Metabolic syndrome and acute pancreatitis: Current status and future prospects

Abstract

Rising incidence of a complicated disorder with a multifarious etiology is acute pancreatitis. Growing numbers of cases of acute pancreatitis are linked to obesity, hyperlipidemia, hyperglycemia, hypertension, and other metabolic diseases. Trends driven by better living standards and unhealthy lifestyle choices both in China and abroad. Furthermore common diagnosis for many patients is metabolic syndrome. Predicting the adverse effect of metabolic syndrome on the severity and prognosis of acute pancreatitis is a main focus of present clinical research. Our next studies seek to investigate the fundamental causes of this link and create preventative plans meant to lower the incidence of pancreatitis linked to metabolic syndrome and enhance the prognosis.

Key Words: Metabolic syndrome; Acute pancreatitis; Obesity; Hypertension; Hyperlipidemia; Hyperglycaemia

Core Tip: Closely linked with metabolic syndrome, acute pancreatitis has a multifactorial etiology. The combination of several elements of metabolic syndrome could affect the prognosis of acute pancreatitis. Reducing the effect of metabolic syndrome depends on early intervention via lifestyle modification. Still, future studies should focus especially on the development of precision treatment plans and focused pharmacological therapies.

TO THE EDITOR

The primary cause of acute pancreatitis (AP) is the aberrant activation of pancreatic enzymes, which results in digestion of the pancreas and surrounding tissues, so triggering localized edema, necrosis, and pancreatic inflammation[1]. AP has a complex etiology that has been well investigated all around. Gallstones[2], hypertriglyceridemia (HTG)[3], too much alcohol consumption[4], genetic predispositions[5], and drug-induced pancreatitis[6] are the most often occurring causes). Although HTG and alcohol-induced AP mostly affect younger and middle-aged men, biliary pancreatitis is more common among the elderly[7]. Especially, new research indicates that HTG has replaced too much alcohol intake as the second most common cause of AP and that the prevalence of AP connected with metabolic syndrome (MS) is increasing. Changes in eating patterns and better living standards most certainly help to explain this trend[5].

Professor Reaven[8] first proposed MS in 1988, outlining the accumulation of metabolic risk factors including central/abdominal obesity, hyperglycemia, dyslipidemia, and hypertension, which taken together cause systemic organ damage. With patients getting younger from low-fiber, high-calorie diets and sedentary lifestyles, the worldwide frequency of MS is rising[9]. Key component of MS, HTG is closely associated with the onset of AP, sometimes known as HTG-AP[10]. Previous studies have looked at the clinical outcomes of HTG-AP in a cohort of 255 patients using individual MS components including obesity, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol. These investigations show that coexistence of several MS components can aggravate the HTG-AP severity[11]. Still, the exact pathophysiological processes and the evolution of focused therapeutic and preventive strategies remain subjects of active research since they highlight the need of more study to direct clinical management.

CORRELATION MECHANISM BETWEEN MS AND AP

Common systemically inflammatory disease, AP can vary in degree from mild to life-threatening[12]. Many AP patients are obese, and studies point to a relationship between growing obesity rates and AP prevalence that is rising. Moreover, the degree of obesity increases the severity of AP[13]. Many times, seen in obese people is HTG. By means of mechanisms including inhibition of mitochondrial complexes I and V, lowering of ATP levels, release of intracellular calcium ions, and induction of pancreatic acinar cell necrosis, unsaturated fatty acids can induce inflammatory reactions. Furthermore, high levels of free fatty acids can activate lysosomal cathepsin B and trypsinogen, so generating active trypsin and so causing pancreatic inflammation and self-digestion[14]. Numerous clinical studies have linked accumulating adipose tissue, especially visceral adipose tissue, to increased multi-system organ damage and pancreatic necrosis in AP[15]. Released biologically active fat factors by adipose tissue help to control immunity, inflammation, and metabolism. But obesity throws off the equilibrium of these fat components, increasing the risk of obesity-related diseases. The enhanced systemic inflammatory response seen in AP[16] mirrors this imbalance. Studies show that higher levels of adipokines cause chronic inflammation and remodeling of adipose tissue, which finally results in systemic insulin resistance (IR)[17]. The main cause of MS is inflammation (IR), which can result in a range of inflammatory responses[18], lead the body to become hypercoagulable and disturbs the coagulation and fibrinolysis systems, so aggravating AP by ischemia and hypoxia of the pancreatic tissue. Two absolutely important features of diabetes mellitus are hyperglycemia and IR. Based on epidemiological data, diabetes patients may be more prone to acquire AP, but the underlying mechanism is yet unknown[19]. Tumor necrosis factor α, NF-κB and islet amyloid peptide may all affect IR; these then mix with hyperglycemia to increase reactive oxygen species generation in acinar cells and boost lipid peroxidation, which causes AP[20]. People with MS also run more danger of gallstones[21]. While lowered bile acid levels in MS patients promote cholestasis and gallstone formation, which finally results in gallstone-induced pancreatitis, prolonged lipid accumulation can lead to larger and more numerous cholesterol crystals. Though little is known about the link between hypertension and AP incidence, some studies indicate that antihypertensive drugs might raise AP risk in those with hypertension[22].

