L’Asse ipotalamo-ipofisi GH-IGF-1 nel diabete mellito di tipo 2 e nel LADA: ruolo dell’adiponectina

Introduction: Growth hormone (GH) neurosecretion is often impaired in patients with diabetes mellitus. GH secretion is reduced in patient with type 2 diabetes mellitus (T2D), whereas is normal - or even enhanced - in patients with type 1 diabetes mellitus. Less is known in latent autoimmune diabetes in adults (LADA) patients. Differences in adipose tissue distribution may partly account for these findings. The dysregulated expression of various bioactive substances secreted by adipose tissue are clearly linked to metabolic diseases. Moreover, these adipokines can alter anterior pituitary function and may contribute to a dysregulation of the GH-IGF-1 axis. Aim: This study was conceived to evaluate GH secretion in LADA and T2D patients by measuring the GH-dependent protein insulin-like growth factor-1 (IGF-1), and to investigate a possible correlation between IGF-1 and adipocytokines serum levels in these patients. Methods: The study group consisted of 100 LADA, 100 T2D, and 100 healthy controls. Serum IGF-1, leptin, and total adiponectin were measured in all subjects. Results: Simple correlation analysis showed that IGF-1 levels significantly correlated with adiponectin in LADA as well in T2D and healthy controls (p <0.01 for all). These results were confirmed in multiple regression analysis after adjusting for confounders (p < 0.01). Conclusions: These data suggest a dysregulation of GH-IGF-1 axis in the LADA and T2D patients and possible impact of adiponectin on IGF-1 levels

A Case of thyroid metastasis from pancreatic cancer: case report and literature review

Background: Thyroid metastases are clinically rare, and usually occur in patients with a history of prior malignancy and when there are metastases elsewhere. Metastases of pancreatic carcinoma to the thyroid are extremely rare, with only three cases reported in the literature. Case presentation: We report a patient who had a pancreatic carcinoma with metastasis to the thyroid as initial clinical presentation of the disease. A 63-year-old man with a history of weight loss and fatigue presented with cervical lymphadenopathies and a large nodule in the right lobe of the thyroid. A fine needle aspiration of the nodule gave inconclusive cytological results for the origin of the neoplastic cells. An ultrasound-guided core biopsy revealed the presence of a poorly differentiated adenocarcinoma infiltrating the thyroid with atrophic thyroid follicles. Immunohistochemical staining of the lesion was strongly positive for Cytokeratin 19 suggesting a pancreatic origin of the metastasis. A contrast CT scan demonstrated an enlargement of the pancreatic body, dilatation of the pancreatic duct, diffuse retroperitoneal, paraaortic and cervical lymphadenopathy and secondary lesions in the liver. Conclusion: Metastases to the thyroid from pancreatic carcinoma are extremely rare. A core biopsy of the lesion excluded a thyroid carcinoma and permitted the diagnosis of the primary neoplasm

Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults

Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of type 2 diabetes (T2D) with the presence of islet cell antigens detected in type 1 diabetes (T1D). Heterogeneous clinical picture have led to the classification of patients based on the levels of antibodies against glutamic acid decarboxylase 65 (GADA) that correlate with clinical phenotypes closer to T1D or T2D when GADA titers are high or low, respectively. To date, LADA etiology remains elusive despite numerous studies investigating on genetic predisposition and environmental risk factors. To our knowledge, this is the first study aimed at evaluation of a putative role played by Mycobacterium avium subsp. paratuberculosis (MAP) as an infective agent in LADA pathogenesis. MAP is known to cause chronic enteritis in ruminants and has been associated with autoimmune disorders in humans. We analyzed seroreactivity of 223 Sardinian LADA subjects and 182 healthy volunteers against MAP-derived peptides and their human homologs of proinsulin and zinc transporter 8 protein. A significantly elevated positivity for MAP/proinsulin was detected among patients, with the highest prevalence in the 32-41-year-old T1D-like LADA subgroup, supporting our hypothesis of a possible MAP contribution in the development of autoimmunity

