Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

11beta-hydroxysteroid dehydrogenase Type 1 (11HSD1) catalyses regeneration of active 11-hydroxy glucocorticoids from inactive 11-keto metabolites within target tissues. Inhibition of 11HSD1 has been proposed as a novel strategy to lower intracellular glucocorticoid concentrations, without affecting circulating glucocorticoid levels and their responsiveness to stress. Increased 11HSD1 activity may be pathogenic, for example, in adipose tissue in obesity. Experiments in transgenic mice and using prototype inhibitors in humans show benefits of 11HSD1 inhibition in liver, adipose and brain tissue in treating features of the metabolic syndrome and cognitive dysfunction with ageing. The clinical development of potent selective 11HSD1 inhibitors is now a high priority.
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PMID:11beta-hydroxysteroid dehydrogenase type 1 as a novel therapeutic target in metabolic and neurodegenerative disease. 1464 Sep 12

Elevated cortisol in a subset of depressed patients is an enduring and well-replicated finding. Much interest has focused on the possible effects of depression on the hippocampus; however, an emerging body of evidence suggests an association between depression and non-central nervous system illnesses. In this review, data on the effects of depression on the brain and other organ systems sensitive to elevated cortisol are discussed. From searches of the MEDLINE, PSYCHINFO, and Current Contents databases, and other sources, articles were found specifically related to depression and physical changes or medical conditions associated with corticosteroid excess in patients with Cushing's disease, including cognitive impairment, hippocampal atrophy, increased waist-to-hip ratio, bone loss, hypertension, diabetes, peptic ulcers, and hyperlipidemia. Data are strongest for a relationship between elevated cortisol and depression, hippocampal atrophy, cognitive impairment, abdominal obesity, and loss of bone density. Some evidence suggests an association between depression and hypertension, peptic ulcers, and diabetes. Depression does not appear to be associated with hyperlipidemia. The data provide some support for similar health effects in depressed patients and patients with Cushing's disease or the metabolic syndrome; however, additional studies are needed relating systemic effects of depression to cortisol. Limitations of the current literature, treatment implications, and possible directions for future research are discussed.
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PMID:Association of depression with medical illness: does cortisol play a role? 1470 19

1. It has been suggested that hypertension, hyperlipidaemia and diabetes participate in the onset and development of dementia. 2. To understand cognitive dysfunction in metabolic syndrome, the relationship between the plasma and the hippocampus regarding fatty acid composition and lipid peroxidation was estimated in genetically hypertensive and obese SHR/NDmcr-cp rats (SHR-cp) aged 7-9 and 18-20 weeks. 3. Levels of total fatty acids and lipid peroxide in the plasma were much higher (by 200-500%) in SHR-cp compared with age-matched control rats (Wistar-Kyoto rats). However, in the hippocampus these levels were not significantly different between the two groups of rats. 4. Levels of hippocampal lipid peroxide in both groups increased significantly with ageing. 5. These results indicate that, in SHR-cp, lipid peroxidation in the hippocampus would not be affected even if plasma levels of fatty acids and lipid peroxide increased markedly, when ageing is not a predicative factor.
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PMID:Relationship between plasma and hippocampal lipid peroxidation in obese and hypertensive SHR/NDmcr-cp rats. 1564 93

While considerable research has examined diminished insulin responses within peripheral tissues, comparatively little has been done to examine the effects of this metabolic disruption upon the CNS. The present study employed biochemical and electrophysiological assays of acutely prepared brain slices to determine whether neural insulin resistance is a component of the metabolic syndrome observed within the fructose-fed (FF) hamster. The tyrosine phosphorylation levels of the insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) in response to insulin were significantly reduced within FF hamsters. Also, insulin-mediated phosphorylation of both residues necessary for activation of the serine-threonine kinase Akt/PKB, a key effector of insulin signaling, was markedly decreased. Elevated levels of the protein tyrosine phosphatase 1B, which dephosphorylates the IR and IRS-1, were also observed within the cerebral cortex and hippocampus of FF hamsters. Examination of whether a nutritionally induced compromise of neural insulin signaling altered synaptic function revealed a significant attenuation of insulin-induced long-term depression, but no effect upon either paired-pulse facilitation or electrically induced long-term potentiation. Collectively, our results demonstrate, for the first time, that nutritionally induced insulin resistance significantly affects the neural insulin signaling pathway, and suggest that brain insulin resistance may contribute to cognitive impairment.
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PMID:A biochemical and functional characterization of diet-induced brain insulin resistance. 1593 73

