Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six fractions of serum apolipoproteins (apolipoprotein A-I, A-II, B, C-II, C-III and E) obtained from 100 patients with diabetes mellitus not administered any antihyperlipidemic drugs were measured to clarify the relationship between diabetes mellitus and the abnormal lipidosis. The serum concentrations of apolipoprotein B, C-II and C-III were significantly higher in these diabetics than in the controls (p < 0.05), and that of apolipoprotein E was significantly lower (p < 0.01). The serum concentrations of apolipoprotein C-II, C-III and E (p < 0.05) as well as HbA1C and FRA (p < 0.001) were significantly higher in the insufficient control group (FPG > or = 140 mg/dl) of diabetes mellitus. The serum concentrations of apolipoprotein C-II, C-III and E were significantly higher in the treated groups (p < 0.05). The serum concentrations of apolipoprotein B, C-II, C-III and E were significantly higher (p < 0.01) in the high cholesterol group (> 220mg/dl) and the high triglyceride group (> 150mg/dl) among the diabetic groups, but no significant differences were observed in the concentrations of apolipoprotein A-I and A-II.
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PMID:[Evaluation for serum apolipoproteins in patients with diabetes mellitus]. 813 26

The effects of long-term monotherapy with felodipine, a calcium antagonist, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 51 hypertensive patients: 13 with normal glucose tolerance and 38 with glucose intolerance. The levels of plasma glucose, serum lipids, and glycosylated hemoglobin A1c were determined before and during long-term (7.5 +/- 0.5 months; range, 6 to 9 months) therapy with felodipine. A 75-g oral glucose tolerance test was performed before and during long-term felodipine therapy. Significant decreases in both systolic and diastolic blood pressures in both patient groups were maintained during the therapy. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patients with normal glucose tolerance developed diabetes mellitus during the study. Serum lipid levels did not change significantly in either group of patients except for significant decreases in high-density lipoprotein cholesterol and apolipoprotein A-I in the group with normal glucose tolerance tests, but those changes remained within the normal range. Furthermore, neither serum lipid nor apolipoprotein levels were altered, even in patients with hypercholesterolemia (total cholesterol levels, > 5.69 mmol/L = 220 mg/dL). These results suggest that long-term therapy with felodipine may not alter glucose and lipid metabolism in hypertensive patients, and felodipine appears to be useful as an antihypertensive agent for hypertensive patients with either dyslipidemia or impaired glucose metabolism.
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PMID:Felodipine therapy may not alter glucose and lipid metabolism in hypertensives. Felodipine Multicenter Prospective Study Group in Japan. 828 62

Non-enzymatic glycation of plasma proteins may contribute to the excess risk of developing atherosclerosis in patients with diabetes mellitus. Glycated apolipoprotein A-I isolated from diabetic subjects was tested in vitro for its ability to activate lecithin:cholesterol acyltransferase, the principal cholesterol-esterifying enzyme in plasma. Activation by glycated apolipoprotein A-I was significantly lower at all concentrations than the activation by normal apolipoprotein A-I. Linear regression analysis of the kinetic data shows that the ratio app Vmax/app Km was significantly lower (p < 0.01) for glycated apolipoprotein A-I (0.29 nmol.l/h.mumol) than for normal apolipoprotein A-I (0.78 nmol.l/h.mumol). Because lecithin:cholesterol acyltransferase provides a driving force in reverse cholesterol transport by esterifying the cellular cholesterol removed by HDL, it is tempting to postulate that this abnormal activation may be associated with a reduction in reverse cholesterol transport and associated with the accelerated development of atherosclerosis in diabetic patients.
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PMID:Decreased activation of lecithin:cholesterol acyltransferase by glycated apolipoprotein A-I. 831 68

