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Biomedical subjects

R Miccoli

Publications and source records attributed to R Miccoli.

At least 19 recordsLinked to original sources
PubMed2005

Maternal triglyceride levels and newborn weight in pregnant women with normal glucose tolerance.

OBJECTIVE: To determine the predictive value of serum triglyceride levels (TG) for neonatal weight in pregnant women with positive diabetic screening but normal glucose tolerance. RESEARCH DESIGN AND METHODS: We enrolled 180 pregnant Caucasian women with positive diabetic screening. All women underwent a 3-h 100-g oral glucose tolerance test (OGTT) at 27th +/- 4 week of gestation. At the time of OGTT, we measured: fasting plasma glucose, fasting lipids profile and determined ApoE polymorphisms to evaluate the effects on lipid levels. In 83 women with normal glucose tolerance and at term delivery we evaluated the association between maternal serum TG, specific maternal parameters known to affect fetal growth and newborn weight. RESULTS: Based on OGTT, gestational diabetes mellitus (GDM) was diagnosed in 36 women (20%), impaired glucose tolerance (IGT) in 23 (13%), and normal glucose tolerance (NGT) in 121 (67%). Serum TG concentration was significantly higher in women with GDM (2.47 +/- 0.77 mmol/l) as compared with NGT (1.99 +/- 0.64 mmol/l) or IGT (1.98 +/- 0.81 mmol/l) (P < 0.01). ApoE3 allelic frequency was 86%, ApoE2 and ApoE4 were 5 and 9%, respectively. We found no clear-cut association between apoE genotype and serum TG concentration. Macrosomia and LGA newborns were more frequent in IGT than in GDM or NGT (P < 0.01). In the 83 women with positive diabetic screening but normal glucose tolerance who delivered at term, the incidence of LGA infants was significantly higher in those with TG levels higher than the 75th percentile (> 2.30 mmol/l) (21%) than in mothers who had normal TG levels (4.5%) (P < 0.05). Pre-pregnancy BMI (r(2) = 0.067), weight gain during pregnancy (r(2) = 0.062), fasting serum TG (r(2) = 0.09), and 2-h post-OGTT glucose levels (r(2) = 0.044) were all associated with neonatal body weight (all P < 0.05 or less). However, on a multiple regression analysis, only pre-pregnancy BMI (F-test = 7.26, P < 0.01), and fasting serum TG (F-test = 4.07, P < 0.01) were independently associated with birth weight. CONCLUSIONS: Pre-pregnancy BMI and fasting maternal serum TG determined in the last trimester of gestation were independently associated with neonatal birth weight in women with normal glucose tolerance, but positive screening test. TG levels measured in the third trimester of pregnancy are independent of the genetic polymorphism of ApoE.

Adult↗
PubMed2003

Hyperglycaemia and cardiovascular risk.

Cardiovascular diseases represent, today, the principal cause of mortality in the general population, especially in subjects with type 2 diabetes mellitus. In these patients the risk of death from cardiovascular diseases is equal to that of non-diabetic subjects with a previous episode of myocardial infarction. Many factors concur to determine such high risk. Hyperglycaemia contributes to the increase in morbidity and cardiovascular mortality associated with diabetes mellitus. Hyperglycaemia acts as a multiplier of cardiovascular risk due to frequent association of multiple risk factors in diabetic patients. Therefore, effective treatment requires a more complete assessment of quantitative and qualitative aspects of glycemic control as well as all components of the diabetic syndrome or, more commonly, metabolic syndrome.

Biomarkers↗
PubMed2003

Prevalence and risk factors for gestational diabetes assessed by universal screening.

