The Efficacy of Treatment Intensification by Quadruple Oral Therapy Compared to GLP-1RA Therapy in Poorly Controlled Type 2 Diabetes Mellitus Patients: A Real-world Data Study.

We compared the glycemic efficacy of treatment intensification between quadruple oral antidiabetic drug therapy and once-weekly glucagon-like peptide-1 receptor agonist (GLP-1RA)-based triple therapy in patients with poorly controlled type 2 diabetes mellitus refractory to triple oral therapy. For 24 weeks, changes in glycosylated hemoglobin (HbA1c) from baseline were compared between the two treatment groups. Of all 96 patients, 50 patients were treated with quadruple therapy, and 46 were treated with GLP-1RA therapy. Reductions in HbA1c for 24 weeks were comparable (in both, 1.1% reduction from baseline; P=0.59). Meanwhile, lower C-peptide level was associated with a lower glucose-lowering response of GLP-1RA therapy (R=0.3, P=0.04) but not with quadruple therapy (R=-0.13, P=0.40). HbA1c reduction by GLP-1RA therapy was inferior to that by quadruple therapy in the low C-peptide subgroup (mean, -0.1% vs. -1.3%; P=0.04). Treatment intensification by switching to quadruple oral therapy showed similar glucose-lowering efficacy to weekly GLP-1RA-based triple therapy. Meanwhile, the therapeutic response was affected by C-peptide levels in the GLP-1RA therapy group but not in the quadruple therapy group.

Similarities and differences between bone quality parameters, trabecular bone score and femur geometry.

Bone quality is a critical factor that, along with bone quantity, determines bone strength. Image-based parameters are used for assessing bone quality non-invasively. The trabecular bone score (TBS) is used to assess quality of trabecular bone and femur geometry for cortical bone. Little is known about the associations between these two bone quality parameters and whether they show differences in the relationships with age and body mass index (BMI). We investigated the associations between the trabecular bone score (TBS) and femur cortical geometry. Areal bone mineral density (BMD) was assessed using dual energy X-ray absorptiometry (DXA) and the TBS was assessed using iNsight software and, femur geometry using APEX (Hologic). A total of 452 men and 517 women aged 50 years and older with no medical history of a condition affecting bone metabolism were included. Z-scores for TBS and cortical thickness were calculated using the age-specific mean and SD for each parameter. A 'discrepancy group' was defined as patients whose absolute Z-score difference between TBS and cortical thickness was > 1 point. TBS and cortical thickness correlated negatively with age both in men and women, but the associations were stronger in women. Regarding the associations with BMI, TBS provided significant negative correlation with BMI in the range of BMI > 25 kg/m2. By contrast, cortical thickness correlated positively with BMI for all BMI ranges. These bone quality-related parameters, TBS and cortical thickness, significantly correlated, but discordance between these two parameters was observed in about one-third of the men and women (32.7% and 33.4%, respectively). Conclusively, image-based bone quality parameters for trabecular and cortical bone exhibit both similarities and differences in terms of their associations with age and BMI. These different profiles in TBS and FN cortical thickness might results in different risk profiles for the vertebral fractures or hip fractures in a certain percentage of people.

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Health in Patients with Type 2 Diabetes Mellitus.

Patients with type 2 diabetes (T2DM) have a higher risk of bone fracture even when bone mineral density (BMD) values are normal. The trabecular bone score (TBS) was recently developed and used for evaluating bone strength in various diseases. We investigated the effect of DPP-4 inhibitors on bone health using TBS in patients with T2DM. This was a single-center, retrospective case-control study of 200 patients with T2DM. Patients were divided into two groups according to whether they were administered a DPP-4 inhibitor (DPP-4 inhibitor group vs. control group). Parameters related to bone health, including BMD, TBS, and serum markers of calcium homeostasis, were assessed at baseline and after one year of treatment. We found TBS values increased in the DPP-4 group and decreased in the control, indicating a significant difference in delta change between them. The BMD increased in both groups, with no significant differences in delta change between the two groups observed. Serum calcium and 25-hydroxy vitamin D3 increased only in the DPP-4 inhibitor group, while other glycemic parameters did not show significant differences between the two groups. Treatment with DPP-4 inhibitors was associated with favorable effects on bone health evaluated by TBS in patients with T2DM.

Glucocorticoid-Induced Hypokalemic Periodic Paralysis after Short-Term Use of Tenofovir with Hypophosphatemia: A Case Report.

Hypokalemic periodic paralysis (HPP) is a neuromuscular disorder associated with muscular dysfunction caused by hypokalemia. There are various causes of HPPs and rarely, HPP appears to be relevant to tenofovir or glucocorticoid treatment. There have been several case reports of tenofovir-related nephrotoxicity or tenofovir-induced HPP. However, a case report of glucocorticoid-induced HPP in a patient using tenofovir temporarily has not been reported. Herein, we report a case of glucocorticoid-induced HPP with short-term use of tenofovir. A 28-year-old man visited the emergency room with decreased muscle power in all extremities (2/5 grade). In their past medical history, the patient was treated with tenofovir for two months for a hepatitis B virus infection. At the time of the visit, the drug had been discontinued for four months. The day before visiting the emergency room, betamethasone was administered at a local clinic for herpes on the lips. Laboratory tests showed hypokalemia, hypophosphatemia, and mild metabolic acidosis. However, urinalysis revealed no abnormal findings. Consequently, it can be postulated that this patient developed HPP by glucocorticoids after taking tenofovir temporarily. This is the first case report of glucocorticoid-induced HPP in a patient using tenofovir. Clinicians who prescribe tenofovir should be aware of HPP occurring when glucocorticoids are used.

