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

Central obesity is increasingly recognized as a risk factor for atherosclerosis and type 2 diabetes mellitus. Here we present a hypothesis that may explain the excess atherosclerosis, endothelial dysfunction and progressive beta-cell failure. Central obesity is associated with increased cytosolic triglyceride stores in non-adipose tissues such as muscles, liver and pancreatic beta-cells. A high cytosolic triglyceride content is accompanied by elevated concentrations of cytosolic long-chain acyl-CoA esters, the metabolically active form of fatty acids. These esters inhibit mitochondrial adenine nucleotide translocators, resulting in an intramitochondrial ADP deficiency. In vitro, such ADP deficiency is a potent stimulator of mitochondrial oxygen free radical production, and we assume that this mechanism is also active in vivo. The decline of organ function with normal ageing is thought to be due, at least partly, to a continuous low-grade mitochondrial oxygen free radical production. In tissues containing increased cytosolic triglyceride stores this process will be accelerated. Tissues with a high-energy demand or poor free radical scavenging capacity, such as pancreatic beta-cells, are likely to be more susceptible to this process. This is how we explain their gradual dysfunctioning in central obesity. Likewise we propose that the enhanced production of oxygen free radicals in endothelial cells, or vascular smooth muscle cells, leads to the increased subendothelial oxidation of LDL and atherosclerosis, as well as to the endothelial dysfunction and microalbuminuria.
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PMID:Cytosolic triglycerides and oxidative stress in central obesity: the missing link between excessive atherosclerosis, endothelial dysfunction, and beta-cell failure? 1058 Jan 66

To study the contributions of body mass, body fat distribution and family history of type 2 diabetes mellitus to hyperinsulinaemia, insulin secretion and resistance in polycystic ovarian syndrome (PCOS), 17 lean (LC) and 17 obese (OC) healthy control subjects, and 15 lean (LPCOS) and 28 obese (OPCOS) women with PCOS were investigated. Waist:hip ratio (WHR), serum concentrations of sex steroids, glucose and insulin during a 75 g oral glucose tolerance test (OGTT), and insulin and C-peptide early phase secretion, and insulin sensitivity index using a euglycaemic hyperinsulinaemic clamp were assessed. The PCOS subjects had a higher mean WHR than the controls. A trend towards hyperinsulinaemia and impairment of insulin sensitivity (including the rates of both glucose oxidation and non-oxidation) was observed in LPCOS subjects, but only in OPCOS subjects were these changes significant. Early phase insulin secretion but not the early phase C-peptide secretion was increased in PCOS subjects compared to controls, suggesting that peripheral hyperinsulinaemia in PCOS women was mainly due to the observed lowered hepatic insulin extraction and insulin resistance in skeletal muscle. Moreover, the presence of a family history of type 2 diabetes did not affect early phase insulin or C-peptide secretion in the PCOS group. These results confirm and strengthen earlier contentions, that insulin resistance is a characteristic defect in PCOS and is worsened particularly by abdominal obesity.
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PMID:Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovarian syndrome. 1083 53

To determine whether fasting glucose/insulin (FG/I) ratio and insulin levels 2 h after 75-g oral load of glucose (IL-2 h PG) are predictors for type 2 diabetes mellitus, a comparative 2 year follow-up study was conducted. Ninety-six healthy subjects 30 years of age or older, randomly selected from the general population of Durango, Mexico were included in two groups: 1) risk group: members had both baseline FG/I ratio and IL 2-h PG within the lower and upper quartile, respectively, and 2) control group, whose members had baseline FG/I ratio and IL 2-h PG within the second and third quartiles, respectively. Multivariate logistic regression was used to compute the relative risk for the development of type 2 diabetes. The family history of diabetes (RR 10.1; IC95% 2.7-15.8, p < 0.01), glucose intolerance (RR 9.8; IC95% 1.7-13.4, p < 0.01), abdominal obesity (RR 6.1; IC95% 1.5-10.1, p < 0.01), and the low FG/I ratio and high IL 2-h PG (RR 3.3; IC95% 1.4-8.2, p < 0.05) were strong predictors for type 2 diabetes. Critical values for predicting criteria of FG/I ratio and IL 2-h PG were of 4.0 y 180 microUI/ml, respectively. In conclusion, the measurement of FG/I ratio and IL 2-h PG is an accurate indicator for estimating the risk of developing type 2 diabetes.
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PMID:[Fasting glucose/insulin index and insulin levels 2-h after glucose load are predictors of the development of type 2 diabetes]. 1089 48

