Journal of Clinical Endocrinology & Metabolism, Vol 78, 960-967, Copyright © 1994 by Endocrine Society

ARTICLES

Fasting affects serum insulin-like growth factors (IGFs) and IGF- binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects

P Bang, K Brismar, RG Rosenfeld and K Hall
Department of Endocrinology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.

In the present study we have 1) assessed how differences in insulin and GH status between obese patients with noninsulin-dependent diabetes mellitus (NIDDM) and healthy obese (OB) and nonobese (NOB) subjects are associated with different responses of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) to fasting, and 2) determined whether the IGF-I response to fasting in healthy subjects is secondary to changes in IGFBP-3. In patients with NIDDM, there was a lack of response of serum IGF-I concentrations to 4 days of fasting, contrasted with the significant decrease in IGF-I concentrations in NOB subjects (37%; P < 0.001) and the delayed and attenuated decrease in OB subjects (23%; P < 0.01). Insulin and the insulin-regulated IGFBP-1 were also unchanged during fasting in NIDDM, whereas insulin was decreased and IGFBP-1 was increased in both NOB and OB subjects. Insulin-resistant NIDDM patients, with high basal glucose and insulin, normal IGFBP-1, and low GH, had decreased prefasting serum IGF-I concentrations, similar to the values in fasted body mass index- and age-matched OB subjects. IGFBP-3, the major determinant of the IGF-I turnover rate in serum, was unchanged by fasting, as determined by RIA and Western ligand blot analysis. In accordance, no induction of IGFBP-3 proteolytic activity by fasting could be demonstrated. Serum IGF-II concentrations were also unchanged by fasting. Basal immunoreactive IGFBP-3 levels did not differ among the groups, whereas IGFBP-3 by Western ligand blot analysis was decreased in NIDDM in accordance with the finding of increased IGFBP-3 proteolysis in NIDDM. In conclusion, 1) differences in GH status and modulation of GH induction of IGF-I by insulin resistance could contribute to low basal IGF-I levels and lack of a IGF-I response to fasting in patients with NIDDM; and 2) the turnover rate of IGF-I in serum, which is largely determined by IGFBP- 3, is not likely to be altered by short term fasting, suggesting that the decrease in serum IGF-I concentrations is a result of decreased IGF- I production.

This article has been cited by other articles:

				H. Norrelund, J. Frystyk, J. O. L. Jorgensen, N. Moller, J. S. Christiansen, H. Orskov, and A. Flyvbjerg The Effect of Growth Hormone on the Insulin-Like Growth Factor System during Fasting J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3292 - 3298. [Abstract] [Full Text] [PDF]

				J. Nygren, C. Carlsson-Skwirut, K. Brismar, A. Thorell, O. Ljungqvist, and P. Bang Insulin infusion increases levels of free IGF-I and IGFBP-3 proteolytic activity in patients after surgery Am J Physiol Endocrinol Metab, October 1, 2001; 281(4): E736 - E741. [Abstract] [Full Text] [PDF]

				A. Ferreira, A. Ghazali, J. Galvao, J.-C. Souberbielle, P. M. Jehle, S. Mohan, B. Descamps-Latscha, R. Oprisiu, A. Fournier, and T. B. Drueke Effect of type of dialysis membrane on bone in haemodialysis patients Nephrol. Dial. Transplant., June 1, 2001; 16(6): 1230 - 1238. [Abstract] [Full Text] [PDF]

				I. M. Holdaway, A. E. Lethaby, B. H. Mason, V. Singh, J. E. Harman, M. MacCormick, and I. D. Civil Effect of Breast Surgery on Serum Levels of Insulin-Like Growth Factors (IGF-I, IGF-II, and IGF Binding Protein-3) in Women With Benign and Malignant Breast Lesions Ann. Surg. Oncol., January 1, 2001; 8(1): 25 - 31. [Abstract] [Full Text] [PDF]

				H. J. H. M. T. van Dessel, P. D. K. Lee, G. Faessen, B. C. J. M. Fauser, and L. C. Giudice Elevated Serum Levels of Free Insulin-Like Growth Factor I in Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3030 - 3035. [Abstract] [Full Text]

				G. GAYAN-RAMIREZ, F. VANDERHOYDONC, G. VERHOEVEN, and M. DECRAMER Acute Treatment with Corticosteroids Decreases IGF-1 and IGF-2 Expression in the Rat Diaphragm and Gastrocnemius Am. J. Respir. Crit. Care Med., January 1, 1999; 159(1): 283 - 289. [Abstract] [Full Text]

				N. Attia, W. V. Tamborlane, R. Heptulla, D. Maggs, A. Grozman, R. S. Sherwin, and S. Caprio The Metabolic Syndrome and Insulin-Like Growth Factor I Regulation in Adolescent Obesity J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1467 - 1471. [Abstract] [Full Text]

				S. B. Cichy, S. Uddin, A. Danilkovich, S. Guo, A. Klippel, and T. G. Unterman Protein Kinase B/Akt Mediates Effects of Insulin on Hepatic Insulin-like Growth Factor-binding Protein-1 Gene Expression through a Conserved Insulin Response Sequence J. Biol. Chem., March 13, 1998; 273(11): 6482 - 6487. [Abstract] [Full Text] [PDF]

				C. Heinrichs, M. Colli, J. A. Yanovski, L. Laue, N. A. Gerstl, A. D. Kramer, J. A. Uyeda, and J. Baron Effects of Fasting on the Growth Plate: Systemic and Local Mechanisms Endocrinology, December 1, 1997; 138(12): 5359 - 5365. [Abstract] [Full Text] [PDF]