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Biomedical subjects

M Muggeo

Publications and source records attributed to M Muggeo.

At least 91 records · Page 5Linked to original sources
PubMed1996

Relationship of uric acid concentration to cardiovascular risk factors in young men. Role of obesity and central fat distribution. The Verona Young Men Atherosclerosis Risk Factors Study.

OBJECTIVE: To examine the relationships of serum uric acid concentration with several risk factors of cardiovascular diseases (CVD). SUBJECTS: 957 men 18 y old participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. MEASUREMENTS: Body mass index (BMI), waist/hip ratio (WHR), serum uric acid, serum lipids, blood pressure, fasting insulin and behavioural variables. RESULTS: Serum uric acid concentration showed positive associations with BMI (r = 0.24; P < 0.0001), WHR (r = 0.19; P < 0.0001) and serum triglyceride levels (r = 0.19; P < 0.0001); it was also significantly correlated to systolic (r = 0.08; P < 0.01) and diastolic (r = 0.11; P < 0.001) blood pressure, fasting insulin (r = 0.11; P < 0.001), total (r = 0.12; P < 0.001) and LDL cholesterol (r = 0.10; P < 0.01) plasma concentrations. Life-style characteristics, such as smoking and physical activity did not show any significant association, while daily alcohol intake was positively associated with uric acid concentration (r = 0.09; P < 0.01). While the adjustment for fasting insulin did not substantially change these results, the magnitude of the correlations between uric acid and CVD risk factors markedly decreased when allowance was made for BMI and WHR. Only triglycerides maintained an independent correlation with uric acid levels (r = 0.17; P < 0.0001). In multivariate regression analysis, serum triglycerides, BMI and WHR (at borderline significance) were independent positive predictors of uric acid (R2 of the model 0.122, P < 0.001), while fasting insulin concentration did not give any independent contribution to explain the variability uric acid levels. CONCLUSIONS: These data indicate that, already in young, essentially health subjects, hyperuricaemia associates with several components of the so-called insulin resistance syndrome, thus suggesting that increased levels of uric acid might be another member of this syndrome. In addition, these data suggest that obesity and central body fat distribution, rather than hyperinsulinaemia/insulin resistance, play a major role in linking hyperuricaemia with CVD risk factors clustering in the insulin resistance syndrome. Nevertheless, hypertrigliceridemia is related to hyperuricemia independently of obesity and central body fat distribution.

Adipose Tissue↗
PubMed1995

Non-invasive detection of early endothelial dysfunction in hypercholesterolaemic subjects.

Hypercholesterolaemia is associated with accelerated atherogenesis. Before the evidence of morphological lesions or plaques, endothelial dysfunctions, such as impairment in endothelium-dependent vascular tone regulation, may occur. We studied 32 subjects, 16 with primary hypercholesterolaemia and 16 normocholesterolaemic controls. Flow-dependent vasodilation, an endothelium-dependent phenomenon, was evaluated by measuring femoral artery diameter and flow velocity in basal conditions and during distal post-ischemic hyperaemia, using a high resolution echo-Doppler. Arterial distensibility and compliance were evaluated for the common carotid and femoral arteries, using a pulsed echo-tracking system and measuring the absolute and relative stroke change in arterial diameter. In the hypercholesterolaemic group there was no flow-dependent arterial relaxation, indicated by the area under the curve of percentage diameter variation as a function of time. This parameter was inversely correlated with both total and LDL-cholesterol values in all population subjects. No difference was observed between the two groups in endothelium-independent vasodilation induced by glyceryl trinitrate administration or arterial wall distensibility and compliance, confirming the hypothesis of a functional defect.

Adult↗
PubMed1995

The Verona diabetes study: a population-based survey on known diabetes mellitus prevalence and 5-year all-cause mortality.

