Central diabetes insipidus following COVID-19 mRNA vaccination: a case report / 고신대학교의과대학학술지

The coronavirus disease 2019 (COVID-19) has been a major public health emergency worldwide. Vaccines were rapidly developed and approved to prevent the spread of viral infection. However, various side effects of the COVID-19 messenger RNA (mRNA) vaccines have been reported after their commercialization. A 24-year-old man visited our emergency department with polyuria and polydipsia that occurred after he received a COVID-19 mRNA vaccine 10 days beforehand. The initial laboratory findings showed very low urine osmolality with hyperosmolar hypernatremia. Based on these findings, diabetes insipidus was suspected, and sella magnetic resonance imaging showed an enlarged pituitary gland and the absence of posterior pituitary higher intensity. After 12 hours of using oral desmopressin acetate, urine volume decreased, and after 5 days of administration, serum electrolyte and serum osmolality improved. This case report of diabetes insipidus occurring after vaccination with the BNT162b2 mRNA COVID-19 vaccine is presented as a reminder that close monitoring is necessary for patients with polyuria and polydipsia after vaccination.

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.

Predictive Performance of Glycated Hemoglobin for Incident Diabetes Compared with Glucose Tolerance Test According to Central Obesity

Background@#To examine whether glycated hemoglobin (HbA1c) test would be a suitable screening tool for detecting high-risk subjects for diabetes compared to oral glucose tolerance test (OGTT) according to accompanied central obesity. @*Methods@#In this prospective population-based cohort study, both OGTT and HbA1c tests were performed and continued every 2 years up to 12 years among individuals with non-diabetic state at baseline (aged 40 to 69 years, n=7,512). Incident diabetes was established by a doctor, HbA1c ≥6.5%, and/or fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-hour postprandial glucose (2hPG) level based on OGTT ≥200 mg/dL. Discriminative capacities of high HbA1c (≥5.7%) versus high 2hPG (≥140 mg/dL) for predicting incident diabetes were compared using Cox-proportional hazard regression and C-index. @*Results@#During the median 11.5 years of follow-up period, 1,341 (17.6%) developed diabetes corresponding to an incidence of 22.1 per 1,000 person-years. Isolated high 2hPG was associated with higher risk for incident diabetes (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.56 to 5.17) than isolated high HbA1c (HR, 2.79; 95% CI, 2.40 to 3.26; P<0.05). In addition, high 2hPG provided better discriminatory capacity than high HbA1c (C-index 0.79 vs. 0.75, P<0.05). Meanwhile, in subjects with central obesity, the HR (3.95 [95% CI, 3.01 to 5.18] vs. 2.82 [95% CI, 2.30 to 3.46]) and discriminatory capacity of incident diabetes (C-index 0.75 vs. 0.75) between two subgroups became comparable. @*Conclusion@#Even though the overall inferior predictive capacity of HbA1c test than OGTT, HbA1c test might plays a complementary role in identifying high risk for diabetes especially in subjects with central obesity with increased sensitivity.

Predictive Performance of Glycated Hemoglobin for Incident Diabetes Compared with Glucose Tolerance Test According to Central Obesity

Background@#To examine whether glycated hemoglobin (HbA1c) test would be a suitable screening tool for detecting high-risk subjects for diabetes compared to oral glucose tolerance test (OGTT) according to accompanied central obesity. @*Methods@#In this prospective population-based cohort study, both OGTT and HbA1c tests were performed and continued every 2 years up to 12 years among individuals with non-diabetic state at baseline (aged 40 to 69 years, n=7,512). Incident diabetes was established by a doctor, HbA1c ≥6.5%, and/or fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-hour postprandial glucose (2hPG) level based on OGTT ≥200 mg/dL. Discriminative capacities of high HbA1c (≥5.7%) versus high 2hPG (≥140 mg/dL) for predicting incident diabetes were compared using Cox-proportional hazard regression and C-index. @*Results@#During the median 11.5 years of follow-up period, 1,341 (17.6%) developed diabetes corresponding to an incidence of 22.1 per 1,000 person-years. Isolated high 2hPG was associated with higher risk for incident diabetes (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.56 to 5.17) than isolated high HbA1c (HR, 2.79; 95% CI, 2.40 to 3.26; P<0.05). In addition, high 2hPG provided better discriminatory capacity than high HbA1c (C-index 0.79 vs. 0.75, P<0.05). Meanwhile, in subjects with central obesity, the HR (3.95 [95% CI, 3.01 to 5.18] vs. 2.82 [95% CI, 2.30 to 3.46]) and discriminatory capacity of incident diabetes (C-index 0.75 vs. 0.75) between two subgroups became comparable. @*Conclusion@#Even though the overall inferior predictive capacity of HbA1c test than OGTT, HbA1c test might plays a complementary role in identifying high risk for diabetes especially in subjects with central obesity with increased sensitivity.

