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

Cardiovascular disease is often present in patients with newly diagnosed type 2 diabetes. It is hypothesized that both type 2 diabetes and cardiovascular disease arise from an underlying insulin resistance syndrome, including impaired glucose tolerance, hypertension, dyslipidemia, and abdominal obesity. We reviewed the literature using various epidemiologic techniques to evaluate the relation between the insulin resistance syndrome components and incident cardiovascular disease. We found that although insulin resistance is likely important in the development of cardiovascular disease seen in diabetes, lipid and blood pressure abnormalities associated with the syndrome appear to be equally important. Future studies are needed to determine the most effective treatment strategies for preventing cardiovascular disease associated with the insulin resistance syndrome and type 2 diabetes.
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PMID:Are there specific components of the insulin resistance syndrome that predict the increased atherosclerosis seen in type 2 diabetes mellitus? 1476 76

Caloric restriction in animal models delays many age-related pathological conditions. Ageing rats have characteristically increased body weight, fat mass and a specific body fat distribution. This report will focus on the potential cause-effect relationship between increased fat mass and accelerated ageing. In humans, increased fat mass (obesity), and in particular increases in abdominal obesity as a result of deposition of visceral fat, are associated with the metabolic syndrome of ageing. This syndrome is associated with hyperinsulinaemia, dyslipidaemia, type 2 diabetes mellitus, atherosclerosis, hypercoagulability and hypertension. Fat tissue, however, plays a major role by secreting multiple metabolically active factors, which are potentially responsible for the development of insulin resistance. This article will review various experimental models (in animals) used to prevent insulin resistance of ageing by decreasing fat mass, and in particular, decreasing visceral fat. We suggest that this decrease in fat mass and its beneficial repercussions observed in ageing animal models may apply also to human ageing and its related pathology.
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PMID:Caloric restriction, body fat and ageing in experimental models. 1496 3

Abdominal obesity and insulin resistance are central findings in metabolic syndrome. Since treatment with recombinant human growth hormone (rhGH) can reduce body fat mass in patients with organic GH deficiency, rhGH therapy may also have favourable effects on patients with metabolic syndrome. However, due to the highly increased risk for type 2 diabetes in these patients, strategies are needed to reduce the antagonistic effect of rhGH against insulin. We conducted a 18-month randomised, double-blind, placebo-controlled study to assess the effect of rhGH in combination with metformin (Met) in patients with metabolic syndrome. 25 obese men (55 +/- 6 years, BMI 33.4 +/- 2.9 kg/m (2)) with mildly elevated fasting plasma glucose (FPG) levels at screening (6.1-8.0 mmol/l) were included. All patients received metformin (850 mg twice daily) either alone or in combination with rhGH (daily dose 9.5 microg/kg body weight). An oGTT was performed at baseline, after 6 weeks, and after 3, 6, 12, and 18 months of therapy. Glucose disposal rate (GDR) was measured by euglycemic hyperinsulinemic clamp at 0 and 18 months and body composition was measured by DEXA every 6 months. In the Met + GH group, IGF-I increased from 146 +/- 56 microg/l to 373 +/- 111 microg/l (mean +/- SD) after 3 months and remained stable after that. BMI did not change significantly in either group during the study. Total body fat decreased by -4.3 +/- 5.4 kg in the Met + GH group and by -2.7 +/- 2.9 kg in the Met + Placebo group (differences between the two groups: p = n. s.). Waist circumference decreased in both groups (Met + GH: 118 +/- 8 cm at baseline, 112 +/- 10 cm after 18 months; Met + Placebo: 114 +/- 7 cm vs. 109 +/- 8 cm; differences between the two groups: p = 0.096). In the Met + GH group, FPG increased significantly after 6 months (5.9 +/- 0.7 vs. 6.7 +/- 0.4 mmol/l; p = 0.005), but subsequently decreased to baseline levels (18 months: 5.8 +/- 0.2 mmol/l). FPG remained stable in the Met + Placebo group until 12 months had elapsed, and then slightly decreased (baseline: 6.2 +/- 0.3, 18 months: 5.5 +/- 0.6 mmol/l, p = 0.02). No significant changes were seen in either group regarding glucose and insulin AUC during oGTT or HbA (1c) levels. GDR at 18 months increased by 20 +/- 39% in Met + GH-group and decreased by -11 +/- 25% in the Met + Placebo group (differences between the two groups: p = 0.07). In conclusion, treatment of patients with metabolic syndrome and elevated FPG levels did not cause sustained negative effects on glucose metabolism or insulin sensitivity if given in combination with metformin. However, since our data did not show significant differences between the two treatment groups with respect to body composition or lipid metabolism, future studies including larger numbers of patients will have to clarify whether the positive effects of rhGH on cardiovascular risk factors that have been shown in patients with GH deficiency are also present in patients with metabolic syndrome, and are additive to the effects of metformin.
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PMID:Effects of a combination of recombinant human growth hormone with metformin on glucose metabolism and body composition in patients with metabolic syndrome. 1498 8