Older obese postmenopausal women have an increased risk for type 2 diabetes and cardiovascular disease. Increased abdominal obesity may contribute to these comorbidities. There is considerable controversy, however, regarding the effects of visceral adipose tissue as a singular predictor of insulin resistance compared to the other constituents of adiposity. To address this issue, we examined the independent association of regional adiposity and total fat mass with glucose disposal in obese older postmenopausal women. A secondary objective examined the association between glucose disposal with markers of skeletal muscle fat content (muscle attenuation) and physical activity levels. We studied 44 healthy obese postmenopausal women between 50 and 71 yr of age (mean +/- SD, 56.5 +/- 5.3 yr). The rate of glucose disposal was measured using the euglycemic/hyperinsulinemic clamp technique. Visceral and sc adipose tissue areas and midthigh muscle attenuation were measured from computed tomography. Fat mass and lean body mass were estimated from dual energy x-ray absorptiometry. Peak VO2 was measured from a treadmill test to volitional fatigue. Physical activity energy expenditure was measured from indirect calorimetry and doubly labeled water. Pearson correlations indicated that glucose disposal was inversely related to visceral adipose tissue area (r = -0.40; P < 0.01), but not to sc adipose tissue area (r = 0.17), total fat mass (r = 0.05), midthigh muscle attenuation (r = 0.01), peak VO2 (r = -0.22), or physical activity energy expenditure (r = -0.01). The significant association persisted after adjusting visceral adipose tissue for fat mass and abdominal sc adipose tissue levels (r = -0.45; P < 0.005; in both cases). Additional analyses matched two groups of women for fat mass, but with different visceral adipose tissue levels. Results showed that obese women with high visceral adipose tissue levels (283 +/- 59 vs. 137 +/- 24 cm2; P < 0.0001) had a lower glucose disposal per kg lean body mass compared to those with low visceral adipose tissue levels (0.44 +/- 0.14 vs. 0.66 +/- 0.28 mmol/kg x min; P < 0.05). Visceral adipose tissue is an important and independent predictor of glucose disposal, whereas markers of skeletal muscle fat content or physical activity exhibit little association in obese postmenopausal women.
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PMID:Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women. 1090 82

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of type 2 diabetes, characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and its related complications, we used representational difference analysis and identified the genes more abundantly and specifically expressed in the visceral adipose tissue (VAT) of obese OLETF rats compared with the diabetes-resistant counterpart, that is, Long-Evans Tokushima Otsuka (LETO) rats. By Northern blot analysis, we confirmed the differential expression of 13 genes, including 3 novel genes. The upregulated expression of well-characterized lipid metabolic enzymes, such as lipoprotein lipase, phosphoenolpyruvate carboxykinase, and cholesterol esterase, were observed in VAT of OLETF rats. We demonstrated the differential expression of secreted proteins in VAT of OLETF rats, such as thrombospondin 1 and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the secreted proteins revealed exclusive mRNA expression and they were not detected in VAT of LETO rats. Furthermore, the novel genes OL-16 and OL-64 were also expressed specifically in VAT of OLETF rats and were absent in that of LETO rats and other tissues, including subdermal and brown adipose tissues. The C-terminal partial amino acid sequence of OL-64 revealed that it showed approximately 40% homology with alpha(1)-antitrypsin and it seemed to be a new member of the serine proteinase inhibitor (SERPIN) gene family. VAT of OLEFT rats had a unique gene expression profile, and the accumulated VAT-specific known and novel secreted proteins may play a role(s) in the pathogenesis of obesity and its related complications.
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PMID:Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats. 1101 3

New-onset diabetes mellitus, clinically similar to type 2 diabetes, will affect a small proportion (1%-6%) of patients infected with human immunodeficiency virus (HIV) who are treated with HIV-1 protease inhibitors (PIs). However, insulin resistance and impaired glucose tolerance will develop during PI treatment in a considerable proportion of patients. Dyslipidemia, abdominal obesity, and loss of peripheral fat frequently coexist with insulin resistance, but it is not clear whether all of these result from a common pathogenic mechanism. Recent data suggest that insulin resistance may also be associated with HIV infection in patients not receiving PI therapy. The long-term consequences of insulin resistance in this population are not known. The effect of switching to other antiretroviral therapies has not been fully determined. Treatment of established diabetes mellitus should generally follow existing guidelines. There is no clinically useful screening test that will determine the existence and degree of insulin resistance in individual patients. It is therefore reasonable to recommend general measures to increase insulin sensitivity in all patients infected with HIV, such as weight reduction for obese persons and regular aerobic exercise.
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PMID:Disorders of glucose metabolism in patients infected with human immunodeficiency virus. 1109 14

