UNLABELLED: The shape of the glycemic curve during the oral glucose tolerance test (OGTT), interpreted in the correct context, can predict impaired glucose homeostasis. Our aim was to reveal information inherent in the 3 h glycemic trajectory that is of physiological relevance concerning the disruption of glycoregulation and complications beyond, such as components of metabolic syndrome (MS). METHODS: In 1262 subjects (1035 women, 227 men) with a wide range of glucose tolerance, glycemic curves were categorized into four groups: monophasic, biphasic, triphasic, and multiphasic. The groups were then monitored in terms of anthropometry, biochemistry, and timing of the glycemic peak. RESULTS: Most curves were monophasic (50%), then triphasic (28%), biphasic (17.5%), and multiphasic (4.5%). Men had more biphasic curves than women (33 vs. 14%, respectively), while women had more triphasic curves than men (30 vs. 19%, respectively) (p < 0.01). Monophasic curves were more frequent in people with impaired glucose regulation and MS compared to bi-, tri-, and multiphasic ones. Peak delay was the most common in monophasic curves, in which it was also most strongly associated with the deterioration of glucose tolerance and other components of MS. CONCLUSION: The shape of the glycemic curve is gender dependent. A monophasic curve is associated with an unfavorable metabolic profile, especially when combined with a delayed peak.

• Keywords
• beta cell function, delayed glucose peak, glucose curve shape, glucose tolerance, glycemic curve, insulin sensitivity, oral glucose tolerance test, type 2 diabetes mellitus,
• Publication type
• Journal Article MeSH

Vitamin D is no longer considered an agent only affecting calcium phosphate metabolism. A number of studies over the past few years have demonstrated its role in immunomodulation and its influence on the development and functioning of the brain and nervous system. In the current epidemiological crisis caused by coronavirus disease 2019 (COVID-19), the immunoprotective role of vitamin D has been discussed by some authors regarding whether it contributes to protection against this serious disease or whether its use does not play a role. Non-standard approaches taken by laboratories in examining the serum levels of the vitamin D metabolite calcidiol have contributed to inconsistent results. We examined the serum of 60 volunteers in the spring and autumn of 2021 who declared whether they were taking vitamin D at the time of sampling. Furthermore, the tested participants noted whether they had experienced COVID-19. A newly developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to measure calcidiol levels. The analysis of variance (ANOVA) model of Statgraphics Centurion 18 statistical software from Statgraphics Technologies was used for calculations. The results of this study showed that those who took vitamin D suffered significantly less often from COVID-19 than those who did not take vitamin D.

• Keywords
• COVID-19, LC-MS/MS determination, vitamin D,
• MeSH
• Chromatography, Liquid methods   MeSH
• COVID-19 * epidemiology   prevention & control   MeSH
• Calcifediol MeSH
• Humans MeSH
• Tandem Mass Spectrometry methods   MeSH
• Vitamin D * metabolism   MeSH
• Vitamins MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Calcifediol MeSH
• Vitamin D * MeSH
• Vitamins MeSH

Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM- women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM- women (n = 33), in weeks 24-28, 30-36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.

• Keywords
• gas chromatography-tandem mass spectrometry, gestational age, gestational diabetes mellitus, immunoprotective steroids, maternal blood, mixed cord blood, neuroactive steroids, steroidome,
• MeSH
• 20-Hydroxysteroid Dehydrogenases metabolism   MeSH
• Chromatography, Gas MeSH
• Cytochrome P-450 CYP3A metabolism   MeSH
• Pregnancy Trimester, Second metabolism   MeSH
• Diabetes, Gestational metabolism   MeSH
• Humans MeSH
• Metabolomics methods   MeSH
• Oxidoreductases metabolism   MeSH
• Steroid 17-alpha-Hydroxylase metabolism   MeSH
• Steroids analysis   MeSH
• Tandem Mass Spectrometry MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 20-Hydroxysteroid Dehydrogenases MeSH
• 3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase MeSH Browser
• 3-oxo-5 beta-steroid delta 4-dehydrogenase MeSH Browser
• CYP17A1 protein, human MeSH Browser
• CYP3A7 protein, human MeSH Browser
• Cytochrome P-450 CYP3A MeSH
• Oxidoreductases MeSH
• Steroid 17-alpha-Hydroxylase MeSH
• Steroids MeSH

