title: Plasma proneurotensin and incidence of diabetes, cardiovascular disease, breast cancer, and mortality.
abstract: BACKGROUND
  Neurotensin regulates both satiety and breast cancer growth in the experimental setting, but little is known about its role in the development of breast cancer or cardiometabolic disease in humans.
  
  
  OBJECTIVE
  To test if fasting plasma concentration of a stable 117-amino acid fragment from the neurotensin precursor hormone proneurotensin is associated with development of diabetes mellitus, cardiovascular disease, breast cancer, and mortality.
  
  
  METHODS
  Proneurotensin was measured in plasma from 4632 fasting participants of the population-based Malmö Diet and Cancer Study baseline examination 1991-1994. Multivariate Cox proportional hazards models were used to relate baseline proneurotensin to first events and death during long-term follow-up until January 2009, with median follow-up ranging from 13.2 to 15.7 years depending on the disease.
  
  
  METHODS
  Incident diabetes mellitus, cardiovascular disease, breast cancer, and mortality.
  
  
  RESULTS
  Overall, proneurotensin (hazard ratio [HR] per SD increment of log-transformed proneurotensin) was related to risk of incident diabetes (142 events; HR, 1.28; 95% CI, 1.09-1.50; P = .003), cardiovascular disease (519 events; HR, 1.17; 95% CI, 1.07-1.27; P < .001), and cardiovascular mortality (174 events; HR, 1.29; 95% CI, 1.12-1.49; P = .001) with a significant interaction between proneurotensin and sex (P < .001) on risk of cardiovascular disease. Exclusively in women, proneurotensin was related to incident diabetes (74 events; HR, 1.41; 95% CI, 1.12-1.77; P = .003), cardiovascular disease (224 events; HR, 1.33; 95% CI, 1.17-1.51; P < .001), breast cancer (123 events; HR, 1.44; 95% CI, 1.21-1.71; P < .001), total mortality (285 events; HR, 1.13; 95% CI, 1.01-1.27; P = .03), and cardiovascular mortality (75 events; HR, 1.50; 95% CI, 1.20-1.87; P < .001).
  
  
  CONCLUSIONS
  Fasting proneurotensin was significantly associated with the development of diabetes, cardiovascular disease, breast cancer, and with total and cardiovascular mortality.
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden. olle.melander@med.lu.se
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.forename: Alan S
authors.initials: AS
authors.lastname: Maisel
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.forename: Mattias
authors.initials: M
authors.lastname: Belting
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.forename: Ute
authors.initials: U
authors.lastname: Kilger
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood* / Q000401:mortality; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009496:Neurotensin / Q000097:blood*; D016017:Odds Ratio; D011498:Protein Precursors / Q000097:blood*; D012306:Risk; D013548:Sweden / Q000453:epidemiology
chemical_list: D011498:Protein Precursors; C411471:proneurotensin; D009496:Neurotensin