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Biomedical subjects

R Pasquali

Publications and source records attributed to R Pasquali.

At least 91 records · Page 5Linked to original sources

Interrelationships between body weight, body fat distribution and insulin in obese women before and after hypocaloric feeding and weight loss.

The effects were investigated of weight loss on the relationship between hyperinsulinemia, body weight and body fat distribution in two groups of women with central-type obesity (CTO) (waist-to-hip ratio WHR greater than 0.85) or peripheral-type obesity (PTO) (WHR less than 0.85). An oral glucose tolerance test was carried out before and after a hypocaloric nutritional treatment lasting 4 months. Both groups were matched for age, body mass index and amount of body fat. At the basal condition, group CTO had fasting and glucose-stimulated insulin levels significantly higher than group PTO; fasting (but not stimulated) C peptide levels were also higher in CTO compared with PTO. Weight and fat loss were significantly higher in CTO than in PTO women. Moreover, unlike PTO, CTO subjects significantly reduced their WHR values. In both groups weight loss led to a significant drop in fasting and glucose-stimulated insulin and C peptide levels. However, PTO women reduced their C peptide levels significantly less than CTO. In conclusion, weight loss only modified body fat distribution in women with CTO, who appeared to be prone to a greater weight loss than the PTO women. Compared to PTO, CTO women were characterized by higher insulin levels and peripheral insulin resistance, which improved during hypocaloric feeding probably due to the combined effect of weight loss and the change in body fat distribution.

Adipose Tissue↗

Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss.

We studied a group of obese hyperandrogenic amenorrheic women to determine the effects of weight loss on anthropometry, hormonal status, menstrual cycles, ovulation, and fertility. Fourteen women had polycystic ovaries, two the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome, one hirsutism of adrenal origin, and three idiopathic chronic anovulation. The duration of amenorrhea before the study ranged from 3-17 months [mean, 8.6 +/- 4.5 (+/- SD)]. All women ate a hypocaloric diet for a period of 8.0 +/- 2.4 months. Weight loss ranged from 4.8 to 15.2 kg (mean, 9.7 +/- 3.1 kg; 1.35 +/- 0.56 kg/month) and the waist to hip ratio, which was used as a measurement of body fat distribution, decreased from 0.86 +/- 0.1 to 0.81 +/- 0.06 (P less than 0.0001). The women's mean plasma testosterone and LH concentrations decreased significantly (P less than 0.001 and P less than 0.005, respectively). A significant positive correlation was found between the decreases in plasma testosterone levels and the decreases in glucose-stimulated insulin levels. Moreover, the decreases in the waist to hip ratio correlated positively with the decreases in glucose-stimulated insulin levels and inversely with the decreases in plasma 17 beta-estradiol. No relationships were found between weight loss and the changes in plasma insulin, steroid, and gonadotropin concentrations. The responsiveness to the weight reduction program was evaluated by comparing the number of menstrual cycles during the study period with the number reported before it. Eight women had significantly improved menstrual cyclicity (responders), while 12 did not (nonresponders). The clinical characteristics and hormone values were similar in responder and nonresponder women. In the group as a whole, 33% of the menstrual cycles during the study were ovulatory, and 4 pregnancies occurred. Hirsutism improved significantly in more than half of the women, as did acanthosis nigricans when present. We conclude that weight loss is beneficial in all obese hyperandrogenic women regardless of the presence of polycystic ovaries, the degree of hyperandrogenism, and the degree and distribution of obesity.

Adult↗

Weight loss and sex steroid metabolism in massively obese man.

