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

Fatty liver disease is now recognized as a major health burden, due to the greater number of cases that are being diagnosed. This trend could partly be explained by the increased use of liver ultrasonography in asymptomatic patients for various reasons, mainly persistent transaminase elevation. The most commonly reported risk factors associated with fatty liver disease are chronic alcohol intake, obesity, type 2 diabetes mellitus, hyperlipidemia, and some drugs. When these factors have been ruled out in a patient with a fatty liver, less frequent causes such as certain inherited metabolic disorders should be considered. Familial hypobetalipoproteinemia is characterized by an alteration of apolipoprotein B (apo B) synthesis, leading to the secretion of truncated forms of the protein, which in turn leads to a marked reduction in excretion of very low-density lipoproteins from the liver and consequently to lipid deposits, especially triglycerides, in the hepatocytes. We report the case of a 23-year-old man who met the diagnostic criteria for heterozygous familial hypobetalipoproteinemia. He presented with mild transaminase elevation and fatty liver. Total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and apo B were below normal limits, while levels of high-density lipoprotein cholesterol were normal. Lipid profile determination and liver ultrasonography of first and second-degree relatives were also performed. Molecular studies of the index case revealed an unaffected apo B gene.
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PMID:[Hepatic steatosis associated with heterozygotic familial hypobetalipoproteinemia]. 1505 12

Regional body fat distribution has an important influence on metabolic and cardiovascular risk factors. Increased abdominal (visceral) fat accumulation is a risk factor for coronary artery disease (CAD), dyslipidemia, hypertension, stroke, and type 2 diabetes. The recent emphasis on treatment of the dyslipidemia of the metabolic syndrome (hypertriglyceridemia, reduced high-density lipoprotein, and increased small, dense low-density lipoprotein particle number) has compelled practitioners to consider lipid-lowering therapy in a greater number of their patients, as one in two individuals over age 50 has the metabolic syndrome. Individuals with the metabolic syndrome typically have normal low-density lipoprotein cholesterol levels, and current lipid-lowering guidelines may underestimate their cardiovascular risk. Two subgroups of patients with the metabolic syndrome are at particularly high risk for premature CAD. One, individuals with type 2 diabetes, accounts for 20-30% of early cardiovascular disease. The second, familial combined hyperlipidemia, accounts for an additional 10-20% of premature CAD. Familial combined hyperlipidemia is characterized by the metabolic syndrome in addition to a disproportionate elevation of apolipoprotein B levels. The measurement of fasting glucose and apolipoprotein B, in addition to the fasting lipid profile, can help to estimate CAD risk in patients with the metabolic syndrome.
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PMID:Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk. 1518 Oct 30

Nonenzymatic glycation of apolipoprotein B in the low-density lipoprotein (LDL) complex has been considered a proatherogenic modification contributory to the increased susceptibility of patients with diabetes to atherosclerosis. We postulated that glycated LDL concentrations might be associated with other markers of cardiovascular disease. To explore this hypothesis, we measured glycated LDL concentrations by a monospecific immunoassay in 50 patients with type 1 and 100 patients with type 2 diabetes and examined relationships with the amount of albumin excretion and the serum cholesterol and triglyercide concentrations. Plasma glycated LDL showed a significant positive correlation (r = 0.325; P < 0.001) with urinary albumin excretion that was higher in type 1 (r = 0.463) than in type 2 (r = 0.245) patients. The mean glycated LDL concentration progressively increased with increasing albumin excretion when patients were subcategorized into groups of normoalbuminuria, low (</=100 microg/mg of creatinine), and high (101-300 microg/mg) microalbuminuria, and proteinuria. Glycated LDL also correlated positively and significantly with cholesterol (r = 0.578) and triglyceride (r = 0.350) concentrations. The significant correlations in this cross-sectional analysis between glycated LDL and urinary albumin excretion, an index of cardiovascular mortality, and cholesterol and triglyceride concentrations, traditional markers of risk for cardiovascular disease, support the hypothesis that an elevated level of glycated LDL represents an atherogenic risk factor in patients with diabetes.
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PMID:Increased plasma glycated low-density lipoprotein concentrations in diabetes: a marker of atherogenic risk. 1519 38

