autophagy pathway Conflicts of interest br Acknowledgments T
Conflicts of interest
Acknowledgments This article was supported by grants from the Ministry of Science and Technology, Executive Yuan (MOST 103-2314-B-010-043-MY3), and Taipei Veterans General Hospital (V103C-112; V104C-095; and V105C-096). We also appreciate the Clinical Research Core Laboratory and the Medical Science & Technology Building of Taipei Veterans General Hospital for providing experimental space and facilities.
Introduction Metabolic syndrome (MS) has several risk factors, including central obesity, dyslipidemia, raised blood pressure, and fasting glucose for cardiovascular disease and Type 2 diabetes mellitus. Fatty liver disease used to be considered an incidental pathological finding in Type 2 diabetes and obesity; however, it is found to be strongly related with features of MS and even considered to be included in the definition of MS. Higher PC is associated with cardiovascular disease and vascular complications as a result of its role in inflammation and thrombosis; also, platelet activation is observed in people with diabetes, hypertriglyceridemia, and insulin resistance. Diabetes, hypertriglyceridemia, and insulin resistance are strongly associated with MS, and previous studies have found that PC is also elevated in patients with MS after adjustment for age, gender, ethnicity, and total cholesterol. On the contrary, decreased PC is observed when significant hepatic fibrosis develops in patients with fatty liver, especially in conditions of nonalcoholic steatohepatitis, which is another disease that is highly associated with MS.
Discussion The prevalence of MS is nearly 35% in the United States, according to a recent analysis of the population from 2003 to 2012. While the prevalence of MS was approximately 12% between 1999 and 2002 in Taiwan, it was much higher in the current study (28%), which may have been because of westernization of diet, greater awareness of the syndrome, or higher socioeconomic status of the patients. Nonalcoholic fatty liver disease (NAFLD) is strongly associated with MS, which is demonstrated by the fact that approximately 90% of the patients with fatty liver have more than one feature of MS, and 33% of them have three or more. NAFLD has also been seen as the hepatic expression of MS. The association between NAFLD and MS exists in not only obese and type 2 autophagy pathway patients but also nonobese and nondiabetic individuals. In concordance with previous published results, our current study showed that the prevalence of MS increased with age (Fig. 2B), and that fatty liver was the strongest association factor with MS in both genders (Table 3). Of note, people with fatty liver disease who had active hepatic necroinflammation and elevated serum ALT levels were correlated with an even higher rate of MS, and the association existed among all age groups (Fig. 2C and 2D). Regarding the pathogenic role of mean platelet volume (MPV) and PC in the development of MS, growing evidence suggests that MPV should be regarded as a new inflammation marker and associated with the risk of cardiovascular disease, Type 2 diabetes, and MS. Information with respect to MPV might not have been available in the current study because the data were obtained from routine health check-ups; however, a recently published study demonstrated a close association between MPV and PC. According to published literature, more and larger reactive platelets develop in the presence of conditions such as obesity and endothelial dysfunction under the influence of growth factors and cytokines. Additionally, platelets are associated with cardiovascular disease and vascular complications because of their role in inflammation and thrombosis. Stokes et al mentioned that platelets deposited chemoattractants on the vessel wall and directly interact with leukocytes and the vessel wall through the mediation of factors, such as P-selectin, glycoprotein (GP)1a, GPIIb/IIIa, and CD40L. Platelet activation has also been observed in people with Type 2 diabetes, hypertriglyceridemia, and insulin resistance through the decreased production of nitric oxide and increased oxidative stress. Insulin resistance, obesity, and high triglyceride are the underlying factors for MS, and previous studies have found that PC is elevated in patients with MS after adjustment for age, gender, ethnicity, and total cholesterol. The present study confirmed that PC was significantly associated with MS after adjustment for age, gender, and status of fatty liver (Table 3 and Fig. 4). Although other factors, such as age, BMI, and fatty liver, had higher odds ratios than PC had, multivariate analysis and stratified analysis confirmed that a higher PC was correlated with MS. It indicated that platelet activation might also play an important and independent role in MS. Further prospective studies are warranted to validate this phenomenon.