Type II diabetes mellitus (DM2) is associated with an increased risk of cognitive dysfunction and dementia. The increased risk of dementia concerns both Alzheimer's disease and vascular dementia. Although some uncertainty remains into the exact pathogenesis, several mechanisms through which DM2 may affect the brain have now been identified. First, factors related to the 'metabolic syndrome', a cluster of metabolic and vascular risk factors (e.g. dyslipidaemia and hypertension) that is closely linked to DM2, may be involved. A number of these risk factors are predictors of cerebrovascular disease, accelerated cognitive decline and dementia. Secondly, hyperglycaemia may be involved, through adverse effects of potentially 'toxic' glucose metabolites on the brain and its vasculature. Thirdly, insulin itself may be involved. Insulin can directly modulate synaptic plasticity and learning and memory, and disturbances in insulin signalling pathways in the periphery and in the brain have recently been implicated in Alzheimer's disease and brain aging. Insulin also regulates the metabolism of beta-amyloid and tau, the building blocks of amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease. In this paper, the evidence for the association between DM2 and dementia and for each of these underlying mechanisms will be reviewed, with emphasis on the role of insulin itself.
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PMID:Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology? 1624 41

The Mediterranean Diet has been associated with greater longevity and quality of life in epidemiological studies, the majority being observational. The application of evidence-based medicine to the area of public health nutrition involves the necessity of developing clinical trials and systematic reviews to develop sound recommendations. The purpose of this study was to analyze and review the experimental studies on Mediterranean diet and disease prevention. A systematic review was made and a total of 43 articles corresponding to 35 different experimental studies were selected. Results were analyzed for the effects of the Mediterranean diet on lipoproteins, endothelial resistance, diabetes and antioxidative capacity, cardiovascular diseases, arthritis, cancer, body composition, and psychological function. The Mediterranean diet showed favorable effects on lipoprotein levels, endothelium vasodilatation, insulin resistance, metabolic syndrome, antioxidant capacity, myocardial and cardiovascular mortality, and cancer incidence in obese patients and in those with previous myocardial infarction. Results disclose the mechanisms of the Mediterranean diet in disease prevention, particularly in cardiovascular disease secondary prevention, but also emphasize the need to undertake experimental research and systematic reviews in the areas of primary prevention of cardiovascular disease, hypertension, diabetes, obesity, infectious diseases, age-related cognitive impairment, and cancer, among others. Interventions should use food scores or patterns to ascertain adherence to the Mediterranean diet. Further experimental research is needed to corroborate the benefits of the Mediterranean diet and the underlying mechanisms, and in this sense the methodology of the ongoing PREDIMED study is explained.
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PMID:Scientific evidence of interventions using the Mediterranean diet: a systematic review. 1653 97

High fat diets and sedentary lifestyles are becoming major concerns for Western countries. They have led to a growing incidence of obesity, dyslipidemia, high blood pressure, and a condition known as the insulin-resistance syndrome or metabolic syndrome. These health conditions are well known to develop along with, or be precursors to atherosclerosis, cardiovascular disease, and diabetes. Recent studies have found that most of these disorders can also be linked to an increased risk of Alzheimer's disease (AD). To complicate matters, possession of one or more apolipoprotein E epsilon4 (APOE epsilon4) alleles further increases the risk or severity of many of these conditions, including AD. ApoE has roles in cholesterol metabolism and Abeta clearance, both of which are thought to be significant in AD pathogenesis. The apparent inadequacies of ApoE epsilon4 in these roles may explain the increased risk of AD in subjects carrying one or more APOE epsilon4 alleles. This review describes some of the physiological and biochemical changes that the above conditions cause, and how they are related to the risk of AD. A diversity of topics is covered, including cholesterol metabolism, glucose regulation, diabetes, insulin, ApoE function, amyloid precursor protein metabolism, and in particular their relevance to AD. It can be seen that abnormal lipid, cholesterol and glucose metabolism are consistently indicated as central in the pathophysiology, and possibly the pathogenesis of AD. As diagnosis of mild cognitive impairment and early AD are becoming more reliable, and as evidence is accumulating that health conditions such as diabetes, obesity, and coronary artery disease are risk factors for AD, appropriate changes to diets and lifestyles will likely reduce AD risk, and also improve the prognosis for people already suffering from such conditions.
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PMID:Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease. 1678 33

