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Biomedical subjects

R Giorgino

Publications and source records attributed to R Giorgino.

At least 37 records · Page 2Linked to original sources

Lower insulin sensitivity as an independent risk factor for carotid wall thickening in normotensive, non-diabetic, non-smoking normal weight and obese premenopausal women.

OBJECTIVE: Increased thickness of the intima-media complex of the common carotid artery (IMT-CCA) is an early marker of atherosclerosis. The aim of the present study was to investigate the relationship between insulin resistance and IMT-CCA in premenopausal women. SUBJECTS: 86 young women, aged 18-31 y, were recruited for the study: 28 were normal weight (BMI<25 kg/m2), 23 were overweight (BMI 25-30 kg/m2) and 35 were obese (BMI>30 kg/m2). MEASUREMENTS: The IMT-CCA was measured by high resolution 'B-mode' ultrasonography; insulin sensitivity was determined by insulin tolerance test (ITT) and quantitated by calculation of KITT. Fasting plasma glucose and lipids (triglycerides, total and HDL-cholesterol) were also measured by enzymatic methods. Central fat accumulation was evaluated by measuring waist circumference (WC). RESULTS: IMT-CCA showed an inverse association with KITT (P<0.05). When the IMT-CCA was considered as the dependent variable in a forward stepwise multiple regression analysis, it maintained an independent association with KITT (P<0.05), after adjusting data for age, BMI, WC, mean blood pressure levels and plasma glucose and lipids. CONCLUSION: These results suggest that IMT-CCA is significantly associated with insulin resistance, independent of other well-known CVD risk factors. Since the IMT-CCA is an earlier asymptomatic sign of atherosclerosis, this study indicates that insulin resistance per se may accelerate atherogenesis.

Adolescent↗

Resting energy expenditure, growth hormone indices, body composition and adipose tissue distribution in premenopausal women.

OBJECTIVES: A significant growth hormone (GH) contribution to interindividual variance in energy expenditure (REE) in women can be hypothesized. The present study examines the independent association between physiological levels of GH function indices and REE. SETTING: All subjects were hospitalized in the Institute of Internal Medicine of the University of Verona. SUBJECTS: Twenty-four premenopausal overweight (BMI = 28-55 kg m-2) women aged 18-49 years. INTERVENTIONS: REE was estimated by indirect calorimetry and body composition and fat distribution by single slice computed tomography method. GH activity and GH status were determined by measuring serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3). RESULTS: GH indices did not show any significant correlation with REE. The relation between GH indices and REE was also examined by multiple regression analysis to account for possible confounders such as body composition, adipose tissue distribution and age. When body composition was considered, body fat and fat-free mass were the only significant predictors of REE (R2 = 0.699, P = 0.0001). The contributions of GH indices were not significant. CONCLUSIONS: Our findings do not support the hypothesis that GH in physiological conditions could be an independent determinant of REE in women with obesity.

Adipose Tissue↗

Prevalence and mechanisms of diurnal hypercapnia in a sample of morbidly obese subjects with obstructive sleep apnoea.