Metabolic syndrome is defined as a clustering of cardiovascular risk factors (abdominal obesity, hyperinsulinemia, atherogenic dyslipidemia, hypertension and hypercoagulability) that together increase the risk of developing coronary heart disease and type 2 diabetes. Inhibition of acetyl-CoA carboxylase (ACC), which results in inhibition of fatty acid synthesis and stimulation of fatty acid oxidation, has the potential to favorably affect a multitude of cardiovascular risk factors associated with metabolic syndrome. ACC exists as two tissue-specific isozymes, ACC1 present in lipogenic tissues (liver and adipose) and ACC2 present in oxidative tissues (liver, heart and skeletal muscle). Studies in both ACC2 knockout mice and animals administered isozyme-nonselective ACC inhibitors have demonstrated the utility of treating metabolic syndrome through this modality. An isozyme-non-selective ACC inhibitor may potentially provide the optimal therapeutic for beneficially affecting metabolic syndrome. However, demonstration of the full potential of isozyme-selective inhibitors, once identified, should reveal advantages and liabilities associated with single isozyme inhibition. While demonstrating clinical efficacy of an ACC inhibitor should be relatively straightforward, the heterogeneity of the patient population and the absence of established guidelines regarding approval endpoints for agents simultaneously affecting multiple aspects of metabolic syndrome will pose developmental challenges for initial market entries.
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PMID:Acetyl-CoA carboxylase inhibition for the treatment of metabolic syndrome. 1508 94

The prevalence of the polycystic ovaries syndrome (PCOS) is high but it is a heterogeneous disorder with implications in numerous medical domains. Abdominal obesity and insulin resistance, which are the main metabolic disorders, are strong links between hormonal abnormalities and long-term medical consequences. The latter begin to be better understood. Some studies suggest that PCOS may increase the risk for several conditions, including type 2 diabetes, dyslipidemia, hypertension, cardiovascular disease and some cancers.
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PMID:[Long-term risks of polycystic ovaries syndrome]. 1512 16

Alstrom syndrome (ALMS) is a very rare genetic autosomal recessive disease, characterized by early-onset severe abdominal obesity, impaired glucose tolerance or type 2 diabetes with insulin resistance, acanthosis nigricans, hyperlipidemia, childhood progressive retinal degeneration or retinitis pigmentosa and neurosensory hearing loss or deafness, cardiomyopathy, and other endocrine disorders. Genetic studies locate the ALMS gene on chromosome 2p12-13. The aim of this paper is to describe and discuss two unrelated cases of a mild ALMS form diagnosed after the age of 40 and 60, respectively, in adult fertile female patients. These cases showed several features of the disease plus other alterations characteristic of the classic "metabolic syndrome," including hypertension, hyperfibrinogenemia, and thrombotic states. Moreover, the patients had very high fasting serum free fatty acid (FFA) levels (2150 and 1919 micromol/L, respectively), which proved to be sensitive to inhibition by oral glucose tolerance test (OGTT)-induced hyperinsulinemia as well as to caloric restriction. ALMS may have an adverse prognosis and is often underdiagnosed. Its mild form, which allows a long survival, may also be associated with the late complications of the metabolic syndrome, leading to increased vascular risk.
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PMID:A mild form of Alstrom disease associated with metabolic syndrome and very high fasting serum free fatty acids: two cases diagnosed in adult age. 1516 53

