Plasminogen activator inhibitor-1 and the risk of Type 2 diabetes mellitus in American Indians: the Strong Heart Study.
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Diabetes Mellitus, Type 2↗
Biomedical subjects
G Ruotolo
Publications and source records attributed to G Ruotolo.
[Evaluation of thyroid function in a group of over-eighty year-old people].
AIM: A number of studies has shown that during aging thyroid presents some structural changes, whilst no data agree about secretory activity. The aim of the present study was to evaluate thyroid function in a group of healthy over-80 years old people vs a group of young subjects. METHODS: This study was performed on 48 old people, 33 women (68.75%) and 15 men (31.25%), mean age 86.38+/-5.20 years old and 43 young subjects, mean age 33.35+/-3.75 years old; all of them were euthyroid and were not affected with any acute or chronic diseases and did not take any drugs which could interfere with thyroid function. A blood sample was taken from each patient, for dosing TT3, TT4, FT3, FT4, TSH, TgAb, TPOAb. RESULTS: The results of the present study show low serum levels of TT3 in healthy over-80 year old people compared to young people, even if serum levels of TT4, FT3, FT4, TSH have no significant changes. CONCLUSIONS: Functional reduction in thyroid activity during aging has not to be considered responsible for senile involution; it is more appropriate to define it as the expression of a metabolic slow down in the elderly.
Adult↗
[Falls in the elderly].
Falls are the main causes of accidental death and disability in elderly people, since they may especially cause hip fractures and a number of related complications. Available incidence estimates are surely in defect, because falls are often omitted both by patients, their family and caregivers. Risk factors may be classified in intrinsic and extrinsic; the former include muscular and osteoarticular diseases or other favouring conditions, whilst the latter include environmental or iatrogenic factors, such as drugs or alcohol consumption. Extrinsic factors may be rapidly modified in the elderly and thus prevented. In fact, prevention of falls is the main intervention of geriatrist, both at patient's home and if patient is hospitalized. In order to reduce the risk of falls, it is sometimes sufficient to stop a treatment or to reduce the doses of drugs causing sedation or orthostatic hypotension, to avoid if possible, the use of sedative-hypnotics, to use non-pharmacological methods for treating insomnia. The introduction of the necessary changes in the environment, the promotion of physical activity, the individuation of the subjects with a high risk of falls and the use of hip protectors are useful means for preventing falls and avoiding their harmful consequences.
Accidental Falls↗
Human evidence that the apolipoprotein a-II gene is implicated in visceral fat accumulation and metabolism of triglyceride-rich lipoproteins.
BACKGROUND: Apolipoprotein (apo) A-II is a major structural protein of plasma HDLs, but little is known regarding its functions. METHODS AND RESULTS: To investigate the physiological role of apoA-II in humans, we screened the promoter region of the apoA-II gene for a functional polymorphism and used this polymorphism as a tool in association studies. A common, functional polymorphism in the promoter region of the apoA-II gene, a T to C substitution at position -265, was found. Electrophoretic mobility shift assays demonstrated that the -265T/C polymorphism influences the binding of nuclear proteins, whereas transient transfection studies in human hepatoma cells showed a reduced basal rate of transcription of the -265C allele compared with the -265T allele. The -265C allele was associated with decreased plasma apoA-II concentration and decreased waist circumference in healthy 50-year-old men. In addition, oral fat tolerance tests provided evidence that the -265C allele enhances postprandial metabolism of large VLDLs. CONCLUSIONS: ApoA-II appears to promote visceral fat accumulation and impair metabolism of large VLDLs.
Adipose Tissue↗
Serum insulin-like growth factor-I level is independently associated with coronary artery disease progression in young male survivors of myocardial infarction: beneficial effects of bezafibrate treatment.