It is well known that obstructive sleep apnoea is especially frequent in the morbidly obese. In these subjects diurnal chronic hypercapnia, whose mechanism is still debated, may be present. Our study was performed to evaluate the prevalence and the mechanism of diurnal hypercapnia in the morbidly obese affected by obstructive sleep apnoea. From a population referred to our centre because of suspicion of sleep related breathing disorders, we selected 285 subjects without cardiopulmonary, neuromuscular or endocrinological diseases: 89 (36 M and 53 F, aged 46+/-13 years) had body mass index (BMI) > or = 40 kg m(-2) (MO group: morbidly obese subjects) and 196 (99 M and 97 F, aged 48+/-16 years) had BMI <40 kg m(-2) (NMO group: non-morbidly obese subjects). Then the MO group was divided into three subgroups: normocapnic subjects without obstructive sleep apnoea, normocapnic subjects with obstructive sleep apnoea, hypercapnic subjects with obstructive sleep apnoea; while we found no hypercapnic subject without obstructive sleep apnoea. All subjects underwent anthropometric evaluations and bioelectrical impedance analyses, respiratory function tests and arterial blood gas analysis, a modified version of the Sleep and Healthy questionnaire and a full night polysomnography. Our results showed that hypercapnia (PaCO2 > or = 45 mm Hg) associated with obstructive sleep apnoea [respiratory disturbance index (RDI) > or = 10 h(-1)] was found in 27% of the morbidly obese subjects, but only in 11% of the nonmorbidly obese ones (P<0.01). The comparison among the three subgroups, in which we divided the morbidly obese subjects, shows that those with hypercapnia and obstructive sleep apnoea had significantly more important ventilatory restrictive defects [forced vital capacity (FVC)% of pred 73.27+/-14 81 vs. 82.37+/-16.93 vs. 87.25+/-18.14 respectively; total lung capacity (TLC)% of pred 63.83+/-16.35 vs. 79.11+/-14.15 vs. 87.01+/-10.5], a significantly higher respiratory disturbance index (RDI 46.34+/-26.90 vs. 31.79+/-22.47 vs. 4.98+/-3.29) a longer total sleep time with oxyhaemoglobin saturation<90% [total sleeptime (TST)SaO2<90% 63.40+/-33.86 vs. 25.95+/-29.34 vs. 8.22+/-22.12] and a lower rapid eye movement (REM) stage (9.5+/-1.2 vs. 14.0+/-0.9 vs. 17.05+/-1.2) than normocapnic subjects with obstructive sleep apnoea or subjects without obstructive sleep apnoea. The best model to predict PaCO2 resulted from a combination of TSTSaO2<90% (r2 = 0.22, P<0.001), forced expiratory volume in 1 sec (FEV1)% of pred (r2 = 0.09, P<0.01), FVC % of pred (r2 = 0.075, P<0.01). In conclusion our study suggests that diurnal hypercapnia is frequently associated with obstructive sleep apnoea in the morbidly obese without chronic obstructive pulmonary disorder (COPD) and that ventilatory restriction and sleep related respiratory disturbances correlate to diurnal hypercapnia.

Adult↗

[Incidence of thyroid diseases in pregnant women with type I diabetes mellitus].

The interaction between pregnancy, Diabetes Mellitus and thyroid disturbance needs a particular attention. The antithyroid antibodies are more frequent in pregnant women with insulin-dependent diabetes mellitus (IDDM) than in normal pregnant women. Beside, an increased prevalence of subclinic ipotyroidism has been described in pregnant diabetic women. The object of this study is to verify if women with insulin-dependent diabetes mellitus have more probability than normal women to develop a thyroid pathology in pregnancy, in an area with sufficient iodine. Twenty-eight women have been studied: 15 with IDDM, with age 20-37 years, and 13 healthy women, with the same age. Patients were evaluated at the following time-intervals: 9-12 and 18-20 weeks' gestation, at delivery and six months after delivery. Diabetic women followed an insulinic therapy optimized for to reach a good metabolic control. All follow the patients had a thyroid ecography to evaluate thyroid volume and possible presence of nodular formation or others pathologic signs. A blood sample to assay FT3, FT4, TSH, of the antibodies Anti-Thyreoperoxidase (Anti-TPO) and Anti-Thyreoglobulin (Anti-TG). A urine specimen taken to evaluate the iodine excretion. No significant difference was observed between diabetic and normal women, for the values of TSH (p < 0.2), FT4(p < 0.7), FT3(p < 0.6). Instead a significant difference was found between the thyroid volume (p < 0.04), in the diabetic patients versus the normal women, at delivery and six months after delivery. The results of this study underline the importance of the screening of the thyroid function and morphology, in all the pregnant women and, particularly, in the diabetic patients, to find the presence of glandular alterations as early as possible.

Adult↗

Plasma plasminogen activator inhibitor-I is associated with plasma leptin irrespective of body mass index, body fat mass, and plasma insulin and metabolic parameters in premenopausal women.

