ACTA ENDOCRINOLOGICA (BUC)

Aims. This study investigated the relationship between proteinuria levels, clinicopathological features, and renal prognoses in Chinese patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods. Three hundred patients with T2DM and biopsy-proven DN were enrolled. Patients were stratified by 24-h proteinuria levels: Group 1:≤1g/24h); Group 2:1-3g/24h; and Group 3:≥3g/24h. Renal outcomes were defined as having reached end-stage renal disease (ESRD). The proteinuria level’s influence on the renal outcomes was evaluated using Cox regression analysis. Results. Among subgroups stratified by proteinuria levels, systolic blood pressure, serum creatinine, BUN, cholesterol, DR and hypertension incidence, the incidences of patients who progressed to ESRD were the lowest in group 1 (P<0.05). However, eGFR, serum albumin and hemoglobin were highest in group 1. Patients with higher proteinuria levels had much lower five-year renal survival rates. Univariate analyses revealed that higher proteinuria levels were significant clinical predictors of renal prognosis (P<0.05), although they were not independent risk factors for progression to ESRD in the multivariate Cox proportional hazard analysis (P>0.05). Conclusions. The higher the level of proteinuria, the lower the 5-year renal survival rate of DN patients, but there was no significant correlation between proteinuria level and 5-year renal survival rate. Other factors in the proteinuria group may have more significant effects on the 5-year renal survival rate, such as lower baseline eGFR, serum albumin, hemoglobin and higher cholesterol, higher incidences of DR and more severe lesions.

Aims. Resistin has been reported to impair the pancreatic beta cells and associated with insulin resistance. MicroRNAs (miRNAs) are short, endogenously produced non-coding ribonucleotides that bind mRNAs and function mainly as negative regulators in mammals. MiRNAs have been implicated in many diseases, including insulin resistance and diabetes. A considerable body of evidence has indicated an important function for miRNAs in insulin secretion. The current study was designed to investigate the effects of miR-494 in the reductions in insulin secretion attributable to resistin. Methods. Insulin secretion was determined by ELISA, and expressions of genes were identified using quantitative RT-PCR (qRT-PCR) or Western blot analysis. Results. Insulin secretion was significantly reduced by resistin. Overexpression of miR-494 inhibited insulin secretion both in diet culture and high glucose medium in MIN6 cell lines. MiR-494 down-regulated the protein level of STXBP5 by pairing with sites in the 3′UTR. Conclusion. miR-494 is involved in the insulin secretion regulated by resistin via its effects on STXBP5 in MIN6 cells.

Objective. This study was to investigate RIP140 expression levels in the pancreas and islet β-cells in mice and rats and the role of RIP140 in cultured β-cells using the mouse pancreatic β-cell line MIN6. Methods. The MIN6 cell line stably overexpressing RIP140 was used. The effects of RIP140 on cell viability, cell cycle, apoptosis, insulin secretion, and its regulated genes were analyzed using flow cytometry, the MTT assay, Western blot analysis, reverse transcriptase (RT)-PCR, and enzyme-linked immunosorbent assay (ELISA). Results. Most of insulin-positive cells in islets expressed RIP140. In MIN6 cells, overexpression of RIP140 inhibited cell viability by reducing the number of cells in S phase and inhibiting proliferating cell nuclear antigen (PCNA) expression. We also found that overexpression of RIP140 inhibited Bcl-2 and mRNA expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and uncoupling protein 2 (UCP2) and increased levels of phosphorylated extracellular signalregulated protein kinases 1/2 (p-ERK1/2). However, apoptosis rate and levels of basal level of insulin secretion (BIS) and glucose-stimulated insulin (GSIS) were not significantly altered in MIN6 cells. Conclusions. RIP140 was expressed in the pancreas of mice and rats, particularly in β-cells, and participated in regulating β-cell function and proliferation.

Context. Rapidly progressive precocious puberty (RPPP) is a rare condition in Turner syndrome (TS), with no consensus on treatment and follow-up. Only 12 cases have been reported so far. Objective. We aimed to evaluate the effects of the GnRH analog (GnRHa) on growth and anti-mullerian hormone (AMH) levels in TS and RPPP. Design. The clinical and laboratory data was recorded at baseline and after treatment. Subjects and methods. An 8.1-year old girl with a karyotype of 45, X/46, XX presented with breast development at Tanner stage-2. Breast development advanced to Tanner stage-3 at the age of 8.7 years. Growth velocity (GV) was 8 cm/year. Bone age was 11 years with a predicted adult height of 152 cm. Luteinizing hormone (LH) was 1.69mIU/mL and estradiol was 33pg/mL, confirming the central puberty. AMH level was 6.33ng/mL. The sizes of ovaries and uterus were compatible with the pubertal stage, with an endometrial thickness of 5 mm. GnRHa was started for RPPP. Results. After three months, GV declined to 0 cm/3 months and AMH level to 50% of the baseline. Growth hormone (GH) treatment was started for insufficient growth. GV improved with GH treatment, as well as a far more decreased AMH level. Conclusion. GV usually declines before puberty in patients with TS, even if the mid-parental height is tall. RPPP should be considered if GV is increased. Excessive suppression of growth may be prevented with GH treatment. GnRHa treatment also plays a role in reducing AMH levels in patients with TS.

Severe hypercalcemia is often caused by primary hyperparathyroidism (PHP), which is not commonly seen in patients with systemic lupus erythematosus (SLE). In this case report a 77 years old woman with a history of SLE develops mild hypercalcemia secondary to unrecognized PHP that leads to a hypercalcemic crisis with a prolonged recovery. Therefore, early diagnostic evaluation of persistent hypercalcemia in patients with SLE is important for detection and appropriate treatment of PHP to avoid a hypercalcemic crisis and associated prolonged morbidity.