This population-based survey aimed to determine the prevalence of known diabetes mellitus on 31 December 1986, and to assess all-cause mortality in the subsequent 5 years (1987-1991) in Verona, Italy. In the study of prevalence, 5996 patients were identified by three independent sources: family physicians, diabetes clinics, and drug prescriptions for diabetes. Mortality was assessed by matching all death certificates of Verona in 1987-1991 with the diabetic cohort. Overall diabetes prevalence was 2.61% (95% confidence interval 2.56-2.67). Prevalence of insulin-dependent and non-insulin-dependent diabetes mellitus was 0.069% (0.059-0.078) and 2.49% (2.43-2.54), respectively. Diabetes prevalence sharply increased after age 35 years up to age 75-79, and finally declined. Prevalence was higher in men up to age 69 years, in women after age 75 years. Of the diabetic cohort 1260 patients (592 men, 668 women) died by 31 December 1991, yielding an overall standardized mortality ratio of 1.46 (CI 1.38-1.54). Even though the differences narrowed with age, mortality rates in the diabetic cohort were higher than in the non-diabetic population at all ages. Women aged 65-74 years showed observed/expected ratio higher than men (2.27, CI 1.92-2.66, vs 1.50, CI 1.30-1.72), while in other age groups the sex-related differences were not significant. Pharmacological treatment of diabetes was associated with an excess mortality, while treatment with diet alone showed an apparent protective effect on mortality (observed/expected ratio 0.73, CI 0.58-0.92).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Long-term instability of fasting plasma glucose predicts mortality in elderly NIDDM patients: the Verona Diabetes Study.

The aim of this study was to evaluate whether long-term glucose control, as assessed by fasting plasma glucose determinations during 3 years, is a predictor of all-cause mortality in elderly NIDDM patients. Five hundred and sixty-six NIDDM patients attending the Verona Diabetes Clinic, aged 75 years and over, were followed-up from 1 January 1987 to 31 December 1991 to assess all-cause mortality. From their clinical records all fasting plasma glucose determinations available for the years 1984 to 1986 were collected and analysed. Patients were grouped in tertiles according to mean (M-FPG), coefficient of variation (CV-FPG) and trend over time (slope, S-FPG) of fasting plasma glucose during the period of retrospective evaluation. Mortality was assessed by observed/expected ratios, univariate Kaplan-Meier survival analysis and multivariate Poisson regression model. By 31 December 1991, 61 men and 127 women had died. Increased observed/expected ratios were found in women from the top M-FPG tertile, in patients (men and women) from the top CV-FPG tertile and in patients with a S-FPG less than -0.30 mmol/l per year (lowest tertile). Patients in the lowest tertile of CV-FPG and in the middle tertile of S-FPG had a reduced mortality risk. Kaplan-Meier survival analysis indicated that patients with high CV-FPG as well as those in tertiles I and III of S-FPG (i.e., those with a definitely negative or definitely positive slope) had an increased probability of dying, without any significant differences between the three tertiles of M-FPG.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Is it possible to derive a reliable estimate of human visceral and subcutaneous abdominal adipose tissue from simple anthropometric measurements?

