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

Resistin, the peptide specifically secreted from adipocytes, is a hormone antagonistic to insulin action and, thus, may serve as a link between human obesity due to adiposity and insulin resistance associated with type 2 diabetes. To test this hypothesis, we studied the gene expression of resistin in adipocytes isolated from rats fed with a fructose diet which induced insulin resistance. Compared to the control rats (C) on a normal chow diet, the fructose-fed rats (F) developed hyperinsulinemia, glucose intolerance, hypertriglyceridemia and hypertension, a profile reminiscent of the syndrome X of patients with non-insulin-dependent diabetes mellitus (NIDDM). The F rats had significantly elevated plasma free fatty acids (FFA), enlarged epididymal fat pads, and increased adipocyte size compared with the C rats. We examined the glucose transport and the relative quantity of resistin mRNA produced in the adipocytes of these two groups of rats. Compared to the C rats, the F rats had a clearly reduced insulin-stimulated glucose transport. The gene expression of resistin and other adipocyte peptides was measured on the mRNA by semiquantitative RT-PCR; the validity of this technique was established in advance with a rat-fasting and then refeeding experiment. The F rats showed a decreased expression of the resistin gene, whereas gene expression of leptin and angiotensinogen in contrast increased. Free fatty acids were found to suppress the expression of resistin gene in normal rat adipocytes. These results demonstrate that an insulin-resistant instance in the fructose diet rat model exists with the decreased gene expression of resistin.
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PMID:Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids. 1174 41

The underlying determinants of cardiovascular risk are governed by both genetic and lifestyle factors. One of the major adverse outcomes of unhealthy lifestyles is obesity, the genesis of which begins in childhood. Obesity, an important risk factor for atherosclerotic cardiovascular disease, type 2 diabetes, and hypertension, persists (tracks) strongly from adolescent years to adulthood. Secular trends toward increased obesity in the past 25 years have occurred in children and adults alike. Of interest, baseline adiposity precedes hyperinsulinemia in all age groups, independently of race, sex, and baseline insulin levels. Adiposity is an independent predictor of the risk of developing the cluster of risk variables of the metabolic syndrome X, beginning in childhood. Exposure to a multiple risk factor burden over time enhances the development of coronary atherosclerosis and hypertensive cardiovascular disease. In fact, autopsy studies in youths have shown that the extent of fibrotic atherosclerotic plaques in coronary arteries, measured antemortem, increases markedly with the presence of syndrome X risk variables. Further, in overweight children, insulin levels are associated with left ventricular mass. In young people, overnutrition, coupled with physical inactivity, leads to weight gain. Since obesity, unhealthy dietary habits, and a sedentary lifestyle are interrelated and modifiable, prevention and intervention must begin in early life. (c)2001 CHF, Inc.
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PMID:Emergence of obesity and cardiovascular risk for coronary artery disease: the Bogalusa Heart Study. 1182 87

Insulin resistance is a common metabolic disorder. It plays an important role in the metabolic syndrome (or syndrome X), type 2 diabetes, obesity and in the lipodystrophic syndromes recently described, associated with treatments of HIV disease and represent a worrying cardiovascular risk. However, its pathophysiology remains poorly understood in these situations. Syndromes of major insulin resistance, although rare, allow investigations of the mechanisms leading to alterations in the insulin transduction pathways. Mutations of the insulin receptor gene have been discovered in rare patients. Therefore alterations at the post-receptor level are probably causative in other cases. Furthermore, the role of body fat repartition seems determinant in the apparition of insulin resistance, as attested by the clinical characteristics of lipodystrophies, either congenital or acquired. The two lipodystrophic syndromes which molecular defect is identified are the familial partial lipodystrophy of the Dunnigan type, due to mutations of the lamin A/C gene, and the congenital generalized lipodystrophy, linked to alterations in the protein seipin. However, their physiopathology remains mysterious. Lamin A/C is indeed an ubiquitous nuclear protein, which is also mutated in a genetic squelettic and/or cardiac myopathy, and seipin is a protein of unknown function mainly expressed in brain. Progresses in the understanding of these syndromes, in particular lipodystrophies which can be considered as caricatural models of the metabolic syndrome, will probably allow to clarify the physiopathology of the more common forms of insulin resistance.
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PMID:[Major insulin resistance syndromes: clinical and physiopathological aspects]. 1183 62

