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Biomedical subjects

C Carella

Publications and source records attributed to C Carella.

At least 37 records · Page 2Linked to original sources

Long-term treatment with interferon-beta therapy for multiple sclerosis and occurrence of Graves' disease.

Interferon (IFN)-beta has become a widespread therapy for multiple sclerosis. As already reported for IFN-alpha, thyroid autoimmunity and dysfunctions have been observed also in course of IFN-beta therapy. Nevertheless, very few cases of Graves' disease, occurred in such condition, have been reported in literature. We here describe the case of a 40-year-old female affected by multiple sclerosis, who received IFN-beta-1b, 8 million IU s.c. every other day for her condition. After 22 months of cytokine administration, she developed a severe Graves' disease with persistently positive TR-Ab which suggested the withdrawal of the treatment. Our patient had performed a complete thyroid evaluation with normal findings, before and during the first 6 months of therapy. This case suggests that patients undergoing long-term IFN-beta therapy should be monitored for thyroid hormones and antibodies throughout the treatment as thyroidal side effect can be a late event.

Adult↗

Postintervention serum TSH levels may be useful to differentiate patients who should undergo levothyroxine suppressive therapy after thyroid surgery for multinodular goiter in a region with moderate iodine deficiency.

Recent studies have raised doubts about the efficacy of the postoperative use of levothyroxine (LT4) suppressive doses in patients who underwent thyroid surgery for multinodular goiter. The purpose of this retrospective study was to examine the efficacy of different doses of LT4 in preventing postsurgical recurrences of simple multinodular goiter and to identify a marker that could be useful in discriminating patients with a higher risk of developing recurrence. Two hundred thirty-two patients (57 male, 175 female) operated for nontoxic multinodular goiter were divided into two groups: (I) patients with normal postsurgery thyrotropin (TSH) levels (0.25 to 4.5 mU/L) and (II) patients with elevated postsurgery TSH levels (>4.5 mU/L). All patients were subjected to replacement (1.3 microg LT4/kg/day) or suppressive (1.7 microg LT4/kg/day) doses of LT4, and they were followed for a median period of 6 years (range 2 to 12). No statistical difference was found for sex, age, and postsurgery serum TSH between patients submitted to suppressive and replacement therapy. The ultrasound (US) detection of new postsurgery nodules of at least 0.5 cm maximum diameter was considered a recurrence of disease and was found in 10% of the cases studied. Patients with normal postsurgery serum TSH showed a high recurrence rate (30.4%) when submitted to lower daily doses of LT4. In patients with elevated postsurgery serum TSH, the rate of nodular goiter recurrence did not vary with different types of LT4 therapy. In conclusion, our results suggest that the postsurgical serum TSH is useful for prediction of nodular goiter recurrence, as it reflects the amount of residual functioning thyroid tissue in the cervical area. It may also be indicative of patients who might benefit from LT4 suppressive therapy.

Adult↗

Recombinant growth hormone (GH) therapy in GH-deficient adults: a long-term controlled study on daily versus thrice weekly injections.