To evaluate the prevalence and risk factors of asymptomatic carotid artery disease, we analyzed a sample of 909 men and women (aged 40-79 years) drawn from the community-based Bruneck Ischemic Heart Disease and Stroke Prevention Study. For the four decades of age (40-49, 50-59, 60-69, and 70-79 years), respective prevalence rates as assessed by duplex scanning were found to be 8.2%, 39.7%, 66.4%, and 82.5% in men and 3.3%, 22.3%, 48.7%, and 76.7% in women. High-grade stenosis (> 80%) classified by Doppler criteria was twice as frequent in men (2.4%) as in women (1.1%). Age and sex were found to be particularly strong and independent predictors of asymptomatic carotid artery disease. Accordingly, separate logistic regression models were developed for both men and women in the elderly (65-79 years) and middle-aged (50-64 years) groups. Systolic blood pressure turned out to be the only attribute with independent significance in all subgroups examined. Cigarette smoking, recorded as pack-years, emerged as the leading risk factor of carotid atherosclerosis in men. Serum fibrinogen levels were found to be highly indicative of carotid artery disease in elderly men and women. For apolipoprotein B predictive significance was observed in the middle-aged populations, whereas apolipoprotein A-I had a protective effect in elderly women. Diabetes mellitus completed the risk factor profile for elderly men. In summary, the relation between cardiovascular risk factors and asymptomatic carotid artery disease showed a dynamic dependence on sex and age. These findings may help to improve the efficacy of risk prediction in the general population and facilitate well-directed preventive measures.
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PMID:Prevalence and risk factors of asymptomatic extracranial carotid artery atherosclerosis. A population-based study. 848 16

The serum concentration of lipoprotein(a) [Lp(a)], lipids, lipoproteins, apolipoprotein A-I, and apolipoprotein B were determined in 228 patients with cerebral infarction, composed of 87 cases of asymptomatic lacunar infarction, 99 cases of lacunar infarction, and 42 cases of atherothrombotic infarction, and in a control group of 138 healthy subjects with normal MRI. Observations were made on the distribution of Lp(a), Lp(a) and other risk factors for cerebral infarction and these were statistically analyzed, primarily by multiple logistic regression analysis. The diagnosis of these cases was based on the Classification of Cerebrovascular Diseases III of the National Institute of Neurological Disorders and Stroke. The following results were obtained. 1) Lipoprotein (a) (1) Lp(a) did not show a normal distribution with the curve showing a gradual declining slope to the right. It was therefore considered not appropriate in our analysis to use as a means or standard deviation. (2) The 25th percentile, 50th percentile, and 75th percentile of the control group were 5.0 mg/dl, 11.0 mg/dl, and 22.4 mg/dl, respectively. In studying the distribution in these percentile ranges by subtypes of infarction, an increase in cases showing values greater than the median of the control group was observed in asymptomatic lacunar infarction, lacunar infarction, and atherothrombotic infarction, when compared to the control group. In asymptomatic lacunar infarction and lacunar infarction in particular, Lp(a) showed a significantly higher value compared to the control group. (3) However, by multiple logistic regression analysis to adjust for age and sex, Lp(a) did not show a significant odds ratio for asymptomatic lacunar infarction, lacunar infarction and atherothrombotic infarction. 2) Various serum lipids and other parameters (1) The various serum lipids did not show any involvement in asymptomatic lacunar infarction. However, involvement of HDLC and Apo A-I in lacunar infarction and atherothrombotic infarction was observed with the odds ratios in lacunar infarction being 4.2 with a confidence interval of 2.9-9.4 and 4.7 with a confidence interval of 2.2-10.1, and the odds ratios in atherothrombotic infarction being 3.1 with a confidence interval of 1.1-9.0 and 9.6 with a confidence interval of 3.0-30.5, respectively. (2) Involvement of diabetes mellitus in asymptomatic lacunar infarction and lacunar infarction was small, but a strong involvement in atherothrombotic infarction was observed with the odds ratio being 4.3 with a confidence interval of 1.2-16.2. (3) Involvement of hypertension in asymptomatic lacunar infarction and lacunar infarction was observed with the odds ratios being 2.6 with a confidence interval of 1.4-5.2 and 5.6 with a confidence interval of 2.4-13.0, respectively, but the involvement in atherothrombotic infarction was low. The foregoing results indicated that there was no involvement of Lp(a) as a risk factor for any type of cerebral infarction, unlike its involvement in coronary heart diseases. Only blood pressure was involved as a risk factor for asymptomatic lacunar infarction, but for lacunar infarction not only blood pressure but also HDLC and Apo A-I were involved as risk factors. HDLC, Apo A-I, and diabetes mellitus were involved as risk factors for atherothrombotic infarction, but the involvement of hypertension was minimal.
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PMID:Lipoprotein(a) and other risk factors for cerebral infarction. 856 15

