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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study of childhood obesity has continued to grow exponentially in the past decade. This has been driven in part by the increasing prevalence of this problem and the widespread potential effects of increased obesity in childhood on lifelong chronic disease risk. The focus of this review is on recent findings regarding the link between obesity and disease risk during childhood and adolescence. We describe recent reports relating to type 2 diabetes in youth (2), prediabetes (69, 166), metabolic syndrome (33, 35), polycystic ovarian syndrome (77), and nonalcoholic fatty liver disease (58, 146), and the mediating role of insulin resistance in these conditions. In addition, we review the implications of this research for the design of more effective treatment and prevention strategies that focus more on the improvement of obesity-related metabolic abnormalities and chronic disease risk reduction than on the conventional energy balance approach that focuses on weight management.
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PMID:Pediatric obesity and insulin resistance: chronic disease risk and implications for treatment and prevention beyond body weight modification. 1601 74

Otsuka Long-Evans Tokushima fatty (OLETF) rats lack the CCK-1 receptor, are hyperphagic, progressively become obese, and develop type-2 diabetes. We recently demonstrated an increased preference for both real and sham feeding of sucrose in this strain, suggesting altered orosensory sensitivity. To investigate taste functions, we used an automated gustometer with 10-s access to different concentrations of various sapid stimuli. Tests were repeated at 10 and 18 wk of age to assess the early and advanced stages of prediabetes, respectively. Compared with age-matched, nonmutant controls, the OLETF rats showed higher avidity for sucrose at both ages. This difference increased as a function of age and tastant concentration. An exaggerated response also occurred for saccharin, alanine, and fructose, but not for Polycose. Similarly, OLETF rats consumed monosodium-glutamate more at the lower concentrations compared with controls, an effect that age also accentuated. In contrast, there was no statistical strain or age differences in responses to NaCl, MgCl2, citric acid, quinine-HCl, and the trigeminal stimulus capsaicin. These findings demonstrate that compared with controls, OLETF rats differ in their gustatory functions with an overall augmented sensitivity for sweet that progresses during prediabetes. This effect explains their overconsumption of sweet solutions and may contribute to the overall hyperphagia and obesity in this strain.
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PMID:Altered taste sensitivity in obese, prediabetic OLETF rats lacking CCK-1 receptors. 1608 77

The peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid receptors, which contain a type II zinc finger DNA binding motif and a hydrophobic ligand binding pocket. These receptors are thought to play an important role in metabolic diseases such as obesity, insulin resistance, and coronary artery disease. Three subtypes of PPAR receptors have been described: PPARalpha, PPARdelta/beta, and PPARgamma. PPARalpha is found in the liver, muscle, kidney, and heart. In the liver, its role is to up-regulate genes involved in fatty acid uptake (beta-oxidation and omega-oxidation). PPARdelta/beta is involved in fatty acid oxidation in muscle. PPARgamma has high expression in fat, low expression in the liver, and very low expression in the muscle. The thiazolidinediones (TZD) are synthetic ligands of PPARgamma. By activating a number of genes in tissues, PPARgamma increases glucose and lipid uptake, increases glucose oxidation, decreases free fatty acid concentration, and decreases insulin resistance. There is a sound rationale for the use of TZDs in patients with type 2 diabetes mellitus and promising preliminary data in patients with patients with pre-diabetes. In patients with type 2 diabetes, thiazolidinediones had been shown to decrease mean HbA(1c)by 1.5% and lower HbA(1c) to less than 7% in 30% of patients. Decreased muscle insulin resistance primarily mediates the glucose lowering effect. In addition, there are several nonhypoglycemic effects of TZDs which may be beneficial to both diabetics and patients with pre-diabetes. These include effects on lipid metabolism, blood pressure, endothelial function, atherosclerotic plaque, coagulation, and albuminuria. In a pilot study, we recently demonstrated that insulin sensitizers such as thiazolidinediones appear to be associated with better clinical outcomes compared to insulin providers in diabetic patients presenting with acute coronary syndromes. In another study, we showed that the prediabetic state is a marker for worse prognosis in patients with acute coronary syndromes. In this article, we review the existing literature on the effectiveness of PPAR-gamma agonists in patients with either overt diabetes or a prediabetic state.
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PMID:Role of PPAR- gamma agonist thiazolidinediones in treatment of pre-diabetic and diabetic individuals: a cardiovascular perspective. 1624 30