Type 2 diabetes is a heterogeneous condition that is not attributable to a single pathophysiological mechanism. In general, both insulin resistance and impaired insulin secretion are required for the disease to become manifest. Thus, as long as the pancreatic beta cells can compensate for the degree of insulin resistance, glucose tolerance remains normal. Clustering of type 2 diabetes in certain families and ethnic populations points to a strong genetic background for the disease. However, environmental factors such as obesity and a sedentary lifestyle are usually required to unmask the genes. Impaired insulin-stimulated glucose metabolism (particularly non-oxidative) in skeletal muscle represents a key feature of type 2 diabetes and is observed early in the pre-diabetic state. It is not clear, though, whether this represents an inherited defect in muscle or whether it develops secondarily, for example, to abdominal obesity. In favour of the latter hypothesis are findings that abdominal obesity and a low metabolic rate seem to precede the development of insulin resistance in offspring of type 2 diabetic patients. According to the thrifty gene hypothesis, individuals living in an environment with an unstable food supply could increase their probability of survival if they could maximize storage of surplus energy, for instance, as abdominal fat. Exposing this energy-storing genotype to the abundance of food typical of westernized societies is detrimental, causing insulin resistance and, subsequently, type 2 diabetes. There are a number of potential thrifty genes, including those that regulate lipolysis or code for the beta3-adrenergic receptor, the hormone-sensitive lipase, and lipoprotein lipase. Type 2 diabetes develops as a consequence of a collision between thrifty genes and a hostile affluent environment. Insulin resistance is a key trigger for the disease, and optimal management of type 2 diabetes should therefore aim to ameliorate insulin resistance early.
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PMID:Insulin resistance: the fundamental trigger of type 2 diabetes. 1122 Feb 83

Obesity is commonly cited as a risk factor for the development of coronary heart disease (CHD). Epidemiologic studies tend to support this contention, particularly those focusing on patients with central obesity. Such studies however, are imprecise and prone to misclassification bias. Angiographic and post mortem studies have demonstrated little or no correlation of total fat mass and coronary atherosclerosis except in those with abdominal obesity. There is a strong association of obesity, particularly central obesity, and traditional risk factors for CHD such as hypertension, type II diabetes mellitus, and dyslipidemia. There may also be an association between obesity and several nontraditional risk factors such as hyperhomocystinemia, elevated Lp(a) levels and factors that increase thrombogenesis. Obesity may also alter endothelial function. Weight loss, although associated with favorable modification of multiple risk factors for CHD, has not been shown to independently and definitively reduce CHD risk.
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PMID:Obesity and coronary heart disease. 1130 63

Stroke is a major cause of morbidity and mortality. Risk factors for stroke have been determined through prospective epidemiologic study. Control of risk factors has been demonstrated to reduce stroke incidence, either through controlled trials or inferred from observational studies. In the past few years, new approaches to the treatment of established risk factors have been discovered. These include aggressive control of hypertension in diabetes patients, prevention of type 2 diabetes through lifestyle modification, carotid endarterectomy for moderate symptomatic carotid stenosis, encouragement of a high level of physical activity, and control of abdominal obesity and elevated body mass index. In addition, new strategies for stroke prevention have been identified, including encouragement of a diet high in fruits, vegetables, whole grains, and omega-3 fatty acids, the use of vitamins B12, B6, and folic acid in hyperhomocysteinemia, and moderate alcohol consumption. Clinical trial data support the use of hydroxy-methyl-coenzyme A inhibitors in patients with coronary artery disease, and ramipril in high-risk patients with coronary artery disease and diabetes, for the primary prevention of stroke. New risk factors for stroke are being investigated, including the role of chronic inflammation and infection, and these may provide future strategies for stroke prevention.
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PMID:Prevention of strokes. 1138 98

The first unifying definition for the metabolic syndrome was proposed by WHO in 1998. In accordance to this, patients with type 2 diabetes mellitus or impaired glucose tolerance have the syndrome if they fulfil two of the criteria: hypertension, dyslipidaemia, obesity/abdominal obesity and microalbuminuria. Persons with normal glucose tolerance (NGT) should also be insulin resistant. About 40% of persons with impaired glucose tolerance (IGT) and 70% of patients with type 2 diabetes have features of the syndrome. Importantly, presence of the dysmetabolic syndrome is associated with reduced survival, particularly because of increased cardiovascular mortality. The dysmetabolic syndrome most likely results from interplay between several genes and an affluent environment. Compatible with the thrifty gene theory, common variants in genes regulating lipolysis, thermogenesis and glucose uptake in skeletal muscle account for a large part of such thrifty genes. However, hitherto unknown genes may still be identified by random gene approaches.
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PMID:The dysmetabolic syndrome. 1148 60


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