Bardet-Biedl syndrome (BBS) is a rare developmental disorder with the cardinal features of abdominal obesity, retinopathy, polydactyly, cognitive impairment, renal and cardiac anomalies, hypertension, and diabetes. BBS is genetically heterogeneous, with nine genes identified to date and evidence for additional loci. In this study, we performed mutation analysis of the coding and conserved regions of BBS1, BBS2, BBS4, and BBS6 in 48 French Caucasian individuals. Among the 36 variants identified, 12 were selected and genotyped in 1,943 French-Caucasian case subjects and 1,299 French-Caucasian nonobese nondiabetic control subjects. Variants in BBS2, BBS4, and BBS6 showed evidence of association with common obesity in an age-dependent manner, the BBS2 single nucleotide polymorphism (SNP) being associated with common adult obesity (P = 0.0005) and the BBS4 and BBS6 SNPs being associated with common early-onset childhood obesity (P = 0.0003) and common adult morbid obesity (0.0003 < P < 0.007). The association of the BBS4 rs7178130 variant was found to be supported by transmission disequilibrium testing (P = 0.006). The BBS6 variants also showed nominal evidence of association with quantitative components of the metabolic syndrome (e.g., dyslipidemia, hyperglycemia), a complication previously described in BBS patients. In summary, our preliminary data suggest that variations at BBS genes are associated with risk of common obesity.
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PMID:Bardet-Biedl syndrome gene variants are associated with both childhood and adult common obesity in French Caucasians. 1700 56

Over 33% of women and 20% of men aged 65 and older will develop dementia during their lifetime, and many more will develop a milder form of cognitive impairment. Given the anticipated exponential increase in both the incidence and prevalence of cognitive impairment in the next century, it is critical to identify preventative strategies to thwart this critical public health issue. The metabolic syndrome is comprised of five cardiovascular risk factors that include abdominal obesity, hypertriglyceridemia, low high density lipoprotein (HDL) levels, hypertension, and hyperglycemia. The prevalence of the metabolic syndrome, similar to that for cognitive disorders, increases dramatically with age. While several of the individual components of the metabolic syndrome have been linked to risk of developing dementia and cognitive impairment, few studies have looked at the components of the metabolic syndrome as a whole. We found, in two separate studies involving elders of different ethnicities, that the metabolic syndrome is a risk factor for accelerated cognitive aging. This was especially true for elders with the metabolic syndrome and with elevated serum level of inflammation. Several possible mechanisms may explain the association between the metabolic syndrome and cognitive decline including micro- and macro-vascular disease, inflammation, adiposity and insulin resistance. If metabolic syndrome is associated with increased risk of developing cognitive impairment, regardless of mechanism, then early identification and treatment of these individuals might offer avenues for disease course modification.
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PMID:Metabolic syndrome and cognitive decline. 1743 Feb 34

Diabetes mellitus as well as psychiatric disorders are common. These may occur with one another and/or one may worsen the other. Psychological stress may follow screening for diabetes, as well as when diabetes is first identified. Acting through the hypothalamo-pituitary-adrenal axis, stress may initiate or worsen hyperglycaemia. Depression may be a risk factor for the development of diabetes; it also commonly occurs in subjects with diabetes. Identification and management are both important in preventing the disability. A variety of antipsychotic medications, especially the newer agents can induce weight gain, dyslipidaemia, insulin resistance and diabetes. Therefore in choosing a drug, one must consider the risk factors and screen for metabolic syndrome. Subjects with type 1 diabetes can have cognitive dysfunction, eating disorders and developmental disturbances. Physicians caring for people with diabetes must be trained to recognize and manage co-morbid psychiatric conditions that commonly occur. A biopsychosocial disease model for both conditions can leverage the social strengths and medical knowledge in developing countries.
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PMID:Psychiatric co-morbidity & diabetes. 1749 58


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