Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective.

It has been generally accepted that insulin resistance (IR) and reduced insulin secretory capacity are the basic pathogenesis of type 2 diabetes mellitus (T2DM). In addition to genetic factors, the persistence of systemic inflammation caused by obesity and the associated threat of lipotoxicity increase the risk of T2DM. In particular, the main cause of IR is obesity and subjects with T2DM have a higher body mass index (BMI) than normal subjects according to recent studies. The prevalence of T2DM with IR has increased with increasing BMI during the past three decades. According to recent studies, homeostatic model assessment of IR was increased compared to that of the 1990s. Rising prevalence of obesity in Korea have contributed to the development of IR, non-alcoholic fatty liver disease and T2DM and cutting this vicious cycle is important. My colleagues and I have investigated this pathogenic mechanism on this theme through clinical and experimental studies over 20 years and herein, I would like to summarize some of our studies with deep gratitude for receiving the prestigious 2023 Sulwon Award.

A potential association between COVID-19 vaccination and development of alzheimer's disease.

BACKGROUND: The challenges of the COVID-19 pandemic extend to concerns about vaccine side effects, particularly potential links to neurodegenerative diseases such as Alzheimer's disease (AD). AIM: This study investigates the association between COVID-19 vaccination and the onset of AD and its prodromal state, mild cognitive impairment (MCI). DESIGN: A nationwide, retrospective cohort study leveraging data from the Korean National Health Insurance Service was conducted. METHODS: The study, conducted in Seoul, South Korea, analyzed data from a random 50% sample of city residents aged 65 and above, totaling 558,017 individuals. Participants were divided into vaccinated and unvaccinated groups, with vaccinations including mRNA and cDNA vaccines. The study focused on AD and MCI incidences post-vaccination, identified via ICD-10 codes, using multivariable logistic and Cox regression analyses. Patients with vascular dementia or Parkinson's disease served as controls. RESULTS: Findings showed an increased incidence of MCI and AD in vaccinated individuals, particularly those receiving mRNA vaccines, within three months post-vaccination. The mRNA vaccine group exhibited a significantly higher incidence of AD (Odds Ratio [OR]: 1.225; 95% Confidence Interval [CI]: 1.025-1.464; p = 0.026) and MCI (OR: 2.377; CI: 1.845-3.064; p < 0.001) compared to the unvaccinated group. No significant relationship was found with vascular dementia or Parkinson's disease. CONCLUSIONS: Preliminary evidence suggests a potential link between COVID-19 vaccination, particularly mRNA vaccines, and increased incidences of AD and MCI. This underscores the need for further research to elucidate the relationship between vaccine-induced immune responses and neurodegenerative processes, advocating for continuous monitoring and investigation into the vaccines' long-term neurological impacts.

Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Background: Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD. Methods: We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573). Results: Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria. Conclusion: Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.

Effect of gout and diabetic kidney disease on renal cancer development in Korea.

Background: Chronic kidney disease (CKD) and gout are risk factors for renal cancer. We analysed the effects of comorbid diabetic kidney disease and gout on renal cancer. Methods: This retrospective cohort study enrolled 847 884 patients with type 2 diabetes mellitus (T2DM) who underwent health assessments provided by the Korean National Health Insurance Service in 2009. Based on CKD occurrence (glomerular filtration rate <60 ml/min/1.73 m2) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD-Gout- (87.5%), CKD-Gout+ (2.5%), CKD+Gout- (9.3%) and CKD+Gout+ (0.7%). Patients with incident renal cancer (International Classification of Diseases code C64) were followed up until December 2018. Results: Renal cancer was diagnosed in 2376 patients (0.3%). Renal cancer incidence increased in sequential order of CKD-Gout- [0.29/1000 person-years (PY), CKD+Gout- and CKD-Gout+ (0.44 and 0.48/1000 PY, respectively) and CKD+Gout+ (1.14/1000 PY). Comorbid gout increased renal cancer risk depending on CKD occurrence {hazard ratio [HR] 1.28 [95% confidence interval (CI) 1.04-1.58 among those without CKD; HR 1.95 [95% CI 1.45-2.63] among those with CKD; P-value for interaction = 0.024}. The interaction was significant, particularly in men and patients with a shorter diabetes duration (<5 years) and lesser medication use (no insulin or fewer than three classes of oral hypoglycaemic agents). Conclusions: CKD and gout individually contributed to renal cancer incidence, and the risk is further increased when gout coexists with CKD. Screening for gout and appropriate management of CKD at an early T2DM stage may be beneficial.

