Lipoprotein(a) levels in type II diabetic patients are not influenced by metabolic control or by microalbuminuria.
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Albuminuria↗
Biomedical subjects
G Crepaldi
Publications and source records attributed to G Crepaldi.
Dyslipoproteinaemia in manifest diabetes.
The prevalence of hypercholesterolaemia is similar in non-insulin-dependent diabetic (NIDDM) patients and in non-diabetic subjects. The prevalence of hypertriglyceridaemia and of low high-density-lipoprotein (HDL) cholesterol is roughly double the norm in NIDDM, but the exact prevalence varies greatly from study to study. Obesity and a familial form of hypertriglyceridaemia (conditions that may alter plasma lipoprotein levels) are frequently observed in NIDDM patients. In carefully controlled NIDDM patients without concomitant primary hyperlipoproteinaemia, body weight may be more important than glycaemic control or the type of treatment plan adopted in determining lipoprotein levels. Hypertriglyceridaemia in NIDDM is a result of both increased very-low-density-lipoprotein (VLDL) synthesis and impaired VLDL catabolism. Whilst low-density-lipoprotein (LDL) levels are normal, the LDL synthesis and removal rates may be increased. Low high-density-lipoprotein (HDL) levels may be due to increased catabolism. In addition to quantitative changes in plasma lipids and lipoproteins. NIDDM patients demonstrate qualitative lipoprotein alterations. The size and density of LDL particles in NIDDM patients are greatly affected by triglyceride levels. Smaller, denser LDL particles have been observed in hypertriglyceridaemic subjects. Glycosylation of apolipoproteins may alter the metabolic properties of lipoproteins. Glycosylated and small, dense LDL have an increased susceptibility to oxidation.
Diabetes Mellitus, Type 2↗
Effect of ursodeoxycholic acid on intracellular pH in a bile duct epithelium-like cell line.
Recent studies in perfused livers and isolated hepatocytes indicate that ursodeoxycholic acid-induced HCO3-rich hypercholeresis originates at the ductule/duct level. The bile duct epithelium may be involved in bile alkalinization by passively reabsorbing the protonated unconjugated ursodeoxycholic acid, by directly secreting in response to an ursodeoxycholic acid-induced increase in acid/base transporter activity or by taking up UDCA- in exchange for a base equivalent. To investigate these processes in more detail, we studied the effects of ursodeoxycholic acid on intracellular pH in SK-ChA-1, a well-differentiated human cholangiocarcinoma cell line similar to bile duct epithelium in terms of intracellular pH regulatory mechanisms and morphological markers. Intracellular pH changes were monitored with a microfluorimetric setup using the fluorescent indicator 2'-7'-bis(2-carboxyethyl)-5,6,carboxy fluorescein. Administration of 50 to 1,000 mumol/L UDCA in the absence of HCO3 caused dose-dependent intracellular acidification (intracellular pH = -0.13 +/- 0.03 pH/U after 500 mumol/L ursodeoxycholic acid). Acidification was not prevented by preincubation of cells with 0.5 mmol/L 4,4-diisothiocyanatostilbene-2,2,-disulfonic acid (DIDS) for 30 min or by furosemide administration (1 mmol/L), thus ruling out the stimulation of Cl/HCO3 exchange or the presence of an ursodeoxycholic acid/base exchange. Ursodeoxycholic acid also acidified human fibroblasts, a cell type with no transport capability for ursodeoxycholic acid. In addition, direct measurement of the activities of the three major acid/base transporters in Sk-ChA-1 cells (Na+/H+ exchange, sodium-dependent and sodium-independent Cl/HCO3 exchange) failed to show significative differences between cells treated with 500 mumol/L UDCA and controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Acid-Base Equilibrium↗
Levels and physicochemical properties of lipoprotein subclasses in moderate hypertriglyceridemia.