Phenotypic heterogeneity of latent autoimmune diabetes in adults identified by body composition analysis

Background: In patients with Latent Autoimmune Diabetes in Adults (LADA) a lower body mass index was reported compared with classical type 2 diabetes (T2D), and was found to be associated with a faster progression to insulin-dependence. In this study we determined the body composition in a cohort of LADA patients from Sardinia, Italy, and compared it with age– and gender–matched patients diagnosed as having adult-onset type 1 diabetes (T1D) and non-autoimmune T2D. Methods: In 210 LADA patients, 210 T2D patients and 30 adult-onset T1D patients of Sardinian origin we assessed total and segmental body composition (weight-adjusted percent fat mass and lean mass) by using Dual Energy X-rays Absorptiometry (DXA). Results: In the whole cohort of LADA patients total fat mass was significantly smaller compared with T2D patients (p &lt; 0.0001), while no difference was found between LADA and T1D patients. In LADA men fat depletion involved all body segments, while in LADA women it was observed only in the truncal segment (p &lt; 0.0001), as in the upper and lower regions fat deposits were larger compared to T2D (p &lt; 0.0001). However, LADA women showed a significantly elevated truncal fat compared to T1D women (p &lt; 0.004), whereas no difference was detected in the extremities. Conclusions: Body composition in LADA patients shows substantial difference, in a gender-dependent way, compared to classic T2D. In women fat deposits tend to accumulate in peripheral regions rather than centrally, whereas in men the distribution is more homogeneous. In addition, central fat depletion in LADA women appears to be a significant predictor of faster progression to insulin dependence. Thus, routine assessment of body composition may help the physician identify LADA patients who require early insulin treatment in order to delay beta-cell exhaustion, as well those with increased CV risk due to excess truncal adiposity.</br

Management of Obesity and Obesity-Related Disorders: From Stem Cells and Epigenetics to Its Treatment

: Obesity is a complex worldwide disease, characterized by an abnormal or excessive fat accumulation. The onset of this pathology is generally linked to a complex network of interactions among genetic and environmental factors, aging, lifestyle, and diets. During adipogenesis, several regulatory mechanisms and transcription factors are involved. As fat cells grow, adipose tissue becomes increasingly large and dysfunctional, losing its endocrine function, secreting pro-inflammatory cytokines, and recruiting infiltrating macrophages. This long-term low-grade systemic inflammation results in insulin resistance in peripheral tissues. In this review we describe the main mechanisms involved in adipogenesis, from a physiological condition to obesity. Current therapeutic strategies for the management of obesity and the related metabolic syndrome are also reported

Melatonin and Vitamin D Interfere with the Adipogenic Fate of Adipose-Derived Stem Cells

Adipose-derived stem cells (ADSCs) represent one of the cellular populations resident in adipose tissue. They can be recruited under certain stimuli and committed to become preadipocytes, and then mature adipocytes. Controlling stem cell differentiation towards the adipogenic phenotype could have a great impact on future drug development aimed at counteracting fat depots. Stem cell commitment can be influenced by different molecules, such as melatonin, which we have previously shown to be an osteogenic inducer. Here, we aimed at evaluating the effects elicited by melatonin, even in the presence of vitamin D, on ADSC adipogenesis assessed in a specific medium. The transcription of specific adipogenesis orchestrating genes, such as aP2, peroxisome proliferator-activated receptor \u3b3 (PPAR-\u3b3), and that of adipocyte-specific genes, including lipoprotein lipase (LPL) and acyl-CoA thioesterase 2 (ACOT2), was significantly inhibited in cells that had been treated in the presence of melatonin and vitamin D, alone or in combination. Protein content and lipid accumulation confirmed a reduction in adipogenesis in ADSCs that had been grown in adipogenic conditions, but in the presence of melatonin and/or vitamin D. Our findings indicate the role of melatonin and vitamin D in deciding stem cell fate, and disclose novel therapeutic approaches against fat depots

Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs)

A positive correlation between Thyroid-Stimulating Hormone (TSH) and Body Mass Index (BMI) has been reported in many studies, but data on this topic remain controversial, especially when TSH values are in the normal range. Moreover, few studies have evaluated the co-existence of thyroid autoimmunity. This study investigated the role of thyroid autoimmunity in the interconnection between TSH, BMI, and waist circumference (WC) in euthyroid patients with overweight or obesity. We enrolled 902 patients (213 males; mean age +/- SD: 45 +/- 14 years; mean BMI +/- SD: 35.8 +/- 6.5 kg/m(2)), with normal serum TSH concentration; anti-thyroid autoantibodies (ATAs) were evaluated in 752 patients (186 males). Patients were divided into four BMI classes, based on WHO criteria, and the relationship between BMI, WC, and TSH was evaluated in the whole sample and compared to ATAs positivity, observed in 235 patients (44 males). No significant difference was found between TSH levels in the BMI classes. A statistically significant correlation between TSH and BMI was found only in ATAs-positive females (N = 191, Spearman rho: 0.149; p-value: 0.040). However, this finding was not confirmed when considering the WC. Our study shows a positive correlation only between TSH and BMI in obese women with positive ATAs, suggesting that in these patients, the high normal levels of TSH could be attributed to a mild thyroid failure with a possible worsening obesity-related effect, and both need a careful evaluation

Melatonin and Vitamin D Orchestrate Adipose Derived Stem Cell Fate by Modulating Epigenetic Regulatory Genes

Melatonin, that regulates many physiological processes including circadian rhythms, is a molecule able to promote osteoblasts maturation in vitro and to prevent bone loss in vivo, while regulating also adipocytes metabolism. In this regard, we have previously shown that melatonin in combination with vitamin D, is able to counteract the appearance of an adipogenic phenotype in adipose derived stem cells (ADSCs), cultured in an adipogenic favoring condition. In the present study, we aimed at evaluating the specific phenotype elicited by melatonin and vitamin D based medium, considering also the involvement of epigenetic regulating genes. ADSCs were cultured in a specific adipogenic conditioned media, in the presence of melatonin alone or with vitamin D. The expression of specific osteogenic related genes was evaluated at different time points, together with the histone deacetylases epigenetic regulators, HDAC1 and Sirtuins (SIRT) 1 and 2. Our results show that melatonin and vitamin D are able to modulate ADSCs commitment towards osteogenic phenotype through the upregulation of HDAC1, SIRT 1 and 2, unfolding an epigenetic regulation in stem cell differentiation and opening novel strategies for future therapeutic balancing of stem cell fate toward adipogenic or osteogenic phenotype

Activation of α1-adrenoceptors inhibits growth hormone secretion in humans

In order to determine whether an α1-adrenergic mechanism is involved in the secretion of Growth Hormone (GH) in humans, we studied the effect of the α1-adrenergic-stimulating agent methoxamine on serum GH levels in twelve normal males (age range 22-32 years). Intravenous infusion of methoxamine (dose: 6 μg/kg/min; duration: 150 min) significantly reduced serum GH levels at time 120 and 150, and on integrated concentrations. These data suggest that α1-adrenergic receptors inhibit tonic GH secretion in humans

Primary hyperparathyroidism revealed by gluten-free diet in a woman with celiac disease

Normocalcemic primary hyperparathyroidism (NPH) is a condition characterized by elevated parathyroid hormone (PTH) and consistent normal serum calcium levels, in patients in whom secondary causes of hyperparathyroidism have been excluded. NPH may represent the earliest presentation of frank (hypercalcemic) primary hyperparathyroidism (HPH). In a recently published case report, asymptomatic celiac disease (CD) is reported in a woman with NPH. The authors of this report conclude that CD may be the underlying cause for some cases of NPH, and the diagnosis of CD should thus be considered in this setting. We report a case in which calcium malabsorption due to CD was able to mask HPH