Non-Alcoholic Fatty Liver Disease with Sarcopenia and Carotid Plaque Progression Risk in Patients with Type 2 Diabetes Mellitus

Background@#We aimed to evaluate whether non-alcoholic fatty liver disease (NAFLD) with or without sarcopenia is associated with progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). @*Methods@#We investigated 852 T2DM patients who underwent abdominal ultrasonography, bioelectrical impedance analysis, and carotid artery ultrasonography at baseline and repeated carotid ultrasonography after 6 to 8 years. NAFLD was confirmed by abdominal ultrasonography, and sarcopenia was defined as a sex-specific skeletal muscle mass index (SMI) value <2 standard deviations below the mean for healthy young adults. SMI was calculated by dividing the sum of appendicular skeletal mass by body weight. We investigated the association between NAFLD with or without sarcopenia and the progression of carotid atherosclerosis. @*Results@#Of the 852 patients, 333 (39.1%) were classified as NAFLD without sarcopenia, 66 (7.7%) were classified as sarcopenia without NAFLD, and 123 (14.4%) had NAFLD with sarcopenia at baseline. After 6 to 8 years, patients with both NAFLD and sarcopenia had a higher risk of atherosclerosis progression (adjusted odds ratio, 2.20; P<0.009) than controls without NAFLD and sarcopenia. When a subgroup analysis was performed on only patients with NAFLD, female sex, absence of central obesity, and non-obesity were significant factors related to increased risk of plaque progression risk in sarcopenic patients. @*Conclusion@#NAFLD with sarcopenia was significantly associated with the progression of carotid atherosclerosis in T2DM patients.

Advanced Liver Fibrosis Is Associated with Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease

Background@#Nonalcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). However, the causal relationship between NAFLD and CKD is uncertain, particularly in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the association between the presence and severity of NAFLD and incident CKD in patients with T2DM. @*Methods@#In this longitudinal cohort study of patients with T2DM, 3,188 patients with preserved renal function were followed up for the occurrence of incident CKD. NAFLD was defined as the presence of hepatic steatosis on ultrasonography, without any other causes of chronic liver disease. Advanced liver fibrosis of NAFLD was defined as a fibrosis-4 index ≥2.67. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. @*Results@#At baseline, 1,729 (54.2%) patients had NAFLD, of whom 94 (5.4%) had advanced liver fibrosis. During the follow-up of 8.3±3.6 years, 472 (14.8%) patients developed incident CKD: 220 (15.1%) in the non-NAFLD group, 231 (14.1%) in the NAFLD without advanced fibrosis group and 28 (31.1%) in the NAFLD with advanced fibrosis group. There was no increased risk of incident CKD in the NAFLD group compared to the non-NAFLD group (P=0.435). However, among patients with NAFLD, advanced liver fibrosis was associated with an increased risk of CKD (adjusted hazard ratio, 1.75; 95% confidence interval, 1.15 to 2.66; P=0.009). @*Conclusion@#Advanced liver fibrosis in patients with NAFLD is independently associated with an increased risk of incident CKD in patients with T2DM.

State-of-the-Art Overview of the Pharmacological Treatment of Non-Alcoholic Steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, and non-alcoholic steatohepatitis (NASH), a subtype of NAFLD, can progress to cirrhosis, hepatocellular carcinoma, and death. Nevertheless, the current treatment for NAFLD/NASH is limited to lifestyle modifications, and no drugs are currently officially approved as treatments for NASH. Many global pharmaceutical companies are pursuing the development of medications for the treatment of NASH, and results from phase 2 and 3 clinical trials have been published in recent years. Here, we review data from these recent clinical trials and reports on the efficacy of newly developed antidiabetic drugs in NASH treatment.

