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International Journal of Endocrinology publishes original research articles, review articles, and clinical studies that provide insights into the endocrine system and its associated diseases at a genomic, molecular, biochemical and cellular level.
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Different Formulations of Levothyroxine for Treating Hypothyroidism: A Real-Life Study
Objective. Hypothyroid patients are treated by sodium levothyroxine (LT4). Tablet is the mostly used LT4 formulation, and the fasting regimen is required for the absorption of active principle. Also, gastrointestinal diseases and drugs may impair the LT4 bioavailability when tablet is used. Nonsolid LT4 formulations (i.e., liquid solution (LS) and soft gel (SG) capsule) were manufactured to overcome the limitations of LT4 tablet. This study was conceived to evaluate the performance of nonsolid LT4 formulations in a real-life scenario. Methods. Two institutions participated in the study that was conducted in two phases (i.e., enrollment and re-evaluation). Adults with autoimmune or postsurgical hypothyroidism and on LT4 from a few months were selected. A nonparametric statistical analysis for paired or unpaired data was performed. Results. 121 consecutive cases were included. At the enrollment phase, a 52% of patients took the therapy at least 30 min before breakfast with no difference between tablet and SG/LS users. TSH was 1.65 mIU/L (0.86–2.70) in patients on LT4 tablet and 1.70 mIU/L (1.10–2.17) in those on SG/LS (). At the re-evaluation phase, among the patients using correct LT4 assumption, the TSH value was stable in the tablet group () and significantly reduced in SG/LS group (); among the patients using incorrect LT4 assumption, TSH was significantly increased in those on tablet () and stable in those on SG/LS (). Conclusion. The performance of nonsolid LT4 formulations is not influenced by correct or incorrect use of therapy. On the contrary, LT4 tablet does not guarantee euthyroidism when it is ingested without waiting for at least 30 minutes before breakfast. These new data, obtained in a real-life scenario, suggest that LT4 SG/LS should be regarded as first-line therapy for treating adults with newly diagnosed hypothyroidism.
Dysregulation in the Unfolded Protein Response in the FGR Rat Pancreas
Accumulating evidence suggests that fetal growth restriction (FGR) leads to the development of diabetes mellitus in adults. The aim of this study was to investigate the effect of protein malnutrition in utero on the pancreatic unfolded protein response (UPR) pathway in FGR offspring. An FGR model was developed by feeding a low-protein diet to pregnant rats throughout gestation. Eighty-four UPR pathway components in the pancreas were investigated by quantitative PCR arrays and confirmed by qPCR and western blotting. Activating transcription factor (Atf4 and Atf6), herpud1, protein kinase R-like endoplasmic reticulum kinase (Perk), X-box binding protein 1 (Xbp1), and the phosphorylation of eIF2α were upregulated, while cyclic AMP-responsive element-binding protein 3-like protein was markedly downregulated in FGR fetuses compared with controls. Investigation in adult offspring revealed temporal changes, for most UPR factors restored to normal, except that dysregulation of Atf6 and Creb3l3 maintained until adulthood. Moreover, autophagy was suppressed in FGR fetal pancreas and may be associated with decreased activation of AMP-activated protein kinase (Ampk). Apoptosis regulators Bax and cleaved-caspase 3 and 9 were upregulated in FGR fetal pancreas. Given that islet size and number were decreased in FGR fetus, we speculated that the aberrant intrauterine milieu impaired UPR signaling in fetal pancreas development. Whether these alterations early in life contribute to the predisposition of FGR fetuses to adult metabolic disorders invites further exploration.
Prevalence of Erectile Dysfunction in Patients with Diabetes Mellitus and Its Association with Body Mass Index and Glycated Hemoglobin in Africa: A Systematic Review and Meta-Analysis
Background. Mortality and morbidity in patients with diabetes mellitus (DM) are attributed to both microvascular and macrovascular complications. However, there is a significant amount of variation in the primary studies on DM regarding the prevalence of erectile dysfunction (ED) in Africa. Therefore, this study was aimed to estimate the pooled prevalence of ED patients with DM and its association with body mass index (BMI) and glycated hemoglobin in Africa. Methods. PubMed, Web of Science, Cochrane Library, Scopus, PsycINFO, African Journals Online, and Google Scholar were searched for studies that looked at ED in DM patients. A funnel plot and Egger’s regression test were used to determine publication bias. The I2 statistic was used to check heterogeneity between the studies. DerSimonian and Laird random-effects model was applied to estimate the pooled effect size. The subgroup and meta-regression analyses were conducted by country, sample size, and year of publication. Sensitivity analysis was deployed to see the effect of a single study on the overall estimation. STATA version 14 statistical software was used for the meta-analysis. Result. A total of 13 studies with 3,501 study participants were included in this study. We estimated that the pooled prevalence of ED in patients with DM in Africa was 71.45% (95% CI: 60.22–82.69). Diabetic patients whose BMI was ≥30 kg/m2 were 1.26 times more likely to develop ED (AOR = 1.26; 95% CI: 0.73–2.16) and whose glycated hemoglobin was <7% were 7% less likely to develop ED (AOR = 0.93; 95% CI: 0.5–5.9), although they were not significantly associated with ED. Conclusions. The prevalence of ED in DM patients in Africa remains high. Therefore, situation-based interventions and country context-specific preventive strategies should be developed to reduce the prevalence of ED among patients with DM.