Visceral obesity is frequently associated with high plasma triglycerides and low plasma high density lipoprotein-cholesterol (HDL-C), and with high plasma concentrations of apolipoprotein B (apoB)-containing lipoproteins. Atherogenic dyslipidemia in these patients may be caused by a combination of overproduction of very low density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles, and increased catabolism of HDL-apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance. Weight reduction, increased physical activity, and moderate alcohol intake are first-line therapies to improve lipid abnormalities in visceral obesity. These lifestyle changes can effectively reduce plasma triglycerides and low density lipoprotein-cholesterol (LDL-C), and raise HDL-C. Kinetic studies show that in visceral obesity, weight loss reduces VLDL-apoB secretion and reciprocally upregulates LDL-apoB catabolism, probably owing to reduced visceral fat mass, enhanced insulin sensitivity and decreased hepatic lipogenesis. Adjunctive pharmacologic treatments, such as HMG-CoA reductase inhibitors, fibric acid derivatives, niacin (nicotinic acid), or fish oils, may often be required to further correct the dyslipidemia. Therapeutic improvements in lipid and lipoprotein profiles in visceral obesity can be achieved by several mechanisms of action, including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. Clinical trials have provided evidence supporting the use of HMG-CoA reductase inhibitors and fibric acid derivatives to treat dyslipidemia in patients with visceral obesity, insulin resistance and type 2 diabetes mellitus. Since drug monotherapy may not adequately optimize dyslipoproteinemia, dual pharmacotherapy may be required, such as HMG-CoA reductase inhibitor/fibric acid derivative, HMG-CoA reductase inhibitor/niacin and HMG-CoA reductase inhibitor/fish oils combinations. Newer therapies, such as cholesterol absorption inhibitors, cholesteryl ester transfer protein antagonists and insulin sensitizers, could also be employed alone or in combination with other agents to optimize treatment. The basis for a multiple approach to correcting dyslipoproteinemia in visceral obesity and the metabolic syndrome relies on understanding the mechanisms of action of the individual therapeutic components.
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PMID:Dyslipidemia in visceral obesity: mechanisms, implications, and therapy. 1528 98

Metabolic syndrome is a cluster of cardiovascular risk factors. Pathogenesis of metabolic syndrome implies 3 potential etiological mechanisms: obesity and adipose tissue disorders, insulin resistance, and a constellation of independent factors. Clinical recognition of the metabolic syndrome is based on finding several well-recognized signs in clinical practice: abdominal obesity, elevated triglycerides, reduced HDL cholesterol, raised blood pressure, and elevated plasma glucose. In addition, other components commonly aggregate with the major components: elevated apolipoprotein B, small LDL particles, insulin resistance and hyperinsulinemia, impaired glucose tolerance (IGT), elevated C-reactive protein (CRP), and variation in coagulation factors (plasminogen activator inhibitor [PAI]-I and fibrinogen). Cardiovascular disease (CVD) is the primary clinical outcome of metabolic syndrome. Additionally, risk for type 2 diabetes is higher. Diabetes is itself a major risk factor for CVD. ATP III criteria for diagnosis of metabolic syndrome provide a practical tool to identify patients at increased risk for CVD. World Health Organization (WHO) and American Association of Clinical Endocrinologists (AACE) criteria require further oral glucose testing if IFG and diabetes are absent. IGT on OGTT denotes greater risk for diabetes than does metabolic syndrome without elevated fasting glucose.
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PMID:Metabolic syndrome--new insights into a growing entity. 1552 16

Impaired course of inflammation is a likely mechanism behind a number of diabetic complications. The present study was undertaken to investigate lipopolysaccharide-induced production of tumour necrosis factor (TNF)-alpha in monocytes from patients with type 2 diabetes and to assess its relationship with diabetes-associated metabolic abnormalities. Monocytic TNF-alpha mRNA production was lower in the diabetic participants compared to their corresponding controls. Diabetic subjects who had been receiving simvastatin treatment had TNF-alpha mRNA production similar to that of the healthy participants. The release of TNF-alpha from diabetic cells correlated negatively with serum levels of apolipoprotein B (apoB) (R = -0.755, P = 0.001), total plasma cholesterol (R = - 0.702, P = 0.002) and the presence of retinopathy (R = -0.572, P = 0.021). No such associations were found in the control subjects. In a multiple linear regression model, only the level of apoB and diabetes duration demonstrated significant effects on the release of TNF-alpha, with apoB alone accounting for 57% of the variation. We conclude that production of TNF-alpha mRNA in response to the bacterial stimulant is compromised in poorly controlled type 2 diabetes. Lipid abnormalities are associated with the observed defect. Impaired cytokine production represents a significant defect in the functioning of the immune system and may contribute to aberrations in the course of inflammation in the diabetic state.
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PMID:Release of TNF-alpha from in vitro-stimulated monocytes is negatively associated with serum levels of apolipoprotein B in patients with type 2 diabetes. 1554 Oct 48

