Suppression of BMP signaling restores mitral cell development impaired by FGF signaling deficits in mouse olfactory bulb.

Fibroblast growth factors (FGFs) and bone morphogenic proteins (BMPs) play various important roles in the development of the central nervous system. However, the roles of FGF and BMP signaling in the development of the olfactory bulb (OB) are largely unknown. In this study, we first showed the expression of FGF receptors (FGFRs) and BMP receptors (BMPRs) in OB RGCs, radial glial cells (RGCs) in the developing OB, which generate the OB projection neurons, mitral and tufted cells. When the FGF signaling was inhibited by a dominant-negative form of FGFR1 (dnFGFR1), OB RGCs accelerated their state transition to mitral cell precursors without affecting their transcription cascade and fate. However, the mitral cell precursors could not radially migrate to form the mitral cell layer (MCL). In addition, FGF signaling inhibition reduced the expression of a BMP antagonist, Noggin, in the developing OB. When BMP signaling was suppressed by the ectopic expression of Noggin or a dominant-negative form of BMPR1a (dnBMPR1a) in the developing OB, the defect in MCL formation caused by the dnFGFR1 was rescued. However, the dnBMPR1a did not rescue the accelerated state transition of OB RGCs. These results demonstrate that FGF signaling is important for OB RGCs to maintain their self-renewal state and MCL formation. Moreover, the suppression of BMP signaling is required for mitral cells to form the MCL. This study sheds new light on the roles of FGFs and BMPs in OB development.

[A Case of Desmoid Fibromatosis of the Small Intestinal Mesentery Institutions].

The patient was a 27-year-old man. He was referred to our hospital because he was aware of a mass in his abdomen. An abdominal ultrasound showed a 70-mm mass lesion. Enhanced computed tomography showed a 70-mm mass with well- defined margins and heterogeneous internal enhancement near the proximal jejunum. The patient was diagnosed with a suspected primary submucosal tumor of the duodenum or small intestine, and surgery was planned to diagnose and treat the tumor. The tumor was located in the upper jejunal mesentery, and tumor resection and partial small bowel resection were performed. Histopathological examination revealed proliferation of spindle-shaped cells without karyomitosis, and mixed collagen fibers in the tissue. Immunohistochemistry showed ß-catenin(+), SMA(+), AE1/AE3(-), KIT(-), CD34(-), and S-100(-). Based on these findings, we diagnosed primary desmoid fibromatosis of the small intestinal mesentery. In this report, we describe a case of primary desmoid fibromatosis of the small intestinal mesentery with a review of the literature.

In Vivo Digestibility of Carbohydrate Rich in Isomaltomegalosaccharide Produced from Starch by Dextrin Dextranase.

Slowly digestible carbohydrates are needed for nutritional support in diabetic patients with malnutrition. They are a good source of energy and have the advantage that their consumption produces a low postprandial peak in blood glucose levels because they are slowly and completely digested in the small intestine. A high-amount isomaltomegalosaccharide containing carbohydrate (H-IMS), made from starch by dextrin dextranase, is a mixture of glucose polymers which has a continuous linear structure of α-1,6-glucosidic bonds and a small number of α-1,4-glucosidic bonds at the reducing ends. It has a broad degree of polymerization (DP) distribution with glucans of DP 10－30 as the major component. In our previous study, H-IMS has been shown to exhibit slow digestibility in vitro and not to raise postprandial blood glucose to such levels as that raised by dextrin in vivo. This marks it out as a potentially useful slowly digestible carbohydrate, and this study aimed to evaluate its in vivo digestibility. The amount of breath hydrogen emitted following oral administration of H-IMS was measured to determine whether any indigestible fraction passed through to and was fermented in the large intestine. Total carbohydrate in the feces was also measured. H-IMS, like glucose and dextrin, did not result in breath hydrogen excretion. Carbohydrate excretion with dietary H-IMS was no different from that of glucose or water. These results show that the H-IMS is completely digested and absorbed in the small intestine, indicating its potential as a slowly digestible carbohydrate in the diet of diabetic patients.

Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons.

