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C Bianchi, R Miccoli,
R C Bonadonna,
F Giorgino,
S Frontoni,
E Faloia,
G Marchesini,
M A Dolci,
L Alviggi,
A Gnasso,
A Consoli,
F Cavalot,
M G Cavallo,
F Leonetti,
A Giaccari,
S Del Prato
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ABSTRACT: We evaluated the relationship between insulin resistance (IR) and insulin secretion with the metabolic syndrome (MS) in 885 subjects (377 men/508 women, age 49±11 years, BMI 29±5.2kgm(-2)) at risk of diabetes enrolled in the genetics, pathophysiology and evolution of type 2 diabetes (GENFIEV) study.
All subjects underwent a 75-g oral glucose tolerance test (OGTT) for the estimation of plasma levels of glucose and C-peptide, as well as fasting insulin and lipid profile. IR was arbitrarily defined as HOMA-IR value above the 75th centile of normal glucose tolerance (NGT) subjects. Overall MS prevalence (National Cholesterol Treatment Panel-Adult Treatment Panel (NCEP-ATPIII) criteria) was 33%, 19% in subjects with NGT, 42% in impaired fasting glucose (IFG), 34% in impaired glucose tolerance (IGT), 74% in IFG+IGT subjects, and 56% in newly diagnosed diabetic patients. Prevalence was slightly higher with IDF criteria. MS prevalence was >50% in subjects with 2h glucose >7.8mmoll(-1), independently of fasting plasma glucose. IR prevalence was higher in subjects with MS than in those without (63% vs. 23%; p<0.0001) and increased from 54% to 73% and 88% in the presence of three, four or five traits, respectively. IR occurred in 42% of subjects with non-diabetic alterations of glucose homeostasis, being the highest in those with IFG+IGT (IFG+IGT 53%, IFG 45%, IGT 38%; p<0.0001). Individuals with MS were more IR irrespective of glucose tolerance (p<0.0001) with no difference in insulinogenic index. Hypertriglyceridaemia (OR: 3.38; Confidence Interval, CI: 2.294.99), abdominal obesity (3.26; CI: 2.18-4.89), hyperglycaemia (3.02; CI: 1.80-5.07) and hypertension (1.69; CI: 1.12-2.55) were all associated with IR.
These results show that in subjects with altered glucose tolerance (in particular IFG+IGT) MS prevalence is high and is generally associated to IR. Some combinations of traits of MS may significantly contribute to identify subjects with IR.
Nutrition, metabolism, and cardiovascular diseases: NMCD 11/2010; 21(9):699-705. · 3.52 Impact Factor
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ABSTRACT: To determine the relationships between metabolic syndrome (MetS), diabetic nephropathy (DN) and renal function in Type 2 diabetes.
In a clinic-based cohort of 1314 Type 2 diabetic patients (58% male; age 62 +/- 10 years), we analysed MetS, detected DN and estimated glomerular filtration rate (eGFR).
Prevalence of both microalbuminuria and macroalbuminuria were higher in subjects with MetS than in those without. Prevalence of DN (microalbuminuria and macroalbuminuria) increased with the number of MetS components. eGFR was lower in subjects with MetS than in those without (87 +/- 23 vs. 92 +/- 20 ml/min per 1.73 m2; P < 0.001). The lowest eGFR values were found in those with four or more components of the MetS. Prevalence of low eGFR increased with the stage of DN and was affected by MetS only in normoalbuminuric patients. MetS was independently associated with DN, also after adjustment for confounders [odds ratio (OR) 2.82, confidence interval (CI) 1.93, 4.11] and the presence of low eGFR in the model (OR 2.74, CI 1.87, 4.01). Similarly, MetS was a predictor of low eGFR (OR 1.93, CI 1.11, 3.36), but after adjustment for DN, the association was lost. Finally, MetS per se was independently associated with DN, but not with low eGFR after adjustment for all of the individual components of the MetS.
This study suggests a close and independent association between MetS and renal impairment. However, it is unclear whether and to what extent treating MetS by an intensive multifactorial therapeutic approach will prevent or delay progression to renal failure.
Diabetic Medicine 01/2009; 25(12):1412-8. · 2.90 Impact Factor
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G P Fadini,
L Pucci,
R Vanacore,
I Baesso,
G Penno,
A Balbarini,
R Di Stefano, R Miccoli,
S de Kreutzenberg,
A Coracina,
A Tiengo,
C Agostini,
S Del Prato,
A Avogaro
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ABSTRACT: Circulating progenitor cells participate in cardiovascular homeostasis. Depletion of the pool of endothelial progenitor cells (EPCs) is associated with increased cardiovascular risk. Furthermore, EPCs are reduced in the presence of classical risk factors for atherosclerotic disease, including diabetes mellitus. This study was designed to evaluate progenitor cell levels in volunteers with different degrees of glucose tolerance.