Impact of Chronic Kidney Disease and Gout on End-Stage Renal Disease in Type 2 Diabetes: Population-Based Cohort Study.

Background: We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status. Methods: Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD-Gout-, CKD- Gout+, CKD+Gout-, and CKD+Gout+. Patients with incident ESRD were followed up until December 2018. Results: Among 847,884 patients, 11,825 (1.4%) experienced progression to ESRD. ESRD incidence increased in the following order: 0.77 per 1,000 person-years (PY) in the CKD-Gout- group, 1.34/1,000 PY in the CKD-Gout+ group, 8.20/1,000 PY in the CKD+Gout- group, and 23.06/1,000 PY in the CKD+Gout+ group. The presence of gout modified the ESRD risk in a status-dependent manner. Hazard ratios (HR) were 1.49 (95% confidence interval [CI], 1.32 to 1.69) and 2.24 (95% CI, 2.09 to 2.40) in patients without and with CKD, respectively, indicating a significant interaction (P<0.0001). The CKD+Gout+ group had a markedly higher risk of developing ESRD (HR, 18.9; 95% CI, 17.58 to 20.32) than the reference group (CKD-Gout-). Conclusion: Gout substantially enhances the risk of ESRD, even in the absence of CKD. Concurrent CKD and gout synergistically increase the risk of ESRD. Therefore, physicians should carefully screen for hyperuricemia to prevent progression to ESRD.

Attention to Innate Circadian Rhythm and the Impact of Its Disruption on Diabetes.

Novel strategies are required to reduce the risk of developing diabetes and/or clinical outcomes and complications of diabetes. In this regard, the role of the circadian system may be a potential candidate for the prevention of diabetes. We reviewed evidence from animal, clinical, and epidemiological studies linking the circadian system to various aspects of the pathophysiology and clinical outcomes of diabetes. The circadian clock governs genetic, metabolic, hormonal, and behavioral signals in anticipation of cyclic 24-hour events through interactions between a "central clock" in the suprachiasmatic nucleus and "peripheral clocks" in the whole body. Currently, circadian rhythmicity in humans can be subjectively or objectively assessed by measuring melatonin and glucocorticoid levels, core body temperature, peripheral blood, oral mucosa, hair follicles, rest-activity cycles, sleep diaries, and circadian chronotypes. In this review, we summarized various circadian misalignments, such as altered light-dark, sleep-wake, rest-activity, fasting-feeding, shift work, evening chronotype, and social jetlag, as well as mutations in clock genes that could contribute to the development of diabetes and poor glycemic status in patients with diabetes. Targeting critical components of the circadian system could deliver potential candidates for the treatment and prevention of type 2 diabetes mellitus in the future.

Association of physical activity with total and cause-specific mortality in patients with diabetes: A nationwide population-based cohort study.

AIMS: Physical inactivity is a modifiable risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM); however, little is known about its association with mortality due to other causes. Herein, we investigated the association between physical activity (PA) and cause-specific mortality in patients with T2DM. METHODS: We analyzed data from the Korean National Health Insurance Service and claims database of adults with T2DM aged >20 years at baseline (n = 2,651,214). Each participant's PA volume was measured as the metabolic equivalent of tasks (METs)-min per week, and hazard ratios of all-cause and cause-specific mortality relative to PA levels were estimated. RESULTS: During the 7.8 years of follow-up, all-cause, CVD, respiratory, cancer, and other causes of mortality were lowest in patients engaged in vigorous PA. MET-min/week was inversely associated with mortality after adjusting for covariates. The reduction in total and cause-specific mortality was greater in patients aged ≥65 years than in those aged <65 years. CONCLUSIONS: Increasing PA may facilitate a reduction in mortality from various causes, especially among older patients with T2DM. Clinicians should encourage such patients to increase their daily PA levels to reduce their risk of mortality.