OBJECTIVES: We investigated whether the effect of bezafibrate on progression of coronary atherosclerosis in the BEzafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was related to insulin-like growth factor (IGF)-I and glucose-insulin homeostasis. BACKGROUND: BECAIT, the first double-blind, placebo-controlled, randomized, serial angiographic trial of a fibrate compound, demonstrated that progression of focal coronary atherosclerosis in young patients after infarction could be retarded by bezafibrate treatment. METHODS: The treatment effects on serum concentrations of IGF-I and insulin-like growth factor binding protein (IGFBP)-1, as well as on basal and postload glucose and insulin levels, were examined, and on-trial determinations were related to the angiographic outcome measurements. RESULTS: Bezafibrate treatment resulted in a significant reduction of serum IGF-I levels, both at two and five years, and on-trial serum IGF-I levels were directly related to changes in both minimal lumen diameter (r = 0.25, p < 0.05) and mean segment diameter (r = 0.29, p < 0.05). In contrast, none of the available indexes of insulin resistance (homeostasis model assessment estimate, basal and postload plasma insulin concentrations and serum IGFBP-1 levels) were related to the angiographic changes, nor were they significantly affected by bezafibrate treatment. Multiple stepwise regression analysis showed that the relation between on-trial serum IGF-I level and coronary artery disease (CAD) progression was independent of baseline angiographic score, age, body mass index, serum lipoprotein and plasma fibrinogen concentrations and measures of glucose-insulin homeostasis. CONCLUSIONS: IGF-I could be implicated in the progression of premature CAD, and a reduction of serum IGF-I concentration could account partly for the effect of bezafibrate on progression of focal coronary atherosclerosis.
Adult↗
Insulin and non-esterified fatty acid relations to alimentary lipaemia and plasma concentrations of postprandial triglyceride-rich lipoproteins in healthy middle-aged men.
AIMS/HYPOTHESIS: Enhanced and prolonged postprandial lipaemia is related to cardiovascular disease but how postprandial lipaemia is regulated is poorly known. We therefore determined the relations of fasting insulin concentrations to fasting and postprandial lipids, lipoproteins and non-esterified fatty acids in middle-aged men. METHODS: The subjects, 99 healthy 50-year-old men with an apolipoprotein E3/3 genotype, ate a mixed meal. The apolipoprotein B-48 and B-100 contents were determined in triglyceride-rich lipoproteins as a measure of chylomicron remnant and very low density lipoprotein particle concentrations. RESULTS: Fasting plasma insulin was associated with the triglyceride response to the test meal, independently of body mass index, waist-to-hip circumference ratio, blood glucose and the insulin effect on fasting plasma triglycerides. Exaggerated and prolonged postprandial lipaemia in subjects in the upper quartile of the plasma insulin distribution was largely accounted for by large (Svedberg flotation rate > 60) very low density lipoproteins and chylomicron remnants. Insulin relations to large postprandial triglyceride-rich lipoproteins exclusively reflected the association between plasma insulin and the fasting plasma concentrations of these lipoprotein species, whereas plasma insulin and late postprandial plasma concentrations of small (Svedberg flotation rate 20-60) chylomicron remnants were related, independently of insulin influences on fasting concentrations. Strong positive relations were found between the late increases in large triglyceride-rich lipoproteins and plasma non-esterified fatty acid concentrations after 6 h. CONCLUSION/INTERPRETATION: The degree of insulin sensitivity is a major determinant of postprandial lipaemia in healthy middle-aged men and could add to the regulation of the basal production of large triglyceride-rich lipoproteins.
Analysis of Variance↗
The Q/E27 polymorphism in the beta2-adrenoceptor gene is associated with increased body weight and dyslipoproteinaemia involving triglyceride-rich lipoproteins.
