Low IGF-I and elevated testosterone during puberty in subjects with type 1 diabetes developing microalbuminuria in comparison to normoalbuminuric control subjects: the Oxford Regional Prospective Study.
OBJECTIVE
To describe longitudinal variations in pubertal hormonal variables in subjects with and without microalbuminuria (MA).


METHODS
Blood samples collected annually from subjects recruited at diagnosis of type 1 diabetes and followed prospectively through puberty (median follow-up 9.3 years, range 4.7-12.8) were analyzed for total and free IGF-I, IGF binding protein-1, testosterone, sex hormone-binding globulin, and HbA(1c). A total of 55 subjects who developed MA (MA(+) group) were compared with 55 age-, sex-, and duration-matched control subjects who did not develop MA (MA(-) group).


RESULTS
For female subjects, total IGF-I (MA(+) 1.2 mU/l vs. MA(-) 1.4 mU/l, P = 0.03) and free IGF-I levels (MA(+) 1,767 ng/l vs. MA(-) 2010 ng/l, P = 0.002) were lower, whereas the free androgen index (MA(+) 2.4 vs. MA(-) 2.0, P = 0.03) was higher in those with MA. These changes were less pronounced in male subjects. For both sexes, in a Cox model after adjusting for puberty, the presence of MA was associated with lower free IGF-I levels, higher testosterone standard deviation score (SDS), and poor glycemic control. We found that 22 of 55 case subjects (40%) developed persistent MA, whereas 33 (60%) had transient MA. In the persistent MA group compared with the transient and control groups, total IGF-I levels were lower (1.1 vs. 1.3 vs. 1.4 mU/l, P = 0.002) as were free IGF-I levels (1,370.9 vs. 1,907.3 vs. 1,886.7 ng/l, P < 0.001), whereas HbA(1c) levels were higher (11.8 vs. 10.3 vs. 9.9%, P < 0.001).


CONCLUSIONS
Poor glycemic control and differences in IGF-I levels and androgens, particularly in female subjects, accompany development of MA at puberty. These differences may in part account for the sexual dimorphism in MA risk during puberty and could relate to disease progression.
Amin
Rakesh
R
University Department of Pediatrics, Addenbrookes Hospital, Cambridge, UK.
Schultz
Carl
C
Ong
Ken
K
Frystyk
Jan
J
Dalton
R Neil
RN
Perry
Les
L
Ørskov
Hans
H
Dunger
David B
DB
D000293:Adolescent; D000419:Albuminuria / Q000453:epidemiology*; D003404:Creatinine / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D011627:Puberty / Q000502:physiology*; D012016:Reference Values; D018401:Sample Size; D012709:Serum Albumin / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood*; D013997:Time Factors
D003404:Creatinine; D006442:Glycated Hemoglobin; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D012709:Serum Albumin; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone