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

This is a unifying theory that cholesterol metabolites (isoprenoids) are an integral component of the signaling pathway for interleukin-6 (IL-6) mediated inflammation. IL-6 inflammation is the common causative origin for atherosclerosis, peripheral vascular disease, coronary artery disease, and age-related disorders including osteoporosis, dementia, Alzheimer's disease and type 2 diabetes. Therapeutic effects of bisphosphonates and statins are mediated by isoprenoid depletion. Statins and bisphosphonates act in the cholesterol pathway to deplete isoprenoids. Anti-inflammatory properties of statins and bisphosphonates are due to isoprenoid depletion with subsequent inhibition of IL-6 mediated inflammation. Therapeutic targets for the prevention and control of all the above diseases should focus on cholesterol metabolites and IL-6 mediated inflammation. Prevention of atherosclerotic vascular disease and age-related disorders will be by utilization of cholesterol lowering agents or techniques and/or treatment with statins and/or bisphosphonates to inhibit IL-6 inflammation through regulation of cholesterol metabolism.
 ...
PMID:Cholesterol synthesis is the trigger and isoprenoid dependent interleukin-6 mediated inflammation is the common causative factor and therapeutic target for atherosclerotic vascular disease and age-related disorders including osteoporosis and type 2 diabetes. 1593 63

Accumulating evidence exists that regular exercise offers protection against chronic disorders such as cardiovascular diseases, type 2 diabetes, dementia, and depression. Although acute and chronic exercise has numerous consequences, it is still discussed how contracting skeletal muscles mediate metabolic and physiological effects of benefits on health. For years the search for the stimulus that initiates and maintains the change of excitability or sensibility of the regulating centers in exercise has been progressing. For lack of more precise knowledge, it has been called the 'work stimulus,' 'the work factor' or 'the exercise factor.' In other terms, the big challenge for muscle and exercise physiologists has been to determine how muscles signal to central and peripheral organs. Recently, we identified that muscle fibers produce and release the cytokine IL-6 into the circulation during exercise. We further proposed that IL-6 and other cytokines, which are produced and released by skeletal muscles, exerting their effects in other organs of the body, should be named 'myokines.' In line with that adipokines have been suggested as a term, which is restricted to cover cytokines and other peptides which are produced and secreted by adipocytes, we suggest that the term "myokines" should be used exclusively to describe cytokines or other peptides, which are produced and released by muscle fibers per se. Myokines may represent the link from working muscle to other organs such as the adipose tissue, the liver, and the vascular compartments. Here, we review the literature on muscle- and brain-derived IL-6. We further suggest that myokines may also provide an explanation as to how regular muscle activity influences mood, performance, and cognitive function.
 ...
PMID:Muscle-derived interleukin-6--a possible link between skeletal muscle, adipose tissue, liver, and brain. 1593 12

Type 2 diabetes mellitus and higher total plasma homocysteine concentrations are each associated with an increased incidence of cardiovascular disease and with diminished cognitive performance. Relations between homocysteine concentrations and cardiovascular disease incidence are stronger in the presence of type 2 diabetes mellitus. Therefore, we hypothesized that relations between homocysteine concentrations and cognitive performance would be stronger in the presence of type 2 diabetes. We related homocysteine concentrations and cognitive performance on the Mini-Mental State Examination in 817 dementia- and stroke-free participants of the Maine-Syracuse Study, 90 of whom were classified with type 2 diabetes mellitus. Regardless of statistical adjustment for age, sex, gender, vitamin co-factors (folate, vitamin B6, vitamin B12), cardiovascular disease risk factors, and duration and type of treatment for type 2 diabetes mellitus, statistically significant inverse associations between homocysteine concentrations and cognitive performance were observed for diabetic individuals. The weaker inverse associations between homocysteine concentrations and cognitive performance obtained for non-diabetic individuals were not robust to statistical adjustment for some covariates. Interactions between homocysteine concentrations and type 2 diabetes mellitus are observed such that associations between homocysteine and cognitive performance are stronger in the presence of diabetes.
 ...
PMID:Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study. 1619 5

Diabetes mellitus is associated with modest impairments in cognition, particularly in the elderly. In addition, the risk of dementia is increased. We review herein studies in rodent models that may help to identify the mechanisms that underlie these adverse effects of diabetes on the brain. Abnormalities in learning and memory, synaptic plasticity, and glutamatergic neurotransmission have now been identified in a number of these models. In general, observations in models characterized by chronic hyperglycaemia and hypoinsulinaemia (referred to as models of type 1 diabetes) are quite consistent, and these models are being increasingly used to study the pathogenesis and to develop new treatments. However, results from models characterized by insulin resistance, hyperinsulinaemia, and modest hyperglycaemia (referred to as models of type 2 diabetes) are much more variable. Moreover, the possible interaction between diabetes and aging has not been examined in sufficient detail. Because clinically relevant cognitive deficits mainly occur in elderly patients with type 2 diabetes, the challenge for researchers in this field will be to further develop adequate models.
 ...
PMID:The impact of diabetes on cognition: what can be learned from rodent models? 1622 48

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.
 ...
PMID:Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology? 1624 41