Moderate hypertriglyceridemia is associated with several abnormalities of the plasma lipoprotein particles and it may be a risk factor for atherosclerotic vascular diseases. Plasma lipid, lipoprotein and apolipoprotein levels, as well as lipoprotein composition and physical properties, were examined by ultracentrifugation in a zonal rotor and by gradient gel electrophoresis in 14 patients with moderate hypertriglyceridemia (plasma triglycerides 4.00 +/- 0.32 mmol/l, mean +/- S.D.) and in 14 control subjects. Based on zonal ultracentrifugation hypertriglyceridemic patients have higher levels of cholesterol in all VLDL subclasses (Sf > 200, 100-200, 60-100 and 20-60), in IDL and in small and dense LDL. Both HDL2 and HDL3 cholesterol levels are reduced. The LDL flotation rate is inversely related to plasma triglyceride levels, thus indicating that the higher the plasma triglycerides the smaller and/or denser the LDL are. The triglyceride percent content of LDL2 and HDL3 is increased, while that of esterified cholesterol is reduced in hypertriglyceridemic patients. Gradient gel electrophoresis shows that the LDL peak size is lower (25.2 +/- 0.5 nm, mean +/- S.D.) in hypertriglyceridemic than in control subjects (27.1 +/- 0.4 nm; P < 0.0001). Considering both hypertriglyceridemic and control subjects the LDL peak effluent volume from the zonal rotor (which reflects the LDL flotation rate) is inversely related to the LDL peak size determined by gradient gel electrophoresis (r = -0.71; P = 0.0006) and the plasma triglyceride levels are related to LDL peak effluent volume (r = 0.74; P = 0.0002) and to LDL peak size (r = -0.95; P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Apolipoproteins↗
Comparison of lipoprotein(a) assay methods in serum and in a plasminogen-free fraction.
We compared five immunoassays for lipoprotein(a) (Lp(a)) determination (end-point immunonephelometry, two-site IRMA and three different ELISA methods) in order to verify their agreement. Since it has been demonstrated that human apo(a) structure is closely similar to that of plasminogen, cross-reactivity of apo(a) antibodies with plasminogen represents an important technical problem in serum Lp(a) quantification. On this account we used a plasminogen-free fraction obtained by one-step ultracentrifugation at a density of 1.125 g/ml, in which no plasminogen activity was found. A satisfactory correlation between serum and plasminogen-free fraction Lp(a) values was found for all the methods; the limits of agreement were too high, however, to use serum and fraction interchangeably. Furthermore, it emerged that the different assays were more comparable and individual Lp(a) differences between methods were less spread when plasminogen-free fraction was used instead of serum.
Analysis of Variance↗
Lipoprotein compositional abnormalities in type 1 (insulin-dependent) diabetic patients.
Patients with type 1 (insulin-dependent) diabetes mellitus in good metabolic control usually have normal plasma lipid levels yet they have an increased incidence of vascular complications. Abnormalities in the distribution and composition of lipoprotein subfractions might in part be responsible for the macroangiopathy seen in type 1 diabetes mellitus. The plasma lipids, lipoproteins and apolipoproteins were studied in 9 type 1 diabetic patients during conventional insulin therapy and in 14 healthy controls. Plasma lipoproteins were analysed by ultracentrifugation in a zonal rotor to evaluate their concentrations and flotation properties and for compositional analysis. In diabetic patients the mean glycosylated haemoglobin (HbA1c) was 9.44 +/- 1.02% and the plasma lipid concentrations were not significantly different from healthy controls. The very low density lipoprotein (VLDL) subclass cholesterol concentrations were no different in diabetic patients and control subjects, but the VLDL cholesterol/triglyceride ratio was significantly lower in diabetic patients than in control subjects (0.43 +/- 0.05 vs 0.85 +/- 0.14; p < 0.05). The flotation rate LDL2, the major component of low density lipoprotein (LDL) was lower in the diabetic patients compared with the control subjects. The cholesterol concentrations of intermediate density lipoprotein and LDL3, the minor component of LDL, were significantly higher (0.17 +/- 0.03 and 0.83 +/- 0.14 mmol/l respectively) in diabetic patients than in control subjects (0.05 +/- 0.02 and 0.24 +/- 0.08 mmol/l). The flotation properties and cholesterol concentrations of the high density lipoprotein (HDL) subclass, and the protein-lipid composition of LDL2, HDL2 and HDL3, were no different in diabetic patients and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration.
This double-blind study assesses the therapeutic efficacy and the safety of oral treatment with phosphatidylserine (BC-PS) vs placebo (300 mg/day for 6 months) in a group of geriatric patients with cognitive impairment. A total of 494 elderly patients (age between 65 and 93 years), with moderate to severe cognitive decline, according to the Mini Mental State Examination and Global Deterioration Scale, were recruited in 23 Geriatric or General Medicine Units in Northeastern Italy. Sixty-nine patients dropped out within the 6-month trial period. Patients were examined just before starting therapy, and 3 and 6 months thereafter. The efficacy of treatment compared to placebo was measured on the basis of changes occurring in behavior and cognitive performance using the Plutchik Geriatric Rating Scale and the Buschke Selective Reminding Test. Statistically significant improvements in the phosphatidylserine-treated group compared to placebo were observed both in terms of behavioral and cognitive parameters. In addition, clinical evaluation and laboratory tests demonstrated that BC-PS was well tolerated. These results are clinically important since the patients were representative of the geriatric population commonly met in clinical practice.
