Katerina Dvorakova

Incretin levels in polycystic ovary syndrome

OBJECTIVEnPolycystic ovary syndrome (PCOS) has been linked to a high risk of type 2 diabetes mellitus. Disturbances in the secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) have been observed in states with impaired glucose regulation. This paper considers the secretion of GIP and GLP-1 after oral glucose load in a group of lean, glucose-tolerant PCOS women in comparison with age- and body mass index (BMI)-matched healthy women.nnnDESIGNnCase control.nnnMETHODSnPCOS (n=21, 25.8+/-4.1 years, BMI 21.6+/-1.7 kg/m(2)) and control healthy women (CT, n=13, 28.5+/-7.2 years, BMI 20.3+/-2.5 kg/m(2)) underwent oral glucose tolerance test (OGTT) with blood sampling for glucose, insulin, C-peptide, total GIP, and active GLP-1. Insulin sensitivity was determined both at fasting and during the test.nnnSTATISTICSnRepeated measures ANOVA.nnnRESULTSnGlucose levels and insulin sensitivity did not differ between PCOS and CT. PCOS had significantly higher levels of C-peptide (P<0.05) and tended to have higher insulin levels. The levels of total GIP were significantly higher in PCOS than in CT (P<0.001). Active GLP-1 levels exhibited a significantly different time-dependent pattern in PCOS (P<0.002 for PCOS versus time interaction). GLP-1 concentrations were similar in PCOS and CT in the early phase of OGTT and then reached significantly lower levels in PCOS than in CT at 180 min (P<0.05).nnnCONCLUSIONSnIncreased total GIP and lower late phase active GLP-1 concentrations during OGTT characterize PCOS women with higher C-peptide secretion in comparison with healthy controls, and may be the early markers of a pre-diabetic state.

Prevalence of insulin resistance and prediction of glucose intolerance and type 2 diabetes mellitus in women with polycystic ovary syndrome.

Abstract Background: Diabetes mellitus type 2 (DM2) affects 10% of women with polycystic ovary syndrome (PCOS). We evaluated the sensitivity and specificity of clinical and fasting biochemical parameters in screening for impaired glucose tolerance (IGT) and DM2. Methods: Women with PCOS [n=244, age 27.4±7.5 years, body mass index (BMI) 27.5±6.9 kg/m2] and healthy women (n=57, age 26.8±5.8 years, BMI 21.3±2.1 kg/m2) underwent basal blood sampling and an oral glucose tolerance test (oGTT). Results: Insulin resistance was identified in 40.2% of PCOS women. Impaired fasting glucose (5.6–6.9 mmol/L) was found in 30 subjects (12.3%), but the oGTT revealed IGT in only six of these cases and DM2 in one subject. IGT was found in 23 (9.4%) and DM2 in four (1.6%) of the women with PCOS. The conventional upper limits for total cholesterol, triglycerides, systolic and diastolic blood pressure and fasting glucose revealed low sensitivity for the identification of impaired glucose metabolism. Conclusions: No single parameter nor any combination of them showed an accuracy sufficient for screening of IGT or DM2 in PCOS patients. All PCOS patients should be screened using an oGTT to identify disturbances in glucose metabolism. Clin Chem Lab Med 2007;45:639–44.

Determinants of circulating adiponectin in women with polycystic ovary syndrome.

Background and Aim: Adiponectin is regarded as a possible link between adiposity and insulin resistance. Ghrelin and leptin are considered as signals of energy status. We evaluated the relationships between these peptides, androgens and insulin sensitivity in women affected by polycystic ovary syndrome. Methods: Thirty-six women with PCOS were examined with euglycemic hyperinsulinemic clamp (to determine M/I, index of insulin sensitivity). Leptin, ghrelin, adiponectin, androgens, and SHBG were determined. Statistics was done using correlation analysis and backward stepwise multiple regression. Results: The positive correlation of adiponectin with testosterone remains significant even after adjustment for BMI (p = 0.01), M/I (p = 0.009) and for both M/I and BMI (p = 0.02). In multiple regression with testosterone, M/I, leptin and ghrelin as independent variables, the model including testosterone (p = 0.03) and ghrelin (p = 0.002) explained 49% of the variability (p < 0.0012) of adiponectin. Conclusions: Both adiponectin and ghrelin can be involved in the pathophysiology of PCOS but their relation must be delineated further.

