MECHANISMS IN ENDOCRINOLOGY: Metabolic syndrome through the female life cycle

The normal function of the female reproductive system is closely linked to energy homeostasis with the ultimate scope of fertility and human race perpetuation through the centuries. During a woman's lifetime there are normal events such as puberty, pregnancy and menopause which are related to alterations in energy homeostasis and gonadal steroids levels followed by increase of body fat and insulin resistance, important components of metabolic syndrome (MetS). Pathological conditions such as premature adrenarche, polycystic ovary syndrome and gestational diabetes also present with shifts in gonadal steroid levels and reduced insulin sensitivity. The aim of this review is to discuss these conditions, both normal and pathological, analyzing the changes or abnormalities in ovarian function that coexist with metabolic abnormalities which resemble MetS in relationship with environmental, genetic and epigenetic factors

Favorable Effect of Anti-TNF Therapy on Insulin Sensitivity in Nonobese, Nondiabetic Patients with Inflammatory Bowel Disease

Background. The aim of this study was to investigate the effect of anti-TNF therapy on glucose and lipid metabolism in nondiabetic, nonobese patients with inflammatory bowel disease (IBD). Patients and Methods. We studied 44 patients with IBD, without a known history of diabetes. Three of the patients were diagnosed with overt diabetes and were excluded. Eighteen of the remaining patients (9 M/9 F, 33.6 ± 8.8 years) were on anti-TNF therapy for longer than 1 year, while 23 patients (16 M/7 F, 38.7 ± 12.5 years) were treated with aminosalicylates (AMSs). Twelve of the patients from the second group were then treated with anti-TNF and reassessed 6 months later. Fasting glucose, insulin, c-peptide, HbA1c, lipid, CRP, and fibrinogen levels were determined, and HOMA-IR index was calculated in all patients. Results. Patients from the two therapy groups were matched for age and BMI and were not obese. We did not find any differences between patients from the two therapy groups regarding fasting glucose, c-peptide, HbA1c, total cholesterol, HDL, LDL, triglycerides, CRP, and HOMA-IR index. In patients who were treated for 6 months with anti-TNF, a statistically significant decrease in insulin (before 15.5 ± 5.9 versus after 9.9 ± 2.9 μIU/ml, p=0.042) and c-peptide (before 2.4 ± 1 versus after 1.3 ± 0.4 ng/ml, p=0.030) levels as well as the HOMA-IR index (before 4.2 ± 1.9 versus after 2.2 ± 0.9, p=0.045) was observed, without any changes in weight, BMI, glucose, HbA1c, lipid, CRP, and fibrinogen levels. Conclusion. Anti-TNF therapy exerts a favorable effect on insulin sensitivity, while it has no effect on lipid levels in nondiabetic, nonobese patients with inflammatory bowel disease

Menopause and diabetes : EMAS clinical guide

Introduction: Whether menopause increases the risk of type 2 diabetes mellitus (T2DM) independently of ageing has been a matter of debate. Controversy also exists about the benefits and risks of menopausal hormone therapy (MHT) in women with T2DM. Aims: To summarise the evidence on 1) the effect of menopause on metabolic parameters and the risk of T2DM, 2) the effect of T2DM on age at menopause, 3) the effect of MHT on the risk of T2DM, and 4) the management of postmenopausal women with T2DM. Materials and methods: Literature review and consensus of experts' opinions. Results and conclusion: Metabolic changes during the menopausal transition include an increase in and the central redistribution of adipose tissue, as well as a decrease in energy expenditure. In addition, there is impairment of insulin secretion and insulin sensitivity and an increase in the risk of T2DM. MHT has a favourable effect on glucose metabolism, both in women with and in women without T2DM, while it may delay the onset of T2DM. MHT in women with T2DM should be administered according to their risk of cardiovascular disease (CVD). In women with T2DM and low CVD risk, oral oestrogens may be preferred, while transdermal 17 beta-oestradiol is preferred for women with T2DM and coexistent CVD risk factors, such as obesity. In any case, a progestogen with neutral effects on glucose metabolism should be used, such as progesterone, dydrogesterone or transdermal norethisterone. Postmenopausal women with T2DM should be managed primarily with lifestyle intervention, including diet and exercise. Most of them will eventually require pharmacological therapy. The selection of antidiabetic medications should be based on the patient's specific characteristics and comorbidities, as well on the metabolic, cardiovascular and bone effects of the medications.Peer reviewe

