The Association of Smoking Status with Diabetic Microvascular Complications in Korean Patients with Type 2 Diabetes.

PURPOSE: Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM. MATERIALS AND METHODS: From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies. RESULTS: Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07-1.97, p=0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p<0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61-8.87), p=0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p<0.05). CONCLUSION: Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking.

Impact of diabetes distress on glycemic control and diabetic complications in type 2 diabetes mellitus.

The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy.

Association between age at diagnosis of type 2 diabetes and cardiovascular morbidity and mortality risks: A nationwide population-based study.

AIMS: We aimed to investigate the association between the age at diagnosis of type 2 diabetes and the risk of cardiovascular (CVD) outcomes in comparison with nondiabetic counterparts. METHODS: A total of 634,350 patients with newly diagnosed type 2 diabetes between January 1, 2012, and December 31, 2014 were included in a Korean population cohort study. Nondiabetic matched controls were selected from the general population in a 1:2 ratio. Participants were followed until the end of 2019 for CVD outcomes and mortality. RESULTS: During 5.7 years of follow-up, patients with type 2 diabetes diagnosed at ≤40 years of age had the highest excess risk for most outcomes relative to controls, with an adjusted hazard ratio (HR) (95 % CI) of 6.08 (5.51-6.70) for total mortality, 7.10 (6.66-7.58) for hospitalization for heart failure, and 5.04 (4.86-5.24) for coronary heart disease. All risks attenuated progressively with each increasing decade of diagnostic age. CONCLUSION: In this population-based cohort study, a younger age at diagnosis of type 2 diabetes was associated with a higher relative risk of mortality and CVD outcomes. Therefore, primary prevention of type 2 diabetes is desirable at all ages but is particularly important at younger ages.

Familial Correlation and Heritability of Hand Grip Strength in Korean Adults (Korea National Health and Nutrition Examination Survey 2014 to 2019).

BACKGRUOUND: The onset and progression of sarcopenia are highly variable among individuals owing to genetic and environmental factors. However, there are a limited number of studies measuring the heritability of muscle strength in large numbers of parent-adult offspring pairs. We aimed to investigate the familial correlation and heritability of hand grip strength (HGS) among Korean adults. METHODS: This family-based cohort study on data from the Korea National Health and Nutrition Examination Survey (2014 to 2019) included 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations of HGS were calculated in different pairs of relatives. Variance component methods were used to estimate heritability. RESULTS: The heritability estimate of HGS among Korean adults was 0.154 (standard error, 0.066). Correlation coefficient estimates for HGS between parent-offspring, sibling, and spouse pairs were significant at 0.07, 0.10, and 0.23 (P<0.001, P=0.041, and P<0.001, respectively). The total variance in the HGS phenotype was explained by additive genetic (15.4%), shared environmental (11.0%), and unique environmental (73.6%) influences. The odds of weak HGS significantly increased in the offspring of parents with weak HGS (odds ratio [OR], 1.69-3.10; P=0.027-0.038), especially in daughters (OR, 2.04-4.64; P=0.029-0.034). CONCLUSION: HGS exhibits a familial correlation and significant heritable tendency in Korean adults. Therefore, Asian adults, especially women, who have parents with weak HGS, need to pay special attention to their muscle health with the help of healthy environmental stimuli.

Age- and dose-dependent effect of statin use on the risk of osteoporotic fracture in older adults.

Previous studies have revealed the protective effects of statins on bone but the association of statins use with osteoporosis-related measurement has shown controversial results. In this study, we found an age, dose andduration-dependent osteoprotective effect of statins in general older population. PURPOSE: Previous studies have revealed the protective effects of statins on bone but the association of statins use with osteoporotic fractures has shown controversial results. METHODS: In this study with Korean National Health Insurance Service-Senior cohort database, a total of 365,656 elderly without previous history of osteoporosis and who were started on statin since January 1 2004 were included and observed until December 31 2012. Hazard rations (HR) for major osteoporotic fractures were calculated using the weighted Cox proportional hazards model with inverse-probability of treatment weighting method. RESULTS: During 6.27 years of follow-up period, 54,959 osteoporotic fractures occurred and the majority of fractures (69.5%) were vertebral fractures. Compared with non-users, statin use was associated with a decreased risk of all outcomes with adjusted HR (95% CI) of 0.77 (0.72-0.83; P < 0.001) for major osteoporotic fractures, 0.49 (0.38-0.62; P < 0.001) for hip fractures, and 0.70 (0.64-0.77; P < 0.001) for vertebral fractures. When outcomes were examined separately by sex, the results were broadly comparable in terms of patterns of risk reduction by statin use. The patients with statin initiated at age ≥ 80 years had the highest risk reduction for most outcomes relative to non-users. Higher cumulative dose of statin was negatively associated with the osteoporotic fracture risk; 0.97 (0.91-1.02) for 30-364 cumulative daily defined dose (cDDD), 0.45 (0.40-0.51) for 365-1,094 cDDD, and 0.22 (0.15-0.33) for ≥ 1,095 cDDD. CONCLUSIONS: Our results showed that statin use was associated with significant reduction in the risk of osteoporotic fractures in general older population.

