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

Atherosclerosis is the main cause of death in diabetes mellitus. This may at least in part be due to lipoprotein abnormalities which have been described in these patients. Apolipoprotein-E is a component of most lipoprotein fractions and plays an important role in the catabolism of VLDL. The different apolipoprotein-E phenotypes determined genetically are associated with certain hyperlipoproteinemias in a various degree in nondiabetic patients. In most cases apolipoprotein-E phenotype E2/2 is characteristic for familial dysbetalipoproteinemia. Phenotype E3/2 was found to be more frequent in hypertriglyceridemia while phenotype E4/3 was associated with hypercholesterolemia as well as with type V hyperlipoproteinemia. We studied apolipoprotein-E phenotypes and serum lipids in 141 type II diabetic patients (36 normolipidemic 41 type IIa hyperlipidemic, 32 type IIb hyperlipidemic, 24 type II hyperlipidemic, 8 type V hyperlipidemic). the phenotype E3/3 was more common in normolipidemic diabetic (77.8%) than in hyperlipoproteinemic diabetic patients (42.9%) or in the control group (57.5%). On the other hand phenotype E3/2 was more frequent in hypertriglyceridemic (50%) than in normolipidemic (5.6%) or hypercholesterolemic (hyperlipoproteinemia IIa: 4.9%, IIb: 9.4%) diabetic patients. The phenotype E4/3 was more frequent in all hyperlipoproteinemic diabetic patients, especially in those having hypercholesterolemia (34.2%) or mixed hyperlipidemia (50%). In conclusion we found a strong association between apo-E2 and hypertriglyceridemia in diabetic patients. This association was stronger than the one found in the general population. The association between apo-E4 and hypercholesterolemia in diabetic patients was similar to the one described in non-diabetic patients. We therefore conclude that type II diabetes mellitus is a possible cofactor in the apolipoprotein-E2 associated hyperlipoproteinemia.
 ...
PMID:Apolipoprotein E phenotype frequency in type II diabetic patients with different forms of hyperlipoproteinemia. 227 5

We examined the long-term effect of pravastatin, a new potent inhibitor of endogenous cholesterol biosynthesis, on glucose and lipid metabolism in hyperlipidemic NIDDM. Ten patients (5 on sulfonylurea, 5 on diet) were studied over 12 months. Five were WHO type IIa and 5 were type IIb. Blood was taken before and then 1, 6 and 12 months after initiating 10 or 20 mg daily of pravastatin. The cholesterol concentration in whole plasma and very low density lipoprotein (VLDL), plasma triglyceride and apolipoprotein (apo) B were all significantly decreased within the first month. These changes lasted for 1 year. High density lipoprotein (HDL)-cholesterol increased in the first month but returned to base line thereafter. Low density lipoprotein (LDL)-cholesterol tended to decrease in the first month, and was suppressed significantly from the 6th month (11%) to the 12th month (16%). The effect of pravastatin on LDL-cholesterol in NIDDM was slower and weaker than that published for non-diabetic hypercholesterolemia. Therefore, the mechanism by which pravastatin suppresses plasma cholesterol levels in these two conditions may differ. After 1 year, no adverse effects were noted on hematopoietic, hepatic or renal function. Blood glucose level, hemoglobin A1c and the insulin response to oral glucose were unchanged. In addition, serum creatine phosphokinase showed no abnormal increase. Careful ophthalmological examinations before and after pravastatin treatment revealed no development of new lenticular opacities. Thus, pravastatin appears to be a safe and effective drug for the long-term treatment of NIDDM with hypercholesterolemia.
 ...
PMID:Long-term treatment of hypercholesterolemic non-insulin dependent diabetics (NIDDM) with pravastatin (CS-514). 249 12

The effect of sample pre-treatment as a source of variability of apolipoprotein (apo) AI, AII and B assays was demonstrated with lipid dissociating agents. The average mean percentage change ranged from -58 to +133% compared with untreated samples. The apolipoprotein method selected was validated by comparing their concentrations with their corresponding lipoprotein lipid or protein in normal controls and Type 2 (non-insulin-dependent) diabetic patients. The coefficient of variation was maintained below 3.5% for apo AI, AII, B and HDL2-apo AI. The apolipoprotein concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of non-obese (body-mass index less than or equal to 30) patients with Type 2 diabetes mellitus. Compared with normal subjects matched for sex, age, body-mass index, exercise, alcohol consumption and smoking. Type 2 patients at diagnosis showed reduced apo AI and HDL2-apo AI concentrations, lowered apo AI:B ratio and increased concentrations of apo B. Type 2 patients treated by diet alone (for 6-72 months) and diet plus glibenclamide (2.5-15 mg/day for 6-48 months) exhibited similar abnormalities of plasma apolipoprotein concentration to Type 2 patients at diagnosis. However, in Type 2 patients treated with insulin (25-65 U/day for 8-144 months) concentrations of apo AI and HDL2-apo AI, and the apo AI:B ratio were normal. Apo B concentrations were generally lower compared with all groups of non-insulin treated patients. These abnormalities of apolipoprotein metabolism, which are associated with premature coronary disease, are still evident in patients treated by diet and diet plus glibenclamide, but are not seen in Type 2 patients treated with insulin.
 ...
PMID:Apolipoprotein assays: methodological considerations and studies in non-insulin-dependent diabetes treated by diet, glibenclamide and insulin. 250 Jun 99

