Showing papers in "international journal of endocrinology and metabolism in 2019"

Cardiovascular and Renal Benefits of SGLT2 Inhibitors: A Narrative Review

Abstract: Context Most recently developed anti-hyperglycemic drugs have offered cardiovascular and renal benefits. In this narrative review, we discuss the cardiovascular and renal benefits of novel antidiabetic drugs, sodium glucose cotransporter type 2 (SGLT2) inhibitors, in type 2 diabetes. Evidence acquisition The literature published in PubMed, Scopus, Web of Science, Google Scholar, and Cochrane library were reviewed up to January 2019. The keywords including SGLT2 inhibitor, type 2 diabetes, cardiovascular effect, and renal effect were used in different combinations. Results Cardiovascular disease represents a large health burden in patients with diabetes. The prevention of cardiovascular events is a major concern in the treatment of patients with diabetes. Diabetes is also associated with an increased risk of adverse renal events and diabetic nephropathy is the leading cause of end-stage renal disease worldwide. SGLT2 inhibitors as new glucose-lowering agents act by inhibiting glucose reabsorption in the proximal tubule of the kidney, which is independent of insulin secretion. We reviewed the cardiovascular effects of these drugs including effects on triple MACE (major adverse cardiovascular events), myocardial infarction, heart failure, cardiovascular and all-cause mortality, and stroke, as well as renal effects including albuminuria, serum creatinine, the rate of renal replacement therapy, and renal function over time, along with the mechanisms of these effects. Conclusions Given the suboptimal glycemic and cardiovascular risk control in type 2 diabetes, novel therapies such as SGLT2 inhibitors seem to have an important clinical advantage to improve glycemic control and cardiovascular and renal outcomes.

Effects of Daily Consumption of Cashews on Oxidative Stress and Atherogenic Indices in Patients with Type 2 Diabetes: A Randomized, Controlled-Feeding Trial.

Abstract: Background Cashews, as the main source of monounsaturated (MUFAs) and polyunsaturated (PUFAs) fatty acids, are associated with reduced risk of cardiovascular diseases. Despite evidence for beneficial effects of nuts on lipid profile and glycemic control, to the authors' best knowledge, little is known about cashews. Methods An eight-week, randomized, isocaloric, controlled-feeding study was conducted on 50 patients with type 2 diabetes mellitus (T2DM) randomly assigned to either the control or intervention group (10% of total calorie from cashews). Weight, fasting plasma glucose (FPG), serum insulin concentration and sensitivity, lipid profile ratio, high-sensitive C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) were measured at baseline and after eight weeks of intervention adjusted for age, gender, baseline values of FPG, insulin, HOMA-IR (homeostatic model assessment of insulin resistance), fiber, and both baseline and post-intervention vitamin C levels as covariates. Results Weight, body mass index (BMI), and waist circumference (WC) were not significantly different in the groups after eight weeks of intervention, as well as between the two groups, compared with the baseline measures. At the end of the study, serum insulin and low-density lipoprotein-cholesterol-to-high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratio significantly decreased in the cashews group compared with those of the controls (P = 0.01 and P = 0.04, respectively). Although, HOMA-IR decreased significantly in the cashews group (P = 0.03), changes were not significant compared with the baseline measures (P = 0.056). Despite more increase in PON-1 activity in the cashews group, the changes were not statistically significant. Conclusions Daily consumption of cashews reduced serum insulin and LDL-C/HDL-C ratio in patients with T2DM. However, further studies with larger sample sizes and more duration are needed to confirm the current study results.

The Influence of Psychological Stress on the Initiation and Progression of Diabetes and Cancer

Abstract: Context: Psychological stress can be considered a risk factor for the initiation and progression of many pathological conditions, including type 1 and 2 diabetes mellitus and cancer. Objectives: The aim of this review article was to evaluate the molecular and cellular mechanisms linking psychological stress to the onset and progression of diabetes and cancer. Evidence Acquisition: The current review was conducted to survey and analyze studies related to the effects of psychological stress on diabetes and cancer. Results: Psychological stress may make individuals prone to the development of diabetes through the impairment of the hypothalamic–pituitary–adrenal (HPA) axis function, sympathetic nerves system (SNS), lipid profile, cytokines balance, renin-angiotensin system (RAS), and insulin signaling pathway. Additionally, psychological stress can contribute to the development of cancer through the perturbation in the HPA axis, SNS function, and cytokines balance. Psychological stress is also capable of decreasing the levels of oxytocin and dopamine, leading to an increased risk of cancer in susceptible individuals. Conclusions: It seems that psychological stress plays a significant role in the onset and progression of diabetes and cancer. The identification of the pathways triggered by psychological stress would open up a new avenue for the understanding of molecular mechanisms by which diabetes and cancer could be managed or even prevented.

Polycystic Ovary Syndrome in Adolescents: Challenges in Diagnosis and Treatment.

