Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to characterize abnormalities of triglyceride-rich apolipoprotein (apo) B-containing lipoproteins in type I diabetic patients with elevated albumin excretion rates (AERs). Sixty-four patients (31 men, 33 women) with normoalbuminuria (AER <20 microg/min), 52 (35 men, 17 women) with microalbuminuria (AER 20-200 microg/min), and 37 (17 men, 20 women) with albuminuria (AER >200 microg/min) and 56 healthy control subjects matched for age and body weight were studied. The major finding was increased mass concentrations of the highly atherogenic intermediate-density lipoprotein fraction in patients with microalbuminuria (P < 0.05) and albuminuria (P < 0.05), compared with those with normoalbuminuria. Triglyceride, free cholesterol, cholesterol ester, and phospholipid concentrations in the VLDL, intermediate-density lipoprotein, and LDL (P < 0.05-0.01), as well as total cholesterol, total triglyceride, and apoB concentrations were higher in patients with renal disease than in those without. Notably, there were no differences between patients with microalbuminuria and albuminuria. Only minor compositional changes could be detected. Postheparin plasma lipoprotein lipase (LPL) activities were identical, but hepatic lipase activities were higher in microalbuminuric and albuminuric patients than in normoalbuminuric patients (P < 0.01). LPL activity and VLDL1, (Sf 60-400) (r = -0.528; P < 0.001) and VLDL2 (Sf 20-60) mass concentrations (r = -0.471; P < 0.001) were negatively related. In conclusion, in type I diabetic patients with early renal disease, there are multiple lipoprotein changes, which are potentially atherogenic and may contribute to the excess of macrovascular complications seen in such patients.
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PMID:Multiple lipoprotein abnormalities in type I diabetic patients with renal disease. 866 51

In an attempt to identify genetic factors underlying extreme alterations of serum HDL cholesterol (HDL-C) concentrations, we examined two probands with HDL-C levels <0.2 mmol/L and subsequently screened two large cohorts of smoking men, one with very low (0.2 to 0.7 mmol/L, n=156) and the other with elevated (1.9 to 3.6 mmol/L, n=160) HDL-C levels, for the newly detected mutations as well as some other mutations proposed to affect HDL-C levels. One of the probands had corneal opacities, microalbuminuria, hypertriglyceridemia, and reduced LDL apoprotein B concentration; the other had anemia and presented with stomatocytosis in his peripheral blood. The first proband was found to be homozygous for a novel LCAT Gly230Arg (LCAT[Fin]) mutation, and the second was homozygous for an Arg399Cys mutation we described previously. Transient expression of the mutant LCAT(Fin) cDNA in COS cells disclosed markedly diminished LCAT enzyme activity. In the low-HDL-C group of men (n=156), 8 carriers of LCAT(Fin) and 1 carrier of the LCAT Arg399Cys were identified. In addition, the frequency of the lipoprotein lipase (LPL) Asn291Ser mutation was significantly (P<.05) higher in the low-HDL-C group (4.8%) than in the high-HDL-C group (1.6%). In addition, we identified 1 carrier of the intron 14G-->A mutation of cholesterol ester transfer protein (CETP) in the high-HDL-C group and subsequently demonstrated cosegregation of the mutant allele with elevated HDL-C levels in the proband's family. In conclusion, we have identified a novel LCAT gene Gly230Arg mutation (LCAT[Fin]), which, together with the LPL Asn291Ser mutation, represents a relatively common genetic cause of diminishing HDL-C levels, at least among Finns. This article also reports occurrence of a CETP mutation in subjects having non-Japanese roots.
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PMID:Molecular genetic study of Finns with hypoalphalipoproteinemia and hyperalphalipoproteinemia: a novel Gly230 Arg mutation (LCAT[Fin]) of lecithin:cholesterol acyltransferase (LCAT) accounts for 5% of cases with very low serum HDL cholesterol levels. 955 65

The excess of glucose appears to play an important and specific role in the genesis of macroangiopathy in diabetics. Activation of protein kinase-C, the sorbitol pathway, and AGE formation are thought to be the major pathways linking the degree of glycaemic compensation with the pathogenetic process of macrovascular disease. HSPG is likely to be a key element in this process since it is a regulator of endothelial permeability, vascular antithrombotic capacity, insulin sensitivity (with respect to lipoprotein lipase availability), and vascular extracellular matrix content and smooth-muscle-cell activation. Loss of HSPG is suggested clinically by the presence of microalbuminuria, to the development of which diabetic control also contributes significantly. However, genetic factors also seem to be involved. Much more insight into the precise mechanismus is necessary to unravel the cellular and molecular chains of events for the premature and accelerated atherosclerosis in diabetic patients.
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PMID:The atherosclerotic process and its exacerbation by diabetes. 1146 May 93