OBJECTIVES: To investigate whether a substitution of glutamine by glutamic acid at amino acid position 27 (Q/E27) and an arginine to glycine transition at amino acid 16 (R/G16) in the beta2-adrenoceptor gene are associated with lipid and lipoprotein disturbances and/or increased body weight in men. DESIGN: Population-based study. SETTING: Department of medicine at a university hospital. SUBJECTS: A total of 180 healthy men, aged 30-45 years, were recruited at random from a register containing all permanent residents in Stockholm County (response rate of 70%). MAIN OUTCOME MEASURES: Frequency of beta2-adrenoceptor genotypes and alleles in relation to plasma lipid and lipoprotein levels and body mass index. RESULTS: Individuals carrying the E27 allele and/or the G16 allele had significantly higher body mass index (BMI). Furthermore, carriers of the E27 allele had significantly higher plasma concentrations of cholesterol, triglycerides, VLDL cholesterol and VLDL triglycerides than did subjects homozygous for the Q allele. CONCLUSION: The E27 allele of the beta2-adrenoceptor gene is associated with slightly to moderately elevated BMI and dyslipoproteinaemia involving triglyceride-rich lipoproteins in healthy younger and middle-aged men.
Adult↗
Alimentary lipemia, postprandial triglyceride-rich lipoproteins, and common carotid intima-media thickness in healthy, middle-aged men.
BACKGROUND: Alimentary lipemia has been associated with coronary heart disease and common carotid artery intima-media thickness (IMT). This study was designed to investigate the relations of subclasses of postprandial triglyceride-rich lipoproteins (TRLs) with IMT. METHODS AND RESULTS: Ninety-six healthy 50-year-old men with an apolipoprotein (apo) E3/E3 genotype underwent an oral fat tolerance test and B-mode carotid ultrasound examination. The apo B-48 and apo B-100 contents of each fraction of TRLs were determined as a measure of chylomicron remnant and VLDL particle concentrations. In the fasting state, LDL cholesterol (P<0.05) and basal proinsulin (P<0. 05) were significantly related to IMT, whereas HDL cholesterol, plasma triglycerides, and insulin were not. In the postprandial state, plasma triglycerides at 1 to 4 hours (P<0.01 at 2 hours), total triglyceride area under the curve (AUC) (P<0.05), incremental triglyceride AUC (P<0.01), and the large VLDL (Sf 60 to 400 apo B-100) concentration at 3 hours (P<0.05) were significantly related to IMT. Multivariate analyses showed that plasma triglycerides at 2 hours, LDL cholesterol, and basal proinsulin were consistently and independently related to IMT when cumulative tobacco consumption, alcohol intake, waist-to-hip circumference ratio, and systolic blood pressure were included as confounders. CONCLUSIONS: These results provide further evidence for postprandial triglyceridemia as an independent risk factor for early atherosclerosis and also suggest that the postprandial triglyceridemia is a better predictor of IMT than particle concentrations of individual TRLs.
Alcohol Drinking↗
Persisting obesity starting before puberty is associated with stable intraabdominal fat during adolescence.
OBJECTIVES: To observe the evolution of intraabdominal adipose tissue (IAT) in obese prepubertal children, who did not change their degree of obesity during adolescence and to evaluate its relationship with metabolic risk indexes (RI). DESIGN: Longitudinal study of 16 obese adolescents (eight male and eight female) in whom relative body weight (RBW) did not change significantly and pubertal development was completed during the study period. MEASUREMENTS: Magnetic resonance imaging (MRI) scan at lumbar level (L4) three times during a 4 y period. At basal and at four years biochemical assays for metabolic indexes. RESULTS: IAT did not differ significantly over the three measurement times and showed significant correlations between first and second (r = 0.66, P < 0.005), first and third (r = 0.61, P < 0.01) and second and third values (r = 0.84, P < 0.0001). Subcutaneous adipose tissue (SAT) increased significantly from basal to third evaluation (P < 0.002). At baseline, IAT correlated significantly with lipids (total and LDL cholesterol r = 0.72, P < 0.004), while at the end of the study, IAT correlated positively with insulin (fasting insulin r = 0.55, P < 0.008, insulin area after oral glucose tolerance test (OGTT) r = 0.60, P < 0.03, fasting insulin/glucose r = 0.67 P < 0.006) and negatively with high density lipoprotein (HDL) cholesterol (r = -0.55, P < 0.04). CONCLUSIONS: Obesity achieved before puberty, and stable during adolescence, showed a relatively stable amount of IAT. In post pubertal children the relationship of IAT to clinically significant risk factors resemble the pattern in obese adults.
