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Background/Aims@#The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased rapidly as a consequence of more sedentary lifestyles and a Westernized diet. Fracture is a major clinical problem in older people, but few large-scale cohort studies have evaluated the relationship between NAFLD and fracture. Therefore, we aimed to determine whether the fatty liver index (FLI), which represents the severity of NAFLD, can predict fracture risk. @*Methods@#We analyzed the relationship between the FLI and incident fracture using multivariate Cox proportional hazards models and data for 180,519 individuals who underwent National Health check-ups in the Republic of Korea between 2009 and 2014. @*Results@#A total of 2,720 participants (1.5%) were newly diagnosed with fracture during the study period (median 4.6 years). The participants were grouped according to FLI quartiles (Q1, 0 to <5.653; Q2, 5.653 to <15.245; Q3, 15.245 to <37.199; and Q4 ≥37.199). The cumulative fracture incidence was significantly higher in the highest FLI group than in the lowest FLI group (Q4, 986 [2.2%] and Q1, 323 [0.7%]; p<0.001). The adjusted hazard ratio indicated that the highest FLI group was independently associated with a higher incidence of fracture (hazard ratio for Q4 vs Q1, 2.956; 95% confidence interval, 2.606 to 3.351; p<0.001). FLI was significantly associated with a higher incidence of fracture, independent of the baseline characteristics of the participants. @*Conclusions@#Our data imply that the higher the FLI of a Korean patient is, the higher their risk of osteoporotic fracture, independent of key confounding factors.
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Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia.
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Background@#CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated. @*Methods@#KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis. @*Results@#CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1). @*Conclusion@#Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.
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It has been suggested that the coronavirus disease 2019 (COVID-19) pandemic has had a negative impact on glycemic control in patients with type 2 diabetes mellitus (T2DM). However, no study has examined yearly trends in glycated hemoglobin (HbA1c) levels after the start of the COVID-19 outbreak. Here, we performed a retrospective analysis of HbA1c concentrations during the early period of the COVID-19 outbreak (COVID-19 cohort) and then compared the yearly trend in the mean HbA1c level, along with fluctuations in HbA1c levels, with those during previous years (non-COVID-19 cohorts). We observed that the mean HbA1c level in patients with T2DM increased during the first 6 months of the COVID-19 outbreak. After 6 months, HbA1c levels in the COVID-19 cohort returned to levels seen in the non-COVID-19 cohorts. The data suggest that vulnerable patients with T2DM should be monitored closely during the early period of a pandemic to ensure they receive appropriate care.
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Background/Aims@#Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than 13,000 people in South Korea by July 2020. To prevent spread of COVID-19, tele-prescription was permitted temporarily. This study investigated the impact of tele-prescription on glycemic control in patients with type 2 diabetes. @*Methods@#Glycated hemoglobin (HbA1c) concentrations were retrospectively analyzed in patients with type 2 diabetes who were treated with tele-prescription because of COVID-19 and those who were treated by face-to-face care (non-tele-prescription group) enrolled at the same period of time. Mean HbA1c concentrations and mean change in HbA1c concentration (ΔHbA1c) were compared in these two groups. @*Results@#The mean HbA1c levels of patients were significantly higher after than before the tele-prescription period (7.46% ± 1.24% vs. 7.27% ± 1.13%, p < 0.05). Mean ΔHbA1c was significantly higher in the tele-prescription than in the non-tele-prescription group (0.19% ± 0.68% vs. 0.04% ± 0.95%, p < 0.05). HbA1c was significantly greater in patients taking fewer oral hypoglycemic agents, no insulin, fewer comorbidities (e.g., coronary artery disease, cerebrovascular accident, and diabetic neuropathy), and higher baseline HbA1c. @*Conclusions@#Tele-prescription may worsen glycemic control in patients with type 2 diabetes during public health crises.