Metabolic syndrome is a term linking the clinical profiles of some of the world's major health problems today: obesity, heart disease, and diabetes. It is predicated on dietary patterns, and particularly on the delivery of fuel. The effects may be seen first in the development of abdominal obesity and insulin resistance leading to Type 2 diabetes mellitus and coronary heart disease. This review examines the role resistant starch might play in the prevention and management of these conditions. Beginning with a definition of resistant starch, a critical review of the scientific literature is presented. Current knowledge suggests that resistant starch in the diet may assist in the prevention and management of conditions associated with the metabolic syndrome via its potential effects on delaying the delivery of glucose as fuel with subsequent fat utilization and appetite control benefits. There is still a great deal of research to be undertaken in this area, but it is clearly warranted, given the position of starches in the global food supply and the potential impact on population health.
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PMID:Diet and metabolic syndrome: where does resistant starch fit in? 1528 76

The present article addresses the hypothesis that disturbances in skeletal muscle fatty acid handling in abdominal obesity and type 2 diabetes mellitus may play a role in the aetiology of increased adipose tissue stores, increased triacylglycerol storage in skeletal muscle and skeletal muscle insulin resistance. The uptake and/or oxidation of fatty acids have been shown to be impaired during post-absorptive conditions in abdominally-obese subjects and/or subjects with type 2 diabetes. Also, human studies have shown that muscle of subjects that are (abdominally) obese and/or have type 2 diabetes is characterized by an inability to increase fatty acid uptake and/or fatty acid oxidation during beta-adrenergic stimulation and exercise. This disturbance in fat oxidation may promote, on one hand, the development of increased adipose tissue stores and obesity. On the other hand, fatty acids that are taken up by muscle and not oxidized may increase triacylglycerol storage in muscle, which has been associated with skeletal-muscle insulin resistance. Disturbances in the capacity to increase fat oxidation during post-absorptive conditions, beta-adrenergic stimulation and exercise in subjects who are obese and/or have type 2 diabetes persist after weight reduction, indicating that the diminished fat oxidation may be a primary factor leading to the obese and/or insulin-resistant state rather than an adaptational response. Clearly, the precise sequence of events leading to an increased adiposity and insulin resistance in obesity and type 2 diabetes mellitus is not yet fully understood.
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PMID:Basic disturbances in skeletal muscle fatty acid metabolism in obesity and type 2 diabetes mellitus. 1529 50