Insulin Resistance and the Risk of Diabetes and Dysglycemia in Korean General Adult Population.

BACKGROUND: Insulin resistance is a major pathogenic hallmark of impaired glucose metabolism. We assessed the accuracy of insulin resistance and cut-off values using homeostasis model assessment of insulin resistance (HOMA-IR) to classify type 2 diabetes mellitus (T2DM) and dysglycemia according to age and sex. METHODS: In this cross-sectional study, we analyzed 4,291 anti-diabetic drug-naïve adults (≥20 years) from the 6th Korea National Health and Nutrition Examination Survey in 2015. Metabolic syndrome (MetS) was defined by the modified National Cholesterol Education Program III guideline. Diagnosis of dysglycemia and T2DM were based on fasting glucose and glycosylated hemoglobin levels. The receiver operating characteristic curve and optimal cut-off values of HOMA-IR were assessed to identify T2DM/dysglycemia according to sex and were further analyzed by age. RESULTS: Sex differences were found in the association of MetS and the different MetS components with T2DM/dysglycemia. The overall optimal cut-off value of HOMA-IR for identifying dysglycemia was 1.6 in both sex. The cut-off values for T2DM were 2.87 in men and 2.36 in women. However, there are differences in diagnostic range of HOMA-IR to distinguish T2DM according to sex and age, and the accuracy of HOMA-IR in identifying T2DM gradually decreased with age especially in women. CONCLUSION: Insulin resistance is closely associated with the risk for T2DM/dysglycemia. The accuracy of HOMA-IR levels is characterized by sex- and age-specific differences in identifying T2DM. In addition to insulin resistance index, insulin secretory function, and different MetS components should be considered in the detection of early T2DM, especially in elderly.

Are pregnancy, parity, menstruation and breastfeeding risk factors for thyroid cancer? Results from the Korea National Health and Nutrition Examination Survey, 2010-2015.

CONTEXT: It is unclear whether reproductive factors such as pregnancy, parity, menstruation, and breastfeeding are risk factors for thyroid cancer. The aim of this study was to evaluate the association of reproductive factors with thyroid cancer risk. DESIGN/SETTING: Large-scale nation-wide cross-sectional data were analysed from representative samples from the Korea National Health and Nutrition Examination Survey V-VI (2010-2015). RESULTS: In this study, 38 086 people over the age of 18 years were enrolled, of which 241 had a diagnosis of thyroid cancer. Of 21 543 female subjects, 210 had thyroid cancer. In logistic regression analysis, pregnancy, parity and number of reproductive years (period between menarche and menopause, excluding breastfeeding period) were significantly associated with thyroid cancer after adjusting for age, body mass index and smoking. However, the number of pregnancies did not show a linear relationship with thyroid cancer. Among breastfeeding women, total duration of breastfeeding and number of babies breastfed significantly decreased the risk for thyroid cancer. CONCLUSION: Our findings suggest that reproductive factors can be associated with the development of thyroid cancer. A large prospective cohort study is needed to clarify the causality.

Comparisons of TBS and lumbar spine BMD in the associations with vertebral fractures according to the T-scores: A cross-sectional observation.

Trabecular bone score (TBS) is a parameter of bone quality that has been shown to be related to vertebral fractures. This study aimed to analyze the difference in discriminatory power of TBS for vertebral fractures according to the bone mineral density (BMD) T-score. Areal BMD at the lumbar spine (LS, L1-L4), femur neck (FN) and total hip were assessed using dual x-ray absorptiometry (Discovery W, Hologic, Bedford, MA) in 929 women aged 50years or older. TBS was analyzed using iNsight software (Med-Imaps, Pessac, France). Vertebral fractures were identified on lateral X-ray films of the thoracic and lumbar spine using a semi-quantitative method. The study subjects consisted of 158 subjects (17.0%) with normal BMD, 461 (49.6%) with osteopenia and 310 (33.4%) with osteoporosis. The incident vertebral fractures were observed in 92 (9.9%) subjects, including 59 fractures in osteoporosis, 29 fractures in osteopenia, and only 4 fractures in normal BMD. We stratified study subjects into two groups according to their BMD T-scores, osteoporosis or osteopenia/normal BMD. The logistic regression model showed that LS BMD values per each 1 standard deviation (SD) decrease were significantly associated with increased risk of vertebral fracture in both osteoporosis and osteopenia/normal BMD group with stronger association in osteoporosis group. However, a TBS value that was lower by 1SD was significantly associated with vertebral fracture risk only in the osteopenia/normal BMD group. The TBS use in addition to FN BMD and age also showed significantly better discriminatory power for vertebral fracture only in the osteopenia/normal BMD group, but not osteoporosis group. In conclusion, TBS is significantly associated with vertebral fractures in subjects with osteopenia/normal BMD levels. Additional assessment of bone microarchitecture using TBS is better able to identify women at risk of fracture, in particular, those with relatively higher BMD.