The aim of the study was to generate equations predicting visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue (AT) from simple anthropometric measurements. Magnetic resonance imaging (MRI) was used to measure VAT and SAT cross-sectional areas at the level of L4 in 49 subjects (19 men and 30 women) with a large range of age and body mass index (BMI). BMI, waist and hip circumferences, waist to hip ratio (WHR), subscapular and paraumbilical skinfolds (i.e., "simple" anthropometric measurements), total body fat content by the isotope-dilution method, and abdominal sagittal diameter by MRI (i.e., "nonsimple" anthropometric measurements) were also measured. Equations to estimate VAT and SAT from age and simple anthropometric measurements (i.e., excluding total body fat and abdominal sagittal diameter) were developed. These equations were then used in 24 subjects (nine men and 15 women) to cross-validate them. The best regression equations, including waist circumference in men and waist circumference and age in women, explained 56% and 68% of VAT variability, respectively. The corresponding standard error of the estimate (SEE) in men was approximately 40% and in women approximately 37% of the mean value of VAT measured by MRI. The best regression equations developed to predict SAT had a higher explained variability (approximately 87% in both men and women) and a lower SEE (< 20% of the mean values of SAT measured by MRI). In men, the equation included BMI and hip circumference, and in women, BMI and age. The inclusion of a higher number of simple anthropometric parameters in the predictive models neither significantly increased the explained variability of VAT or SAT nor significantly decreased the SEE of VAT or SAT. Also, inclusion in the multiple regression analysis of total body fat content and abdominal sagittal diameter did not improve prediction. In the cross-validation study, differences between predicted and observed values of VAT were large, with a tendency to overestimation in both men and women. In contrast, differences between predicted and observed values of SAT were small. We suggest that SAT but not VAT can be estimated from age and simple anthropometric measurements. Direct methods (MRI, computed tomography [CT], or other options) should be used for assessment of VAT.

Abdomen↗
PubMed1995

Serum retinol levels throughout 2 years of cholesterol-lowering therapy.

Some studies have reported an inverse correlation between serum cholesterol level and risk of cancer. This correlation might be due to a decrease in serum retinol, a lipid-soluble vitamin that controls cell proliferation and differentiation. We evaluated the influence of cholesterol-lowering therapy on serum retinol in 102 subjects (mean +/- SE: aged 47.1 +/- 4.1 years; body mass index, 23.8 +/- 0.6 kg/m2) with primary hypercholesterolemia treated for 2 years with different therapeutic protocols. Twenty-two subjects had been treated with diet alone, 35 with diet and fibrates, 37 with diet and hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), and eight with diet and cholestyramine. Postabsorptive serum retinol, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were determined at baseline and every 3 months. Baseline TC and LDL-C were significantly lower in the diet-treated group than in other groups. No intergroup differences were found in pretreatment levels of triglycerides and serum retinol. After 2 years of treatment, TC and LDL-C serum levels were not significantly decreased in the diet-alone group, whereas they were decreased by 20% and 24%, respectively, in the gemfibrozil group, 28% and 34% in the statins group; and 21% and 27% in the cholestyramine group. In the entire population (N = 102), serum retinol was 3.46 +/- 0.08 mumol/L before therapy and 3.76 +/- 0.07 after 2 years of therapy (P < .001). Serum retinol increased in diet- and statin-treated groups, but not in fibrate- and resin-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor behavior.

OBJECTIVE: To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters, as well as on the androgen receptor status, in hirsute women. DESIGN: Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide, three times per day for 12 months. Barrier or intrauterine contraception was used during the study in sexually active women. Safety parameters were assessed throughout the study. Hirsutism, graded by the modified Ferriman-Gallwey score, and hormonal parameters were evaluated basally and at 4-month intervals during treatment. Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy. In addition, the concentration of androgen receptors in mononuclear leukocytes was measured, in both the follicular and luteal phases of the menstrual cycle, basally and after 4 months of flutamide treatment. RESULTS: Flutamide was well tolerated in all women, with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy. Hirsutism markedly improved in all women during the treatment (Ferriman-Gallwey score after 1 year: 4.1 +/- 0.5 versus 14.1 +/- 0.9). A reduction of serum androgens was found, whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH. Cycles remained ovulatory. Before treatment, the number of androgen receptors was higher in the luteal than in the follicular phase. This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug. CONCLUSIONS: Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function. Androgen receptor blockade might be potentiated by a reduction of serum androgens. Flutamide affects androgen receptor behavior during the menstrual cycle. The meaning of this finding remains to be elucidated.

Acne Vulgaris↗
PubMed1995

Sustained therapy with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors does not impair steroidogenesis by adrenals and gonads.