Background: Anorexia nervosa (AN) is a life-threatening illness with poor treatment outcomes. Although transcranial direct current stimulation (tDCS) is a promising non-invasive brain stimulation method, its effect in patients with AN remains unclear. Objective: This study investigated changes in maladaptive eating behavior, body mass index (BMI), and depression after 10 sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC). Methods: In this double-blind, randomized controlled trial, 43 inpatients with AN were divided to receive either active (n = 22) or sham (n = 21) tDCS over the left DLPFC (anode F3/cathode Fp2, 2 mA for 30 min). All patients filled the Eating Disorder Examination Questionnaire (EDE-Q) and Zung Self-Rating Depression Scale (ZUNG), and their BMI was measured. These values were obtained repeatedly in four stages: (1) before tDCS treatment, (2) after tDCS treatment, (3) in the follow-up after 2 weeks, and (4) in the follow-up after 4 weeks. Results: Primary outcomes (EDE-Q) based on the ANOVA results do not show any between-group differences either after the active part of the study or in the follow-up. Secondary analysis reveals a reduction in some items of EDE-Q. Compared with sham tDCS, active tDCS significantly improved self-evaluation based on body shape (p < 0.05) and significantly decreased the need of excessive control over calorie intake (p < 0.05) in the 4-week follow-up. However, the results do not survive multiple comparison correction. In both sham and active groups, the BMI values improved, albeit not significantly. Conclusion: We did not observe a significant effect of tDCS over the left DLPFC on complex psychopathology and weight recovery in patients with AN. tDCS reduced the need to follow specific dietary rules and improved body image evaluation in patients with AN. Tests with a larger sample and different positions of electrodes are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03273205.

• Keywords
• EDE-Q, Zung scale of depression, anorexia nervosa, brain stimulation, self-perception, tDCS, transcranial direct current stimulation,
• Publication type
• Journal Article MeSH

The aim of this prospective study was the validation of the risk stratification of thyroid nodules using ultrasonography with the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) and partly in comparison to American Thyroid Association (ATA) guidelines in a secondary referral center. Fine needle aspiration biopsy (FNA) (n=605) and histological examinations (n=63) were the reference standards for the statistical analysis. ACR TI-RADS cut-off value: TR4 with sensitivity 85.7 %, specificity 54.1 %, PPV 58.5 %, accuracy 67.7 % (AUC 0.738; p<0.001). ATA cut-off value: "high suspicion" with sensitivity 80 %, specificity 83.3 %, PPV 80 %, accuracy 81.8 % (AUC 0.800; p=0.0025). 18.4 % nodules (3 malignant) could not be assigned to a proper ATA US pattern group (p<0.0001). Both ACR TI-RADS and ATA have allowed fair selection of nodules requiring FNA with superiority of ACR TI-RADS according to classification of all thyroid nodules to the proper group. According to ACR TI-RADS almost one third of the patients were incorrectly classified with 17.9 % missed thyroid carcinomas, exclusively micropapillary carcinomas, even though, the amount of FNA would be reduced to 48 %.

• MeSH
• Secondary Care Centers standards   MeSH
• Middle Aged MeSH
• Humans MeSH
• Thyroid Neoplasms diagnosis   diagnostic imaging   surgery   MeSH
• Prospective Studies MeSH
• Reference Standards MeSH
• Thyroid Gland diagnostic imaging   pathology   surgery   MeSH
• Biopsy, Fine-Needle MeSH
• Ultrasonography methods   MeSH
• Thyroid Nodule diagnosis   diagnostic imaging   surgery   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Obesity increases the incidence of hypogonadism in men, and hypogonadism in turn plays a role in obesity. One of the first mechanisms proposed to explain this was a hypothesis based on the principle that obese men have higher estrogen levels, and that increased estrogens provide feedback to the hypothalamic-pituitary-testicular axis, reducing the secretion of gonadotropins and leading to a decrease of overall testosterone levels. This concept has since been questioned, though never completely disproven. In this study we compared hormone levels in three groups of men with differing BMI levels (between 18-25, 25-29, and 30-39), and found correlations between lowering overall testosterone, SHBG and increased BMI. At the same time, there were no significant changes to levels of free androgens, estradiol or the gonadotropins LH and FSH. These findings are in line with the idea that estrogen production in overweight and obese men with BMI up to 39 kg/m(2) does not significantly influence endocrine testicular function.

• MeSH
• Androgens blood   MeSH
• Adult MeSH
• Estradiol blood   MeSH
• Estrogens blood   MeSH
• Follicle Stimulating Hormone blood   MeSH
• Hypogonadism blood   epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Luteinizing Hormone blood   MeSH
• Young Adult MeSH
• Obesity blood   epidemiology   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Androgens MeSH
• Estradiol MeSH
• Estrogens MeSH
• Follicle Stimulating Hormone MeSH
• Luteinizing Hormone MeSH

OBJECTIVE: Patients with type 2 diabetes (T2DM) generally experience a higher incidence of cancer. However, the association between T2DM and thyroid cancer is inconclusive. METHODS: Case-control prospective study, where 722 patients were screened for T2DM and prediabetes (PDM) and underwent thyroid ultrasound and biochemical tests. The patients were assigned to groups of PDM (n = 55), T2DM (n = 79) or a non-diabetes group (NDM) (n = 588). Fine-needle aspiration biopsy was carried out in 263 patients. Histological examinations were done for 109 patients after surgery, with findings of 52 benign (BS) and 57 malignant tumors (MS). RESULTS: Thirty-three percent of patients with T2DM and especially PDM were newly diagnosed by our screening: 6.5% with T2DM and 72% with PDM, respectively. The percentage of thyroid cancers did not significantly differ between the groups (χ2 test = 0.461; P = 0.794). Relevant positive thyroid predictors for T2DM (t-statistic = 25.87; P < 0.01) and PDM (21.69; P < 0.01) contrary to NDM (-26.9; P < 0.01) were thyroid volume (4.79; P < 0.01), thyroid nodule volume (3.25; P < 0.01) and multinodular thyroid gland (4.83; P < 0.01), while negative relevant predictors included the occurrence of autoimmune thyroid disease (AITD) (-2.01; P < 0.05). CONCLUSION: In general, we did not observe an increased risk for thyroid cancer in the diabetic and prediabetic groups in comparison to controls, in spite of well-established increased risk for other malignancies. Structural and benign changes such as larger and multinodular thyroid glands, in comparison to autoimmune thyroid disease, are present more often in diabetics.