Recent evidence from the United Kingdom Prospective Diabetes Study convincingly demonstrates that good glycaemic control is difficult to achieve and, despite its positive impact on microvascular complications, is not sufficient to reduce the risk of coronary heart disease (CHD). Syndrome X--a cluster of abnormalities associated with resistance to insulin-mediated glucose uptake that have been implicated in accelerating atherogenesis--provides a useful clinical concept to prevent CHD in patients with type 2 diabetes. Components of syndrome X can include hypertension, hyperinsulinaemia, dyslipidaemia, and a procoagulant state, changes that contribute to the development of atherosclerosis. Low-density lipoprotein cholesterol (LDL-C) levels are usually close to normal, but the LDL-C is present in abnormally small and dense particles. Triglyceride levels are elevated and are associated with an increase in postprandial accumulation of atherogenic, remnant lipoprotein particles. High-density lipoprotein cholesterol levels are typically low. This particular dyslipidaemia, along with hyperinsulinaemia, induces expression of plasminogen activator inhibitor-1, contributing to a prothrombotic state. In addition, plaque formation may be accelerated in insulin-resistant subjects by increased expression of adhesion molecules on endothelial cells and increased rate of monocyte adhesion to cultured endothelial cells. Syndrome X and type 2 diabetes are associated with multiple abnormalities that enhance the atherosclerotic process. The opportunities for new therapeutic approaches to reduce cardiovascular risk will undoubtedly evolve along with our understanding of the complex factors responsible for insulin resistance, compensatory hyperinsulinaemia, and CHD.
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PMID:Multiple CHD risk factors in type 2 diabetes: beyond hyperglycaemia. 1184 50

The term metabolic syndrome is used for describing a cluster of cardiovascular risk factors comprising abdominal obesity, glucose intolerance/type 2 diabetes mellitus, dyslipidaemia and hypertension. A concomitant presentation of all components of the syndrome is rare, therefore, in the view of most experts three out of the four main components are sufficient for defining the syndrome. Another recently identified component of high clinical significance is the impairment of the fibrinolytic system which is now frequently mentioned in extended definitions. This clustering of metabolic risk factors has been described in various combinations and given different names including insulin resistance syndrome or syndrome X. Unfortunately, there is no generally accepted definition so far. The original mentioning of the syndrome goes back to the late sixties, when the metabolic syndrome was described as a 'disorder of genetic adaptation becoming manifest following unrestricted food intake and/or muscular inacitvity'. In its modern meaning this term was propagated by Hanefeld and Leonhardt and by Kaplan, who also called the syndrome the 'deadly quartet' to emphasize its high atherogenic potential.
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PMID:Insulin resistance and the metabolic syndrome-a challenge of the new millennium. 1196 19

In the past, type 2 diabetes mellitus was considered a disease of adults and older individuals, not a paediatric condition. Over the last decade, however, in the USA and the rest of the world there has been a disturbing trend of increasing cases of type 2 diabetes in children, mirroring increasing rates of obesity. The risk factors for paediatric type 2 diabetes are: (1) obesity and increased body mass index; (2) family history of type 2 diabetes; (3) membership of ethnic minority; (4) puberty (mean age of diagnosis is approximately 13.5 years); (5) female gender; and (6) features of 'syndrome X'. The common link among these risk factors is insulin resistance, which plays a pivotal role in the pathophysiology of type 2 diabetes. Both insulin resistance and beta-cell failure are present in the fully established diabetes state. Data will be presented on how these risk factors impact on insulin sensitivity and insulin secretion in childhood, ultimately leading to type 2 diabetes. The clinical presentation of type 2 diabetes in children and its distinction from type 1 diabetes will be discussed.
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PMID:Type 2 diabetes in children: clinical aspects and risk factors. 1197 18

Insulin resistance represents a common metabolic abnormality leading to cardiovascular disease, the major cause of morbidity and mortality in most parts of the world. Insulin resistance is also associated with an increased risk of type 2 diabetes which is strongly associated with obesity. The insulin resistance of obese people and subjects with type 2 diabetes is characterised by defects at many levels, affecting insulin receptor concentration, glucose transport mechanisms and the activities of intracellular enzymes. Around 25% of western populations show some features of the insulin resistance syndrome (often referred to as syndrome X or the metabolic syndrome) ie, a clustering of metabolic, atheromatous risk factors, including hypertriglyceridaemia, hyperinsulinaemia, hyper-tension, hypercholesterinaemia and obesity. However, the known metabolic cardiovascular risk factors associated with the insulin resistance syndrome do not sufficiently explain the excess vascular risk attributed to this syndrome. The observation, that increased plasma plasminogen activator inhibitor 1 (PAI-1) levels were associated with insulin resistance and atherothrombosis added for the first time a pathological basis for an association of the insulin resistance syndrome not only with metabolic, atheromatous (atherosclerotic) risk but also with atherothrombotic risk. It is very likely that not only PAI-1, but also other abnormalities in haemostatic variables contribute to this excess vascular risk. Knowledge of how haemostatic variables cluster with classical metabolic risk factors associated with the insulin resistance syndrome could help to better understand the pathogenesis of cardiovascular diseases. Indeed, many coagulation and fibrinolytic proteins have been shown to be associated with features of the insulin resistance syndrome and these associations suggest that some coagulation and fibrinolytic proteins have a role in atherothrombotic disorders, principally through an association with other established metabolic (atheromatous) risk factors in the presence of underlying insulin resistance. Interestingly, new therapeutic approaches in the prevention and treatment of insulin resistance do show some influence on coagulation and fibrinolysis. The newest drugs are the thiazolidinediones, a totally novel class of insulin sensitisers. They have the potential to offer improvements both in glycaemic control and in cardiovascular events.
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PMID:Insulin resistance syndrome: interaction with coagulation and fibrinolysis. 1214 78

