The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid ...control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.
The association of metabolic syndrome (MetS) with the development of Parkinson disease (PD) is currently unclear. We sought to determine whether MetS and its components are associated with the risk ...of incident PD using large-scale cohort data for the whole South Korean population.
Health checkup data of 17,163,560 individuals aged ≥40 years provided by the National Health Insurance Service (NHIS) of South Korea between January 1, 2009, and December 31, 2012, were included, and participants were followed up until December 31, 2015. The mean follow-up duration was 5.3 years. The hazard ratio (HR) and 95% confidence interval (CI) of PD were estimated using a Cox proportional hazards model adjusted for potential confounders. We identified 44,205 incident PD cases during follow-up. Individuals with MetS (n = 5,848,508) showed an increased risk of PD development compared with individuals without MetS (n = 11,315,052), even after adjusting for potential confounders including age, sex, smoking, alcohol consumption, physical activity, income, body mass index, estimated glomerular filtration rate, and history of stroke (model 3; HR, 95% CI: 1.24, 1.21-1.27). Each MetS component was positively associated with PD risk (HR, 95% CI: 1.13, 1.10-1.16 for abdominal obesity; 1.13, 1.10-1.15 for hypertriglyceridemia; 1.23, 1.20-1.25 for low high-density lipoprotein cholesterol; 1.05, 1.03-1.08 for high blood pressure; 1.21, 1.18-1.23 for hyperglycemia). PD incidence positively correlated with the number of MetS components (log-rank p < 0.001), and we observed a gradual increase in the HR for incident PD with increasing number of components (p < 0.001). A significant interaction between age and MetS on the risk of incident PD was observed (p for interaction < 0.001), and people aged ≥65 years old with MetS showed the highest HR of incident PD of all subgroups compared to those <65 years old without MetS (reference subgroup). Limitations of this study include the possibilities of misdiagnosis of PD and reverse causality.
Our population-based large-scale cohort study suggests that MetS and its components may be risk factors of PD development.
Aims
To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with ...glimepiride in Korean patients with type 2 diabetes.
Materials and Methods
This was a 52‐week, multicentre, randomized, parallel‐group, open‐label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1‐2 mg/day for 12 months as an add‐on to metformin. Baseline and end of study body composition evaluations included dual‐energy X‐ray absorptiometry and abdominal computed tomography scans.
Results
Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: −2.59 kg BF mass, −1.94% BF%, −17.55 cm2 VAT area, −18.39 cm2 SAT area, −0.46% glycated haemoglobin, −18.25 mg/dl fasting blood glucose, −3.7 kg weight, −2.21 cm waist circumference, −1.37 kg/m2 body mass index, −6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group.
Conclusion
Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well‐tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add‐on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes.
MYC in Brain Development and Cancer Zaytseva, Olga; Kim, Nan-Hee; Quinn, Leonie M
International journal of molecular sciences,
10/2020, Letnik:
21, Številka:
20
Journal Article
Recenzirano
Odprti dostop
The MYC family of transcriptional regulators play significant roles in animal development, including the renewal and maintenance of stem cells. Not surprisingly, given MYC's capacity to promote ...programs of proliferative cell growth, MYC is frequently upregulated in cancer. Although members of the MYC family are upregulated in nervous system tumours, the mechanisms of how elevated MYC promotes stem cell-driven brain cancers is unknown. If we are to determine how increased MYC might contribute to brain cancer progression, we will require a more complete understanding of MYC's roles during normal brain development. Here, we evaluate evidence for MYC family functions in neural stem cell fate and brain development, with a view to better understand mechanisms of MYC-driven neural malignancies.
Previous studies have shown that nonalcoholic fatty liver disease (NAFLD) and sarcopenia may share pathophysiological mechanisms, such as insulin resistance, inflammation, vitamin D deficiency, and ...decreased physical activity. However, their direct relationship has not been investigated. The association between NAFLD and sarcopenia was examined in 452 apparently healthy adults enrolled in the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective observational cohort study. The liver attenuation index (LAI), which was measured using abdominal computed tomography (CT), was used as a parameter for the diagnosis of NAFLD. Sarcopenia was defined using a skeletal muscle mass index (SMI) SMI (%) = total skeletal muscle mass (kg) / weight (kg) × 100 that was measured by dual energy X‐ray absorptiometry (DXA). After adjusting for age and sex, both SMI and LAI were negatively correlated with the homeostasis model assessment of insulin resistance (HOMA‐IR) (P < 0.001) and high sensitivity C‐reactive protein (hsCRP) (P < 0.001) as well as brachial‐ankle pulse wave velocity (baPWV), an indicator of arterial stiffness. Furthermore, SMI and LAI had positive relationships with high‐density lipoprotein (HDL)‐cholesterol, but both had a negative relationship with triglyceride, alanine aminotransferase (ALT), and total body fat. In a multiple logistic regression analysis, the odds ratio for NAFLD risk was 5.16 (95% confidence interval CI = 1.63‐16.33) in the lowest quartile of SMI compared to the highest after adjusting for potential confounding factors. Conclusion: Individuals with lower muscle mass exhibited increased risk of NAFLD. This result may provide a novel insight into the mechanism linking between sarcopenia and NAFLD. (Clinical trial no. NCT01594710.) (Hepatology 2014;59:1772–1778)
In our ongoing project directed toward the discovery of novel treatments for diabetic complications from herbal medicines, sixteen compounds including three caffeoylquinic acids and four flavonoids ...were isolated from an EtOAc-soluble extract of the stems and leaves of Erigeron annuus. All the isolates were evaluated in vitro for inhibitory activity on the formation of advanced glycation end products (AGEs) and rat lens aldose reductase (RLAR). Of these, 3,5-di-O-caffeoyl-epi-quinic acid (3) exhibited the most potent inhibitory activity in both the AGEs and aldose reductase (AR) assays. Compound 3 markedly reduced AGEs-bovin serum albumin (BSA) cross-linking in a dose-dependent manner. Furthermore, opacity of lenses was significantly prevented when they were treated with 3 in an ex vivo experiment.
