title: High IGFBP2 levels are not only associated with a better metabolic risk profile but also with increased mortality in elderly men.
abstract: OBJECTIVE
  Serum IGF-binding protein 2 (IGFBP2) concentrations are reduced in obese humans and increase after a prolonged period of fasting. We investigated the association between IGFBP2 levels and mortality together with other factors that are related to IGFBP2, including the metabolic syndrome and physical function.
  
  
  METHODS
  A prospective observational study at a clinical research center of 403 independently living elderly men (aged 73-94 years).
  
  
  METHODS
  Mortality was registered during 8.6 years of follow-up. Physical performance score (PPS), grip strength (GS), and bone mineral density (BMD) were measured. The measurements taken a baseline were: IGF1; IGFBP1, -2, and -3; IGF1 bioactivity; triiodothyronine (T(3)); and reverse T(3). Further, BMI, insulin sensitivity, cholesterol, inflammatory markers, and albumin levels were also measured.
  
  
  RESULTS
  During the follow-up, 180 men died. Higher PPS, GS, and BMD were independently related to a reduced mortality (hazard ratio (HR)=0.87/point, 95% confidence interval (95% CI)=0.82-0.91, P<0.001; HR=0.96/kp, 95% CI 0.94-0.98, P<0.001; and HR=0.21/(g/cm(2)), 95% CI 0.07-0.61, P<0.01). Higher serum IGFBP2 levels were strongly related to mortality (HR=2.26/(mg/l), 95% CI 1.57-3.27, P<0.001). This was independent of comorbidity, physical function, IGF1 bioactivity, and other somatotropic parameters, including BMI and the metabolic syndrome. In addition, IGFBP2 levels were higher in subjects with nonthyroidal illness, and higher IGFBP2 levels were significantly associated with lower albumin concentrations.
  
  
  CONCLUSIONS
  Despite the strong relationship between high IGFBP2 and low physical function, both were strongly and independently related to increased 8-year mortality in elderly men. IGFBP2 may be a useful biomarker integrating the nutritional status, as well as the biological effects of GH, IGF1, and insulin.
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. annewieke.van.den.beld@ghz.nl
authors.forename: Annewieke W
authors.initials: AW
authors.lastname: van den Beld
authors.forename: Werner F
authors.initials: WF
authors.lastname: Blum
authors.forename: Michael P
authors.initials: MP
authors.lastname: Brugts
authors.forename: Joop A M J L
authors.initials: JA
authors.lastname: Janssen
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000502:physiology; D005500:Follow-Up Studies; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D055442:Metabolome / Q000502:physiology*; D053580:Muscle Strength / Q000502:physiology; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2