Insulin‐like growth factor binding protein‐1 as glucose regulator in adolescent boys with type 1 diabetes

Abstract

The aim of the present study was to investigate whether the diurnal variability of B‐Glucose is dependent on GH, IGF‐I and IGFBP‐I levels, apart from insulin, and if there is any difference between Tanner stages 3 and 5. Five boys in Tanner stage 3 and 6 boys in stage 5 with type 1 diabetes were included. Blood was continuously collected from a cubital vein for 24 h. S‐Insulin, S‐GH, S‐IGF‐I and S‐IGFBP‐1 were analysed. B‐Glucose was analysed hourly at bedside. One week before and 1 wk after the 24‐h study period the participants performed self‐monitoring of blood glucose (SMBG) during normal physiologic conditions. In the 24‐h profile of B‐Glucose, insulin, IGFBP‐I and GH, we found a significant positive correlation between B‐Glucose and log IGFBP‐1 (r=0.5, p= 0.005) and an inverse correlation to insulin (r=‐0.5, p= 0.004) but no correlation to logGH (r=‐0.04, p= 0.831). In multiple regression analysis, B‐Glucose was still significantly correlated to log IGFBP‐1, when adjusting for insulin and GH, in Tanner stage 5. We found a difference between Tanner stages 3 and 5 in the variability of B‐Glucose over a longer period during normal daily activity (p= 0.02), but not over the 24‐h study period. Conclusion: We have demonstrated in type 1 diabetes adolescent boys a relationship between simultaneously measured blood‐glucose and IGFBP‐1 levels independent of the insulin and GH levels, suggesting that the free fraction of IGF‐I influences the glucose metabolism.

Lower HbA1c after 1 year, in children with type 1 diabetes treated with insulin glargine vs. NPH insulin from diagnosis: a retrospective study

“…They found higher IGF-I SDS in pubertal (mean -1.2) than prepubertal (mean -1.6). Also this contrasts our findings in paper IV and our previous work (Zachrisson, Brismar et al 1997;Zachrisson, Dahlquist et al 2000), but it is in line with what others have found (Strasser-Vogel, Blum et al 1995). Taking data from papers I and IV together, recently diagnosed pubertal subjects have IGF-SDS closer to normal than those with a longer diabetes duration, which suggests that endogenous insulin may still have an impact on the levels of IGF-I.…”

“…This is shown to be more prominent in girls and does not affect only nightly GH secretion (Halldin, Tylleskar et al 1998). Circulating IGF-I is lower (Zachrisson, Brismar et al 1997), and IGFBP-1 is further increased (Zachrisson, Dahlquist et al 2000), leading to increased insulin resistance and often to deteriorated metabolic control (Acerini, Williams et al 2001). Increased IGFBP-3 proteolytic activity (IGFBP3-PA) is also present and may play a compensatory role in attenuating the decreased free IGF-I and thus to some extent increasing insulin sensitivity and restoring glycemic control (Zachrisson, Brismar et al 2000).…”

“…IGFBP-1 binds to IGF-I and thereby down-regulates circulating IGF-I activity (Bereket, Lang et al 1999). In adolescents IGF-I is relatively lower compared to prepubertal children, a finding that may be due to increased insulin resistance (Zachrisson, Dahlquist et al 2000). The suppression of IGFBP-1 by long-acting insulin analogs, seen in both papers I and IV, indicates that hepatic insulin action/sensitivity is increased, which could also impact on the production of IGF-I (Shishko, Dreval et al 1994).…”

Low Insulin-like Growth Factor-II Levels Predict Weight Gain in Normal Weight Subjects with Type 2 Diabetes

“…In physiological conditions IGF is regulated by GH, insulin and nutrition. The hypoglycaemic potential of circulating IGF (Zachrisson, Dahlquist et al 2000) is reported to be 50 times that of insulin although most of it is inhibited by IGFBP: s (Lewitt 1994). IGFBP-1 has a diurnal rhythm and is regulated by insulin and counter regulatory hormones (Baxter and Cowell 1987;Yeoh and Baxter 1988).…”

Postprandial paradoxical IGFBP-1 response in obese patients with Type 2 diabetes

“…Regulation of circulating IGF-1 bioavailability is a key function of the IGFBPs [10]. IGFBP-1 has been suggested to modulate the short term bioavailability and activity of IGF-1 [9,10] and plays a role for the glucose homeostasis [12,13]. IGFBP-1 are secreted as phosphoprotein [14], and the affinity of phosphorylated human IGFBP-1 for IGF-I is six fold higher than for the nonphosphorylated protein [14].…”