Long noncoding RNAs (lncRNAs) are a group of noncoding RNAs that are longer than 200 nucleotides without protein-coding potential. Becasuse of which these RNAs have no significant protein-coding potential, they were initially considered as “junk-products” of transcription without biological meaning. Nevertheless, recent research advancements have shown that lncRNAs are involved in many physiological processes such as cell cycle regulation, cell apoptosis and survival, cancer migration and metabolism. This review described the function of lncRNAs and the potential underlying mechanism involved in diabetes and diabetic microvascular complications. The roles of lncRNAs in the pathogenesis of type 2 diabetes mellitus have only recently been recognized, involving hepatic glucose production and insulin resistance. We further investigated the mechanisms of lncRNAs in diabetic nephropathy (DN), including the roles of lncRNAs in mesangial cells (MCs) proliferation and fibrosis, inflammatory processes, extracellular matrix accumulation in the glomeruli and tubular injury. We also discussed the potential mechanism of lncRNAs in diabetic retinopathy (DR), including aberrant neovascularization and neuronal dysfunction. This review summarized the current knowledge of the functions and underlying mechanisms of lncRNAs in type 2 diabetes mellitus and related renal and retinal complications. Accumulating evidence suggests the potential of lncRNAs as therapeutic targets for clinical applications in the management of diabetes.

The Japan Associations of Endocrine Surgeons has developed the revised version of the Clinical Practice Guidelines for Thyroid Tumors. This article describes the guidelines translated into English for the 35 clinical questions relevant to the therapeutic management of thyroid cancers. The objective of the guidelines is to improve health-related outcomes in patients with thyroid tumors by enabling users to make their practice evidence-based and by minimizing any variations in clinical practice due to gaps in evidential knowledge among physicians. The guidelines give representative flow-charts on the management of papillary, follicular, medullary, and anaplastic thyroid carcinoma, along with recommendations for clinical questions by presenting evidence on the relevant outcomes including benefits, risks, and health conditions from patients’ perspective. Therapeutic actions were recommended or not recommended either strongly (◎◎◎ or XXX) based on good evidence (😊)/good expert consensus (+++), or weakly (◎, ◎◎ or X, XX) based on poor evidence (😣)/poor expert consensus (+ or ++). Only 10 of the 51 recommendations given in the guidelines were supported by good evidence, whereas 35 were supported by good expert consensus. While implementing the current guidelines would be of help to achieve the objective, we need further clinical research to make our shared decision making to be more evidence-based.

The goal of this study was to review relevant randomized controlled trials in order to determine the clinical efficacy of levothyroxine in the treatment of overt or subclinical hypothyroidism. Using appropriate keywords, we identified relevant studies using PubMed, the Cochrane library, and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through December 2019 were considered for inclusion. For each study, we assessed odds ratios (ORs), mean difference (MD), and 95% confidence interval (95%CI) to assess and synthesize outcomes. We included 25 studies with totally 1,735 patients in the meta-analysis. In the patients with hypothyroidism, compared with L-T4, L-T4 plus L-T3 significantly decreased TSH levels and increased FT3 levels. Compared with placebo, L-T4 significantly increased FT4 levels and decreased TSH levels. In patients with subclinical hypothyroidism, compared with placebo, L-T4 significantly decreased SBP, TSH, T3 and TC and increased FT3 and FT4.

We have previously reported that the creatinine (Cre) to cystatin C (CysC) ratio is associated with height-adjusted skeletal muscle mass index (SMI). However, weight-adjusted SMI is reported to be a more useful marker of insulin sensitivity than height-adjusted SMI. Thus, we hypothesized that the creatinine to (cystatin C × body weight [BW]) relationship (Cre/[CysC × BW]) might be associated with weight-adjusted SMI. In this cross-sectional study of 169 males and 132 females, a body composition analyzer was used and the weight-adjusted SMI was calculated as (absolute muscle mass [kg]/BW [kg]) × 100. The cut-off of low muscle mass was defined as weight-adjusted SMI <37.0% for males and <28.0% for females. The Cre/(CysC × BW) was correlated with weight-adjusted SMI in both males (r = 0.484, p < 0.001) and females (r = 0.538, p < 0.001). In addition, Cre/(CysC × BW) was associated with weight-adjusted SMI in both males (standardized β = 0.493, p < 0.001) and females (standardized β = 0.570, p < 0.001) after adjusting for covariates. According to the receiver operator characteristic (ROC) curve analysis, the optimal cut-off point of Cre/(CysC × BW) for low muscle mass was 0.0145 (area under the ROC curve [AUC] 0.756 [95% confidence interval {95% CI} 0.644–0.842], sensitivity = 0.96, specificity = 0.47, p < 0.001) in males and 0.0090 (AUC 0.976 [95% CI 0.894–0.995], sensitivity = 1.00, specificity = 0.93, p < 0.001) in females. There is a correlation between Cre/(CysC × BW) and weight-adjusted SMI. The Cre/(CysC × BW) could be a practical screening marker for low muscle mass.

