Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 16, Issue 4, 2016

Background: Insulin Autoimmune Syndrome (IAS) is a rare condition characterized by the combination of recurrent severely spontaneous hypoglycemia without evidence of exogenous insulin administration, high concentration of total serum insulin, and the presence of a high titer of insulin autoantibody (IAA). But now we describe a case with IAS caused by gliclazide and hardly occuring hypoglycemia. Case Report: A 70-year-old man with type 2 diabetes presented to our department with poor glycemic control without evidence of hypoglycemia, but the levels of serum insulin and IAA were very high. He had no exogenous insulin administration history. Switching antidiabetic therapy from gliclazide to acarbose and metformin, the patient’s serum insulin level and IAA decreased gradually. Accordingly, the glycemic control improved and there was no episode of hypoglycemia. Conclusion: Hence, clinicians should pay more attention to type 2 diabetic patients treated with gliclazide and detect their serum insulin concentration and IAA to exclude or diagnose IAS and perform the best therapeutic regimen to these patients.

Tumors are complex tissues in which transformed cells communicate with the surrounding microenvironment and evolve traits promoting their own survival and malignancy. Hypoxia and inflammation are constant characteristics of prostate tumor microenvironment influencing both cancer stem cells and differentiated tumor cells. HIFs and NF-kB are the key regulators of the transcriptional response to hypoxic and inflammatory stresses, respectively, and a crosstalk between HIFs and NF-kB pathways has been widely documented. Similarly, androgen and estrogen signaling, that play important roles in the growth and function of normal prostate gland, when deregulated, have a significant part in the acquisition of hallmarks of malignant diseases. Moreover, androgen and estrogen receptors have been shown to intersect with the HIF/NF-kB signaling in prostate cancer. Aim of this review is to present the current knowledge regarding the crucial role, in prostate cancer progression, of a molecular network linking hypoxia, pro-inflammatory response and steroid receptors.

Background: Patients with hypothalamic-pituitary disorders (HPD) may be of increased risk to develop overweight and obesity, thereby fostering cardiovascular events. However, it remains unclear if patients with pituitary dysfunctions per se have an increased risk of becoming obese. Objective: The objective of this study was to evaluate prevalence and to identify possible predictors of overweight and obesity in patients with pituitary dysfunctions. Methods: A total of 121 out-patients having various causes for HPD were assessed for height and body weight; body mass index (BMI) was calculated and correlated with clinical features. Patients were divided into various subgroups depending on underlying conditions and therapeutic modalities. Results: Most of the HPD patients were overweight or obese with males being significantly more affected. Of interest, patients with macroadenomas suffered significantly more often from overweight and obesity than individuals with microadenomas (73.4% vs. 43.5%, p= 0.006). Increased BMI (≥25 kg/m2) tended to be more common in patients with prolactinomas (70.0%), hormone deficiencies (76.1%) and hormone replacement therapies (76.6%) than in a healthy population. Conclusion: In conclusion, we showed that patients with HPD: (i) frequently suffer from overweight and obesity; (ii) prevalence of overweight and obesity however is comparable to that in the general population; (iii) only patients with macroadenomas seem to have a significantly higher risk; (iv) hormone deficiencies and hormonal replacement therapy may foster weight gain and (v) radiation and surgical tumour therapy per se do not seem to be additional risk factors for weight gain.

Background: Measuring indicators of oxidative protein and lipid metabolism is a diagnostic criterion of oxidative metabolism disruption at the early stages of chronic somatic pathology formation. Purpose was to assess the status of protein and lipid oxidative metabolism as a pathogenic link of acute rheumatic fever by measuring markers of early lesion. Methods: Research included measurement of lipid peroxidation products and efficiency of antioxidant protection. Results: It revealed unidirectional changes that confirm significant cellular membrane lesion. Determined changes correlated with the activity level of the pathological process while comparing the indicators of ill children in remission and during exacerbation. It was found that despite the active traditional treatment in hospitals for in-patients, a number of studied indicators did not return to normal in remission. This shows the persistence of membrane destruction processes in the body, which supports the pathological process and requires an investigation of the lesion severity at the level of cell metabolism. Conclusion: Determination of disruption in the oxidative metabolism system of lipids and proteins, and the presence of mitochondrial insufficiency signs are universal pathogenic mechanism that reflects the multifactorial nature of the lesion with acute rheumatic fever.

Background: Rhinocerebral mucormycosis is a rare, rapidly progressive and potentially lethal disease almost exclusively affecting immunocompromised hosts or patients with metabolic disorders, such as poorly controlled diabetes mellitus. Methods: This work is aimed to describe five cases of rhinocerebral mucormycosis to review and possibly define diagnostic and surgical treatment guidelines. In all the patients, surgical debridement, systemic and local antifungal therapy, and oral rehabilitation using filling prostheses were performed. Results: None of the patients revealed recurrence of the infection, as confirmed by radiological and clinical long term follow up. Conclusion: Given the lethal nature of the disease, the authors underline the importance of early diagnosis and of a multidisciplinary approach in order to undertake correct surgical and medical treatments, while keeping the underlying disease under control.