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Obesity, which is one of the most important noncommunicable diseases, has become an epidemic. With the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the collision of these two health risks has increased the threat of adverse events and serious threats to public health. In this review, the impact of obesity on COVID-19 severity and mortality is presented. The mechanism by which obesity increases susceptibility and severity is discussed. As a low-grade inflammatory disease, obesity provides a pro-inflammatory milieu by which adipose tissue expressing angiotensin converting enzyme 2, which is known as a receptor for severe acute respiratory syndrome coronavirus 2, works as a viral reservoir. Finally, the role of metabolic and bariatric surgeries during the COVID-19 era will be discussed.
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Background@#Based on recent evidence on the importance of the presence of diabetes mellitus (DM) and fibrosis-4 (FIB-4) index in coronavirus disease 2019 (COVID-19) mortality, we analyzed whether these factors could additively predict such mortality. @*Methods@#This multicenter observational study included 1,019 adult inpatients admitted to university hospitals in Daegu. The demographic and laboratory findings, mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM and/or a high FIB-4 index. The mortality risk and corresponding hazard ratio (HR) were analyzed using the Kaplan-Meier method and Cox proportional hazard models. @*Results@#The patients with DM (n=217) exhibited significantly higher FIB-4 index and mortality compared to those without DM. Although DM (HR, 2.66; 95% confidence interval [CI], 1.63 to 4.33) and a high FIB-4 index (HR, 4.20; 95% CI, 2.21 to 7.99) were separately identified as risk factors for COVID-19 mortality, the patients with both DM and high FIB-4 index had a significantly higher mortality (HR, 9.54; 95% CI, 4.11 to 22.15). Higher FIB-4 indices were associated with higher mortality regardless of DM. A high FIB-4 index with DM was more significantly associated with a severe clinical course with mortality (odds ratio, 11.24; 95% CI, 5.90 to 21.41) than a low FIB-4 index without DM, followed by a high FIB-4 index alone and DM alone. The duration of quarantine and hospital stay also tended to be longer in those with both DM and high FIB-4 index. @*Conclusion@#Both DM and high FIB-4 index are independent and additive risk factors for COVID-19 mortality.
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Background/Aims@#Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than 13,000 people in South Korea by July 2020. To prevent spread of COVID-19, tele-prescription was permitted temporarily. This study investigated the impact of tele-prescription on glycemic control in patients with type 2 diabetes. @*Methods@#Glycated hemoglobin (HbA1c) concentrations were retrospectively analyzed in patients with type 2 diabetes who were treated with tele-prescription because of COVID-19 and those who were treated by face-to-face care (non-tele-prescription group) enrolled at the same period of time. Mean HbA1c concentrations and mean change in HbA1c concentration (ΔHbA1c) were compared in these two groups. @*Results@#The mean HbA1c levels of patients were significantly higher after than before the tele-prescription period (7.46% ± 1.24% vs. 7.27% ± 1.13%, p < 0.05). Mean ΔHbA1c was significantly higher in the tele-prescription than in the non-tele-prescription group (0.19% ± 0.68% vs. 0.04% ± 0.95%, p < 0.05). HbA1c was significantly greater in patients taking fewer oral hypoglycemic agents, no insulin, fewer comorbidities (e.g., coronary artery disease, cerebrovascular accident, and diabetic neuropathy), and higher baseline HbA1c. @*Conclusions@#Tele-prescription may worsen glycemic control in patients with type 2 diabetes during public health crises.
ABSTRACT
Obesity, which is one of the most important noncommunicable diseases, has become an epidemic. With the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the collision of these two health risks has increased the threat of adverse events and serious threats to public health. In this review, the impact of obesity on COVID-19 severity and mortality is presented. The mechanism by which obesity increases susceptibility and severity is discussed. As a low-grade inflammatory disease, obesity provides a pro-inflammatory milieu by which adipose tissue expressing angiotensin converting enzyme 2, which is known as a receptor for severe acute respiratory syndrome coronavirus 2, works as a viral reservoir. Finally, the role of metabolic and bariatric surgeries during the COVID-19 era will be discussed.