Identification of genetic polymorphisms as risk factors for complex diseases affecting older people can be relevant for their prevention, diagnosis and management. The -1131T-->C polymorphism of the apolipoprotein A-V gene (APO A-V) is tightly linked to lipid metabolism and has been associated with increased triglyceride levels and familial dyslipidemia. The aims of this study were to analyze the allele and genotype frequencies of this polymorphism in a Brazilian elderly population and to investigate any association between the polymorphism and major morbidities affecting elderly people. This polymorphism was investigated in 371 individuals, aged 66-97 years, in a Brazilian Elderly Longitudinal Population Study. Major morbidities investigated were: cerebrovascular diseases (CVD); myocardial infarction (MI); type 2 diabetes; hypertension; obesity; dementia; depression; and neoplasia. DNA was isolated and amplified by PCR and its products were digested with restriction enzyme Tru1I. T and C allele frequencies were 0.842 and 0.158, respectively. Our population showed allele frequencies that were similar to European and Afro-American and different from Asiatic populations. Genotype distributions were not within Hardy-Weinberg equilibrium only for the obesity subject sample. On the other hand, a significant association between the C allele and obesity in the presence of CVDxdepression interaction was observed. Logistic analysis showed no association of the polymorphism with each morbidity group. Therefore, the C allele in elderly Brazilian subjects may represent a risk factor for these morbidity interactions, which may lead to better comprehension of their pathophysiology.
 ...
PMID:APO A-V-1131T-->C polymorphism frequency and its association with morbidity in a Brazilian elderly population. 1637 82

Dementia and cognitive decline are among the most common and most feared conditions of old age making the identification of modifiable risk factors for dementia an urgent public health priority. Recently, an increasing body of data suggests that type 2 diabetes mellitus, a common condition in older persons, is associated with the development of dementia and cognitive decline. A systematic review of the medical literature of the past 15 years identified 40 original-report articles in the English language pertaining to the relation of diabetes to dementia and cognitive function in older persons. Most, but not all, of these studies suggest a detrimental effect of diabetes on cognitive function. Current research efforts are aimed at understanding the underlying neurobiologic mechanisms whereby diabetes causes dementia and cognitive impairment in order to develop rational interventions to prevent this recently documented adverse consequence.
 ...
PMID:Diabetes mellitus, dementia, and cognitive function in older persons. 1698 85

Type 2 diabetes is a common metabolic disease with a rising global prevalence. It is associated with slowly progressive end-organ damage in the eyes and kidneys, but also in the brain. The latter complication is often referred to as "diabetic encephalopathy" and is characterized by mild to moderate impairments in cognitive functioning. It is also associated with an increased risk of dementia. To date, its pathogenetic mechanisms are largely unclear. Cognitive impairments in patients with type 2 diabetes have been associated both with vascular risk factors, such as hypertension and dyslipidemia, and with diabetes-related factors, such as glycemic control, duration of the disease and treatment modality. Studies that address these associations generally focus on statistical (in)dependence of certain risk factors in the association between type 2 diabetes and cognitive decline rather than the causality of the association, which, from a mechanistic point of view, is more relevant. In this review we describe the association between type 2 diabetes and cognitive dysfunction and dementia. Furthermore, potential determinants of impaired cognition in type 2 diabetes are addressed both from the perspective of statistical associations and from a mechanistic point of view.
 ...
PMID:Type 2 diabetes, cognitive function and dementia: vascular and metabolic determinants. 1738 Feb 17

Data from 1294 patients with diabetes mellitus admitted to the Endocrinology Department of the Institute of Medical Sciences, Srinagar, Kashmir, from 1986 to 1994, were analyzed for frequency of various neurological problems. Of 1294 patients, 46.29% had clinical evidence of one or more neurological problems. The frequency of neurological problems was significantly more in patients with type II diabetes mellitus (P<0.001). Predominant neurological problems included peripheral neuropathy (96.66%), stroke (5.51%), Parkinsonism (1.50%), seizure disorder (1.17%) and dementia (1%). Mean (+/- SD) age of patients with neurological problems was significantly more (P<0.001) than those without neurological problems (52.07+/- 9.52 versus 47.45+/- 12.87 years for type II diabetes mellitus; 26.73+/- 8.40 versus 18.0+/- 3.62 for type I diabetes mellitus). Mean duration of diabetes in patients with neurological problems was significantly more than those without neurological problems (6.70+/- 6.04 versus 3.95+/- 4.22 years for type II diabetes mellitus; 5.63+/- 3.67 versus 1.89+/- 2.57 for type I diabetes mellitus). At the time of admission, fasting blood glucose was lower in patients without neurological problems as compared to patients with problems (9.08+/- 2.22 versus 11.05+/- 4.91 mmol/L for type II diabetes mellitus; 9.44+/- 2.80 versus 13.01+/- 5.01 mmol/L for type I diabetes mellitus; P7lt;0.001).
 ...
PMID:Profile of neurological problems in diabetes mellitus retrospective analysis of data from 1294 patients. 1737 58

Type 2 diabetes is a common metabolic disease with a rising global prevalence. It is associated with slowly progressive end-organ damage in the eyes and kidneys, but also in the brain. The latter complication is often referred to as "diabetic encephalopathy" and is characterized by mild to moderate impairments in cognitive functioning. It is also associated with an increased risk of dementia. To date, its pathogenetic mechanisms are largely unclear. Cognitive impairments in patients with type 2 diabetes have been associated both with vascular risk factors, such as hypertension and dyslipidemia, and with diabetes-related factors, such as glycemic control, duration of the disease and treatment modality. Studies that address these associations generally focus on statistical (in)dependence of certain risk factors in the association between type 2 diabetes and cognitive decline rather than the causality of the association, which, from a mechanistic point of view, is more relevant. In this review we describe the association between type 2 diabetes and cognitive dysfunction and dementia. Furthermore, potential determinants of impaired cognition in type 2 diabetes are addressed both from the perspective of statistical associations and from a mechanistic point of view.
 ...
PMID:Type 2 diabetes, cognitive function and dementia: vascular and metabolic determinants. 1717 Nov 93


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