Plasma lipoproteins are a major source of cholesterol for steroid hormone synthesis. 3-Hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors, which reduce both intracellular cholesterol synthesis and serum cholesterol levels, thus have a potential negative impact on steroidogenesis. In this study, we evaluated basal and maximally stimulated adrenocortical and testicular steroidogenesis in 24 hypercholesterolemic male subjects during 6-36 months of statin treatment. One group was evaluated before treatment and after 6 months of treatment. A second group, which received long term treatment, was evaluated after 24-36 months and then 2 months after treatment had been discontinued. Fourteen subjects were given simvastatin, and 12 were given pravastatin, both at the maximum therapeutic dosage of 40 mg/day. During statin therapy, serum cholesterol was lowered by about 30%. Basal serum and urinary cortisol levels as well as serum cortisol response to ACTH were not influenced by statin therapy. Basal serum testosterone and its response to hCG were also unchanged by statin treatment. In addition, steroid hormone urinary metabolites were strikingly similar when patients were given HMG-CoA reductase inhibitors and when they were not. These results indicate that maximum therapeutic doses of statins have no negative impact on adrenocortical and testicular steroidogenesis even when these glands are maximally stimulated.

Adolescent↗
PubMed1995

Noninvasive detection of functional alterations of the arterial wall in IDDM patients with and without microalbuminuria.

OBJECTIVE: To test endothelial function in a group of 10 normoalbuminuric and eight microalbuminuric insulin-dependent diabetes mellitus patients (ages 28 +/- 3 [mean +/- SE] and 28 +/- 1 years, respectively), in comparison with 16 control subjects (age 35 +/- 2 years, normal subjects vs. diabetic subjects P = NS), to identify prestructural abnormalities of the arterial wall. An early stage of vascular involvement seems in fact to be characterized by functional alterations of endothelial control on vascular tone and wall interaction with circulating cells. Furthermore, many recent studies suggest the importance of microalbuminuria as an early marker not only of nephropathy but also of retinopathy and macroangiopathy. RESEARCH DESIGN AND METHODS: Endothelium-mediated flow-dependent vasodilation and endothelium-independent vasodilation (induced by glyceryl trinitrate administration) were evaluated in the right common femoral artery by echo-Doppler ultrasound. Arterial wall distensibility was evaluated at the common femoral artery by an echo-tracking system. RESULTS: In spite of a comparable increase in flow velocity, endothelium-mediated vasodilation was significantly reduced in diabetic subjects, particularly in microalbuminuric patients. Endothelium-independent vasodilation was also significantly impaired in diabetic subjects, particularly in microalbuminuric subjects; whereas arterial wall distensibility, an index of the viscoelastic properties of the wall, was similar in the three groups. CONCLUSIONS: These results confirm a reduced vasodilatory capacity in diabetes mellitus, with a more marked alteration in microalbuminuric diabetic subjects. This reliable, noninvasive evaluation of arterial function is particularly useful for early diagnosis of vascular involvement.

Adult↗
PubMed1995

Hyperuricaemia: relationships to body fat distribution and other components of the insulin resistance syndrome in 38-year-old healthy men and women.

The aim of this work was to evaluate whether hyperuricaemia correlates with the cluster of metabolic and haemodynamic disorders closely associated with insulin resistance syndrome (IRS) in young apparently healthy individuals also, and, if so, whether hyperinsulinaemia itself or some other component of this syndrome, are independently associated with hyperuricaemia. The subjects were a random population sample of 181 (M = 94/F = 87) 38-year-old apparently healthy subjects, non-diabetic, without a history of gout. Obesity (overall and regional), serum lipid profile, uric acid, fasting glucose and insulin, 2 h insulin after glucose-load (only in men), blood pressure and main behavioural variables were measured. As expected, most parameters were statistically different between men and women. In particular, serum uric acid levels were significantly higher in the male group than in female group (348 +/- 59 mumol l-1 vs 277 +/- 59 mumol l-1, P < 0.0001). After adjustment for sex, in pooled individuals, serum uric acid concentration showed positive associations with BMI (r = 0.21; P < 0.001), waist/hip girth (WHR; r = 0.45; P < 0.0001), waist/thigh girth (WTR; r = 0.35; P < 0.0001) and subscapula/triceps skinfold ratios (STR; r = 0.30; P < 0.001). Furthermore, serum uric acid was also positively correlated with fasting insulin (r = 0.23; P < 0.001), serum triglycerides (r = 0.34; P < 0.0001), LDL cholesterol (r = 0.16; P = < 0.01), diastolic blood pressure (r = 0.26; P < 0.001), and negatively with HDL/total cholesterol ratio (r = 0.28; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Two mutations in a conserved structural motif in the insulin receptor inhibit normal folding and intracellular transport of the receptor.