In order to evaluate the prevalence of gestational diabetes mellitus (GDM) and the presence of risk factors for GDM, we conducted a retrospective study of a cohort of Italian women. In addition, we compared universal versus selective screening to validate the ADA's recommendations in our population. From June 1st, 1995 to December 31st, 2001, universal screening for GDM was performed in 3950 women. The glucose challenge test (GCT) was positive (GCT+) in 1389 cases (35.2%). The 1-h glucose level after GCT enabled us to diagnose GDM directly in 24 pregnant women. Oral glucose tolerance test (OGTT) was performed in 1221 GCT+ women (144 cases with GCT+ dropped out) and GDM was diagnosed in 284 (23.2%) of them. OGTT was also performed in 391 randomly chosen, women from the GCT negative (GCT-) group. In this last group 25 (6.3%) women had GDM. Thus, the total number of subjects with GDM was 333 out of 3806 with a prevalence of 8.74% in the entire cohort. Assuming that the rate of GDM observed in the random sample of GCT- women is applicable to the whole group of 2561 GCT- women, then 161 GCT- patients could also have GDM. This will further increase the estimated prevalence for the whole cohort up to 12.3% (i.e. 469 out of 3806 pregnant women). There were 236 (5.6%) women with a low risk for GDM (normal weight, age less than 25 years and without a family history of diabetes). In this group we found 34 cases and five cases with positive screening test and GDM, respectively. Thus, if we excluded low risk women from the screening test, as suggested by ADA recommendations, only five women with GDM would have been missed. However, about 95% of our population were at medium or high risk for GDM and, therefore, would have been screened. The rate of GDM was significantly higher in women with a positive history of diabetes, increasing age, previous pregnancies, pre-pregnancy overweight and short stature. After logistic regression analysis, GDM diagnosis was significantly correlated with age (P<0.0001), pre-pregnancy BMI (P<0.0001), weight gain (P<0.0001) and family history of diabetes (P<0.01).

Adult↗
PubMed1999

[Atherogenic dyslipidemia, metabolic syndrome and cardiovascular risk].

The combination of high serum triglyceride levels and small low density lipoprotein particles, with a reduction in high density lipoprotein cholesterol levels has been named atherogenic lipoprotein phenotype or, simply, lipid triad. These lipid factors are commonly associated with peripheral resistance to the action of insulin, hyperinsulinism, central and visceral obesity, hypertension, hyperuricemia, hypercoagulability. The clustering of these nonlipid factors along with the lipid factors has been called metabolic syndrome. Insulin resistance plays a central role in the development of the lipid triad increasing the production of triglyceride-rich lipoproteins and decreasing their catabolism. There is currently great interest about the origins of the metabolic syndrome. One question under considerable research is whether genetic or acquired factors predominate in causing this syndrome. There seems to be little doubt that the metabolic syndrome taken as a whole constitutes a major risk factor for coronary heart disease. What is less certain is that each component of the syndrome is an independent risk factor. People with lipid triad are at very high risk of developing coronary heart disease, and careful management is warranted. Nonetheless, appropriate therapeutic strategies that will modify the metabolic syndrome as a whole are needed. More investigations about key metabolic steps that simultaneously affect multiple pathways will be required to yield a satisfactory therapy for high risk patients exhibiting the metabolic syndrome.

Cardiovascular Diseases↗
PubMed1998

Lipid-free apolipoprotein (apo) A-I is converted into alpha-migrating high density lipoproteins by lipoprotein-depleted plasma of normolipidemic donors and apo A-I-deficient patients but not of Tangier disease patients.

Plasma of patients with Tangier disease (TD) is devoid of alpha-LpA-I (apolipoprotein A-I-containing lipoprotein), which in normolipidemic plasma constitutes the majority of high density lipoprotein (HDL). The residual amounts of apolipoprotein A-I (apo A-I) in TD plasma have electrophoretic prebeta1-LpA-I mobility. We have previously demonstrated that TD plasma does not convert prebeta1-LpA-I into alpha-LpA-I. In this study we found that plasmas of normolipidemic controls, apo A-I-deficient patients and patients with fish-eye disease, but not plasmas of six TD patients, convert biotinylated lipid-free apo A-I into alpha-LpA-I. Supplementation of plasma with free oleic acid or fatty acid free albumin neither inhibited conversion activity in normal plasmas nor reconstituted it in TD plasma. In normal plasma the conversion activity was assessed in HDL and in the lipoprotein-free fraction. The latter fraction, however, generated larger particles only in the presence of exogenous phospholipid vesicles. To obtain particles with alpha-mobility, these vesicles had to contain phosphatidylinositol and/or cholesterol. Lipoprotein-depleted TD plasma did not convert lipid-free apo A-I into alpha-LpA-I even in the presence of exogenous vesicles with phospholipids or cholesterol. Taken together we conclude that disturbed transfer of glycerophospholipds onto apo A-I or prebeta1-LpA-I prevents maturation of HDL and thereby possibly causes deficiency of HDL cholesterol in patients with TD. Moreover, the lack of alpha-LpA-I in TD plasma together with its failure to convert exogenous apo A-I into an alpha-migrating particle provide specific tests for the diagnosis of TD.

