Objective: Unlike IGF-I and its principal binding proteins, data regarding IGF-II levels have not been well defined in normal subjects and those with insulin-dependent diabetes mellitus (IDDM). We have therefore measured IGF-II, as well as IGF-I, and IGFBP-3, levels in a large cohort of subjects with IDDM and in age/sex matched controls.
Patients: One hundred and fourteen patients with IDDM (57 males, 57 females) and 89 control subjects (49 males, 40 females).
Measurements: Random blood samples were obtained from each subject for the measurement of IGF-II, IGF-I and IGFBP-3 levels.
Results: Mean values of IGF-II (+/- SEM) were 630 (+/- 27.8) micrograms/l and 646 (+/- 32.3) micrograms/l in female and male controls, compared to 569 (+/- 23.3) micrograms/l and 623.3 (+/- 28.1) micrograms/l in female and male diabetics respectively. IGF-II levels did not differ significantly between the sexes or show any change with transition through puberty in either control or diabetic groups. In contrast, IGF-I levels increased through puberty peaking at stages 3-5 in controls (P < 0.001) and G4-5 (P = 0.002) in diabetic males but not females. IGF-I levels in all diabetics were generally lower than in controls, differences reaching significance at G4-5 in males (P = 0.002) and B5 in females (P = 0.002). IGFBP-3 levels did not show any variation with puberty stage in diabetics, in contrast to controls where levels increased, peaking at G4-5 in males (P = 0.001) and B3 in females. IGFBP-3 levels were lower in diabetics of both sexes and at all stages compared to controls (P range 0.047 to < 0.001). Multiple regression analysis revealed significant correlations between IGF-II and IGFBP-3 (F = 20.1, P = < 0.001) and reaffirmed previously observed associations for IGF-I and IGFBP-3. The sum of IGF-I and IGF-II (expressed as nmol/l) correlated with IGFBP-3; r = 0.47 in controls and 0.60 in diabetics.
Conclusions: Insulin-dependent diabetes mellitus is not associated with any significant changes in IGF-II levels during puberty. The binding of IGFBP-3 for both IGF-I and IGF-II is unaltered by insulin-dependent diabetes mellitus.