Chronic olfactory inflammation (COI) in conditions such as chronic rhinosinusitis significantly impairs the functional and anatomical components of the olfactory system. COI induced by intranasal administration of lipopolysaccharide (LPS) results in atrophy, gliosis, and pro-inflammatory cytokine production in the olfactory bulb (OB). Although chronic rhinosinusitis patients have smaller OBs, the consequences of olfactory inflammation on OB neurons are largely unknown. In this study, we investigated the neurological consequences of COI on OB projection neurons, mitral cells (MCs) and tufted cells (TCs). To induce COI, we performed unilateral intranasal administration of LPS to mice for 4 and 10 weeks. Effects of COI on the OB were examined using RNA-sequencing approaches and immunohistochemical analyses. We found that repeated LPS administration upregulated immune-related biological pathways in the OB after 4 weeks. We also determined that the length of TC lateral dendrites in the OB significantly decreased after 10 weeks of COI. The axon initial segment of TCs decreased in number and in length after 10 weeks of COI. The lateral dendrites and axon initial segments of MCs, however, were largely unaffected. In addition, dendritic arborization and AIS reconstruction both took place following a 10-week recovery period. Our findings suggest that olfactory inflammation specifically affects TCs and their integrated circuitry, whereas MCs are potentially protected from this condition. This data demonstrates unique characteristics of the OBs ability to undergo neuroplastic changes in response to stress.

Expression of Maf family proteins in glutamatergic neurons of the mouse olfactory bulb.

The fate of neurons in the developing brain is largely determined by the combination of transcription factors they express. In particular, stem cells must follow different transcriptional cascades during differentiation in order to generate neurons with different neurotransmitter properties, such as glutamatergic and GABAergic neurons. In the mouse cerebral cortex, it has been shown that large Maf family proteins, MafA, MafB and c-Maf, regulate the development of specific types of GABAergic interneurons but are not expressed in glutamatergic neurons. In this study, we examined the expression of large Maf family proteins in the developing mouse olfactory bulb (OB) by immunohistochemistry and found that the cell populations expressing MafA and MafB are almost identical, and most of them express Tbr2. As Tbr2 is expressed in glutamatergic neurons in the OB, we further examined the expression of glutamatergic and GABAergic neuronal markers in MafA and MafB positive cells. The results showed that in the OB, MafA and MafB are expressed exclusively in glutamatergic neurons, but not in GABAergic neurons. We also found that few cells express c-Maf in the OB. These results indicate that, unlike the cerebral cortex, MafA and/or MafB may regulate the development of glutamatergic neurons in the developing OB. This study advances our knowledge about the development of glutamatergic neurons in the olfactory bulb, and also might suggest that mechanisms for the generation of projection neurons and interneurons differ between the cortex and the olfactory bulb, even though they both develop from the telencephalon.

Incidental Bladder Cancer Found on Cystoscopy during Prostate Biopsy: Prevalence, Pathological Findings, and Oncological Outcome.

INTRODUCTION: We examined the prevalence, pathological findings, and oncological outcomes of incidental bladder cancer found on cystoscopy among patients eligible for prostate biopsy (PB). METHODS: We retrospectively reviewed 803 patients who underwent cystoscopy prior to PB between January 2010 and September 2020. In cases of bladder tumor-like findings on cystoscopy, biopsy or transurethral resection of the bladder tumor was performed. The primary and secondary outcomes were the prevalence of incidental bladder cancer and pathological and oncological outcomes of incidental bladder cancer, respectively. RESULTS: Incidental findings were observed in 31/803 patients (3.9%). Bladder tumor-like findings were found in 24/803 patients (3%), while 9/803 patients (1.1%) were pathologically diagnosed with urothelial carcinoma. The stage and grade of incidental bladder cancer were pTa in 8/9 patients and pT1 in 1/9 and low grade in 8/9 and high in 1/9, respectively. The median tumor size of the papillary pedunculated type was 0.5 cm. At 26-month median follow-up, no recurrence was observed. CONCLUSION: Cystoscopy during PB may yield incidental bladder cancer findings, although the prevalence is very low. Incidental bladder cancer was of low stage and grade, which seemed unrelated to survival. Moreover, performing routine cystoscopy in conjunction with PB is not recommended as it may lead to overdiagnosis of low-risk bladder cancer.

Positive Culture Prior to Transperineal Prostate Biopsy Was Not Associated with Post-Biopsy Febrile Urinary Tract Infection Development.

