Tae Sik Jung

α‐lipoic acid prevents non‐alcoholic fatty liver disease in OLETF rats

Insulin resistance, oxidative stress, inflammation and innate immune system activation contribute to the development of non‐alcoholic fatty liver disease (NAFLD) through steatosis and inflammation in the liver. The powerful antioxidant α‐lipoic acid (ALA) has been shown to improve insulin sensitivity and suppress inflammatory responses. This study explores how ALA administration protects against NAFLD.

Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

BackgroundHyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA) on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF) rats.MethodsAnimals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO) rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day) administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry.ResultsWestern blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK) signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA.ConclusionsALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.

Fermented mushroom milk‐supplemented dietary fibre prevents the onset of obesity and hypertriglyceridaemia in Otsuka Long‐Evans Tokushima fatty rats

Aim:  Fermented milk product containing edible mushroom water extracts (mushroom yogurt; MY) has been reported to have glycaemic control and triglyceride‐lowering effects in streptozotocin (STZ)‐induced diabetic rats and Zucker diabetic fatty (ZDF) rats. Here, we investigated how MY‐supplemented dietary fibre (10 and 20%, v/w) influences the onset of obesity and hypertriglyceridaemia in Otsuka Long‐Evans Tokushima fatty (OLETF) rats.

Clinical Significance of the Presence of Autonomic and Vestibular Dysfunction in Diabetic Patients with Peripheral Neuropathy

Background We investigated the prevalence of diabetic autonomic neuropathy (DAN) and vestibular dysfunction (VD) in diabetic patients with peripheral neuropathy. Methods Thirty-five diabetic patients with peripheral neuropathy were enrolled from August 2008 to July 2009. All subjects underwent autonomic function tests. Nineteen of the patients (54.3%) underwent videonystagmography. Results Diabetic autonomic neuropathy was observed in 28 patients (80%). A mild degree of autonomic failure was observed in 18 patients (64.3%), and a moderate degree of autonomic failure was observed in ten patients (35.7%). Factors related to DAN included diabetic nephropathy (P=0.032), degree of chronic kidney disease (P=0.003), and duration of diabetes (P=0.044). Vestibular dysfunction was observed in 11 of 19 patients (57.9%). There was no significant association between DAN and VD. Conclusion Diabetic autonomic neuropathy was observed in 28 diabetic patients (80%) with peripheral neuropathy. Vestibular dysfunction was observed in nearly 60% of diabetic patients with peripheral neuropathy who complained of dizziness but showed no significant association with DAN. Diabetic patients who complained of dizziness need to examine both autonomic function and vestibular function.

Identification and characterization of D410E, a novel mutation in the loop 3 domain of CASR, in autosomal dominant hypocalcemia and a therapeutic approach using a novel calcilytic, AXT914

Activating mutations of the calcium‐sensing receptor (CASR) gene are associated with autosomal dominant hypocalcemia (ADH) characterized by benign hypocalcemia, inappropriately low (PTH) levels and mostly hypercalciuria. Herein, we report a novel activating mutation in the CASR gene in a Korean family with ADH.

A case of hypothyroidism and type 2 diabetes associated with type V hyperlipoproteinemia and eruptive xanthomas.

Primary hypothyroidism and type 2 diabetes are both typically associated with the increased level of triglycerides. To date, there have been only a few case reports of type 2 diabetes patients with both type V hyperlipoproteinemia and eruptive xanthomas, but there have been no reports of hypothyroidism patients associated with eruptive xanthomas. We report here on a case of a 48-yr old female patient who was diagnosed with type 2 diabetes and primary hypothyroidism associated with both type V hyperlipoproteinemia and eruptive xanthomas. We found rouleaux formation of RBCs in peripheral blood smear, elevated TSH, and low free T4 level, and dyslipidemia (total cholesterol 18.1 mM/L, triglyceride 61.64 mM/L, HDL 3.0 mM/L, and LDL 2.54 mM/L). She has taken fenofibrate, levothyroxine, and oral hypoglycemic agent for 4 months. After treatment, both TSH level and lipid concentration returned to normal range, and her yellowish skin nodules have also disappeared.