Obese Subjects with Non-Alcoholic Fatty Liver Disease Have a Higher Risk of Thyroid Dysfunction / 고신대학교의과대학학술지

OBJECTIVES: The effects of obesity on thyroid function have not been well established. The aim of this study was to investigate the effects of body mass index (BMI) and/or non-alcoholic fatty liver disease (NAFLD) on thyroid function.METHODS: A retrospective longitudinal analysis was conducted among subjects who underwent comprehensive health check-ups at least four times between 2008 and 2017. Thyroid function was investigated according to BMI or presence of NAFLD at the end of follow-up. The subjects were divided into four groups: control (n = 216), subjects with obese (n = 94), subjects with NAFLD (n = 48), and subjects with obese + NAFLD (n = 93). Obesity was defined as BMI ≥ 25 kg/m².RESULTS: During the mean follow-up of 6.8 years (6.8 ± 1.2 years), 42 of the 451 subjects (9.3%) had subclinical hypothyroidism (SCH) but no subjects developed overt hypothyroidism. In multivariate Cox proportional hazard analysis, after adjustment for age, sex, smoking, and baseline thyroid stimulating hormone level, obese subjects with NAFLD had a higher risk of SCH than the control group.CONCLUSIONS: The obese subjects with NAFLD had a higher risk for SCH in the future.

Association between Green Tea Consumption and Sarcopenia in Menopausal Women: a Cross Sectional Analysis of the Korea National Health and Nutrition Examination Survey 2008-2011

BACKGROUND: Many studies of the effect of catechins, a major substance in green tea, on sarcopenia have been conducted using animal models or as in vitro experiments, revealing that they increase muscle mass, inhibit proteases, and promote satellite cell proliferation. No study has been conducted targeting human subjects relative to the correlation between green tea and sarcopenia. The purpose of this study was to investigate the correlation between green tea intake and sarcopenia in menopausal women using the Korea National Health and Nutrition Examination Survey (2008–2011).METHODS: This study included 3,473 menopausal women after excluding those diagnosed with gastric cancer and other cancers. The frequency of green tea intake was determined based on the Food Frequency Questionnaire, and the value acquired from calibrating the extremity muscle mass measured using dual-energy X-ray absorptiometry with weight was used as the muscle mass. Sarcopenia was defined using values less than two standard deviations as cut-offs after determining the mean and standard deviation of the muscle mass in the group of young and healthy women.RESULTS: In menopausal women, the odds ratio of the group drinking a cup or less and two or more cups of green tea to that of the group not drinking green tea was 1.170 (0.891–1.536), and the 95% confidence interval was 1.530 (0.744–3.146). A significant linear trend was not observed in the result (P for trend 0.148).CONCLUSION: There was no significant correlation between green tea intake and sarcopenia in menopausal women in Korea.

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.