Abdomen↗
[Recommendations for cardiovascular assessment and risk reduction in diabetes--1999. Società Italiana di Diabetologia, the Diabetes and Atherosclerosis Study Group, Associazione Medici Diabetologi].
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Cardiovascular Diseases↗
Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).
OBJECTIVES: To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements. BACKGROUND: BECAIT, the first double-blind, placebo-controlled, randomized serial angiographic trial of a fibrate compound, showed that progression of focal coronary atherosclerosis in young survivors of myocardial infarction could be retarded by bezafibrate treatment. METHODS: A total of 92 dyslipoproteinemic men who had survived a first myocardial infarction before the age of 45 years were randomly assigned to treatment for 5 years with bezafibrate (200 mg three times daily) or placebo; 81 patients underwent baseline and at least one post-treatment coronary angiography. RESULTS: In addition to the decrease in very low density lipoprotein (VLDL) cholesterol (-53%) and triglyceride (-46%) and plasma apolipoprotein (apo) B (-9%) levels, bezafibrate treatment resulted in a significant increase in high density lipoprotein-3 (HDL3) cholesterol (+9%) level and a shift in the low density lipoprotein (LDL) subclass distribution toward larger particle species (peak particle diameter +032 nm). The on-trial HDL3 cholesterol and plasma apo B concentrations were found to be independent predictors of the changes in mean minimum lumen diameter (r=-0.23, p < 0.05), and percent (%) stenosis (r = 0.30, p < 0.01), respectively. Decreases in small dense LDL and/or VLDL lipid concentrations were unrelated to disease progression. CONCLUSIONS: Our results suggest that the effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins.
Adult↗
Hypobetalipoproteinemia associated with apo B-48.4, a truncated protein only 14 amino acids longer than apo B-48.
Familial hypobetalipoproteinemia is an autosomal codominant trait that can be caused by mutations in the apo B gene. Here we report a novel apo B gene mutation causing hypobetalipoproteinemia, that is associated with the synthesis of a truncated apo B protein in a young healthy male subject and his mother. The mutation is an A deletion at position 6627 of the apo B cDNA leading to a truncated protein of 2166 amino acids (apo B-48.4). This truncated apo B was detected mainly in VLDL, LDL and in trace amounts in HDL, but not in the lipoprotein deficient plasma fraction. Affected family members present with elevated levels of HDL-cholesterol, mainly due to an increase in HDL2 particles. Postprandial triglycerides and retinyl esters in the d < 1.006 g/ml lipoprotein in the proband showed a normal response to an oral fat load compared to a group of eight matched healthy controls. In summary this novel mutation is associated with hypobetalipoproteinemia with a normal fat absorption as expected for a protein with a length similar to that of apo B-48.
Adult↗
Effects of a cardioselective beta-blocker on postprandial triglyceride-rich lipoproteins, low density lipoprotein particle size and glucose-insulin homeostasis in middle-aged men with modestly increased cardiovascular risk.