To evaluate the effect of weight loss and diet therapy on plasma sex hormone behavior in male obesity, 9 men with a BMI of 43.4 +/- 6.3 participated in an 8-week semistarvation program [whose energy content ranged from 320 to 500 k calorie/day (proteins 44 to 60 g and carbohydrates 54 to 81 g per day)] followed by a two-week hypocaloric (1000 k calorie/day) refeeding. In basal conditions, obese patients presented higher estrogen and lower dehydroepiandrosterone sulphate, testosterone (total and free) and sex-hormone binding globulin concentrations with respect to a group of control normal-weight subjects. Cumulative weight loss was 23.9 +/- 3.6 kg after semistarvation and 24.4 +/- 4.8 kg after refeeding (p = NS). A significant increase in testosterone, free testosterone and dehydroepiandrosterone sulfate was observed throughout the study, irrespective of dietary intake. A transient increase occurred in estrone levels while 17B-estradiol did not change. Gonadotropins and sex-hormone binding globulin values remained unaltered. No relationship was found between sex hormones and dietary energy content or composition. Daily urine free cortisol, which was used as a parameter of adrenal function, fell approximately 50% during semistarvation but returned to baseline values after refeeding. These results show that in massively obese patients weight loss per se may partially reverse sex hormone abnormalities but not sex-hormone binding globulin concentrations. It remains to be determined whether the return to "normal weight" can normalize steroid metabolic derangements in the obese man.

Adult↗

Erythrocyte Na-K-ATPase membrane activity in obese patients fed over a long-term period with a very-low-calorie diet.

In a search for the role of long-term hypocaloric feeding on the expression of the erythrocyte Na pump in obesity, we examined three groups of subjects. Group 1 consisted of 10 obese subjects who had been under treatment for a long period of time with a very-low-calorie diet (500 kcal/d) while group 2 consisted of 10 age-, sex-, and body mass index-matched obese subjects on their usual diet; in the third group, 12 normal-weight subjects on a free diet served as controls. There was no difference between the groups in the number of erythrocyte binding sites per cell. On the contrary, the Na-K-ATPase activity was significantly lower in the obese group 1 (0.35 +/- 0.09 mumol Pi x mg protein-1 x h-1) compared to that observed in the obese group 2 (0.42 +/- 0.07, P less than .05) and in control subjects (0.45 +/- 0.06, P less than .05). Sex, duration of hypocaloric feeding, and the amount of weight loss before the study in the obese group 1 seemed not to be related to the Na pump parameters. We conclude that long-term severe hypocaloric feeding may be a factor in altered erythrocyte Na-K-ATPase in obese individuals.

Adult↗

Evidence for a hypothalamic alteration of catecholamine metabolism in polycystic ovary syndrome.

The role of brain catecholamine (CA) activity in the neuroendocrine regulation of the GnRH-LH system in polycystic ovary syndrome (PCO) was investigated by high-performance liquid chromatography (HPLC) with electrochemical detector. We measured urinary dopamine (DA), noradrenaline (NA), adrenaline (A), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and total 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in a group of 12 women with PCO before and during peripheral dopa-decarboxylase blockade, by carbidopa. HVA and DOPAC concentrations were significantly lower (P less than 0.001 and P less than 0.005, respectively) in PCO patients compared with twelve control subjects in early follicular phase, whereas total MHPG concentrations and MHPG/VMA ratio were significantly higher (P less than 0.005) in PCO patients. Moreover, HVA and DOPAC concentrations in PCO patients were similar to those of the control subjects in preovulatory phase, while MHPG concentrations remained higher in PCO patients (P less than 0.01). DA, NA, A and VMA concentrations were similar to those of control subjects in both phases of the cycle. During carbidopa administration the concentrations of all urinary CAs and metabolites were unchanged, except those of DA which dropped markedly (P less than 0.001). These data suggest that (1) an altered central catecholamine metabolism consisting of DA deficiency and NA excess is present in PCO, and (2) the site of DA deficiency may be located in the hypothalamus.

3,4-Dihydroxyphenylacetic Acid↗

Urinary excretion rate of C-peptide in fed and fasted obese humans.