Diabetes Fact Sheets in Korea, 2020: An Appraisal of Current Status

Background@#This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data. @*Methods@#This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated. @*Results@#In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes. @*Conclusion@#The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

Association Between Serum Bilirubin and the Progression of Carotid Atherosclerosis in Type 2 Diabetes

OBJECTIVE: This study investigated whether serum bilirubin levels can predict the progression of carotid atherosclerosis in individuals with type 2 diabetes mellitus (T2DM).METHODS: This observational study included 1,381 subjects with T2DM in whom serial measurements of carotid intima-media thickness (CIMT) were made at 1- to 2-year intervals for 6–8 years. The progression of carotid atherosclerosis was defined as newly detected plaque lesions on repeat ultrasonography. After dividing total serum bilirubin levels into tertiles, the association between total serum bilirubin at baseline and plaque progression status was analyzed.RESULTS: Among 1,381 T2DM patients, 599 (43.4%) were categorized as having plaque progression in their carotid arteries. Those with plaque progression were significantly older; showed a higher prevalence of hypertension, abdominal obesity, and chronic kidney disease; and had a longer duration of T2DM, higher levels of total cholesterol (TC), triglycerides, and insulin resistance, and lower total bilirubin concentrations than those with no plaque progression. When total serum bilirubin levels were divided into tertiles, the highest tertile group was younger than the lowest tertile group, with higher levels of TC and high-density lipoprotein cholesterol. Multiple logistic regression analysis demonstrated that higher serum bilirubin levels were associated with a significantly lower risk of CIMT progression (odds ratio, 0.584; 95% confidence interval, 0.392–0.870; p=0.008). Age (p<0.001), body mass index (p=0.023), and TC (p=0.019) were also associated with the progression of carotid atherosclerosis in T2DM patients.CONCLUSION: Total serum bilirubin is independently associated with progression of atherosclerosis in the carotid arteries in T2DM patients.

Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors

BACKGROUND: We investigated the predictive markers for the therapeutic efficacy and the best combination of sodium-glucose co-transporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and ipragliflozin) therapy in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 804 patients with T2DM who had taken SGLT2 inhibitor as monotherapy or an add-on therapy were analyzed. Multivariate regression analyses were performed to identify the predictors of SGLT2 inhibitor response including the classes of baseline anti-diabetic medications. RESULTS: After adjusting for age, sex, baseline body mass index (BMI), diabetes duration, duration of SGLT2 inhibitor use, initial glycosylated hemoglobin (HbA1c) level, estimated glomerular filtration rate (eGFR), and other anti-diabetic agent usage, multivariate analysis revealed that shorter diabetes duration, higher initial HbA1c and eGFR were associated with better glycemic response. However, baseline BMI was inversely correlated with glycemic status; lean subjects with well-controlled diabetes and obese subjects with inadequately controlled diabetes received more benefit from SGLT2 inhibitor treatment. In addition, dipeptidyl peptidase 4 (DPP4) inhibitor use was related to a greater reduction in HbA1c in patients with higher baseline HbA1c ≥7%. Sulfonylurea users experienced a larger change from baseline HbA1c but the significance was lost after adjustment for covariates and metformin and thiazolidinedione use did not affect the glycemic outcome. CONCLUSION: A better response to SGLT2 inhibitors is expected in Korean T2DM patients who have higher baseline HbA1c and eGFR with a shorter diabetes duration. Moreover, the add-on of an SGLT2 inhibitor to a DPP4 inhibitor is likely to show the greatest glycemic response.

Corrigenda: Table Correction. Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis

In this article, the description of one equation named “NAFLD liver fat score” in the Table 3 was miswritten.

Effectiveness of Exercise Intervention in Reducing Body Weight and Glycosylated Hemoglobin Levels in Patients with Type 2 Diabetes Mellitus in Korea: A Systematic Review and Meta-Analysis