Background: Osteocalcin, a protein synthesized by osteoblasts during the bone formation phase of bone remodeling, is used as a biomarker for the bone production process, and its serum levels are positively correlated with bone mineral density during treatment with anabolic bone drugs for osteoporosis. Higher fat mass has been shown to be a risk factor for osteoporosis and fragility fractures and body fat and bone interplay through several adipokines and bone-derived molecules, regulating bone remodeling, adipogenesis, body weight control, and glucose homeostasis. Aim: The aim of this study was to evaluate the relationship between total osteocalcin levels and obesity, hypertension and type 2 diabetes. Methods: The present study was performed in a cohort of 298 patients including a) 121 overweight and obese patients, unaffected by hypertension or type 2 diabetes, b) 129 subjects affected by hypertension and not by type 2 diabetes, and c) 48 subjects affected by both hypertension and type 2 diabetes. No subject of the group of overweight and obese patients was taking any kind of drug. All patients affected by hypertension, with or without type 2 diabetes, were taking drugs for hypertension. Examining only patients affected by type 2 diabetes (n: 48), 43 (90% of all) were taking drugs to reduce blood glucose levels, 26 (54% of all) were taking drugs to reduce cholesterol levels (statins and/or ezetimide, etc), and 4 (8% of all) were taking ω-3 for hypertriglyceridemia. Each patient was evaluated for anthropometric measurements as well as for serum osteocalcin and uric acid, and plasma glucose, HbA1c, and lipid determination. Results: Osteocalcin levels were significantly and negatively associated with BMI, waist circumference, and HbA1c, and significantly and positively correlated with HDL-cholesterol and systolic blood pressure in the whole population. Osteocalcin levels did maintain an independent negative association with BMI, and HbA1c, and positive association with HDL cholesterol and systolic blood pressure when a multiple regression analyses was performed by considering osteocalcin levels as the dependent variable and BMI, systolic blood pressure, HbA1c, and HDL cholesterol as independent variables. When age was included in the analyses among the independent variables, osteocalcin levels maintained an independent association with BMI, systolic blood pressure, HbA1c, and HDL cholesterol, but not with age. Discussion and Conclusion: The results of the present study seem to suggest that patients with obesity and type 2 diabetes are at higher risk of lower osteocalcin levels and bone formation, whereas higher HDLcholesterol levels and systolic blood pressure seem to be associated to higher osteocalcin production.

Background: Magnocellular neurosecretory neurons of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei synthesize vasopressin and oxytocin in response to signals generated by osmoreceptors and baroreceptors and, respectively, by receptors of the nipples and cervix. Methods: We analyzed the literature identifying relevant articles dealing with synaptic inputs of neural afferent pathways to Vasopressin-and Oxytocin-secreting neurons of SON and PVN. Results: This article focuses on the multisynaptic pathways involved in the regulation of Vasopressin and Oxytocin secretion. Conclusion: An updated topographic description of the afferent pathways involved in the regulation of VPergic and OTergic neurons and their synaptic inputs inducing the stimulus-secretion-coupling has been depicted.

Background: Alterations of glucose metabolism represent well known risk factors for the atherosclerotic process and then for cardiovascular disease. Objective: To investigate the association between fasting glucose and early signs of atherosclerosis, by means of carotid intima-media thickness (c-IMT) in a population of apparently healthy overweight/obese subjects. In addition, we evaluated the possible existence of a glycemic threshold above which the risk of atherosclerosis significantly increases. Methods: 179 overweight/obese (mean BMI: 32 ± 5 kg/m2) subjects, 44 men, aged 40 ± 12.4 years, were enrolled in the study. Blood glucose, insulin, total cholesterol, high and low density lipoprotein cholesterol and triglycerides were detected in all subjects. The Homeostasis Model Assessment of insulin resistance index (HOMA-IR) was also obtained. All subjects underwent carotid echo color Doppler ultrasound to identify c-IMT. Results: In our population of obese/overweight subjects with insulin resistance (HOMA-IR=3.4 ± 2), c- IMT was positively related to male gender (r = 0.23, P<0.01), age (r = 0.53, P<0.001), waist circumference (r = 0.15, P=0.04), systolic and diastolic blood pressure (r=0.27, P<0.001 and r=0.24, P<0.001 respectively), fasting glucose (r=0.29, P<0.001), triglycerides (r= 0.16 P=0.03), total and low density lipoprotein cholesterol levels (r=0.25 P<0.001 and r=0.21, P<0.01 respectively). Only male gender and fasting glycemia were associated to c-IMT (P<0.01 and P< 0.001, respectively) at multiple regression analysis. Conclusion: Blood glucose represented an independent predictor of atherosclerosis in our study population. Moreover, this seemed to be able to favor c-IMT progression for values greater than 90 mg/dl.