Currently, replacement recombinant GH (rGH) therapy in GH-deficient (GHD) adults is performed in daily injections. This modality of treatment is not complied with by the totality of GHD patients, who are supposed to receive life-long replacement. The aim of our study was to compare daily vs. thrice weekly (TIW) rGH injection effects on lipid profile, body composition, bone metabolism, and bone density in 34 GHD patients (13 women and 21 men; median age, 39 yr; range, 30-55 yr) randomly assigned to different therapeutic regimens. Group A included 18 patients receiving daily rGH injections, and group B included 16 patients receiving TIW injections of rGH. The starting dose of rGH was 10 microg/kg x day in both groups. Subsequently, the dose was adjusted to maintain serum insulin-like growth factor I (IGF-I) concentrations in the normal age-adjusted range. IGF-I levels were assessed before and after 1, 3, 6, and 12 months of rGH treatment, and lipid profile, body composition, bone metabolism, and bone density were evaluated before and after 6 and 12 months of treatment. Thirty-four healthy subjects served as controls. In the basal condition, lipid profile, body composition, bone metabolism, and bone density were significantly different in patients compared to controls. Conversely, patients included in groups A and B had similar serum IGF-I levels, lipid profile, body composition, bone metabolism, and bone density. After 3 months of rGH treatment, IGF-I levels were normalized in 15 of 18 patients (83.3%) in group A and in 7 of 16 patients (43.7%) in group B (chi2 = 4.21; P = 0.04). At this time point, serum IGF-I levels in patients in group A (202+/-57.5 microg/L) were significantly higher than those in patients in group B (155+/-45.1 microg/L; P = 0.001). After 6 months of therapy, serum IGF-I levels were normalized in all patients and were similar in both groups (223+/-35.2 vs. 212+/-41.4 microg/L, A vs. B, respectively). IGF-I levels remained normal until the 12-month follow-up. After 6 months of rGH replacement, total cholesterol, low density lipoprotein cholesterol, triglycerides, bioelectrical impedance, and body fat mass were significantly reduced, whereas high density lipoprotein cholesterol levels and lean body mass were significantly increased in both groups of patients, without any difference between them. No further change in lipid profile and body composition was observed after 12 months of treatment. Serum bone GLA protein and procollagen III levels were significantly increased after 6 months, and a downward trend was observed after 12 months of rGH replacement. However, a slight, but significant, increase in bone mineral density was observed in both groups only after 12 months (P = 0.0001). All patients in group B had good compliance to the TIW treatment, whereas 5 patients in group A had poor compliance to the treatment (chi2 = 3.2; P = 0.07). In conclusion, our randomized, prospective, and controlled study confirmed that rGH therapy with TIW injection regimen is effective in normalizing IGF-I levels and improving lipid profile, body composition, bone metabolism, and bone density. It also demonstrated that this efficacy is comparable to that observed in patients treated with daily rhGH therapy, with few side-effects and good compliance.

Adult↗

Parity as a thyroid size-determining factor in areas with moderate iodine deficiency.

Among the factors that may influence thyroid size, pregnancy and its goitrogenic effect have been widely investigated, but thyroid volume and pregnancy have never been compared retrospectively, and there are no data on the possible relationship between thyroid size and parity. The purpose of this work was to evaluate the effects of pregnancy on thyroid volume in a moderate iodine deficiency area, to assess the possibility of a relationship between thyroid size and parity status in healthy females. A group of 208 nongoitrous healthy women underwent thyroid volume estimation by ultrasound examination. All subjects were euthyroid and negative for thyroid autoantibodies. They were assigned to different groups, according to the number of completed pregnancies. Five groups were formed (0, 1, 2, 3, 4 or more term pregnancies). Mean thyroid volume increased progressively among the groups: group 0 (14.8 +/- 0.7 mL); group I (16.0 +/- 0.9 mL); group II (17.1 +/- 0.6 mL); group III (18.2 +/- 0.6 mL); group IV (20.3 +/- 0.9 mL). The increment in thyroid volume was statistically significant between group 0 and groups III (P: < 0.01) and IV (P: < 0.001), and also between group I and group IV (P: < 0. 05). No independent effect of body weight and age on thyroid volume was seen. Our results indicate that, in an area with moderate iodine deficiency, the goitrogenic effect of pregnancy is not fully reversible. Moreover, the statistically significant increase in thyroid volume, observed in relation to parity, is the first clinical demonstration of a cumulative goitrogenic effect of successive pregnancies, providing a strong argument to increase the iodine supply during pregnancy, even in conditions with moderate iodine deficiency.

Adult↗

Tissue inhibitor of metalloprotease (TIMP)-1 and proliferative behaviour of clonal breast cancer cells.

In the present paper, we have examined whether human tissue inhibitor of metalloprotease-1 (hTIMP-1) is able to exert a growth factor-like effect on two clonal cell lines (BC-3A and BC-61), isolated from a parental line of human breast carcinoma cells (8701-BC), and endowed with different growth and invasive behaviour 'in vitro' and in nude mouse. The data obtained indicate that only the more tumorigenic clonal cell line (BC-61) is responsive to hTIMP-1 treatment by increasing its proliferative rate in a dose-dependent manner. It was also found that BC-61 cells selectively express a transmembrane protein of about 80 kDa able to bind hTIMP-1 'in vitro' and 'in vivo' with high affinity (Kd of 0.07 +/- 0.004 nM), and that treatment of BC-61 cells with a proliferation-promoting concentration of hTIMP-1 is able to stimulate tyrosine-targeted phosphorylation. The cumulative results obtained strongly support the hypothesis that hTIMP-1, 'classically' regarded as a collagenase inhibitor, may be a crucial element of the extracellular signalling network during breast cancer development by controlling cell growth phenotype in autocrine and paracrine manner, and that intratumoural heterogeneity for the biological response to TIMP-1 may exist within the composite cell population of the primary tumour site.

