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OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide while still lacks drugs for treatment or prevention. We aimed to investigate the causal role of glucose-dependent insulinotropic polypeptide receptor agonists (GIPRAs) on NAFLD and identify the mediated risk factors by which GIPRAs exert their therapeutic effects. METHODS: Genetic proxies of GIPRAs were identified as cis-SNPs of GIPR associated with both the gene expression level and HbA1c and analyses including colocalization and linkage disequilibrium (LD) were performed for validation. We then performed two-sample two-step mendelian randomization to determine the causal effect of GIPRAs on NAFLD. RESULTS: The MR analysis suggested genetic proxies of GIPRAs were causally associated with reduced risk of NAFLD (Odds ratio (OR): 0.46, 95 % confidence interval (95 % CI): 0.24-0.88, P = 0.02) and T2DM (OR: 0.10, 95 % CI: 0.07-0.13, P < 0.01). In addition, Mediation analysis showed evidence of indirect effect of GIPRAs on NAFLD via TRIG (0.88, [0.85-0.92], P < 0.01) and HDL-C (0.85, [0.80-0.90], P < 0.01). CONCLUSIONS: Our study provided strong evidence to support the causal role of GIPRAs on reducing the risk of NAFLD probably through improving lipid metabolism, especially TG and HDL-C, providing guidance for future clinical trials.
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BACKGROUND: Minute gastric cancers (MGCs) have a favorable prognosis, but they are too small to be detected by endoscopy, with a maximum diameter ≤ 5 mm. AIM: To explore endoscopic detection and diagnostic strategies for MGCs. METHODS: This was a real-world observational study. The endoscopic and clinicopathological parameters of 191 MGCs between January 2015 and December 2022 were retrospectively analyzed. Endoscopic discoverable opportunity and typical neoplastic features were emphatically reviewed. RESULTS: All MGCs in our study were of a single pathological type, 97.38% (186/191) of which were differentiated-type tumors. White light endoscopy (WLE) detected 84.29% (161/191) of MGCs, and the most common morphology of MGCs found by WLE was protruding. Narrow-band imaging (NBI) secondary observation detected 14.14% (27/191) of MGCs, and the most common morphology of MGCs found by NBI was flat. Another three MGCs were detected by indigo carmine third observation. If a well-demarcated border lesion exhibited a typical neoplastic color, such as yellowish-red or whitish under WLE and brownish under NBI, MGCs should be diagnosed. The proportion with high diagnostic confidence by magnifying endoscopy with NBI (ME-NBI) was significantly higher than the proportion with low diagnostic confidence and the only visible groups (94.19% > 56.92% > 32.50%, P < 0.001). CONCLUSION: WLE combined with NBI and indigo carmine are helpful for detection of MGCs. A clear demarcation line combined with a typical neoplastic color using nonmagnifying observation is sufficient for diagnosis of MGCs. ME-NBI improves the endoscopic diagnostic confidence of MGCs.