Pubertal growth in IDDM is determined by HbA1c levels, sex, and bone age

In cross-sectional studies of subjects with IDDM, the relationship between suboptimal pubertal growth, glycemic control, and abnormal insulin-like growth factor I (IGF-I) levels has proved difficult to define. The objective of this study was to examine these relationships in a longitudinal prospective study.

A total of 46 children (23 boys) were measured every 3 months, and their bone age was assessed annually. Blood samples were obtained for HbA1c, IGF-I, and C-peptide. Growth data were compared with national standards, and IGF-I data were compared with a parallel longitudinal study of normal schoolchildren. Data were analyzed as SD scores (mean +/- SD).

The onset of puberty was not delayed, although in the girls, bone age was advanced (bone age, 11.48 +/- 1.01 years vs. chronological age, 10.93 +/- 0.86 years [mean +/- SD]; P = 0.04). The timing of peak height velocity (PHV) was normal in both sexes, but the magnitude was reduced in girls (PHV SDS = -0.56 +/- 0.90, P < 0.02), and reductions in height SDS between diagnosis and final height were observed (P = 0.014). At PHV, IGF-I levels were reduced in both sexes, and there were no sex differences in HbA1c levels and insulin doses. IGF-I SDS correlated with insulin dose (r = 0.47, P = 0.004) but not with PHV SDS, whereas HbA1c correlated negatively with PHV SDS in both sexes (r = -0.35, P = 0.03). In a stepwise multiple regression analysis, the major determinants of PHV SDS were HbA1c (P = 0.04), sex (P = 0.0007), and bone age (P = 0.01).

We conclude that the magnitude of the pubertal growth spurt is related to HbA1c levels in both sexes, but it is reduced only in girls. This sexual dimorphism cannot be explained by differences in IGF-I levels and may relate to the bone age advance at the onset of puberty in the girls.