Breast Neoplasms↗

Lack of association between changes in plasma leptin concentration and in food intake during the menstrual cycle.

BACKGROUND: Changes in plasma leptin concentration and food intake occur during the menstrual cycle; because leptin regulates food intake, one could hypothesize that changes in plasma leptin concentration and in food intake are associated throughout the menstrual cycle. However, no data have ever been provided to support such a relationship. The aim of our study was to investigate, during the different phases of the menstrual cycle, (a) the changes in plasma leptin concentration and, if such changes were demonstrated, (b) the potential relationship between the changes in plasma leptin concentration and food intake. DESIGN: The study was designed as an observational study. The plasma leptin concentration was determined in 16 healthy, young women during different phases of the menstrual cycle. At the same time, the basal metabolic rate (BMR), respiratory quotient (RQ) and food intake (FI) were also determined. RESULTS: The plasma leptin concentration increased throughout the menstrual cycle (P < 0.01 for trend) and was significantly correlated with plasma progesterone concentration (r = 0.55, P < 0.007, for follicular phase, r = 0.58, P < 0.02, for the periovulatory period and r = 0.57, P < 0.02, for the luteal phase). No significant differences in BMR and fasting RQ throughout the different phases of the menstrual cycle were found. In contrast, FI significantly declined in the periovulatory phase. No significant correlations between BMR, RQ and FI values and fasting plasma leptin concentration at all menstrual phases were found. CONCLUSION: Changes in plasma leptin concentration and in food intake were found at different phases of the menstrual cycle. Nevertheless, no correlation among those parameters at any phase of the menstrual cycle was observed.

Adult↗

Successful outcome of pregnancy in a thyroidectomized-parathyroidectomized young woman affected by severe hypothyroidism.

Severe hypothyroidism was discovered in a young woman in her 29th week of pregnancy. Previously, at the age of 12 years, she had undergone thyroid surgery for Graves' disease that resulted in persistent hypothyroidism and hypoparathyroidism. After surgical excision, the patient started levothyroxine replacement therapy and had regular control of thyroid function with normal findings throughout the years. The dose of levothyroxine had not been adjusted when the pregnancy started, and at the 29th week of gestation the patient had a thyrotropin (TSH) of 72.4 microU/mL. Ultrasound studies were performed in order to monitor fetal development. The fetal parameters analyzed before the adjustment of levothyroxine therapy showed growth retardation of various degrees. All analyzed fetal parameters (biparietal diameter, cranial and abdominal circumference, humerus and femur length) improved during the last 6 weeks of gestation, showing a good correlation with the newly achieved euthyroid state of the mother. The infant was clinically euthyroid at birth and was found normal at all evaluations of the neonatal hypothyroidism screening program (1, 5, 30 days).

Adult↗

Mean arterial blood pressure and serum levels of the molar ratio of insulin-like growth factor-1 to its binding protein-3 in healthy centenarians.