The objective of this study was to evaluate the effect of a high fat or high carbohydrate breakfast on postprandial lipid profile in healthy subjects with or without family history of type 2 diabetes mellitus. A single blind, controlled clinical trial with parallel groups was performed in 20 healthy subjects; 10 subjects with family history of type 2 diabetes mellitus and 10 individuals without that background. Each group was randomized to receive a high fat or high carbohidrate breakfast. A metabolic profile that included fasting and postprandial lipids, as well as, the assessment of insulin sensitivity were performed. Lower high-lipoprotein cholesterol (p < 0.02) and apolipoprotein A1 (p < 0.03) concentrations were found in subjects with family history of type 2 diabetes mellitus than those without that background. In this same above mentioned group with the high carbohydrate breakfast, there were significant increments in apoliprotein B at minute 300 (p < 0.03) and in triglycerides at minute 360 (p < 0.03). In the group without family history of diabetes that received the high fat breakfast, there were increments in triglycerides (p < 0.03) and very-low density lipoprotein concentrations at minute 180 (p < 0.03). In conclusion, healthy subjects with family history of type 2 diabetes showed some atherogenic characteristics in their metabolic profile, and the high carbohydrate breakfast produced in them increments in apolipoprotein B and in triglycerides, meanwhile that, in those subjects without such background the high fast breakfast produced unfavorable effects on their lipid concentrations.
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PMID:[Effect of a high fat or high carbohydrate breakfast on postprandial lipid profile in healthy subjects with or without family history of type 2 diabetes mellitus]. 1580 1

Diabetic dyslipidaemia is characterised by retention of atherogenic particles, which are depleted of cholesterol. Therefore, calculating or measuring LDL or VLDL cholesterol may not reflect the actual number of these atherogenic particles. We examined the potential role of apolipoprotein B in the risk stratification of Omani patients with type 2 diabetes and dyslipidaemia. Two hundred and twenty-one subjects with type 2 diabetes and 67 healthy controls were recruited. Diabetic subjects had significantly higher serum levels of triglycerides (P<0.0001), non-HDL cholesterol (P<0.0001), and total/HDL cholesterol ratio (P<0.04) and lower levels of HDL cholesterol (P<0.0001) and lipoprotein(a) compared to nondiabetic subjects. The ratio of apoB/LDL cholesterol ratio was significantly higher (P<0.002) among diabetic compared to nondiabetic subjects. Sixty percent of the diabetic subjects with abnormal apoB of >1.2g/L had an LDL cholesterol of less than 4.2 mmol/L compared to 7% of the nondiabetic subjects (sensitivity; 40% versus 93%, respectively). Furthermore, diabetic subjects with ischaemic heart disease (IHD) had significantly higher (P<0.003) apoB/non-HDL cholesterol ratio compared to those without IHD. These findings suggest that the ratios of apoB/LDL cholesterol and apoB/non-HDL cholesterol may have a role in the risk stratification of diabetic patients with dyslipidaemia.
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PMID:A potential role of apolipoprotein B in the risk stratification of diabetic patients with dyslipidaemia. 1595 92

Increased plasma levels of triglycerides (TG) in very low density lipoproteins (VLDL) are not only common characteristics of the dyslipidemia associated with insulin resistance and type 2 diabetes mellitus (T2DM) but are the central pathophysiologic feature of the abnormal lipid profile. Overproduction of VLDL leads to increased plasma levels of TG which, via an exchange process mediated by cholesterol ester transfer protein (CETP), results in low levels of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I, and the generation of small, dense, cholesterol ester depleted low density lipoproteins (LDL). Increased assembly and secretion of VLDL by the liver results from the complex, post-transcriptional regulation of apolipoprotein B (apoB) metabolism in the liver. In the presence of low levels of hepatic TG and cholesterol, much of the constitutively synthesized apoB is degraded by both proteasomal and non-proteasomal pathways. When excess TG, and to a lesser extent, cholesterol, are present, and in the presence of active microsomal triglycerides transfer protein, apoB is targeted for secretion. The major sources of TG in the liver: uptake of fatty acids (FA) released by lipolysis of adipose tissue TG, uptake of TGFA in VLDL and chylomicrons remnants, and hepatic de novo lipogenesis (the synthesis of FA from glucose) are all abnormally increased in insulin resistance. Treatment of the dyslipidemia in insulin resistant individuals and patients with T2DM has been successful in reducing cardiovascular disease; LDL cholesterol, TG, and HDL cholesterol are all appropriate targets for therapy when diet, exercise, and weight loss do not achieve goals.
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PMID:Regulation of plasma triglycerides in insulin resistance and diabetes. 1592 13

The aim of this study is to develop a convenient method for monitoring glycated apolipoprotein B levels. Serum sample was treated with dextran-magnesium and the resulting precipitates were subjected to glycated albumin assay. Dissolving the precipitates by Triton X-100 and digesting by proteinase K enable the establishment of stable and sensitive assay. Intra- and inter assay coefficients of variation were 1.5-3.5% and 1.6-3.3%, respectively. The serum glycated apolipoprotein B values by present method correlated well with those by enzyme-linked immunosorbent assay (r=0.979). The serum glycated apolipoprotein B values in healthy subjects was 4.14+/-0.51% (mean+/-SD) with no significant difference between men and women and with no age-dependent variation. Patients with type 2 diabetes mellitus had higher serum glycated apolipoprotein B levels than the healthy subjects. This assay should further be investigated to establish the validity of glycated apolipoprotein B measurement in clinical field.
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PMID:[Convenient assay for glycated apolipoprotein B using protease]. 1602 76


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