RET mutation Tyr791Phe the genetic cause of different diseases derived from neural crest

Activating germline RET mutations are presented in patients with familial medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia (MEN) types 2A and 2B, whereas inactivating germline mutations in patients with Hirschsprung’s disease (HSCR). The aim of this study was to evaluate genotype–phenotype correlations of the frequently discussed Tyr791Phe mutation in exon 13 of the RET proto-oncogene. Screening of three groups of patients was performed (276 families with medullary thyroid carcinoma (MTC), 122 families with HSCR, and 29 patients with pheochromocytoma). We found this mutation in 3 families with apparently sporadic MTC, 3 families with FMTC/MEN2, 1 patient with pheochromocytoma, and 3 families with HSCR. All gene mutation carriers have a silent polymorphism Leu769Leu in exon 13. In three families second germline mutations were detected: Cys620Phe (exon 10) in MEN2A family, Met918Thr (exon 16) in MEN2B family, and Ser649Leu (exon 11) in HSCR patient. Detection of the Tyr791Phe mutation in MEN2/MTC and also in HSCR families leads to the question whether this mutation has a dual character (gain-of-function as well as loss-of-function). A rare case of malignant pheochromocytoma in a patient with the Tyr791Phe mutation is presented. This study shows various clinical characteristics of the frequently discussed Tyr791Phe mutation.

Plasma thiols and androgen levels in polycystic ovary syndrome.

Abstract Homocysteine is a risk factor for ischemic heart disease; similarly as is hyperlipidemia or insulin resistance, which frequently occur in women with polycystic ovary syndrome. We examined the relationships between thiols and hormonal status or insulin resistance in 40 women (aged 25.8±7 years) with polycystic ovary syndrome and in 11 controls (33±5 years). Blood levels of homocysteine, glutathione, total and high density lipoprotein (HDL)-cholesterol, triglycerides, insulin, sex hormone-binding globulin, testosterone, androstenedione, dehydroepiandrosterone sulfate, and estradiol were determined. Students t test and Spearman correlations were computed after adjustment for body mass index (BMI) and age. Homocysteine was significantly higher in polycystic ovary syndrome patients than in the control group (10.3±2.87 vs. 8.78±2.75 μmol/l; p < 0.05). In women with polycystic ovary syndrome, there were significant positive correlations between homocysteine and androstenedione (r = 0.329; p < 0.05) and glutathione and dehydroepiandrosterone sulfate (DHEA-S) (r = 0.469; p < 0.05). We conclude that homocysteine is increased in women with polycystic ovary syndrome and is probably linked to androgen levels but not to markers of insulin resistance or with lipid metabolism.

Beta cell function and insulin sensitivity in women with polycystic ovary syndrome: Influence of the family history of type 2 diabetes mellitus

Aim.u2003To study the impact of family history (FH) of type 2 diabetes mellitus on β-cell compensatory mechanism in women with polycystic ovary syndrome (PCOS). Subjects and methods.u2003A total of 70 women with PCOS, 14 with first-degree relative with type 2 diabetes mellitus (T2DM) (FH+), 56 with negative FH of T2DM (FH−) and 72 age and BMI matched control healthy women (CNT) underwent oral glucose tolerance test (OGTT). Insulin resistance was evaluated as oral glucose index (OGIS); insulin and C-peptide secretion as the insulinogenic index in 30th min of OGTT. Results.u2003Fasting blood glucose levels were significantly higher in FH+ than in FH− (p < 0.05). Fasting insulin was higher in FH+ than in CNT (p < 0.05). Fasting C-peptide was significantly higher in both FH− and FH+ than in CNT (p < 0.05 and p < 0.01, respectively). OGIS was lower in FH+ than in FH− or in CNT (p < 0.05). Insulinogenic index calculated from C-peptide values (II-Cp) was lower in FH+ than in CNT (p < 0.05). Adaptation index calculated from the values of OGIS and insulinogenic index was significantly lower in FH+ than in CNT or in FH− (p < 0.0001 and p < 0.01, respectively). Conclusions.u2003Insulin resistance and defective early-phase insulin secretion is present only in those PCOS-affected subjects who had positive FH of T2DM.

Insulin sensitivity and secretion in obese Type 2 diabetic women after various bariatric operations

Objective: To compare the effects of biliopancreatic diversion (BPD) and laparoscopic gastric banding (LAGB) on insulin sensitivity and secretion with the effects of laparoscopic gastric plication (P). Methods: A total of 52 obese women (age 30-66 years) suffering from type 2 diabetes mellitus (T2DM) were prospectively recruited into three study groups: 16 BPD; 16 LAGB, and 20 P. Euglycemic clamps and mixed meal tolerance tests were performed before, at 1 month and at 6 months after bariatric surgery. Beta cell function derived from the meal test parameters was evaluated using mathematical modeling. Results: Glucose disposal per kilogram of fat free mass (a marker of peripheral insulin sensitivity) increased significantly in all groups, especially after 1 month. Basal insulin secretion decreased significantly after all three types of operations, with the most marked decrease after BPD compared with P and LAGB. Total insulin secretion decreased significantly only following the BPD. Beta cell glucose sensitivity did not change significantly post-surgery in any of the study groups. Conclusion: We documented similar improvement in insulin sensitivity in obese T2DM women after all three study operations during the 6-month postoperative follow-up. Notably, only BPD led to decreased demand on beta cells (decreased integrated insulin secretion), but without increasing the beta cell glucose sensitivity.