To our knowledge, this is the first case-control study demonstrating the relationship between metabolic syndrome and occurrence of AP in Asian population. Our results showed that metabolic syndrome was a risk factor of AP. Among metabolic components, we revealed that the increased values of TC, TG, FPG and decreased values of Apo A were independently associated with AP.
Hyperglycemia has been considered to be associated with AP for decades[16]. However, only few studies have shown higher incidence rate of AP patients with hyperglycemia[17–20]. Our results revealed that hyperglycemia would lead to a 2.345-fold increased risk of AP. Moreover, Shih-Wei Lai et, al observed a significant reduction of AP risk if patients with T2DM received anti-diabetic treatment. This further supported a causal relationship between hyperglycemia and AP[20]. Although the exact mechanism between hyperglycemia and AP remains unclear, several underlying biological theories have been proposed. High plasma glucose enhances mitochondria oxidative stress by promoting the production of reactive oxygen species(ROS) and lipid oxidation through cytosolic Ca2+ accumulation[21–23]. Meanwhile, owing to the dysfunction of Beta cell and resultant hyperinsulinemia, the inhibitory hormone named somatostatin may lose its sensitivity to Beta cell, which may be an important factor to induce AP[24]. Moreover, insulin resistance, as a crucial pathophysiological factor of hyperglycemia, its involvement in AP development was reported. Various proinflammatory factors or cytokines were activated due to insulin resistance, including Nuclear factor κB (NF κB), Tumour necrosis factor α (TNF-α), amylin and interleukin-6, and these proinflammatory factors may be responsible for the initiation and progression of AP[25–29].
It is well known that hypertriglyceridemia is associated with the morbidity and mortality of AP[30–32]. Our study showed TG had a 2.058-fold increased risk of AP compared to controls. Furthermore, we found that there were 1.831-fold increases and 0.247-fold decreases in risk associated with TC and Apo A, which demonstrated that atherogenic lipid profiles also participated in the development of AP. Triantafilou M et, al reported that cholesterol may trigger the inflammatory responses that could lead to chronic inflammation and insulin resistance via TLR4, and ultimately causes lysosomal damage, ROS generation and proinflammatory cytokines secretion[33, 34]. This theory may explain why acinar injury would be induced by hypercholesterolemia through inflammation response. Furthermore, as lipoprotein, HDL often opposes cholesterol accumulation and reduces inflammation by ATP-binding cassette transporter A1(ABCA1) pathway[35]. This ability may be impaired if Apo A is oxidized by macrophage myeloperoxidase (MPO). Shao B et, al reported the impaired function of HDL and Apo A in patients with atherosclerosis[36], which may be similar in AP. However, our results only showed that the value of Apo A was negatively associated with the incidence rate of AP while we did not observe the association between HDL and AP. Based on our present study, it is hard to tease out the exact role of HDL in AP. In future studies, it will be important to find out the exact function that HDL and Apo A exert in AP development.
Nowadays obesity is considered as a global pandemic which poses great threat to human health. Some studies have shown that obesity was positively correlated with severity of AP[37, 38, 12]. However, due to the paucity of studies between obesity and incidence of AP, their relationship has been a matter of dispute. Blomgren et al. found that the crude risk ratio (RR) between obesity and occurrence of AP was 1.8 (95% CI:1.3 to 2.6) while the author did not display the results after adjustment[39]. Contrary to previous beliefs, our current study did not find an association between BMI and AP (p = 0.186), which is consistent with a recent large scale prospective cohort study (RR = 1.02, 95%CI: 0.68 to 1.53)[40]. In animal model, obesity was shown related to an inflammatory status by secreting proinflammatory cytokines such as TNF and interleukin-6[41]. Moreover, the level of adiponectin, an anti-inflammatory cytokine, will be reduced under an obesity environment. Therefore, according to our results, we suppose that obesity may aggravate the severity of AP but is not enough to initiate the development of AP without other risk factors in a non-AP person.
Limitations of our study are as followings: (1) Our study is a retrospective hospital-based case-control study, which may inevitably produce selection bias, especially on control subjects. (2) Although we found strong association between metabolic syndrome components and AP, we did not evaluate the effect of treatment of each component on individual, which may have an impact on the results. Major strengths are as followings: (1) This is the first study to illustrate the association between metabolic syndrome and development of AP in Asian population. (2) Given the completeness of behavior and epidemiologic data, we can ensure the accuracy of clinical diagnosis and high quality of data and minimize the recall bias.