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)

Several studies have provided evidence that the remnants of lipoproteins may be the atherogenic components of triglyceride-rich lipoproteins. The purpose of this study was to investigate whether the remnant-like particle cholesterol (RLP-C) is an independent risk factor for coronary artery disease (CAD) and non-insulin dependent diabetes mellitus (NIDDM) in the Korean population and to explore the relationship between RLP-C and other biochemical markers as well as the apolipoprotein (apo) E genotypes. Lipid and lipoproteins including RLP-C and apo E genotypes were analyzed in 98 normal adults (control group), 68 patients with CAD (CAD group), 88 patients with NIDDM (DM group), and 19 patients with both CAD and NDDM (CAD + DM group). RLP-C levels were significantly higher in the DM (p < 0.0001), CAD (p = 0.0012) and the CAD + DM groups (p = 0.0184) than in the controls. To determine which variable could discriminate most effectively and independently among the different groups, stepwise linear discriminant analysis was performed for all the variables that showed p < 0.15 by univariate analysis. RLP-C was selected as an independent discriminator between the control and patient groups. RLP-C levels showed a strong positive correlation with trigylceride levels in the control, CAD and DM groups (r = 0.783, r = 0.610 and r = 0.746, respectively). In overall groups, apo epsilon4 and epsilon2 carrier genotypes showed a significant increase in RLP-C levels compared with epsilon3/3 wild-type (p = 0.0085). After adjusting for the effect of apo E genotypes, a significant increase of the RLP-C levels in the disease groups remained. In conclusion, RLP-C was determined to be an independent risk factor in Korean patients with CAD and NIDDM and showed a strong correlation with triglyceride levels. We suggest that the increased cardiovascular risk associated with the epsilon4 and epsilon2 allele may be mediated by more atherogenic RLP-C.
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PMID:Remnant-like particle cholesterol levels in Korean patients with coronary artery disease and non-insulin dependent diabetes mellitus. 1095 26

In 56 adult normoglycemic nondiabetic (WHO criteria) subjects, whose both parents had type 2 diabetes, and in 68 control probants, matched for age, sex and body mass without family history of diabetes, the OGTT (75 g) was carried out, including measurement of serum insulin (IRI) and C-peptide (CP). In fasting state also the blood lipid profile was determined: serum triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein AI (apoAI) and apolipoprotein B (apoB). In comparison with the control group, the offspring had significantly lower mean glycaemia on fasting, and non significantly elevated from the 60 min of the test, the significantly higher values of serum IRI and CP in fasting state and at the end of the test (120-180 min), and significantly lower serum CP:IRI molar ratio, expressing the reduced hepatic clearance of insulin. The offspring had significantly higher mean values of serum LDL-cholesterol, and significantly lower of serum HDL-cholesterol and apoAI, not disclosing significant differences in the serum levels of triglycerides, total cholesterol and apoB with the control group. Only serum HDL-cholesterol was significantly (negatively) correlated wit serum IRI and CP-values. The covariance analysis, eliminating the influence of age, body mass and the secretory activity of pancreatic B-cells, revealed the significant correlation of the presence of parental diabetes with serum levels of LDL-cholesterol (increase), and HDL-cholesterol and apoAI (decrease) in the offspring. These results prove indirectly, that in subjects genetically predisposed to type 2 diabetes, before the manifestation of glucose intolerance are present other effects of insulin resistance, expressed in increased activity of pancreatic B-cells, increased transfer of insulin to extrahepatic tissues, and in changes of concentration/composition of some lipoproteins dues to reduced influence of insulin on the enzymes which control their metabolism.
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PMID:[Glucose tolerance, function of pancreatic B-cells and blood lipids in "healthy" offspring of parents with conjugal type 2 diabetes]. 1123 42