Many times, in clinical practice, MS patients show several comorbidities, which are connected and contribute to the development and progression of AP[23]. This synergy aggravates general prognosis[24], raises the possibility of AP-related complications, and magnifies local and systemic inflammation. Comparatively to non-MS patients, MS patients have lower survival rates, more frequent local and systemic sequelae, and a higher risk of severe AP according to clinical studies[25]. Patients having both AP and several MS components should thus get more attention in clinical environments. More study is required to fully grasp how MS affects the pathogenesis and prognosis of AP.

TREAMENT MEASURES OF AP ASSOCIATED WITH MS

Key component of MS, HTG greatly influences the start and course of HTG-AP. Apart from being the etiology of AP, HTG is a common outcome of AP since it is usually brought on by stress and inflammatory responses[23]. Dietary changes, insulin treatment, heparin administration, antihyperlipidemic drugs, and plasma exchange[26] are the main therapy modalities used for AP linked with MS. Above all, bad lifestyle choices including binge eating, smoking, too much alcohol, and drug use must be cut off[27]. Management of HTG depends much on a well-balanced diet. A high-fat diet increases MS risk; a diet high in fiber, omega-3 and omega-9 fatty acids, complex carbohydrates, antioxidants, minerals, vitamins, and bioactive compounds (such as polyphenols) can reduce obesity, dyslipidemia, hypertension, and diabetes, so addressing components of MS[28]. Still, pharmacotherapy must start right away. Patients with HTG-AP could gain from anti-lipid drugs in cases when serum triglyceride levels keep increasing. Usually prescribed are fenofibrate and omega-3 fatty acids. Twelve months of omega-3 fatty acid treatment notably lowered glutamyl transpeptidase activity, liver fat, and produced positive changes in the lipid profile of MS patients[29]. Furthermore, under research are new pharmacological compounds aiming at apolipoprotein C-III and angiopoietin-like proteins[30]. Comparatively to a placebo group, a 40-person randomized trial including colchicine found that it greatly reduced inflammatory markers linked with obesity and improved inflammatory outcomes in MS patients[31]. Apart from controlling blood glucose, insulin treatment improves immune response, so lowering the infection risks. Moreover, insulin can raise lipoprotein lipase activity in adipose tissue, so improving the prognosis of AP patients[32,33]. Heparin reduces inflammation by preventing intravascular micro thrombosis, so improving pancreatic microcirculation. It forms a complex with antithrombin III that inhibits trypsin and chymotrypsin activities, so lowering pancreatic inflammation and acting therapeutively[34].

Also used in HTG-AP treatment is plasma exchange, although plasma exchange quickly lowers triglyceride levels, a prospective study of 267 HTG-AP patients found that its clinical advantages, especially with relation to organ failure incidence and duration, remain unclear[35]. Another good choice, especially for AP linked to MS, is bariatric surgery. In obesity-related metabolic diseases, it has been clearly shown to help weight loss, cardiovascular risk, dyslipidemia, nonalcoholic fatty liver disease, and glucose homeostasis[36]. Metabolic surgery can reduce type 2 diabetes by 23%-60%, cause steady weight loss of 20%-30%, and lower cardiovascular risk factors including dyslipidemia and hypertension[37]. When MS-related AP presents itself, timely surgical intervention, such as partial or complete pancreatic resection or drainage tube placement, can improve patient outcomes. Increased free fatty acids can cause acidosis, which releases trypsin and then causes pancreatic tissue autolysis. Early surgery reduces mortality by stopping pancreatic autolysis and the dissolution of surrounding tissues, so improving patient survival[38]. For patients with severe AP complicated by MS, then, a more aggressive approach might produce better therapeutic results. New developments in minimally invasive endoscopic procedures present substitutes for treating MS-associated AP. Researchers have created duodenal mucosal thermal ablation techniques and high-performance metal stents meant to treat metabolic diseases linked to IR. Although more clinical research is required to evaluate its safety and efficacy in human patients, this method, shown in pig models, offers a fresh direction for treating MS-related AP[39].

CLINICAL IMPLICATIONS

There are three primary justifications for the classification of AP associated to Three main factors contribute to the consideration of AP linked with MS as a major clinical issue. First, MS's frequency is gradually rising in China. Second, the second most common cause of AP now is HTG, which has exceeded even high alcohol intake. At last, lifestyle changes and possible pharmacological treatments provide efficient ways for treating AP related to MS as well as for preventing it.

CONCLUSION

Increased degree of AP is much correlated with obesity, HTG, hyperglycemia, hypertension, and other components of MS. While the presence of several elements may aggravate the negative consequences of AP, each individual component can independently influence the course, start, and prognosis of the condition. Patients should start significant dietary and lifestyle changes early on to help to offset these effects. Clinically, improving the prognosis, preventing the start of severe AP, and enabling early diagnosis and treatment of MS depend on the evaluation of risk factors in patients with MS-associated AP. More study is needed to clarify the exact processes driving the evolution of MS-related AP. Furthermore, it is prudent to explore potential pharmacological treatments for MS-related AP, as they may offer patients supplementary therapeutic alternatives.