Leptin, the satiety hormone expressed almost exclusively in adipose tissue, is a marker of body fat accumulation in humans. Recent studies have shown that plasminogen activator inhibitor-1 (PAI-1), a prothrombotic factor associated with atherosclerosis complications, is also produced in adipose tissue. The objective of the present study was to determine whether PAI-1 antigen plasma concentrations are associated with leptin plasma levels or the body fat mass (FM) independently of the variables known to influence PAI-1 production. Sixty-one nondiabetic women aged 18 to 45 years with a wide range of values for the body mass index ([BMI] 18.1 to 37.7 kg/m2) were evaluated for (1) body FM and fasting plasma levels of (2) PAI-1 antigen, (3) PAI-1 activity, (4) leptin, (5) insulin, (6) blood glucose, and (7) lipids (cholesterol, high-density lipoprotein [HDL]-cholesterol, and triglycerides [TG]). Body FM and fat-free mass (FFM) were estimated during fasting conditions by the bioimpedance analysis (BIA) method using a tetrapolar device. Body fat distribution was evaluated by the waist circumference and the waist to hip ratio (WHR). FM was directly associated with both PAI-1 antigen (r = .585, P < .001) and PAI-1 activity (r = .339, P < .001). Seemingly, leptin was positively related to both PAI-1 antigen (r = .630, P < .001) and PAI-1 activity (r = .497, P < .001). Moreover, both PAI-I antigen and PAI-1 activity were directly correlated with FFM (r = .285, P < .05, and r = .336, P < .01, respectively), BMI (r = .594, P < .001, and r = .458, P < .001, respectively), and WHR (r = .510, P < .001, and r = .391, P < .005, respectively). Insulin was directly related to PAI-1 antigen (r = .540, P < .001), PAI-1 activity (r = .259, P < .05), leptin (r = .447, P < .001), and FM (r = .435, P < .001). The association between PAI-1 antigen (dependent variable) and leptin or FM was tested by a stepwise regression model simultaneously including leptin, FM, BMI, WHR, age, FFM, and fasting insulin, blood glucose, TG, cholesterol, and HDL-cholesterol as independent variables. PAI-1 antigen maintained a significant positive independent relationship only with leptin (t = 2.923, P < .01), insulin (t = 3.489, P < .001), and fasting blood glucose (t = 2.092, P < .05), and a negative independent relationship with HDL-cholesterol (t = -2.634, P < .05). In conclusion, the strong relationship between PAI-1 antigen and leptin irrespective of other variables known to influence these factors seems to indicate that leptin per se may potentially increase PAI-1 plasma concentrations in obese subjects.

Adipose Tissue↗

Microcirculatory damage of common carotid artery wall in obese and non obese subjects.

The objective of the present study was to determine whether the intima-media thickness (IMT) is independently related with obesity, and central fat accumulation in healthy subjects. Common carotid artery IMT, parameters of body fat accumulation and distribution (body mass index, waist circumference, waist-to-hip ratio), blood pressure levels, and circulating fasting insulin, glucose, and lipid (cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol) levels were determined in a population of non-diabetic normal weight and obese subjects. Smoking habits (packs-years) were also taken into account. 239 healthy subjects (143 women and 96 men), with age ranging between 18 and 45 years, were enrolled into the study. They were divided indo two groups according to the body mass index (BMI), obese (132 subjects, 77 woman and 55 men, with BMI greater than 27.0) and controls (107 subjects: 66 women and 41 men, with BMI lower than 27.0). Common carotid artery intima-media thickness was measured by B-mode ultrasound imaging. Fasting plasma metabolic parameters (glucose and lipids) and insulin levels were determined by enzymatic and radioimmunological assays, respectively. Insulin sensitivity was estimated by insulin tolerance test (ITT) and the rate constant for plasma glucose disappearance (KITT) during the 3- to 15-min period following the regular insulin injection was taken as a measure of in vivo insulin action. Obese patients showed higher IMT than controls, and IMT was significantly associated with BMI in the whole population (r = 0.316, p < 0.001). Age (r = 0.327, p < 0.001), KITT (r = -0.201, p < 0.01), fasting blood glucose (r = 0.187, p < 0.01), LDL-chol (r = 0.201, p < 0.01), smoking (r = 0.147, p < 0.05), MBP levels (r = 0.154, p < 0.05), cholesterol (r = 0.152, p < 0.05) and HDL-chol (r = -0.159, p < 0.05) were also significantly associated with IMT. Age (r = 0.330, p < 0.05), BMI (r = 0.299, p < 0.01), waist (r = 0.312, p < 0.001), WHR (r = 0.266, p < 0.001) and KITT (r = -0.259, p < 0.01) were the parameters most strongly correlated with IMT in women, and age (r = 0.324, p < 0.001), BMI (r = 0.338, p < 0.001) waist (r = 0.325, p < 0.001) and LDL-chol (r = 0.283, p < 0.01) where the parameters most strongly correlated with IMT in men. When a stepwise multiple regression analysis was performed for the whole population, only age (p < 0.001) and BMI (p < 0.001) maintained a significant positive relationship with IMT. When a stepwise multiple regression analysis was performed separately for men and women, BMI or waist circumference or WHR were alternatively entered into the model; interestingly, only age, BMI and waist were still significantly correlated with IMT, whereas WHR did not maintain a significant correlation with IMT. In conclusion, BMI and waist circumference, but not WHR, are strongly and independently associated with the IMT of common carotid artery. These results suggests that central fat accumulation may accelerate the development of earlier clinically silent stages of atherosclerosis, thus possibly explaining the higher prevalence of cardiovascular diseases in patients with abdominal obesity.

