title: Nonlinear association of BMI with all-cause and cardiovascular mortality in type 2 diabetes mellitus: a systematic review and meta-analysis of 414,587 participants in prospective studies.
abstract: The relationship between BMI and mortality has been extensively investigated in the general population; however, it is less clear in people with type 2 diabetes. We aimed to assess the association of BMI with all-cause and cardiovascular mortality in individuals with type 2 diabetes mellitus.
  
  
  
  We searched electronic databases up to 1 March 2016 for prospective studies reporting associations for three or more BMI groups with all-cause and cardiovascular mortality in individuals with type 2 diabetes mellitus. Study-specific associations between BMI and the most-adjusted RR were estimated using restricted cubic splines and a generalised least squares method before pooling study estimates with a multivariate random-effects meta-analysis.
  
  
  
  We included 21 studies including 24 cohorts, 414,587 participants, 61,889 all-cause and 4470 cardiovascular incident deaths; follow-up ranged from 2.7 to 15.9 years. There was a strong nonlinear relationship between BMI and all-cause mortality in both men and women, with the lowest estimated risk from 31-35 kg/m2and 28-31 kg/m2(p value for nonlinearity <0.001) respectively. The risk of mortality at higher BMI values increased significantly only in women, whilst lower values were associated with higher mortality in both sexes. Limited data for cardiovascular mortality were available, with a possible inverse linear association with BMI (higher risk for BMI <27 kg/m2).
  
  
  
  In type 2 diabetes, BMI is nonlinearly associated with all-cause mortality with lowest risk in the overweight group in both men and women. Further research is needed to clarify the relationship with cardiovascular mortality and assess causality and sex differences.
authors.affiliation: Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, LE5 4PW, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaccardi
authors.affiliation: Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, LE5 4PW, UK. nnd2@le.ac.uk.
authors.forename: Nafeesa N
authors.initials: NN
authors.lastname: Dhalwani
authors.affiliation: Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, LE5 4PW, UK.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Papamargaritis
authors.affiliation: Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, LE5 4PW, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Webb
authors.affiliation: University of Leicester, Department of Cardiovascular Sciences, Clinical Sciences Wing, Glenfield General Hospital, Leicester, LE3 9QP, UK.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Murphy
authors.affiliation: Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, LE5 4PW, UK.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Davies
authors.affiliation: Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, LE5 4PW, UK.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Khunti
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
keywords: BMI; Body mass index; Cardiovascular disease; Diabetes; Meta-analysis; Mortality; Nonlinearity; Systematic review