Association Between Seafood Consumption And Type 2 Diabetes Mellitus Based On Cohort Study And Bioinformatics

Background and objective:The incidence of type 2 diabetes mellitus(T2DM)is increasing annually,with its concomitant life-threatening complications of cardiovascular disease,nervous system disease,eye problems and foot diseases.There are some inconsistencies in association between seafood intake and T2 DM,although the seafood and its nutrients are beneficial to human health.However,there is little research about molecular mechanism between seafood and T2 DM.Therefore,this study intends to investigate the association between shellfish intake and the T2 DM incidence,and to explore the internal biological mechanism on shellfish nutrients and T2 DM using bioinformatics methods.It provides scientific theory for dietary guidance in seafood intake for adults.Methods:A cohort study was used to analyse the association between seafood intake and the risk of T2 DM incidence.Three surveys were conducted from 2009 to 2021.A total of 4539 subjects without T2 DM were recruited at baseline in 2009,and were followed up in2012-2015 and 2019-2021.Actually,3 251 subjects were followed up.We had used exclusion criteria of no data of seafood intake information at baseline and glucose at baseline and follow-up.Finally,2 675 individuals were included in this cohort study.Cox proportional hazards regression analyses were used to analyze the association between seafood(fish and shellfish)intake and the incidence of T2 DM.Bioinformatics study was used to investigate the internal molecular mechanism on shellfish nutrients and T2 DM.The genes about shellfish nutrients [n-3 polyunsaturated fatty acids(PUFA),zinc,selenium] and T2 DM were obtained from comparative toxicogenomics Database(CTD)and Pub Med GEO datasets.And the differentially expressed genes(DEGs)about shellfish nutrients and T2 DM were screened by jevvn online.Gene ontology(GO)and KEGG pathway on DEGs was performed by DAVID online software.Results:1.The cohort study showed that there were 376 patients with T2 DM,and the incidences of T2 DM were14.1%.Adults with shellfish intake yielded a significantly low risk of T2 DM against adults without shellfish intake after adjusting age,gender,body mass index,family history of diabetes,hypertension,staple food,fresh vegetables,fresh fruit,meat,the RR(95%CI)was 0.77(0.61,0.97).Adults consuming >2 time/week of shellfish had a significantly low risk of T2 DM compared to those consuming 0 time/week after adjusting age,gender,body mass index,family history of diabetes,hypertension,staple food,fresh vegetables,fresh fruit,meat,the RR(95%CI)was 0.63(0.46,0.88).Adults with a shellfish intake of >22 g/d had a significantly low risk of T2 DM compared to those with an intake of 0 g/d after adjusting age,gender,body mass index,family history of diabetes,hypertension,staple food,fresh vegetables,fresh fruit,meat,the RR(95%CI)was 0.70(0.53,0.92).Men with a total seafood intake of >44 g/d had a significantly low risk of T2 DM compared to those with an intake of 0 g/d afteradjusting age,family history of diabetes,smoking,hypertension,staple food,fresh vegetables,fresh fruit,meat,the RR(95%CI)was 0.47(0.24,0.90).Men consuming >2 time/week of fish had a significantly low risk of T2 DM compared to those consuming 0 time/week after adjusting age,family history of diabetes,smoking,hypertension,staple food,fresh vegetables,fresh fruit,meat,the RR(95%CI)was 0.53(0.29,0.96).Men with a fish intake of >30 g/d had a significantly low risk of T2 DM compared to those with an intake of 0g/d after adjusting age,family history of diabetes,smoking,hypertension,staple food,fresh vegetables,fresh fruit,meat,the RR(95%CI)was 0.51(0.27,0.94).Men with shellfish intake yielded a significantly low risk of T2 DM against men without shellfish intake after adjusting age,family history of diabetes,smoking,hypertension,staple food,fresh vegetables,fresh fruit,meat,the RR(95%CI)was 0.67(0.46,0.96).Men consuming >0～≤2 time/week and >2 time/week of shellfish had significantly low risks of T2 DM compared to those consuming 0 time/week after adjusting age,family history of diabetes,smoking,hypertension,staple food,fresh vegetables,fresh fruit,meat,the RR(95%CI)were 0.67(0.46,0.97),0.60(0.37,0.99).Men with a shellfish intake of >22 g/d had a significantly low risk of T2 DM compared to those with an intake of 0 g/d after adjusting age,family history of diabetes,smoking,hypertension,staple food,fresh vegetables,fresh fruit,meat,the RR(95%CI)was 0.58(0.38,0.89).Total seafood intake,fish intake and shellfish intake were not associated with T2 DM risk in women.2.GEO and CTD database analysis showed that there were 11 DEGs associated with T2 DM and n-3 PUFA,40 DEGs associated with T2 DM and zinc,25 DEGs associated with T2 DM and selenium.Go analysis indicated that n-3 PUFA,zinc,selenium and T2 DM were mainly involved in biological processes,cell components and molecular functions,such as cellular response to cytokine-mediated signaling pathway,inflammatory response,MAPK cascade,neutrophil chemotaxis,cellular response to lipopolysaccharide,extracellular space,oxidoreductase activity.KEGG analysis showed that n-3 PUFA,zinc,selenium and T2 DM were mainly involved in IL-17 signaling pathway,TNF signaling pathway,NF-kappa B signaling pathway,NOD-like receptor signaling pathway,and so on.Conclusions:Shellfish intake of >2 time/week and >22 g/d were negatively associated with T2 DM in general population.Total seafood intake of >44 g/d,fish intake of >2 time/week and >30 g/d,shellfish intake of >0～2 time/week,>2 time/week,>22 g/d were negatively associated with T2 DM in men,however,not in women.N-3 PUFA,zinc,selenium may affect T2 DM through cellular response to cytokine-mediated signaling pathway,inflammatory response,MAPK cascade,neutrophil chemotaxis,cellular response to lipopolysaccharide,extracellular space,oxidoreductase activity,IL-17 signaling pathway,TNF signaling pathway,NF-kappa B signaling pathway and NOD-like receptor signaling pathway.Furthermore,it should be validated through the long and intervention study.