Growth differentiation factor 15 (GDF15) is receiving great interest beyond its role as an aging and disease-related biomarker. Recent discovery of its receptor, glial cell line-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL), suggests a central role in appetite regulation. However, there is also considerable evidence that GDF15 may have peripheral activity through an as-of-yet undiscovered mode of action. This raises the question as to whether increased GDF15 induction during pathophysiologic conditions also suppresses appetite. The present review will briefly introduce the discovery of GDF15 and describe the different contexts under which GDF15 is induced, focusing on its induction during mitochondrial dysfunction. We will further discuss the metabolic role of GDF15 under various pathophysiological conditions and conclude with possible therapeutic applications.
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Diabetes has been associated with more severe outcomes and higher mortality in coronavirus disease 2019 (COVID-19) patients compare to morbidity and mortality in patients without diabetes. Several mechanisms may play a role in this greater morbidity and mortality, especially uncontrolled hyperglycemia, an impaired immune system, pre-existing proinflammatory states, multiple comorbidities, and dysregulated angiotensin-converting enzyme 2 signaling. Thus, the diabetes medical community emergently needs to know about COVID-19 and its effects on patients with diabetes, as they must take precautions to carefully manage these patients during the COVID-19 pandemic. The Korean Diabetes Association provides some guidance and practical recommendations for the management of diabetes during the pandemic. This report provides insight into the association between diabetes and COVID-19, proper management of diabetes in patients with COVID-19 and an official suggestion by the Korean Diabetes Association for managing the COVID-19 outbreak.
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This clinical practice position statement, a product of the Fatty Liver Research Group of the Korean Diabetes Association, proposes recommendations for the diagnosis, progression and/or severity assessment, management, and follow-up of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NAFLD have an increased risk of non-alcoholic steatohepatitis (NASH) and fibrosis and a higher risk of cardiovascular diseases and diabetic complications compared to those without NAFLD. With regards to the evaluation of patients with T2DM and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or the NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging-proton density fat fraction are recommended. After the diagnosis of NAFLD, the stage of fibrosis needs to be assessed appropriately. For management, weight reduction achieved by lifestyle modification has proven beneficial and is recommended in combination with antidiabetic agent(s). Evidence that some antidiabetic agents improve NAFLD/NASH with fibrosis in patients with T2DM is emerging. However, there are currently no definite pharmacologic treatments for NAFLD in patients with T2DM. For specific cases, bariatric surgery may be an option if indicated.
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To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM.
This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group.
After exclusion, 110 participants were finally included. DM patients (
The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.
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This study sought to investigate the associations between metabolic health status, obesity, and incidence of primary open-angle glaucoma (POAG).
In this nationwide, population-based, longitudinal prospective cohort study conducted using the Korean National Health Insurance System, we categorized all subjects based on presence and severity of metabolic syndrome and obesity. Insurance claims data were used to identify POAG development. Then, Cox regression was applied to calculate the hazard of developing POAG in people with various components of metabolic syndrome, obesity, or their combination.
Of the total 287,553 subjects, 4,970 (1.3%) developed POAG. High fasting glucose, blood pressure, and total cholesterol levels were all associated with increased risk of developing POAG. Regarding obesity level, people with body mass index (BMI) greater than 30 kg/m2 were more likely to develop POAG than those with normal BMI. Also, people with greater number of metabolic syndrome components showed a greater POAG incidence. People who are metabolically unhealthy and obese (adjusted hazard ratio [HR], 1.574; 95% confidence interval [CI], 1.449 to 1.711) and those who are metabolically unhealthy nonobese (MUNO: adjusted HR, 1.521; 95% CI, 1.405 to 1.645) but not those who are metabolically healthy obese (MHO: adjusted HR, 1.019; 95% CI, 0.907 to 1.144) had an increased hazard of developing POAG compared with metabolically healthy nonobese (MHNO) subjects.
Metabolic health status and obesity were significantly associated with increased risk of POAG incidence. MUNO subjects but not MHO subjects showed a higher risk of POAG development than did MHNO subjects, suggesting that metabolic status is more important than obesity in POAG.
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No study has assessed association between cigarette smoking and new-onset diabetes mellitus (NODM) incidence using two different smoking classification systems: self-reported questionnaire and urine cotinine. The objective of this longitudinal study was to evaluate NODM risk using the above two systems in Korean adults.
Among individuals enrolled in Kangbuk Samsung Health Study and Cohort Study who visited between 2011 and 2012 at baseline and 2014 at follow-up, 78,212 participants without baseline diabetes mellitus were followed up for a median of 27 months. Assessment of NODM incidence was made at the end of follow-up period. Cotinine-verified current smoking was having urinary cotinine ≥50 ng/mL.