Sustained exposure to high serum insulin-like growth factor (IGF-1) levels is likely to play a role in the development of the thyroid tumor in acromegaly; however, there is no report that indicate a promoting effect on the secretion of hormones by the thyroid tumor. We report a case of acromegaly in a seventy-one-year-old female with primary subclinical hyperthyroidism. Autoantibodies including\r\nanti-thyroglobulin antibody, anti-thyroid peroxidase antibody and thyroid stimulating hormone (TSH) receptor antibody were all negative. Ultrasonography of the thyroid\r\ndemonstrated a solid adenoma in the left thyroid lobe and Technetium-99m thyroid scintigraphy showed a high level of\r\naccumulation into the same lesion, indicating that toxic nodular goiter (TNG) was the cause of hyperthyroidism. Despite serum thyroid hormones remaining at normal levels,\r\nserum TSH levels went on decreasing gradually until transsphenoidal surgery to treat a growth hormone (GH) secreting pituitary adenoma. Interestingly, as IGF-I\r\nand GH levels normalized after operation, the serum TSH level increased and finally reached the normal level without\r\nintervention to the thyroid. Additionally, accumulation of Technetium-99m seen with thyroid scintigraphy slightly decreased. The evidence obtained from this case may\r\nsuggest a novel mechanism whereby excessive secretion of thyroid hormones from TNG in an acromegalic patient is\r\nregulated by IGF-I.

Context. It is well known that thyroid hormones are important, being involved in affects the metabolism of carbohydrate, protein, lipids. The relationship between thyroid hormones and lipid metabolism is the focus of recent research. Objective. To investigate the relationship between subclinical hypothyroidism and lipid metabolism in women. Design. We conducted an epidemiological survey of thyroid diseases among women in Northeast China from September 2014 to December 2014. Subjects and Methods. A total of 1397 women underwent physical examinations and laboratory tests for thyroid function and lipid metabolism. Results. We found that the detection rate of subclinical hypothyroidism was 13.03%. Patients with subclinical hypothyroidism showed significantly higher levels of triglyceride (1.69±1.9 vs. 1.45±1.4) and the risk of hyper triglyceridemia in women with thyroid stimulating hormone (TSH) levels ≥10mIU/L was 4.96-fold higher compared with that in the normal population (P<0.01). Conclusion. Disorders of lipid metabolism in women with subclinical hypothyroidism show a direct correlation with the level of TSH, and the risk of hyper triglyceridemia is significantly increased when the level of TSH ≥10mIU/L.

Aims. To investigate the changes in the miRNAs and mRNAs expressed in the liver upon induction of “hyperresistinemia”. Methods. We identified mRNA and miRNAs that were differentially expressed between normal and resistin-treated liver tissue using microarrays. Expression was validated using quantitative RT-PCR (qRT-PCR). The putative targets and pathways of the differentially expressed miRNAs and mRNAs were investigated, respectively, using various computational algorithms. In addition, the interactions between differentially expressed miRNAs and mRNAs were analyzed. Results. After the filtration of the signals below the threshold level, we identified 34 miRNAs and 875 genes with expression levels different by more than 1.5-fold and 2.0-fold, respectively, between the two groups. These observations were confirmed by qRT-PCR. Bidirectional prediction analyses showed that the differentially expressed miRNAs may be inversely regulated by their predicted targets. Conclusion. Hyperresistinemia results in changes in the miRNAs and mRNAs expressed in the liver.

Background. Hashimoto thyroiditis (HT) is an autoimmune disease and the most common cause of hypothyroidism. The widespread lymphocyte infiltration in the thyroid gland and intolerance of the body against its thyroid antigens leads to the destruction of thyroid cells and impaired thyroid function. Granulysin (GNLY) is a cytolytic antimicrobial peptide that has been associated with a wide range of diseases such as various infections, cancer, transplantation, and skin problems. However, there are a few studies investigating the relationship between HT and granulysin. Aim. Our study aims to investigate whether granulysin levels and GNLY gene polymorphism contribute to the damaged immune response leading to HT. Material and Methods. 100 unrelated patients diagnosed with HT and 140 healthy individuals were included in our study. Frequencies of GNLY rs10180391 and rs7908 gene polymorphisms were determined using PCR- RFLP method and serum granulysin levels were determined using ELISA. Results. There is no statistical significance between patient and control groups in terms of genotype and allele frequencies of GNLY gene polymorphisms and serum levels of granulysin. Conclusion. In conclusion, granulysin and GNLY gene polymorphisms do not appear to relate to HT disease.

Introduction. Irisin is a recently discovered novel adipomyokine that induces an increase in total body energy expenditure, improves insulin sensitivity and glucose tolerance. It has been shown that circulating levels of irisin are low in patients with obesity, diabetes mellitus and impaired glucose tolerance. However, the information about the level of circulating irisin in gestational diabetes mellitus (GDM) is controversial. Material and Methods. Serum irisin was measured by an ELISA in a longitudinal prospective cohort study in 221 women. There were 156 healthy pregnant and 65 women with GDM. Results. Circulating irisin levels were significantlly higher in the middle pregnancy compared with early pregnancy levels in healthy pregnant women and in women with GDM. Serum irisin levels were found to be lower in GDM compared to healthy pregnant women during first trimester but the difference was not observed throughout the pregnancy and it was comparable in middle pregnancy. There was a significant inverse correlation of BMI with serum irisin (r = -0.193, p = 0.004) and between HbA1c and mean glucose of OGTT with serum irisin (r =-0.377, p =0.0001) and (r = -0.147, p:0.03) in the early pregnancy of pregnant women repectively. Conclusions. The present study shows that serum irisin level increases throughout the gestational period from early to middle pregnancy in women with GDM, but there is no effect of irisin on the development of GDM.