Abstract: Context Despite the importance of timely diagnosis and treatment of polycystic ovary syndrome (PCOS) among adolescent females, considering the paucity of data focusing on this group and controversies documented on its recognition and management, the purpose of this review was to summarize challenges and recommendations of diagnosis and treatment for adolescents with PCOS. Evidence acquisition This review summarizes papers documented on PCOS among adolescent females. PubMed, Scopus, Web of Science, and Google Scholar databases were searched for retrieving studies conducted on PCOS among adolescent females up to March, 2019. The final selection of papers was made based on their relevancy with the fields of diagnosis and treatment of PCOS in this age group. Results Oligo-anovulation in adolescents, if persistent, is a matter for concern. Hirsutism and moderate to severe acne in adolescent females should be considered as clinical manifestations of hyperandrogenism (HA). Diagnosis of biochemical HA in adolescents with PCOS requires reliable tests using well-defined normal ranges. In adolescent females, an elevated androgen level (hyperandrogenemia) alone is not enough to detect HA, unless it is persistent and associated with anovulation. Metabolic disorders should not be used as diagnostic criteria of PCOS among adolescent females. Re-assessment of all adolescent females with probable PCOS, using reliable diagnostic criteria, is needed to avoid over diagnosis and unnecessary treatment in healthy normal females without HA. In adolescent females with PCOS, the main clinical problem is the control of menstrual irregularity and hirsutism; treatment approaches for these patients are primarily directed at the major clinical manifestations and complaints. Lifestyle modifications are baseline interventions, which can be added to special treatments, such as Oral Contraceptives (OCs), metformin, or antiandrogens for most adolescents with PCOS, particularly those with overweight or obesity. Conclusions This review emphasizes the use of standard diagnostic criteria for PCOS, developed for adolescents. Although early recognition and management of PCOS in adolescents can prevent long-term complications associated with this syndrome, clinicians should re-evaluate all such patients with features very similar to PCOS to avoid over/incorrect diagnosis using precise criteria, suggested for this age group.

Clinical Trials in Management of Anaplastic Thyroid Carcinoma; Progressions and Set Backs: A Systematic Review.

Abstract: Context: Anaplastic thyroid carcinoma (ATC) is associated with rapid tumor growth and extremely poor prognosis. Although ATC is found in only 2% of all thyroid carcinomas, it accounts for up to 50% of thyroid cancer mortality. Objective: To understand the effect of different treatment modalities upon anaplastic thyroid cancer outcomes. Methods: A systematic review of studies from 1995 to 2017 was performed employing the search terms “anaplastic thyroid” and “treatment” in PubMed. Studies comparing patients receiving any type of therapy for ATC and measuring either survival as primary outcome or the percentage of patient surviving more than 1 year as secondary outcome were included for review. We did not limit sample size or subject condition. A total of 40 articles were returned from our database search, of which 25 met the inclusion criteria. Results: A review of the 25 published studies indicated that early multidisciplinary approaches using extensive radical surgery, in combination with adjuvant chemo-radiation using either docetaxel/pacitaxel or cisplatin, provided the best chance of disease control. Targeted multi-tyrosine kinases inhibitors helped to limit disease progression. Also, the finding of foci of differentiated thyroid cancer within the anaplastic tumor was associated with increased long-term survival. Conclusions: ATC remains a fatal disease. Despite aggressive therapy the median survival has not significantly changed over the last 20 years. However, the percentage of patients surviving longer than 1 year continues to increase. Novel approaches incorporating multiple targeted therapy and immune therapies are critically needed.

The Principles of Biomedical Scientific Writing: Results.

Abstract: The "results section" of a scientific paper provides the results related to all measurements and outcomes that have been posted earlier in the materials and methods section. This section consists of text, figures, and tables presenting detailed data and facts without interpretation and discussion. Results may be presented in chronological order, general to specific order, most to least important order, or may be organized according to the topic/study groups or experiment/measured parameters. The primary content of this section includes the most relevant results that correspond to the central question stated in the introduction section, whether they support the hypothesis or not. Findings related to secondary outcomes and subgroup analyses may be reported in this section. All results should be presented in a clear, concise, and sensible manner. In this review, we discuss the function, content, and organization of the "results section," as well as the principles and the most common tips for the writing of this section.

The Principles of Biomedical Scientific Writing: Title.

Abstract: The title of a paper is "like a hat on a head or the front door to a house" and its initial impression. Writing a good and effective title makes the paper more retrievable by search engines and maximizes its impact in the scientific community. The paper's title presents what has been studied, how it has been done, and what are the major results. A well-written title is balanced for being informative and concise, as well as attractively conveying the main topic, highlighting the importance of the study. For writing a good title, it should be drafted correctly, accurately, carefully, and meticulously by the main study keywords. By removing extra and unspecific words, the final title should be unambiguous, memorable, captivating, and informative. Here, we provided an overview of the importance and function of the title as well as different types of titles in scientific medical writing. We also focused on the content and organization of the title of a hypothesis-testing paper. In addition, the features of a good title were discussed.

Data Extraction from Graphs Using Adobe Photoshop: Applications for Meta-Analyses.

Abstract: Graphs, an effective form of data presentation, are used for summarizing complex information and making them easier to understand. Extracting numerical data from graphs, which is commonly required in systematic reviews and meta-analyses, is however a challenging issue. Since this kind of results presentation is common, ignorance of such data may result in publication bias when conducting meta-analyses. On the other hand, contacting the authors of a particular publication in order to retrieve the data may take a long time and is often not very fruitful. In this case, there are a few software and methods that may be used for data extraction; however, using these software is costly and not simple as well as different types of graphs need different extraction methods. Here, we have described a simple reproducible method for extracting data from graphs using Adobe Photoshop.

Gestational Diabetes Mellitus Regulatory Network Identifies hsa-miR-145-5p and hsa-miR-875-5p as Potential Biomarkers.