Delayed Surgery for Parathyroid Adenoma Misdiagnosed as a Thyroid Nodule and Treated with Radiofrequency Ablation

Primary hyperparathyroidism occurs as a result of isolated parathyroid adenoma in 80% to 85% of all cases. A 99mtechnetium (99mTc) sestamibi scan or neck ultrasonography is used to localize the neoplasm prior to surgical intervention. A 53-year-old female was referred for the exclusion of metabolic bone disease. She presented with low back pain that had persisted for the past 6 months and elevated serum alkaline phosphatase (1,253 IU/L). Four years previously, she had been diagnosed at a local hospital with a 2.3-cm thyroid nodule, which was determined to be pathologically benign. Radiofrequency ablation was performed at the same hospital because the nodule was still growing during the follow-up period 2 years before the visit to our hospital, and the procedure was unsuccessful in reducing the size of the nodule. The results of the laboratory tests in our hospital were as follows: serum calcium, 14.6 mg/dL; phosphorus, 3.5 mg/dL; and intact parathyroid hormone (iPTH), 1,911 pg/mL. Neck ultrasonography and 99mTc sestamibi scan detected a 5-cm parathyroid neoplasm in the left lower lobe of the patients thyroid; left parathyroidectomy was performed. This case indicated that thyroid ultrasonographers and pathologists need to be experienced enough to differentiate a parathyroid neoplasm from a thyroid nodule; 99mTc sestamibi scan, serum calcium, and iPTH levels can help to establish the diagnosis of parathyroid neoplasm.

Improvement of Glycemic Control after Re-Emphasis of Lifestyle Modification in Type 2 Diabetic Patients Reluctant to Additional Medication

Purpose The aim of this study is to observe glycemic changes after emphasizing the importance of lifestyle modification in patients with mild or moderately uncontrolled type 2 diabetes. Materials and Methods We examined 51 type 2 diabetic patients with 7.0-9.0% hemoglobin A1c (HbA1c) who preferred to change their lifestyle rather than followed the recommendation of medication change. At the enrollment, the study subjects completed questionnaires about diet and exercise. After 3 months, HbA1c levels were determined and questionnaires on the change of lifestyle were accomplished. We divided the study subjects into 3 groups: improved (more than 0.3% decrease of HbA1c), aggravated (more than 0.3% increase of HbA1c) and not changed (-0.3% <HbA1c change <0.3%). Results Among the total 51 subjects, 18 patients (35.3%) showed the decreased levels of HbA1c after 3 months with mean change of -0.74±0.27%, and HbA1c values of 11 patients (21.5%) were less than 7%. In addition, the HbA1c level was significantly reduced in patients who reportedly followed the lifestyle modification such as diet and exercise for 3 months, compared with the one obtained from patients who refused this lifestyle change (p=0.002). Conclusion In this study, 35.3% of the patients with mild or moderately uncontrolled type 2 diabetes showed the significant improvement of HbA1c levels after 3 months by simply regulating their daily diet and exercise without change of medication. This suggests that the lifestyle modification is significantly associated with the improvement of glucose control.

Genetic and Clinical Characteristics of Korean Patients with Isolated Hypoparathyroidism: From the Korean Hypopara Registry Study

Isolated hypoparathyroidism (IH) shows heterogeneous phenotypes and can be caused by defects in a variety of genes. The goal of our study was to determine the clinical features and to analyze gene mutations in a large cohort of Korean patients with sporadic or familial IH. We recruited 23 patients. They showed a broad range of onset age and various values of biochemical data. Whole exome sequencing was performed on two affected cases and one unaffected individual in a family. All coding exons and exon-intron borders of GCMB, CASR, and prepro-PTH were sequenced using PCR-amplified DNA. In one family who underwent the whole exome sequencing analysis, approximately 300 single nucleotide changes emerged as candidates for genetic alteration. Among them, we identified a functional mutation in exon 2 of GCMB (C106R) in two affected cases. Besides, heterozygous gain-of-function mutations in the CASR gene were found in other subjects; D410E and P221L. We also found one single nucleotide polymorphism (SNP) in the prepro-PTH gene, five SNPs in the CASR gene, and four SNPs in the GCMB gene. The current study represents a variety of biochemical phenotypes in IH patients with the molecular genetic diagnosis of IH.

Spurious Elevation of Glucose Concentration during Administration of High Dose of Ascorbic Acid in a Patient with Type 2 Diabetes on Hemodialysis

We describe herein a case of life-threatening hypoglycemia due to spurious elevation of glucose concentration during the administration of ascorbic acid in a type 2 diabetic patient. A 31-year-old female was admitted for proliferative diabetic retinopathy treatment and prescribed high dose ascorbic acid. During hospitalization, she suddenly lost her consciousness and her glucose concentration was 291 mg/dL, measured using self-monitoring blood glucose (SMBG) device, while venous blood glucose concentration was 12 mg/dL. After intravenous injection of 50% glucose solution, the patient became alert. We reasoned that glucose measurement by SMBG device was interfered by ascorbic acid. Physicians should be aware of this interference; high dose ascorbic acid may cause spurious elevation of glucose concentration when measuring with SMBG devices.