Effectiveness of a simultaneous inhibition of cholesterol absorption and synthesis, caused by sitostanol ester margarine and pravastatin, was studied to control mild hypercholesterolemia in men with non-insulin-dependent diabetes mellitus (NIDDM) (n = 8). Margarine, 24 g daily, was a basal dietary treatment. Four 7-week intervention periods included margarine, sitostanol (3 g/day) ester margarine, pravastatin (40 mg/day), and sitostanol ester margarine plus pravastatin in a random order. Pravastatin lowered serum total (-32%) and LDL cholesterol (-38%) and apolipoprotein B (-39%) because of enhanced removal (+20%) and decreased production (-26%) of LDL apolipoprotein B, and reduced synthesis (-9%) and turnover (-8%) of cholesterol, which resulted in reduced biliary cholesterol seretion (-18%). Even though serum triglycerides were lowered by 28%, VLDL, IDL, and light and dense LDL became triglyceride-enriched. Despite increasing cholesterol synthesis, sitostanol lowered LDL cholesterol (-14%) by inhibiting cholesterol absorption (-68%) and LDL apolipoprotein B production rate (-20%). Combination of pravastatin and sitostanol ester lowered serum total, VLDL, IDL, and LDL cholesterol and LDL apolipoprotein B by the highest rate, 35%, 50%, 35%, 44%, and 45% from the control margarine period, respectively, because of reduced apolipoprotein B transport rate (but unchanged removal), in both the total and dense LDL subfractions. HDL cholesterol and apolipoprotein A-I kinetics were unchanged. In spite of decreased absorption, cholesterol synthesis was not compensatorily increased. In conclusion, simultaneous inhibition of cholesterol absorption and synthesis lowers LDL cholesterol and apolipoprotein B by 44-45% solely through inhibition of LDL apolipoprotein B production rate in hypercholesterolemic NIDDM patients. A combination of statin to sitostanol ester margarine-resistant patients offers a safe and effective measure to normalize abnormally high cholesterol values, probably with a lowered statin dose.
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PMID:Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men. 886 62

Hypercholesterolemia is an important atherogenic risk factor in type II diabetes, and although coronary artery disease (CAD) is frequent in these patients, it is not known whether cholesterol and lipoprotein metabolism differ in patients with (CAD+) and without CAD (CAD-). Our aim was to study cholesterol metabolism and lipoprotein kinetics in mildly hypercholesterolemic type II diabetic men with and without CAD under similar dietary conditions. Despite similar serum and lipoprotein cholesterol levels, and kinetics of total and dense LDL apo B, light and dense LDL particles were cholesterol-enriched only in CAD+ subjects. Apolipoprotein A-II level was lower in CAD+ than in CAD- subjects (27.1 +/- 0.7 versus 30.9 +/- 0.7 mg/dl, P < 0.05), HDL cholesterol and apolipoprotein A-I kinetics were similar in the two groups. Cholesterol absorption was significantly higher in the CAD+ versus CAD- subjects (27 +/- 2 versus 20 +/- 3%, P < 0.05). In multiple logistic stepwise regression analysis with CAD as the dependent variable, cholesterol absorption efficiency and serum plant sterol/cholesterol proportions were the only variables significantly associated with CAD. In conclusion, in mildly hypercholesterolemic type II diabetic patients, the only metabolic parameter differentiating CAD patients from non-CAD ones was significantly higher cholesterol absorption efficiency in the coronary patients, which could contribute to the finding of the atherogenic cholesterol-rich dense LDL subfraction in these patients. Thus, a treatment causing cholesterol malabsorption by sitostanol alone or in combination with statin could be beneficial in these patients.
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PMID:Cholesterol absorption and lipoprotein metabolism in type II diabetes mellitus with and without coronary artery disease. 890 58

