Expression of Selected Genes and Circulating microRNAs in Patients with Celiac Disease.

Background and Objectives: Celiac disease (CD) is an immune-mediated enteropathy with characteristic intestinal alterations. CD occurs as a chronic inflammation secondary to gluten sensitivity in genetically susceptible individuals. Until now, the exact cause of the disease has not been established, which is why new studies have appeared that address the involvement of various genes and microRNAs (miRNAs) in the pathogenesis. The aim of the study is to describe the expression of selected genes (Wnt family member 3, WNT3; Wnt family member 11, WNT11; tumor necrosis factor alpha, TNFα; mitogen-activated protein kinase 1, MAPK1; AKT serine/threonine kinase 3, AKT3; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, PIK3CA; and cyclin D1, CCND1) and miRNAs (miR-192-5p, miR-194-5p, miR-449a and miR-638) in adult patients with CD. Materials and Methods: In total, 15 patients with CD at diagnosis (newly diagnosed), 33 patients on a gluten-free diet (GFD) for at least 1 year and 10 controls (control) were prospectively included. Blood samples were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results show that TNFα, MAPK1 and CCND1 were significantly overexpressed (p = 0.0249, p = 0.0019 and p = 0.0275, respectively) when comparing the newly diagnosed group to the controls. The other genes studied in CD patients were mostly with high values compared to controls, without reaching statistical significance. Among the miRNAs, the closest to a statistically significant value was miR-194-5p when the newly diagnosed group versus control (p = 0.0510) and GFD group versus control (p = 0.0671) were compared. The DIANA and miRNet databases identified significant functional activity for miR-449a and miR-192-5p and an interconnection of miR-194-5p and miR-449a with CCND1. Conclusions: In conclusion, genes and circulating miRNAs require further studies as they could represent important biomarkers in clinical practice.

Interplay between metabolic and thyroid parameters in obese pubertal children. Does visceral adipose tissue make the first move?

Objectives: The mechanisms of obesity-associated thyroid dysfunction in children are incompletely deciphered. We aimed to evaluate whether visceral adipose tissue (VAT), insulin resistance (IR), inflammation, oxidative stress (OS) are involved in thyroid morpho-functional changes in pubertal obese children. Methods: We recruited 43 obese pubertal children without history of thyroid pathology. Metabolic and thyroid parameters (visceral fat thickness [VFT], waist/hip ratio [WHR], waist/height ratio [WHtR], insulin, glucose, liver parameters, thyroid stimulation hormone [TSH], free thyroxine [FT4], free triiodothyronine [FT3], thyroid and abdominal ultrasonography) were evaluated. Serum monocyte chemoattractant protein-1 (MCP-1) and malondialdehyde (MDA) levels were quantified as markers of inflammation and OS. Results: VFT correlated positively both with WHR (p= 0.034) and the presence of thyroid nodules (p= 0.036). WHR associated with TSH (p= 0.005), FT3/FT4 (p= 0.033) and was independently associated with FT3/FT4 increase (p< 0.001). HOMA-IR increased with visceral obesity (waist circumference, p= 0.001; WHR, p= 0.018; WHtR: p< 0.001), hepatic impairment (alanine aminotransferase, p= 0.019) and hepatic steatosis (HS; p= 0.013) and correlated positively with FT3/FT4 (p= 0.036). TSH was significantly higher in subjects with HS versus those without HS (p= 0.007) and logistic regression analysis identified TSH as a risk factor for HS (p= 0.014). MDA correlated positively with MCP-1 (p= 0.021). Conclusion: VAT and IR may be responsible for changes in thyroid parameters associated with obesity: elevated TSH, FT3/FT4 levels and increased prevalence of thyroid nodules. WHR was predictive of increased FT3/FT4. In obese children, there is an interdependent relationship between HS and thyroid function.

Vitamin D deficiency, insulin resistance and thyroid dysfunction in obese patients: is inflammation the common link?

