The Correlation Between Pancreatic Steatosis And Metabolic Syndrome:A 5-year Follow-up Study And A Meta-Analysis

Background and Objection:Probably due to the changes of lifestyle,such as high-caloric,high-fat diet and lack of exercise,the metabolic syndrome（Met S）becomes a worldwide social and psychological issue that affects all levels of age and socioeconomic groups.Ectopic fat can accumulate in the organs such as liver,muscles,heart,and pancreas,which is an important pathophysiologic abnormality of Met S.Pancreatic steatosis is the description of fat accumulation in the pancreatic gland.The complete natural history of nonalcoholic fatty pancreas disease（NAFPD）is unknown because few high-quality follow-up studies have been conducted to date.The prevalence and development mechanisms of pancreatic steatosis in patients with Met S and its components still remain unclear.We did a retrospective cohort study and a Meta-analysis in this study.We aimed to investigate the association of fatty pancreas（FP）with the incidence of Met S and its components and to systematically review the association between pancreatic steatosis and metabolic co-morbidities.Methods:Part1 The association between pancreatic steatosis and metabolic syndrome:a 5-year follow-up study among a general Chinese populationThree independent cross-sectional surveys carried out in 2013,2015 and 2018 at a health checkup at the Health Examination Center of Shandong Province Hospital affiliated to Shandong University.The study population consis ted of subjects took part in the annual or biennial comprehensive health screening exa minations at the center.On thebaseline visit and the follow-up visits,all subjects wer e fasted overnight prior to undergoing a comprehensive medical examination,includi ng a face-to-face interview,clinical and anthropometric measurements（weight,height and blood pressure）,biochemical and serological tests,and abdominal ultrasound for the diagnosis of pancreatic steatosis and nonalcoholic fatty liver disease（NAFLD）.Metabolic syndrome was confirmed according to the Chinese Diabetes Society（CDS）criteria.Logistic regression analysis was used to estimate the correlation between pancreatic fatty infiltration and metabolic syndrome.A model adjusted for age,gender,drinking,smoking,eating habits,exercise and sleep status was constructed to correct for confounders and calculate OR and 95%CI.The new cases of Met S,T2DM,hypertension and NAFLD were estimated by Cox proportional hazards models adjusted for age,gender and life habits.A value of P<0.05 was considered statistically significant.Part 2 The association between pancreatic steatosis and metabolic syndrome:a systematic review and Meta-analysisWe performed a systematic search strategy using three electronic databases（MEDLINE,Scopus,and Embase）for relevant studies concerning the associations of pancreatic steatosis with metabolic syndrome and its clinical relevance from inception until September 30,2018.Two independent reviewers verified that the studies were eligible for inclusion if they provided data on NAFPD prevalence,assessed the quality of the studies and extracted their relevant characteristics.The data were descriptively pooled using random-effects relative risk Meta-analysis.Results:1.Cross-sectional study:12551 individuals classified into FP（n=1010）and non-FP（n=11541）groups were finally enrolled at baseline.The FP group had a greater proportion of subjects with Met S（40.1%versus 21.4%）,diabetes（19.5%versus 8.98%）,NAFLD（76.24%versus 34.33%）,hypertension（30.59%versus 21.81%）,compared with the non-FP group（P<0.001）.There were significant differences in age,gender,BMI,systolic/diastolic blood pressure,fasting plasma glucose,alanine transaminase（ALT）,aspartate transaminase（AST）,gamma-glutamyl transferase（GGT）,creatinine,total cholesterol（TC）,triglycerides（TG）,HDL cholesterol,and LDL cholesterol,serum uric acid,serum total bilirubin,serum direct bilirubin,indirect bilirubin,alkaline phosphatas,albumin,free triiodothyronine（FT3）.After adjusting for several factors,including gender and age、diet、drinking、smoking,the odds ratio（OR）of pancreatic steatosis was 2.033（95%CI 1.76-2.349;P<0.001）.The OR for type 2 diabetes in the group with fatty pancreatic fat infiltration was 1.897（95%CI 1.574-2.286;P<0.001）,the OR for hypertension was 1.590（95%CI 1.369-1.846;P<0.001）,the OR for NAFLD was 4.913（95%CI 4.177-5.779;P<0.001）.2.Longitudinal study:Met S occurred in 999 participants（10.57%）during the follow-up period of 5 years.After adjusting for several factors,including gender and age、diet、drinking、smoking,pancreatic steatosis was associated with the occurrence of Met S（HR=2.274;95%CI 1.569-3.297;P<0.001）,T2DM（HR=13.99;95%CI 7.865-24.883;P<0.001）and hypertension（HR=12.801;95%CI 7.323-22.38;P<0.001）,NAFLD（HR=31.843;95%CI 7.73-131.171;P<0.001）.In lean participants（BMI<25kg/m2）,fatty pancreas was associated with increased T2DM incidence（HR=40.342;95%CI 8.733-186.363;P<0.001）.3.Meta-analysis:1351 references identified in the initial search,and a total of 13 studies involving 49329 subjects were included.This analyses elucidated the presence of NAFPD was associated with a significant increased risk of metabolic syndrome（RR=2.25;95%CI 2.00-2.53;P<0.0001;I2=42.8%;8 studies included）,hypertension（RR=1.43;95%CI 1.08-1.90;P=0.013;I2=94.7%;9 studies included）and NAFLD（RR=2.49;95%CI 2.06-3.02;P<0.0001;I2=96.9%;9 studies included）and diabetes mellitus（RR=1.99;95%CI 1.18-3.35;P=0.01;I2=97.6%;10 studies included）and central obesity（RR=1.91;95%CI 1.67-2.19;P<0.0001;I2=95.9%;6 studies included）.The association between NAFPD and hyperlipidemia was not statistically significant（RR=1.33;95%CI 0.82-2.17;P=0.249;I2=97%;5 studies included）.Conclusion:The existing evidences of our study indicate that NAFPD is significantly associated with an increased risk of metabolic syndrome and its components.The pancreatic steatosis may increase the occurrence of metabolic syndrome and hypertension,diabetes,and NAFLD.