Clinical and Lifestyle Determinants of Continuous Glucose Monitoring Metrics in Insulin-Treated Patients with Type 2 Diabetes Mellitus.

BACKGRUOUND: There was limited evidence to evaluate the association between lifestyle habits and continuous glucose monitoring (CGM) metrics. Thus, we aimed to depict the behavioral and metabolic determinants of CGM metrics in insulin-treated patients with type 2 diabetes mellitus (T2DM). METHODS: This is a prospective observational study. We analyzed data from 122 insulin-treated patients with T2DM. Participants wore Dexcom G6 and Fitbit, and diet information was identified for 10 days. Multivariate-adjusted logistic regression analysis was performed for the simultaneous achievement of CGM-based targets, defined by the percentage of time in terms of hyper, hypoglycemia and glycemic variability (GV). Intake of macronutrients and fiber, step counts, sleep, postprandial C-peptide-to-glucose ratio (PCGR), information about glucose lowering medications and metabolic factors were added to the analyses. Additionally, we evaluated the impact of the distribution of energy and macronutrient during a day, and snack consumption on CGM metrics. RESULTS: Logistic regression analysis revealed that female, participants with high PCGR, low glycosylated hemoglobin (HbA1c) and daytime step count had a higher probability of achieving all targets based on CGM (odds ratios [95% confidence intervals] which were 0.24 [0.09 to 0.65], 1.34 [1.03 to 1.25], 0.95 [0.9 to 0.99], and 1.15 [1.03 to 1.29], respectively). And participants who ate snacks showed a shorter period of hyperglycemia and less GV compared to those without. CONCLUSION: We confirmed that residual insulin secretion, daytime step count, HbA1c, and women were the most relevant determinants of adequate glycemic control in insulin-treated patients with T2DM. In addition, individuals with snack consumption were exposed to lower times of hyperglycemia and GV.

Sleep Duration and the Risk of Type 2 Diabetes: A Community-Based Cohort Study with a 16-Year Follow-up.

BACKGRUOUND: We aimed to investigate the moderating effects of obesity, age, and sex on the association between sleep duration and the development of diabetes in Asians. METHODS: We analyzed data from a cohort of the Korean Genome and Epidemiology Study conducted from 2001 to 2020. After excluding shift workers and those with diabetes at baseline, 7,407 participants were stratified into three groups according to sleep duration: ≤5 hours/night, >5 to 7 hours/night (reference), and >7 hours/night. The Cox proportional hazards analyses were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes mellitus (T2DM). Subgroup analyses were performed according to obesity, age, and sex. RESULTS: During 16 years of follow-up, 2,024 cases of T2DM were identified. Individuals who slept ≤5 h/night had a higher risk of incident diabetes than the reference group (HR, 1.17; 95% CI, 1.02 to 1.33). The subgroup analysis observed a valid interaction with sleep duration only for obesity. A higher risk of T2DM was observed in the ≤5 hours/night group in non-obese individuals, men, and those aged <60 years, and in the >7 hours/night group in obese individuals (HRs were 1.34 [95% CI, 1.11 to 1.61], 1.22 [95% CI, 1 to 1.49], and 1.18 [95% CI, 1.01 to 1.39], respectively). CONCLUSION: This study confirmed the effect of sleep deprivation on the risk of T2DM throughout the 16-year follow-up period. This impact was confined to non-obese or young individuals and men. We observed a significant interaction between sleep duration and obesity.

Changes in Patterns of Physical Activity and Risk of Heart Failure in Newly Diagnosed Diabetes Mellitus Patients.