Cardiovascular parameters and the levels of circulating CD34(+) and CD34(+) kinase insert domain receptor (KDR)(+) cells were determined in 219 middle-aged individuals with no pre-diagnosed alterations in carbohydrate metabolism. Glucose tolerance was determined by fasting and 2 h post-challenge glucose levels, with IFG and IGT considered as pre-diabetic states.
CD34(+) and CD34(+)KDR(+) cells were significantly reduced in individuals who were found to have diabetes mellitus, and were negatively correlated with both fasting and post-challenge glucose in the whole population. While only CD34(+) cells, but not CD34(+)KDR(+) cells, were significantly reduced in pre-diabetic individuals, post-challenge glucose was an independent determinant of the levels of both CD34(+) and CD34(+)KDR(+) cells.
Glucose tolerance was negatively associated with progenitor cell levels in middle-aged healthy individuals. Depletion of endothelial progenitors with increasing fasting and post-meal glucose may be one cause of the high incidence of cardiovascular damage in individuals with pre-diabetes.
Diabetologia 11/2007; 50(10):2156-63. · 6.81 Impact Factor
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ABSTRACT: The impact of the diabetes epidemic will be staggering in terms of costs to individuals and society. Social educational initiatives are imperative to altering the lifestyle trends that drive the growth of the epidemic. Targeted lifestyle or drug interventions aimed at preventing progression from prediabetes to type 2 diabetes mellitus carry costs and risks that need to be considered in the context of expected benefits, which also need to be carefully defined. In terms of pharmacological intervention as part of a primary prevention programme, the risk/benefit assessment must include the potential for adverse effects in a large population of asymptomatic individuals, a significant proportion of whom would not progress to diabetes in the absence of treatment and in whom impaired glucose regulation may reflect different underlying pathogenetic mechanisms. Improving the balance of risks and benefits in drug interventions will require a greater ability to determine which treatments are likely to safely improve glucose regulation and prevent diabetes and its adverse cardiovascular outcomes in individual patients.
Diabetes Obesity and Metabolism 10/2007; 9 Suppl 1:17-22. · 3.38 Impact Factor
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ABSTRACT: We hypothesized that molecules active in vascular remodeling (i.e. MMPs and their TIMPs) could be modified in diabetic patients, as indirect markers of the diabetes related generalized abnormality of vascular activity. To test this hypothesis, we measured the plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in type 2 diabetic patients and in healthy subjects.
We enrolled 181 diabetic patients and 165 controls. We measured body mass index (BMI), glycosylated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment index (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct) fibrinogen (Fg), high sensitivity C-reactive protein (hs-CRP), and plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2.
A significant increase (P<0.0001) of BMI, HbA(1c), FPG, FPI, HOMA index, SBP, DBP, TC, LDL-C, Tg, Lp(a), PAI-1, Hct, Fg, and hs-CRP was present in the diabetic group, with a significant decrease (P<0.0001) of HDL-C levels compared to healthy subjects. MMP-2 and MMP-9 levels were significantly higher (P<0.0001) in diabetic patients. Significant TIMP-1, and TIMP-2 increase was also observed (P<0.0001) in the diabetic group.
Plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 are increased in diabetic patients which may reflect abnormal extracellular matrix (ECM) metabolism.
Diabetes & Metabolism 04/2007; 33(2):129-34. · 2.41 Impact Factor
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ABSTRACT: This study evaluates the presence of metabolic syndrome (MS) and its association with C-reactive protein (CRP) and other cardiovascular (CV) risk factors, in a sample of women with and without previous Gestational Diabetes (pGDM).
One hundred and sixty-six women with pGDM and 98 women (controls) with uncomplicated pregnancy were studied 16 months after delivery. In all women, plasma glucose, insulin, lipid profile, serum uric acid, C-reactive protein, fibrinogen and homocysteine were measured. MS was defined according to NCEP ATPIII criteria.
MS was identified in 15 pGDM women (9%) versus 1 control (1%) (p < 0.001). The more frequent metabolic traits were abdominal obesity (36% vs 17%) and low HDL-cholesterol (34% vs 17% in pGDM women and controls, respectively; all p < 0.01). HOMA-R, LDL-cholesterol, fibrinogen, serum uric acid and CRP resulted significantly higher in pGDM women with MS as compared to those without MS after adjustment for BMI. In women with no criteria for MS, only CRP levels were found to be higher in pGDM women compared to controls (p < 0.05). Seventeen percent of pGDM women with no criteria for MS had CRP levels >or=1 mg/L (all controls showed CRP levels <1 mg/L). After a stepwise regression analysis, CRP levels were independently correlated to HOMA-R (r2 = 0.27, p < 0.001) and fibrinogen (r2 = 0.30, p < 0.001).