PURPOSE: To investigate the association between urine culture before transperineal prostate biopsy and post-biopsy febrile urinary tract infection (fUTI). PATIENTS AND METHODS: We retrospectively reviewed 307 patients who underwent urine culture before transperineal prostate biopsy between April 2017 and September 2020. Patients with indwelling urinary catheters (n=7) were excluded. Urine culture was performed 1-3 days before the biopsy, and all patients received prophylactic cefazolin regardless of culture results. A urine culture was defined as positive if cell density was more than 1×105 colony-forming units per mL. Baseline characteristics and the incidence of post-biopsy fUTI were compared between patients showing positive pre-biopsy culture results and those showing negative findings. RESULTS: Out of 300, seven patients (2.3%) had positive urine culture results before the biopsy. Age (p=0.077); prostate-specific antigen at diagnosis (p=0.267); prostate volume (p=0.78); number of biopsy cores (p=0.277); percentage of patients testing positive for cancer on biopsy (p=0.71); and percentages of patients with a history of biopsy (p>0.999), diabetes mellitus (p=0.604), and immunosuppressive medication use (p>0.999) were similar between the two groups. No patient in the positive urine culture group had post-biopsy fUTI. However, 1.7% (five patients) of the negative urine culture group had the disease (p>0.999) (four patients with prostatitis and one with pyelonephritis). Among them, two patients were diagnosed by urine culture at the time of post-biopsy fUTI. CONCLUSION: In asymptomatic patients, positive pre-biopsy cultures were not associated with the development of post-biopsy fUTI.

Bihormonal dysregulation of insulin and glucagon contributes to glucose intolerance development at one year post-delivery in women with gestational diabetes: a prospective cohort study using an early postpartum 75-g glucose tolerance test.

Gestational diabetes mellitus (GDM) is known to be a significant risk factor for the future development of type 2 diabetes. Here, we investigated whether a precise evaluation of ß- and α-cell functions helps to identify women at high risk of developing glucose intolerance after GDM. Fifty-six women with GDM underwent a 75-g oral glucose tolerance test (OGTT) at early (6-12 weeks) postpartum. We measured their concentrations of glucose, insulin, proinsulin and glucagon at fasting and 30, 60 and 120 min. At 1-year post-delivery, we classified the women into a normal glucose tolerance (NGT) group or an impaired glucose tolerance (IGT)/diabetes mellitus (DM) group. Forty-three of the 56 women completed the study. At 1-year post-delivery, 17 women had developed IGT/DM and 26 women showed NGT. In the early-postpartum OGTTs, the IGT/DM group showed a lower insulinogenic index, a less glucagon suppression evaluated by the change from fasting to 30 min (ΔGlucagon 30 min), and a higher glucagon-to-insulin ratio at 30 min compared to the NGT group. There were no significant between-group differences in proinsulin levels or proinsulin-to-insulin ratios. Insulinogenic index <0.6 and ΔGlucagon 30 min >0 pg/mL were identified as predictors for the development of IGT/DM after GDM, independent of age, body mass index, and lactation intensity. These results suggest that the bihormonal disorder of insulin and glucagon causes the postpartum development of glucose intolerance. The measurement of plasma insulin and glucagon during the initial OGTT at early postpartum period can help to make optimal decisions regarding the postpartum management of women with GDM.

A single-arm, open-label, intervention study to investigate the improvement of glucose tolerance after administration of the 5-aminolevulinic acid (5-ALA) in the patients with mitochondrial diabetes mellitus.

BACKGROUND: Mitochondrial diabetes mellitus (MDM) is characterized by maternal inheritance, progressive neurosensory deafness, insulin secretory disorder, and progressive microvascular complications. Mitochondria are critical organelles that provide energy in the form of adenosine triphosphate (ATP). An impairment of ATP production in pancreatic ß cells is regarded as the main cause of the insulin secretory disorder in patients with MDM, and these patients require insulin replacement therapy early after the diagnosis. The amino acid 5-aminolevulinic acid (5-ALA), a precursor of heme metabolites, is a non-proteinogenic δ amino acid synthesized in mitochondria. An addition of ferrous iron to 5-ALA enhances heme biosynthesis and increases ATP production through an upregulation of the respiratory complex. Several studies have reported that the administration of 5-ALA and ferrous iron to existing treatment improved the glycemic control in both patients with prediabetes and those with type 2 diabetes mellitus. The additional administration of 5-ALA and ferrous iron to MDM patients on insulin therapy may improve their insulin secretory capacity and glycemic control by improving their mitochondrial function. The findings of this study are expected to provide new treatment options for MDM and improve the patients' glycemic control and prognosis. METHODS/DESIGN: This study is a single-arm, open-label pilot intervention study using clinical endpoints to investigate the effects of treatment with 5-ALA plus sodium ferrous citrate (SFC) to patients with MDM on their glucose tolerance. A total of 5 patients with MDM will be administered 5-ALA/SFC (200 mg/d) for 24 weeks. We will perform a 75-g oral glucose tolerance test before and at 24 weeks after the start of this 5-ALA/SFC treatment to evaluate glucose-dependent insulin responses. DISCUSSION: To the best of our knowledge, this study will be the first assessment of the effects of 5-ALA/SFC in patients with MDM. This study will obtain an evidence regarding the effectiveness and safety of 5-ALA/SFC for patients with MDM. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN000040581) on July 1, 2020 and with the Japan Registry of Clinical Trials (jRCTs071200025) on August 3, 2020.