OBJECTIVE: Healthy centenarians have a greater molar ratio of plasma insulin-like growth factor-1 to insulin-like growth factor binding protein-3 than that of aged subjects. We investigated the question of whether differences in mean arterial pressure and in this plasma ratio were related in healthy centenarians. SUBJECTS AND METHODS: We studied 52 subjects in total, 30 aged subjects (70-99 years) and 22 healthy centenarians (> 100 years) to determine differences in mean arterial pressure, endothelial function and intracellular cation levels. RESULTS: In the healthy centenarians, the molar ratio of fasting plasma insulin-like growth factor-1 to its binding protein-3 was significantly correlated with mean arterial pressure (r = -0.66, P < 0.001). Baseline (19.3 +/- 1.5 versus 27.6 +/- 2.2 mumol/l, P < 0.05) and L-arginine-stimulated percentage increases in the plasma total nitrate: nitrite ratio (67 +/- 3.4 versus 48 +/- 4.5%, P < 0.03) were greater in the healthy centenarians than in the aged subjects. An L-arginine bolus elicited an increase in forearm blood flow which was correlated with the percentage increase in the plasma total nitrate: nitrite ratio (r = 0.79, P < 0.001) and with the fasting erythrocyte magnesium concentration (r = 0.80, P < 0.001) in healthy centenarians. Both correlations remained significant (P < 0.01) after adjustment for sex, body mass index and the waist: hip ratio. Moreover, the fasting plasma molar ratio of insulin-like growth factor-1 to its binding protein-3 was correlated with the percentage increase in forearm blood flow (r = 0.59, P < 0.005) and with the percentage increase in the plasma total nitrate: nitrite ratio (r = 0.54, P < 0.009) in healthy centenarians. The centenarians had higher baseline total erythrocyte magnesium and lower calcium concentrations than the aged subjects. The addition of insulin growth factor-1 to the incubation medium increased the total intracellular erythrocyte magnesium content and decreased the calcium content in both groups of subjects. Nevertheless, the percentage increase in total erythrocyte magnesium (33 +/- 3.8 versus 12 +/- 3.4%, P < 0.03) and decline in intracellular calcium (17 +/- 2.8 versus 8 +/- 3.1%, P < 0.02) concentrations were greater in the healthy centenarians than the aged subjects. CONCLUSION: In healthy centenarians, insulin-like growth factor-1 may preserve endothelial function and modulate the intracellular cation content, thus contributing to a lower mean arterial pressure than that in aged subjects.

Aged↗

Low plasma insulin-like growth factor-1 concentrations predict worsening of insulin-mediated glucose uptake in older people.

OBJECTIVE: The relationship among insulin action, advancing age, and insulin like growth factor-1 (IGF-1) is poorly understood. To gain further insight, the predictive role that low plasma IGF-1 concentration may have on insulin- mediated glucose uptake in older persons was investigated. DESIGN: The study was designed as a longitudinal, observational trial. PARTICIPANTS: Fifty-eight healthy aged (73.1+/-9.4 years) subjects (31 males/27 females) were followed up for 12 months. MEASUREMENTS: At baseline and at the end of the follow-up, insulin-mediated glucose uptake was assessed by euglycemic glucose clamp and plasma total IGF-1 and IGF-binding protein 3 (IGF-BP-3) in each subject, and concentrations were determined. RESULTS: At baseline, plasma IGF-1 concentrations correlated with whole body glucose uptake (WBGD) (r = 0.39, P < .003), insulin-stimulated glucose oxidation (GOX) (r = 0.35, P < .009), and non-oxidative glucose metabolism (r = 0.37, P < .007). Such correlations were also independent of age, sex, body fat, and waist/hip ratio. Fasting plasma total IGF-1 concentrations (84+/-56 vs 63+/-44 microg/L, P < .040), plasma IGF-1/IGF-BP3 molar ratio (0.13+/-0.05 vs 0.10+/-0.03 P < .050), and WBGD (34.8+/-5.0 vs 23.1+/-4.6 micromol/kg x min, P < .010) were more elevated at baseline than at the end of the follow-up. Low baseline fasting plasma IGF-1 concentration (RR = 1.5, 95%CI = 1.3-1.7) and plasma IGF-1/IGFBP-3 molar ratio (RR = 1.4, 95% CI = 1.3-1.8) predicted a decline in WBGD. The predictive role of plasma IGF-1 on age-related decline in WBGD was independent of age, sex, body fat, waist/hip ratio, and degree of physical activity (model 1), or of fasting plasma free fatty acid and triglyceride concentrations, LDL/HDL ratio, and basal adjusted respiratory quotient (model 2). Finally, low plasma IGF-1 concentration predicts a decline in WBGD independent of body fat, free fatty acids, waist/hip ratio, and basal adjusted respiratory quotient (model 3). CONCLUSION: Our study demonstrates that fasting plasma IGF-1 concentration may have a modulatory role on insulin action in older people. This finding might prompt an evaluation of the direct effect of IGF-1 administration on insulin sensitivity in older adults.

Adipose Tissue↗

Plasma leptin level is associated with myocardial wall thickness in hypertensive insulin-resistant men.