Transfers or exchanges of cholesterol esters and triglycerides between lipoproteins are mediated by a specialized protein referred to as cholesteryl ester transfer protein (CETP), whereas those of phospholipids (PLs) are facilitated by both CETP and a specific phospholipid transfer protein (PLTP). In the present study, the authors compared phospholipid transfer (PLT) in normal subjects and in patients with non-insulin-dependent diabetes (NIDD), which is associated with an increased risk of atherosclerosis. PLT was measured in different recombination experiments using an isotopic assay in which the transfer of labelled PLs from very low-density lipoprotein (VLDLs) and low-density lipoproteins (LDLs) to high-density lipoproteins (HDLs) was determined. This allowed discrimination between the roles of VLDLs + LDLs, HDLs, and plasma PLT activity (PLTA). VLDL + LDL-dependent PLT, HDL-dependent PLT and PLTA were decreased in NIDD. VLDL + LDL-dependent PLT was found to be negatively correlated with the PL/apolipoprotein B ratio, whereas HDL-dependent PLT was positively correlated with the HDL2/HDL3 and PL/apolipoprotein A-I ratios and negatively correlated with the flow activation energy at the HDL surface. The HDL2/HDL3 ratio was positively correlated with PLTA but not with CETP, which confirms previous reports suggesting that PLTP might act as an HDL conversion factor. These data show that several abnormalities in PLT occur in NIDD and raise the question as to whether a lowered PLT might be a new characteristic of dis factors associated with an increased risk of atherosclerosis.
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PMID:Multiple abnormalities in the transfer of phospholipids from VLDL and LDL to HDL in non-insulin-dependent diabetes. 890 50

Glucokinase is the predominant hexokinase in pancreatic beta-cells and liver parenchymal cells and functions as a critical component of the glucose-sensing apparatus in these glucose-responsive cell types. In the beta-cells, the sensing leads to insulin secretion, while the role in hepatocytes is thought to be in hepatic glucose uptake. To determine the physiological response to an increase in hepatic glucokinase expression, transgenic mice expressing the human hepatic glucokinase gene under the control of a liver-specific human apolipoprotein A-I gene enhancer were generated. Transgenic mice had twofold higher total fasting hepatic glucokinase mRNA, which resulted in a modest 20% increase in fasting glucokinase activity. These animals showed lower fasting plasma glucose, insulin, and lactate levels and improved tolerance to glucose. In addition, glucokinase transgenic animals weighed less and had lower BMI than nontransgenic animals. Thus, glucokinase transgenic animals demonstrate that a modest change in hepatic glucokinase activity enhances the metabolism of glucose.
Diabetes 1997 Jan
PMID:Expression of human hepatic glucokinase in transgenic mice liver results in decreased glucose levels and reduced body weight. 897 Oct 74

Sequential chromatography of human follicular fluid (hFF) on Sephadex G-50, Q-Sepharose and finally Cibracon Blue yielded a protein molecule which biologically had a stimulating effect on steroid secretion (SSF) by ovarian granulosa cells in vitro. SDS-gel electrophoresis followed by blotting on PVDF membrane of the biologically active fraction revealed 3 bands of ca. 28, 27 and 24 kDa. The N-terminal sequence of the 3 bands corresponded completely with that of apolipoprotein A-I. In view of this, it was of interest to examine whether human ovary expresses apo A-I. Using specific primers for apo A-I and apo A-I-like protein (ALP; Richardson et al., 1996), we could demonstrate the presence of mRNA for apo A-I as well as ALP in the granulosa cells. The expression of ALP was found to be much higher than that of apo A-I. Like hFF-protein, purified apo A-I could also stimulate steroid secretion by human granulosa cells incubated in the presence of cholesterol. The functional role of ovarian apo A-I/ALP may be speculated as a transport molecule for steroid precursors.
Exp Clin Endocrinol Diabetes 1997
PMID:Expression of mRNA for ovarian steroid-stimulating factor (apolipoprotein A-I and apolipoprotein A-I-like protein) in human granulosa cells. 913 45


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