The aim of this study was to delineate the role of lipoprotein lipase (LPL) activity in the kinetic alterations of high density lipoprotein (HDL) metabolism in patients with type II diabetes mellitus compared with controls. The kinetics of HDL were studied by endogenous labeling of HDL apolipoprotein AI (HDL-apo AI) using a primed infusion of D(3)-leucine. The HDL-apo AI fractional catabolic rate (FCR) was significantly increased (0.32 +/- 0.07 vs. 0.23 +/- 0.05 pool/day; P < 0.01), and HDL composition was changed [HDL cholesterol, 0.77 +/- 0.16 vs. 1.19 +/- 0.37 mmol/L (P < 0.05); HDL triglycerides, 0.19 +/- 0.12 vs. 0.10 +/- 0.03 mmol/L (P < 0.05)] in diabetic patients compared with healthy subjects. HDL-apo AI FCR was correlated to plasma and HDL triglyceride concentrations (r = 0.82; P < 0.05 and r = 0.80; P < 0.05, respectively) and to homeostasis model assessment (r = 0.78; P < 0.05). Postheparin plasma LPL activity was decreased in type II diabetes (6.8 +/- 2.8 vs. 18.1 +/- 5.2 micromol/mL postheparin plasma.h; P < 0.005) compared with that in healthy subjects and was correlated to the FCR of HDL-apo AI (r = -0.63; P < 0.05). LPL activity was also correlated with HDL cholesterol (r = 0.78; P < 0.05), plasma and HDL triglycerides (r = -0.87; P < 0.005 and r = -0.83; P < 0.05, respectively), and homeostasis model assessment (r = -0.79; P < 0.05). In addition, the LPL to hepatic lipase ratio was correlated with the catabolic rate of HDL (r = -0.76; P < 0.06). These results suggest that a decrease in the LPL to hepatic lipase ratio in type II diabetes mellitus, mainly related to lowered LPL activity, could induce an increase in HDL catabolism. These alterations in HDL kinetics in type II diabetes proceed to some extent from changes in their composition, probably linked to an increase in triglyceride transfer from very low density lipoprotein particles, in close relationship with LPL activity and resistance to insulin.
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PMID:In vivo evidence for the role of lipoprotein lipase activity in the regulation of apolipoprotein AI metabolism: a kinetic study in control subjects and patients with type II diabetes mellitus. 1134 92

Mutations in the HNF4alpha gene are responsible for type 1 maturity-onset diabetes of the young (MODY1), which is characterized by a defect in insulin secretion. Hepatocyte nuclear factor (HNF)-4alpha is a transcription factor that plays a critical role in the transcriptional regulation of genes involved in glucose metabolism in both hepatocytes and pancreatic beta-cells. Recent evidence has implicated AMP-activated protein kinase (AMPK) in the modulation of both insulin secretion by pancreatic beta-cells and the control of glucose-dependent gene expression in both hepatocytes and beta-cells. Therefore, the question could be raised as to whether AMPK plays a role in these processes by modulating HNF-4alpha function. In this study, we show that activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) in hepatocytes greatly diminished HNF-4alpha protein levels and consequently downregulates the expression of HNF-4alpha target genes. Quantitative evaluation of HNF-4alpha target gene expression revealed diminished mRNA levels for HNF-1alpha, GLUT2, L-type pyruvate kinase, aldolase B, apolipoprotein (apo)-B, and apoCIII. Our data clearly demonstrate that the MODY1/HNF-4alpha transcription factor is a novel target of AMPK in hepatocytes. Accordingly, it can be suggested that in pancreatic beta-cells, AMPK also acts by decreasing HNF-4alpha protein level, and therefore insulin secretion. Hence, the possible role of AMPK in the physiopathology of type 2 diabetes should be considered.
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PMID:Hepatocyte nuclear factor-4alpha involved in type 1 maturity-onset diabetes of the young is a novel target of AMP-activated protein kinase. 1142 71