Aim
To assess the efficacy and safety of add‐on therapy with the dipeptidyl peptidase‐4 inhibitor teneligliptin compared with sitagliptin in patients with type 2 diabetes (T2DM) inadequately ...controlled with metformin and glimepiride.
Materials and Methods
This was a phase 3, randomized, double‐blind, non‐inferiority study of adult Korean subjects with T2DM (n = 201), with HbA1c ranging from 7.0% to 11.0%, on stable doses of metformin plus glimepiride. Subjects were randomized in a 1:1 fashion to receive either oral teneligliptin 20 mg or sitagliptin 100 mg for 24 weeks. The primary endpoint was change from baseline in HbA1c.
Results
At baseline, mean age was 60.56 ± 9.41 years, body mass index was 25.23 ± 2.85 kg/m2 and HbA1c was 8.11% ± 0.79%. At 24 weeks, both groups achieved significant reductions from baseline in HbA1c (teneligliptin, −1.03% ± 0.10% P < 0.0001; sitagliptin, −1.02% ± 0.10% P < 0.0001). The inter‐group difference was −0.01% (95% confidence interval CI: −0.28, 0.26; P = 0.9497); the upper limit of the 95% CI was within the preset limit for non‐inferiority (0.4%). There were no significant differences between groups in the proportion of patients achieving HbA1c targets, or changes from baseline in fasting plasma glucose, body weight or lipid levels at 24 weeks. Rates of adverse events (teneligliptin, n = 63 61.76%; sitagliptin, n = 61 62.24%; P = 0.9442) and hypoglycaemia (teneligliptin, n = 32 31.37%; sitagliptin, n = 28 28.57%; P = 0.6656) were similar.
Conclusion
Teneligliptin was non‐inferior to sitagliptin in the context of triple therapy for T2DM and is an important option in this setting.
The triglyceride-glucose (TyG) index is a simple surrogate marker of insulin resistance. We evaluated the association of the TyG index with low muscle mass using a nationwide population-based ...representative data. This is a cross-sectional study that included 9477 participants aged ≥ 40 years from the Korea National Health and Nutrition Examination Survey between 2008 and 2011. The TyG index was calculated as lntriglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2. Dual-energy X-ray absorptiometry was used to measure appendicular lean mass (ALM). Low muscle mass was defined an ALM/weight of 2 standard deviations (SD) below of young participants. The overall prevalence of low muscle mass was 4.7%. The prevalence of low muscle mass increased linearly with the quartiles of the TyG index, 2.5%, 4.2%, 5.6%, and 6.7% in Q1-Q4, respectively. The TyG index was negatively associated with ALM/weight both in men (r = - 0.302) and women (r = - 0.230). The odds ratio (OR) for low muscle mass was 2.08 in the highest quartile compared to the lowest quartile. High TyG index was associated with an increased risk of low muscle mass (OR for 1SD increase: 1.13). Increased TyG index was associated with the risk of low muscle mass independent of confounding factors.
The aim of this study is to investigate whether GGT variability is able to predict the risk of end-stage renal disease (ESRD). The study subjects were Koreans who conducted health exams supported by ...the Korean National Health Insurance Corporation during 2009-2012 (baseline). After excluding individuals aged < 40 years, heavy alcoholics, or those with histories of chronic liver disease or ESRD, we followed 6,058,995 individuals. We calculated the average successive variability (ASV) of GGT values during the 5 years before the baseline as a parameter of variability. Using Cox proportional analyses, we evaluated the risk of ESRD according to GGT ASV quartiles, defined as the initiation of renal replacement therapy or kidney transplantation, or December 31, 2016. During 38,663,279.3 person-years of follow-up, 12,057 cases of ESRD were identified. Compared with GGT ASV quartile 1, the risk of ESRD was higher in ASV quartiles 3-4 and increased serially, even after adjustment for several metabolic parameters, baseline renal function, presence of comorbidities, low income, and baseline GGT and hemoglobin level. The fully adjusted hazard ratios (95% confidence intervals) of GGT ASV quartiles 3 and 4 were 1.06 (1.01-1.12) and 1.12 (1.06-1.18), respectively. In conclusion, GGT variability is a putative risk factor for ESRD in Koreans.
Diabetic kidney disease (DKD) is a prevalent renal complication of diabetes mellitus that ultimately develops into end-stage kidney disease (ESKD) when not managed appropriately. Substantial risk of ...ESKD remains even with intensive management of hyperglycemia and risk factors of DKD and timely use of renin-angiotensin-aldosterone inhibitors. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce hyperglycemia primarily by inhibiting glucose and sodium reabsorption in the renal proximal tubule. Currently, their effects expand to prevent or delay cardiovascular and renal adverse events, even in those without diabetes. In dedicated renal outcome trials, SGLT2 inhibitors significantly reduced the risk of composite renal adverse events, including the development of ESKD or renal replacement therapy, which led to the positioning of SGLT2 inhibitors as the mainstay of chronic kidney disease management. Multiple mechanisms of action of SGLT2 inhibitors, including hemodynamic, metabolic, and anti-inflammatory effects, have been proposed. Restoration of tubuloglomerular feedback is a plausible explanation for the alteration in renal hemodynamics induced by SGLT2 inhibition and for the associated renal benefit. This review discusses the clinical rationale and mechanism related to the protection SGLT2 inhibitors exert on the kidney, focusing on renal hemodynamic effects.
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