In our population, MS occurs in a sizable proportion of pGDM women and is associated with increased levels of CRP, fibrinogen, uric acid and LDL-cholesterol. Moreover, higher levels of CRP, a marker of chronic low-grade inflammation, are present in a subset of women with pGDM, independently of MS.
Diabetes/Metabolism Research and Reviews 02/2007; 23(2):135-40. · 3.37 Impact Factor
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G Di Cianni, R Miccoli,
L Volpe,
C Lencioni,
A Ghio,
M G Giovannitti,
I Cuccuru,
G Pellegrini,
K Chatzianagnostou,
A Boldrini,
S Del Prato
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ABSTRACT: To determine the predictive value of serum triglyceride levels (TG) for neonatal weight in pregnant women with positive diabetic screening but normal glucose tolerance.
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.
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.
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.
Diabetic Medicine 02/2005; 22(1):21-5. · 2.90 Impact Factor
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ABSTRACT: 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.
Acta Diabetologica 01/2004; 40 Suppl 2:S362-9. · 2.78 Impact Factor
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Graziano Di Cianni,
L Volpe,
C Lencioni, R Miccoli,
I Cuccuru,
A Ghio,
K Chatzianagnostou,
P Bottone,
G Teti,
S Del Prato,
L Benzi
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ABSTRACT: 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).
Diabetes Research and Clinical Practice 11/2003; 62(2):131-7. · 2.75 Impact Factor
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ABSTRACT: 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.
Cardiologia (Rome, Italy) 11/1999; 44(10):885-99.
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ABSTRACT: 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.
Atherosclerosis 08/1998; 139(1):77-82. · 3.79 Impact Factor
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ABSTRACT: 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.
Atherosclerosis 06/1998; 138(1):25-34. · 3.79 Impact Factor
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A von Eckardstein,
A Chirazi,
S Schuler-Lüttmann,
M Walter,
J J Kastelein,
J Geisel,
J T Real, R Miccoli,
G Noseda,
G Höbbel,
G Assmann
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ABSTRACT: 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.
The Journal of Lipid Research 06/1998; 39(5):987-98. · 5.56 Impact Factor
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ABSTRACT: 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.
The Journal of Lipid Research 07/1997; 38(6):1242-53. · 5.56 Impact Factor
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ABSTRACT: 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.
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.
Apo A-I deficiency may lead to premature atherosclerosis if present in conjunction with additional cardiovascular risk factors.
Circulation 10/1996; 94(7):1622-8. · 14.74 Impact Factor
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The Lancet 10/1995; 346(8976):708-9. · 38.28 Impact Factor
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Contributions to nephrology 02/1993; 101:127-34. · 1.49 Impact Factor
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ABSTRACT: Supranormal urinary albumin excretion (microalbuminuria) is an early indicator of microangiopathy, i.e. diabetic nephropathy, and is associated with higher cardiovascular mortality in both type 1 and type 2 diabetes. The relationship between the presence of microalbuminuria and some atherosclerotic risk factors has been evaluated in 318 (170 male, 148 female) type 2 (non-insulin-dependent) diabetic subjects [age 6310 years; known duration of diabetes 10.98.8 years; age at diabetes diagnosis 5211 years; systolic blood pressure (BP) 15023 mmHg; diastolic BP 8611 mmHg (meanSD)]. In early morning urine samples, albumin (immunonephelometry) and creatinine were assayed. On the basis of the albumin/creatinine ratio (A/C, mg/mmol), patients were categorized as normoalbuminuric (Na; A/Cn=159, 50%), microalbuminuric (ma; A/C 2–20;n=135, 42.5%) or macroalbuminuric (Ma; A/C >20;n=24, 7.5%). The three groups were closely matched for age, age at diagnosis, duration of diabetes, and fasting plasma and urinary glucose levels. Systolic and diastolic BP rose progressively with increasing urinary A/C ratio levels. While high-density lipoprotein (HDL) cholesterol was unaffected by albuminuria, total cholesterol (21845 vs 19843 mg/dl,PPr=0.16,P160/95 mmHg and/or drug treatment (Na, 51%; ma, 65%; Ma, 78%;P30 (Na, 15%; ma, 26%; Ma, 32%;P
Acta Diabetologica 08/1992; 29(3):250-257. · 2.78 Impact Factor
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ABSTRACT: 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.
Contraception 01/1990; 40(6):649-63. · 2.72 Impact Factor
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ABSTRACT: 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.
Minerva ginecologica 10/1989; 41(9):441-4.