The aim of the study was to evaluate the reliability of urinary excretion rate of C-peptide as a marker of B-cell function during fasting. Ten obese subjects of both sexes fasted for 5 days. Diurnal serum C-peptide was collected before and on the 5th day; morning serum samples (for glucose, insulin and C-peptide) and 12-h urine samples (7.00 to 19.00 h) were collected daily. Body weight decreased from 138.7 +/- 15.9 to 132.9 +/- 15.6 kg. Morning glucose, insulin (-40%) and C-peptide (-50%) fell significantly throughout the study. Mean diurnal C-peptide values were 2.19 +/- 0.69 nmol/l before and 0.60 +/- 0.19 nmol/l after fasting (P less than 0.0001) and its secretion rate was 909.4 +/- 297.9 and 244.4 +/- 83.9 nmol/12 h (P less than 0.005), respectively. Excretion rate of C-peptide fell progressively from basal (11.2 +/- 4.2 nmol/12 h) to a nadir value of 1.3 +/- 0.8 nmol/12 h (P less than 0.0005); similarly, the C-peptide to creatinine clearance ratio fell from 0.062 +/- 0.035 to 0.028 +/- 0.015 (P less than 0.05). These results indicate that fasting modifies renal metabolism of C-peptide thus creating several complications in the quantitative interpretation of urinary levels as an index of its secretion rate from the B-cell.

Adult↗

[Effect of guar on plasma lipids and on the biological activity of insulin in patients with type 2 diabetes mellitus].

10 patients with type 2 diabetes mellitus, in stable weight and diet therapy, followed a 2 months nutritional supplementation with guar, 15 g/day. Their previous nutritional and pharmacological therapy was not modified throughout the study. No changes occurred in body weight or major parameters of metabolic control. However, a significant fall occurred in fasting plasma, total and LDL cholesterol, and apolipoprotein B concentrations. Insulin sensitivity, measured by the "steady state plasma glucose", obtained after a 150 min glucose-insulin-somatostatin infusion, improved in all patients but two. A significant correlation was observed between steady state plasma glucose variations, the glycosylated haemoglobin A1c (r = 0.70; p less than 0.005), total (r = 0.77; p less than 0.001), and LDL cholesterol (r = 0.69; p less than 0.005) and apolipoprotein B concentrations (r = 0.75; p less than 0.005).

Adult↗

Insulin as a factor of increased androgen production in women with obesity and polycystic ovaries.

To evaluate the possible role of moderate hyperinsulinemia on abnormal androgen secretion, we examined 4 age and weight-matched groups of obese subjects: 2 groups of women with normal menses whose fasting insulin (IRI) levels were less than or equal to 20 microU/ml (OB-I) or greater than or equal to 40 microU/ml (OB-I) and 2 groups of women with polycystic ovaries who were similarly grouped. All subjects underwent an oral glucose tolerance test, blood sex hormone determination and multiple LH determinations. Compared to OB, OB-PCO women showed significantly higher values of LH, androgen and estrogen concentrations. OB-I and OB-II showed similar hormonal patterns. On the contrary, OB-PCO-II presented significantly (p less than 0.05) higher androstenedione concentrations (348.7 +/- 129.9 ng/dl) (m +/- SD) than OB-PCO-I women (237.0 +/- 73.7 ng/dl). These differences were evident despite similar plasma LH concentrations. In conclusion, these results suggest that insulin may be a factor amplifying LH-dependent androgen secretion in hyperandrogenized women with obesity and PCO.

Androgens↗

Sex hormones in obese premenopausal women and their relationships to body fat mass and distribution, B cell function and diet composition.

We examined sex hormone blood concentrations in a group of 33 obese non-hirsute premenopausal women with normal menses and in 14 age-matched normal-weight controls, and evaluated their relationship with anthropometric parameters, dietary habits and insulin levels. Obese women showed lower than control sex hormone-binding globulin (24.9 +/- 14.6 vs 38.6 +/- 12.5 nmol/l; p less than 0.005) and 5 alpha-dihydrotestosterone (13.7 +/- 5.4 vs 18.2 +/- 4.8 ng/dl; p less than 0.005) values. Despite their consensual behavior, the correlation coefficient between 5 alpha-dihydrotestosterone and sex hormone-binding globulin was not significant in the obese while in controls it was 0.68 (p less than 0.01). This suggests that mechanisms operating to lower the plasma levels of these compounds may be regulated differently in obesity. Body Mass Index, per cent body fat and its distribution showed a highly significant negative correlation with sex-hormone binding-globulin and 5 alpha-dihydrotestosterone values. Insulin levels did not appear to be correlated with sex hormone values. On the contrary, in the obese women we found a highly significant correlation between dietary lipids and sex-hormone-binding-globulin levels (r = -0.54; p less than 0.005) and between dietary carbohydrates and estrone values (r = 0.47; p less than 0.005); all these relationships were independent of body weight. These results confirm that in premenopausal women obesity may be characterized by detectable changes in sex steroid metabolism and suggest a possible causal role not only of the excessive quantity of metabolically active adipose tissue but also of specific dietary factors.