Abstract: Background Gestational diabetes mellitus (GDM) is pregnancy-related diabetes with vital risks for both mother and the fetus. Molecular studies represent one of the popular approaches for investigating mechanisms associated with the disease nature. One of which is through interaction network analysis via Cytoscape V. 3.6.1. Methods In this study, the microRNA (miRNA) expression array of GSE98043 from gene expression omnibus (GEO) database was retrieved and screened. We identified 12 differentially expressed (DE) miRNAs (P ≤ 0.05) and nine target hub-bottleneck genes (disease score > 1) for GDM based on miRNA-target interactions created via plugin ClueGO + Cluepedia + STRING. Results MiRNA-target information showed that the miRNAs are mostly up-regulated and hsa-miR-145-5p and hsa-miR-875-5p targets the most genes. Among target genes, IL6, GCG, APOB, and ALB have the highest associations with DE-miRNAs. Gene ontology analysis based on biological processes identification via ClueGO + CluePedia, in addition, showed that target hub-bottlenecks are mainly related to metabolism functions and any changes in this regulatory network could impose fundamental alterations in these processes. Conclusions It can be concluded that via these introduced miRNAs and their targets, the molecular tests for diagnosis and treatment of GDM can be improved after applying validation approaches.

The Principles of Biomedical Scientific Writing: Discussion.

Abstract: The discussion section of a scientific paper is supposed to interpret and elucidate the significance of the study findings, highlight current knowledge available on the research problem being investigated, and explain the novel aspects emerging from the findings of the study in moving the field forward. A well-written discussion should provide clear "statements of the main findings", "possible explanations and implications", "strengths and weaknesses of the study and other studies", "unanswered questions", and "suggestions for future research". The authors also need to clarify the external validity of the findings and show how the findings can be generalized. In this review, we focus on the function, content, and organization of the "discussion section" of a hypothesis-testing paper. Beyond providing the most important principles and common strategies for organizing the discussion section, we also discuss metadiscourse, scientific explanation (reasoning and contextualization), and models of scientific explanation.

Serum Uric Acid Status and Its Association with Bone Mineral Density in the Elderly People Aged 60 Years and More

Abstract: Background Osteoporosis is associated with decreased antioxidant defenses and serum uric acid (UA) as an antioxidant may exert a protective effect on bone mass. Objectives This study aimed to determine the association between serum UA and bone mineral density (BMD) in the elderly population. Methods All participants of the Amirkola Health and Ageing Project aged ≥ 60 years entered the study. BMD in the femoral neck (FN-BMD) and lumbar spine (LS-BMD) was determined by dual energy X-ray absorptiometry and osteoporosis was defined as BMD T-score 7 mg/dL. In statistical analysis, the value of BMD as well as frequency of osteoporosis in each subgroup were compared with the control group (UA Results A total of 1080 patients were studied. By increasing serum UA from 7 mg/dL the BMD at both measurement sites increased as well. The serum UA was associated with decreased risk of osteoporosis. In multivariate analysis, the odds of osteoporosis in the subgroup with serum UA levels between 4 - 4.99 mg/dL was significantly lower than the control group (OR = 0.66, 95% CI, 0.44 - 0.99). Age and female sex were associated with increased odds of osteoporosis (OR = 1.08, 95% CI, 1.05 - 1.10 and OR = 10.62, 95% CI, 7.53 - 14.97 respectively). Conclusions These findings indicate a negative association between serum UA and osteoporosis in the elderly population aged ≥ 60 years.

Vitamin D Increases Glucose Stimulated Insulin Secretion from Insulin Producing Beta Cells (INS1E).

Abstract: Background: Vitamin D affects the pancreatic beta cell function and in vitro studies have shown that vitamin D may influence insulin secretion, apoptosis, and gene regulation. However, the outcomes have differed and there has been uncertainty regarding the effect of different vitamin D metabolites on insulin secretion. Objectives: We hypothesized that vitamin D could increase insulin secretion in insulin producing beta cells and investigated the effect of 25(OH) vitamin D and 1,25(OH)2 vitamin D on insulin secretion. Methods: The study was conducted in INS1E cells, an established insulinoma cell line from rat. The cells were divided into three groups; a control group, a group with 1,25(OH)2 vitamin D enriched medium (10 nM), and a group with 25(OH) vitamin D (10 nM) supplemented medium. After 72 hours of treatment, the cells underwent glucose stimulation at different concentrations (0, 5, 11, and 22 mM) for 60 minutes. Results: INS1E cells treated with 1,25(OH)2 vitamin D showed a trend towards increased insulin secretion at all glucose concentrations compared to control cells and at 22 mM glucose, the difference was significant (18.40 +/- 1.97 vs 12.90 +/- 2.22 nmol/L, P < 0.05). However, pretreatment with 25(OH) vitamin D did not show any significant increase in insulin secretion compared to cells without vitamin D treatment. There was no difference in insulin secretion in cells not stimulated with glucose. Conclusions: Treatment with 1,25(OH)2 vitamin D combined with high levels of glucose increased insulin secretion in INS1E cells, whereas 25(OH) vitamin D had no effect. This suggests that glucose stimulated insulin secretion in INS1E beta cells appears to be related to the type of vitamin D metabolite treatment.

Association of Circulating Branched-Chain Amino Acids with Gestational Diabetes Mellitus: A Meta-Analysis.

Abstract: Context: Recently, the relationship between branched-chain amino acids (BCAAs) and diabetes mellitus (DM) has attracted worldwide attention. However, the results related to plasma BCAAs concentrations and gestational diabetes mellitus (GDM) lack statistical power due to the small sample size of a single article. Objectives: This study quantitatively summarized current observational studies to evaluate the association between plasma BCAAs concentration levels and GDM. Methods: A systematic search was performed to select eligible publications using PubMed and EMBASE databases until July 23, 2018. The references of relevant articles were also manually searched. The quality evaluation of included studies was according to the guidelines of the Newcastle-Ottawa Scale (NOS). Data were analyzed with Review Manager 5.3 and STATA 14.0 software. In total, seven articles (including eight studies) involving 432 subjects were included. Results: The results showed that all three-individual plasma BCAAs concentration levels in the GDM group were higher than those in the control group (leucine: SMD = 3.76, 95% CI: 1.70 - 5.82, P (SMD) < 0.001; isoleucine: SMD = 3.15, 95% CI: 1.42 - 4.87, P (SMD) < 0.001; valine: SMD = 2.77, 95% CI: 1.21 - 4.32, P (SMD) = 0.001), and the differences were statistically significant. In addition, subgroup analysis indicated that age, body mass index (BMI), publication year, and ethnicity were positively associated with plasma BCAAs concentrations in GDM. Conclusions: Plasma BCAAs, as potential biomarkers, might be associated with GDM risk, which provides useful information for the prevention and early diagnosis of GDM.

