Carlo Carella

Advancing age and insulin resistance: role of plasma tumor necrosis factor-α

In 70 healthy subjects with a large age range, the relationships between plasma tumor necrosis factor-alpha (TNF-alpha) and body composition, insulin action, and substrate oxidation were investigated. In the cross-sectional study (n = 70), advancing age correlated with plasma TNF-alpha concentration (r = 0.64, P < 0.001) and whole body glucose disposal (WBGD; r= -0.38, P < 0.01). The correlation between plasma TNF-alpha and age was independent of sex and body fat (BF; r = 0.31, P < 0.01). Independent of age and sex, a significant relationship between plasma TNF-alpha and leptin concentration (r = 0.29, P < 0.02) was also found. After control for age, sex, BF, and waist-to-hip ratio (WHR), plasma TNF-alpha was still correlated with WBGD (r = -0.33, P < 0.007). Further correction for plasma free fatty acid (FFA) concentration made the latter correlation no more significant. In a multivariate analysis, a model made by age, sex, BF, fat- free mass, WHR, and plasma TNF-alpha concentrations explained 69% of WBGD variability with age (P < 0.009), BF (P < 0.006), fat-free mass (P < 0.005), and plasma TNF-alpha (P < 0.05) significantly and independently associated with WBGD. In the longitudinal study, made with subjects at the highest tertiles of plasma TNF-alpha concentration (n = 50), plasma TNF-alpha concentration predicted a decline in WBGD independent of age, sex, BF, WHR [relative risk (RR) = 2.0; 95% confidence intervals (CI) = 1.2-2.4]. After further adjustment for plasma fasting FFA concentration, the predictive role of fasting plasma TNF-alpha concentration on WBGD (RR = 1.2; CI = 0.8-1.5) was no more significant. In conclusion, our study demonstrates that plasma TNF-alpha concentration is significantly associated with advancing age and that it predicts the impairment in insulin action with advancing age.

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.

Long‐term effects of lanreotide SR and octreotide LAR® on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly

background and objective The therapeutic efficacy of lanreotide SR and octreotide LAR® has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long‐term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR® in previously untreated patients with acromegaly. We aimed to investigate the long‐term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy.

Effect of metformin on food intake in obese subjects

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.

Serum and follicular fluid cytokines in polycystic ovary syndrome during stimulated cycles

OBJECTIVE To investigate the serum and intrafollicular tumor necrosis factor–α and interleukin-6 concentrations in infertile women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). METHODS Thirty-one patients with PCOS undergoing IVF were studied. Thirty-nine normally ovulating women matched for age and body mass index and undergoing IVF for male infertility were the control group. Serum tumor necrosis factor–α, interleukin-6, and estradiol levels were assayed before recombinant follicle-stimulating hormone stimulation under gonadotropin-releasing hormone analogue suppression and 34–36 hours after human chorionic gonadotropin (hCG) administration at the time of the oocyte retrieval. Cytokine and estradiol concentrations were also evaluated in the follicular fluids obtained at the time of oocyte retrieval. RESULTS The patients with PCOS had higher serum and follicular fluid tumor necrosis factor–α and interleukin-6 concentrations (P < .001) and lower follicular fluid estradiol levels (P < .05) than control women. In both groups, the serum tumor necrosis factor–α, interleukin-6, and estradiol values increased significantly after hCG stimulation. In both groups, the follicular fluid cytokine concentrations were higher than those found in the serum. In the PCOS women the follicular fluid tumor necrosis factor–α values were significantly and inversely correlated to the follicular fluid estradiol values (ρ = −0.79; P < .001); this correlation was not found in the control subjects. CONCLUSION In infertile women with PCOS, 1) serum and follicular fluid interleukin-6 and tumor necrosis factor–α values were higher than those found in control women, 2) the cytokine concentrations were higher in the follicular fluid than in the serum, and 3) the intrafollicular tumor necrosis factor–α concentrations were significantly and inversely correlated to the estradiol levels. These results suggest an involvement of the immune system in PCOS.

Recombinant Human TSH Modulates In Vivo C‐Telopeptides of Type‐1 Collagen and Bone Alkaline Phosphatase, but Not Osteoprotegerin Production in Postmenopausal Women Monitored for Differentiated Thyroid Carcinoma

In women monitored for thyroid carcinoma, short‐term stimulation with rhTSH induced an acute decrease in serum C‐telopeptides of type‐1 collagen and an increase in serum BALP levels without any effect on OPG production. The inhibitory effect of TSH on bone resorption occurred only in postmenopausal women who showed low BMD and a high bone turnover rate as an effect of L‐thyroxine suppressive therapy.

Leptin as a marker of multiple sclerosis activity in patients treated with interferon-beta

The role of leptin was investigated in relapsing-remitting multiple sclerosis (MS). Control and MS patients showed comparable baseline serum leptin levels. During the first year of IFNbeta-1a treatment, leptin significantly decreased since 2 months after starting therapy in 11 patients who had no relapses. A significant decrease in IL12/IL10 ratio was observed in this group of patients only after 1 year of treatment. An increase of leptin was observed before the first clinical exacerbation in 13 relapsing patients. Leptin may play a pathogenic role in MS and can be a useful marker of disease activity and response to therapy.

Longitudinal Study of Antibodies against Thyroid in Patients Undergoing Interferon-α Therapy for HCV Chronic Hepatitis

Seventy-five patients (50 M, 25 F), affected by chronic hepatitis caused by hepatitis C virus (HCV), without clinically overt thyroid disease, underwent r-interferon (IFN)-alpha-2a treatment (3-6 MU, 3 times/week) for 12 months. They were tested for thyroid function and for thyroid autoantibodies before (A), 6 (B) and 12 (C) months after the beginning of treatment and after 6 (D) months off therapy. Antithyroglobulin antibodies (Tg-Ab) and TSH were measured by IRMA, antiperoxidase antibodies (TPO-Ab), free T3 (FT3) and free T4 (FT4) by RIA, thyrotropin receptor antibodies (TR-Ab) by RRA. None of the patients showed TR-Ab positivity throughout the study. The number of the patients with one or both antithyroid antibodies progressively increased during treatment (A 10.7%; B 26.7%; C 45.3%) and decreased when off therapy (D 22.7%) with none of them positive for Tg-Ab alone (TPO-Ab 6.7%; Tg-Ab+TPO-Ab 16%). Tg-Ab increased during rIFN (median: A 29.0; B 35.0; C 73.0 U/ml) but decreased when off therapy (D 29.0 U/ml). Instead, TPO-Ab significantly increased throughout the study (A 1.0; B 3.0; C 6.0; D 7.0 U/ml). However, some patients showed for the first time an appearance of antibodies when off therapy. Five patients showed both antibodies and thyroid dysfunction: 2 at B, 2 at C, and 1 at D. Only 1 developed mild transient hyperthyroidism while the other 4 developed hypothyroidism, persistent however only in 1 case. Our study confirms that rIFN-alpha-2a frequently induces thyroid autoimmunity. TPO-Ab seems more useful than Tg-Ab in monitoring the immunological response.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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.

Grey-scale analysis allows a quantitative evaluation of thyroid echogenicity in the patients with Hashimoto's thyroiditis

objective In the present study we have performed a grey‐scale quantitative analysis of thyroid echogenicity in the patients affected by Hashimotos thyroiditis (HT), obtaining a numerical estimate of the degree of hypoecogenicity associated with the appearance of thyroid dysfunction.