The aim of this article is to study the possible relation of serum vitamin D concentrations to body mass index (BMI), visceral fat thickness (VFT), insulin resistance (IR), inflammation (serum monocyte chemoattractant protein-1 - MCP-1) and thyroid parameters in obese patients. A total of 158 non-diabetic, obese patients aged 19-68 without a history of thyroid pathology were recruited. Biochemical markers, insulin, 25-OH vitamin D, thyroid parameters (TSH, FT3, FT4, TPO antibodies, TG antibodies) and VFT were measured. Serum MCP-1 evaluated the inflammation. A HOMA-IR cut-off value of 2.5 defined IR. Most patients had severe (70.3%) or moderate (25.3%) vitamin D deficiency. Vitamin D level was negatively associated with BMI (p = .043) and during the cold season with VFT (p = .009). Vitamin D deficiency correlated with Hashimoto's thyroiditis prevalence during the warm season (p = .047) and was a risk factor for its occurrence (p = .021). At 15 ng/mL cut-off value, vitamin D was negatively correlated with MCP-1 (p = .0006). Also, MCP-1 was positive correlated with HOMA- IR (p = .042), TPO-Ab levels (p = .011) and with Hashimoto's thyroiditis (p = .027). MCP-1 was a risk factor for vitamin D deficiency (p < .0001). Our study supports a bidirectional interaction between vitamin D and systemic inflammation in obese patients. Moreover, systemic inflammation is related to the severity and frequency of Hashimoto's thyroiditis. Vitamin D deficiency is the single independent factor associated with Hashimoto's thyroiditis in obese patients.

Thyroid disorders in obese patients. Does insulin resistance make a difference?

ABSTRACT Objective: The aim of this study was to evaluate the association between insulin resistance and thyroid pathology in obese patients, and compare the results between insulin-resistant and noninsulin-resistant patients. Subjects and methods: Obese/nondiabetic patients, aged 18-70 years, attending the outpatient endocrinology service for 2 years were consecutively included. We evaluated the patients' fasting plasma glucose, insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), thyroid-stimulating hormone (TSH), free thyroxine (FT4), antithyroperoxidase antibodies (TPO-Ab), antithyroglobulin antibodies (Tg-Ab), and thyroid ultrasound. Results: We included 82 patients with a mean age 44.21 ± 12.67 years. The thyroid disorders encountered and their prevalences were: hypothyroidism (14.6%, 95% confidence interval [CI] 8.6-23.8%), hyperthyroidism (1.2%, 95% CI 2.0-6.6%), goiter (28.0%, 95% CI 19.5-3.6%), thyroid nodules (35.4%, 95% CI 25.9-46.2%), and Hashimoto's thyroiditis (32.9%, 95% CI 23.7-43.7%). HOMA-IR correlated positively with TSH levels (r = 0.24, p = 0.028), and this correlation remained after adjustment for body mass index (BMI), waist/hip ratio (WHR), serum cortisol, subcutaneous fat thickness (SFT), visceral fat thickness (VFT), triglycerides, γ-glutamyl transpeptidase (GGT), and alanine aminotransferase (ALT) in multivariate regression analysis (b = 0.207, 95% CI, 0.09-0.385, p = 0.023). TSH levels were significantly higher in patients with HOMA-IR ≥ 2.5 than in those with HOMA-IR < 2.5 (2.03 μIU/mL, interquartile range [IQR] 1.59-2.69 μIU/mL) versus 1.59 μIU/mL, IQR 0.94-2.26 μIU/mL, p = 0.023). Conclusions: The most prevalent thyroid disorder in patients attending our endocrinology clinic for investigation of obesity was thyroid nodules. One in seven patients had hypothyroidism. Our findings suggest that TSH levels correlate with insulin resistance in obese patients.

Thyroid disorders in obese patients. Does insulin resistance make a difference?