BACKGROUND: This study aimed to assess the effectiveness of exercise intervention in reducing body weight and glycosylated hemoglobin (HbA1c) level in patients with type 2 diabetes mellitus (T2DM) in Korea. METHODS: Cochrane, PubMed, Embase, KoreaMed, KMbase, NDSL, KCI, RISS, and DBpia databases were used to search randomized controlled trials and controlled clinical trials that compared exercise with non-exercise intervention among patients with non-insulin-treated T2DM in Korea. The effectiveness of exercise intervention was estimated by the mean difference in body weight changes and HbA1c level. Weighted mean difference (WMD) with its corresponding 95% confidence interval (CI) was used as the effect size. The pooled mean differences of outcomes were calculated using a random-effects model. RESULTS: We identified 7,692 studies through literature search and selected 23 articles (723 participants). Compared with the control group, exercise intervention (17 studies) was associated with a significant decline in HbA1c level (WMD, −0.58%; 95% CI, −0.89 to −0.27; I 2=73%). Although no significant effectiveness on body weight was observed, eight aerobic training studies showed a significant reduction in body weight (WMD, −2.25 kg; 95% CI, −4.36 to −0.13; I 2=17%) in the subgroup analysis. CONCLUSION: Exercise significantly improves glycemic control; however, it does not significantly reduce body weight. Aerobic training can be beneficial for patients with non-insulin-treated T2DM in Korea.

Aromatase inhibitor use is a risk factor of carotid plaque presence in endocrine-responsive breast cancer patients

BACKGROUND/AIMS@#The aromatase inhibitors (AIs) are well known anti-hormonal therapy in endocrine-responsive breast cancer patients. It can lead to dyslipidemia and be the risk factor of cardiovascular disease due to low estrogen level. However, some recent studies comparing AIs with placebo have shown controversial results. The aim of this study was to investigate lipid profiles, measurement of carotid intima-media thickness (IMT) and the presence of plaque among endocrine-responsive breast cancer treated with AIs compared to ones that were not treated with AIs.@*METHODS@#A total of 85 postmenopausal women, who underwent breast cancer surgery during the age of 50 to 64 without history of statin use were included. There were 42 patients who were treated with AIs over 1 year (group 1) and 43 patients without AIs use (group 2). Serum total cholesterol, high density lipoprotein cholesterol, triglycerides, fasting blood glucose, carotid IMT, and presence of plaque were assessed.@*RESULTS@#The baseline characteristics were similar between two groups and there was no significant difference in carotid IMT irrespective of AIs administration. However, ultrasonographic evaluation of carotid artery revealed that the presence of plaque in AI users was significantly higher than in non-AI users (66.7% vs. 41.9%, p = 0.02; odds ratio, 4.21 in adjusted model; p = 0.01). History of diabetes was also the significant risk factor for the plaque formation.@*CONCLUSIONS@#There was no significant difference in lipid profile itself between two groups, but more importantly the presence of the plaque was much higher indicating possible detrimental effect of AI on cardiovascular system.

Cardiovascular Outcome Trials of Sodium Glucose Cotransporter 2 Inhibitor and Its Possible Cardioprotective Mechanism

Patients with type 2 diabetes (T2D) have a significantly higher risk of developing cardiovascular diseases such as myocardial infarction, heart failure, and stroke. Current anti-diabetic drugs are highly effective for managing hyperglycemia. However, most T2D patients are still at high risk for cardiovascular disease. Over the past decade, many studies have assessed the efficacy of anti-diabetic drugs in regards to cardiovascular disease outcomes in T2D patients. However, despite the effective glycemic control of these drugs, they failed to show significant benefits that impact the morbidity and mortality of cardiovascular disease (CVD). In recent years, anti-diabetic drugs, developed with other mechanisms, have shown significant results for improving the risk of CVD. In addition, sodium glucose cotransporter 2 inhibitors have shown promising results that impact CVD outcomes in several trials. This article will review the cardiovascular outcomes and possible cardioprotective mechanisms of sodium glucose cotransporter 2 inhibitors.