One hallmark of the insulin-resistant state of prediabetes and overt type 2 diabetes is an impaired ability of insulin to activate glucose transport in skeletal muscle, due to defects in IRS-1-dependent signaling. An emerging body of evidence indicates that one potential factor in the multifactorial etiology of skeletal muscle insulin resistance is oxidative stress, an imbalance between the cellular exposure to an oxidant stress and the cellular antioxidant defenses. Exposure of skeletal muscle to an oxidant stress leads to impaired insulin signaling and subsequently to reduced glucose transport activity. Numerous studies have demonstrated that treatment of insulin-resistant animals and type 2 diabetic humans with antioxidants, including alpha-lipoic acid (ALA), is associated with improvements in skeletal muscle glucose transport activity and whole-body glucose tolerance. An additional intervention that is effective in ameliorating the skeletal muscle insulin resistance of prediabetes and type 2 diabetes is endurance exercise training. Recent investigations have demonstrated that the combination of exercise training and antioxidant treatment using ALA in an animal model of obesity-associated insulin resistance provides a unique interactive effect resulting in a greater improvement in insulin action on skeletal muscle glucose transport than either intervention individually. Moreover, this interactive effect of exercise training and ALA is due in part to improvements in IRS-1-dependent insulin signaling. These studies highlight the effectiveness of combining endurance exercise training and antioxidants in beneficially modulating the molecular defects in insulin action observed in insulin-resistant skeletal muscle.
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PMID:Exercise training and the antioxidant alpha-lipoic acid in the treatment of insulin resistance and type 2 diabetes. 1633 74

Peripheral neuropathy is a common problem encountered by neurologists and primary care physicians. While there are many causes for peripheral neuropathy, none can be identified in a large percentage of patients ("idiopathic neuropathy"). Despite its high prevalence, idiopathic neuropathy is poorly studied and understood. There is evolving evidence that impaired glucose tolerance (prediabetes) is associated with idiopathic neuropathy. Preliminary data from a multicenter study of diet and exercise in prediabetes (the Impaired Glucose Tolerance Neuropathy Study) suggests a diet and exercise counseling regimen based on the Diabetes Prevention Program results in improved metabolic measures and small fiber function. Prediabetes is part of the Metabolic Syndrome, which also includes hypertension, hyperlipidemia and obesity. Individual aspects of the Metabolic Syndrome influence risk and progression of diabetic neuropathy and may play a causative role in neuropathy both for those with prediabetes, and those with otherwise idiopathic neuropathy. Thus, a multifactorial treatment approach to individual components of Metabolic Syndrome may slow prediabetic neuropathy progression or result in improvement.
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PMID:Idiopathic neuropathy, prediabetes and the metabolic syndrome. 1644 68

Low socioeconomic status (SES) is associated with type 2 diabetes. Inflammatory markers like C-reactive protein (CRP) are predictive of diabetes. It is unclear, whether inflammation may be a mechanism linking low SES to type 2 diabetes. In the population-based KORA Survey 2000, 766 men and 710 women aged 55 to 74 years were randomly selected in the Augsburg region (Southern Germany). An index for SES was defined using education, occupation, and income. In women but not in men, increased CRP concentrations were found with lower SES (p<0.01). This significant trend was no longer observed after adjusting for BMI and waist circumference (p=0.23). Low SES was significantly associated with the age-adjusted odds of having type 2 diabetes both in men (OR; 95%CI: 1.35; 1.14-1.60) and in women (2.01; 1.37-2.96). The risk of having diabetes associated with low SES was only slightly changed after adjusting for CRP, which was itself significantly related to diabetes. In multivariate analyses, adjusting for age, obesity, physical activity, smoking, alcohol intake, and CRP, low SES yielded only a borderline statistical significance in women (p=0.07), whereas no significant association with diabetes remained in men (p=0.14). After CRP was dropped from the full model, there was no change in the OR obtained for low SES (men: 1.30; 0.92-1.83; women: 1.54; 0.97-2.45). Low SES was not related to prediabetes (IFG, IGT), whereas CRP was significantly associated with diabetes precursors. In conclusion, inflammation appears not to play a major role linking low SES and type 2 diabetes in the elderly population.
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PMID:Is inflammation a causal chain between low socioeconomic status and type 2 diabetes? Results from the KORA Survey 2000. 1645 Feb 7