Adult↗

Protein metabolism in obese patients during very low-calorie mixed diets containing different amounts of proteins and carbohydrates.

To assess long-term nitrogen sparing capacity of very low-calorie mixed diets, we administered two isoenergetic (2092KJ) liquid formula regimens of different composition for 8 weeks to two matched groups of massively obese patients (group 1: proteins 60 g, carbohydrate 54 g; group 2: proteins 41 g, carbohydrates 81 g). Weight loss was similar in both groups. Daily nitrogen balance (g) during the second month resulted more a negative in group 2 with respect to group 1. However, within the groups individual nitrogen sparing capacity varied markedly; only a few in group 1 and one in group 2 were able to attain nitrogen equilibrium throughout the study. Daily urine excretion of 3-methylhistidine fell significantly in group 1 but did not change in group 2. Unlike total proteins, albumins, and transferrin, serum levels of retinol-binding protein, thyroxin-binding globulin, and complement-C3 fell significantly in both groups but per cent variations of complement-C3 were more pronounced in the first group. Prealbumin levels fell persistently in group 1 and transiently in group 2. The results indicate that even with this type of diet an adequate amount of dietary protein represents the most important factor in minimizing whole body protein catabolism during long-term semistarvation in massively obese patients. Moreover, they confirm the possible role of dietary carbohydrates in the regulation of some visceral protein metabolism.

Adult↗

Interrelationships between dietary carbohydrates, B cell function and rate of ketogenesis during underfeeding in obese patients.

Six matched groups of obese patients underwent 3-week selective hypocaloric regimens which consisted of a 240 or 480 kcal/day liquid formula diets for groups 1-4 and an 800 kcal/day conventional diet for groups 5 and 6. Carbohydrate intake ranged from 19 to 112 g/day so that for each energy level two different amounts of carbohydrates were administered. Body weight loss was similar in groups 1-4 and significantly lower in groups 5 and 6. During treatment fasting serum insulin (but not serum C-peptide) levels and the daily urine excretion rate of C-peptide showed quite a similar fall in all groups. Fasting glucagon levels did not change. The rate of ketogenesis which developed during each nutritional treatment was inversely related to the amount of dietary carbohydrates; moreover, a significant correlation was found between percent variation of ketoacids and those of fasting IRI (r = -0.42; p less than 0.01) and glucose (r = -0.52; p less than 0.01) concentrations, but not with those of fasting C-peptide and its daily urine excretion rate. In conclusion, it seems that during underfeeding (1) low- and high-carbohydrate-containing regimens are substantially equipotent stimuli secretagogues of insulin secretion, and (2) carbohydrate (or glucose) availability affects ketogenesis even through noninsulin-mediated mechanisms.

Adult↗

Evidence for a physiological reduction in brain dopamine but not norepinephrine metabolism during the preovulatory phase in normal women.

To investigate the role of brain catecholamine (CA) activity in the mechanisms related to physiological ovulatory function, we used high-performance liquid chromatography with electrochemical detector to measure the levels of urinary dopamine (DA), norepinephrine (NE), epinephrine (E), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and total 3-methoxy-4-hydroxy-phenylglycol (MHPG) in a group of 12 normal women during both the early follicular and pre-ovulatory phases of the menstrual cycle. The mean (+/- SEM) concentrations of HVA and DOPAC were significantly lower (P less than 0.001) during the pre-ovulatory phase than during the early follicular phase, whereas those of DA, NE, E, VMA and total MHPG were unaltered. A significant negative correlation between urinary HVA and plasma LH (r = -0.70, P less than 0.01) was also found during the pre-ovulatory period, whereas no significant negative correlations were found between urinary HVA and plasma PRL, progesterone and oestradiol. These data show: 1) reduced brain DA activity and 2) unchanged brain NE activity at the time of the midcycle surge in normal women, suggesting a physiological variation of the central DA metabolism in ovulatory function.