Systemic Thyroid Hormone Status in Treated Graves' Disease.

Abstract: Objectives: We aimed to compare the markers of thyroid hormone status in treated euthyroid Graves’ patients and levothyroxine (LT4)-treated hypothyroid Graves’ patients. Methods: We collected the data of 277 patients, including 140 radioiodine-treated hypothyroid Graves’ patients on LT4 treatment (group 1), 83 euthyroid Graves’ patients on methimazole (MMI) therapy (group 2), and 54 euthyroid Graves’ patients off MMI or radioiodine therapy for > 2 years (group 3). After the exclusion of diabetic patients, 130, 73, and 52 patients remained for analysis in groups 1, 2, and 3, respectively. Pearson and Spearman correlation coefficients were employed to assess the relationships between T3:T4 ratio and variables in each group along with univariate and multivariate linear regression models. Results: The mean age and female/male ratio were similar in the three groups. Serum fT4 was significantly higher and T3, TSH, TPOAb, and TRAb were significantly lower in group 1 than in group 2 and combined groups 2 and 3, which translated to 27% lower serum T3:T4 ratio in group 1. Higher BMI, serum cholesterol, and LDL cholesterol and lower HDL cholesterol were observed in group 1 than in combined groups 2 and 3. In multivariate regression analysis, the T3:T4 ratio was significantly higher in combined groups 2 and 3 than in group 1 in the presence of BMI and serum fasting blood glucose, triglycerides, and TSH. Conclusions: Hypothyroid Graves’ patients using LT4 exhibited lower T3:T4 ratio despite lower TSH levels and their BMI and lipid parameters differed from those of euthyroid Graves’ patients.

Orbital Radiotherapy Plus Concomitant Steroids in Moderate-to-Severe Graves’ Ophthalmopathy: Good Results After Long-Term Follow-Up

Abstract: Background Orbital radiotherapy (RT) is an effective and consolidate treatment for steroid-refractory Graves' ophthalmopathy (GO); however, long term effects are not well known. Objectives The aim of this study was to evaluate the long term efficacy and toxicity of orbital RT plus concomitant systemic steroids in a population of patients with moderate-to-severe GO or with eyesight threatening symptoms refractory to steroids. Methods Forty patients with moderate-to-severe GO or with eyesight threatening symptoms not responsive/resistant to steroids were treated with orbital RT at the dose of 20 Gy in 10 fractions plus concomitant steroids. Clinical activity score (CAS) and symptoms status were evaluated to determine response to the treatment. Results We reported overall improvement of symptoms, in particular, a regression at 1-year of diplopia in 32.5% eye movement impairment in 42.5%, eyesight in 27.5% and a 2 point reduction in CAS. After a median time of 56 months 21.9% of the patients underwent orbital decompression for relapse of GO, 4.8% received surgical correction of strabismus, and 2.4% received eyelid lipectomy. Acute toxicity was mild; grade 1 - 2 keratitis occurred in 19.5% of the patients and grade 3 keratitis was observed in 2.4% of the patients. Cataract occurred in 7.4% of the patients after a median time of 24-month-follow-up. No secondary malignancies were reported. Conclusions Our results reported the long-term efficacy and the good tolerance of orbital RT. The combination of RT plus steroids in this setting may avoid or delay performing the surgery in some cases.

The Principles of Biomedical Scientific Writing: Materials and Methods

Abstract: The materials and methods (MM these could help authors effectively prepare the M&M section of a scientific biomedical manuscript.

Effects of Dimethyl Phthalate (DMP) on Serum Sex Hormone Levels and Apoptosis in C57 Female Mice.

Abstract: Background The effects of dimethyl phthalate (DMP) on the reproductive system of mammal females are unclear because no studies have been conducted on this topic. Methods In this study, 40 C57 female mice were used as experimental subjects and evenly divided into 8 groups, which were fed with mixed DMP (0, 0.5, 1, and 2 g/kg bw/day) and corn oil. After 20 days and 40 days of gavage, the mice were weighed and their individual ovary organ coefficients measured. Results Changes were discovered on progesterone, estradiol, follicle-stimulating hormone and luteinizing hormone in mouse serum, and on the apoptosis rate of ovarian granulosa cells. Conclusions Prolonged exposure to DMP led to decreased secretion of FSH hormones and increased secretion of E2 and LH hormones. Furthermore, DMP interfered with the pituitary-ovary axis and increased the apoptosis rate of ovarian granulosa cells. Therefore, prolonged exposure to DMP is likely to have negative effects on reproduction and development.

Sleep Quality and Blood Lipid Composition Among Patients with Diabetes.