BACKGROUND: Exercise is recommended for type 2 diabetes mellitus (T2DM) patients to prevent cardiovascular disease. However, the effects of physical activity (PA) for reducing the risk of heart failure (HF) has yet to be elucidated. We aimed to assess the effect of changes in patterns of PA on incident HF, especially in newly diagnosed diabetic patients. METHODS: We examined health examination data and claims records of 294,528 participants from the Korean National Health Insurance Service who underwent health examinations between 2009 and 2012 and were newly diagnosed with T2DM. Participants were classified into the four groups according to changes in PA between before and after the diagnosis of T2DM: continuously inactive, inactive to active, active to inactive, and continuously active. The development of HF was analyzed until 2017. RESULTS: As compared with those who were continuously inactive, those who became physically active after diagnosis showed a reduced risk for HF (adjusted hazard ratio [aHR], 0.79; 95% confidence interval [CI], 0.66 to 0.93). Those who were continuously active had the lowest risk for HF (aHR, 0.77; 95% CI, 0.62 to 0.96). As compared with those who were inactive, those who exercised regularly, either performing vigorous or moderate PA, had a lower HF risk (aHR, 0.79; 95% CI, 0.69 to 0.91). CONCLUSION: Among individuals with newly diagnosed T2DM, the risk of HF was reduced in those with higher levels of PA after diagnosis was made. Our results suggest either increasing or maintaining the frequency of PA after the diagnosis of T2DM may lower the risk of HF.

Increased Risk of NAFLD in Adults with Glomerular Hyperfiltration: An 8-Year Cohort Study Based on 147,162 Koreans.

This study evaluated whether glomerular hyperfiltration (GHF) could predict nonalcoholic fatty liver disease (NAFLD) and fibrosis. A longitudinal cohort study including 147,479 participants aged 20-65 years without NAFLD and kidney disease at baseline was performed. GHF cutoff values were defined as age- and sex-specific estimated glomerular filtration rate (eGFRs) above the 95th percentile, and eGFR values between the 50th and 65th percentiles were used as reference groups. NAFLD was diagnosed via abdominal ultrasonography, and the fibrosis status was evaluated using the NAFLD fibrosis score and Fibrosis-4. During 598,745 person years of follow-up (median, 4.6 years), subjects with GHF at baseline had the highest hazard ratio (HR) for the development of NAFLD (HR 1.21; 95% CI 1.14-1.29) and fibrosis progression (HR 1.42; 95% CI 1.11-1.82) after adjusting for confounding factors. A higher baseline eGFR percentile maintained a higher risk of NAFLD and fibrosis probability. The persistent GHF group during follow-up had the highest HR for NAFLD compared to the persistent non-GHF group (HR 1.31; 95% CI 1.14-1.51). These results were consistent in all subgroups and statistically more prominent in participants without diabetes. GHF was positively associated with increased risk of NAFLD and probability of liver fibrosis in healthy adults.

Current Advances of Artificial Pancreas Systems: A Comprehensive Review of the Clinical Evidence.

Since Banting and Best isolated insulin in the 1920s, dramatic progress has been made in the treatment of type 1 diabetes mellitus (T1DM). However, dose titration and timely injection to maintain optimal glycemic control are often challenging for T1DM patients and their families because they require frequent blood glucose checks. In recent years, technological advances in insulin pumps and continuous glucose monitoring systems have created paradigm shifts in T1DM care that are being extended to develop artificial pancreas systems (APSs). Numerous studies that demonstrate the superiority of glycemic control offered by APSs over those offered by conventional treatment are still being published, and rapid commercialization and use in actual practice have already begun. Given this rapid development, keeping up with the latest knowledge in an organized way is confusing for both patients and medical staff. Herein, we explore the history, clinical evidence, and current state of APSs, focusing on various development groups and the commercialization status. We also discuss APS development in groups outside the usual T1DM patients and the administration of adjunct agents, such as amylin analogues, in APSs.

Increased Risk of Nonalcoholic Fatty Liver Disease in Individuals with High Weight Variability.