Adult↗
PubMed1998

Modulated serum activities and concentrations of paraoxonase in high density lipoprotein deficiency states.

Paraoxonase is a high density lipoprotein (HDL) associated enzyme with a hypothesised role in the protection of low density lipoproteins (LDL) from oxidative stress. The present study examined paraoxonase in several genetically distinct HDL deficiency states. Despite reduction or even absence of detectable HDL, enzyme activity was present in sera from A-I-Pisa, A-I-Helsinki, A-I-Milano and Tangier patients. Both enzyme activities and peptide concentrations were modulated (reduced) but specific activities were broadly similar to controls, suggesting an impact on peptide concentration rather than an inhibition of enzyme activity. Despite the absence of HDL in A-I-Pisa and Tangier subjects, there was no association of paraoxonase with very low density lipoproteins or LDL. Paraoxonase function is maintained in HDL deficient states. It implies that certain HDL-associated anti-atherogenic processes may not be entirely compromised by HDL deficiency. This has important implications for the cardiovascular risk associated with modulated HDL concentrations.

Adult↗
PubMed1998

Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I.

Plasmas of patients with Tangier disease (TD) lack lipid-rich alpha-HDL which, in normal plasma, constitutes the majority of high density lipoprotein (HDL). Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or even lipid-free prebeta-HDL. By contrast to normal plasma, TD plasma does not convert prebeta-HDL into alpha-HDL. Moreover, fibroblasts of TD patients were found to be defective in secreting cholesterol or phospholipids in the presence of lipid-free apoA-I. We have therefore hypothesized that both defective conversion of prebeta-HDL into alpha-HDL and defective lipid efflux from TD cells onto lipid-free apoA-I result from a disturbance in phospholipid transfer occurring in both cellular and extracellular compartments. To test this hypothesis we established an assay that measures the activity of plasma, cells, and cell culture media to transfer radiolabeled phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) from vesicles onto apoA-I, apoA-II, albumin, or reconstituted HDL. Plasmas, HDL, and lipoprotein-depleted plasma of normolipidemic probands as well as cell homogenates and culture media of normal fibroblasts were active at 37 degrees C but not at 4 degrees C in transferring radiolabeled PC, PI, and PE dose- and time-dependently onto either lipid-free apoA-I or reconstituted HDL. Transfer of glycerophospholipids onto apoA-II was much lower than onto apoA-I; transfer onto albumin was close to background. Compared to ten normolipidemic plasmas and four apoA-I-deficient plasmas, plasmas of six TD patients were significantly reduced by 40-50% in their glycerophospholipid transfer activities. Compared to eight normal fibroblast cell lines, homogenates and culture media of four TD fibroblast cell lines were reduced by 40-50% and 30-35%, respectively, in their activity to transfer PC, PI, or PE onto apoA-I. Our data suggest that in TD the same mechanism underlies both defective conversion of prebeta-HDL into alpha-HDL and impaired efflux of cellular lipids, namely a defective phospholipid transfer.

Adult↗
PubMed1997

A natural apolipoprotein A-I variant, apoA-I (L141R)Pisa, interferes with the formation of alpha-high density lipoproteins (HDL) but not with the formation of pre beta 1-HDL and influences efflux of cholesterol into plasma.

