METHODS AND RESULTS: Transverse aortic constriction (TAC)/sham surgery were carried out in both IL-33 and WT-littermates. Echocardiographic measurements were performed at frequent interval during the study period. Heart was harvested for RNA and histological measurements. Following mechanical overload by TAC, myocardial mRNA expressions of Th1 cytokines, such as TNF-α were enhanced in IL-33(-/-) mice than in WT mice. After 8-weeks, IL-33(-/-) mice exhibited exacerbated left ventricular hypertrophy, increased chamber dilation, reduced fractional shortening, aggravated fibrosis, inflammation, and impaired survival compared with WT littermates. Accordingly, myocardial mRNA expressions of hypertrophic (c-Myc/BNP) molecular markers were also significantly enhanced in IL-33(-/-) mice than those in WT mice.
CONCLUSIONS: We report for the first time that ablation of IL-33 directly and significantly leads to exacerbate cardiac remodeling with impaired cardiac function and survival upon mechanical stress. These data highlight the cardioprotective role of IL-33/ST2 system in the stressed myocardium and reveal a potential therapeutic role for IL-33 in non-ischemic HF.
METHODS: A cross-sectional study was conducted on T2DM patients at a tertiary hospital outpatient using the Malay and English version of the EQ-5D-5L questionnaire. Health utility values were derived using the Malaysian EQ-5D-5L value set. Ordinary least squares (OLS) multivariable regression model was used to estimate the health utility decrements associated with T2DM-related complications and clinical characteristics.
RESULTS: A total of 513 T2DM patients were recruited. Overall, pain was the most affected of all five EQ-5D-5L dimensions. Patients with foot ulcer, amputation, severe heart failure and frequent hypoglycemia reported more problems collectively in all EQ-5D-5L dimensions. Older age, lower education level, longer duration of T2DM, urine protein creatine index (UPCI) > 0.02 g/mmol, and injection therapy were significantly associated with lower EQ-5D-5L utility values (p heart failure 0.65 (interquartile range, IQR 0.50), frequent hypoglycemia 0.74 (0.22) and being amputated 0.78 (0.47). In the multivariable regression model after controlling for sociodemographic and clinical characteristics, the largest utility value decrement was observed for amputation (- 0.158, SE 0.087, p = 0.05), frequent hypoglycemia (- 0.101, SE 0.030, p = 0.001), myocardial infarction (-0.050, SE 0.022, p = 0.022) and obesity (-0.034, SE 0.016, p = 0.029).
CONCLUSION: Larger utility value decrements were found for severe stages of complications. These findings suggest the value of defining severity of complications in utility elicitation studies. The utility decrement quantified for different T2DM complication severity will be useful for economic evaluations within diabetic-related fields.