BACKGROUND: Weight loss through lifestyle modification is recommended for patients with nonalcoholic fatty liver disease (NAFLD). Recent studies have suggested that repeated loss and gain of weight is associated with worse health outcomes. This study aimed to examine the association between weight variability and the risk of NAFLD in patients without diabetes. METHODS: We examined the health-checkup data of 30,708 participants who had undergone serial examinations between 2010 and 2014. Weight variability was assessed using coefficient of variation and the average successive variability of weight (ASVW), which was defined as the sum of absolute weight changes between successive years over the 5-year period divided by 4. The participants were classified according to the baseline body mass index and weight difference over 4 years. RESULTS: On dividing the participants into four groups according to ASVW quartile groups, those in the highest quartile showed a significantly increased risk of NAFLD compared to those in the lowest quartile (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.63 to 2.19). Among participants without obesity at baseline, individuals with high ASVW showed increased risk of NAFLD (OR, 1.80; 95% CI, 1.61 to 2.01). Participants with increased weight over 4 years and high ASVW demonstrated higher risk of NAFLD compared to those with stable weight and low ASVW (OR, 4.87; 95% CI, 4.29 to 5.53). CONCLUSION: Regardless of participant baseline obesity status, high weight variability was associated with an increased risk of developing NAFLD. Our results suggest that further effort is required to minimize weight fluctuations after achieving a desirable body weight.

Baseline homeostasis model assessment of insulin resistance associated with fibrosis progression in patients with nonalcoholic fatty liver disease without diabetes: A cohort study.

BACKGROUND AND AIMS: Fibrosis progression is the most important prognostic factor, and insulin resistance is one of the main mechanisms associated with fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD). We evaluate the association between baseline insulin resistance and future fibrosis progression in patients with NAFLD without diabetes. APPROACH AND RESULTS: This retrospective longitudinal study with 8-year follow-up period included 32,606 (men, 83%) participants aged >20 years (average age, 38.0 years) without diabetes at baseline who completed at least two comprehensive health checkups from January 1, 2010 to December 31, 2018. NAFLD was diagnosed based on ultrasonography. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate baseline insulin resistance. Fibrosis progression was assessed using the aspartate aminotransferase to platelet ratio index (APRI). The advanced liver fibrosis with an APRI value above the intermediate fibrosis probability (≥0.5) developed in a total of 2,897 participants during 136,108 person-years. 114 participants progressed to a high fibrosis probability stage (APRI >1.5) during 141,064 person-years. Using the lowest baseline HOMA-IR quartile group (Q1) as a reference, the multivariate-adjusted hazard ratio (HR) for development of advanced liver fibrosis (APRI ≥0.5) in the highest baseline HOMA-IR quartile group (Q4) was 1.95 (95% confidence interval [CI] 1.74-2.19; Model 4). And the HR for development of advanced liver fibrosis with high fibrosis probability was 1.95 (95% CI 1.10-3.46; Model 4). The positive association was maintained throughout the entire follow-up period. The baseline HOMA-IR model was superior to the baseline body mass index (BMI) model in predicting the progression of fibrosis probability. CONCLUSIONS: In this longitudinal study, we found that the degree of baseline insulin resistance, assessed by HOMA-IR values, was positively associated with future fibrosis progression in patients with NAFLD without diabetes.

The Effects of Glucose Lowering Agents on the Secondary Prevention of Coronary Artery Disease in Patients with Type 2 Diabetes.

BACKGROUND: Patients with diabetes have a higher risk of requiring repeated percutaneous coronary intervention (PCI) than non-diabetic patients. We aimed to evaluate and compare the effects of anti-diabetic drugs on the secondary prevention of myocardial infarction among type 2 diabetes mellitus patients. METHODS: We analyzed the general health check-up dataset and claims data of the Korean National Health Insurance Service of 199,714 participants (age ≥30 years) who underwent PCIs between 2010 and 2013. Those who underwent additional PCI within 1 year of their first PCI (n=3,325) and those who died within 1 year (n=1,312) were excluded. Patients were classified according to their prescription records for glucose-lowering agents. The primary endpoint was the incidence rate of coronary revascularization. RESULTS: A total of 35,348 patients were included in the study. Metformin significantly decreased the risk of requiring repeat PCI in all patients (adjusted hazard ratio [aHR], 0.77). In obese patients with body mass index (BMI) ≥25 kg/m2, patients treated with thiazolidinedione (TZD) exhibited a decreased risk of requiring repeat revascularization than those who were not treated with TZD (aHR, 0.77; 95% confidence interval, 0.63 to 0.95). Patients treated with metformin showed a decreased risk of requiring revascularization regardless of their BMI. Insulin, meglitinide, and alpha-glucosidase inhibitor were associated with increased risk of repeated PCI. CONCLUSION: The risk of requiring repeat revascularization was lower in diabetic patients treated with metformin and in obese patients treated with TZD. These results suggest that physicians should choose appropriate glucose-lowering agents for the secondary prevention of coronary artery disease.

