ACTA ENDOCRINOLOGICA (BUC)

The mechanism underlying anovulation in the polycystic ovary syndrome (PCOS) remains unclear, although an excessive number of small antral follicles at ultrasound scans and discrepancies with selected follicles sustain the hypothesis of altered follicular development. Anti-M?llerian (AMH) hormone is a member of TGF-b super family of growth factors produced by granulosa cells of pre- and small-antral follicle. The 2 to 3 fold increase in the number of growing follicles in the ovary from PCOS women is reflected by an increase in serum concentration of AMH and thus, this hormone may be a good marker of PCOS.\r\nAim. This study was intended to implement ultra-sensitive ELISA measurement of serum AMH from PCOS women and search for a potential correlation with clinical and laboratory parameters.\r\nSubjects and methods. Sera from patients with PCOS (n = 42) and control women (n = 22) were used for ELISA measurement of AMH (AMH-EIA, Beckman Coulter) with sensitivity of 0.7 pmol/L.\r\nResults. We found a serum concentration of AMH almost 3 folds higher in patients with PCOS compared to controls (73.7 ? 7.5 vs. 25.7 ? 3.9 pmol/L, P < 0.0001). Differences were even higher in lean subjects. A positive correlation was found between total testosterone and LH levels, but not with serum FSH or insulin. Moreover, AMH concentration was correlated to more hyperandrogenic PCOS and with amenorrhea, and thus to the severity of the syndrome.\r\nConclusion. Measurement of serum AMH may be used as a valuable marker for PCOS to confirm diagnosis and evaluate the extent of follicular dysfunction in relation with hyperandrogenism and menstrual disturbances.

Abstract Introduction. Turner syndrome, a genetic disorder with an exclusively feminine phenotype, is caused by complete or partial X monosomy in some or all cells. Although the condition is usually diagnosed after birth, now, it is possible to detect the syndrome prenatally. Case reports. We present two cases of Turner syndrome diagnosed during the first trimester of pregnancy. The condition was suspected because of several ultrasound signs and was confirmed in both cases after an invasive prenatal technique. In one case, the fluorescent in situ hybridization technique was applied. In the other case, the chromosomal anomaly was detected using the G banding technique. Threedimensional ultrasound and HDlive technology were extremely useful in helping the patients to better understand the fetal pathology and accept an invasive procedure as a final step in establishing the diagnosis. Conclusion. These cases demonstrate the importance of using ultrasound as a screening method to detect suspected cases of Turner syndrome, however, the disorder needs to be confirmed with chromosomal analysis after performing an invasive prenatal technique.

Vertebrate nonapeptide neurohormones constitute an evolutionarily conserved family, involved in vital functions, such as hydro-osmotic balance regulation, reproduction and social behaviour. Two human members of this family are known, vasopressin (AVP) and oxytocin (OXT), with their highly homologous genes closely located on Chr 20p13. Presence of vasotocin (AVT) in man has been suggested, but remains controversial, and genetic evidence is lacking. AVT activity could be explained by the presence of a third distinct gene for AVT or an RNA-processing mechanism involving products of AVP and/or OXT genes. To test the first hypothesis, we developed bioinformatics and experimental approaches using genomic DNA and fetal tissues mRNAs. Family-specific primers for AVT and neurophysin were designed based on CODEHOP strategy and used in our experiments. Results of bioinformatics and genomic DNA experiments (family-specific and Alu step-out PCR) suggest there is no evidence for an AVT gene in the genome. RNA-based techniques 3?-RACE and Family-Specific Domain Restriction Fragment RTPCR provided evidence for new transcript species that could code for AVT. Further experiments will be needed to characterize them. We discuss potential mechanisms of AVT mRNA generation based on AVP and OXT mRNAs, by alternative splicing, heterologous transsplicing or RNA-editing. While all methods we developed proved feasible, current results suggest there is no AVT gene in the genome, but specific mRNAs could be present in fetal tissues. Their full characterization may potentially allow identification of vasotocin mRNA and shed light on a subject of fundamental scientific interest.

