Malnutrition occurs when nutrient intake is too low for any reason and occurs regardless of gender or age. Therefore, besides loss of eating or digestive functionality due to illness, malnutrition can occur when a healthy individual undergoes an extreme diet and biases their nutrition, or when athletes exerts more energy than they can replenish through food. It has recently been reported that in Japan, the mortality rate of leaner individuals is equal to or higher than that of obese people. It is important to understand what homeostatic maintenance mechanism is behind this when the body is under hypotrophic conditions. Such mechanisms are generally endocranially controlled. We address this fundamental concern in this paper by focusing on peptide hormones. We introduce a mechanism for survival in a malnourished state via the regulation of food intake and temperature. Additionally, we will discuss the latest findings and future prospects for research on changes in the endocrine environment associated with malnutrition associated with exercise. We also review changes in next-generation endocrine environments when caused by malnutrition brought on by dieting.

Previous reports by us and other investigators showed that among athyreotic patients on levothyroxine (LT₄) following total thyroidectomy patients with normal serum thyroid-stimulating hormone (TSH) levels had mildly low serum free triiodothyronine (FT₃) levels, whereas patients with mildly suppressed serum TSH levels had normal serum FT₃ levels and patients with strongly suppressed serum TSH had elevated serum FT₃ levels. The objective of this study was to clarify which of these three patient groups are closer to their preoperative euthyroid condition based on reported subjective symptoms. We prospectively studied 148 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy. Symptoms reflecting thyroid function documented preoperatively and following 12 months of LT₄ after thyroidectomy were compared. In 65 patients with strongly suppressed TSH levels significant changes in symptoms with tendencies towards thyrotoxicosis were seen with regards to heat and cold tolerance (p < 0.01), bowel movements (p < 0.05), and hand tremors (p < 0.05). In 33 patients with normal TSH levels, significant changes in symptoms with tendencies towards hypothyroidism were seen with regards to heat and cold tolerance (p < 0.05) and activity (p < 0.05). Lastly, in 50 patients with mildly suppressed TSH levels and FT₃ levels equivalent to preoperative levels, all symptom items remained equivalent to their preoperative levels. Symptoms reflecting thyroid function in patients on LT₄ following total thyroidectomy suggested that patients with mildly suppressed TSH levels were closest to a euthyroid status. These data provide useful findings regarding the management of patients following total thyroidectomy.

Werner syndrome (WS) is a rare, adult-onset progeroid syndrome. Classic WS is caused by WRN mutation and partial atypical WS (AWS) is caused by LMNA mutation. A 19-year-old female patient with irregular menstruation and hyperglycemia was admitted. Physical examination revealed characteristic faces of progeria, graying and thinning of the hair scalp, thinner and atrophic skin over the hands and feet, as well as lipoatrophy of the extremities, undeveloped breasts at Tanner stage 3, and short stature. The patient also suffered from severe insulin-resistant diabetes mellitus, hyperlipidemia, fatty liver, and polycystic ovarian morphology. Possible WS was considered and both WRN and LMNA genes were analyzed. A novel missense mutation p.L140Q (c.419T>A) in the LMNA gene was identified and confirmed the diagnosis of AWS. Her father was a carrier of the same mutation. We carried out therapy for lowering blood glucose and lipid and improving insulin resistance, et al. The fasting glucose, postprandial glucose and triglyceride level was improved after treatment for 9 days. Literature review of AWS was performed to identify characteristics of the disease. Diabetes mellitus is one of the clinical manifestations of WS and attention must give to the differential diagnosis. Gene analysis is critical in the diagnosis of WS. According to the literature, classic and atypical WS differ in incidence, pathogenic gene, and clinical manifestations. Characteristic dermatological pathology may be significantly more important for the initial identification of AWS. Early detection, appropriate treatments, and regular follow-up may improve prognosis and survival of WS patients.