The Correlation between Hormonal Disturbance in PCOS Women and Serum Level of Kisspeptin
Background. Kisspeptin is a neuropeptide that upregulates gonadotropin-releasing hormone (GnRH) secretion. It is an essential element for the luteinizing hormone (LH) surge and ovulation. Women with polycystic ovary syndrome (PCOS) expose alteration in both GnRH and LH secretion levels. Objective. This paper aims to evaluate serum kisspeptin levels in healthy and polycystic ovarian syndrome women. Furthermore, it investigates the effect of obesity and age on circulating kisspeptin levels in both normal and PCOS women. Moreover, it points out the correlation between kisspeptin and other hormonal parameters. Methods and Patients. One hundred women (60 are with PCOS and 40 are normal) were enrolled in the study. Five milliliter samples of blood from all the patients and control women were obtained twice during the menstrual cycle. All the study samples were classified depending on the age factor for several subgroups. Results. Kisspeptin levels were higher in PCOS patients than those in the normal group. Kisspeptin correlated with serum free testosterone level (). In healthy women, preovulatory kisspeptin levels were higher than follicular kisspeptin levels (), while this difference was insignificant in PCOS patients. The variation in serum kisspeptin levels between overweight/obese and normal-weight women was insignificant. In normal women, serum kisspeptin levels were higher in women >35 years than those <24 years at (). Conclusion. The serum kisspeptin level is higher in PCOS women. Its levels fluctuate during the menstrual cycle, but these fluctuations are disturbed in PCOS women. The effect of BMI on serum kisspeptin levels is insignificant, and kisspeptin serum levels increase with age.
The Accuracy and Precision of the Continuously Stored Data from Flash Glucose Monitoring System in Type 2 Diabetes Patients during Standard Meal Tolerance Test
Background. The purpose of this study was to investigate the accuracy of the continuously stored data from the Abbott FreeStyle Libre flash glucose monitoring (FGM) system in Chinese diabetes patients during standard meal tests when glucose concentrations were rapidly changing. Subjects and Methods. Interstitial glucose levels were monitored for 14 days in 26 insulin-treated patients with type 2 diabetes using the FGM system. Standard meal tests were conducted to induce large glucose swings. Venous blood glucose (VBG) was tested at 0, 30, 60, and 120 min after standard meal tests in one middle day of the first and second weeks, respectively. The corresponding sensor glucose values were obtained from interpolating continuously stored data points. Assessment of accuracy was according to recent consensus recommendations with median absolute relative difference (MARD) and Clarke and Parkes error grid analysis (CEG and PEG). Results. Among 208 paired sensor-reference values, 100% were falling within zones A and B of the Clarke and Parkes error grid analysis. The overall MARD was 10.7% (SD, 7.8%). Weighted least squares regression analysis resulted in high agreement between the FGM sensor glucose and VBG readings. The overall MTT results showed that FGM was lower than actual VBG, with MAD of 22.1 mg/dL (1.2 mmol/L). At VBG rates of change of -1 to 0, 0 to 1, 1 to 2, and 2 to 3 mg/dl/min, MARD results were 11.4% (SD, 8.7%), 9.4% (SD, 6.5%), 9.9% (SD, 7.5%), and 9.5% (SD, 7.7%). At rapidly changing VBG concentrations (>3 mg/dl/min), MARD increased to 19.0%, which was significantly higher than slow changing BG groups. Conclusions. Continuously stored interstitial glucose measurements with the FGM system were found to be acceptable to evaluate VBG in terms of clinical decision during standard meal tests. The continuously stored data from the FGM system appeared to underestimate venous glucose and performed less well during rapid glucose changes.
The Association of Autoimmune Diseases with Type 1 Diabetes Mellitus in Children Depends Also by the Length of Partial Clinical Remission Phase (Honeymoon)
Type 1 diabetes mellitus (DM) is characterized by irreversible, autoimmune, pancreatic β-cell destruction. During the disease, some patients experience a phase of Partial Clinical Remission (PCR) known as “honeymoon.” This is a transitory period that is characterized by insulin production by residual β cells following DM diagnosis and initiating the insulin therapy. In this study, we aimed to evaluate the influence of insulin production on immune system after the onset of diabetes, and we showed that the duration of honeymoon period could be related to the onset of other autoimmune conditions. For this retrospective study, 159 children aged between 11 and 18 years with type 1 DM were eligible. They have been diagnosed diabetes at least 10 years ago and use exogenous insulin. Our results showed that younger age at the onset of Type 1 DM in children, predicts Celiac Disease. Female sex and low HCO3 levels at the onset of DM had a high predictive value on patients who did not experience longer Partial Clinical Remission phase. Patients with higher BMI at the diagnosis of DM experienced shorter honeymoon period than the average. Smaller of our patients who diagnosed just DM have more than 297 days honeymoon period with respect to patients with one associated autoimmune disease. This may be due to a continuous and prolonged stimulation of immune system during the period of honeymoon that predispose the patient to develop other TH1 diseases. The patients who experienced more than 297 days Partial Clinical Remission seem under risk of developing one other autoimmune disease more than the patients who experienced less than 297 days Partial Clinical Remission. We have to consider that this observation is very intriguing because many protocols spring-up to try prolonging the honeymoon period in patients with autoimmune DM. If this aim is important from a metabolic point of view, long follow-ups are needed to be sure that the risk of other autoimmune diseases does not increase.