Changes in Insulin Resistance Index and the Risk of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease without Diabetes: Kangbuk Samsung Health Study.

BACKGROUND: Fibrosis is the most important prognostic factor for nonalcoholic fatty liver disease (NAFLD). Insulin resistance plays a key role of fibrosis progression. We evaluated the association between changes in homeostasis model assessment of insulin resistance (HOMA-IR) values and changes in fibrosis status in NAFLD. METHODS: We analyzed the data of 15,728 participants with NAFLD (86% men, mean age 40.5 years) who had no diabetes at baseline and visited our centers for health check-ups both in 2012 and 2016. The participants were classified into four groups according to the degree of change in HOMA-IR values from baseline to the end of follow-up: G1 (<0), G2 (0-0.50), G3 (0.51-1.00), and G4 (>1.00). NAFLD was assessed by ultrasonography, and fibrosis status was evaluated by the NAFLD fibrosis score (NFS) and the aspartate aminotransferase to platelet ratio index (APRI). RESULTS: After the 4-year follow-up, the multivariable-adjusted odds ratio (OR) for progression of fibrosis probability increased with increasing HOMA-IR values (OR, 2.25; 95% confidence interval [CI], 1.87 to 2.71 for NFS; and OR, 2.55; 95% CI, 2.05 to 3.18 for APRI, G4). This tendency remained consistent throughout the subgroup analyses, except in those for female sex and a body mass index <25 kg/m2. The OR for regression of fibrosis probability decreased with increasing HOMA-IR values (OR, 0.33; 95% CI, 0.25 to 0.43 for NFS, G4). CONCLUSION: Changes in HOMA-IR values were associated with changes in fibrosis status in patients with NAFLD without diabetes, which underscores the role of insulin resistance in liver fibrosis.

Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study.

BACKGROUND: Previous studies have suggested that depression in patients with diabetes is associated with worse health outcomes. The aim of this study was to evaluate the risk of cardiovascular disease (CVD) and mortality in patients with diabetes with comorbid depression. METHODS: We examined the general health check-up data and claim database of the Korean National Health Insurance Service (NHIS) of 2,668,615 participants with type 2 diabetes mellitus who had examinations between 2009 and 2012. As NHIS database has been established since 2002, those who had been diagnosed with depression or CVD since 2002 were excluded. The 2,228,443 participants were classified into three groups according to the claim history of depression; normal group (n=2,166,979), transient depression group (one episode of depression, n=42,124) and persistent depression group (at least two episodes of depression, n=19,340). The development of CVD and mortality were analyzed from 2009 to 2017. RESULTS: Those with depression showed a significantly increased risk for stroke (transient depression group: hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.15 to 1.26) (persistent depression group: HR, 1.54; 95% CI, 1.46 to 1.63). Those with depression had an increased risk for myocardial infarction (transient depression group: HR, 1.25; 95% CI, 1.18 to 1.31) (persistent depression group: HR, 1.38; 95% CI, 1.29 to 1.49). The persistent depression group had an increased risk for all-cause mortality (HR, 1.66; 95% CI, 1.60 to 1.72). CONCLUSION: Coexisting depression in patients with diabetes has a deleterious effect on the development of CVD and mortality. We suggest that more attention should be given to patients with diabetes who present with depressive symptoms.