Insulin initiates its biological response by binding to the extracellular domain of the insulin receptor. The N-terminal half of the alpha-subunit contains several repeats of a loosely conserved motif consisting of a central glycine plus several hydrophobic amino acid residues upstream from the glycine, Hy phi-Xaa-Xaa-Hy phi-Xaa-Hy phi-Hy phi-Xaa-Gly (where Hy phi represents a hydrophobic amino acid residue). This structural motif has been proposed to be important in determining the three-dimensional structure of the insulin binding domain. We have identified two naturally occurring mutant alleles of the insulin receptor gene in an insulin-resistant patient, substitution of Ala for Val28 and Arg for Gly366. The mutations alter conserved amino acid residues in two distinct repeats of the structural motif described above. When mutant cDNAs were expressed in NIH-3T3 cells, both mutations severely impaired proteolytic processing of the proreceptor to mature alpha- and beta-subunits. Transport of mutant receptors to the plasma membrane was also impaired. However, the minority (< 10%) of receptors that were eventually transported to the plasma membrane retained the ability to bind insulin with normal affinity and to undergo insulin-stimulated phosphorylation. In conclusion, the effects of these naturally occurring mutations provide experimental support for the importance of the conserved glycine-containing structural motifs described above. By interrupting these structural motifs, the Ala28 and Arg366 mutations prevent normal folding of the insulin receptor alpha-subunit, thereby inhibiting post-translational processing and intracellular transport of the mutant receptors.

3T3 Cells↗
PubMed1994

Plasma fibrinogen in relation to serum insulin, smoking habits and adipose tissue fatty acids in healthy men.

Recent prospective studies have reported an independent association between fibrinogen plasma levels and risk of cardiovascular events. Aim of this study was to investigate the relationships between fibrinogen level and conventional cardiovascular risk factors in a random sample of 38 year-old apparently healthy men (n = 94), and to verify whether the fatty acid composition of the diet might influence those relations. Anthropometric measurements, serum lipids, blood pressure, and smoking habits were evaluated. In addition, fasting and after glucose-load serum glucose and insulin concentrations were measured. The most significant difference in fibrinogen level was found among the tertiles of fasting serum insulin (F-ANOVA = 4.5; P < 0.01) with the highest plasma fibrinogen values in the third insulin tertile, whereas body mass index (BMI), waist/hip circumference ratio (WHR) and serum triglycerides were more weakly related. The current smokers had substantially higher levels of fibrinogen than subjects who never smoked (P < 0.001). A multivariate regression analysis showed that, among the above reported variables, only serum insulin and smoking were independently associated with plasma fibrinogen. Furthermore, as the possible association between fatty acid composition of the diet and fibrinogen level regards, we have examined the fatty acid composition of adipose tissue, as a good and objective index of quality of the dietary fat intake. It was found that, fibrinogen level was not associated with any adipose tissue fatty acid. In conclusion, this study performed in a random sample of healthy men indicates an independent relationship of fasting insulin and smoking to fibrinogen plasma level.

Adipose Tissue↗
PubMed1994

Phosphotyrosine protein profiles in monocytes after insulin and IGF-1 stimulation.