ApoA-I(L141R)Pisa is a naturally occurring apolipoprotein A-I variant that causes virtual absence of HDL in hemizygotes and hypoalphalipoproteinemia with half-normal levels of HDL-cholesterol in heterozygotes. In this study we analyzed the distribution of HDL subclasses in plasmas of four hemizygotes for this mutation. We also investigated the abilities of these plasmas to esterify cholesterol and to promote cholesterol efflux. Residual apoA-I-containing lipoproteins in plasmas of hemizygotes for apoA-I(L141R)Pisa correspond to pre beta 1-LpA-I and small alpha-LpA-I. Unlike normal pre beta 1-LpA-I, pre beta 1-LpA-I of apoA-I(L141R)Pisa hemizygotes was not converted into a larger alpha-migrating particle. Plasmas of apoA-I(L141R)Pisa hemizygotes were significantly reduced in their activity to esterify cholesterol in either endogenous or exogenous lipoproteins. Cholesterol efflux capacity was significantly lower than that of normal plasma. Efflux of [3H] cholesterol from radiolabeled fibroblasts into apoB-depleted plasma of normal probands was biphasic with fast cholesterol efflux occurring in the first minute. Thereafter, cholesterol efflux was slow and unsaturable. After incubation with radiolabeled fibroblasts, efflux values of [3H]cholesterol into apoB-depleted plasma from normal controls and from apoA-I(L141R)Pisa hemizygotes were indistinguishable at 1 min. Longer incubations with apoB-free plasma from apoA-I(L141R)Pisa hemizygotes did not, however, lead to the unsaturable increase in cholesterol efflux that was observed during incubations with apoB-free plasma of normolipidemic probands. Pre beta 1-LpA-I of apoA-I(L141R)Pisa hemizygotes took up significantly less cell-derived [3H]cholesterol than pre beta 1-LpA-I of normal donors. We conclude that apoA-I(L141R)Pisa interferes with the formation of lipid-rich alpha-HDL but not with that of lipid-poor pre beta 1-LpA-I. Very low concentrations of alpha-HDL in plasmas of apoA-I(L141R)Pisa hemizygotes combined with reduced LCAT activity cause a decrease of the slow, unspecific, and LCAT-dependent components of cholesterol efflux into plasma.

Animals↗
PubMed1996

Compound heterozygosity for a structural apolipoprotein A-I variant, apo A-I(L141R)Pisa, and an apolipoprotein A-I null allele in patients with absence of HDL cholesterol, corneal opacifications, and coronary heart disease.

BACKGROUND: The concentration of HDL cholesterol is inversely correlated with the risk of coronary heart disease (CHD). Some rare mutations in the apolipoprotein (apo) A-I gene are associated with low levels of HDL cholesterol. Their association with cardiovascular risk is controversial. METHODS AND RESULTS: We studied the molecular defects underlying corneal opacities and absence of HDL cholesterol in three brothers and a sister. In a family study, the importance of these defects for lipid metabolism and manifestation of coronary heart disease was investigated. The frequency of these apo A-I defects was assessed by genotype and phenotype analysis of 477 DNA- and plasma samples, respectively, from the population. The four patients were compound heterozygotes for a null allele and a missense mutation in the apo A-I gene that leads to a leucine-->arginine substitution at residue 141 [apo A-I(L141R)Pisa]. Heterozygotes for either the null allele or the structural variant had half-normal concentrations of HDL cholesterol and apo A-I compared with unaffected family members. Apo A-I(L141R)Pisa was detected in one more unrelated subject. Coronary angiography of the four compound heterozygotes revealed the presence of CHD in all male patients, whose ages ranged between 45 and 52 years. They presented with additional risk factors, including elevated LDL cholesterol levels, obesity, and arterial hypertension. Despite complete HDL deficiency and hypercholesterolemia, CHD was absent in the 51-year-old premenopausal sister. CONCLUSIONS: Apo A-I deficiency may lead to premature atherosclerosis if present in conjunction with additional cardiovascular risk factors.

Adolescent↗
PubMed1989

Metabolic effects of three new low-dose pills: a six-month experience.

We evaluated the effects on glucose and lipid metabolism in 57 healthy volunteers randomly assigned to one of three low-dose oral contraceptives: two monophasic (desogestrel + ethinylestradiol, EE, and cyproterone acetate + EE) and one triphasic (gestodene + EE) contraceptives. Glucose and insulin responses during OGTT were slightly affected by the cyproterone pill. The insulin area/glucose area ratio and HbA1c level were unchanged in all women. No preparation affected total and LDL-cholesterol levels. Triglycerides rose in all groups, while HDL-CH did only in women taking the two monophasic pills. The three low-dose pills assessed in this study have negligible effects on glucose and lipid metabolism.

Adult↗
PubMed1989

Clinical and metabolic effects of a pill containing 30 mcg ethinylestradiol plus 75 mcg gestodene.