Notion of consumers-producers co-operation allows better understanding of the basic mechanisms of homeostasis. This concept refers to the biological variables (BV) that are produced by tissues and organs (producers) and used for provision of functional activity of other organs and tissues (consumers). The rate of BV consumption is a major BV down-regulation factor, which participates in two kinds of imbalance: feedback and feedforward. When consumers are activates prior to producers, BV decrease and up-regulation forces are activated to counteract the decrease (feedback imbalance). Feedforward imbalance appears when producers are activated and BV consumption is postponed or suppressed. Prolonged feedforward imbalance is supposed to lead to chronic metabolic disturbances and diseases (obesitas, atherosclerosis, hypertension, NIDDM, Syndrome X, etc.).
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PMID:Consumer-producer relationship and homeostasis. 1220 69

About 15% of the adult Kuwaiti population has type 2 diabetes and over 50% are hyperlipidaemic by current diagnostic criteria. Not surprisingly, coronary heart disease (CHD) is the leading cause of death in Kuwait. Reports from coronary care units in Kuwait suggest that 40-80% of the CHD patients were diabetic and 50-80% hyperlipidaemic. The pattern worldwide is similar. International guidelines have therefore consistently recognised diabetes as a major risk factor for CHD. In our Lipid Clinic population in Kuwait, about 30% are diabetic. The commonest lipid abnormalities seen in Kuwaiti diabetic patients, as elsewhere, are hypertriglyceridaemia with low HDL levels and variable LDL levels. About 75% of the subjects had either mixed hyperlipidaemia or predominant hypertriglyceridaemia. There are possibly some compositional changes in LDL in the diabetic subjects in that there were important differences in the statistical relationships between LDL and HDL and their respective apolipoproteins - apo B and apo A-1 in diabetic as compared to non-diabetic subjects. Other important observations made in diabetic subjects in Kuwait are: (i) similar serum Lp (a) levels and pattern of apo(a) polymorphism with non-diabetic subjects, with no demonstrable relationship between serum levels of Lp(a) and insulin/insulin sensitivity, although with CHD, Lp(a) levels were increased; (ii) diabetic hyperlipidaemic subjects had elevated PAI-1 levels with significant correlations between blood PAI-1 and insulin levels suggesting underlying insulin resistance (syndrome X). Various landmark trials of cholesterol-lowering therapies in the prevention of CHD have consistently demonstrated near-normalization of the increased CHD risk in diabetes. Our experience in Kuwait suggests that diabetic patients and others with mixed hyperlipidaemia benefit from tight glycaemic control, appropriate advice on diet and exercise with regular reinforcement by continuing contact with professional dietitians and regular availability of drugs where prescribed. Often, it is the regular compliance with medication that is important, rather than the specific medication used particularly where HMG CoA reductase inhibitors (statin drugs) are not always available. A useful guideline for management of dyslipidaemia in diabetes is suggested.
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PMID:Diabetic dyslipidaemia in Kuwait. 1244 10

The metabolic and cardiovascular complications associated with reduced fetal growth have been identified during the past 10 years. These complications that encompass cardiovascular diseases and insulin resistance syndrome consist of dyslipidemia, impaired glucose tolerance or type 2 diabetes and appear to result from the initial development of insulin resistance. The association of reduced fetal growth with the other parameters of the syndrome X appear less constant than with insulin resistance and the expression and/or the age of onset seem to depend on the degree of genetic predisposition of the population. Although the mechanisms underlying the development of the insulin resistance associated with reduced fetal growth remain unclear, some evidence argues in favor of a key role of the adipose tissue. Several hypotheses have been proposed over the past 10 years to understand this unexpected association. Each of them points to either a detrimental fetal environment or genetic susceptibilities or interactions between these two components as playing a critical role in this context. Although not confirmed, the hypothesis suggesting that this association could be the consequence of genetic/environmental interactions remains at the moment the most attractive.
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PMID:Low birth weight: effect on insulin sensitivity and lipid metabolism. 1256 28


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