Activities of Daily Living↗
Prevalence of extracranial carotid artery lesions at duplex in primary aldosteronism.
Renovascular hypertension and high renin hypertension were found to be associated with an excess prevalence of carotid artery atherosclerotic lesions and to a higher risk of stroke, respectively, as compared to low-to-normal renin hypertension. Primary aldosteronism, being characterized by hypertension and a chronically suppressed plasma renin activity, should be accompanied by a low prevalence of carotid artery lesions. To verify this hypothesis we investigated prospectively, by a high resolution duplex ultrasound technique, the prevalence of extracranial carotid artery lesions in a case-controlled study of 34 (22 women and 12 men, aged 22 to 76 years) patients with no history or symptoms of cerebrovascular disease. Primary aldosteronism was diagnosed in 17 patients; 12 had a surgically confirmed unilateral aldosterone-secreting adenoma; and 5 had idiopathic hyperaldosteronism. Each primary aldosteronism patient was individually matched with a control with primary hypertension for sex, race, age, body mass index, casual blood pressure levels, duration of hypertension, smoking, diabetes mellitus, total serum cholesterol, and triglycerides. After the matching, the two groups were similar in terms of demographic features and overall cardiovascular risk profile (all P = NS). However, plasma renin activity and aldosterone levels were significantly lower and higher, respectively, in primary aldosteronism than in primary hypertensive patients. In primary aldosteronism the overall prevalence of carotid artery lesions at duplex was 59%, not significantly different from that (53%) found in primary hypertensives. Thus, at variance with renovascular hypertension, primary aldosteronism is not associated with an excess prevalence of carotid artery lesions.
Adult↗
Heterozygous apolipoprotein C-II deficiency: lipoprotein and apoprotein phenotype and RsaI restriction enzyme polymorphism in the Apo C-IIPadova kindred.
Deficiency of apolipoprotein C-II (apo C-II), the cofactor for lipoprotein lipase, results in the familial chylomicronaemia syndrome characterized by severe hypertriglyceridaemia and fasting chylomicronaemia. To investigate the biochemical features of the heterozygous state for apo C-II deficiency, we characterized the lipid, lipoprotein and apolipoprotein profiles in 18 relatives of two affected individuals (brother and sister) homozygous for the apo C-IIPadova gene defect which results in the synthesis of a truncated 36 amino acid apolipoprotein. Carrier status was established in first degree relatives as well as in seven non-obligate heterozygotes by restriction enzyme analysis of amplified apo C-II genomic DNA using RsaI. No significant differences in lipid, lipoprotein and apo C-II levels were observed in heterozygotes when compared to unaffected family members. Thus, in this study, the carrier state was not associated with hypertriglyceridaemia or reduced plasma levels of apo C-II. However, analysis of amplified DNA from members of the apo C-IIPadova kindred by digestion with the enzyme RsaI, which identifies the mutant apo C-II, permitted the identification of heterozygous family members which could not be recognized by measuring either fasting triglycerides or plasma apo C-II levels. This study provides further evidence that apo C-II deficiency syndrome is a heterogeneous disease not only at the molecular level but also on the clinical ground with variable phenotypic expression in heterozygous individuals from different kindreds.
Adolescent↗
Lipoprotein abnormalities in hypertriglyceridaemic patients on long-term haemodialysis.
OBJECTIVES: To analyse by ultracentrifugation in a zonal rotor the plasma lipoproteins in hypertriglyceridaemic patients on long-term haemodialysis. DESIGN: Case-control study. SETTING: Tertiary referred care centre. SUBJECTS: Ten consecutive hypertriglyceridaemic patients on haemodialysis and 12 consecutive healthy controls. MAIN OUTCOME MEASURES: Plasma lipid and lipoprotein cholesterol concentrations, lipoprotein physical properties and compositions, apolipoprotein concentrations. RESULTS: Hypertriglyceridaemia in patients undergoing haemodialysis is characterized by an increased amount of small and slow floating very-low density lipoproteins (VLDL), higher concentrations of intermediate density lipoproteins (IDL) and small and dense low-density lipoprotein (LDL) particles; reduced levels of high-density lipoproteins (HDL), in particular of HDL2. The lipoprotein composition of such patients indicates reduced cholesterol ester and increased triglyceride content. Compared to controls, they have lower levels of plasma apolipoprotein A-I and A-II and higher B, C-II, C-III and E values. CONCLUSIONS: The lipoprotein abnormalities observed in hypertriglyceridaemic patients undergoing haemodialysis have recently been associated with an increased incidence of vascular complications and may in part explain the high incidence of vascular disease reported in these subjects.