Type 2 diabetes is characterised by both impaired insulin secretion and insulin resistance but their relative contribution to the development of hyperglycaemia may differ due to heterogeneity of the disease. Under most circumstances, insulin resistance is the earliest detectable defect in pre-diabetic individuals but it is not known whether this is the primary defect or secondary to other abnormalities such as abdominal obesity with excessive free fatty acid turnover and increased lipid deposits in muscle. Initially, enhanced insulin secretion can compensate for the insulin resistance but early phase insulin secretion is impaired. In the transition from normal to impaired and diabetic glucose tolerance, insulin sensitivity deteriorates about 40% whereas insulin secretion deteriorates 3-4 fold. In addition to insulin resistance, the metabolic syndrome includes hypertension, dyslipidaemia, obesity and microalbuminuria. In patients with manifest diabetes, chronic hyperglycaemia can result in further deterioration of insulin sensitivity and secretion (glucotoxicity), which is aggravated by elevated free fatty acids (lipotoxicity). Abdominal obesity and insulin resistance are strongly correlated and studies have aimed at understanding the genetic basis. Candidate genes for the metabolic syndrome include those for the beta 3-adrenergic receptor, lipoprotein lipase, hormone sensitive lipase, peroxisome proliferator-activated receptor-gamma, insulin receptor substrate-1 and glycogen synthase. Therefore, type 2 diabetes is multigenic and appears to represent a collision between thrifty genes and an affluent society. Successful management will require treatments targeted at defects of both insulin secretion and insulin resistance.
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PMID:Pathogenesis of type 2 diabetes: the relative contribution of insulin resistance and impaired insulin secretion. 1196 29

Microalbuminuria (MAU) is a strong predictor of diabetic nephropathy (DN), which is the main cause of morbidity and mortality in patients with diabetes mellitus (DM). Dyslipidemia exists in the majority of patients with DM and contributes to micro- and macrovascular complications associated with DM. Apolipoprotein CIII (apoCIII) is an inhibitor of the activity of lipoprotein lipase, which metabolizes triglyceride (TG) in very low-density lipoprotein (VLDL) and facilitates its clearance from plasma. The aim of the present study was to investigate the associations between apoCIII and MAU and the effects of atorvastatin in type 2 diabetes. In total, 120 subjects were divided into type 2 diabetes and type 2 DN groups, while 60 healthy subjects were selected as controls. The patients with DN were administered 20 mg atorvastatin daily for 16 weeks. Blood pressure, body mass index (BMI) and levels of HbA1c, FBG, TG, VLDL-cholesterol (VLDL-C), apoCIII and MAU were markedly elevated in the type 2 diabetes and type 2 DN groups compared with those in the control group (P<0.01), while high-density lipoprotein-cholesterol (HDL-C) levels were decreased significantly (P<0.01). All patients with type 2 DN showed significantly elevated blood pressure, apoCIII levels, MAU, course of the disease and rate of stroke and retinopathy compared with the patients with type 2 diabetes (P<0.01). MAU was significantly positively correlated with the course of the disease, systolic blood pressure, diastolic blood pressure, BMI and HbA1c, FBG, TG, total cholesterol, low-density lipoprotein-cholesterol, VLDL-C and apoCIII levels (P<0.05), whereas negatively correlated with HDL-C levels (r=-0.194, P=0.020). Logistic regression analysis showed that apoCIII levels were independently associated with MAU (odds ratio, 1.100; 95% confidence interval, 1.037-1.153; P<0.001). Atorvastatin improved the lipid profile and MAU in patients with type 2 DN (P<0.01). Therefore, the present study demonstrated that an independent positive correlation exists between the levels of apoCIII and MAU in patients with type 2 diabetes. Furthermore, atorvastatin may be used to improve the lipid profile and MAU in type 2 DN.
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PMID:Associations between apolipoprotein CIII concentrations and microalbuminuria in type 2 diabetes. 2512 Jun 29