Adolescent↗

Assessment of cardiac vagal activity in patients with hyperthyroidism.

Previous studies suggested that in patients with hyperthyroidism an autonomic imbalance and in particular a lower than normal vagal activity might be present. To verify this hypothesis we have evaluated the respiratory sinus arrhythmia (RSA, a measure of cardiac vagal activity) in ten hyperthyroid patients and in ten normal subjects. RSA was calculated from the power of the spectral component of the heart rate variability in high frequency band (HF-RR) during both spontaneous (supine and passive head-up tilt) and controlled breathing (supine). During controlled breathing the phase relation between heart rate and respiratory has been computed. The hyperthyroid patients showed a higher heart rate in all three conditions (P<0.001) and higher spontaneous respiratory rate in supine position (centered frequency of HF-RR: 0.342+/-0.015 vs 0.262+/-0.016 Hz; P<0.001). No difference was found in hyperthyroid patients compared to controls in terms of the HF-RR power in normalized units both during spontaneous breathing (supine, 43+/-8.3 vs 39.7+/-6.7%; tilt 18.8+/-5.9 vs 19.3 vs 4.1%; mean+/-SE) and controlled breathing (45.4+/-7.1 vs 48.9+/-6.9%). No difference was found also in terms of the phase relationship between the heart rate and the respiratory signals (77.5+/-32.3 vs 77.5+/-28.1, degrees). Hyperthyroid patients seem not to have an impaired cardiac vagal activity.

Adult↗

Divergent effects of short-term, very-low-calorie diet on insulin-like growth factor-I and insulin-like growth factor binding protein-3 serum concentrations in premenopausal women with obesity.

OBJECTIVE: Insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) serum concentrations provide a good measure of the biological effects of growth hormone. The aims of the present study were to: (1) investigate the associations of IGF-I and IGFBP-3 with body fat mass and distribution, and (2) evaluate the effects of 3 weeks of very-low-calorie diet (VLCD) (318 kcal/day, with 40 g protein, 35 g carbohydrate, and 2 g fat) on IGF-I and IGFBP-3 serum concentrations. RESEARCH METHODS AND PROCEDURES: The study was performed in 21 nondiabetic premenopausal women with obesity (body mass index >27.0 kg/m2; age: ranging from 18 to 48 years). Body fat mass and distribution were measured by computed tomography. RESULTS: Before dietary treatment, IGF-I and IGFBP-3 serum concentrations were inversely associated with visceral adipose tissue (VAT) area (p<0.005 and p<0.05, respectively), but not with either total body fat or subcutaneous adipose tissue area. VLCD produced a significant decrease of body mass index (p<0.001), total body fat (p<0.001), VAT (p<0.005), subcutaneous adipose tissue (p<0.001), IGF-I concentrations (p<0.05), and an increase of IGFBP-3 serum levels (p<0.001). The association of VAT with either IGF-I or IGFBP-3 serum concentrations was not maintained following VLCD. DISCUSSION: Our study suggests that visceral adipose tissue, rather than adiposity per se, accounts for IGF-I and IGFBP-3 serum concentrations, and that rapid weight loss, possibly due to nutritional changes, results in lower IGF-I concentrations, higher IGFBP-3 concentrations, and abrogation of the inverse associations of VAT with IGF-I and IGFBP-3.

Adipose Tissue↗

High prevalence of risk factors for cardiovascular disease in parents of IDDM patients with albuminuria.