The fattening of the human species and the accompanying emergence of the metabolic syndrome and of type 2 diabetes as remarkably frequent clinical entities are among the major epidemiologic events of our time. Control of the diabetes epidemic requires a greater understanding of the pathophysiologic processes underlying these phenomena. Many epidemiologic studies have now shown associations between inflammation markers and diabetes, with the most consistent being for leukocytes and the strongest being for C-reactive protein. Consistent protective associations have also been reported for adiponectin, an adipocyte secretory protein with antiinflammatory actions. Although great variability is seen between reported associations, as a whole these studies suggest a role for inflammation linked to obesity. The variability reported is in part due to differences in model adjustment, in how diabetes was ascertained, and in the different means used to operationalize the concept of low-grade chronic systemic inflammation. It is also due, in part, to sample characterization, as findings are heterogeneous across some subgroups, such as those defined by smoking. Consistent with their association with type 2 diabetes, inflammation markers have also be shown to predict conditions present in the prediabetes state such as weight gain, hypertension, gestational diabetes, and decline in insulin sensitivity.
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PMID:The epidemiology of low-grade chronic systemic inflammation and type 2 diabetes. 1647 45

Type 2 diabetic patients pass through a phase of impaired glucose tolerence and/or impaired fasting glucose known as 'prediabetic state'. Prediabetic state form a part of syndrome X, other components being obesity, hypertension, dyslipidaemia, hyperinsulinaemia and insulin resistance. The pathophysiology of prediabetes is similar to type 2 diabetes mellitus, two basic defects are insulin resistance and early beta cell failure. In prediabetes, the rapid oscillations of insulin secretion are lost and amplitude of large pulses are decreased. When insulin is delivered in a pulsatile fashion that mimics the normal rapid oscillation, its hypoglycaemic effects are greater. In prediabetes, the glycaemic excursions after each meal are high and early insulin responses to meals tend to be lower than normal but the second phase of insulin secretion is delayed and prolonged.
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PMID:Pathophysiology of prediabetes. 1657 Jul 62

Due to global lifestyle changes, obesity (the main driver of type 2 diabetes and cardiovascular disease ) is reaching pandemic proportions. The metabolic syndrome, which is regarded as a prediabetic state, is characterized by a concurrence of interrelated cardiovascular risk factors, including abdominal obesity, insulin resistance, hypertension, dyslipidemia, and glucose intolerance. Endothelial dysfunction (ED) is common in the metabolic syndrome and is associated with increased risk for T2D and CVD. This review focuses on the mechanisms linking ED to the metabolic syndrome, T2D, and CVD, and the possible therapies that may improve ED and reduce T2D and CVD risk.
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PMID:The metabolic syndrome and endothelial dysfunction: common highway to type 2 diabetes and CVD. 1687 79

Stroke and peripheral neuropathy are recognized neurological complications of diabetes. Increasing epidemiological evidence also implicates the prediabetic state of impaired glucose tolerance (IGT) as a risk factor for cerebrovascular events and peripheral neuropathy. Data linking IGT to cognitive decline or deficits, however, are less robust. IGT is one component of metabolic syndrome, together with central obesity, hypertension, hypertriglyceridemia and reduced HDL. Each component of metabolic syndrome is an independent risk factor for stroke, but hyperglycemia might be more important than other components in the pathogenesis of neuropathy. Goal-driven diet and exercise regimens, together with pharmacological treatment of hyperlipidemia and hypertension, reduce stroke risk, but the effect of these interventions on neuropathy has not been fully explored.
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PMID:Therapy insight: neurological complications of prediabetes. 1693 64


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