In response to increasing interest of the European Commission on large-scale\r\ngenotyping for complex diseases, including variability in ethnic minorities in\r\nEurope (HEALTH-2009-4.3.3-1), at the end of 2008 we composed the\r\nHAPLOGENDIS consortium with partners from Russia and European countries. A\r\nfirst program (SICA) was proposed in cooperation with Russian Federal Agency for\r\nScience and Innovation, focusing on comparative population genetics on diseases\r\naccompanied by insulin resistance. Beside the specificity in analyzing the human\r\ngenome with SNP (single nucleotide polymorphism) and defining haplotype\r\nstructure of genes, the program rises new hypotheses which directly link\r\ncolonization of Europe at the Neolithic period from Eastern Ukraine or Anatolia\r\nwith the development of agriculture and major dietary and life style changes that\r\nmay have an impact on the genome. Although there will be many occasions to\r\nreview both genetic and clinical detailed aspects, this short note will expose some\r\nunifying ideas that joint these partners.

A certain degree of insulin resistance in patients with Gaucher disease type 1 (GD) under enzyme replacement therapy (ERT) was reported. Data on insulin sensitivity in treatment naïve patients are inconsistent. Objective. To analyse prospectively changes in parameters of insulin resistance under ERT and to estimate when they occur. Design. prospective, controlled study; three years follow-up. Patients and methods. 12 treatment naïve patients with GD type 1 (M/W 8/4), 29.5±12.9 years, without overweight, diagnosed enzymatically and by genotyping, without previous diabetes mellitus. Patients were evaluated before and every 6 months up to 3 years under ERT and compared at baseline and after 3 years with matched healthy controls. Fasting-glucose (FG), - insulin (FI), C-peptide, HOMA-IR, IRI, HOMA-B, blood count, hepatic and splenic volume, chitotriosidase, severity score index di Rocco (SSI) were assessed. Results. Baseline glycemic parameters did not differ from controls. FG increased from baseline after two years of ERT (+16.4%,p<0.010), FI (+40.3%,p=0.030), HOMA-IR (+61.2%,p=0.007) and IRI (+9.1%,p=0.010) after 18 months, HOMA-B after 2.5 years (+51%, p=0.015. After 3 years of ERT patients were more insulin resistant compared to controls (p<0.001): FG (96.0±6.2 vs. 73.2±6.4 mg/dL), FI (11.2±2.4 vs. 5.6±1.3 μU/L), HOMA-IR (2.7±0.6 vs. 1.0+0.3), IRI (3.02±0.10 vs. 2.62±0.13). FG, FI, HOMAIR, IRI, HOMA-B correlated with disease severity markers. Conclusions. This is the first controlled study which evaluates prospectively insulin resistance in GD patients, finding significant differences compared to baseline starting with 18 months ERT.

Aim: to evaluate the impact of hyperthyroidism on glycemic control among patients with diabetes mellitus (DM).\r\nResearch design and methods: This retrospective study included patients with hyperthyroidism and DM admitted in Endocrinology, Nutrition Diseases and Diabetes Department of Elias University Emergency Hospital. We evaluated 37 patients (35 women/ 2 men), with a mean age of 54.7?15.3 years and duration of diabetes 8.1?7.49 years; 20 patients with Graves diseases (54%), 10 with toxic multinodular goiter (27%), 5 with autonomous hyperfunctioning adenoma (13%) and 2 with amiodarone induced hyperthyroidism (5.4%). Clinical data were recorded for all our patients, as well as thyroid ultrasound exploration, laboratory analyses (glycosylated hemoglobin, free thyroxine FT4, triiodothyronine T3, thyroid stimulating hormone TSH).\r\nResults: Diabetes control was achieved with: insulin in 23 (62%) patients, antidiabetic oral agents in 9 (24%) and solely diet in 5 patients (13.5%). Hyperthyroid patients had a mean value of glycosylated hemoglobin of 9.3%?2.4% (poor glycemic control) versus 7.2%?1.6% after the treatment of hyperthyroidism. Among insulin-treated patients, the average need of insulin in hyperthyroid status was 0.72 u/kg versus 0.55 u/kg when the patients became euthyroid (p<0.01). We found a significant association between type 1 diabetes mellitus and Graves&#8217; disease compared to toxic multinodular goiter (80% vs 50%, p<0.01).\r\nConclusions: The presence of hyperthyroidism aggravates glycemic control of the patients with diabetes mellitus and increases insulin need in insulin-treated patients. Once the thyroid function was stable, the insulin need decreased significantly (p<0.01). Hyperthyroidism should be radically treated to obtain a good glycemic control. Type 1 diabetes is significantly associated to Graves&#8217;s disease by an autoimmune mechanism.