The predictive factor for pathological downgrading after prostatectomy in patients with biopsy Gleason score 4+3 or 4+4 prostate cancer.

The proportion of Gleason pattern (GP) 4 prostate cancers at prostate biopsy has a clinically significant impact on risk stratification for patients with prostate cancer. In pathological diagnosis including GP 4, a biopsy Gleason score (GS) of 3+4 has a more favorable prognosis than a GS of 4+3 and 4+4. However, the discrepancy between biopsy and prostatectomy specimens is well known. The current study investigated the clinical parameters and biopsy specimens associated with pathological downgrading after prostatectomy in biopsies with a GS of 4+3 or 4+4 prostate cancer. A total of 302 patients with prostate cancer who underwent robot-assisted radical prostatectomy between August 2013 and May 2019 were retrospectively reviewed. A total of 103 patients had biopsies with GSs of 4+3 and GS 4+4 (unfavorable pathology). The proportion of patients who were downgraded from unfavorable disease to GS ≤3+4 (favorable pathology) in prostatectomy specimens was investigated. Logistic regression analysis was used to explore the association between clinical parameters and downgrading in prostatectomy specimens. A total of 43 patients (41.7%) were downgraded from biopsy GS to prostatectomy GS. The proportions of downgrade in biopsy GS 4+4 and 4+3 were 14.6 and 27.1%, respectively. The percentage of highest GS out of positive biopsy cores and the maximum percentage of cancer involvement within a positive core with the highest GS were lower in the downgrade group than in the no downgrade group (45 vs. 66.7%, P=0.025; 20 vs. 30%, P=0.048, respectively). When performing multivariate logistic regression analysis, the only significant predictor for downgrade was lower percentage of highest GS cores out of positive biopsy cores (odds ratio, 2.469; 95% confidence interval, 1.029-5.925 P=0.043). In conclusion, patients with biopsy GS 4+4 and 4+3 often exhibit a downgrade to GS 3+4 or less in prostatectomy specimens. The lower percentage of highest GS cores out of positive biopsy cores was associated with downgrade.

Impact of glucagon response on early postprandial glucose excursions irrespective of residual ß-cell function in type 1 diabetes: A cross-sectional study using a mixed meal tolerance test.

AIMS/INTRODUCTION: Controlling postprandial glucose levels in patients with type 1 diabetes is challenging even under the adequate treatment of insulin injection. Recent studies showed that dysregulated glucagon secretion exacerbates hyperglycemia in type 2 diabetes patients, but little is known in type 1 diabetes patients. We investigated whether the glucagon response to a meal ingestion could influence the postprandial glucose excursion in patients with type 1 diabetes. MATERIALS AND METHODS: We enrolled 34 patients with type 1 diabetes and 23 patients with type 2 diabetes as controls. All patients underwent a liquid mixed meal tolerance test. We measured levels of plasma glucose, C-peptide and glucagon at fasting (0 min), and 30, 60 and 120 min after meal ingestion. All type 1 diabetes patients received their usual basal insulin and two-thirds of the necessary dose of the premeal bolus insulin. RESULTS: The levels of plasma glucagon were elevated and peaked 30 min after the mixed meal ingestion in both type 1 diabetes and type 2 diabetes patients. The glucagon increments from fasting to each time point (30, 60 and 120 min) in type 1 diabetes patients were comparable to those in type 2 diabetes patients. Among the type 1 diabetes patients, the glucagon response showed no differences between the subgroups based on diabetes duration (<5 vs ≥5 years) and fasting C-peptide levels (<0.10 vs ≥0.10 nmol/L). The changes in plasma glucose from fasting to 30 min were positively correlated with those in glucagon, but not C-peptide, irrespective of diabetes duration and fasting C-peptide levels in patients with type 1 diabetes. CONCLUSIONS: The dysregulated glucagon likely contributes to postprandial hyperglycemia independent of the residual ß-cell functions during the progression of type 1 diabetes.