ß-hydroxybutyrate as a biomarker of ß-cell function in new-onset type 2 diabetes and its association with treatment response at 6 months.

AIMS: Increasing attention has been paid to the potential metabolic benefits of ketone bodies, but the clinical relevance of ketone bodies in newly diagnosed type 2 diabetes mellitus (T2D) remains unclear. We investigated the clinical implications of ketone bodies at the time of diagnosis in patients with drug-naïve T2D. METHODS: Clinical data including serum ß-hydroxybutyrate (ßHB) levels, were collected from 369 patients with newly diagnosed drug-naïve T2D from 2017 to 2021. Subjects were categorized into four ßHB groups based on the level of initial serum ßHB. The associations of initial serum ßHB and urinary ketone levels with glucometabolic indices were analyzed. RESULTS: Higher serum ßHB group was associated with higher levels of glycemic parameters including glycated hemoglobin (HbA1c) with lower levels of indices for insulin secretory function at the point of initial diagnosis of T2D. Nevertheless, higher serum ßHB group was an independent determinant of a greater relative improvement in HbA1c after 6 months of anti-diabetic treatment, regardless of the type of anti-diabetic drug. In addition, patients in higher serum ßHB group were more likely to have well-controlled HbA1c levels (≤6.5%) after 6 months of anti-diabetic treatment. CONCLUSION: In patients with newly diagnosed T2D, a higher initial ßHB level was a significant predictive marker of greater glycemic improvement after antidiabetic treatment, despite its associations with hyperglycemia and decreased insulin secretion at baseline.

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.

Prevalence and risk of diabetic complications in young-onset versus late-onset type 2 diabetes mellitus.

AIMS: To compare the prevalence and risk of diabetic complications between people with young-onset and late-onset type 2 diabetes mellitus (T2DM). METHODS: In this observational study, 10,447 people with T2DM had at least one study of diabetic complications: retinopathy, neuropathy, chronic kidney disease (CKD), carotid artery plaque. We use odds ratios to compare complications between young-onset T2DM (YOD) and late-onset T2DM (LOD). RESULTS: We compare 1,791 people with YOD (diagnosed < 40 years) and 8,656 with LOD (diagnosed ≥ 40 years). The YOD had a higher prevalence of these complications than the LOD (p < 0.011) after adjustment for confounding factors. Further adjustment for diabetes duration greatly attenuated the odds ratios however, neuropathy remained significantly more frequent in people with YOD (adjusted odds ratio: 1.39, 95% confidence interval: 1.13-1.71, p = 002). In cluster analysis on the 2,126 study participants who were diagnosed with T2DM within the previous two years, 47% of the YOD group were in the severe insulin-deficient diabetes cluster in comparison to 23% LOD; 28% and 44% respectively were in the mild age-related diabetes. CONCLUSION: People with YOD had a higher prevalence of complications than those with LOD, but this was mostly attributed to a longer duration of diabetes. However, the prevalence of neuropathy remained significantly higher even after adjusting for factors including the duration of diabetes.

Effect of low skeletal muscle mass and sarcopenic obesity on chronic kidney disease in patients with type 2 diabetes.