Dynamic postural stability in patients with diabetic peripheral neuropathy and relationship to presence of autonomic neuropathy

@#Diabetic neuropathy is a common complication that can negatively influence balance and is a major cause of falls. We evaluated the association between postural sway and diabetic autonomic neuropathy (DAN) among patients with diabetic peripheral neuropathy (DPN). Patients with DPN documented by typical symptoms with abnormal results of nerve conduction study were included and postural stability was assessed using dynamic posturography. Composite autonomic scoring scale (CASS) score was calculated by evaluating sudomotor, cardiovagal, and adrenergic functions. CASS score ≥2 indicated DAN and the severity of DAN was indicated by the CASS scores divided into three subscales of 10-point total CASS: none or mild autonomic failure (0-3), moderate failure (4-6), and severe failure (7-10). A total of 34 patients comprised the DAN group (n=19) and non-DAN group (n=15). Patients with DAN had higher prevalence of diabetic retinopathy(p=0.011), higher urine albumin-creatinine ratio (p = 0.009), and lower HbA1c levels (p<0.001) than those with non-DAN. With regard to dynamic postural instability, the presence (p=0.025) as well as the severity of DAN (p<0.05) was associated with postural instability in the eyes-opencondition. Interestingly, the poorer dynamic postural instability in moderate/severe DAN compared to mild DAN was observed only in medio-lateral direction and this association remained significant after adjusting for age, sex, and glycemic control state (HbA1c). In patients with DAN accompanied by DPN, the dynamic postural instability was affected by visual feedback and medio-lateral directional instability was closely associated with the severity of DAN.

Prognosis of Differentiated Thyroid Carcinoma with Initial Distant Metastasis: A Multicenter Study in Korea

BACKGROUND: Most patients with differentiated thyroid cancer (DTC) have a favorable prognosis. However, patients with DTC and initial distant metastasis have not been commonly found, and their clinical characteristics have seldom been reported. In this study, we analyzed the clinical features and prognosis of patients with DTC and initial distant metastasis in Korea. METHODS: We retrospectively reviewed the clinical data of 242 patients with DTC and initial distant metastasis treated from 1994 to 2013, collected from five tertiary hospitals in Korea. RESULTS: The patients' median age was 51 years, and 65% were women. They were followed for a median of 7 years. Lung was the most common site of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other single site one (pleura), and combined sites 43 (40 were lung and bone, two were bone and other site, and one was lung and other site). At the time of diagnosis, 50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease-specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than those in previous studies. After multivariate analysis, old age, male sex, metastatic site, and histologic type (follicular type) were significant factors for poor prognosis. However, negative RAI avidity status was not a significant prognostic factor after adjusting for other variables. CONCLUSION: The prognosis of Korean patients with DTC and initial distant metastasis was better than in previous studies. Old age, male sex, metastasis site, and histologic type were significant prognostic factors.

A Case of Frontoethmoidal Mucopyocele Combined with Cerebrospinal Fluid Leak and Complicated Tension Pneumocephalus after Marsupialization

After the trauma of frontoethmoidal sinus, post-traumatic mucocele may occur. Surgical removal of the lesions rarely produces cerebrospinal fluid (CSF) leakage and even delayed tension pneumocephalus. We experienced a case of fronto-ethmoid mucocele complicated with peri-operative CSF leakage and post-operative tension pneumocephalus which was improved by conservative treatment. It is imperative to take into account the potential for tension pneumocephalus when a patient suffers from severe headache after sinus surgery.

Fulminant Type 1 Diabetes Developing during Pregnancy in Patient with Gestational Diabetes Mellitus / 대한내과학회지

A 32-year-old pregnant woman (34 + 5 weeks) was admitted with dizziness, nausea, and vomiting. Previously, she was diagnosed with gestational diabetes mellitus at 28 weeks with 100 g-OGTT and insulin therapy was started. Her average fasting glucose level was 97 mg/dL and postprandial 1-hour glucose level was 130 mg/dL with basal-bolus insulin therapy (total dose of 28-30 IU/day). At 34 + 0 weeks of gestational age, polyuria and unexpected weight loss (2 kg/week) with hyperglycemia occurred, and total dose of daily insulin requirement was increased up to 50 IU/day. At admission, her serum glucose level was high (502 mg/dL), and urinalysis revealed ketonuria +3. Arterial blood gas analysis revealed pH of 6.83, pCO2 of 9 mmHg, and bicarbonate of 2 mmol/L with an anion gap of 23.5 mmol/L. The diagnosis of diabetic ketoacidosis was established and emergency caesarean section was conducted due to fetal distress. She was finally diagnosed with fulminant type 1 diabetes mellitus, and multiple daily insulin injection therapy was continued after delivery.