ABSTRACT
This study investigated the impact of social distancing due to coronavirus disease 2019 (COVID-19) on glycemic control in people with type 2 diabetes mellitus (T2DM). We retrospectively analyzed the change in glycosylated hemoglobin level (ΔHbA1c) in people with T2DM who undertook social distancing because of COVID-19. We compared the ΔHbA1c between COVID-19 and non-COVID-19 cohorts that were enrolled at the same time of year. The ΔHbA1c of the COVID-19 cohort was significantly higher than that of two non-COVID-19 cohorts. Subgroup analysis according to age and baseline HbA1c level showed that social distancing significantly increased the mean HbA1c level of participants of <50 years. The ΔHbA1c of participants of <50 years and with HbA1c <7.0% in the COVID-19 cohort showed larger changes than other subgroups. In adjusted model, adjusted ΔHbA1c levels in the COVID-19 cohort remained significantly higher than those in the two other cohorts. Social distancing negatively impacts blood glucose control in people with T2DM, especially those who are younger and have good blood glucose control.
ABSTRACT
Background@#Based on recent evidence on the importance of the presence of diabetes mellitus (DM) and fibrosis-4 (FIB-4) index in coronavirus disease 2019 (COVID-19) mortality, we analyzed whether these factors could additively predict such mortality. @*Methods@#This multicenter observational study included 1,019 adult inpatients admitted to university hospitals in Daegu. The demographic and laboratory findings, mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM and/or a high FIB-4 index. The mortality risk and corresponding hazard ratio (HR) were analyzed using the Kaplan-Meier method and Cox proportional hazard models. @*Results@#The patients with DM (n=217) exhibited significantly higher FIB-4 index and mortality compared to those without DM. Although DM (HR, 2.66; 95% confidence interval [CI], 1.63 to 4.33) and a high FIB-4 index (HR, 4.20; 95% CI, 2.21 to 7.99) were separately identified as risk factors for COVID-19 mortality, the patients with both DM and high FIB-4 index had a significantly higher mortality (HR, 9.54; 95% CI, 4.11 to 22.15). Higher FIB-4 indices were associated with higher mortality regardless of DM. A high FIB-4 index with DM was more significantly associated with a severe clinical course with mortality (odds ratio, 11.24; 95% CI, 5.90 to 21.41) than a low FIB-4 index without DM, followed by a high FIB-4 index alone and DM alone. The duration of quarantine and hospital stay also tended to be longer in those with both DM and high FIB-4 index. @*Conclusion@#Both DM and high FIB-4 index are independent and additive risk factors for COVID-19 mortality.
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Background@#Coronavirus disease 2019 (COVID-19) has become a global pandemic, which prompts a consensus for the necessity to seek risk factors for this critical disease. Risk factors affecting mortality of the disease remain elusive. Diabetes and hyperglycemia are known to negatively affect a host’s antiviral immunity. We evaluated the relationship between a history of diabetes, fasting plasma glucose (FPG) levels and mortality among severely ill patients with COVID-19. @*Methods@#This was a retrospective cohort study that assessed 106 adult inpatients (aged ≥18 years) from two tertiary hospitals in Daegu, South Korea. The participants were transferred to tertiary hospitals because their medical condition required immediate intensive care. The demographic and laboratory data were compared between COVID-19 patients who survived and those who did not. @*Results@#Compared with the survivor group, age, and the proportions of diabetes, chronic lung disease and FPG were significantly higher in the deceased group. In the Cox proportional hazards regression model for survival analysis, FPG level and age were identified as significant predictors of mortality (P68 years and FPG of 168 mg/dL, respectively. Among those without diabetes, high FPG remained a significant predictor of mortality (P<0.04). @*Conclusion@#High FPG levels significantly predicted mortality in COVID-19, regardless of a known history of diabetes. These results suggest intensive monitoring should be provided to COVID-19 patients who have a high FPG level.