Beta-adrenergic receptor-blocking agents are commonly used for treatment of hypertension, angina pectoris and arrhythmias and as secondary prevention after myocardial infarction. The modest protection against myocardial infarction conferred by these compounds in primary-preventive studies has suggested that beneficial effects of beta-blockade are counteracted by known adverse influences on lipid and glucose metabolism. As most beta-blockers increase plasma triglycerides and decrease the high density lipoprotein (HDL) cholesterol concentration, a randomized, double-blind, cross-over study was conducted to evaluate whether a 12-week treatment with metoprolol (100 mg o.d.) or placebo affected the metabolism of postprandial triglyceride-rich lipoproteins in 15 middle-aged men with a modestly increased cardiovascular risk. Metoprolol treatment significantly increased the postprandial responses of very low density lipoprotein (VLDL) and VLDL remnants to a mixed meal-type of oral fat tolerance test. The effect was particularly prominent for larger (Svedberg flotation rate (Sf) > 400 and Sf 60-400) particle species (P < 0.001 in repeated measures ANOVA), whereas the smaller (Sf 20-60) particles were less affected (P < 0.05). The changes in the postprandial responses of the different VLDL species were mainly related to an effect on the fasting plasma concentrations, with limited or no influences on VLDL catabolism during the postprandial state. In contrast, metoprolol treatment did not significantly influence the postprandial responses of chylomicrons and chylomicron remnants. Notably, the enhanced fasting and postprandial triglyceridaemia during metoprolol treatment was neither accompanied by a rise in fasting or postprandial free fatty acid concentrations, nor by alterations of the glucose and insulin responses to a standard oral glucose challenge. The ensuing shift in the LDL particle size distribution towards smaller particles was limited (fraction small LDL: metoprolol 22.8 +/- 15.7% versus placebo 19.3 +/- 15.0%, P < 0.05). In conclusion, metoprolol treatment primarily enhances fasting and postprandial triglyceridaemia in middle-aged men by increasing the basal hepatic production of VLDL.
Adrenergic beta-Antagonists↗
Smaller, denser LDL particles are not a risk factor for cardiovascular disease in healthy nonagenarian women of the Cremona Population Study.
We evaluated LDL particle size and its relation with other established risk factors for cardiovascular disease in a group of healthy nonagenarian ( > or = 90 years) women participating in the Cremona Population Study. A group of younger healthy postmenopausal women (45-75 years) was used as control group. Nonagenarian women had significantly lower body mass index, systolic and diastolic blood pressure, and fasting insulin concentrations. Plasma total, LDL and HDL cholesterol, apo AI and apo B concentrations, and LpAI and LpAI:AII particles were significantly lower in the nonagenarian group as well. LDL particle size (262.7+/-0.9 vs. 270.1+/-1.1 A) was also lower in the nonagenarian group. The presence of the E4 isoform of apo E in the nonagenarian group resulted in significantly higher levels of plasma apo AI and LpAI:AII particles, and a trend toward larger LDL particles, and a lower diastolic blood pressure. In conclusion, smaller and denser LDL particles might not represent an important risk factor for cardiovascular disease in healthy nonagenarian women of the Cremona Population Study, characterised by a reduced number of LDL particles and other protective factors, like low systolic and diastolic blood pressure, body mass index, and plasma insulin levels.
Aged↗
New lysosomal acid lipase gene mutants explain the phenotype of Wolman disease and cholesteryl ester storage disease.
Deficiency of lysosomal acid lipase (LAL) leads to either Wolman disease (WD) or the more benign cholesteryl ester storage disease (CESD). To identify the molecular basis of the different phenotypes we have characterised the LAL gene mutations in three new patients with LAL deficiency. A patient with WD was homozygote for a null allele Y303X. The other two patients, with CESD, presented either homozygosity for T267I or compound heterozygosity consisting of Q64R and an exon 8 donor splice site substitution (G-->A in position -1). The mutants T267I and Q64R and the previously reported L273S, G66V, and H274Y CESD substitutions, overexpressed in stable clones, were found to be fully glycosylated and show an enzymatic activity of 3-8% of that of normal LAL. On the other hand, the delta254-277 mutant protein derived from exon 8 skipping and the Y303X protein were totally inactive. By transient transfection of hybrid minigene constructs, the CESD G-->A (-1) substitution resulted in partial exon inclusion, thus allowing the production of a small amount of normal LAL mRNA and hence of a functional enzyme. In contrast, a G-->A substitution observed in WD at position + 1 of the same exon 8 donor site resulted in complete exon skipping and the sole production of an inactive delta254-277 protein. In conclusion, LAL genotypes determine the level of residual enzymatic activity, thus explaining the severity of the phenotype.
