The relation between adiposity throughout the life course and variation in IGFs and IGFBPs: evidence from the ProtecT (Prostate testing for cancer and Treatment) study.
OBJECTIVE
Adiposity is positively associated with advanced, metastatic, and fatal prostate cancer. Obesity-related variations in insulin-like growth factors (IGF-I and -II) and their binding proteins (IGFBPs) could underlie these associations.


METHODS
We investigated associations of adiposity throughout the life course (determined retrospectively) with serum levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in a population-based study of 1,106 healthy men.


RESULTS
IGF-I and IGF-II showed inverted U-shaped associations with adult body mass index (BMI) (p quadratic model = 0.04 and 0.06, respectively), although differences between quartiles with the highest and lowest IGF-I levels were small (no more than 5 ng/ml). IGFBP-2 was strongly inversely related to adult BMI (-22% change per SD increase in BMI; 95% confidence interval (CI) -24% to -19%) and waist circumference (-18% change per SD increase in waist circumference; 95% CI -20% to -15%) (p < 0.001). IGFBP-3 was positively related to BMI (63.5 ng/ml increase per SD increase in BMI; 95% CI -2.69 to 129.8, p = 0.06). IGFBP-2 and IGFBP-3 were strongly related to body shape change from childhood to adulthood, with men who gained the most weight having the lowest IGFBP-2 (9% lower per category body shape change; 95% CI -11% to -7%, p < 0.001) and the highest IGFBP-3 (50 ng/ml increase per category; 95% CI 8 to 92, p = 0.02).


CONCLUSIONS
We provide evidence that adiposity and change in body shape through the life course are related to the IGF system, with the largest effect of adiposity being to lower IGFBP-2, a possible marker of insulin resistance. The results suggest that circulating IGF-I levels may not be important mediators of the association of adiposity with aggressive prostate cancer, but the role of IGFBP-2 deserves further investigation.
Rowlands
Mari-Anne
MA
Department of Social Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK. Mari-anne.rowlands@bristol.ac.uk
Holly
Jeff M P
JM
Gunnell
David
D
Gilbert
Rebecca
R
Donovan
Jenny
J
Lane
J Athene
JA
Marsden
Gemma
G
Collin
Simon M
SM
Hamdy
Freddie
F
Neal
David E
DE
Martin
Richard M
RM
D050154:Adiposity; D000328:Adult; D001823:Body Composition; D015992:Body Mass Index; D015331:Cohort Studies; D006801:Humans; D007333:Insulin Resistance; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000097:blood; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013002:Somatomedins / Q000378:metabolism*; D055105:Waist Circumference
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II