Life expectancy is shorter in the subset of insulin-dependent diabetic (IDDM) patients who are susceptible to kidney disease. Familial factors may be important. In this study the prevalence of cardiovascular disease mortality and morbidity and of risk factors for cardiovascular disease was compared in the parents of 31 IDDM patients with elevated albumin excretion rate (AER > 45 microg/min; group A) with that of parents of 31 insulin-dependent diabetic patients with normoalbuminuria (AER < 20 microg/min; group B). The two diabetic patient groups were matched for age and duration of disease. Information on deceased parents was obtained from death certificates and clinical records and morbidity for cardiovascular disease was ascertained using the World Health Organization questionnaire and Minnesota coded ECG. Hyperlipidaemia was defined as serum cholesterol higher than 6 mmol/l and/or plasma triglycerides higher than 2.3 mmol/l and/or lipid lowering therapy; arterial hypertension as systolic blood pressure higher than 140 mmHg and/or diastolic blood pressure higher than 90 mmHg and/or antihypertensive treatment. The percentage of dead parents was similar in the two groups (26 vs 20% for parents of group A vs group B, respectively), but the parents of the diabetic patients with elevated AER had died at a younger age (58 +/- 10 vs 70 +/- 14 years; p < 0.05). Parents of diabetic patients with nephropathy had a more than three times greater frequency of combined mortality and morbidity for cardiovascular disease than that of the parents of diabetic patients without nephropathy (26 vs 8%; odds ratio 3.96, 95% CI 1.3 to 12.2; p < 0.02). Living parents of group A had a higher prevalence of arterial hypertension (42 vs 14% p < 0.01) and hyperlipidaemia (49 vs 26% p < 0.05) as well as higher levels of lipoprotein (a) [median (range) 27.2 (1-107) vs 15.6 (0.2-98) mg/dl; p < 0.05]. They also had reduced insulin sensitivity [insulin tolerance test: median (range) K(itt) index: 3.7 (0.7-6.2) vs 4.8 (0.7-6.7)% per min; p < 0.05]. In the families of IDDM patients with elevated AER there was a higher frequency of risk factors for cardiovascular disease as well as a predisposition to cardiovascular disease events. This may help explain, in part, the high prevalence of cardiovascular disease mortality and morbidity in those IDDM patients who develop nephropathy.

Adult↗

Lower androgenicity is associated with higher plasma levels of prothrombotic factors irrespective of age, obesity, body fat distribution, and related metabolic parameters in men.

The purpose of this study was to examine the relationships between androgenic status and plasma levels of both prothrombotic and antithrombotic factors in men, irrespective of obesity, body fat distribution, and metabolic parameters. Sixty-four apparently healthy men, 40 with a body mass index (BMI) greater than 25 kg/m2 (overweight and obese [OO]) and 24 non-obese controls with a BMI less than 25, were selected and evaluated for (1) plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) antigen, PAI-1 activity, fibrinogen, von Willebrand factor (vWF) antigen, vWF activity, and factor VII (FVII) as the prothrombotic factors; (2) plasma levels of tissue plasminogen activator (TPA) antigen, protein C, and antithrombin III as the antithrombotic factors; (3) fasting plasma concentrations of insulin and glucose and the lipid pattern (triglycerides [TG] and total and high-density lipoprotein [HDL] cholesterol) as the metabolic parameters; and (4) free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) serum levels as the parameters of androgenicity. Body fat distribution was evaluated by the waist to hip ratio (WHR). In OO and non-obese subjects taken together, plasma levels of PAI-1 antigen, fibrinogen, and FVII were inversely associated with FT (r = .255, P < .05, r = -3.14, P < .05, and r = -.278, P < .05, respectively), and the negative relationships of both fibrinogen and FVII with FT were maintained after stepwise multiple regression analysis. Plasma concentrations of PAI-1 antigen and PAI-1 activity were also negatively correlated with SHBG (r = -.315, P < .05 and r = -.362, P < .01, respectively), and these associations held irrespective of the other parameters investigated. None of the antithrombotic and fibrinolytic factors were independently related to serum androgen levels. Subjects with a BMI higher than 25 kg/m2 had higher plasma concentrations of PAI-1 antigen, PAI-1 activity, and fibrinogen as compared with non-obese controls (P < .001, P < .001, and P < .01, respectively). In addition, in OO and control subjects as a whole, multiple stepwise regression analysis showed that the associations of BMI with PAI-1 activity, fibrinogen, vWF antigen, and vWF activity were independent of any other metabolic and hormonal parameters. Plasma concentrations of PAI-1 antigen, PAI-1 activity, and fibrinogen were also directly correlated with WHR in all subjects taken together, irrespective of the other parameters investigated. Evaluation of antithrombotic factors showed that OO subjects had higher TPA plasma concentrations than non-obese controls (P < .001), whereas protein C and antithrombin III did not differ in the two groups. TPA was also directly correlated with BMI (r = .415, P < .001) and WHR (r = .393, P < .001) in all subjects. The results of this study indicate that (1) men with lower FT serum levels have higher fibrinogen and FVII plasma concentrations, and those with lower SHBG serum levels also have higher levels of PAI-1 antigen and activity; (2) irrespective of other factors, obesity per se may account for higher concentrations of PAI-1, fibrinogen, and vWF; (3) plasma levels of PAI-1 (antigen and activity) and fibrinogen correlate independently with WHR; and (4) among the investigated antithrombotic factors (TPA antigen, protein C, antithrombin III), only TPA antigen plasma concentrations are higher in men with abdominal obesity. Thus, because of the increase in several prothrombotic factors, men with central obesity, particularly those with lower androgenicity, seem to be at greater risk for coronary heart disease (CHD). Apparently, this risk is not counteracted by a parallel increase in plasma concentrations of antithrombotic factors.

