Although sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus, real-world evidence regarding their benefits to ...diabetic patients with acute myocardial infarction (AMI) is insufficient. This study evaluated cardiovascular outcomes by comparing SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4i) in combination with metformin in diabetic patients with AMI.
This study involved 779 diabetic participants with AMI from a Korean nationwide multicenter observational cohort, who were divided into two groups: (1) metformin plus SGLT2i group (SGLT2i group, n = 186) and (2) metformin plus DPP-4i (DPP-4i group, n = 593). The primary endpoint was one year of major adverse composite events (MACEs), a composite outcome of all-cause mortality, non-fatal myocardial infarction, any revascularization, cerebrovascular accident, and stent thrombosis. To balance the baseline differences, inverse probability of treatment weighting (IPTW) was performed.
After IPTW, the rate of MACEs in the SGLT2i group was not significantly lower than that in the DPP-4i group (hazard ratio HR, 0.99; 95% confidence interval Cl, 0.46 to 2.14, p = 0.983). In the unadjusted and adjusted analyses, all items for clinical outcomes were comparable between the two groups. In our exploratory analysis, the left ventricular ejection fraction showed a significant improvement in the SGLT2i group than in the DPP-4i group before achieving statistical balancing (6.10 ± 8.30 versus 2.95 ± 10.34, p = 0.007) and after IPTW adjustment (6.91 ± 8.91 versus 3.13 ± 10.41, p = 0.027).
Our findings demonstrated that SGLT2i did not influence the rate of MACEs compared with DPP-4i in combination with metformin in diabetic patients with AMI but did improve left ventricular ejection fraction.
Not applicable (retrospectively registered).
We assessed the efficacy and safety of enavogliflozin (0.3 mg), a newly developed SGLT-2 inhibitor, in patients with type 2 diabetes mellitus based on kidney function via pooled analysis of two ...24-week, randomized, double-blind phase III trials.
Data from 470 patients were included (enavogliflozin: 0.3 mg/day, n = 235; dapagliflozin: 10 mg/day, n = 235). The subjects were classified by mildly reduced (60 ≤ eGFR < 90 mL/min/1.73 m², n = 247) or normal eGFR (≥ 90 mL/min/1.73 m², n = 223).
In the mildly reduced eGFR group, enavogliflozin significantly reduced the adjusted mean change of HbA1c and fasting plasma glucose levels at week 24 compared to dapagliflozin (- 0.94% vs. -0.77%, P = 0.0196). Enavogliflozin exhibited a more pronounced glucose-lowering effect by HbA1c when combined with dipeptidyl peptidase-4 inhibitors than that observed in their absence. Enavogliflozin showed potent blood glucose-lowering effects regardless of renal function. Conversely, dapagliflozin showed a significant decrease in the glucose-lowering efficacy as the renal function decreased. Enavogliflozin showed a higher urinary glucose excretion rate in both groups. The homeostatic model assessment showed that enavogliflozin markedly decreased the insulin resistance. The blood pressure, weight loss, or homeostasis model assessment of beta-cell function values did not differ significantly between enavogliflozin and dapagliflozin. Adverse events were similar between both drugs.
The glucose-lowering efficacy of enavogliflozin is superior to that of dapagliflozin in patients with type 2 diabetes mellitus with mild renal function impairment; this is attributed to its potent urinary glucose excretion-promoting ability. The emergence of new and potent SGLT-2 inhibitors is considered an attractive option for patients with inadequate glycemic control and decreased renal function.
Not applicable (pooled analysis).
We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection ...was observed in Balb/c （wild type, WT） and STAT4-/-, but not in STAT6-/- mice. Moreover, the expression levels of the protein and mRNA of pro- inflammatory cytokines, including TNF-u, IL-Ⅱ, and IL-6, were markedly increased in the serum and cochlea of WT and STAT4-/-, but not STAT6-/- mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6-j- mice were intact after treatment with cisplatin, where- as those from WT and STAT4-/- mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory ceils, and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphoryla- tion of STAT6 by binding with IL-4 receptor alpha and IL-13Rul. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.
Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of ...the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).
From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.
In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, -1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy.
This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.
