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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evolutionary pressures have probably amplified the mechanisms for minimizing the impact of environmental factors through compensatory maternal mechanisms. Nevertheless, experimentally there are clear long-term programming effects of manipulations to the maternal diet on the likelihood of neural-tube defects associated with folate deficiency The fat/lean ratios of the newborn, and subsequent development, seem to be linked to amino acid or folate supply. An altered balance in the hypothalamic-pituitary-adrenal axis, which experimentally has profound effects on brain development, is induced by low-protein maternal diets. Such diets are linked to a reduced pancreatic capacity for insulin production and to an altered hepatic architecture, with a change in the control of glucose metabolism. Human studies suggest that what happens in pregnancy is modified by the child's diet in the first months of life. Low birthweight is linked to early stunting, and predisposes to abdominal obesity and metabolic syndrome in later life. Metabolic syndrome amplifies the risks of diabetes, hypertension, coronary heart disease and probably some cancers. Mothers with gestational diabetes are themselves prone to early type 2 diabetes and produce heavier babies prone to childhood obesity and adolescent type 2 diabetes. There is increasing evidence of an intergenerational effect, with big babies being prone to excess weight gain, which then, in girls, predisposes them to diabetes in pregnancy, which, in turn, promotes an accelerating cycle of early diabetes in subsequent generations. Essential fatty acids and fat soluble vitamins are important, but we need early interventions and monitoring systems to justify coherent policies.
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PMID:Will feeding mothers prevent the Asian metabolic syndrome epidemic? 1249 42

Abdominal obesity and physical inactivity are associated with insulin resistance in humans and contribute to the development of type 2 diabetes. Likewise, sustained increases in the concentration of malonyl coenzyme A (CoA), an inhibitor of fatty-acid oxidation, have been observed in muscle in association with insulin resistance and type 2 diabetes in various rodents. In the present study, we assessed whether these factors are present in a defined population of slightly overweight (body mass index, 26.2 kg/m2), insulin-resistant patients with type 2 diabetes. Thirteen type 2 diabetic men and 17 sex-, age-, and body mass index-matched control subjects were evaluated. Insulin sensitivity was assessed during a two-step euglycemic insulin clamp (infusion of 0.25 and 1.0 mU/kg x min). The rates of glucose administered during the low-dose insulin clamp were 2.0 +/- 0.2 vs. 0.7 +/- 0.2 mg/kg body weight x min (P < 0.001) in the control and diabetic subjects, respectively; rates during the high-dose insulin clamp were 8.3 +/- 0.7 vs. 4.6 +/- 0.4 mg/kg body weight x min (P < 0.001) for controls and diabetic subjects. The diabetic patients had a significantly lower maximal oxygen uptake than control subjects (29.4 +/- 1.0 vs. 33.4 +/- 1.4 ml/kg x min; P = 0.03) and a greater total body fat mass (3.7 kg), mainly due to an increase in truncal fat (16.5 +/- 0.9 vs. 13.1 +/- 0.9 kg; P = 0.02). The plasma concentration of free fatty acid and the rate of fatty acid oxidation during the clamps were both higher in the diabetic subjects than the control subjects (P = 0.002-0.007). In addition, during the high-dose insulin clamp, the increase in cytosolic citrate and malate in muscle, which parallels and regulates malonyl CoA levels, was significantly less in the diabetic patients (P < 0.05 vs. P < 0.001). Despite this, a similar increase in the concentration of malonyl CoA was observed in the two groups, suggesting an abnormality in malonyl CoA regulation in the diabetic subjects. In conclusion, the results confirm that insulin sensitivity is decreased in slightly overweight men with mild type 2 diabetes and that this correlates closely with an increase in truncal fat mass and a decrease in physical fitness. Whether the unexpectedly high levels of malonyl CoA in muscle, together with the diminished suppression of plasma free fatty acid, explains the insulin resistance of the diabetic patients during the clamp remains to be determined.
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PMID:Insulin resistance in type 2 diabetes: association with truncal obesity, impaired fitness, and atypical malonyl coenzyme A regulation. 1251 34