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Background@#Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. @*Methods@#We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. @*Results@#Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease. @*Conclusion@#DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.
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Neutrophils are innate immune cells that constitute the first line of defense against invading pathogens. Due to this characteristic, they are exposed to diverse immunological environments wherein sources for nutrients are often limited. Recent advances in the field of immunometabolism revealed that neutrophils utilize diverse metabolic pathways in response to immunological challenges. In particular, neutrophils adopt specific metabolic pathways for modulating their effector functions in contrast to other immune cells, which undergo metabolic reprogramming to ensure differentiation into distinct cell subtypes. Therefore, neutrophils utilize different metabolic pathways not only to fulfill their energy requirements, but also to support specialized effector functions, such as neutrophil extracellular trap formation, ROS generation, chemotaxis, and degranulation. In this review, we discuss the basic metabolic pathways used by neutrophils and how these metabolic alterations play a critical role in their effector functions.
ABSTRACT
Neutrophils are innate immune cells that constitute the first line of defense against invading pathogens. Due to this characteristic, they are exposed to diverse immunological environments wherein sources for nutrients are often limited. Recent advances in the field of immunometabolism revealed that neutrophils utilize diverse metabolic pathways in response to immunological challenges. In particular, neutrophils adopt specific metabolic pathways for modulating their effector functions in contrast to other immune cells, which undergo metabolic reprogramming to ensure differentiation into distinct cell subtypes. Therefore, neutrophils utilize different metabolic pathways not only to fulfill their energy requirements, but also to support specialized effector functions, such as neutrophil extracellular trap formation, ROS generation, chemotaxis, and degranulation. In this review, we discuss the basic metabolic pathways used by neutrophils and how these metabolic alterations play a critical role in their effector functions.
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BACKGROUND: Chronic hyperglycemia has deleterious effects on pancreatic β-cell function and turnover. Recent studies support the view that cyclin-dependent kinase 5 (CDK5) plays a role in β-cell failure under hyperglycemic conditions. However, little is known about how CDK5 impair β-cell function. Myricetin, a natural flavonoid, has therapeutic potential for the treatment of type 2 diabetes mellitus. In this study, we examined the effect of myricetin on high glucose (HG)-induced β-cell apoptosis and explored the relationship between myricetin and CDK5. METHODS: To address this question, we subjected INS-1 cells and isolated rat islets to HG conditions (30 mM) in the presence or absence of myricetin. Docking studies were conducted to validate the interaction between myricetin and CDK5. Gene expression and protein levels of endoplasmic reticulum (ER) stress markers were measured by real-time reverse transcription polymerase chain reaction and Western blot analysis. RESULTS: Activation of CDK5 in response to HG coupled with the induction of ER stress via the down regulation of sarcoendoplasmic reticulum calcium ATPase 2b (SERCA2b) gene expression and reduced the nuclear accumulation of pancreatic duodenal homeobox 1 (PDX1) leads to β-cell apoptosis. Docking study predicts that myricetin inhibit CDK5 activation by direct binding in the ATP-binding pocket. Myricetin counteracted the decrease in the levels of PDX1 and SERCA2b by HG. Moreover, myricetin attenuated HG-induced apoptosis in INS-1 cells and rat islets and reduce the mitochondrial dysfunction by decreasing reactive oxygen species production and mitochondrial membrane potential (Δψm) loss. CONCLUSION: Myricetin protects the β-cells against HG-induced apoptosis by inhibiting ER stress, possibly through inactivation of CDK5 and consequent upregulation of PDX1 and SERCA2b.