The clinical and metabolic effects of a short-term treatment with a combination contraceptive pill containing 30 mcg ethinylestradiol and 75 mcg gestodene were evaluated in a group of 31 healthy women. The pill exerted good cycle control and the incidence of irregular bleeding was low. Side effects rarely occurred, and an improvement in premenstrual symptoms was reported during pill intake. Among the different biochemical parameters tested to monitor the coagulatory system, the only modification observed was an increase of fibrinopeptide A plasma levels, confirming that low-dose pills have less effects on the haemostatic system than oral contraceptives with a higher estrogen content. No significant modification in plasma total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-CH), HDL2-CH, nor low density lipoprotein-cholesterol were observed. HDL3-CH levels were significantly increased. Moreover, the pill did not significantly alter the fasting insulin and glucose levels nor their response to an oral glucose tolerance test. It may be suggested that this new formulation has high efficacy and clinical acceptability, primarily due to the total absence of any adverse metabolic effect.

Adult↗
PubMed1989

[Effects of low-dose oral contraceptives on sugar metabolism].

The effects on carbohydrate metabolism by four low-dose oral contraceptives were evaluated in four low-dose oral contraceptives were evaluated-66 young women randomly divided in four groups. In the various preparations there were a different dosage of estrogen (ethinylestradiol) together different doses and types of progestogen (desogestrel, gestodene, cyproterone acetate). After six months of treatment, in all groups a slight increase of glycemic and insulinemic responses during OGTT was observed; the significance was achieved with the preparation containing cyproterone acetate alone. Glycated hemoglobin did not change. Our results suggest that these new low-dose oral contraceptives induced negligible metabolic side effects.

Adolescent↗
PubMed1988

Urinary albumin excretion in normal subjects and in diabetic patients measured by a radioimmunoassay: methodological and clinical aspects.

We have developed a radioimmunoassay method (RIA) to measure urinary albumin excretion. We determined the albumin excretion rate (AER) (micrograms/min) of 122 healthy subjects and 145 diabetic patients (115 type I, 30 type II). The results indicate that the RIA is sensitive (0.39 +/- 0.08 mg/L), precise (CV 5-8%), and gives reliable results on previously frozen urine samples. The distribution of the AER values in healthy subjects and diabetic patients was not normal. It was normalized by log or square-root transformation of the data. Seventy-three percent of diabetic patients lay within the normal range (0.6-10.6 micrograms/min). Twenty percent could be considered "at risk" to develop overt diabetic nephropathy because their albuminuria exceeded a threshold level of 15 micrograms/min chosen previously as the cutoff value for microalbuminuria. We found no correlation between AER and glycated hemoglobin, and only a weak correlation between AER and diabetes duration in type I diabetic patients.

Adolescent↗
PubMed1988

Increased urinary excretion of digoxin-like immunoreactive substance by insulin-dependent diabetic patients: a linkage with hypertension?

Excretion of digoxin-like immunoreactivity (DLIS) was measured by RIA in timed overnight urine collections from 91 normotensive nondiabetic subjects and 104 normotensive insulin-dependent diabetic (IDDM) patients. The mean +/- SD DLIS excretion rate for the diabetic patients significantly exceeded that for the controls (73 +/- 41 vs 63 +/- 36 pg/min, P = 0.024). In both groups, the mean DLIS excretion rates for men were significantly higher (P = 0.0014, P = 0.006) than for women. In the controls, the DLIS excretion rate significantly correlated with the urinary excretion rate of creatinine (P less than 0.01), Na+ (P less than 0.05), and K+(P less than 0.05), and with the subjects' body weight (P less than 0.01), body mass index (P less than 0.05), and systolic blood pressure (P less than 0.05). In the diabetics, the DLIS excretion rate was significantly correlated with body weight (P less than 0.05) and with urinary excretion rates for albumin (P less than 0.01), creatinine (P less than 0.01), Na+ (P less than 0.05), and K+(P less than 0.05). Our data indicate that: (a) increased amounts of a cardiac glycoside-like substance (or a group of substances) are excreted in the urine of IDDM patients; (b) the urinary excretion of DLIS seems to depend on glomerular filtration rate and physiocochemical properties of glomerular membrane, as well as on subjects' body mass; and (c) because cardiac glycoside-like substances may increase peripheral vascular resistance, increased urinary excretion of DLIS by IDDM patients may indicate a tendency to develop hypertension.

Adult↗