About 50% of the individuals with a coronary risk show lipid levels within the normal range. Therefore, apolipoprotein profiles could be better risk indicators than TC or TG. Apolipoproteins generally discussed in this context are apo A1, apo B, and apo E. Their diagnostic validity, however, is ambigously evaluated. The individual iso-protein pattern of apo E is important for the differential diagnosis of the type III hyperlipidemia with its strong predisposition for premature atherosclerosis. Moreover, the extent of the apo E sialylation seems to be important because the modification of apo E by sialic acid alters its metabolism. Our date provide evidence that in IDDM and NIDDM the degree of apo E sialylation is increased. Concerning apo A1 and B we tried to find out parameters suitable for the prediction of the coronary risk both in the hyperlipidemic and the normolipidemic state. 64 male survivors of a myocardial infarc"ion and 60 matched controls were included in the study (group I). From group I a supopulation showing non-pathological values for TC and TG was selected (group II with 31 survivors and 44 controls). The diagnostic validity of the parameters apo A1, apo B, TC, HDL-C, apo A1/apo B, TC/apo B, HDL-C/apo B, TG, TG/apo A1, TG/HDL-C, TC-HDL-C/apo B determined by calculation of their sensitivities, specificities, efficiencies, and predictive values. Only the parameters TC/apo B, HDL-C/apo B, and apo B were suitable in the order given for detection of the coronary risk. Using the TC/apo B ratio 71-76% of the controls and 79% of the survivors could be exactly reclassified independent of the group they belonged to.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Apolipoproteins as risk indicators of ischemic heart disease. 258 87

Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphates and possibly in the prevention of LDL lipid peroxidation. We investigated the serum activity and concentration of paraoxonase in 78 patients with type 1 diabetes mellitus, 92 with type 2 diabetes, and 82 nondiabetic control subjects. Paraoxonase activity was generally lower in diabetics than in control subjects. This decrease was unrelated to differences in paraoxonase phenotype distribution or its serum concentration. Rather, the difference in paraoxonase activity was explained by its specific activity, which was lower in diabetics, indicating either the presence of a circulating inhibitor or disturbance of the interaction of paraoxonase with HDL affecting its activity. Paraoxonase specific activity was lowest in patients with peripheral neuropathy, suggesting an association of paraoxonase with neuropathy. In control subjects but not patients with diabetes, paraoxonase correlated with HDL cholesterol and apolipoprotein A-1. Our results indicate that the low paraoxonase activity in diabetes is due to decreased specific activity. In other studies low serum paraoxonase activity has been associated with increased susceptibility to atherosclerosis, and the present results also suggest an association with peripheral neuropathy, which could be due to reduced capacity to detoxify lipid peroxides in diabetes.
 ...
PMID:Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. 758 60

Amyloidosis is a heterogeneous group of disorders characterized by extracellular deposition of abnormal protein fibrils which are derived from different proteins in different forms of the disease. Asymptomatic amyloid deposition in a variety of tissues is a universal accompaniment of ageing, and clinical amyloidosis is not rare. Intracerebral and cerebrovascular beta-protein amyloid deposits are a hallmark of the pathology of both sporadic and familial Alzheimer's disease, beta 2-microglobulin-derived amyloid is a common complication of long term haemodialysis, and islet amyloid polypeptide is the fibril protein in the universal islet amyloidosis of type II diabetes mellitus. New fibril proteins have lately been identified in hereditary amyloidosis, including variants of gelsolin, apolipoprotein AI, lysozyme and fibrinogen. The development of radiolabelled serum amyloid P component (SAP) scintigraphy has allowed amyloid to be diagnosed non-invasively in vivo for the first time, provided unique insight into the distribution and size of amyloid deposits, and yielded novel information on the natural history and the effects of treatment. Amyloid deposits are in a state of dynamic turnover and can regress if new fibril formation is halted. The recent elucidation of the three dimensional structure of human SAP may enable the design of specific therapeutic agents.
 ...
PMID:Amyloidosis. 786 80

The apolipoprotein CIII allele S2 is associated with hypertriglyceridaemia and myocardial infarction. 15 subjects with type 2 diabetes mellitus and the S2 allele had significantly greater systolic blood pressure than 48 without this allele (mean 142 [SD10]) vs 129 [14] mmHg), despite being on antihypertensives more frequently. S2 patients showed better glycaemic control (glycated haemoglobin [HbA1C] 8.4 [2.0] vs 9.9 [2.0]%). Stepwise multiple regression indicated S2 as an independent predictor of both blood pressure and HbA1C. These findings suggest mechanisms for relations between glucose and triglyceride metabolism and blood pressure.
 ...
PMID:Blood pressure, coronary artery disease, and glycaemic control in type 2 diabetes mellitus: relation to apolipoprotein-CIII gene polymorphism. 790 70