Mononuclear cells are largely used in clinical studies on insulin action because of their accessibility. Insulin acts in monocytes in different ways than it does in other cells, i.e. adipocytes and muscular cells. Therefore, it still remains unclear whether monocytes reflect the same changes that occur in insulin receptors at the level of the major insulin target tissues during different pathophysiologic states. We have studied the phosphotyrosine protein profiles in intact human monocytes after insulin and IGF-1 stimulation with the aim of identifying substrate/s of these receptors and of comparing them to the substrates already described in major insulin target tissues. Mononuclear cells were prepared from peripheral blood by centrifugation on Ficoll Hypaque and by adhesion to tissue-culture plates. Cell stimulation, lysis, immunoprecipitation and western blotting were carried out following the protocol described by P. L. Rothenberg in 1991 and the immunoreactive proteins visualized on film by chemiluminescence. Insulin and IGF-1 rapidly increased the tyrosine phosphorylation of the 95 Kdal beta-subunit of their own receptors. Under our experimental conditions insulin and IGF-1 were not able to stimulate the phosphorylation of IRS-1, a major substrate of the insulin receptor kinase.

Humans↗
PubMed1994

Glucose counterregulatory response to acute hypoglycemia in hyperthyroid human subjects.

To evaluate the impact of hyperthyroidism on the counterregulatory response to hypoglycemia, eight hyperthyroid and eight sex-, age-, and body mass index-matched healthy women were given an iv insulin bolus (0.1 U/kg BW), and blood was drawn from 0-120 min for glucose, epinephrine, norepinephrine, glucagon, GH, ACTH, and cortisol measurements. In the basal state plasma glucose, GH, and cortisol levels were similar in the two groups, whereas plasma glucagon and ACTH were increased (135 +/- 17 vs. 80 +/- 10 ng/L and 6.4 +/- 1.5 vs. 2.6 +/- 0.4 pmol/L, respectively; both P < 0.025), and plasma catecholamines were reduced [epinephrine, 142 +/- 25 vs. 371 +/- 71 pmol/L (P < 0.025); norepinephrine, 0.41 +/- 0.07 vs. 1.41 +/- 0.12 nmol/L (P < 0.001)] in hyperthyroid patients. After insulin injection, plasma glucose similarly declined in the two groups (nadir, 1.5 +/- 0.2 vs. 1.6 +/- 0.2 mmol/L). Conversely, recovery from hypoglycemia was significantly faster in the hyperthyroid patients. In this respect, it is noteworthy that the plasma glucagon response had remarkably increased in the latter (peak, 444 +/- 56 vs. 198 +/- 17 ng/L; P < 0.005). On the other hand, the epinephrine responses were similar in the two groups, whereas norepinephrine levels remained consistently lower (peak, 0.97 +/- 0.20 vs. 2.61 +/- 0.24 nmol/L; P < 0.001), and the GH increase was severely impaired (peak, 10.6 +/- 1.9 vs. 29.6 +/- 6.2 micrograms/L; P < 0.01) in hyperthyroid patients. Plasma ACTH remained slightly higher in hyperthyroid subjects, but there were no substantial differences in the cortisol response between the two groups. In conclusion, hyperthyroidism affects plasma levels of several counterregulatory hormones, either in the fasting state or after insulin-induced hypoglycemia, with increased efficiency of plasma glucose recovery from hypoglycemia.

Acute Disease↗
PubMed1994

Clinical and hormonal effects of the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism.