Anaplastic thyroid cancer (ATC), a rare thyroid malignancy, accounts for only 5% of all thyroid cancers. However, it is the most aggressive form and has a very poor prognosis. Increasing evidence ...suggests that ATC arises from papillary thyroid carcinoma (PTC). However, the exact mechanism underlying this transformation remains unclear. In almost all cases, ATC originates within, but rarely outside, the thyroid gland. Transformation of metastatic PTC into ATC within the cervical lymph nodes is extremely rare. In this report, we present a rare case in a 63-year-old male patient who was initially diagnosed with PTC at his first hospital visit, which underwent anaplastic transformation in lymph node metastasis, and was subsequently diagnosed during the follow-up visit.
Background
The thyroid isthmus is located directly anterior to the trachea and is covered by the strap muscles. Several studies have suggested that papillary thyroid carcinoma (PTC) in the isthmus is ...more aggressive and is associated with a poor prognosis. The purpose of this meta-analysis was to assess the clinicopathological characteristics and recurrence rates of PTC in the isthmus compared to PTC at other sites.
Methods
Relevant articles were obtained by searching the PubMed database. A meta-analysis was performed using 11 eligible studies.
Results
The rate of extrathyroidal extension was 0.502 (95% confidence interval CI: 0.239–0.764) and 0.454 (95% CI: 0.331–0.582) for isthmus PTC and PTC at other site, respectively; however, the difference in the rates was not statistically significant. Lymphovascular invasion did not significantly differ between isthmus PTC (0.179 95% CI: 0.102–0.297) and PTC at other sites (0.114 95% CI: 0.066–0.188). The rate of central lymph node (LN) metastasis was significantly higher in isthmus PTC (0.527 95% CI: 0.435–0.617) than in PTC at other sites (0.352 95% CI: 0.280–0.432). No significant difference was observed between the two groups in terms of lateral cervical LN metastasis rate. Isthmus PTC was more likely to have a prominent recurrence rate (0.046 95% CI: 0.022–0.094) than PTC at other sites (0.010 95% CI: 0.001–0.070); however, the difference was not statistically significant (because of the small number of included studies).
Conclusions
The results of this meta-analysis indicated that isthmus PTC was associated with an increased risk of central LN metastasis. Isthmus PTC seems to have a slightly higher recurrence rate than PTC at other sites. Therefore, considering the potential of the isthmus location as an unfavorable factor, more attention should be focused on isthmus PTC, and a more aggressive approach such as prophylactic central LN dissection might provide better outcomes in PTC management.
Aims
To evaluate the effects of initiating sodium‐glucose cotransporter‐2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase‐4 (DPP‐4) inhibitors as active ...comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI).
Materials and Methods
We used an active‐comparator, new‐user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP‐4 inhibitor users for analysis using propensity‐score matching.
Results
During 13 708.59 person‐years of follow‐up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP‐4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all‐cause death and end‐stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all‐cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio HR 0.574, 95% confidence interval CI 0.36–0.915), all‐cause death (HR 0.731, 95% CI 0.567–0.942), and ESRD (HR 0.076, 95% CI 0.018–0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI.
Conclusions
The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI.
Social jetlag, the circadian misalignment reflecting the discrepancy between the circadian clock and social clock, has been implicated in weight-related issues. The objective of the present study was ...to determine whether there was an association between social jetlag and body weight change among adults in a large, nationally representative general population. This study was based on data from the Korean National Health and Nutrition Examination Survey, conducted during 2016–2017 by the Korean Ministry of Health and Welfare. Of the 16,277 participants, data from 8295 adults were included in the analysis. Men with social jetlag > 2 h had a significantly higher risk of weight gain (odd ratios (OR): 1.787; 95% confident interval (CI): 1.192–2.679) than those with social jetlag < 1 h, after adjustment for age, sociodemographic factors, lifestyle behaviors, chronic disease, obesity and average sleep duration. Women with weight gain had a higher social jetlag (>2 h), and women with social jetlag > 2 h had a higher proportion of weight gain. However, we did not find a significant association of social jetlag with weight gain after adjusting for confounding factors in women. There was no significant association between social jetlag and weight loss in men and women. Higher social jetlag was independently associated with an increased risk of weight gain in men. We propose that social jetlag may contribute to the obesogenic tendency in men, and that there is a potential for body weight to be managed with a circadian approach.
Aim
This study aimed to investigate the effects of repeated detection of non‐alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults.
Materials and Methods
In ...this nationwide population‐based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20‐39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0‐4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points.
Results
The multivariable‐adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57‐2.921), 3.45 (3.221‐3.694), 4.588 (4.303‐4.892) and 6.126 (5.77‐6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores.
Conclusions
Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults.
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