Background and Objectives: Metabolic syndrome (MetS), characterized by central obesity, hyperglycemia, dyslipidemia, and hypertension, is highly prevalent in populations with chronic pancreatitis (CP). However, the role of MetS components in the development of pancreatic exocrine insufficiency (PEI) in patients with CP remains unclear. This review systematically synthesizes evidence to elucidate the relationship between MetS components and PEI pathogenesis. Methods: A structured methodology was employed to evaluate existing literature. Studies were identified through systematic searches of PubMed, Embase, and Scopus using predefined keywords such as “metabolic syndrome,” “pancreatic exocrine insufficiency,” and “chronic pancreatitis.” Inclusion criteria focused on original observational, cohort, and case-control studies reporting associations between individual MetS components and PEI in CP. Data were critically appraised for quality and relevance, and findings were synthesized to highlight trends, inconsistencies, and gaps in the evidence. Results: The review identified hyperglycemia, dyslipidemia, and abdominal obesity as significant contributors to pancreatic damage, mediated by mechanisms such as chronic inflammation, oxidative stress, lipotoxicity, and impaired insulin signaling. However, the role of hypertension in PEI pathogenesis remains less defined. Variability in reported associations was observed, influenced by differences in diagnostic criteria, study populations, and methodologies. Conclusions: Early recognition and management of MetS components are crucial to preventing or mitigating PEI in CP patients. Lifestyle interventions, pharmacological therapies, and pancreatic enzyme replacement therapy (PERT) are key elements of a multidisciplinary care approach. Future research should focus on large-scale prospective studies, mechanistic investigations, and randomized controlled trials to establish causal relationships and develop targeted interventions. These efforts are critical to enhancing diagnostic, preventive, and therapeutic outcomes for CP patients with coexisting metabolic syndrome (MetS).
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