• Keywords
• insulin resistance, obesity, prediabetes, thyroid cancer, thyroid disease, type 2 diabetes mellitus,
• Publication type
• Journal Article MeSH

OBJECTIVE: The aim of the study was to test the effect of transecting the inferior alveolar nerve on the inorganic bone component of the rat mandible. METHODS: 7-9 weeks old, male Wistar rats were used for the study. The animals were divided in 3 groups: control, experimental (nerve was transected) and sham (nerve was only prepared but not transected). After 4 weeks, the animals were killed, their teeth were extracted, and the mandibular bone was divided in 4 parts. Inductively coupled plasma mass spectrometry was used to the levels of 7 elements in the bone. RESULTS: The study results demonstrate that transection of the inferior alveolar nerve caused a decrease in calcium, iron, and strontium, and an increase of zinc. It caused the differences in potassium contents between the sides was significantly lower in the experimental group. The increase in the magnesium content, and decrease of sodium and potassium in the experimental group, as well as differences in the contents of: magnesium, sodium, potassium, iron and zinc between individual locations in the mandible are associated with the surgical approach. CONCLUSION: The results support our hypothesis - that sensory innervation has an impact on the inorganic component of the mandibular bone.

• Keywords
• Elements, Inferior Alveolar Nerve, Mandible, Nerve Transection, Rats,
• MeSH
• Axotomy MeSH
• Rats MeSH
• Mandible chemistry   innervation   MeSH
• Mandibular Nerve physiology   MeSH
• Rats, Wistar MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

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.

• MeSH
• Bariatric Surgery methods   MeSH
• Insulin-Secreting Cells physiology   MeSH
• Biliopancreatic Diversion methods   MeSH
• Diabetes Mellitus, Type 2 complications   metabolism   surgery   MeSH
• Adult MeSH
• Insulin metabolism   MeSH
• Insulin Resistance * MeSH
• Blood Glucose metabolism   MeSH
• Laparoscopy methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Obesity, Morbid complications   metabolism   surgery   MeSH
• Insulin Secretion MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Names of Substances
• Insulin MeSH
• Blood Glucose MeSH

Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 μM) and corresponding controls (n = 17). An age-adjusted linear model, receiver-operating characteristics (ROC), and multivariate regression (a method of orthogonal projections to latent structure, OPLS) were used for data evaluation. While aminotransferases, conjugates of pregnanediols, 17-hydroxypregnenolone and 5β-androstane-3α,17β-diol were higher in ICP patients, 20α-dihydropregnenolone, 16α-hydroxy-steroids, sulfated 17-oxo-C19-steroids, and 5β-reduced steroids were lower. The OPLS model including steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity, while the model including steroids measured by GC-MS in a single sample aliquot showed 93.3% sensitivity and 94.1% specificity. A composite index including ratios of sulfated 3α/β-hydroxy-5α/β-androstane-17-ones to conjugated 5α/β-pregnane-3α/β, 20α-diols discriminated with 93.3% specificity and 81.3% sensitivity (ROC analysis). These new data demonstrating altered steroidogenesis in ICP patients offer more detailed pathophysiological insights into the role of steroids in the development of ICP.

• MeSH
• 17-alpha-Hydroxypregnenolone blood   chemistry   MeSH
• 17-alpha-Hydroxyprogesterone blood   chemistry   MeSH
• Alanine Transaminase blood   MeSH
• Aspartate Aminotransferases blood   MeSH
• Adult MeSH
• Gestational Age MeSH
• Hydrocortisone blood   chemistry   MeSH
• Cholestasis, Intrahepatic diagnosis   metabolism   pathology   MeSH
• Liver Function Tests MeSH
• Pregnancy Complications diagnosis   metabolism   pathology   MeSH
• Humans MeSH
• Dorsal Raphe Nucleus MeSH
• Area Under Curve MeSH
• Gas Chromatography-Mass Spectrometry MeSH
• Radioimmunoassay MeSH
• ROC Curve MeSH
• Steroids blood   chemistry   metabolism   MeSH
• Pregnancy MeSH
• Bile Acids and Salts analysis   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 17-alpha-Hydroxypregnenolone MeSH
• 17-alpha-Hydroxyprogesterone MeSH
• Alanine Transaminase MeSH
• Aspartate Aminotransferases MeSH
• Hydrocortisone MeSH
• Steroids MeSH
• Bile Acids and Salts MeSH