Insulin resistant metabolic syndrome is a major clinical disorder including hyperlipidaemia, hypertension, impaired glucose tolerance and/or type 2 diabetes and central obesity, which are well established cardiovascular risk factors. We report the case of a 61-year-old woman who developed severe hypercholesterolaemia and hypertriglyceridaemia after liver transplantation. In her forties she had hypertension, mixed hyperlipidaemia, mild hyperglycaemia and moderate abdominal obesity, suggesting the presence of the metabolic syndrome. She had liver enzyme elevation and severe steatosis and hepatomegaly at ultrasonography. At age 52, cryptogenic liver cirrhosis was diagnosed and rapidly progressing liver failure developed. In 1992 she underwent liver transplantation. Seven years after transplant the patient had abdominal obesity, high blood pressure, marked hypercholesterolaemia, hypertriglyceridaemia and moderate elevation of alanine aminotransferase. She also had impaired glucose tolerance and markedly increased basal and post-glucose load plasma insulin levels. Steatohepatitis was demonstrated by serial liver biopsies. This is the first case that reports the recurrence of the metabolic syndrome following liver transplantation. We postulate that metabolic syndrome may have promoted fatty liver and subsequent progression to end stage liver disease. We also stress the need for careful management of the metabolic syndrome in order to decrease the long-term risk for cardiovascular disease.
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PMID:Recurrence of insulin resistant metabolic syndrome following liver transplantation. 1254 3

Abdominal obesity has been linked to the development of insulin resistance and Type 2 diabetes mellitus (DM2). By surgical removal of visceral fat (VF) in a variety of rodent models, we prevented insulin resistance and glucose intolerance, establishing a cause-effect relationship between VF and the metabolic syndrome. To characterize the biological differences between visceral and peripheral fat depots, we obtained perirenal visceral (VF) and subcutaneous (SC) fat from 5 young rats. We extracted mRNA from the fat tissue and performed gene array hybridization using Affymetrix technology with a platform containing 9 000 genes. Out of the 1 660 genes that were expressed in fat tissue, 297 (17.9 %) genes show a two-fold or higher difference in their expression between the two tissues. We present the 20 genes whose expression is higher in VF fat (by 3 - 7 fold) and the 20 genes whose expression is higher in SC fat (by 3 - 150 fold), many of which are predominantly involved in glucose homeostasis, insulin action, and lipid metabolism. We confirmed the findings of gene array expression and quantified the changes in expression in VF of genes involved in insulin resistance (PPARgamma leptin) and its syndrome (angiotensinogen and plasminogen activating inhibitor-1, PAI-1) by real-time PCR (qRT-PCR) technology. Finally, we demonstrated increased expression of resistin in VF by around 12-fold and adiponectin by around 4-fold, peptides that were not part of the gene expression platform. These results indicate that visceral fat and subcutaneous fat are biologically distinct.
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PMID:Differential gene expression between visceral and subcutaneous fat depots. 1266 Aug 71

Fifty consecutive younger patients (< or = 40 years) with coronary artery disease, who underwent coronary angiography in National Institute of Cardiovascular Diseases were evaluated clinically and coronary risk factors were analyzed and compared with those of fifty older patients with coronary artery disease. Mean age of younger and older patients were 37.31 and 54.58 years respectively and myocardial infarction was the most common presenting complain in both the groups. Smoking and family history of premature coronary artery disease were more common in younger patients but the older patients were more diabetic and hypertensive. Central obesity and dyslipidemia did not vary between the two groups. Fifty percent of younger patients had one or two modifiable risk factors where sixty four percent of older patients had three or more modifiable risk factors. Forty four percent younger patients had hypercholesterolemia but a majority of patients had either isolated hypertriglyciredemia or decrease high density lipoprotein cholesterol or both with normal total cholesterol level but the total cholesterol and high density lipoprotein cholesterol index were more than 4.5. Younger patients had more number of normal coronary or single vessel diseases but older group had more number of triple vessel diseases. So the higher incidence of non-insulin dependent diabetes mellitus with central obesity suggesting insulin resistance along with unique profile of dyslipidemia, higher incidence of smoking and familial predisposition of premature coronary artery disease may be responsible for higher incidence of coronary artery disease at a premature younger age in this population.
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PMID:Coronary artery disease in young patients: clinical review and risk factor analysis. 1271 32

Insulin resistance and hyperinsulinemia are the critical characteristics of the metabolic syndrome that is associated with abdominal obesity and are the early manifestations of its progression to type 2 diabetes. These metabolic abnormalities are becoming recognized as a major contributor to cardiovascular disease. The experimental studies required to elucidate the underlying mechanisms and to develop effective preventative strategies will require the use of appropriate animal models and these are available. The evidence from such research indicates that a wide range of interventions (including peroxisome proliferator activator receptor agonists, insulin-sensitizing agents, statins, fibrates, angiotensin-converting enzyme inhibitors, estrogen receptor modulators, lipid-based nutriceuticals, and ethanol) can markedly reduce or prevent vasculopathy and ischemic cardiac lesions in animal models. Overall, the results suggest that early damage to the vascular wall, both in function and presenting as atherosclerotic lesions, is secondary to long-term hyperinsulinemia and, especially, to postprandial peaks in plasma insulin levels, and is exacerbated by the accompanying hyperlipidemia. Effective treatment will, of necessity, be preventative and will necessitate diagnostic approaches that can identify asymptomatic individuals at high risk for vascular damage and eventual progression to type 2 diabetes. Therapeutic targets in this population include insulin sensitivity and the associated signal transduction pathways, the peroxisome proliferator activator receptor-alpha and -gamma systems, and the complex pathways leading from acetyl CoA and the citric acid cycle to the synthesis of fatty acid and the storage of triglyceride. These pharmacological approaches offer the prospect of preventing a significant proportion of cardiovascular disease.
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PMID:Reduction and prevention of the cardiovascular sequelae of the insulin resistance syndrome. 1276 60