Lipid abnormalities in diabetic patients, particularly in those with nephropathy, may be partially due to deteriorating atherosclerosis. Therefore, strict control of the lipid metabolism in addition to glycemic control is desirable. Whether or not lipid lowering drugs prevent albuminuria in diabetic patients in the long term remains unclear. This study involved 71 NIDDM patients with hypercholesterolemia (group A: n = 37, group B: N = 34). The effect of bezafibrate (group A) or pravastatin (group B) on the cholesterol (CH) content of apolipoprotein AI, B100 containing particles or remnant-like particles (RLP) or urinary albumin excretion was studied over 4 years. The CH content in apolipoprotein B100 particles after treatment with either bezafibrate or pravastatin decreased significantly (group A: 24.7%, group B: 26.6%). The CH content in RLP after treatment with bezafibrate showed a significant decrease (67.9%). Apolipoprotein AI after treatment with bezafibrate showed a significant increase (10.9%). Apolipoprotein B100 after treatment with either drug decreased significantly (group A: 19.8%, group B: 23.4%). The urinary albumin excretion rate after treatment with either drug showed no significant change over 4 years. Bezafibrate and pravastatin appear to be useful in the preventive treatment of albuminuria as well as in lowering lipid levels in NIDDM patients.
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PMID:Effect of bezafibrate or pravastatin on serum lipid levels and albuminuria in NIDDM patients. 1142 88

The effect of a dietary fish oil supplementation on metabolism of HDL was studied in type II diabetes mellitus. Endogenous labeling of HDL-apo AI was performed using a 14 h primed infusion of D3-leucine in five diabetic patients before and 2 months after treatment with maxEPA(R). Isotopic enrichment curves were analyzed using a monoexponential function. After treatment, plasma cholesterol level remained unchanged (205.4+/-41.9 vs. 206.8+/-30.7 mg/dl, NS), whereas plasma triglycerides were decreased (155.4+/-67.9 vs. 202.6+/-32.2 mg/dl, P=0.06). Plasma apo AI was similar under maxEPA(R) (116.0+/-25.6 vs. 111.8+/-25.4 mg/dl, NS), and HDL-cholesterol and HDL-triglycerides were also not markedly changed (30.2+/-10.0 vs. 27.1+/-10 mg/dl, and 15.3+/-9.8 vs. 19.2+/-10.4 mg/dl, NS). HDL-apo AI fractional catabolic rate (FCR) and absolute production rate (APR) were significantly decreased after treatment with maxEPA(R) (0.27+/-0.09 vs. 0.37+/-0.08 pool day, P<0.05, and 12.1+/-2.8 vs. 16.1+/-3.3 mg/kg per day, P<0.05). These findings showed an effect of maxEPA(R) on kinetics of apolipoprotein AI in type II diabetes mellitus, probably linked to changes in plasma triglyceride level.
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PMID:Effect of dietary omega-3 fatty acids on high-density lipoprotein apolipoprotein AI kinetics in type II diabetes mellitus. 1168 29

Retention of atherogenic apolipoprotein (apo) B- and E- containing lipoproteins by their interaction with arterial wall proteoglycans is important in atherogenesis. Levels of triglyceride (TG)-rich lipoproteins, which contain both apo B and apo E, are increased in type 2 diabetes. Because increased retention of TG-rich lipoproteins in diabetes might explain, in part, the increased atherosclerosis in this disorder, TG-rich lipoproteins were isolated from fasting type 2 diabetic subjects and age-matched controls, and assessed for their ability to bind biglycan, a vascular smooth muscle cell-derived proteoglycan. The binding of TG-rich lipoproteins isolated from diabetic subjects to purified biglycan did not differ from lipoproteins isolated from control subjects. Moreover, contrary to previous reports, no difference in the apo E content of TG-rich lipoproteins was detected between the control and diabetic groups. Additionally, no difference in the binding affinity of TG-rich lipoproteins for the low-density lipoprotein receptor was observed between control and diabetic subjects. Thus, we were unable to confirm previous reports that TG-rich lipoproteins from subjects with diabetes are enriched in apo E compared with age-matched controls, consistent with the lack of difference in binding of these lipoproteins to either biglycan or the low-density lipoprotein receptor. Therefore, increased affinity of TG-rich lipoproteins for biglycan is unlikely to explain the increased atherosclerosis in type 2 diabetes.
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PMID:Triglyceride-rich lipoproteins from subjects with type 2 diabetes do not demonstrate increased binding to biglycan, a vascular proteoglycan. 1178 18