Study of immunoregulation in type 1 diabetes

Introduction: Type 1 diabetes results from autoimmune self destruction of the pancreatic B cells. Over the past few years, there has been a steadily increasing interest in T regulatory lymphocytes (TREGS) described as CD4+, CD25high, FOXP3+, CP127, T cells. Objective: To investigate the various features of Tregs in type 1 diabetes patients as well as controls using flow cytometry. Materials and Methods: Peripheral blood from 13 newly-diagnosed type 1 diabetes patients, 26 long-standing patients and 32 healthy controls was analysed via triple colour flow cytometry for the population of Tregs. All calculations were performed using SPSS. Results-Conclusions: We document a very significant difference in the number of Tregs between newly-diagnosed type 1 diabetes patients and controls, which is only partially corrected in long term patients. A compounding factor in the Tregs of newly-diagnosed diabetics is the lower level of the MFI of TGFβ and its receptor. The higher percent of Tregs expressing CP27 is indicative of Treg proliferation. Long-term tld patients also exhibit higher frequency of CD27 in their Tregs. Yet, the combination of near absence of TGFβ, increased level of TGFβ RII as well as increased frequency of HLA-DR and CD95 are consisted with two parallel processes: Generation and apoptosis of Tregs. The identification of several correlations of important proteins for Tregs function in controls that are absent in newly-diagnosed patients and changed in focus in long-term ones is consistent with an active mechanism disrupting the integrity of the Tregs population.Εισαγωγή: Στον σακχαρώδη διαβήτη τύπου 1 είναι γνωστή η αυτοάνοση αιτιολογία της νόσου χωρίς να είναι γνωστή η ακριβής αλληλουχία των μοριακών γεγονότων και μηχανισμών που οδηγούν στην καταστροφή των Β κυττάρων. Τα τελευταία χρόνια έχει καταδειχθεί ότι στο κύκλωμα της ανοσοαπόκρισης διαδραματίζει σημαντικό ρόλο ο πληθυσμός των Τ ρυθμιστικών λεμφοκυττάρων (Tregs) που ορίζονται ως CD4+, CD25high, FOXP3+, CP127, Τ λεμφοκύτταρα. Σκοπός: Η μελέτη των ποσοτικών και ποιοτικών χαρακτηριστικών των Tregs σε ασθενείς με σακχαρώδη διαβήτη τύπου 1 σε σύγκριση με υγιείς μάρτυρες με τη χρήση κυτταρομετρίας ροής. Υλικά-Μέθοδοι: Περιφερικό αίμα από 13 νεοδιαγνωσθέντες ασθενείς με σακχαρώδη διαβήτη τύπου 1, 26 μακράς διαρκείας διαβητικούς τύπου 1 και 32 φυσιολογικούς μάρτυρες αναλύθηκε με κυτταρομετρία ροής για τον πληθυσμό των Tregs. Η στατιστική επεξεργασία έγινε με το λογισμικό SPSS. Αποτελέσματα-Συμπεράσματα: Παρατηρείται στατιστικά σημαντική διαφορά μεταξύ ασθενών και μαρτύρων στο ποσοστό εμφάνισης των Tregs, που μερικώς διορθώνεται στην πορεία της νόσου. Οι νεοδιαγνωσθέντες διαβητικοί τύπου 1 εμφανίζουν χαμηλότερα επίπεδα έκφρασης του TGFβ και του υποδοχέα του, αλλά μεγαλύτερο ποσοστό Tregs που εκφράζουν CD27. Εδώ ο συνδυασμός της απουσίας σχεδόν του TGFβ, τα αυξημένα επίπεδα του υποδοχέα του, καθώς και η αυξημένη συχνότητα του HLA-DR και του CD95 είναι συμβατός με απόπτωση από τη μια και αναγέννηση από την άλλη. Τέλος, η υψηλά συνδυασμένη έκφραση ρυθμιστικών παραγόντων στα Tregs των μαρτύρων είναι διαταραγμένη στους νεοδιαγνωσθέντες ασθενείς με έκδηλη την προσπάθεια διόρθωσης στην πορεία της νόσου

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and a precursor of nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production of adenosine triphosphate (ATP), NAD+ acts as a substrate for several enzymes including sirtuin 1 (SIRT1) and poly ADP-ribose polymerase 1 (PARP1). Notably, NAM is an inhibitor of both SIRT1 and PARP1. Accumulating evidence suggests that NAM plays a role in cancer prevention and therapy. Phase III clinical trials have confirmed its clinical efficacy for non-melanoma skin cancer chemoprevention or as an adjunct to radiotherapy against head and neck, laryngeal, and urinary bladder cancers. Evidence for other cancers has mostly been collected through preclinical research and, in its majority, is not yet evidence-based. NAM has potential as a safe, well-tolerated, and cost-effective agent to be used in cancer chemoprevention and therapy. However, more preclinical studies and clinical trials are needed to fully unravel its value