Adult↗

Increase in both pro-thrombotic and anti-thrombotic factors in obese premenopausal women: relationship with body fat distribution.

OBJECTIVES: To examine the relationship of obesity, body fat distribution, and fasting plasma insulin concentrations with the plasma levels of both pro-thrombotic and anti-thrombotic factors in premenopausal women. SUBJECTS: 32 obese women with BMI > 28 and 33 age-matched non-obese = women with BMI < 25. MEASUREMENTS: (i) plasma concentrations of plasminogen activator inhibitor-1 antigen (PAI-1 Ag), plasminogen activator inhibitor-1 activity (PAI-1 activity), fibrinogen, von Willebrand factor antigen (vWF Ag), von Willebrand factor activity (vWF activity), and factor VII activity as pro-thrombotic factors; (ii) plasma concentrations of tissue plasminogen activator antigen (t-PA Ag), protein C, and antithrombin III as anti-thrombotic factors; (iii) fasting plasma insulin and glucose concentrations, and the lipid pattern (triglycerides, total and HDL-cholesterol) as metabolic parameters. The body fat distribution was evaluated by measuring the waist circumference and the waist-to-hip ratio (WHR). RESULTS: Obese subjects had higher plasma concentrations of all pro-thrombotic factors as compared to non-obese controls (PAI-1 Ag, P < 0.001; PAI-1 activity, P < 0.05; fibrinogen, P < 0.001; vWF Ag, P < 0.001; vWF activity, P < 0.05; factor VII, P < 0.05). The plasma concentrations of PAI-1 Ag and vWF Ag were directly correlated with the waist circumference independently of other metabolic and non-metabolic variables (P < 0.05). Obese women were also characterized by higher plasma concentrations of anti-thrombotic factors such as t-PA Ag and protein C as compared to non-obese controls (P < 0.001 and P < 0.001, respectively), although these factors were not independently correlated with the waist circumference or the WHR. CONCLUSION: Plasma concentrations of the pro-thrombotic factors are increased in obese women as compared to non-obese controls, and plasma levels of PAI-1 Ag and vWF Ag correlate with central fat accumulation specifically. Plasma concentrations of anti-thrombotic factors (namely protein C and t-PA Ag) are also raised in obese women, but they are not correlated with parameters of body fat distribution. The increase in protein C levels may represent a protective response partly counteracting the increase in pro-thrombotic factors in these individuals.

Adipose Tissue↗

Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sensitivity.

Testosterone levels are decreased in obese men but increased in obese women. The interplay between gonadal steroids and leptin is, at present, far from being elucidated. This study was carried out to investigate the relationship between serum leptin, plasma insulin, insulin sensitivity and free testosterone in 46 men (29 obese and 17 lean) and 65 premenopausal women (42 obese and 23 lean). In all subjects, anthropometric parameters and serum levels of insulin, leptin, free testosterone (T), dehydroepiandrosterone sulphate and sex hormone-binding globulin were measured. An oral glucose tolerance test (OGTT) and an insulin tolerance test were also performed to determine the insulin sensitivity index. Our results show a significant difference in serum leptin between lean and obese men (3.19 +/- 0.71 vs. 20.28 +/- 0.26 ng mL-1; P < 0.0005) as well as between lean and obese women (10.78 +/- 2.14 vs. 34.79 +/- 2.26 ng mL-1; P < 0.00001). Basal T concentration in the obese men was significantly lower than in the control group (18.6 +/- 1.3 vs. 23.3 +/- 1.4 ng L-1; P < 0.01), whereas in the obese women it was significantly higher than in the control group (2.0 +/- 0.2 vs. 1.3 +/- 0.1 ng L-1; P < 0.05). When multiple linear regression was performed without body mass index (BMI) in the statistical model, leptin was correlated with basal insulin (P < 0.0001), insulin sensitivity (P < 0.0001) and T (P < 0.0001) in both men and women. When BMI was included in the model as an independent variable, leptin was significantly correlated only with BMI (P < 0.0001), the degree of insulin resistance (P < 0.05) and T (only in men, P < 0.05). This study confirms that serum leptin is strongly correlated with the degree of obesity and female sex. The negative correlation between leptin and T in men, independent of BMI, is consistent with the hypothesis that T may possess an inhibitory effect on adipocyte ob gene transcription.