OBJECTIVE: This study aimed to investigate the association between low muscle mass or sarcopenic obesity and the risk of incident chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 3123 patients with T2DM with preserved renal function were followed up for incident CKD. Skeletal muscle mass was estimated from bioelectrical impedance analysis. CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 . Sarcopenic obesity was defined as the coexistence of sarcopenia and abdominal obesity. RESULTS: During 8.9 years of follow-up, 530 (17.0%) patients developed incident CKD. When patients were divided into three groups based on sex-specific tertiles, lower muscle mass was not associated with an increased risk of incident CKD after adjustment for risk factors. However, when patients were divided into four groups according to the presence of sarcopenia and obesity, sarcopenic obesity was associated with an increased risk of incident CKD (adjusted hazard ratio 1.77; 95% CI: 1.24-2.51; p = 0.001) compared with the other groups. CONCLUSIONS: Sarcopenic obesity, but not low muscle mass alone, may increase the risk of CKD in patients with T2DM.

Prediction of antidiabetic effect after gastrectomy with Roux-en-Y reconstruction in patients with gastric cancer and type 2 diabetes.

This study investigated the antidiabetic outcomes after gastrectomy with long-limb RY reconstruction (LRYR) and the prognostic factors for remission after 1 year in patients with type 2 diabetes (T2DM) and gastric cancer. In 25 Koreans with T2DM and gastric cancer, plasma glucose and insulin levels were measured during a 75 g oral glucose tolerance test, before and 1 week after gastrectomy with LRYR. Patients were examined after 1 year and we defined glycemic control as "remission" when the HbA1c level after 1 year was <6.0% without medication. One year after surgery, 12 patients achieved HbA1c < 6.0% without medication. Among the preoperative indices, the duration of diabetes was shorter in the remission group than that in the non-remission group (median 2.0 [0-6.5] years vs 7.0 [4.5-10.0] years, P = .023). At 1 week after surgery, significant improvements in fasting, 30 minutes, 60 minutes, 90 minutes stimulated glucose levels and insulin resistance (HOMA-IR and Matsuda index) were found only in the remission group. The multivariable logistic regression analysis results showed that higher 30 minutes stimulated glucose level and HOMA-IR index at 1 week after surgery were independent factors for lower odds of 1-year diabetes remission. Shorter duration of diabetes and early postoperative improvements in 30 minutes stimulated glucose level and HOMA-IR were important determinants of long-term antidiabetic outcomes after gastrectomy with LRYR in patients with T2DM and gastric cancer.

Effect of Dapagliflozin in Combination with Lobeglitazone and Metformin in Korean Patients with Type 2 Diabetes in Real-World Clinical Practice.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of dapagliflozin as an add-on or a switch therapy to lobeglitazone plus metformin (MFM) in Korean patients with inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice. MATERIALS AND METHODS: The study included 109 patients who started dapagliflozin as add-on or switch therapy to lobeglitazone plus MFM. The primary outcome was a change in glycated hemoglobin (HbA1c) level from baseline after 12 months of treatment. Secondary outcomes included changes in fasting plasma glucose (FPG), lipid profiles, body weight, visceral fat area (VFA), and blood pressure after 12 months of treatment. RESULTS: The baseline HbA1c was 8.3±1.3% (8.7±1.5% in the add-on group and 8.1±1.0% in the switch group). After 12 months, mean HbA1c decreased (-0.91%) in all patients (p<0.05) (-1.39% in the add-on group and -0.63% in the switch group). Significant reductions in FPG were also observed in both the add-on and switch groups (-54.37 mg/dL and -24.68 mg/dL, respectively). Overall, there was a significant improvement in serum triglyceride (-24.74 mg/dL), low density lipoprotein cholesterol (-7.92 mg/dL), body weight (-2.98 kg), VFA (-9.00 cm²), and systolic blood pressure (-8.67 mm Hg). Approximately 35.8% of patients achieved HbA1c <7.0% after 12 months. CONCLUSION: Dapagliflozin, as an add-on or a switch therapy to lobeglitazone plus MFM, can be a suitable alternative for Korean patients with inadequately controlled T2DM. The combination therapy resulted in significant reductions in HbA1c levels, body weight, and blood pressure.

Differences in complication patterns in subgroups of type 2 diabetes according to insulin resistance and beta-cell function.