Follow-up of thyroid ultrasonography in patients with hemodialysis / 영남의대학술지

BACKGROUND: Chronic kidney disease is considered a risk factor for thyroid nodules as well as thyroid dysfunction such as hypothyroidism. Among patients on hemodialysis, we assessed the size of thyroid nodule and goiter at baseline and 1 year later with ultrasonography. METHODS: We prospectively selected 47 patients with hemodialysis at January 2012 and reviewed their medical records. We checked goiter and thyroid nodules at January 2012 and December 2012. RESULTS: In the hemodialysis patients (n=47), 24 patients (51.1%) had thyroid nodules and 33 patients (70.2%) had goiter at baseline. Parathyroid hormone (PTH) was higher in patients with thyroid nodules (204.4±102.9 vs. 129.9±93.6 pg/mL, p=0.01). Thyroid ultrasonography was conducted in 29 patients after 1 year. The thickness of the thyroid isthmus increased (2.8±1.6 vs. 3.2±1.9 mm, p=0.003), but the number of nodules did not change (1.2±1.9 vs. 1.4±2.0, p=0.109). PTH was associated with the enlargement of thyroid nodules significantly through logistic regression analysis. CONCLUSION: Thyroid goiter and nodules in hemodialysis patients were more prevalent than in the general population. PTH influenced the production of thyroid nodules in hemodialysis patients. Regular examination with thyroid ultrasonography and thyroid function test should be considered in hemodialysis patients.

Follow-up of thyroid ultrasonography in patients with hemodialysis / 영남의대학술지

BACKGROUND: Chronic kidney disease is considered a risk factor for thyroid nodules as well as thyroid dysfunction such as hypothyroidism. Among patients on hemodialysis, we assessed the size of thyroid nodule and goiter at baseline and 1 year later with ultrasonography.METHODS: We prospectively selected 47 patients with hemodialysis at January 2012 and reviewed their medical records. We checked goiter and thyroid nodules at January 2012 and December 2012.RESULTS: In the hemodialysis patients (n=47), 24 patients (51.1%) had thyroid nodules and 33 patients (70.2%) had goiter at baseline. Parathyroid hormone (PTH) was higher in patients with thyroid nodules (204.4±102.9 vs. 129.9±93.6 pg/mL, p=0.01). Thyroid ultrasonography was conducted in 29 patients after 1 year. The thickness of the thyroid isthmus increased (2.8±1.6 vs. 3.2±1.9 mm, p=0.003), but the number of nodules did not change (1.2±1.9 vs. 1.4±2.0, p=0.109). PTH was associated with the enlargement of thyroid nodules significantly through logistic regression analysis.CONCLUSION: Thyroid goiter and nodules in hemodialysis patients were more prevalent than in the general population. PTH influenced the production of thyroid nodules in hemodialysis patients. Regular examination with thyroid ultrasonography and thyroid function test should be considered in hemodialysis patients.

Predictive Factors for the Therapeutic Response to Concomitant Treatment with DPP-4 Inhibitors in Type 2 Diabetes with Short-Term Follow-Up / 고신대학교의과대학학술지