Subject(s)
Animals , Rats , Apoptosis , Blotting, Western , Calcium-Transporting ATPases , Cyclin-Dependent Kinase 5 , Diabetes Mellitus, Type 2 , Down-Regulation , Endoplasmic Reticulum Stress , Endoplasmic Reticulum , Gene Expression , Genes, Homeobox , Glucose , Hyperglycemia , Insulin-Secreting Cells , Membrane Potential, Mitochondrial , Polymerase Chain Reaction , Reactive Oxygen Species , Reticulum , Reverse Transcription , Up-RegulationABSTRACT
Abnormal thyroid function is associated with impaired glucose homeostasis. This study aimed to determine whether free thyroxine (FT4) influences the prevalence of prediabetes in euthyroid subjects using a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 2,399 male participants of >20 years of age who were euthyroid and non-diabetic. Prediabetic participants had lower FT4 concentrations than those without prediabetes, but their thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, glycosylated hemoglobin (HbA1c) levels significantly decreased with increasing FT4 tertile, whereas fasting plasma glucose (FPG) levels were not associated with FT4 tertiles (HbA1c, P<0.01 in T3 vs. T1; FPG, P=0.489 in T3 vs. T1). The prevalence of prediabetes was significantly higher in T1 (odds ratio, 1.426; 95% confidence interval, 1.126 to 1.806; P<0.01) than in T3. In conclusion, subjects with low-normal serum FT4 had high HbA1c and were more likely to have prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes in male, even when thyroid function is within the normal range.
Subject(s)
Humans , Male , Blood Glucose , Cross-Sectional Studies , Fasting , Glucose , Glycated Hemoglobin , Homeostasis , Korea , Nutrition Surveys , Prediabetic State , Prevalence , Reference Values , Risk Factors , Thyroid Gland , Thyrotropin , ThyroxineABSTRACT
The potential mechanism by which sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent cardiovascular disease (CVD) is being widely investigated. Improved insulin resistance, along with decreased body fat mass associated with SGLT2 inhibitor treatment is consistent with previously well-established factors contributing to the prevention of CVD. These factors are responsible for reduction of oxidative stress as well as improvement of systemic inflammation. Because heart failure was one of the most dramatically improved cardiovascular events in various clinical trials and because SGLT2 inhibitors promote osmotic diuresis and natriuresis, hemodynamic changes are considered as a critical mechanism responsible for the cardioprotective effect of SGLT2 inhibitors. Restored tubuloglomerular feedback by SGLT2 inhibitors might play a role in renoprotection, which in turn, leads to fewer CVDs. Finally, blood ketone body increments in response to SGLT2 inhibition might act as a “super-fuel” for salvaging the failing diabetic heart.
Subject(s)
Adipose Tissue , Cardiovascular Diseases , Diabetes Mellitus , Diuresis , Heart , Heart Failure , Hemodynamics , Inflammation , Insulin Resistance , Ketones , Natriuresis , Oxidative Stress , Sodium-Glucose Transport ProteinsABSTRACT
Mitochondrial dysfunction is a hallmark of metabolic diseases such as obesity, type 2 diabetes mellitus, neurodegenerative diseases, and cancers. Dysfunction occurs in part because of altered regulation of the mitochondrial pyruvate dehydrogenase complex (PDC), which acts as a central metabolic node that mediates pyruvate oxidation after glycolysis and fuels the Krebs cycle to meet energy demands. Fine-tuning of PDC activity has been mainly attributed to post-translational modifications of its subunits, including the extensively studied phosphorylation and de-phosphorylation of the E1α subunit of pyruvate dehydrogenase (PDH), modulated by kinases (pyruvate dehydrogenase kinase [PDK] 1-4) and phosphatases (pyruvate dehydrogenase phosphatase [PDP] 1-2), respectively. In addition to phosphorylation, other covalent modifications, including acetylation and succinylation, and changes in metabolite levels via metabolic pathways linked to utilization of glucose, fatty acids, and amino acids, have been identified. In this review, we will summarize the roles of PDC in diverse tissues and how regulation of its activity is affected in various metabolic disorders.