Background and aims. Differences in the composition of the species of microorganisms in the gut may predict the evolution toward obesity and diabetes mellitus. We carried out a systematic review of the studies dedicated to the role of gut microbiota in diabetes mellitus and obesity. Methods. A systematic literature search of electronic databases was performed, using the search syntax: “Gut microbiota and diabetes and obesity”; abstracts in English, with data about mechanisms of pathogenesis and treatment options by changing the gut composition were included (259 articles). Studies were excluded if they did not have an abstract, or they contained no data about the exact implication mechanism of microbiota. Results. There are differences regarding the composition of the gut microbiota in healthy people and type 2 diabetes mellitus patients; the later proved to have significantly decreased Clostridium components, and increased Lactobacillus and Bifidobacterium populations. The intestines of obese subjects are less rich in microbial genes, have a reduced amount of Bacteroidetes and an increased amount of Firmicutes. Fecal microbiota transplantation from obese subjects resulted in adoption of the donor somatotype. Early differences in gut microbiota composition (higher number of Bifidobacteria) function as diagnostic markers for the development of type 2 diabetes mellitus in high-risk patients. The gut endotoxins contribute to metabolic syndrome manifestation. Experimental studies with prebiotic showed lower levels of cytokines and antiobesity potential. Conclusion. Microbiota composition and its changes since childhood have an important role in the metabolic syndrome. Any intervention in order to prevent or treat obesity and diabetes mellitus should have as target the gut immune system.

Branched chained amino acids (BCAA) are essential components of the human diet and important nutrient signals, which regain particular interest in recent years with the avenue of metabolomics studies suggesting their potential role as biomarkers. There is now compelling evidence for predictive role of BCAA in progression of diabetes, but causality relationship is still debated concerning insulin resistance and genetic versus nongenetic pathogenesis. Mendelian randomization studies in large cohorts of diabetes indicated pathogenic role of PPM1K (protein phosphatase Mg2+/Mn2+ dependent 1K) on Chr 4q22.1 gene, encoding for a phosphatase that activate BCKDH (branched chain keto acid dehydrogenase) complex. Recent studies indicated that insulin rapidly and dose-dependently regulates gene expression of the same complex, but the relationship with systemic insulin resistance and glucose levels is complex. Rare genetic syndromes due to Mendelian mutations in key genes in BCAA catabolism may be good models to understand potential role of gene of BCAA catabolism. However, in studying complex disorders geneticists are faced to complete new aspects of metabolic regulation complicating understanding genetics of obesity, diabetes or metabolic syndrome. A review of genetic syndromes of BCAA metabolism suggests that insulin resistance is not present, except rare cases of methylmalonic aciduria due to MUT (methylmalonyl-coA mutase) gene on Chr 6p12.3. Another aspect that complicates understanding is the new role of central nervous system (CNS) in insulin resistance. For long time the hypothalamic hunger/satiety neuronal system was considered a key site of nutrient regulation. Genes may also affect the brain rewarding system (BRS) that would regulate food intake by modulating the motivation to obtain food and considering hedonic properties. Nutrigenomic and nutrigenetic investigations taking into account concurrently BCAA intake, metabolic regulation and gene variation have large perspectives to merge genetic and nutritional understanding in complex disorders.