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Interrelationships between weight loss, body fat distribution and sex hormones in pre- and postmenopausal obese women.

OBJECTIVES: Relationships between regional body fat distribution and sex hormones as well as changes in sex hormones after weight loss were evaluated. SETTING: All subjects were hospitalized in the Institute of Internal Medicine of the University of Verona. SUBJECTS: Twenty-six premenopausal (age 33.7 +/- 10.2 years) and 15 postmenopausal (age 57.9 +/- 5.9 years) obese women. INTERVENTIONS: Body weight, body-mass index, waist and hip circumferences, visceral fat by computed tomography and sex hormones were evaluated before and after 4 weeks on a very low energy diet. RESULTS: Body-mass index was higher in pre-than in postmenopausal women, although the difference was not significant. Total and free testosterone were significantly higher in the pre- than in the postmenopausal group (P < 0.001). Significant negative correlations were found between age and total testosterone (r = -0.65; P < 0.001), free testosterone (r = -0.54; P < 0.001), androstenedione (r = -0.46; P < 0.01) and urinary cortisol excretion (r = -0.50; P < 0.01). A negative correlation was found between visceral fat and total testosterone (r = -0.41; P < 0.01). After adjusting for age, the negative correlation between total testosterone and visceral fat encountered both in the subject group as a whole and in premenopausal women was no longer significant, whilst a significant negative association between visceral fat and sex hormone binding globulin (SHBG) (r = -0.56; P < 0.001) was always found. When step-down regression analysis was used to evaluate the joint effect of age, menopausal status, and anthropometric and metabolic variables on sex hormones, age was the most powerful independent variable for predicting total testosterone, free testosterone and androstenedione levels, whilst menopausal status was the most powerful predictor of FSH and LH levels. Changes in hormones after VLED were analysed separately in pre- and postmenopausal women. None of the hormones changed significantly after VLED in the postmenopausal group, except for FSH values. LH, free testosterone and urinary cortisol excretion values decreased significantly after VLED in the premenopausal group. CONCLUSIONS: Our data show that age, to a greater extent than visceral fat, seems to be negatively associated with steroid sex hormones. Weight loss seems to be associated with changes in sex hormones only in premenopausal women.

Adolescent↗

Relationship of obesity and body fat distribution with ceruloplasmin serum levels.

OBJECTIVE: To investigate the influence of obesity and body fat distribution on serum levels of ceruloplasmin, a risk factor for myocardial infarction. DESIGN: Fasting concentrations of ceruloplasmin, insulin, glucose, lipid pattern (cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), blood pressure levels, and body fat distribution were determined in a population of non-diabetic subjects. SETTING: University Hospital Outpatient Clinic. SUBJECTS: 87 consecutive individuals (35 men and 52 women), represented by 27 normal weight (BMI: < 25.0), 20 overweight (BMI: > 25.0-30.0) and 40 obese (BMI: > 30.0) subjects. MEASUREMENTS: Serum insulin levels were quantified by radioimmunoassay, plasma glucose and lipid concentrations by enzymatic assays, and serum ceruloplasmin by nephelometry. Intra-abdominal thickness was measured by ultrasound technique. RESULTS: Ceruloplasmin levels were significantly (P < 0.001) higher in obese (36.5 +/- 8.60 mg/dl) than in overweight (30.4 +/- 6.17 mg/dl) and normal weight (29.3 +/- 8.06 mg/dl) subjects. Of several variables associated with ceruloplasmin (BMI, waist circumference, WHR, intra-abdominal thickness, triglycerides, cholesterol, LDL-cholesterol, insulin), only triglycerides (in both men and women) and ultrasound intra-abdominal thickness (in women) maintained a significantly independent relationship with this protein in multiple stepwise analysis. Moreover, both triglycerides and total cholesterol maintained an independent correlation with ceruloplasmin when the data from both men and women were pooled together. CONCLUSION: This study indicates that patients with central obesity have characteristically higher ceruloplasmin serum levels, and that ceruloplasmin concentrations are strongly correlated with serum triglyceride and cholesterol levels (in both sexes) and visceral fat accumulation (in women), independently of the other associated cardiovascular risk factors (insulin and blood pressure levels). Since ceruloplasmin has been shown to increase in response to the atherosclerotic inflammatory process, and to promote coronarosclerosis, the determination of serum ceruloplasmin in subjects with central obesity might be a useful tool to identify patients with the highest risk for myocardial infarction.