3,4-Dihydroxyphenylacetic Acid↗

Effects of short- and long-term administrations of famotidine and ranitidine on some pituitary, sexual and thyroid hormones.

The endocrine effects of short-term (4 weeks) and long-term (6 months) oral administration of famotidine (40 and 20 mg nocte, respectively) and ranitidine (300 and 150 mg nocte, respectively), were investigated in 20 male patients with duodenal ulcers. Basal PRL, LH, FSH and TSH serum levels were evaluated and their response to specific releasing factors, and basal blood levels of some sexual (E2, P, T) and thyroid (T3, T4) hormones. None of the treatments modified basal and RH-stimulated levels of PRL, LH, FSH and TSH, nor basal levels of sexual hormones. Regarding the thyroid hormones, no effect was observed during the administration of famotidine. On the contrary, short-term treatment with ranitidine induced a significant decrease in thyroxine serum levels, while no effect was observed during maintenance treatment.

Adult↗

Does ephedrine promote weight loss in low-energy-adapted obese women?

A double-blind cross-over randomized study was performed in 10 selected adult overweight and obese (body mass index greater than 27) women who had been adapted to low-energy intake for a long period of time and who had shown difficulty in losing weight with conventional hypocaloric treatment. Combined with diet therapy (1000-1400 kcal/day), l(-)ephedrine hydrochloride (50 mg three times a day per os) or placebo were administered daily before each meal, after a period of stabilization with diet only for 1 month. Each pharmacological treatment lasted for 2 months. Weight loss was significantly (P less than 0.05) greater during the ephedrine period (2.41 +/- 0.61 kg) than during the placebo period (0.64 +/- 0.50 kg). None of the patients presented clinically important side-effects. These preliminary results seem to suggest a possible role for a thermogenic compound such as ephedrine in promoting weight loss in low-energy-adapted obese women.

Adult↗

Estimation of B-cell function by the urinary excretion rate of C-peptide in diabetic patients: comparison with C-peptide response to glucagon and to a mixed meal.

This study examined the relationship between the C-peptide response to intravenous glucagon and mixed meal stimulation and the 24 h urinary excretion rate of C-peptide and its urinary excretion during the glucagon test in nine control subjects, eighteen Type 1 (insulin-dependent) and twenty-two Type 2 (non-insulin-dependent) diabetic patients. Compared to controls (61.0 +/- 7.1 micrograms), the 24-h urine excretion rate of C-peptide was 8.2 +/- 3.1 micrograms (p less than 0.001) in Type 1 and 89.8 +/- 12.9 micrograms (p = NS) in Type 2 diabetic patients. C-peptide urinary excretion rate during the glucagon test was 6.92 +/- 1.11 micrograms, 0.42 +/- 0.10 microgram (p less than 0.001) and 6.47 +/- 1.13 micrograms (p = NS) respectively. Fasting serum C-peptide values were 1.53 +/- 0.16 ng/ml in controls, 0.42 +/- 0.09 ng/ml in Type 1 (p less than 0.0001) and 2.08 +/- 0.22 ng/ml in Type 2 diabetics (p = NS); C-peptide areas under the curve after glucagon stimulation were, respectively, 241.6 +/- 20.3 ng/ml, 29.2 +/- 5.9 ng/ml (p less than 0.0001) and 170.9 +/- 17.9 ng/ml (p less than 0.03) and after the meal test they were 204.7 +/- 15.6, 68.7 +/- 19.8 ng/ml (p less than 0.0001) and 265.5 +/- 32.9 ng/ml (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