In Japan, primary aldosteronism (PA) is diagnosed if any one of the captopril challenge test (CCT), saline infusion test (SIT), furosemide-upright test (FUP), and oral salt-loading test (OST) is positive. The present study aimed to investigate if parameters of CCT, the safest confirmatory test, could predict decisions of other tests and propose the next test to diagnose PA in CCT-negative patients. In a cross-sectional design, 142 patients, who were referred to our hospital for the scrutiny of PA and underwent at least two confirmatory tests, were enrolled. While 123 patients underwent all of the CCT, SIT, and FUP, the OST was successfully done in only six patients and excluded from further analyses. CCT parameters showing correlations of higher degrees with SIT and FUP parameters were selected, and their powers to predict SIT and FUP decisions were investigated by receiver operating characteristic analyses. Proposals of the next test based on the CCT parameters were validated with SIT and FUP decisions in subsets of CCT-negative patients divided by cut-offs of the CCT parameters. The plasma aldosterone concentration and plasma renin activity 60 min after the load of CCT (CCT60-PAC and CCT60-PRA) were selected, and CCT60-PAC ≤59.0 pg/mL and CCT60-PRA ≥1.05 ng/mL/h could predict negativities of SIT and FUP, respectively, with >95% specificities. Based on the validation, the present study suggested the SIT as the next test to be done if the CCT-negative patient belonged to the subset with CCT60-PAC >59.0 pg/mL and CCT60-PRA ≥1.05 ng/mL/h, otherwise the FUP should be selected.

The treatment of Graves’ hyperthyroidism (GD) complicated with malignancy is challenging, as anti-thyroid thionamide drugs (ATDs) and anti-cancer chemotherapy are both associated with a risk of neutropenia. Treatment with conventional ATDs, radioactive iodine (RAI) or potassium iodide (KI) was attempted in 8 patients with malignancy (34–80 years of age; 2 males and 6 females) in whom GD had been fortuitously diagnosed during a detailed systematic examination. Three patients requiring surgery were initially treated conventionally with methylmercaptoimidazole (MMI), MMI and KI or RAI (group A; one patient each). The patients became euthyroid on days 17–31 and underwent surgery on days 25–47. RAI therapy was administered to one patient after surgery. The patients were then treated with KI during chemotherapy. Five other patients who did not require surgery were initially treated with 100 mg KI monotherapy (group B). The serum free T₄ level declined immediately in all of these patients, and they became euthyroid on days 7–18, remaining almost entirely euthyroid for more than 120 days. Anti-cancer chemotherapy was successfully completed for three of the patients while taking KI, despite the patients experiencing repeated episodes of anti-cancer chemotherapy-induced neutropenia. Our present findings suggest that, in patients with GD and malignancy, MMI + KI or RAI may be required if immediate surgery is scheduled, but KI monotherapy may be worth trying, if anti-cancer chemotherapy is scheduled, thus avoiding the possibility of thionamide-induced neutropenia.

Calcitonin (CT) is a marker for both initial diagnosis and monitoring of patients with residual or recurrent medullary thyroid carcinoma (MTC). In Japan, serum CT had been measured by radioimmunoassay (RIA) until recently. Electrochemiluminescence immunoassay (ECLIA) became commercially available in 2014, and this technique is now the only method used to examine CT concentration. The purposes of this study were to investigate the correlations between the CT concentration measured with ECLIA (ECLIA-CT) and RIA (RIA-CT) and to explore the clinical characteristics of patients with elevated ECLIA-CT. CT concentrations of 348 sera samples from 334 patients with various thyroid disorders including nine MTC were measured using both assays. The correlation analysis revealed an excellent correlation between ECLIA-CT and RIA-CT among the cases with CT level >150 pg/mL by both assays (r_s = 0.991, p < 0.001). However, 63% of all samples exhibited undetectable ECLIA-CT, while their RIA-CTs were measured between 15 and 152 pg/mL. The ECLIA-CTs in all patients who underwent total thyroidectomy for non-MTC showed low concentrations. High ECLIA-CT was observed in patients with MTC or pancreas neuroendocrine tumor. ECLIA-CT was also increased in 14 other male patients with non-MTC, including four with renal failure. Multivariate logistic regression analysis showed that male sex, negative TgAb, and lower estimated glomerular filtration rate were independent factors to predict detectable ECLIA-CT (≥0.500 pg/mL). These results indicate that ECLIA-CT correlates well with RIA-CT in higher range and is affected by sex, TgAb, and renal function.