Adipose Tissue↗

Body fat accumulation is possibly responsible for lower dehydroepiandrosterone circulating levels in premenopausal obese women.

OBJECTIVE: To determine whether any androgen is independently related with parameters of body fat accumulation and distribution in obese women. DESIGN: Circulating insulin and androgen levels (total testosterone (T), free testosterone (FT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, sex hormone binding globulin (SHBG)) and the parameters of body fat accumulation and distribution (body mass index, waist-to-hip ratio, total body fat volume (TBF), visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) were determined in a population of non-diabetic obese women. SUBJECTS: 28 premenopausal obese women, recruited at the Verona University Hospital Outpatient Clinic. MEASUREMENTS: TBF, VAT and SAT area were quantified by computed tomography. Hormone levels were measured by RIA. RESULTS: SHBG showed an inverse correlation with BMI (r: -0.452, P < 0.05), WHR (r: -0.388, P < 0.05), TBF (r: -0.509, P < 0.01), VAT (r: -0.378, P < 0.05) and SAT (r: -0.449, P < 0.05). DHEA was negatively associated with BMI (r: -0.376, P < 0.05), TBF (r: -0 < 0.05), VAT (r: -0.662, P < 0.001) and SAT (r: -0.401, p < 0.05). T was found to be inversely related with VAT (r: -0.401, P < 0.05). Androstenedione was positively correlated with WHR (r: 0.383, P < 0.05). DHEAS and FT did not show significant associations with BMI, WHR, or any CT-parameters. Stepwise multiple regressions were performed for all androgens: one of the age-adjusted androgens was considered as the dependent variable for each analysis, and insulin, VAT, SAT and all other androgens were entered into the regression model. DHEA was the only hormone to show an independent association (negative) with both SAT (t-value: -3.683, P < 0.01) and VAT (t-value: -2.252, P < 0.05), whereas DHEAS showed an independent positive correlation with SAT (t-value: -2.241, P < 0.05). CONCLUSIONS: Among the androgens, DHEA seems to be the most sensitive to body fat accumulation in premenopausal obese women.

Adipose Tissue↗

Hypertension and non-insulin-dependent diabetes. A comparison between an angiotensin-converting enzyme inhibitor and a calcium antagonist.

The effects of the angiotensin-converting enzyme lisinopril were compared with those of the calcium antagonist nifedipine in 162 non-insulin-dependent diabetic hypertensive patients for a 24-week period. In 83 and 79 patients, respectively, lisinopril and slow-release nifedipine produced similar reductions in blood pressure (systolic/diastolic: -16/-13 mmHg supine and -14/-11 mmHg standing after lisinopril; -15/-12 mmHg supine and -14/-11 mmHg standing nifedipine). Fasting and post-prandial plasma glucose, glycosylated haemoglobin and plasma lipids appeared to be unaffected by either agent. Also, 28% of the patients on lisinopril and 30% of those on nifedipine presented microalbuminuria. Both drugs induced a reduction in the albumin excretion rate (AER). The geometric mean x:tolerance factor of the reduction in AER among the 23 microalbuminuric patients on lisinopril (-10.0 x:1.3 micrograms/min) was greater, though not significantly so, than that observed in the 26 on nifedipine (-0.9 x 1.2 micrograms/min). Moreover, lisinopril appeared to be better tolerated than nifedipine in our study population. Microalbuminuria is an important risk factor for cardiovascular mortality in non-insulin-dependent diabetic patients as well as in the general population. To what extent a reduction in the AER could ameliorate diabetic patients is, at present, unknown. Finally, both lisinopril and nifedipine showed a similar antihypertensive effect in these patients which was not associated with significant differences in plasma glucose, insulin or lipid concentrations. The clinical consequences of the insignificant differences in AER remain unclear.

Albuminuria↗