Optimal follow-up strategies for adrenal incidentalomas: reappraisal of the 2016 ESE-ENSAT guidelines in real clinical practice.

OBJECTIVE: Recently, the European Society of Endocrinology (ESE), in collaboration with the European Network for the Study of Adrenal Tumors (ENSAT), asserted that adrenal incidentalomas (AIs) <4 cm and ≤10 Hounsfield units (HU) do not require further follow-up imaging. To validate the clinical application of the follow-up strategies suggested by the 2016 ESE-ENSAT guidelines, we explored the clinical characteristics and natural course of AIs in a single center over 13 years. DESIGN AND METHODS: This retrospective cohort study included a total of 1149 patients diagnosed with AIs between 2000 and 2013 in a single tertiary center. Hormonal examination and radiological evaluations were performed at the initial diagnosis of AI and during the follow-up according to the appropriate guidelines. RESULTS: The mean age at diagnosis was 54.2 years, and the majority of AIs (68.0%) were nonfunctional lesions. Receiver operating curve analysis was used to discriminate malignant from benign lesions; the optimal cut-off value for mass size was 3.4 cm (sensitivity: 100%; specificity: 95.0%), and that for the pre-contrast HU was 19.9 (sensitivity: 100%; specificity: 67.4%). The majority of nonfunctional lesions did not change in size during the 4-year follow-up period. Applying a cut-off value of 1.8 µg/dL after a 1-mg overnight dexamethasone suppression test, 28.0% of all nonfunctional AIs progressed to autonomous cortisol secretion during the follow-up period. However, we observed no development of overt Cushing's syndrome in the study. CONCLUSIONS: We advocate that no follow-up imaging is required if the detected adrenal mass is <4 cm and has clear benign features. However, prospective studies with longer follow-up are needed to confirm the appropriate follow-up strategies.

Disentangling of Malignancy from Benign Pheochromocytomas/Paragangliomas.

OBJECTIVE: Many malignant tumors initially appear benign but subsequently exhibit extensive metastases. Early identification of malignant pheochromocytomas and paragangliomas (PPGLs) before metastasis is important for improved prognosis. However, there are no robust prognostic indices of recurrence and malignancy. The aim of this study was to identify the clinical and histopathological factors that predict malignant PPGLs. DESIGN: Retrospective follow-up study. METHODS: In this study, we included 223 patients with pathologically confirmed PPGLs who were treated between 2000 and 2015 at the Seoul National University Hospital in South Korea. RESULTS: Of these patients, 29 were diagnosed with malignancy, 12 of whom presented with metastatic lesions at the initial diagnosis while 17 developed metastases during follow-up. Nineteen patients with recurrent PPGLs consisted of ones with malignant PPGLs (n = 17) and multifocal PPGLs (n = 2) who had VHL and RET mutations. The mean age at presentation for malignant PPGLs was significantly younger than that for benign PPGLs (43.0 vs. 49.0 years, respectively; p = 0.023). Tumor size was not a distinguishing factor between malignant and benign PPGLs (5.0 vs. 4.5 cm, respectively; p = 0.316) nor did it predict recurrence. Of 119 patients with available pheochromocytoma of adrenal gland scaled score (PASS) data, those with malignant PPGLs presented PASS values ≥4. Of 12 parameters of PASS, necrosis, capsular invasion, vascular invasion, cellular monotony, high mitosis, atypical mitotic figures, and nuclear hyperchromasia were significant predictors of malignancy. CONCLUSIONS: Tumor size did not predict malignancy or recurrence of PPGLs. PPGL patients with characteristic pathologic findings and PASS ≥4 or germline mutations require close follow-up.

Infectious Spondylitis with Bacteremia Caused by Roseomonas mucosa in an Immunocompetent Patient.

Roseomonas are a gram-negative bacteria species that have been isolated from environmental sources. Human Roseomonas infections typically occur in immunocompromised patients, most commonly as catheter-related bloodstream infections. However, Roseomonas infections are rarely reported in immunocompetent hosts. We report what we believe to be the first case in Korea of infectious spondylitis with bacteremia due to Roseomonas mucosa in an immunocompetent patient who had undergone vertebroplasty for compression fractures of his thoracic and lumbar spine.

Acute pancreatitis induced by methimazole treatment in a 51-year-old korean man: a case report.

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

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%

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 (99m)technetium ((99m)Tc) 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 (99m)Tc sestamibi scan detected a 5-cm parathyroid neoplasm in the left lower lobe of the patient's 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; (99m)Tc sestamibi scan, serum calcium, and iPTH levels can help to establish the diagnosis of parathyroid neoplasm.