Chronic restraint stress (CRS) induces insulin-resistant hyperglycemia by inducing injury to the brain neurons in the nucleus tractus solitarius (NTS). However, the CRS mice did not suffer from hypoglycemia. In this study, mice of both CRS and NTS mechanical injury models were induced to investigate whether impaired glucose metabolism has changed upon the extension of the survival time after modeling. Body weight, food and water intake, fasting blood glucose, glucose tolerance, and glucose metabolism related to blood hormone levels were monitored for 12 weeks following the induction of injury. The mice were also administered with insulin intraperitoneally, and the blood glucose and glucagon levels were measured and compared to those in the control mice administered with saline. The results showed that the body weights of CRS-hyperglycemic mice were significantly higher than those in the control group, while the body weights of NTS mechanically injured mice were significantly lower than those in the control group. The food and water intake of both CRS-hyperglycemic and NTS mechanically injured mice were significantly more than those in the control groups. Although the levels of fasting blood glucose and resting serum hormone in the injured mice have returned to normal levels, the utilization of glucose and hypoglycemic counterregulation (the response that raises the blood glucose levels) was impaired in either CRS-hyperglycemic or NTS mechanically injured mice. The blood glucagon levels following insulin administration showed abnormal increase. These findings suggest that the CRS-induced NTS injury resulted not only in early insulin-resistant hyperglycemia but also impaired the ability to raise blood glucose and glucagon levels when blood glucose levels plummet in the later stage.

Vertebral fracture is the most common type of osteoporotic fracture. However, the prevalence of osteoporosis and osteoporotic vertebral fractures were not explored previously in the United Arab Emirates (UAE). This study aims to describe for the first time the demographic and morphological characteristics of patients with fragility vertebral fractures in the UAE through a retrospective review of the medical records of patients with low-trauma vertebral fractures who visited two tertiary centers during 2011–2016. The sex, age at the time of fracture, nationality, body mass index (BMI), and anatomical fracture location were recorded for each patient. Overall, 143 subjects were diagnosed with low-trauma vertebral fractures in the Emirate of Abu Dhabi during 2011–2016. Of these, 98 were women (68.5%) and 45 were men (31.5%). The overall mean patient age at diagnosis was 62.5 years, and almost half were younger than 65 years. Approximately 60% of the patients were UAE nationals. Fifty-one patients (36.7%) were obese (mean BMI: 35.3 kg/m²), and women with vertebral fractures had a significantly higher mean BMI compared with men (p = 0.041). Nearly 40% of men had a normal BMI, compared with 20% of women. Most fractures were compression fractures (77.6%) in the thoracolumbar transition region. In conclusion, patients with fragility vertebral fractures were predominantly female and tended to be overweight or obese, although male patients tended to have a lower BMI than female patients.

This study aims to investigate the prevalence of islet autoantibodies and other organ-specific autoantibodies in type 1 diabetes mellitus (T1DM) patients and characterize their clinical features. Glutamic acid decarboxylase antibody (GADA), insulinoma antigen 2 antibody (IA-2A), zinc transporter 8 antibody (ZnT8A) and tetraspanin7 antibody (TSPAN7A) were assayed by radioligand or luciferase immunoprecipitation system assays in 205 newly diagnosed acute-onset T1DM patients and 170 healthy controls. Other organ-specific autoantibodies, including thyroid peroxidase antibody (TPOA), thyroglobulin antibody (TGA), tissue transglutaminase antibody (tTGA) and 21-hydroxylase antibody (21-OHA), were also measured. The prevalence of GADA, IA-2A, ZnT8A, TSPAN7A, TPOA, TGA and 21-OHA was higher in T1DM patients than in healthy controls. The combinational assay of various islet autoantibodies could increase the frequency of autoantibody positivity in T1DM to 85.4%. GADA+ IA-2A+ T1DM patients preferentially had TPOA and TGA, while IA-2A+ patients often had tTGA. Patients positive for two or more islet autoantibodies often had TPOA and TGA. BMI of multiple islet autoantibody-positive patients was lower than that of patients with single or no islet autoantibodies, and there were no significant differences in C-peptide and glycated hemoglobin between patients positive for islet autoantibodies combined with other organ-specific antibodies and noncombined patients. Younger female patients who were islet autoantibody positive were more likely to have TPOA and TGA. The frequency of Graves’ disease was much higher in T1DM patients than in healthy controls. T1DM usually occurs together with other organ-specific autoantibodies. Measuring of other organ-specific autoantibodies will be beneficial for T1DM patients.