High-sensitivity C-reactive protein (hs-CRP) levels are closely associated with adiposity and predict coronary heart disease and type 2 diabetes mellitus. However, relationships of CRP to adiponectin and other markers of insulin resistance have been inadequately researched in children. We measured fasting serum levels of adiponectin, insulin, hs-CRP, and lipoproteins, and recorded the anthropometric profile and percentage of body fat (%BF; bioimpedance method) in 62 (36 normal weight, 26 overweight) healthy, urban, postpubertal Asian Indian males (aged 14 to 18 years). Serum levels of adiponectin were lower (P = not significant [NS]), whereas those of fasting insulin (P = .01) and hs-CRP (P = .02) were higher in overweight subjects. Adiponectin levels inversely correlated with body mass index (BMI; r = -0.26, P < .05), %BF (r = -0.24, P < .05), fasting insulin (r = -0.32, P < .05) and insulin resistance measured by the homeostasis model of assessment (HOMA-IR; r = -0.31, P < .05), but not with hs-CRP levels. Fasting insulin and hs-CRP levels correlated significantly with BMI, %BF, waist circumference (WC), waist-to-hip circumference ratio (W-HR), and triceps and subscapular skinfold thickness. The correlation of adiponectin with insulin sensitivity was independent of abdominal obesity, but became nonsignificant after controlling for BMI and %BF. Further, BMI was an independent predictor of adiponectin levels and the ratio of adiponectin and %BF was an independent predictor of fasting insulin levels. Although adiponectin levels did not correlate with hs-CRP levels, we observed dichotomous relationships of adiponectin and hs-CRP levels with generalized and abdominal obesity, respectively. We conclude that generalized obesity affects the adiponectin-insulin relationship in postpubertal Asian Indian males; however, the relationship of adiponectin with hs-CRP needs further evaluation.
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PMID:Adiponectin, insulin resistance, and C-reactive protein in postpubertal Asian Indian adolescents. 1537 91

Although elevated low-density lipoprotein (LDL)-cholesterol is a well established coronary heart disease (CHD) risk factor, the ability to adequately discriminate high-risk individuals by this risk factor alone is limited and other metabolic risk variables are known to modulate CHD risk. For instance, it has been reported that the cluster of metabolic disturbances observed among individuals with abdominal obesity, the so-called metabolic syndrome, is associated with a substantially increased risk of CHD. Among the features of the dyslipidaemic profile observed in these individuals, the high triglyceride-low high-density lipoprotein (HDL)-cholesterol dyslipidaemia is predictive of an elevated risk of CHD. Fibric acid derivatives (fibrates) have been used in clinical practice for more than 2 decades as a class of agents known to decrease triglyceride levels while substantially increasing HDL-cholesterol levels, with a limited but significant additional lowering effect on LDL-cholesterol levels. Although the clinical benefits of HMG-CoA reductase inhibitors (statins) have been well documented by primary and secondary prevention trials that justify their widespread use, it was not until the publication of the VA-HIT (Veterans Affairs High-Density Lipoprotein Intervention Trial) that the relevance of identifying HDL-cholesterol as a therapeutic target to reduce the risk of recurrent CHD events was finally confirmed. The clinical benefits of fibrate therapy are especially important in the subpopulation of patients with low HDL-cholesterol levels with the metabolic syndrome, particularly in patients with type 2 diabetes mellitus or in abdominally obese, hyperinsulinaemic patients. Evidence also suggests that there is a 'fibrate effect' that mediates the reduction in CHD risk beyond the favourable impact of these agents on HDL-cholesterol levels. This last notion is consistent with the pleiotropic effects of fibrates which are known to be related to their mechanisms of action. Through peroxisome proliferator-activated alpha-receptors, fibrates have a significant impact on the synthesis of several apolipoproteins (apo) and enzymes of lipoprotein metabolism as well as on the expression of several genes involved in fibrinolysis and inflammation. Fibrate therapy has been reported to decrease apo CIII levels (a powerful inhibitor of lipoprotein lipase) and increase apo AI levels, as well as to increase lipoprotein lipase activity. Such changes contribute to improve the catabolism of triglyceride-rich lipoproteins, leading to a substantial increase in HDL-cholesterol levels accompanied by a shift in the size and density of LDL particles (from small, dense LDL particles to larger, more buoyant cholesteryl ester-rich LDL). It is proposed that some of these pleiotropic effects could explain some of the clinical benefits of fibrate therapy beyond its HDL-raising properties, particularly among patients with abdominal obesity, hyperinsulinaemia or type 2 diabetes with both low HDL- and low/normal LDL-cholesterol levels.
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PMID:Role of fibric acid derivatives in the management of risk factors for coronary heart disease. 1545 34


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