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
- Rakesh Amin, MRCPCH1,
- Carl Schultz, MD, PHD1,
- Ken Ong, MRCPCH1,
- Jan Frystyk, MD, PHD2,
- R. Neil Dalton, PHD4,
- Les Perry, PHD3,
- Hans Ørskov, MD, DMSC2 and
- David B. Dunger, FRCPCH1
- 1University Department of Pediatrics, Addenbrookes Hospital, Cambridge, U.K.
- 2Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark
- 3Department of Clinical Biochemistry, St Bartholomew’s Hospital, London, U.K.
- 4Children Nationwide Kidney Research Laboratory, Guy’s Hospital, London, U.K.
OBJECTIVE—To describe longitudinal variations in pubertal hormonal variables in subjects with and without microalbuminuria (MA).
RESEARCH DESIGN AND 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 HbA1c. 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 HbA1c 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.
- ACR, albumin-to-creatinine ratio
- CV, coefficient of variation
- FAI, free androgen index
- GH, growth hormone
- IGFBP-1, IGF binding protein-1
- MA, microalbuminuria
- mAb, monoclonal antibody
- ORPS, Oxford Regional Prospective Study of Childhood Diabetes
- PCOS, polycystic ovarian syndrome
- QC, quality control
- RIA, radioimmunoassay
- SDS, standard deviation score
- SHBG, sex hormone-binding globulin
Address correspondence and reprint requests to Prof. David B. Dunger, University Department of Paediatrics, Box 116, Level 8, Addenbrookes Hospital, Hills Road, Cambridge, CB2 2QQ, U.K. E-mail:.
Received for publication 10 December 2002 and accepted in revised form 5 February 2003.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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