clinic and a community health center. Urinary albumin excretion ratios (UAER) were determined from overnight samples. The prevalence of abnormal urinary protein excretion was 51%. Of those with abnormal protein excretion, 36% had microalbuminuria and 15% had macroalbuminuria. Diabetes duration, waist to hip ratio, blood pressure, and total- and LDL cholesterol were significantly higher in subjects with macroalbuminuria. Regression analysis indicated that mean arterial blood pressure, diabetes duration and total cholesterol were independently associated with UAER. Mean UAER significantly increased with the addition of one or more syndrome X risk factors to pure diabetes. Our results indicate that African Americans with type 2 diabetes mellitus have a high prevalence of abnormal urinary protein excretion, which is associated with a clustering of additional cardiovascular risk factors. The fact that this increased risk was associated with hypertension indicates that screening for albuminuria in this population is essential and that a majority of African Americans with diabetes may be at risk for developing cardiovascular complications.
 ...
PMID:Abnormal urinary protein excretion in African Americans with type 2 diabetes mellitus. 1035 70

Individuals with type 2 diabetes mellitus (n = 105; age 36-71 years) on diet therapy alone, and with quite good glycaemic control (mean HbA1c approximately 7.0%) were randomized to receive acarbose (100 mg three times daily) or placebo for 16 weeks, and changes in clinical and metabolic parameters indicative of Syndrome X were monitored. Fasting levels of glucose, glycosylated haemoglobin (HbA1c), true insulin, proinsulin, fibrinogen and lipids were measured four times weekly, and glucose, insulin, proinsulin and triglyceride responses to a standardized 1.6 MJ breakfast were determined at 0, 1 and 2 h post meal. Analysis was on an intention-to-treat basis. Fasting levels of glucose (P < 0.0001), triglycerides (P = 0.03) and HbA1c (P = 0.003) were reduced by acarbose over the 16 weeks of treatment. The mean change in HbA1c from week 0 to 16 differed by 0.4% (P = 0.003) between the two groups. Insulin (P = 0.06), proinsulin (P = 0.07) and glucose (P < 0.0001) responses to the standard meal were reduced. These data show that acarbose reduces fasting glucose and triglyceride levels, lowers HbA1c and limits the glycaemic and insulin response to food in individuals with type 2 diabetes mellitus with Syndrome X. Pharmacological agents that improve the metabolic environment and reduce insulin resistance have the potential to limit the progression of atherogenesis associated with type 2 diabetes mellitus.
Diabetes Res Clin Pract 1999 Mar
PMID:Will acarbose improve the metabolic abnormalities of insulin-resistant type 2 diabetes mellitus? 1036 27

Metformin has been used for over 40 years as an effective glucose-lowering agent in type 2 (noninsulin-dependent) diabetes mellitus. Typically it reduces basal and postprandial hyperglycaemia by about 25% in more than 90% of patients when either given alone or coadministered with other therapies including insulin during a programme of managed care. Metformin counters insulin resistance and offers benefits against many features of the insulin resistance syndrome (Syndrome X) by preventing bodyweight gain, reducing hyperinsulinaemia and improving the lipid profile. In contrast to sulphonylureas, metformin does not increase insulin secretion or cause serious hypoglycaemia. Treatment of type 2 diabetes mellitus with metformin from diagnosis also offers greater protection against the chronic vascular complications of type 2 diabetes mellitus. The most serious complication associated with metformin is lactic acidosis which has an incidence of about 0.03 cases per 1000 patients years of treatment and a mortality risk of about 0.015 per 1000 patient-years. Most cases occur in patients who are wrongly prescribed the drug, particularly patients with impaired renal function (e.g. serum creatinine level > 130 micromol/L or > 1.5 g/L). Other major contraindications include congestive heart failure, hypoxic states and advanced liver disease. Serious adverse events with metformin are predictable rather than spontaneous and are potentially preventable if the prescribing guidelines are respected. Gastrointestinal adverse effects, notably diarrhoea, occur in less than 20% of patients and remit when the dosage is reduced. The life-threatening risks associated with metformin are rare and could mostly be avoided by strict adherence to the prescribing guidelines. Given the 4 decades of clinical experience with metformin, its antihyperglycaemic efficacy and benefits against Syndrome X, metformin offers a very favourable risk-benefit assessment when compared with the chronic morbidity and premature mortality among patients with type 2 diabetes mellitus.
 ...
PMID:A risk-benefit assessment of metformin in type 2 diabetes mellitus. 1039 66


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