The aim of this study was to clarify the relationship between apolipoprotein (a) (apo (a) ) phenotypes and diabetic retinopathy in elderly type 2 diabetes. Serum Lp (a) concentrations and apo (a) phenotypes were analyzed in 250 diabetic patients aged 60 to 88 years old. Apo (a) phenotypes were classified into 7 subtypes (F, B, S1, S2, S3, S4, O (Null) ) by the method SDS electrophoresis with Western blotting. Patients were divided into two groups according to their apo (a) phenotypes:a low molecular weight (LMW) Lp (a) group, and a high molecular weight (HML) Lp (a) group. Patients were classified as having one of 4 types of diabetic retinopathy: no retinopathy (R0), simple retinopathy (R1), pre-proliferative retinopathy (R2), and proliferative retinopathy (R3). There was a significant association between serum Lp (a) levels and severity of diabetic retinopathy (p<0.001). A gradual trend toward increasing serum Lp (a) levels was observed across the groups (from R0 to R3). A significantly greater percentage of LMW Lp (a) was observed in the R1, R2, and R3 groups than in the R0 group (42.9% (p<0.001), 27.0% (p<0.01), and 27.3% (p<0.05) vs. 10.4%). Multiple logistic regression analysis revealed that duration of diabetes and LMW Lp (a) are independent risk factors for diabetic retinopathy. These results provide significant evidence that LMW Lp (a) contributes to an increased risk of diabetic retinopathy in elderly type 2 diabetes.
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PMID:Relation of apolipoprotein (a) phenotypes to diabetic retinopathy in elderly type 2 diabetes. 1184 7

Cholesteryl ester transfer protein (CETP) is a key regulating factor of lipid metabolism, and the polymorphism of its gene may therefore be a candidate for modulating the lipid parameters, altering the susceptibility to atherosclerosis in type 2 diabetic subjects. In a group of 443 unrelated Japanese patients with type 2 diabetes, we studied the B1B2 polymorphism at the CETP locus, which is detectable with the restriction enzyme TaqI. Patients were separated into three groups according to genotype and compared based on their clinical characteristics, lipid parameters, and macrovascular complications. The B2 allele was associated in a dose-dependent fashion with higher HDL cholesterol and apolipoprotein AI levels, together with lower CETP concentrations. Furthermore, the prevalence of macrovascular complications, such as coronary heart disease, arteriosclerosis obliterans, and cerebral vascular disease, was significantly higher in subjects with the B1B1 genotype. Multiple logistic regression analysis also showed that the B1 allele of CETP genotype was associated with the incidence of these three complications independently of other risk factors. Thus, in type 2 diabetic patients, the B1B2 polymorphism of CETP gene is likely to be a strong genetic predictor of macrovascular complications.
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PMID:Relationship between TaqIB cholesteryl ester transfer protein gene polymorphism and macrovascular complications in Japanese patients with type 2 diabetes. 1187 95

Four apolipoprotein (apo) E variants have been reported to be associated with lipoprotein glomerulopathy (LPG), which is characterized by type III hyperlipoproteinemia (type III HLP) and proteinuria and frequently leads to nephrotic syndrome. We report the histologic findings in the kidneys of a type III HLP patient with an apo E variant, apo E Toranomon, in which the glutamine at residue 187 in apo E is substituted by glutamic acid (Q187E). The patient also had type 2 diabetes mellitus. No evidence of lipoprotein thrombi suggestive of LPG was detected, however, and the histologic diagnosis was diabetic nephrosclerosis. This unique case illustrates that not all apo E variants result in LPG, and the location of mutations in the apo E protein is one of the important determinants for the development of LPG.
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PMID:A patient with apolipoprotein E2 variant (Q187E) without lipoprotein glomerulopathy. 1187 95


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