Percentages of self-reported and cotinine-verified current smokers were 25.9% and 23.5%, respectively. Overall incidence of NODM was 1.5%. According to multivariate regression analyses, baseline self-reported current smoking (relative risk [RR], 1.33; 95% confidence interval [CI], 1.07 to 1.65) and cotinine-verified current smoking (RR, 1.27; 95% CI, 1.08 to 1.49) increased NODM risk compared to baseline self-reported never smoking and cotinine-verified current non-smoking. Higher daily amount and longer duration of smoking were also associated with increased NODM risk (
This longitudinal study showed that baseline self-reported and cotinine-verified current smoking were associated with increased risks of NODM, especially in males.
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To examine the prospective association between higher blood pressure (BP) and risk of type 2 diabetes mellitus (T2DM) in middle-aged and elderly Chinese adults.
A total of 9,642 middle-aged and elderly Chinese adults (≥45 years old; 47.30% men) without diabetes from the China Health and Retirement Longitudinal Study were included for analyses. Participants were categorized into three groups: normal BP, prehypertension, and hypertension, according to the 2010 Chinese Guidelines for the Management of Hypertension. The incidence of T2DM was determined by self-reported physician diagnosis during two follow-up surveys conducted in 2013 to 2014 and 2015 to 2016.
During the 4-year follow-up, 429 participants (4.45%) developed T2DM, including 3.51% of the men and 5.29% of the women. The incidence rates of T2DM were 2.57%, 3.75%, and 6.71% in the normal BP, prehypertension, and hypertension groups, respectively. After adjustment for age, sex, education level, residence, smoking status, alcohol consumption, body mass index, waist circumference, and dyslipidemia, both prehypertension (odds ratio [OR], 1.32; 95% confidence interval [CI], 0.98 to 1.77) and hypertension (OR, 2.02; 95% CI, 1.54 to 2.64) were associated with increased risk of T2DM, compared to those with a normal BP. The ORs associated with T2DM were 1.08 (95% CI, 1.03 to 1.13) for an increase of 10 mm Hg in systolic BP and 1.06 (95% CI, 1.01 to 1.10) for an increase of 5 mm Hg in diastolic BP.
Higher BP is a risk factor for T2DM in middle-aged and elderly Chines. It may be a potential target for diabetes prevention.
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We examined the associations between thigh muscle area (TMA) and insulin resistance (IR) according to body mass index (BMI) in middle-aged Korean general population.
TMA was measured using quantitative computed tomography and corrected by body weight (TMA/Wt) in 1,263 men, 788 premenopausal women, and 1,476 postmenopausal women all aged 30 to 64 years. The tertiles of TMA/Wt were calculated separately for men and for premenopausal and postmenopausal women. Homeostatic model assessment for insulin resistance (HOMA-IR) was performed using fasting blood glucose and insulin levels, and increased IR was defined according to sex-specific, top quartiles of HOMA-IR. Associations between the TMA/Wt tertiles and increased IR according to the BMI categories (<25 and ≥25 kg/m2) were assessed using multivariable logistic regression analysis.
In men with higher BMIs, but not in those with lower BMIs, the presence of an increased IR had significantly higher odds ratios in the lower TMA/Wt tertiles, even after adjustment for visceral fat area. However, in premenopausal and postmenopausal women, there was no significant inverse association between TMA/Wt tertiles and increased IR, regardless of BMI category.
Our findings suggest that the thigh muscle is inversely associated with IR in men, particularly in those with higher BMIs.
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To investigate the performance of the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE) in a large, prospective, community-based cohort in Korea and to compare it with that of the Framingham Global Cardiovascular Disease Risk Score (FRS-CVD) and the Korean Risk Prediction Model (KRPM).
In the Korean Genome and Epidemiology Study (KOGES)-Ansan and Ansung study, we evaluated calibration and discrimination of the PCE for non-Hispanic whites (PCE-WH) and for African Americans (PCE-AA) and compared their predictive abilities with the FRS-CVD and the KRPM.
The present study included 7,932 individuals (3,778 men and 4,154 women). The PCE-WH and PCE-AA moderately overestimated the risk of atherosclerotic cardiovascular disease (ASCVD) for men (6% and 13%, respectively) but underestimated the risk for women (−49% and −25%, respectively). The FRS-CVD overestimated ASCVD risk for men (91%) but provided a good risk prediction for women (3%). The KRPM underestimated ASCVD risk for men (−31%) and women (−31%). All the risk prediction models showed good discrimination in both men (C-statistic 0.730 to 0.735) and women (C-statistic 0.726 to 0.732). Recalibration of the PCE using data from the KOGES-Ansan and Ansung study substantially improved the predictive accuracy in men.
In the KOGES-Ansan and Ansung study, the PCE overestimated ASCVD risk for men and underestimated the risk for women. The PCE-WH and the FRS-CVD provided an accurate prediction of ASCVD in men and women, respectively.
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There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis.
We analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent coronary computed tomographic angiography (CCTA) (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (
Compared with normal individuals, there were no statistically significant differences in the risk of for any atherosclerotic plaque (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.98 to 1.38;
Asymptomatic uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events.
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