Subpopulations of Projection Neurons in the Olfactory Bulb.

Generation of neuronal diversity is a biological strategy widely used in the brain to process complex information. The olfactory bulb is the first relay station of olfactory information in the vertebrate central nervous system. In the olfactory bulb, axons of the olfactory sensory neurons form synapses with dendrites of projection neurons that transmit the olfactory information to the olfactory cortex. Historically, the olfactory bulb projection neurons have been classified into two populations, mitral cells and tufted cells. The somata of these cells are distinctly segregated within the layers of the olfactory bulb; the mitral cells are located in the mitral cell layer while the tufted cells are found in the external plexiform layer. Although mitral and tufted cells share many morphological, biophysical, and molecular characteristics, they differ in soma size, projection patterns of their dendrites and axons, and odor responses. In addition, tufted cells are further subclassified based on the relative depth of their somata location in the external plexiform layer. Evidence suggests that different types of tufted cells have distinct cellular properties and play different roles in olfactory information processing. Therefore, mitral and different types of tufted cells are considered as starting points for parallel pathways of olfactory information processing in the brain. Moreover, recent studies suggest that mitral cells also consist of heterogeneous subpopulations with different cellular properties despite the fact that the mitral cell layer is a single-cell layer. In this review, we first compare the morphology of projection neurons in the olfactory bulb of different vertebrate species. Next, we explore the similarities and differences among subpopulations of projection neurons in the rodent olfactory bulb. We also discuss the timing of neurogenesis as a factor for the generation of projection neuron heterogeneity in the olfactory bulb. Knowledge about the subpopulations of olfactory bulb projection neurons will contribute to a better understanding of the complex olfactory information processing in higher brain regions.

Publisher Correction: Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity.

A contribution of epigenetic modifications to B cell tolerance has been proposed but not directly tested. Here we report that deficiency of ten-eleven translocation (Tet) DNA demethylase family members Tet2 and Tet3 in B cells led to hyperactivation of B and T cells, autoantibody production and lupus-like disease in mice. Mechanistically, in the absence of Tet2 and Tet3, downregulation of CD86, which normally occurs following chronic exposure of self-reactive B cells to self-antigen, did not take place. The importance of dysregulated CD86 expression in Tet2- and Tet3-deficient B cells was further demonstrated by the restriction, albeit not complete, on aberrant T and B cell activation following anti-CD86 blockade. Tet2- and Tet3-deficient B cells had decreased accumulation of histone deacetylase 1 (HDAC1) and HDAC2 at the Cd86 locus. Thus, our findings suggest that Tet2- and Tet3-mediated chromatin modification participates in repression of CD86 on chronically stimulated self-reactive B cells, which contributes, at least in part, to preventing autoimmunity.

The effect of luseogliflozin on bone microarchitecture in older patients with type 2 diabetes: study protocol for a randomized controlled pilot trial using second-generation, high-resolution, peripheral quantitative computed tomography (HR-pQCT).

BACKGROUND: Older patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fracture independent of their bone mineral density (BMD), which is explained mainly by the deteriorated bone quality in T2DM compared to that in non-diabetic adults. Sodium-glucose co-transporter (SGLT) 2 inhibitors have been studied in several trials in T2DM, and the Canagliflozin Cardiovascular Assessment Study showed an increased fracture risk related to treatment with the SGLT2 inhibitor canagliflozin, although no evidence of increased fracture risk with treatment with other SGLT2 inhibitors has been reported. The mechanism of the difference in the fracture risk between the SGLT2 inhibitors is unknown, but the differences among the SGLT2 inhibitors in the selectivity of SGLT2 against SGLT1 may affect bone metabolism, since among the SGLT2 inhibitors the selectivity of canagliflozin is lowest. We will investigate whether the SGLT2 inhibitor luseogliflozin, which has the higher SGLT2 selectivity, affects bone metabolism by using high-resolution, peripheral quantitative computed tomography (HR-pQCT) which provides direct in vivo morphometric information about the bone microarchitecture. METHODS/DESIGN: This is a single-center, randomized, open-label, active-controlled, parallel pilot trial. Eligible participants are older (age ≥ 60 years) individuals with T2DM with HbA1c levels at 7.0-8.9%. A total of 24 participants will be allocated to either the luseogliflozin group (taking luseogliflozin) or the control group (taking metformin) in a 1:1 ratio to compare the groups' changes in bone microarchitecture of the radius and tibia which are analyzed by HR-pQCT before and at 48 weeks after the administration of each medication. The laboratory data associated with glycemic control and bone metabolism will be collected every 12 weeks during the study. Recruitment began in June 2019. DISCUSSION: The reason that we use metformin as an active control is to avoid yielding differences in glycemic control between the luseogliflozin and control groups. Besides, metformin is considered to have a neutral effect on bone. This trial should reveal the effect of luseogliflozin on bone metabolism in older patients with T2DM. TRIAL REGISTRATION: The study was registered with the University Hospital Medical Information Network (UMIN000036202) on 1 April 2019 and with the Japan Registry of Clinicla Trials (jRCTs071180061) on 14 March 2019.