Leptin, the product of the ob gene, has been shown to increase heart rate and blood pressure through a stimulation of cardiac sympathetic nervous system activity, a phenomenon also involved in the pathogenesis of left ventricular hypertrophy in hypertensives. Thus, we hypothesize that plasma leptin concentration is associated with left ventricular hypertrophy. Forty hypertensive males and 15 healthy male subjects underwent anthropometric and echocardiographic evaluations, assessment of insulin sensitivity through euglycemic glucose clamp combined with indirect calorimetry, and determination of fasting plasma leptin concentration. Fasting plasma leptin levels were higher in hypertensives than in controls (6.48+/-2.9 versus 4. 62+/-1.5 ng/mL, P<0.05); these results were unchanged after adjustment for body mass index (P<0.05). In the whole group of patients (n=55), fasting plasma leptin concentration was correlated with body mass index (r=0.46, P<0.001) and waist/hip ratio (r=0.50, P<0.001); independent of body mass index and waist/hip ratio, fasting plasma leptin concentration was correlated (n=55) with whole-body glucose disposal (r=-0.27, P<0.04), interventricular septum thickness (r=0.34, P<0.001), posterior wall thickness (r=0.38, P<0.003), and the sum of wall thicknesses (r=0.68, P<0.001). In a multivariate analysis (n=55), age, body mass index, fasting plasma leptin concentration, plasma Na(+) concentration, whole-body glucose disposal, and diastolic blood pressure explained 68% of the variability of the sum of wall thicknesses with fasting plasma leptin concentration (P<0.03), whole body glucose disposal (P<0.002), and diastolic blood pressure (P<0.001), which were significantly and independently associated with the sum of wall thicknesses. In conclusion, our study demonstrates that fasting plasma leptin levels are associated with increased myocardial wall thickness independent of body composition and blood pressure levels in hypertensives.

Adult↗

Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism.

Although subclinical hypothyroidism is frequently diagnosed, the decision to institute a substitutive therapy with L-T4 remains controversial. Because the cardiovascular system is considered a main target for the action of thyroid hormone, we investigated whether subclinical hypothyroidism induces cardiovascular abnormalities. Twenty-six patients (mean age, 36 +/- 12 yr) were evaluated by Doppler-echocardiography, whereas a subgroup of 10 patients, randomly selected, were reevaluated after 6 months of L-T4 substitutive therapy (mean dose, 68 microg daily). Thirty subjects (matched for age, sex, and body surface area) served as controls. Mean plasma TSH was significantly higher in patients (P < 0.001), whereas mean serum free T4 and free T3 concentrations, although in the normal range, were significantly lower (P < 0.001 and P < 0.005, respectively). Blood pressure and heart rate did not differ from control values. Echocardiogram examination showed no abnormalities of the left ventricular morphology and a slight, but not significant, reduction in the systolic function in the patient group. In contrast, Doppler-derived indices of diastolic function showed significant prolongation of the isovolumic relaxation time (94 +/- 13 vs. 84 +/- 8 msec; P < 0.001), increased A wave (55 +/- 13 vs. 48 +/- 9 cm/sec; P < 0.05), and reduced early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.4 +/- 0.3 vs. 1.7 +/- 0.3; P < 0.001). In the subgroup of 10 patients, thyroid hormone profile was normalized by 6 months of L-T4 substitutive therapy, whereas no changes were observed in the left ventricular morphology. Systolic function was significantly enhanced, as compared with pretreatment values (P < 0.01) but did not differ from control values. Also, systemic vascular resistance was significantly decreased by L-T4 replacement therapy. Assessment of diastolic function showed significant shortening of isovolumic relaxation time (77 +/- 15 vs. 91 +/- 8; P < 0.05), reduction of A wave (51 +/- 13 vs. 60 +/- 12; P < 0.01), and increase of early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.7 +/- 0.4 vs. 1.3 +/- 0.3; P < 0.001). These indices, however, were comparable with those of control subjects. These findings indicate that subclinical hypothyroidism affects diastolic function and that this abnormality may be reversed by L-T4 substitutive therapy.

Adult↗

Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters.

OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.

Autoantibodies↗

Occurrence of thyroid autoimmunity and dysfunction throughout a nine-month follow-up in patients undergoing interferon-beta therapy for multiple sclerosis.