The aim of the present study was to determine if low-density lipoproteins (LDLs) and red blood cell (RBC) membranes from diabetic patients present an increased susceptibility to lipoperoxidation, which might be related to the increased incidence of atherosclerosis in diabetes. LDLs and RBC membranes were isolated from 11 insulin-dependent (IDDM) and 18 non-insulin-dependent diabetic (NIDDM) patients and exposed to a peroxidative stress by incubation with phenylhydrazine. The susceptibility to peroxidation was determined by measuring the production of thiobarbituric acid-reactive substances (TBARS) after the incubation. The following parameters were also evaluated: plasma glucose, triglycerides (TG), phospholipids (PL), total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) A-I, apo B, hemoglobin A1c (HbA1c), LDL PL and cholesterol, LDL fatty acid composition, and RBC membrane PL and cholesterol. Although they were apparently normolipidemic, diabetic patients showed an increased susceptibility to peroxidation in LDLs and erythrocyte membranes as compared with control subjects. The amount of arachidonic acid in LDLs and the PL concentration of RBC membranes from diabetic patients were significantly higher than in normal subjects. The increased lipoperoxidability of both RBC membranes and LDLs might play a central role in the pathogenesis of the vascular complications of diabetes mellitus.
 ...
PMID:Increased susceptibility to lipid oxidation of low-density lipoproteins and erythrocyte membranes from diabetic patients. 799 Jun 98

Lipoprotein(a) (Lp(a)) consists of a unique apolipoprotein, apolipoprotein(a), (apo(a)) linked by a disulphide bridge to apolipoprotein B of low density lipoprotein (LDL). Apo(a) is homologous with plasminogen and exhibits genetic polymorphism with the commoner phenotypes due to larger forms being associated with lower plasma levels and the less common phenotypes associated with smaller forms and higher plasma levels. The later are more common in patients with macrovascular disease. In a study of 6448 patients with established coronary heart disease we found that 43% had apo(a) levels above 300 units/litre and 10% had levels above 1000 units/litre and a geometric mean of 201 units/litre in contrast to 140 normal controls in whom 25% exceeded 300 units/litre, 1% exceeded 1000 units/litre and the geometric mean was 107 units/litre. Amongst patients with cholesterol levels < 5.5 mmol/L undergoing coronary artery surgery were patients with low HDL levels and raised apo(a) levels who would not be identified in screening focusing primarily on total cholesterol. In patients with both insulin dependent and non insulin dependent diabetes mellitus those with microalbuminuria or albuminuria (known to be at high risk for macrovascular disease) had apo(a) levels comparable to non diabetic patients with coronary artery disease while diabetic patients without microalbuminuria had normal levels of apo(a). It is likely that apo(a) has a role in the accelerated macrovascular disease in diabetic patients with renal disease.
 ...
PMID:Apolipoprotein(a) and atherogenesis. 826 49

Considerable data support a genetic basis to susceptibility for NIDDM, but previous analysis of candidate genes has failed to identify a major susceptibility locus. Among regions with multiple potential candidates is chromosome 11, which includes the apolipoprotein C3 cluster, muscle glycogen phosphorylase, two insulin-dependent diabetes loci, the sulfonylurea receptor, and ataxia telangiectasia. To test linkage, we initially typed 19 markers at 10- to 15-cM intervals along chromosome 11. Analyses carried out under parametric models in members of 16-19 families of northern European ancestry detected possible linkage of NIDDM to D11S916. Nonparametric methods detected possible linkage to NIDDM at D11S901, which was 5- 10 cM distant, and at D11S935, which was approximately 30 cM distant. Both D11S916 and D11S901 were near the IDDM4 locus. To further test linkage, we typed five additional markers within 5 cM of D11S916 in the initial 19 families. We also tested markers from the linked region in a second set of recently sampled additional families. Two additional markers (D11S527 and D11S534) showed possible linkage in the initial 19 families, but none of the markers were linked to NIDDM in a separate set of families from the same ethnic background. The best evidence for linkage in the combined data set of the initial 19 families and 26 additional families was at D11S534 under parametric analysis (Z = 1.20) and at D11S935 under nonparametric analysis (affected pedigree number, P = 0.0013). Our findings suggest marginal evidence for a diabetes susceptibility locus in the region between D11S901 and D11S935, with the best evidence for a locus at or near D11S935. Replication of these findings in other populations will be necessary to distinguish false-positive linkage from a true NIDDM susceptibility locus.
 ...
PMID:Linkage studies of NIDDM with 23 chromosome 11 markers in a sample of whites of northern European descent. 859 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>