Abstract: Background Recent literature has mentioned that people with sleep disorder, experience insulin sensitivity reduction and accordingly higher levels of blood glucose. Objectives This study aimed to investigate the relationship between sleep quality and blood lipid composition in patients with diabetes referring to Minoodar health center in Qazvin, Iran in 2017. Methods Sleep duration and quality were assessed in 347 patients with diabetes using the Pittsburgh sleep quality index (PSQI). The glycosylated hemoglobin A1c (HbA1c) test was used to measure the glycemic control and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) were used to determine blood lipid composition of the patients. Multiple regression analyses were applied to examine the associations between sleep measures and HbA1c and lipid parameters using SPSS version 20. Results The patients in the poor sleep quality group had higher levels of fasting blood sugar (FBS) (146.07 ± 57.06 versus 132.8 ± 53.3 mg/dL, P = 0.02), body mass index (BMI) (29.1 ± 3.9 versus 27.6 ± 4.2 kg/m2, P = 0.005) and total cholesterol (209.9 ± 53.4 versus 193.4 ± 45.8, P = 0.02). Furthermore, the patients with short sleep duration had higher total cholesterol level compared with long sleep and medium sleep duration group (202.3 ± 50.2 versus 196.6 ± 47.7 and 195.7 ± 47.4, respectively, P = 0.05). Among different PSQI measures, subjective sleep quality was associated with lower TC and TG in unadjusted models (β = -0.0.1, P = 0.05). Furthermore, greater sleep disturbance was positively linked with higher levels of TC and TG (β = 0.1, P = 0.01 and β = 0.02, P = 0.05). Conclusions In an Iranian population with diabetes living in Qazvin city, sleep disorder is common and as study findings revealed sleep quality was recognized as an influencing factor on some of the lipid profiles, including TC and TG. Thus sleep assessment of patients with type 2 diabetes to find the early recognition of their sleep disorder should be considered an important part of the patients' treatment.

Age and Gender Specific Thyroid Hormones and Their Relationships with Body Mass Index in a Large Chinese Population.

Abstract: Objectives: To investigate the associations of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) with body mass index (BMI) and the effect of age and gender on these relationships in a large Chinese population. Methods: A total of 97,997 individuals from a health examination center were selected. The medians (25th and 75th) of TSH, FT3 and FT4 were used to explore the trends based on gender, 10-year age groups and BMI. The relationships of TSH, FT3 and FT4 with BMI were assessed by generalized additive models (GAM) along with adjusting the effect of age and gender. Results: After applying our exclusion criteria, 77,991 euthyroid participants (45,428 males and 32,563 females) were analyzed. The medians of TSH level based on BMI groups were significantly higher in female participants than those in males in all age groups (P < 0.05), and the median FT3 level was lower in female subjects; however, there was no significant difference between male and female subjects in median FT4 level. The GAM analysis showed the non-linear positive association of TSH and FT3 with BMI, and these relationships were markedly influenced by age and gender. However, FT4 had a negative relationship with BMI, with neglectable effect of age and gender. Conclusions: TSH, FT3 and BMI have a non-linear and positive quadratic relationship after age and gender adjustment. FT4, however, has a negative non-linear relationship with BMI with neglectable influence of age and gender.

Associations of Ki-67 Labeling Index with Clinical and Paraclinical Features of Growth Hormone-Secreting Pituitary Adenomas: A Single Center Report from Iran

Abstract: Background Acromegaly is a rare disorder resulting from benign growth hormone (GH)-secreting pituitary adenomas in 90% of the cases. In recent years, many researchers have studied the Ki-67 index level of pituitary tumors and its relationship with demographics, biochemical parameters, clinical behavior, and recurrence rate. Objectives This study aimed to evaluate the correlation of Ki-67 index level with clinicoradiological and endocrinological parameters in confirmed GH-secreting pituitary adenomas, as well as with the surgical response and medical treatment after surgery. Methods We collected the medical and pathologic records of 49 patients with GH-secreting pituitary adenoma who underwent surgeries from 2008 to 2017 in Shariati hospital affiliated to Tehran University of Medical Sciences. Results According to MRI reports, 94% of the tumors were macroadenomas. The MRI findings also revealed the median maximal adenoma diameter of 18.5 mm. About 40% of the patients achieved remission three months after the surgery. Younger patients had a significantly higher Ki-67 index level (P = 0.036). We did not observe any significant difference in the Ki-67 index level regarding gender, tumor type, maximal tumor diameter, tumor invasiveness, tumor secretory type, and remission. Interestingly, the Ki-67 index level was negatively correlated with the insulin-like growth factor-1 (IGF-1) level at the last follow-up (P = 0.02). In logistic regression analysis, patients with higher preoperative GH serum levels had a better outcome. Conclusions Our results indicated a negative correlation between age and Ki-67 index level. However, there was no association between the Ki-67 index level and some tumor behaviors, as well as short- and long-term remission.

Toward Ultimate Care for Graves' Hyperthyroidism.