Implication of Perifollicular Clusters and Folliculotropic Distribution of Dendritic Cells in the Pathogenesis of Seborrhoeic Dermatitis.

The pathogenesis of seborrhoeic dermatitis is controversial and remains unclear. Malassezia is considered to be a commensal fungi and is found not only in the stratum corneum but also in hair follicles. It is an important pathogenic factor in seborrhoeic dermatitis. The aim of this study was to clarify the pathogenesis of seborrhoeic dermatitis, morphologically, through comparison with psoriasis vulgaris. Fifteen cases of seborrhoeic dermatitis, 7 of psoriasis, and 6 of normal skin were examined using routine histopathology, immunohistochemistry, and electron microscopy. Macrophages were found to be diffusely distributed in the upper dermis of seborrhoeic dermatitis and psoriasis. In contrast, a significant increase in the number of dendritic cells in the follicular epithelium and dendritic cell clusters in the perifollicular dermis were found only in seborrhoeic dermatitis. Ultrastructural examination of the clusters demonstrated that dendritic cells interacted with lymphocytes, macrophages, and other dendritic cells. In conclusion, folliculotropic distribution of dendritic cells as well as dendritic cell-immune cell clusters play an important role in the pathogenesis of seborrhoeic dermatitis.

VISCERAL AND SUBCUTANEOUS FAT INCREASED AFTER TREATMENT OF GRAVES DISEASE.

Objective: Patients with Graves disease (GD) tend to gain weight after treatment, but it remains unknown if weight gain is associated with an increase in the visceral and/or subcutaneous fat areas (VFA, SFA). Methods: We enrolled 25 newly diagnosed GD patients (22 females, median age 33.0 years) and studied their clinical parameters, and VFA and SFA measured by a dual bioelectric impedance analysis. We divided them into 2 groups based on the rates of change in the VFA and SFA, and we compared clinical parameters at the baseline between the groups to evaluate factors that influence increases in the VFA and/or SFA with treatment. Results: The patients' body weight (BW), VFA, and SFA were significantly increased after a 6-month treatment (BW: from 54.3 ± 10.3 kg to 58.0 ± 11.2 kg; P<.001; VFA: from 47.1 ± 21.3 cm2 to 54.7 ± 23.4 cm2; P = .004; SFA: from 159.8 ± 85.9 cm2 to 182.2 ± 82.9 cm2; P = .008). The percent changes of BW correlated with the SFA (ρ = .591, P = .002), but not with the VFA. The patients with larger VFA increases had significantly less VFA at the baseline compared to those with smaller increases, expressed as median and interquartile range (33.9 cm2 [22.7 to 47.5 cm2] versus 54.5 cm2 [45.2 to 64.0], respectively; P = .011). A larger increase in the SFA was negatively associated with serum alkaline phosphatase. An increase in the SFA was associated with free triiodothyronine (T3) in a multivariate logistic analysis (odds ratio: 0.80 [0.59 to 0.97]; P = .013). Conclusion: The patients' BW, VFA, and SFA were increased after GD treatment. The increase in SFA seemed to contribute to weight gain and was associated with a low baseline level of free T3. Abbreviations: ALP = alkaline phosphatase; BMI = body mass index; BW = body weight; GD = Graves disease; SFA = subcutaneous fat area; T3 = triiodothyronine; T4 = thyroxine; TG = triglycerides; VFA = visceral fat areas.