The short-term efficacy and safety of insulin degludec U100 (IDeg) in patients with type 2 diabetes have not been reported widely. We compared insulin IDeg and insulin glargine U100 (IGla) for glycemic control and glucose variability in hospitalized patients with type 2 diabetes. In an open-label, multicenter, randomized controlled trial, 74 patients were randomly assigned to either the IDeg (36 patients) or IGla (38 patients) group and were administered with basal-bolus therapy during hospitalization. Following the start of the treatment, on day 11, glucose variability was assessed by continuous glucose monitoring. A fasting blood glucose level of 110 mg/dL and 2-hour postprandial blood glucose level of 180 mg/dL throughout at least one day during the observation period were achieved in 31.3% (10/32) and 30.6% (11/36) of the patients in the IDeg and IGla groups, respectively. The 6-point self-monitoring of blood glucose profiles showed a significant difference between the two groups. On day 7, the intra-day variation was larger in the IDeg group than in the IGla group. The incidence of hypoglycemia or glucose variability was comparable in the two groups. This study suggests that short-term efficacy and safety of IDeg and IGla in patients with type 2 diabetes during the initial phase of basal-bolus therapy were comparable, and these results can help in deciding which treatment to opt for.

Noonan syndrome (NS) is a heterogeneous disorder with multiple congenital malformations. Recent advances in molecular and genetic approaches have identified a number of responsible genes for NS, most of which are components of the RAS/MAPK signaling pathway, and genotype-phenotype correlation analyses have been extensively performed; however, analysis of Japanese NS patients is limited. Here, we evaluated clinical characteristics in genetically diagnosed NS patients and their relationships to genotypes. A total of 48 clinically diagnosed NS were included, and responsible mutations were identified in 39 patients (81.3%) with PTPN11 mutations being the most prevalent followed by SOS1 mutations. Cardiac anomalies including pulmonary stenosis and hypertrophic cardiomyopathy were most prevalent (87.2%), and the prevalence of hypertrophic cardiomyopathy was greater in patients without PTPN11 mutations than in those with PTPN11 mutations. Short stature was the second-most prevalent (69.2%) characteristic, and present height SD score was significantly associated with height SD score at 1 year old. Patients with SOS1 mutations had greater present height SD score and better growth during infancy. These findings suggest the presence of a genotype-phenotype correlation in Japanese patients with NS, which enables us to use genetic information to predict the clinical course and may allow for genotype-based medical interventions.

We investigated the factors associated with fatty liver remission via treatment with ipragliflozin. The analysis was obtained from our multi-center prospective observational study, including 200 Japanese patients with type 2 diabetes treated with ipragliflozin (50 mg/day) for 24 weeks. The extent of fatty liver was estimated using a fatty liver index (FLI). Based on the FLI after the treatment with ipragliflozin, patients were classified into remission group (FLI < 30) and non-remission group (FLI ≥ 30). After treatment with ipragliflozin for 24 weeks, FLI significantly improved from 64.5 ± 21.6 to 51.9 ± 26.5 (p < 0.01). Body weight, body mass index, waist circumference, aspartate aminotransferase, alanine aminotransferase, and FLI in the remission group were significantly lower compared with those of the non-remission group. Stepwise analysis showed that the baseline FLI (Odds ratio 0.86; 95% confidence interval 0.81–0.90, p < 0.01) was an independent factor associated with FLI remission. Using a receiver operating characteristic (ROC) analysis, the adequate cut-off value for the remission was 50. The area under the ROC curve was 0.93 with the sensitivity and specificity 84.6% and 90.1% respectively. In conclusion, ipragliflozin ameliorated fatty liver. These results suggest that patients with fatty liver with a lower FLI are more likely to attain remission by the treatment with ipragliflozin.

İt is known that there is a relationship between some diseases and blood groups. The objective of our study is to investigate how often ABO and Rh blood groups are seen in benign thyroid diseases, especially in autoimmune-mediated thyroid diseases, and hence whether there is an association between blood groups and thyroid diseases. A total of 958 patients who were followed due to any benign thyroid disease were included in the study. The study population comprised 958 patients, 550 with Hashimoto’s hypothyroidism, 160 with non-Hashimoto’s hypothyroidism, 103 with iatrogenic hypothyroidism, 93 with central hypothyroidism, and 28 with Graves’ and 24 with non-Graves’ hyperthyroidism. Of the patients, 47.1% belonged to the O blood group, 30% to the A blood group, 15.2% to the B blood group, and 7.7% to the AB blood group while 90% were Rh-positive. The ratio of those with the O blood group was determined to be significantly higher in the Hashimoto’s hypothyroidism group compared to the other disease groups. In the non-Hashimoto’s hypothyroidism group, however, the ratio of the AB blood group was statistically significantly higher. While autoimmune diseases were more common in those with the O blood group, they were significantly lower in the AB blood group (p < 0.001). In our study, we determined that the ratio of the O blood group was significantly higher among patients with hypothyroidism due to Hashimoto’s thyroiditis. These findings imply that there might be a relation between O blood group and Hashimoto’s thyroiditis.

