Low IGF-I and Elevated Testosterone During Puberty in Subjects With Type 1 Diabetes Developing Microalbuminuria in Comparison to Normoalbuminuric Control Subjects

Abstract

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 HbA 1c . A total of 55 subjects who developed MA (MA ϩ group) were compared with 55 age-, sex-, and duration-matched control subjects who did not develop MA (MA Ϫ group).RESULTS -For female subjects, total IGF-I (MA ϩ 1.2 mU/l vs. MA Ϫ 1.4 mU/l, P ϭ 0.03) and free IGF-I levels (MA ϩ 1,767 ng/l vs. MA Ϫ 2010 ng/l, P ϭ 0.002) were lower, whereas the free androgen index (MA ϩ 2.4 vs. MA Ϫ 2.0, P ϭ 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 ϭ 0.002) as were free IGF-I levels (1,370.9 vs. 1,907.3 vs. 1,886.7 ng/l, P Ͻ 0.001), whereas HbA 1c levels were higher (11.8 vs. 10.3 vs. 9.9%, P Ͻ 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. Diabetes Care 26:1456 -1461, 2003M icroalbuminuria (MA) is a marker of incipient nephropathy in adult subjects with type 1 diabetes (1). There is an unequivocal relationship between poor glycemic control and the development of MA (2). However, independent of poor glycemic control, early diabetic complications risk is increased with the onset of puberty (3). In addition, MA risk is twofold greater in pubertal female patients compared with male patients (3), in contrast to lifetime risk of diabetic nephropathy, which is greater in male patients (4). Sexual dimorphism is also present during puberty for risk of attenuated growth, weight gain, and retinopathy, and again these observations are independent of glycemic control (5-7). These data suggest that the development of diabetic microvascular complications may be associated with abnormalities in hormonal variables related to pubertal development.Cross-sectional data describe abnormalities of the growth hormone (GH)/ IGF-I axis in relation to the development of diabetic complications (8). In type 1 diabetes, bioavailability of circulating IGF-I is low and GH secretion exaggerated (9,10), and these abnormalities may be more marked in female patients (10). Despite evidence of hepatic GH r...

The development of microalbuminuria is associated with raised longitudinal adiponectin levels in female but not male adolescent patients with type 1 diabetes

“…In type 1 diabetes, timing of puberty is altered [26] and BMI and insulin resistance are increased during adolescence, particularly in girls [27,28]. Furthermore, risk of microalbuminuria in female adolescents is associated with higher androgen levels [29]. This may relate to the increased frequency of ovarian hyperandrogenism, which may be present in up to 50% of adolescent girls with type 1 diabetes [30] and is associated with obesity, insulin resistance and peripheral hyperinsulinaemia [31].…”

Natural History and Risk Factors for Microalbuminuria in Adolescents With Type 1 Diabetes

“…Of note, however, the incidence of microalbuminuria in type 1 diabetes increases at puberty (8), a time of exaggerated physiological insulin resistance (15-17). Indeed, higher androgens and growth hormone have been found in adolescents with type 1 diabetes in association with higher albumin excretion (18,19), while the effects of higher BMI and other features of the metabolic syndrome on the risk of microalbuminuria in this age-group are unclear.…”

“…Of note, however, the incidence of microalbuminuria in type 1 diabetes increases at puberty (8), a time of exaggerated physiological insulin resistance (15-17). Indeed, higher androgens and growth hormone have been found in adolescents with type 1 diabetes in association with higher albumin excretion (18,19), while the effects of higher BMI and other features of the metabolic syndrome on the risk of microalbuminuria in this age-group are unclear.The aims of this 15-year longitudinal study were to identify risk factors for early nephropathy and to explore the potential role of insulin resistance in the development of persistent microalbuminuria. We examined putative risk factors at initial assessment for the subsequent development of persistent microalbuminuria and used survival analysis to evaluate risk factors over time.…”

Modern aspects of polycystic ovary syndrome in patients with type 1 diabetes (a review)

“…[4], выявлена взаи-мосвязь гиперандрогении и почечной микроангио-патии как осложнения СД1. Несмотря на то что у обследованных женщин не был установлен диагноз СПЯ, у них был зарегистрирован более высокий уро-вень свободного тестостерона в крови.…”