Thyroid autoimmunity and dysfunction are a well known side effect of IFN alpha therapy for viral hepatitis and tumors, while the IFN beta effects on the thyroid gland in neurological patients have not been studied. The aim of this longitudinal study was to look for the appearance of thyroid autoimmunity as well as for the occurrence of overt thyroid disease in the patients affected by multiple sclerosis (MS) treated with IFN beta 1b. Eight patients (4 males, 4 females) undergoing r-IFN beta 1b treatment (8 M.U. every other day for 9 months) for relapsing remitting multiple sclerosis entered the study. We have analyzed thyroid function parameters and auto antibody levels before and after 1, 2, 3, 6 and 9 months of therapy. None of them referred to familiar thyroid pathology or presented clinically overt thyroid disease except for one patient (case 4) who showed TPO-Ab pretreatment positivity and another (case 8) who was in therapy with Levothyroxine 100 microg/die for multinodular goiter. The number of patients with appearance of thyroid antibodies has slowly increased, until the third month of therapy with 3 patients out of 7 positive for TPO-Ab. The only case of overt thyroid dysfunction reported by us appeared after nine months of therapy and consisted of a hypothyroidism. Our data suggest that short-term interferon beta treatment is able to induce thyroid autoimmunity (42.8%) and dysfunction (12.5%).

Adult↗

Plasma sex hormones are significantly associated with plasma leptin concentration in healthy subjects.

OBJECTIVE: In humans a sexual dimorphism of plasma leptin concentration has been demonstrated but its significance remains to be established. Sex hormones may have a role. PATIENTS: Eighty healthy, non-obese subjects (41M/39F) were studied. MEASUREMENTS: In the whole group of subjects plasma sex hormones, leptin and insulin concentrations were determined, body fat content assessed by bioimpedance analysis, body fat distribution evaluated and insulin-mediated glucose uptake measured by euglycemic hyperinsulinemic glucose. RESULTS: After adjustment for age, gender, amount of body fat, waist/hip ratio (WHR) and fasting plasma insulin concentration, fasting plasma leptin was still significantly correlated with plasma DHEAS (r = -0.30, P < 0.006), oestradiol (r = 0.53, P < 0.001) and testosterone (r = -0.43, P < 0.001) in all subjects (n = 80). Independently of age, amount of body fat and WHR, fasting plasma leptin concentration correlated with plasma oestradiol (r = 0.38, P < 0.01) and total testosterone (r = -0.58, P < 0.001) in males (n = 41) and with fasting plasma oestradiol (r = 0.48, P < 0.002) in females (n = 39). To investigate the independent contribution of anthropometric and hormonal variables to fasting plasma leptin concentration, a multivariate stepwise regression analysis with fasting plasma leptin concentration as dependent variable was made. In the entire group (n = 80), the whole model explained 43% of fasting plasma leptin concentration with fasting plasma insulin, total testosterone and oestradiol concentrations significantly and independently associated with plasma leptin concentration. In this model, fasting plasma DHEAS, testosterone and oestradiol explained 25% of the variability in plasma leptin concentration. CONCLUSION: Our study demonstrates that plasma sex hormone concentrations are associated with plasma leptin concentration.

Analysis of Variance↗

Effect of metformin on food intake in obese subjects.

BACKGROUND: It has been hypothesized that metformin inhibits food intake, but in humans such effect needs to be demonstrated. Our study aims at investigating the effect of metformin administration on food intake in obese, non-diabetic, normotensive patients. METHODS: Thirty patients underwent a double-blind, randomized study. Placebo (P; n = 15) and metformin (M; n = 15) were both given for 15 days, and food intake (FI) was recorded at baseline and in the last 4 days of each treatment period. RESULTS: M administration allowed a stronger decline in body weight (BW) (-2.8 +/- 1.6 vs. -0.3 +/- 0.4 kg P < 0.01), body fat (BF) (-1.4 +/- 1.2 vs. -0.3 +/- 1.1 kg P < 0.01), plasma leptin concentration (-5.2 +/- 8.9 vs. -1.8 +/- 10.4 ng mL-1 P < 0.05) and FI (-642 +/- 491 vs.-70 +/- 1165 kJ per 24 h P < 0.01) than P. In M-treated subjects, changes in FI significantly correlated with those in BW (r = 0.63, P < 0.007) and BF (r = 0.74, P < 0.001). Independently of sex and change in BF, the changes in FI and in fasting plasma leptin concentration (r = 0.58, P < 0.01) were still correlated. CONCLUSION: Our study suggests that metformin administration is useful to inhibit FI and to lower BW and BF in obese non-diabetic patients.

Adolescent↗