Aged↗
Clinical assessment of low molecular weight heparin effects in peripheral vascular disease.
This study was carried out, using the double-blind method vs placebo, on 36 patients suffering from stage II peripheral vascular disease (PVD) according to Leriche, to check the clinical and hemorrheologic effects of the administration of a new low molecular weight heparin (LMWH). After a one-month washout period, the patients were randomly assigned either to the group treated with the LMWH (15,000 aXaU/day sc) or to the group treated with indistinguishable placebo. At the start of the study and after three and six months of treatment, clinical, instrumental, and laboratory tests were performed to assess local and systemic efficacy and tolerance. The LMWH under study caused a statistically significant increase in claudication time, with a parallel increase in the absolute claudication distance and in the interval free of pain. The drug also led to a significant increase in activated partial thromboplastin time, the values of which, however, remained within the normal limits, and to a marked reduction in blood viscosity. No significant variation was observed in the tolerability parameters in the two treatment groups, and no local or systemic adverse reactions occurred.
Aged↗
Lipoprotein abnormalities in well-treated type II diabetic patients.
OBJECTIVE: To investigate lipoprotein levels and composition in well-treated type II diabetic patients. RESEARCH DESIGN AND METHODS: Cholesterol and triglyceride levels were measured in plasma, VLDL, LDL, and HDL in 120 type II diabetic patients in good to fair metabolic control (HbA1c, 7.2 +/- 1.6%) and in 30 normal control subjects. ApoAI, AII, B, CII, CIII, and E levels in plasma were also determined. RESULTS: The diabetic patients have significantly higher levels of mean plasma cholesterol (5.85 vs. 5.43 mM, P = 0.03), LDL triglycerides (0.41 vs. 0.31 mM, P = 0.003), and HDL triglycerides (0.24 vs. 0.19 mM, P = 0.02), whereas total triglycerides, VLDL cholesterol and triglycerides, LDL cholesterol, and HDL cholesterol are not significantly different from normal control subjects. ApoB (150 vs. 135 mg/dl, P = 0.02) and apoCIII (10.6 vs. 8.4 mg/dl, P = 0.01) are significantly higher in diabetic patients compared with control subjects. No significant differences are observed in all the parameters among diabetic patients treated with diet only, sulphonylurea, sulphonylurea plus biguanides, or insulin. Body weight is significantly related to VLDL lipids. The VLDL triglycerides are inversely related to the HDL cholesterol in both diabetic patients and control subjects. The VLDL triglycerides are directly related to the HDL triglycerides only in diabetic patients. No other lipid or lipoprotein parameters are significantly related to body weight or metabolic control. CONCLUSIONS: Type II diabetic patients in good to fair metabolic control are characterized by minor alterations of the plasma lipids, but LDL and HDL triglycerides, apoB, and apoCIII are increased, thus indicating that the lipoprotein composition is altered, possibly because of an abnormal triglyceride metabolism and/or lipid transfer activity.
Aged↗
Effects of different antihypertensive agents on the overall cardiovascular risk profile.
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Antihypertensive Agents↗
Dexfenfluramine and neurotoxicity.
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Animals↗
Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis.
Recently it has been demonstrated that ipriflavone (IP), an isoflavone derivative, is able to increase bone mass in patients with established postmenopausal osteoporosis (PMO). Here we present a preliminary report of a 2-year multicenter, double-blind, placebo-controlled clinical study performed in order to evaluate the efficacy and tolerability of IP in PMO. A large number of patients with PMO, referred to 12 Italian centers, was randomly divided into 2 groups and treated with oral IP (600 mg/day) or placebo (Pl). All patients received an oral Ca supplement (1 g/day). One hundred and twenty six patients completed 1 year of the study. Bone mineral density (BMD) of the distal radius, measured by DPA, serum osteocalcin (BGP), and urinary hydroxyproline excretion (HOP/Cr), were measured before and after 12 months. After 12 months, a significant increase in BMD was observed in the IP-treated group (P < 0.05). IP determined a reduction of HOP/Cr, while in Pl-treated patients a significant increase of this index, as well as of BGP, was observed. After 12 months the difference between the two groups resulted significant (P < 0.05) for BGP. The drug was well tolerated and the patients' compliance to the oral treatment resulted excellent. The results of this study indicate that IP is able to increase bone mass in patients with PMO.