Amino Acid Substitution↗
Increased J774 macrophage cytotoxicity of late postprandial triglyceride-rich lipoproteins from normolipidemic young men expressing an apolipoprotein epsilon 4 allele.
It has been demonstrated that normolipidemic young men with apolipoprotein E4/3 phenotype have a prolonged postprandial clearance of triglyceride-rich lipoproteins following a high-fat diet. In the present study, we isolated fasting and postprandial (3 and 8 h) lipoprotein fraction from normolipidemic young men with E3/3 and E4/3 phenotypes and examined the in vitro cytotoxicity of these lipoproteins towards J774 macrophages. 8 h E4/3 very low density lipoprotein (VLDL) were significantly more cytotoxic than either 8 h E3/3 VLDL or fasting and 3 h E4/3 VLDL (lactate dehydrogenase (LDH) released: 161 +/- 21, 107 +/- 9, 88 +/- 16 and 101 +/- 12 I.U./l, respectively). Fasting E4/3 intermediate density lipoprotein (IDL) were also significantly more cytotoxic than either fasting E3/3 IDL or 3 h and 8 h E4/3 IDL (LDH released: 105 +/- 23, 60 +/- 9, 37 +/- 5 and 53 +/- 16 I.U./l, respectively), whereas either fasting or postprandial low density lipoprotein (LDL) and high density lipoprotein (HDL) samples did not show any difference in cytotoxicity between the two groups studied. 8 h E4/3 VLDL samples incubated with J774 macrophages had a lower esterified cholesterol (40 +/- 3 versus 52 +/- 3 micrograms), and higher triglyceride (783 +/- 133 versus 418 +/- 64 micrograms) and free fatty acid (FFA) (2.0 +/- 0.4 versus 0.9 +/- 0.1 microgram) content than fasting E4/3 VLDL. The increased macrophage cytotoxicity of late postprandial triglyceride-rich lipoproteins seems to be related to the FFA content of E4/3 VLDL.
Adult↗
Influence of breast- and formula-feeding on plasma cholesterol precursor sterols throughout the first year of life.
We evaluated endogenous cholesterol synthesis and plasma lipid profile longitudinally from birth to 1 year old in infants who were exclusively breast-fed (n = 19) or formula-fed (n = 19) for the first 4 months of life. At 1 and 4 months of age, breast-fed infants had higher plasma total and low-density lipoprotein cholesterol and apolipoprotein B levels than formula-fed infants, whereas plasma mevalonate and lanosterol levels were not different between the two study groups.
Analysis of Variance↗
[Echodynamics of the cervical ureter junction].
Transrectal dynamic ultrasonography is a 3 dimensional study that identifies accurately bladder neck (B.N.) diseases during micturition, providing precise noninvasive images of the B.N. orifice and the posterior urethra. This technique requires a 7-10 Mhz high frequency linear transducer. Benign Prostaic Hyperplasia (BPH) may restrict the urethral lumen and deviate its intra prostate tract. The images obtained allow a detailed and precise analysis of the B.N. and intravesical development of the median lobe. The urethra classically has a stretched and elongated appearance. This technique is useful in the diagnosis and in the follow up of neuropathic bladder. It is also useful in morphological and dynamic study of the B.N. after TURP. Diagnosis of B.N. hypertrophy or sclerosis is easy if a posterior beak at internal meatus level and positive stop test are present. After radical prostatectomy or radical cystectomy with orthotopic neobladder, this technique is useful to evaluate the internal urethral meatus and voluntary skeletal sphincter providing to a continence mechanism. We believe dynamic transrectal echography should become a procedure to be included as a part of the routine pre-surgical investigation of the B.N. diseases, for its non invasive nature, easiness to perform, and highly useful information.
Humans↗