Abstract
Insulin is important in glucose metabolism. However, insulin-like growth factor binding protein (IGFBP) also plays an important role in glucose homeostasis, although the IGF-independent role of IGFBP-3 in the glucose intolerance state is poorly understood. We investigated the relationship of serum IGF-I with total IGFBP-3 levels and glucose tolerance in Korean children and adolescents who underwent the oral glucose tolerance test (OGTT). A total of 187 children without known diabetes underwent OGTT, and data related to their clinical and laboratory parameters were collected. Serum IGF-I and total IGFBP-3 levels, fasting plasma glucose levels, lipid profiles, insulin levels, C-peptide levels, homeostasis model assessment of insulin resistance (HOMA-IR) index, and glycated hemoglobin (HbA1c) levels were measured. Serum IGF-I and total IGFBP-3 levels were significantly higher in individuals with impaired glucose tolerance and type 2 diabetes (DM) than in those with normal glucose tolerance (NGT) (P < 0.05). Serum IGF-I and IGFBP-3 levels were correlated with age, HbA1c, C-peptide, insulin, and HOMA-IR in the NGT group. However, these relationships were altered in patients with glucose intolerance, especially in those with DM. In the DM group, serum IGF-I and total IGFBP-3 levels were positively correlated with fasting plasma glucose and HbA1c levels. In addition, total IGFBP-3 levels were positively correlated with total cholesterol and low-density lipoprotein cholesterol and IGF-I levels but not with age or body mass index. The IGF-I-IGFBP-3 axis, especially IGFBP-3, may be involved in the pathogenesis and metabolic control of glucose intolerance, specifically in diabetes patients. Moreover, IGFBP-3 might be a therapeutic marker.
Highlights
Type 1 diabetes is the most common hyperglycemic disease in children and adolescents, but the incidence of type 2 diabetes has significantly increased due to the recent increase in childhood obesity [1]
Because serum insulin-like growth factor (IGF)-I and total insulin-like growth factor binding protein (IGFBP)-3 showed correlation with body mass index (BMI), we examined whether serum IGF-I and total IGFBP-3 levels vary with BMI in subjects with glucose intolerance (Table 3). e normal weight group, overweight group, and obesity group included 23 (31.9%), 12 (16.7%), and 37 (51.4%) subjects, respectively
We found that high serum IGF-I and total IGFBP-3 levels were associated with glucose intolerance and that these associations with clinical variables were altered according to glucose tolerance status, suggesting that the IGF-I-IGFBP-3 axis plays an important role in the pathogenesis and metabolic control of glucose intolerance, especially in DM
Summary
Type 1 diabetes is the most common hyperglycemic disease in children and adolescents, but the incidence of type 2 diabetes has significantly increased due to the recent increase in childhood obesity [1]. E IGF system includes IGF-I/II peptides, IGF-I and IGF-II receptors, and IGF-binding proteins (IGFBPs) [5,6,7]. IGFBPs transport IGFs to their receptors [8, 9]. E pivotal IGFBP species in the serum is IGFBP-3; it binds to 90% or more of circulating IGF-I and makes a large. IGFBP-3 has shown cell growth inhibition and apoptosis by IGF-independent activity in various cell types [11]. It has been reported that the IGF-I/IGFBP-3 ratio can be used as an important indicator for the effect of growth hormone treatment in children [12], but there are limited studies conducted in conditions such as metabolic abnormalities and diabetes
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