Autonomic Imbalance Increases the Risk for Non-alcoholic Fatty Liver Disease.

Background: Although autonomic imbalance is associated with an increased risk for metabolic disease, its effects on nonalcoholic fatty liver disease (NAFLD) remains unclear. We aimed to evaluate whether autonomic dysfunction predicts the risk for nonalcoholic fatty liver disease (NAFLD). Methods: A total of 33,899 participants without NAFLD who underwent health screening programs between 2011 and 2018 were enrolled. NAFLD was identified by ultrasonography. Autonomic activity was estimated using heart rate variability (HRV). Time domain [standard deviation of the normal-to-normal interval (SDNN) and root mean square difference (RMSSD)]; frequency domain [total power (TP), low frequency (LF), and high frequency (HF), and LF/HF ratio were analyzed. Findings: A total 6,466 participants developed NAFLD within a median of 5.7 years. Subjects with incident NAFLD showed decreased overall autonomic modulation and vagal activity with lowered SDNN, RMSSD, HF, normalized HF, compared to those without NAFLD. As the SDNN, RMSSD, TP, LF, and HF tertiles increased, the risk of NAFLD decreased with tertile 1 being the reference group [the hazard ratios (95% confidence intervals) of tertile 3 were 0.90 (0.85-0.96), 0.83 (0.78-0.88), 0.91 (0.86-0.97), 0.93 (0.87-0.99) and 0.89 (0.83-0.94), respectively] after adjusting for potential confounders. The risk for NAFLD was significantly higher in subjects in whom sustained elevated heart rate, normalized LF, and LF/HF ratio values than in those with sustained decrease in these parameters during follow-up. Conclusions: Overall autonomic imbalance, decreased parasympathetic activity, and recently increased sympathetic activity might increase the risk of NAFLD.

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Magnetic resonance imaging (MRI) is an essential modality for the diagnosis of musculoskeletal system defects because of its higher soft-tissue contrast and spatial resolution. With the recent development of MRI-related technology, faster imaging and various image plane reconstructions are possible, enabling better assessment of three-dimensional musculoskeletal anatomy and lesions. Furthermore, the image quality, diagnostic accuracy, and acquisition time depend on the MRI protocol used. Moreover, the protocol affects the efficiency of the MRI scanner. Therefore, it is important for a radiologist to optimize the MRI protocol. In this review, we will provide guidance on patient positioning; selection of the radiofrequency coil, pulse sequences, and imaging planes; and control of MRI parameters to help optimize the MRI protocol for the six major joints of the musculoskeletal system.

The Prevalence and Risk of Type 2 Diabetes in Adults with Disabilities in Korea.

BACKGROUND: People with disabilities are at risk of secondary conditions such as diabetes. The aim of this study was to evaluate the prevalence and risk of type 2 diabetes in South Korea, especially among people with all types of disabilities. METHODS: We conducted a cross-sectional study using data from the Korean National Health Insurance Service, with two disabilityfree controls matched for each participant with disabilities by age and sex. Information regarding the type, severity and grade of disabilities was obtained based on the National Disability Registry. Diagnosis of type 2 diabetes was defined according to the following criteria: presence of International Classification of Diseases, Tenth Revision, Clinical Modification codes E11, E12, E13, or E14 and claims for at least one oral anti-diabetic agent or insulin at baseline, or fasting glucose level ≥126 mg/dL. RESULTS: We included 1,297,806 participants with disabilities and 2,943,719 control. Out of 4,241,525 participants, 841,990 (19.9%) were diagnosed with diabetes. The prevalence of diabetes was higher in the disability group compared with individuals without disabilities (23.1% vs. 18.4%). The odds of having diabetes was higher in the disability group compared with the control group (adjusted odds ratio, 1.34; 95% confidence interval, 1.33 to 1.34). The results showed higher prevalence of diabetes in the mildly disabled group (23.2%) than in the severely disabled group (22.7%). CONCLUSION: The prevalence and risk of diabetes were higher in people with disabilities compared with the general population. Physicians and public health authorities should focus on people with disabilities for proper diabetes management.