OBJECTIVES: To evaluate the efficacy and predictive factors of Dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes mellitus (T2DM) patients who were not well controlled with other oral antidiabetic drugs or insulin in real clinical practice. METHODS: From December 2012 to January 2014, retrospective longitudinal observation study was conducted for patients with T2DM who were not reached a glycemic target (glycated hemoglobin [HbA1c] > 6.5%) with other oral antidiabetic drugs or insulins. Type 1 diabetes or other types of diabetes were excluded. Responders were eligible with decreased HbA1c from baseline for more than 5% during follow up period. RESULTS: Of total 135 T2DM patients having an average 9.0 months follow-up period, 84 (62.2%) of patients were responder to DPP-4 inhibitors. After concomitant treatment with DPP-4 inhibitors, patients had a mean decrease in HbA1c of 0.69 ± 1.3%, fasting plasma glucose of 13 ± 52 mg/㎗, and postprandial plasma glucose of 29 ± 85 mg/㎗ from baseline (all P < 0.05). Independent predictive factor for an improvement of glycemic control with DPP-4 inhibitors was higher baseline HbA1c (odds ratio 2.07 with 95% confidence interval 1.15-3.72) compared with non-responders. CONCLUSIONS: A clinical meaningful improvement in glycemic control was seen when DPP-4 inhibitors were added to other anti-diabetic medications in patients with T2DM regardless of age, duration of T2DM, type of combination treatment regimen. Patients who had higher HbA1c were more easily respond to DPP-4 inhibitors treatment in short-term follow-up period.

A Case of Cerebral Venous Thrombosis in a Patient with Graves' Disease / 고신대학교의과대학학술지

Superior sagittal sinus thrombosis is an uncommon disease, and 25% of cases are considered to be idiopathic. Hypercoagulability, local bloodstream stasis, and vessel wall abnormalities may contribute to the development of this condition. The thyrotoxic phase of Graves’ disease is associated with venous thrombosis caused by hypercoagulability, which is in turn induced by increased levels of homocysteine and factor VIII and decreased fibrinolytic activity. Here, we report the case of a 39-year-old male who presented with superior sagittal sinus thrombosis and concomitant hyperthyroidism.

Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary Adrenal Insufficiency

BACKGROUND: The chronic use of glucocorticoids (GC) suppresses function of the hypothalamic-pituitary-adrenal axis and often results in secondary adrenal insufficiency (AI). The present study aimed to determine the recovery rate of adrenal function in patients with secondary AI within 1 to 2 years and to assess the factors predictive of adrenal function recovery. METHODS: This was a retrospective observational study that enrolled patients diagnosed with GC-induced secondary AI between 2007 and 2013. AI was defined by peak serum cortisol levels <18 µg/dL during a standard-dose short synacthen test (SST). A follow-up SST was performed after 1 to 2 years, and responders were defined as those with adrenocorticotropic hormone (ACTH)-stimulated peak serum cortisol levels ≥18 µg/dL. RESULTS: Of the total 34 patients diagnosed with GC-induced secondary AI at first, 20 patients (58.8%) recovered normal adrenal function by the time of the follow-up SST (median follow-up period, 16.5 months). Although the baseline serum ACTH and cortisol levels at the first SST did not differ between responders and non-responders, the incremental cortisol response during the first SST was higher in responders than that of non-responders (7.88 vs. 3.56, P<0.01). Additionally, higher cortisol increments during the first SST were an independent predictive factor of the adrenal function recovery (odds ratio, 1.58; 95% confidence interval, 1.02 to 2.46; P<0.05). CONCLUSION: In the present study, adrenal function recovery was achieved frequently in patients with GC-induced secondary AI within 1 to 2 years. Additionally, an incremental cortisol response at the first SST may be an important predictive factor of adrenal function recovery.

A Case of Low Grade Osteosarcoma Developing in the Middle Skull Base after Radiotherapy of Adenoid Cystic Carcinoma in the Posterior Nasal Cavity / 대한이비인후과학회지

Adenoid cystic carcinoma arises rarely in the nasal cavity and paranasal sinus. Treatment strategy showing the best survival rate includes surgical excision and adjuvant radiotherapy. There were a few case reports of radiation-induced osteosarcoma from adenoid cystic carcinoma overseas but not in Korea. We experienced a case of radiation-induced low-grade osteosarcoma in the middle skull base including sphenoid bone, which had arisen after 10 years of radiotherapy of adenoid cystic carcinoma. Authors present this case with serial imaging findings and literature review.

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.

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.

Exendin-4 Improves Nonalcoholic Fatty Liver Disease by Regulating Glucose Transporter 4 Expression in ob/ob Mice

Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver, glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters, hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly, Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.