Abstract: Nowadays, throughout the world a majority of patients with Graves’ hyperthyroidism are treated with antithyroid drugs (ATDs) (1, 2); however, hyperthyroidism recurs in almost 20% 70% of patients following discontinuation of medical treatment (3). The 2016 American Thyroid Association (3) and 2018 European Thyroid Association (4) guidelines have recommended that patients with recurrence of Graves’ hyperthyroidism, after the conventional 12 to 18-month ATD therapy, should undergo an ablation treatment with radioactive iodine (RAI) or thyroidectomy. Moreover, findings of the 2010 Cochrane review (5) underscoring the limited number of trials comparing ATD treatment < 12 months versus > 12 months, led to inclusion of continued long-term ATD therapy based only on patient preference being suggested in these guidelines (3, 4). Unfortunately, after both RAI and thyroidectomy, the hyperthyroid patient may often be faced by another disease i.e. hypothyroidism; in addition, RAI-treated patients may have a higher risk of death from solid cancers (6) and patients undergoing thyroidectomy may be prone to several morbidities and complications (3). Over the past 15 years, a few studies (7-11) and two systematic review/meta-analyses (12, 13) have shown that longterm ATD treatment of patients with Graves’ hyperthyroidism, viz. with methimazole, is effective in the maintenance of euthyroidism for up to 15 years without additional adverse effects. Efficacy and safety of long-term ATD therapy have overall been documented in over 1600 children, adolescents, and adult patients with Graves’ disease (7-11, 14-16). The highest remission rate of Graves’ hyperthyroidism occurs after long-term methimazole therapy; it has recently been reported that 84% of adults and 88% of adolescents with Graves’ disease attain cured 4 years after discontinuation of methimazole (17, 18). We believe that recommendations for conventional ATD treatment for 12 18 months should be revised. Considering the effectiveness of long-term medical therapy along with a rarity of side effects with methimazole, physicians should treat patients with Graves’ hyperthyroidism for a minimum of 5 years, and if needed for many years to come. Further research should focus on the 16% of Graves’ patients who have a relapse of hyperthyroidism after discontinuation of long-term ATD therapy for detection of any factors related to the relapse.

Correlation of C1q/TNF-Related Protein-3 with Cardiac Autonomic Tone and Metabolic Parameters in Obesity.

Abstract: Objectives The current study aimed at investigating the correlation of circulating levels of serum C1q/TNF-related protein-3 (CTRP3) with cardiac autonomic functions and metabolic parameters in obesity. Methods Thirty drug naive subjects newly diagnosed with obesity and body mass index (BMI) 25 - 35 kg/m2 of both genders aged 19 - 40 years, with no associated comorbidity were recruited as cases. Same number of age, gender and socioeconomic status matched subjects with BMI 19 - 23 kg/m2 were taken as controls. Autonomic function test results including heart rate variability (HRV) were recorded in both groups. Serum metabolic parameters -CTRP3, leptin, adiponectin, insulin, blood glucose, glycated hemoglobin (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides were also determined and compared between the groups. Results Significantly lower circulating levels of CTRP3 (P ≤ 0.001) and adiponectin (P = 0.025), and significantly higher mean of BMI (P < 0.001), fasting blood glucose (P < 0.001), LDL-cholesterol (P < 0.05), serum triglycerides (P < 0.001), insulin (P = 0.003), HOMA-IR (homeostasis model assessment of insulin resistance) (P < 0.001), and leptin (P = 0.043) were observed in the group with obesity compared to the controls. CTRP3 levels inversely correlated with serum triglyceride (r = -0.09, P < 0.001), atherogenic index (r = -0.37, P = 0.04), leptin (r = -0.39, P = 0.02), and positively with adiponectin (r = 0.42, P = 0.02) in the group with obesity. Significant reduction in the results of parasympathetic autonomic function tests (pNN50, RMSSD, excitation: inhibition (E:I) ratio, 30:15 ratio, and Valsalva ratio) and an increase in sympathovagal balance (low frequency to high frequency (LF:HF) ratio) was also observed (P < 0.05). CTRP3 levels were also positively correlated with parasympathetic indices (pNN50: r = 0.17, P < 0.05); 30:15 ratio: (r = 0.62, P < 0.01), and inversely correlated with LF: HF ratio (r = -0.35, P < 0.01) in the group with obesity. Conclusions Higher circulating levels of CTRP3 promoted a favorable autonomic and metabolic profile in obesity. Hence, CTRP3 may be considered as a potential novel biomarker to facilitate the prognosis of obesity and its comorbidities.

Comparison of the International Association of Diabetes in Pregnancy Study Group Criteria with the Old American Diabetes Association Criteria for Diagnosis of Gestational Diabetes Mellitus.

Abstract: Objectives: This study aimed to assess the prevalence of gestational diabetes mellitus (GDM) based on two sets of criteria, namely the old criteria suggested in 2009 by the American Diabetes Association and new criteria of the International Association of Diabetes in Pregnancy Study Group. We also evaluated the predictive power of the risk factors of GDM. Methods: Pregnant women from three outpatient clinics in Tehran, Iran, participated in this cross-sectional observational study. During the first perinatal visit, demographic data, medical histories, weight, and height of mothers were recorded. The mother’s fasting glucose and glycosylated hemoglobin were measured. An oral glucose tolerance test was also performed. The prevalence of GDM, based on the two criteria, was estimated and its predictive factors were investigated. Results: Of 1,117 pregnant women, 156 (15.6%) and 71 (7.1%) patients had GDM based on the new and old criteria, respectively. Multivariate analysis showed that older age at pregnancy (OR = 1.05; 95% CI: 1.006 - 1.107; P = 0.03), higher body mass index (OR = 1.2; 95% CI: 1.15 - 1.3; P < 0.001), family history of diabetes (OR = 1.97; 95% CI: 1.11 - 3.5; P = 0.02), and history of macrosomia (OR = 7.8; 95% CI: 1.96 - 30.9; P = 0.004) were independent predictive factors for GDM. Conclusions: Using the new criteria, the prevalence of GDM increases by 2.2 folds compared to the old criteria. Several factors can independently predict the occurrence of GDM.

Cause-Specific Risk Factors of Death in Individuals with Diabetes: A Competing Risks Modeling.