LncRNA AK077216 is a novel lncRNA with critical role in osteoclastogenesis and bone resorption. Our preliminary RNA-seq data suggested its downregulated expression pattern in diabetic retinopathy (DR). We therefore further investigated the function of AK077216 in DR. Plasma samples used in this study were derived from blood, which was extracted from 60 diabetic retinopathy patients. AK077216 in plasma of DR patients, diabetic patients (DB) and controls (Control) was detected by RT-qPCR. ROC curve analysis was performed to evaluate the diagnostic value of plasma AK077216 for DR. It was found that plasma AK077216 was downregulated only in DR patients but not in diabetic patients (no obvious complications) comparing to healthy controls. Downregulation of AK077216 distinguished DR patients from diabetic patients and healthy controls. High glucose treatment failed to significantly affect AK077216 expression in cells of human retinal pigment epithelial cell line ARPE-19. MiR-383 was inversely correlated with AK077216 in DR patients. AK077216 overexpression caused miR-383 downregulation, but miR-383 overexpression did not significantly alter AK077216 expression. AK077216 overexpression inhibited ARPE-19 cell apoptosis, while miR-383 overexpression played an opposite role and attenuated the effects of AK077216 overexpression. Therefore, AK077216 is downregulated in diabetic retinopathy and inhibited the apoptosis of ARPE-19 cells by downregulating miR-383.

To study the thyroid regeneration and injury of recurrent laryngeal nerve after irreversible electroporation (IRE). 12 pigs were divided into three groups: six pigs underwent IRE, other pigs were used as controls. IRE was performed near tracheoesophageal groove, to ablate most part of thyroid gland. Parathyroid and thyroid function, recurrent laryngeal nerve injury and thyroid computed tomography (CT) imaging were regularly investigated. The histopathology results were analyzed to detect thyroid regeneration. Masson’s trichrome method for collagen and immunohistochemistry were performed for Soluble protein-100 (S100) and neurofilaments on nerve section. In IRE group, there were no symptoms of recurrent laryngeal nerve-related injury. No abnormalities of recurrent laryngeal nerve were shown on hematoxylin-eosin (HE) staining, Masson’s trichrome staining, Neurofilament (NF) staining and S100 staining. There were no significant changes for thyroid and parathyroid function in all pigs. Immediately after IRE, CT showed hypoattenuation in the ablated thyroid gland and it became swelling. 14 days after IRE, thyroid CT showed hetergenous attenuation in the electroporation zone, and the size and attenuation of thyroid gland were normal after two months. There was cell apoptosis in the thyroid gland after IRE. Seven and 14 days after IRE, there was fragmentation of nucleus within the follicle, and some follicles were empty. Two months later, complete regeneration of thyroid tissue was shown. IRE was shown to be both effective and safe with complete regeneration of thyroid tissue and preservation of the function and structure of the recurrent laryngeal nerve.

In the present study, we investigate the effect of reduced cystathionine-γ-lyase (CSE) expression in high glucose induced metalloproteinases14 (MMP14) expression in adipocytes and visceral adipose tissues. Diabetic mice were prepared by injections of STZ and the expression of CSE, MMP14 in visceral adipose tissues were determined. Adipocytes were differentiated from 3T3-L1 cells and treated with high glucose (HG), H₂S slow-releasing compound GYY4137 or transfected with CSE siRNA. Then the expression of CSE, MMP14 were determined by western blotting. CSE knockout mice were generated by crossing CSE^+/– heterozygous mice and given intraperitoneally (i.p.) injections of GYY4137, and then the expression of CSE and MMP14 in visceral adipose tissues were determined by quantitative real-time PCR and western blotting. The following results were obtained from the study. In adipose tissues of diabetic mice, the mRNA and protein expression of MMP14 increased while the mRNA and protein expression of CSE decreased. In 3T3-L1 adipocytes, both HG DMEM and CSE siRNA transfection increased the mRNA and protein of MMP14. The addition of GYY4137 inhibited HG-induced upregulation of MMP14 expression. In CSE knockout mice, the mRNA and protein expression of MMP14 in adipose tissues increased, which could be inhibited by i.p. injections of GYY4137. In conclusion, high glucose increased the expression of MMP14 in adipocytes and visceral adipose tissues through inhibiting the expression of CSE.