Association Between Lipoprotein(a) and Insulin-Like Growth Factor I During Puberty and the Relationship to Microalbuminuria in Children and Adolescents With IDDM

Abstract

OBJECTIVE To study pubertal changes in serum lipoprotein(a) [Lp(a)] and insulin-like growth factor I (IGF-I) in insulin-dependent diabetes mellitus (IDDM) and the relationship to microalbuminuria. RESEARCH DESIGN AND METHODS Seventy-nine children and adolescents (59 with normoalbuminuria, 20 with microalbuminuria) with ≥ 5 years of IDDM were investigated together with 54 healthy control subjects in a cross-sectional study. Fasting serum Lp(a); apolipoprotein (apo) A-1 and B; total, low-density lipoprotein (LDL), and high-density lipoprotein cholesterol; triglycerides; and IGF-I were analyzed as were HbA1c and overnight albumin excretion rate (AER). Pubertal development was assessed by Tanner staging. RESULTS Lp(a), apoB, triglycerides, and total and LDL cholesterol were higher (P < 0.001) and apoA-1 was lower (P = 0.03) in normoalbuminuric IDDM patients than in healthy control subjects. Lp(a) was increased during puberty (stages 2–4) in IDDM patients but not in healthy subjects, whereas IGF-I was significantly increased during puberty in healthy control subjects only. In IDDM patients Lp(a) correlated to insulin dose, total cholesterol, and LDL cholesterol, but not to IGF-I, HbA1c, systolic and diastolic blood pressure, diabetes duration, age, or sex. In multiple regression analysis with Lp(a) as the dependent variable, puberty was the only significant contributor to the regression (r2 = 0.33, P = 0.008). Microalbuminuria was seen only in the pubertal stage 4–5. Lp(a) tended to be higher (P = 0.06) as did apoB, whereas IGF-I was lower (P < 0.001) in this group than in normoalbuminuric patients of the same pubertal stages. In multivariate analysis, with log AER as the dependent variable, apoB/apoA-1, systolic blood pressure, age, and IGF-I but not Lp(a) added to the regression (r2 = 0.47, P < 0.0001). CONCLUSIONS Lp(a) is elevated during puberty in normoalbuminuric subjects with IDDM, independent of metabolic control and IGF-I. Lp(a) tends to be further increased in microalbuminuria but does not seem to be a contributing determinant of log AER whereas low IGF-I does. Prospective studies are required to establish the temporal relationship between increased Lp(a) and microalbuminuria in children and adolescents with IDDM.