Abstract: Background Diabetes is on the rise worldwide. Objectives This study aimed to evaluate the risk factors of various causes of death in people with type 2 diabetes (T2D). Methods In this cohort study on 2638 people with T2D, we applied cause-specific and sub-distribution hazards models to assess the impact of various factors on the risk of death. Moreover, we plotted a cumulative incidence curve to summarize cumulative failure rates over time. Results About 75% of individuals with T2D died from cardiovascular disease (CVD) and cerebrovascular accidents (CVA). Death from CVD was associated with the increased risk of hypertension (hazard ratio (HR) = 1.83, 95% CI: 1.37 - 2.46), hypercholesterolemia (HR = 1.58, 95% CI: 1.17 - 2.14), and diabetes duration. The risk of death from CVA was related to hypertension (HR = 2.76, 95% CI: 1.67 - 4.55) and hyperglycemia (HR = 4.34, 95% CI: 1.75 - 10.79). The CVA risk in patients with diabetes duration of 10 - 20 years was higher than the risk in patients with diabetes duration > 20 years (diabetes duration of ≤ 10 years as the reference category). Diabetes duration of longer than 20 years was associated with a higher risk of death from cancer (HR = 2.65, 95% CI: 1.05 - 6.68). The risk of death from foot infection and diabetic nephropathy increased in patients with longer diabetes duration after adjustment for sex, age, and body mass index. Conclusions Regardless of the cause, death rates in people with T2D increase over time and risk factors have different impacts on death from each cause. This should be acknowledged in risk management in individuals with T2D.

Assessment of Microvascular Function in Children and Adolescents with Diabetes and Obesity.

Abstract: Background: Endothelial dysfunction (ED) is a marker of vascular damage. Glycated hemoglobin (A1C) predicts vascular complications. The EndoPAT (peripheral arterial tonometry) device calculates the reactive hyperemic index (RHI), a measure of endothelial function. The greater the vasodilation, the higher the RHI. We hypothesized that children with poorly-controlled diabetes mellitus (DM) and non-diabetes mellitus (NDM) obese children have ED. Methods: A cross-sectional study using the EndoPAT device was performed on children with poorly-controlled DM and NDM children. ANOVA, t-test, Mann-Whitney U test, multiple linear regression and Spearman correlation were used. Results: Of 58 children that completed the study (aged 13.1 ± 3.42 years), 33 with type 1 diabetes (T1DM), 8 with type 2 diabetes (T2DM) and 17 were NDM obese children. Eighty-five percent were African-American, 60% were female and 79% entered puberty. The RHI of children with DM (1.42 ± 0.48) versus NDM obese group (1.40 ± 0.34) was not different (P = 0.86) regardless of the type of DM or body mass index. In the DM group, for every 1% increase in latest A1C, the RHI decreased by 0.097 (P = 0.01) after adjusting for age, gender, and type of DM. The RHI of DM patients with latest A1C of < 10% (1.70 ± 0.58) versus those with A1C ≥10% (1.21 ± 0.19) was statistically different (P = 0.02). In the total study population, males had significantly lower RHI (1.28 ± 0.36) when compared to females (1.51 ± 0.46), P = 0.04 but this difference disappeared when considering pubertal status and type of diabetes. Conclusions: Our data showed that patients with poorly-controlled DM as reflected by latest A1C of ≥ 10% had worse endothelial function as reflected by lower RHI score.

Vitamin D Inhibition of TRPV5 Expression During Osteoclast Differentiation.

Abstract: Background Vitamin D is an important steroid that can regulate bone metabolism including osteoclast (OC) differentiation. Transient receptor potential cation channel subfamily V member 5 (TRPV5), is a calcium channel protein involved in OC differentiation. However, the impact of vitamin D on TRPV5 expression during OC differentiation is not clear. Objectives To determine if 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates the expression of TRPV5 during OC differentiation. Methods Bone marrow mononuclear macrophage (BMMs) were induced to differentiate into OC with or without treatment with 10 nM 1,25(OH)2D3. The expression levels of vitamin D receptor (VDR) and TRPV5 were examined. The expression of several OC markers, including tartrate resistant acid phosphatase (TRAP), carbonic anhydrase II (Ca II), cathepsin K (CTSK), and vacuolar-type H+-ATPase (V-ATPase) were also detected. Results We found that the VDR was expressed in murine bone marrow-derived macrophages at the early stage of OC differentiation. TRPV5 expression was increased during OC differentiation, which was down-regulated by 1,25(OH)2D3 after a prolonged exposure. The 1,25(OH)2D3 and TRPV5 inhibitors inhibited OC differentiation. Conclusions 1,25(OH)2D3 can inhibit TRPV5 expression as well as TRPV5 inhibitors during OC differentiation. This suggests that 1,25(OH)2D3 may suppress OC differentiation by inhibiting TRPV5 expression.

Association of Vitamin D Receptor BsmI Gene Polymorphism with BMD Z-Score in Iranian Children and Adolescents (9 - 18 Years Old)