This study aimed to determine whether the patterns of diabetic complications differed when patients with type 2 diabetes mellitus (T2DM) were simply classified according to insulin sensitivity and beta-cell function. This observational study included 8861 patients with T2DM who underwent concurrent testing for fasting glucose, fasting insulin, and one or more diabetic complications. We categorized the patients into four groups according to insulin sensitivity and beta-cell function. Compared with the reference group (mild insulin resistance and beta-cell dysfunction), the "severe beta-cell dysfunction" group had lower odds of chronic kidney disease [adjusted odds ratios (aOR) 0.611]. The "severe insulin resistance" group had higher odds of carotid artery plaque presence (aOR 1.238). The "severe insulin resistance and beta-cell dysfunction" group had significantly higher odds of large fiber neuropathy (aOR 1.397, all p < 0.05). After a median of five years of follow-up, this group distinction did not lead to a difference in risk of new diabetic retinopathy or chronic kidney disease. In addition, there was no significant difference among the groups in plaque progression risk over 8-10 years in the longitudinal follow-up analysis. The patterns of complications differ when patients with T2DM are classified according to insulin resistance and beta-cell dysfunction. However, there were no differences in the risk of developing new complications.

Association of Metabolomic Change and Treatment Response in Patients with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease, yet cost-effective and non-invasive diagnostic tools to monitor the severity of the disease are lacking. We aimed to investigate the metabolomic changes in NAFLD associated with therapeutic responses. It was conducted in 63 patients with NAFLD who received either ezetimibe plus rosuvastatin or rosuvastatin monotherapy. The treatment response was determined by MRI performed at baseline and week 24. The metabolites were measured at baseline and week 12. In the combination group, a relative decrease in xanthine was associated with a good response to liver fat decrease, while a relative increase in choline was associated with a good response to liver stiffness. In the monotherapy group, the relative decreases in triglyceride (TG) 20:5_36:2, TG 18:1_38:6, acetylcarnitine (C2), fatty acid (FA) 18:2, FA 18:1, and docosahexaenoic acid were associated with a decrease in liver fat, while hexosylceramide (d18:2/16:0) and hippuric acid were associated with a decrease in liver stiffness. Models using the metabolite changes showed an AUC of >0.75 in receiver operating curve analysis for predicting an improvement in liver fat and stiffness. This approach revealed the physiological impact of drugs, suggesting the mechanism underlying the development of this disease.

Association between Metabolically Healthy Obesity and Subclinical Atherosclerosis in the Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) Cohort.

We aimed to investigate the association between a new definition of metabolic health (MH) and subclinical atherosclerosis in a cohort of patients without previous cardiovascular disease (CVD). In total, 7824 community-dwelling adults were categorized as normal weight, overweight, or obese. Metabolically healthy obesity (MHO) was defined as obesity accompanied by all of the following criteria: systolic blood pressure (BP) < 130 mmHg, no use of BP-lowering medication, waist-hip ratio <0.832 (women) and <0.887 (men), and no prevalent diabetes. Carotid atherosclerosis was defined as carotid plaque or mean carotid intima-media thickness ≥ 1.1 mm. The prevalence of carotid atherosclerosis was 8.3% and 1113 (14.2%) patients were classified as having MHO. All individuals classified as metabolically unhealthy were at an increased risk of carotid atherosclerosis independent of body mass index categories. Conversely, the risk of carotid atherosclerosis in individuals with MHO was not significantly increased compared to that in metabolically healthy normal weight participants (hazard ratio 1.20, 95% confidence interval 0.87−1.67). This new definition of MH was able to identify people with MHO without an increased risk of CVD in an Asian community cohort.

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.

Ezetimibe combination therapy with statin for non-alcoholic fatty liver disease: an open-label randomized controlled trial (ESSENTIAL study).

BACKGROUND: The effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: A randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change. RESULTS: Combination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; p = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; p < 0.001 and 15.0 to 12.4%; p = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, p > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; p = 0.018), but not in the monotherapy group (323 to 311 dB/m; p = 0.104). CONCLUSIONS: Ezetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (registration number: NCT03434613 ).

Relationships Between Pulmonary Function and Composite Indices of Femoral Neck Strength in Korean Men (KNHANES IV).