The insulin resistance syndrome is composed of risk factors for cardiovascular disease, including insulin resistance with hyperinsulinemia, atherogenic dyslipidemia, hypertension, abdominal obesity, and impaired hemostasis. Patients with type 2 diabetes frequently manifest multiple risk factors for cardiovascular morbidity and mortality. Management of the insulin resistance syndrome often includes antihypertensive, lipid-lowering, and antihyperglycemic agents. Because thiazolidinediones (TZDs) directly improve insulin resistance, early use may provide substantial benefits to patients with type 2 diabetes. TZDs reduce plasma glucose and insulin concentrations, promote relocation of body fat, and have anti-inflammatory effects on the vascular endothelium. Combination oral hypoglycemic therapy may be ideal for maintaining adequate glycemic control in patients with type 2 diabetes. The combination of a TZD and a biguanide, which improves insulin sensitivity and lowers blood glucose through different pathways, offers significant benefits and may help prevent or delay prevent complications associated with type 2 diabetes.
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PMID:Insulin resistance syndrome. Description, pathogenesis, and management. 1278 29

Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Hyperinsulinemia and insulin action were initially proposed as the common preceding factors of hypertension, low high-density lipoprotein cholesterol, hypertriglyceridemia, abdominal obesity, and altered glucose tolerance, linking all these abnormalities to the development of coronary heart disease. The similarities of insulin resistance with another inflammatory state, atherosclerosis, have been described only in the last few decades. Atherosclerosis and insulin resistance share similar pathophysiological mechanisms, mainly due to the actions of the two major proinflammatory cytokines, TNF-alpha and IL-6. Genetic predisposition to increased transcription rates of these cytokines is associated with metabolic derangement and simultaneously with coronary heart disease. Dysregulation of the inflammatory axis predicts the development of insulin resistance and type 2 diabetes mellitus. The knowledge of how interactions between metabolic and inflammatory pathways occur will be useful in future therapeutic strategies. The effective administration of antiinflammatory agents in the treatment of insulin resistance and atherosclerosis is only the beginning of a promising approach in the management of these syndromes.
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PMID:Insulin resistance and chronic cardiovascular inflammatory syndrome. 1278

The metabolic syndrome is a highly prevalent clinical entity. The recent Adult Treatment Panel (ATP III) guidelines have called specific attention to the importance of targeting the cardiovascular risk factors of the metabolic syndrome as a method of risk reduction therapy. The main factors characteristic of this syndrome are abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance (with or without glucose intolerance), prothrombotic and proinflammatory states. An insulin resistance following nuclear peroxisome proliferator activated receptors (PPAR) deactivation (mainly obesity-related) is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) with preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) with massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads to both microvascular and macrovascular complications. We suggest that a PPAR-based appraisal of metabolic syndrome and type 2 diabetes may improve our understanding of these diseases and set a basis for a comprehensive approach in their treatment.
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PMID:Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). 1283 41

Abdominal obesity is associated with metabolic abnormalities, increasing the risk of type 2 diabetes and coronary artery disease (CAD). The Quebec Cardiovascular Survey demonstrated that the atherogenic metabolic triad (AMT) present in abdominally obese (AO) males increases the risk of CAD 20-fold over the course of 5 years. An early detection algorithm was developed to identify individuals presenting these atherogenic abnormalities. It was found that the association of large waist circumference (WC) and moderate hypertriglyceridemia (the "hypertriglyceridemic waist", or HW) could adequately identify a significant portion of individuals with the AMT. It is important to note that even in the absence of classic risk factors, abdominally obese patients can present increased risk of CAD if they have HW. Finally, it has been suggested that the risk of developing an acute coronary syndrome in AO patients is not always related to the degree of coronary stenosis, and the patient s atherothrombotic/inflammatory profile should be taken into account in evaluating risk. Stabilization of the atherosclerotic plaque would become a legitimate therapeutic objective, and more feasible for prevention of CAD, in AO patients.
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PMID:[Treatment of obesity: the need to target attention on high-risk patients characterized by abdominal obesity]. 1288 31


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