Abstract: Background: The vitamin D receptor (VDR) gene variants are known as the main risk factor for low bone mass. Objectives: In this study, the association of vitamin D receptor genetic variants, BsmI (rs1544410) and FokI (rs2228570), with bone mass in Iranian children and adolescents, was evaluated. Methods: The study population comprised of children and adolescents aged between 9 to 18 years (FokI: 123 boys and 120 girls, BsmI: 108 boys and 110 girls). Vitamin D, calcium, phosphorus, total cholesterol (TC), High-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) concentrations were assayed. Bone mineral density and body composition parameters were measured by the Hologic system DXA. BMD Z-score ≤ -2 was considered as low bone density for chronologic age. PCR-restriction fragment length polymorphism was done for genotyping of BsmI and FokI polymorphisms. The association between VDR variants and bone mineral density was investigated using logistic regression analysis. Results: No significant differences in body composition and biochemical parameters were detected among the evaluated VDR genotypes. For VDR BsmI, the mean values for Z-score of the lumbar spine, neck, inter and total femur was greater in the bb genotype compared to BB and Bb genotypes. Logistic regression analysis revealed a significant association between femoral neck Z-score and VDR BsmI genotypes in an additive genetic model (unadjusted model (P = 0.035; Bb vs. bb), model 1 (adjusted for age and sex, P = 0.021; Bb vs. bb), model 2 (adjusted for age, sex and BMI, P = 0.013; Bb vs. bb) and model 3 (adjusted for age, sex, BMI and puberty, P = 0.011; Bb vs. bb, P = 0.049; BB vs. bb)) and dominant genetic model ((unadjusted model, P = 0.033; BB+Bb vs. bb), model 1 (adjusted for age and sex, P = 0.023; BB+Bb vs. bb), model 2 (adjusted for age, sex and BMI, P = 0.012; BB+Bb vs. bb and model 3 (adjusted for age, sex, BMI and puberty, P = 0.012; BB+Bb vs. bb)). Conclusions: This investigation indicated that VDR BsmI polymorphism may be associated with BMD Z-score of the femoral neck but not the lumbar spine, in Iranian children and adolescents.

Relationships Between Various Components of Metabolic Syndrome and Chronic Kidney Disease in Shiraz, Iran.

Abstract: Background: Chronic kidney disease (CKD) can potentially be associated with metabolic syndrome (MetS). Objectives: We aimed to determine the association of MetS and the number of metabolic syndrome components with the risk of CKD in the Iranian population in southern Iran. Methods: A total of 819 subjects aged 18 - 88 years were enrolled using weight-based random cluster sampling. We constructed a logistic regression model to determine the adjusted odds ratios (ORs) and 95% confidence intervals (CI) of the association of MetS individual components and the number of these components with CKD. Results: The prevalence rate of MetS was 25.9% (30.9% in women and 18.8% in men). CKD was present in 16.6% of the participants (men: 14% and women: 19.4%). The most prevalent component was abdominal obesity (63.6%), followed by low HDL cholesterol (36.7%), high triglyceride level (31.7%), hypertension (25.6%) and high fasting blood sugar (21.9%). Central obesity and low HDL level were observed to be more prevalent among women (P < 0.001). The presence of MetS was associated with CKD with an increased OR for CKD (OR: 3.07, 95% CI 2.09 - 4.50; P < 0.001). The adjusted ORs (95% CI) were 1.189 (0.554 - 2.555), 2.025 (0.990 - 4.141) and 4.769 (2.413 - 9.424) as the number of risk factors increased from 1 to ≥ 3. Individuals with hypertension and abdominal obesity had a higher OR of increased susceptibility to CKD in multivariate analysis. Conclusions: Our study indicated a strong association between CKD and MetS in the Iranian population. It is also suggested that individuals with metabolic risk factors should be detected earlier; they should also undergo multidisciplinary interventions to hinder worsening of the individual components of MetS and development of CKD.

Milk products in the treatment of hypophosphatemic rickets: A pilot study

Abstract: Background Standard treatment of hypophosphatemic rickets (HR) is oral phosphate tablets plus vitamin D. Due to the rapid absorption of phosphate tablets, frequent daily doses are necessary, which is cumbersome and may cause fluctuations in plasma phosphate and risk of secondary hyperparathyroidism. It was hypothesized that phosphate from milk or cheese is less rapidly absorbed, and reduces fluctuations in plasma phosphate. Objectives The current randomized, multiple crossover study aimed at investigating if an equivalent phosphate dose given as milk or cheese is comparable to phosphate tablets in patients with HR. Methods Seven females with HR were included. They went through three different four-day treatment sessions of either oral phosphate tablets consisting of 800 mg elemental phosphorus divided into five doses over the day or an equivalent phosphorus dose ingested as skimmed milk or cheese divided over five daily doses. Blood and urine samples were taken from patients after each treatment session. Except the usual doses of vitamin D, no phosphate or calcium-modifying treatments were allowed. Statistical analyses were performed using mixed models. Results Treatment feasibility was independent of the phosphorus source. The study demonstrated reduced plasma levels of parathyroid hormone (PTH), reduced fluctuations in plasma phosphate and plasma PTH, and reduced renal phosphate excretion when ingesting phosphorus supplementation as milk compared to phosphate tablets. The same trend was observed when administering phosphorus as cheese, though not statistically significant. Conclusions Phosphorus supplements can be administered as phosphate tablets, milk or cheese when given in equimolar doses. The current study findings indicated that milk may be superior to phosphate tablets as the phosphate source in patients with HR.

Human Insulin Versus Insulin Analogues: A True Companion Forgotten

Abstract: Insulin, as the oldest therapeutic agent in the management of diabetes mellitus (DM), has always ranked high among different pharmacologic products in all clinical practice guidelines on standard care of DM. Insulin is the most effective agent for glycemic control and glycated hemoglobin (HbA1c) reduction that can be used in all stages of type 2 DM as monotherapy or combined with other glucose-lowering agents (1, 2). Nowadays, in addition to old human insulin products, several rapidand long-acting insulin analogues as pens are available. Arguments, however, continue about the cost-effectiveness of using these new products with pharmacologic profiles closer to normal physiology (3, 4). Based on the American Diabetes Association algorithm for use of glucoselowering medications in type 2 DM, where cost is a major concern, insulin with the lowest cost would be considered (5). According to the World Health Organization guidelines, in low-resource settings, human insulin products, both short-acting regular insulin and intermediate-acting NPH insulin, are strongly recommended as the insulin of choice in adults with type 1 DM and as the third-line treatment for individuals with type 2 DM; long-acting insulin analogues is suggested for patients with frequent severe hypoglycemia with human insulin (6).