Hyperactivity of 5 alpha-reductase in the skin is considered a major mechanism of excessive hair growth in hirsute women with normal levels of serum androgens (idiopathic hirsutism). Preventing the conversion of testosterone to dihydrotestosterone by inhibiting 5 alpha-reductase activity could thus be the most rational and effective treatment in this condition. The present study evaluated the effects of the oral administration of finasteride (5 mg once daily) for 6 months in 17 young women with idiopathic hirsutism, 5 of whom were also given an oral contraceptive. The degree of hirsutism (graded by a modified Ferriman-Gallwey score), serum sex hormone levels, and serum and urinary 5 alpha-metabolism steroid profiles were determined basally and periodically during the treatment period. The modified Ferriman-Gallwey score showed a remarkable reduction after 6 months of finasteride treatment (5.9 +/- 0.6 vs. 11.7 +/- 1.3; P < 0.01). Serum 5 alpha-dihydrotestosterone and 3 alpha-androstanediol glucuronide levels were decreased, and urinary C19 and C21 5 beta/5 alpha metabolite ratios were increased compared with pretreatment values. No significant adverse effect was reported. In women treated with finasteride and oral contraceptive, clinical efficacy was slightly more pronounced. In conclusion, the 5 alpha-reductase inhibitor finasteride is well tolerated and seems to be a useful tool in the treatment of idiopathic hirsutism.

Adult↗
PubMed1993

Mononuclear leukocytes from obese patients with type II diabetes have reduced activity of hexokinase, 6-phosphofructokinase and glucose-6-phosphate dehydrogenase.

In the present study we measured the activity of some cytosolic enzymes involved in intracellular glucose metabolism in mononuclear leukocytes from 77 obese subjects of which 39 were nondiabetic and 38 had newly-diagnosed untreated type II diabetes mellitus. 28 subjects (19 nondiabetic and 18 diabetic) had also a study of insulin binding to monocytes. 35 subjects (14 nondiabetic, 21 diabetic) underwent an insulin tolerance test for the evaluation of in vivo insulin action. Mononuclear leukocytes from diabetic obese patients showed significantly lower activities of hexokinase (HK), 6-phosphofructokinase (PFK) and glucose-6-phosphate dehydrogenase (G6PDH), while pyruvate kinase (PK) and 6-phosphogluconate dehydrogenase (6PGDH) activities were similar in the two groups. In the whole population HK and G6PDH activities inversely correlated with fasting and 2-h OGTT plasma glucose levels. Neither plasma insulin levels nor maximal specific insulin binding to monocytes were significantly correlated with any of the enzyme activities measured. Conversely, the parameter of insulin action generated by insulin tolerance test significantly correlated with HK, G6PDH and 6PGDH. These results indicate that in obese subjects the presence of diabetes is associated with a reduced activity of some enzymes of glucose metabolism in mononuclear leukocytes. This multiple enzymatic defect is correlated with the impairment of in vivo insulin action.

Adult↗
PubMed1992

Studies on the mechanism of action of sulphonylureas in type II diabetic subjects: gliquidone.

The mechanism of action of sulphonylureas is not completely understood. In the present study we evaluated the effects of gliquidone, a second-generation compound, on several metabolic parameters in 22 patients with untreated newly-diagnosed type II (noninsulin-dependent) diabetes mellitus. After either 1 or 6 months of treatment with gliquidone plus isocaloric diet we observed: 1) a significant decrease in fasting plasma glucose and glycemic profile after oral glucose load; 2) unchanged fasting and postglucose plasma insulin levels; 3) no change in fasting C-peptide levels but a significant increase in C-peptide concentrations after glucose challenge; 4) a significant increase in glucose disappearance rate from plasma following iv insulin injection; 5) an increase in the insulin-induced reduction of plasma levels of free-fatty acids; 6) no change in plasma C-peptide levels following iv insulin injection; 7) a significant increase in specific insulin binding to monocytes. After 6 but not 1 month of gliquidone therapy we also found an increase in the activity of hexokinase in circulating mononuclear leukocytes. These results suggest that the hypoglycemic effect of gliquidone occurs through either an increased beta cell response to glucose stimulus or an enhanced insulin sensitivity. The latter effect seems to depend on both receptor and postreceptor mechanisms.

Administration, Oral↗