The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes

BACKGROUND: We evaluated the effects of two dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin and vildagliptin, on metabolic parameters in patients with type 2 diabetes mellitus. METHODS: A total of 170 type 2 diabetes patients treated with sitagliptin or vildagliptin for more than 24 weeks were selected. The patients were separated into two groups, sitagliptin (100 mg once daily, n=93) and vildagliptin (50 mg twice daily, n=77). We compared the effect of each DPP-4 inhibitor on metabolic parameters, including the fasting plasma glucose (FPG), postprandial glucose (PPG), glycated hemoglobin (HbA1c), and glycated albumin (GA) levels, and lipid parameters at baseline and after 24 weeks of treatment. RESULTS: The HbA1c, FPG, and GA levels were similar between the two groups at baseline, but the sitagliptin group displayed a higher PPG level (P=0.03). After 24 weeks of treatment, all of the glucose-related parameters were significantly decreased in both groups (P=0.001). The levels of total cholesterol and triglycerides were only reduced in the vildagliptin group (P=0.001), although the sitagliptin group received a larger quantity of statins than the vildagliptin group (P=0.002).The mean change in the glucose- and lipid-related parameters after 24 weeks of treatment were not significantly different between the two groups (P=not significant). Neither sitagliptin nor vildagliptin treatment was associated with a reduction in the high sensitive C-reactive protein level (P=0.714). CONCLUSION: Vildagliptin and sitagliptin exert a similar effect on metabolic parameters, but vildagliptin exerts a more potent beneficial effect on lipid parameters.

Columnar variant of papillary carcinoma in the thyroglossal duct cyst with progression to lung metastasis / 영남의대학술지

Thyroglossal duct cyst (TGDC) carcinoma generally shows a favorable prognosis. If metastasis is present latently, it may not threaten the patient's life immediately. It has been shown, however, that larger than 1 cm papillary carcinoma (PC), level VI metastasis to the lymph node (LN), which is the nearest to the thyroid, independently predicts a worse prognosis. In the case presented herein, a 61-year-old female patient was diagnosed with an about 3 cm PC in the TGDC, particularly the columnar variant subtype, one of the aggressive variants. She had occult papillary thyroid microcarcinoma, but no LN metastasis. Even though she underwent the Sistrunk procedure and total thyroidectomy with central compartment neck dissection followed by high-dose radioactive iodine remnant ablation, however, the cancer cells spread to level IV neck LN, and finally to the lung. Therefore, when a patient is diagnosed with an aggressive histologic variant of PC in the TGDC, even without LN metastasis, the invasive surgical approach and close postoperative surveillance are necessary, with consideration of the risk of disease progression. Therefore, if it is possible to stratify the risk for patients, higher-risk patients can be offered a more invasive therapeutic approach.

Glycemic Effectiveness of Metformin-Based Dual-Combination Therapies with Sulphonylurea, Pioglitazone, or DPP4-Inhibitor in Drug-Naive Korean Type 2 Diabetic Patients

BACKGROUND: This study compared the glycemic effectiveness of three metformin-based dual therapies according to baseline hemoglobin A1c (HbA1c) to evaluate the appropriateness of the guideline enforced by the National Health Insurance Corporation of Korea for initial medication of type 2 diabetes (T2D). METHODS: This prospective observational study was conducted across 24 weeks for drug-naive Korean T2D patients with HbA1c greater than 7.5%. Subjects were first divided into three groups based on the agent combined with metformin (group 1, gliclazide-modified release or glimepiride; group 2, pioglitazone; group 3, sitagliptin). Subjects were also classified into three categories according to baseline HbA1c (category I, 7.5%< or =HbA1c<9.0%; category II, 9.0%< or =HbA1c<11.0%; category III, 11.0%< or =HbA1c). RESULTS: Among 116 subjects, 99 subjects completed the study, with 88 subjects maintaining the initial medication. While each of the metformin-based dual therapies showed a significant decrease in HbA1c (group 1, 8.9% to 6.4%; group 2, 9.0% to 6.6%; group 3, 9.3% to 6.3%; P<0.001 for each), there was no significant difference in the magnitude of HbA1c change among the groups. While the three HbA1c categories showed significantly different baseline HbA1c levels (8.2% vs. 9.9% vs. 11.9%; P<0.001), endpoint HbA1c was not different (6.4% vs. 6.6% vs. 6.0%; P=0.051). CONCLUSION: The three dual therapies using a combination of metformin and either sulfonylurea, pioglitazone, or sitagliptin showed similar glycemic effectiveness among drug-naive Korean T2D patients. In addition, these regimens were similarly effective across a wide range of baseline HbA1c levels.