BACKGROUND: Despite the close relationship between osteoporosis and chronic pulmonary diseases, few studies have evaluated relationships between pulmonary functions and bone quality. We investigated associations between pulmonary function test results and femoral neck strength indices (SIs) in Korean men. METHODS: This population-based, cross-sectional study was conducted using data from the Korea National Health and Nutrition Examination Survey IV on 936 men aged ≥ 19 years. Pulmonary functions (forced vital capacity [FVC] and forced expiratory volume in one second [FEV1]) were measured using a dry rolling seal spirometer. Femoral neck SIs, relative to load, were calculated by hip dual-energy X-ray absorptiometry for compression strength index (CSI), bending strength index (BSI), and impact strength index (ISI). RESULTS: The 443 (47.3%) of the 936 men were current smokers. FVC, FVC percentage with respect to the expected normal value, FEV1, and FEV1 percentage with respect to the expected normal value (FEV1p) were positively associated with CSI and BSI after adjusting for confounders, including smoking history (ß = 0.003-0.223, P = 0.005-0.036). FEV1 and FEV1p were positively associated with ISI (ß = 0.000-0.014, P = 0.010-0.025). Of components of femoral neck SIs, bone mineral density was correlated with FEV1 and FEV1p (ß = 0.001-0.037, P = 0.017-0.019). After adjusting for all confounders, all femoral neck SIs increased with FVC quintiles (P for trends = 0.001-0.012), and CSI and BSI increased with FEV1 quintiles (P for trends = 0.034-0.043). CONCLUSION: Reduced pulmonary function was correlated with reduced femoral neck strength, even after adjusting for smoking history in Korean men. Femoral neck SIs might be useful tools for evaluating bone health in men with reduced pulmonary function.

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.

Expeditiously Crystallized Pure Orthorhombic-Hf0.5Zr0.5O2 for Negative Capacitance Field Effect Transistors.

Ultralow-power logic devices are next-generation electronics in which their maximum efficacies are realized at minimum input power expenses. The integration of ferroelectric negative capacitors in the regular gate stacks of two-dimensional field-effect transistors addresses two intriguing challenges in today's electronics; short channel effects and high operating voltages. The complementary-metal-oxide-semiconductor-compatible Hf0.5Zr0.5O2 (HZO) is an excellent ferroelectric material crystallized in a noncentrosymmetric o-phase. The present work is the first to utilize pulsed laser deposition (PLD)-grown phase-pure ferroelectric HZO to achieve steep slope negative capacitance (NC) in field effect transistors (FETs). A dual-step growth strategy is designed to achieve phase-pure orthorhombic HZO on silicon and other conducting substrates. The room-temperature PLD-grown amorphous HZO is allowed to crystallize using rapid thermal annealing at 600 °C. The polycrystalline orthorhombic HZO is further integrated with atomic layer deposition-grown HfO2 to achieve a stable NC transition. The stack is further integrated into the molybdenum disulfide channel to achieve steep switching and a hysteresis-free operation of the resulting FETs. The subthreshold swings of the FETs are 20.42 and 26.16 mV/dec in forward and reverse bias conditions, respectively.

Use of statin for the primary prevention of cardiovascular outcomes in elderly patients: A propensity-matched cohort study.

BACKGROUND AND AIMS: Herein, we investigate whether statin treatment as primary prevention reduces cardiovascular outcomes in elderly Asian patients. METHODS: Data were obtained from the Korean National Health Insurance Service-Senior Cohort database (n = 558,147). A total of 81,729 elderly patients (≥75 years) without clinically recognized atherosclerotic cardiovascular disease (CVD) were included. The patients who did not have a history of statin use in year 2003 were followed from January 2004 to the end of 2012. New statin users (n = 3670) were matched on the basis of the propensity score in a 1:2 ratio with non-users. Incidences of myocardial infarction, ischemic stroke, and death from CVD were compared using the Cox proportional hazards model. RESULTS: The risk of cardiovascular death was significantly reduced in the statin treatment group compared with the non-user group (hazard ratio [HR] 0.34, 95% confidence interval [CI] 0.29 to 0.40; p < 0.001). This effect was observed in both patient groups with and without diabetes. In patients with diabetes, the HR for statin use was 0.85 (95% CI 0.55 to 1.33) for myocardial infarction and 0.75 (95% CI 0.60 to 0.93) for ischemic stroke. In participants without diabetes, the HR of statin use was 0.95 (95% CI 0.73 to 1.24) for myocardial infarction and 1.13 (95% CI 1.01 to 1.26) for ischemic stroke. The presence of hypertension was also a significant factor in the prevention of ischemic stroke by statin treatment. CONCLUSIONS: In elderly patients without clinically recognized atherosclerotic CVD, the risk of cardiovascular mortality was significantly reduced with statin treatment than with non-users. In participants with type 2 diabetes, statin treatment was associated with a reduction in ischemic stroke.