This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Janssen, J. A. M. J. L. Articles by Lamberts, S. W. J. Search for Related Content PubMed PubMed Citation Articles by Janssen, J. A. M. J. L. Articles by Lamberts, S. W. J.

Free and Total Insulin-Like Growth Factor I (IGF-I), IGF-Binding Protein-1 (IGFBP-1), and IGFBP-3 and Their Relationships to the Presence of Diabetic Retinopathy and Glomerular Hyperfiltration in Insulin-Dependent Diabetes Mellitus¹

Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. Jamjl Janssen, Department of Internal Medicine III, Room D438, University Hospital Dijkzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.

The existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have greater physiological and clinical relevance than total IGF-I. Recently, a validated method has been developed to measure free IGF-I levels in the circulation.

Serum free and total IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured in 56 insulin-treated IDDM patients and 52 healthy sex- and age-matched controls. Diabetic retinopathy was established by direct fundoscopy. In 54 IDDM patients, the glomerular filtration rate (GFR) and effective renal plasma flow were calculated from the clearance rate of [¹²⁵I]iothalamate and [¹³¹I]iodohippurate sodium.

Fasting free IGF-I, total IGF-I, and IGFBP-3 levels were significantly lower in IDDM patients than in age- and sex-matched healthy controls (free IGF-I, P < 0.005; total IGF-I, P < 0.001; IGFBP-3, P = 0.001), whereas IGFBP-1 levels were higher (P < 0.001).

In IDDM subjects, decreases in free IGF-I, total IGF-I, and IGFBP-3 levels with age were observed (free IGF-I, r = -0.27 and P = 0.05; total IGF-I, r = -0.52 and P < 0.001; IGFBP-3, r = -0.37 and P = 0.005). Free IGF-I was inversely related to fasting glucose in IDDM subjects (r = -0.35; P = 0.01), whereas the relationship between total IGF-I and fasting glucose did not reach significance (r = -0.27; P = 0.06).

Age-adjusted free IGF-I levels were significantly higher (P < 0.05) in IDDM subjects with retinopathy than in subjects without retinopathy after adjustment for age.

Total IGF-I and IGFBP-3 levels were positively related to GFR (total IGF-I, r = 0.35 and P < 0.05; IGFBP-3, r = 0.28 and P < 0.05). Both of these differences lost significance after adjustment for age.

Free IGF-I, total IGF-I, and IGFBP-3 levels were lower and IGFBP-1 levels were higher in insulin-treated IDDM subjects compared to those in age- and sex-matched controls. Free IGF-I, total IGF-I, and IGFBP-3 levels decreased significantly with age in IDDM subjects. Age-adjusted free IGF-I levels in subjects with diabetic retinopathy were higher than those in subjects without diabetic retinopathy. Total IGF-I and IGFBP-3 levels were positively related to GFR in IDDM subjects, but these relations were lost after adjustment for age. Measurement of serum free IGF-I levels in IDDM subjects did not have clear advantages compared to that of total IGF-I, IGFBP-1, and IGFBP-3 levels. Serum IGF-I and IGFBPs reflect their tissue concentrations to a various degree. Consequently, extrapolations concerning the pathogenetic role of the IGF/IGFBP system in the development of diabetic complications at the tissue level remain speculative.

This article has been cited by other articles:

				R. C. Kaplan, A. P. McGinn, M. N. Pollak, L. H. Kuller, H. D. Strickler, T. E. Rohan, A. R. Cappola, X. Xue, and B. M. Psaty Association of Total Insulin-Like Growth Factor-I, Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1), and IGFBP-3 Levels with Incident Coronary Events and Ischemic Stroke J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1319 - 1325. [Abstract] [Full Text] [PDF]

				P. Hovind, S. Lamberts, W. Hop, J. Deinum, L. Tarnow, H.-H. Parving, and J. A M J L Janssen An IGF-I gene polymorphism modifies the risk of developing persistent microalbuminuria in type 1 diabetes Eur. J. Endocrinol., January 1, 2007; 156(1): 83 - 90. [Abstract] [Full Text] [PDF]

				C. F. Liew, S. D. Wise, K. P. Yeo, and K. O. Lee Insulin-Like Growth Factor Binding Protein-1 Is Independently Affected by Ethnicity, Insulin Sensitivity, and Leptin in Healthy, Glucose-Tolerant Young Men J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1483 - 1488. [Abstract] [Full Text] [PDF]

				R. E. Schmidt, D. A. Dorsey, L. N. Beaudet, and R. G. Peterson Analysis of the Zucker Diabetic Fatty (ZDF) Type 2 Diabetic Rat Model Suggests a Neurotrophic Role for Insulin/IGF-I in Diabetic Autonomic Neuropathy Am. J. Pathol., July 1, 2003; 163(1): 21 - 28. [Abstract] [Full Text] [PDF]

				F. F. Lauszus, J. G. Klebe, T. Bek, and A. Flyvbjerg Increased Serum IGF-I During Pregnancy Is Associated With Progression of Diabetic Retinopathy Diabetes, March 1, 2003; 52(3): 852 - 856. [Abstract] [Full Text] [PDF]

				P. H. Lane Diabetic kidney disease: impact of puberty Am J Physiol Renal Physiol, October 1, 2002; 283(4): F589 - F600. [Abstract] [Full Text] [PDF]

				J. Frystyk, K. Hojlund, K. N. Rasmussen, S. P. Jorgensen, M. Wildner-Christensen, and H. Orskov Development and Clinical Evaluation of a Novel Immunoassay for the Binary Complex of IGF-I and IGF-Binding Protein-1 in Human Serum J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 260 - 266. [Abstract] [Full Text] [PDF]

				N. Vaessen, P. Heutink, J. A. Janssen, J. C. M. Witteman, L. Testers, A. Hofman, S. W. J. Lamberts, B. A. Oostra, H. A. P. Pols, and C. M. van Duijn A Polymorphism in the Gene for IGF-I: Functional Properties and Risk for Type 2 Diabetes and Myocardial Infarction Diabetes, March 1, 2001; 50(3): 637 - 642. [Abstract] [Full Text]

				T. Merimee The Interface Between Diabetic Retinopathy, Diabetes Management, and Insulin-Like Growth Factors J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 2806 - 2808. [Full Text] [PDF]

				E. R. Christ, P. V. Carroll, E. Albany, A. M. Umpleby, P. J. Lumb, A. S. Wierzbicki, P. H. Sonksen, and D. L. Russell-Jones Effect of IGF-I therapy on VLDL apolipoprotein B100 metabolism in type 1 diabetes mellitus Am J Physiol Endocrinol Metab, May 1, 2002; 282(5): E1154 - E1162. [Abstract] [Full Text] [PDF]