OBJECTIVE: The aim of this study was to evaluate the association between insulin resistance and thyroid pathology in obese patients, and compare the results between insulin-resistant and noninsulin-resistant patients. SUBJECTS AND METHODS: Obese/nondiabetic patients, aged 18-70 years, attending the outpatient endocrinology service for 2 years were consecutively included. We evaluated the patients' fasting plasma glucose, insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), thyroid-stimulating hormone (TSH), free thyroxine (FT4), antithyroperoxidase antibodies (TPO-Ab), antithyroglobulin antibodies (Tg-Ab), and thyroid ultrasound. RESULTS: We included 82 patients with a mean age 44.21 ± 12.67 years. The thyroid disorders encountered and their prevalences were: hypothyroidism (14.6%, 95% confidence interval [CI] 8.6-23.8%), hyperthyroidism (1.2%, 95% CI 2.0-6.6%), goiter (28.0%, 95% CI 19.5-3.6%), thyroid nodules (35.4%, 95% CI 25.9-46.2%), and Hashimoto's thyroiditis (32.9%, 95% CI 23.7-43.7%). HOMA-IR correlated positively with TSH levels (r = 0.24, p = 0.028), and this correlation remained after adjustment for body mass index (BMI), waist/hip ratio (WHR), serum cortisol, subcutaneous fat thickness (SFT), visceral fat thickness (VFT), triglycerides, γ-glutamyl transpeptidase (GGT), and alanine aminotransferase (ALT) in multivariate regression analysis (b = 0.207, 95% CI, 0.09-0.385, p = 0.023). TSH levels were significantly higher in patients with HOMA-IR ≥ 2.5 than in those with HOMA-IR < 2.5 (2.03 µIU/mL, interquartile range [IQR] 1.59-2.69 µIU/mL) versus 1.59 µIU/mL, IQR 0.94-2.26 µIU/mL, p = 0.023). CONCLUSIONS: The most prevalent thyroid disorder in patients attending our endocrinology clinic for investigation of obesity was thyroid nodules. One in seven patients had hypothyroidism. Our findings suggest that TSH levels correlate with insulin resistance in obese patients.

Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis.

INTRODUCTION: Hyperhomocysteinemia is considered an independent risk factor for cardiovascular disease. Oxidative stress is one of the major pathogenic mechanisms in non-alcoholic fatty liver disease and atherosclerosis. AIM: Our study aimed to evaluate serum homocysteine levels and oxidative stress in patients with biopsy-proven non-alcoholic steatohepatitis and possible association with cardiovascular risk measured by carotid artery intima-media thickness (c-IMT). PATIENTS AND METHODS: 50 patients with non-alcoholic steatohepatitis and 30 healthy controls, age and gender matched, were recruited. Lipid profile, liver biochemical markers, serum homocysteine, vitamins B6 and B12, folic acid, glutathione (reduced and total), erythrocyte superoxide dismutase, whole blood glutathione peroxidase, malondialdehyde and carotid intima-media thickness were assayed. RESULTS: Patients had an altered lipid profile and liver biochemical markers; carotid intima-media thickness and serum homocysteine levels were significantly higher compared to controls, but there were no differences in folate, B12 and B6 vitamins levels. Patients had significantly lower levels of glutathione peroxidase activity, total and reduced glutathione and higher levels of malondialdehyde, but unchanged superoxide dismutase activity compared to control group. Also, serum homocysteine level showed significant positive correlation with waist circumference, body mass index, free cholesterol, triglycerides, LDL-cholesterol, amino transferases and negative correlation with reduced and total glutathione, superoxide dismutase and γ-GT. CONCLUSION: Non-alcoholic steatohepatitis is an independent cardiovascular risk factor, associated with elevated homocysteine levels, oxidative stress and c-IMT. c-IMT could be used as an indicator of early atherosclerotic changes initiated by dyslipidemia and oxidative stress, while higher level of homocysteine might be an effect of liver damage.

The prognosis significance of insulin secretion in liver cirrhosis.

We evaluate the prognostic significance of chronic liver diseases followed by diabetes mellitus in 40 patients by Child class, immunoreactive insulinemia (IRI), C peptide (CP) and pancreolaury-test (PLT) at 5 years. Death and hepatic insufficiency prevalence were significantly higher in cirrhotic diabetics, and in those diabetics with a lower insulin secretion (IRI, CP). Insulin hyposecretion (lower IRI, CP) was found in cirrhotic with abnormal PLT (below 20%). The onset of diabetes mellitus in liver cirrhosis has a bad prognosis when it is caused by decreased insulin secretion produced by chronic pancreatitis or pancreatic insufficiency.