Aged↗
Relationships among natriuresis, atrial natriuretic peptide and insulin in insulin-dependent diabetes.
Insulin-dependent diabetic patients have a large exchangeable body sodium pool, secondary to sodium retention. The pathogenesis of impaired natriuresis in insulin dependent diabetes remains to be elucidated. The present study examines the role of hyperinsulinemia, impaired atrial natriuretic release, and resistance to atrial natriuretic peptide action in determining sodium retention in normotensive and hypertensive insulin-dependent diabetic patients. Eight insulin-dependent diabetic patients had significantly higher daily sodium excretion rate (147 +/- 16 mmol/day; mean +/- SE) during conventional insulin treatment (daily plasma glucose: 11.6 +/- 1.2 mmol/liter; daily plasma insulin: 27 +/- 3 microU/ml) than during intensified insulin treatment (daily sodium excretion rate: 91 +/- 12, P less than 0.01; daily plasma glucose: 6.8 +/- 0.7, P less than 0.01; daily plasma insulin: 44 +/- 4, P less than 0.01). Daily sodium excretion rate was also significantly lower (107 +/- 13, P less than 0.01) in the same diabetic patients during intensified insulin treatment along with hyperglycemic clamp (daily plasma glucose: 12.8 +/- 0.3, NS; plasma insulin 48 +/- 4, P less than 0.01). Seven control subjects had lower extracellular liquid volume than eight insulin-dependent diabetic patients (11.0 +/- 0.8 l/1.73 m2 vs. 14.8 +/- 0.9, P less than 0.05) and also had baseline plasma atrial natriuretic peptide concentrations (18 +/- 5 pg/ml vs. 37 +/- 4, P less than 0.05). Atrial natriuretic peptide response to saline challenge was blunted in insulin-dependent diabetic patients when saline was administered on the basis of body surface area (90 mmol/1.73 m2.90 min) but not when administered on the basis of extracellular liquid volume (ECV) (8.2 mmol/liter ECV.90 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats.
Abnormal glycosaminoglycan metabolism is involved in the onset of anatomo-functional derangements in diabetic nephropathy, and determines the loss of glomerular basement membrane anionic charges leading to albuminuria. Glycosaminoglycan administration was shown to increase the negative electrical potential of the vessel wall, inhibit mesangial cell proliferation, which is an anatomical hallmark of diabetic nephropathy, and slow down the progression to uremia in subtotally nephrectomized rats, a model that shares some pathogenetic key events with diabetic nephropathy. Based on these considerations, we verified the effect of exogenous glycosaminoglycans on renal involvement in streptozotocin diabetic rats. Long-term administration of two glycosaminoglycans (low-molecular weight heparin and dermatan sulphate) prevented glomerular basement membrane thickening, glomerular anionic charge reduction, as well as the onset of albuminuria without affecting glomerular filtration rate and metabolic control of the disease. Our data demonstrate that the long-term administration of glycosaminoglycans has a favorable effect on morphological and functional renal abnormalities in diabetic rats.
Albuminuria↗
Excess prevalence of extracranial carotid artery lesions in renovascular hypertension.
High renin hypertension has been associated with a higher risk of stroke than low-to-normal renin hypertension. Accordingly, we investigated prospectively the prevalence of the extracranial carotid artery lesions in a case-control study of 70 patients (38 women and 32 men, aged 16 to 77 years) without history or symptoms of cerebrovascular disease. Renovascular hypertension was diagnosed in 35 patients on the basis of the angiographic demonstration of renal artery stenosis and of the favorable outcome after revascularization. It was caused by atherosclerosis in 20 patients and by fibrodysplasia in 15. Each renovascular hypertensive patient was individually matched with a control with primary hypertension for sex, race, age, blood pressure levels, duration of hypertension, smoking, diabetes mellitus, total serum cholesterol, and triglycerides. Carotid arteries were evaluated by a High Resolution Duplex system (Biosound 2000, probe 4 cm, 8 mHz). Our results show that after the matching the two groups were similar in terms of demographic features and overall cardiovascular risk profile (all P = NS). In renovascular hypertensives the prevalence of carotid artery lesions (82.6%) was significantly (P less than .01) higher than in primary hypertensives (42.9%). The higher prevalence of lesions in renovascular hypertension was observed not only in patients with atherosclerosis (100% v 55%, P less than .001), but also in those with fibrodysplasia (57% v 27%, P less than .01). Thus, for the same demographic features and overall cardiovascular risk profile, renovascular hypertension carries a more detrimental effect on the carotid artery than primary hypertension.
Adolescent↗