SummaryOBJECTIVEUnlike 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.PATIENTSOne hundred and fourteen patients with IDDM (57 males, 57 females) and 89 control subjects (49 males, 40 females).MEASUREMENTSRandom blood samples were obtained from each subject for the measurement of IGF‐II, IGF‐I and IGFBP‐3 levels.RESULTSMean values of IGF‐II (±SEM) were 630 (±27.8) μg/l and 646 (±32.3) μg/l in female and male controls, compared to 569 (±23.3) μg/l and 623.3 (±28.1) μg/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 (Prange 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 IGFBP3;r= 0.47 in controls and 0.60 in diabetics.CONCLUSIONSInsulin‐dependent diabetes mellitus is not associated with any significant changes in IGF‐II levels during puberty. The binding of IGFBP‐3 for both IGF