Diabetes Care, Vol 15, Issue 5 632-637, Copyright © 1992 by American Diabetes Association

ARTICLES

Elevated proinsulin levels related to islet cell antibodies in first-degree relatives of IDDM patients

GA Spinas, O Snorgaard, SG Hartling, M Oberholzer and W Berger
Department of Internal Medicine, University Hospital Basel, Switzerland.

OBJECTIVE--To assess whether proinsulin levels are elevated in first-degree relatives of insulin-dependent diabetes mellitus (IDDM) patients and whether there is a relationship between proinsulin levels and the occurrence of immunological markers. RESEARCH DESIGN AND METHODS--Fasting proinsulin concentrations were measured in 85 first-degree relatives (54 siblings, 20 parents, 11 children) of IDDM patients and in 90 age- and weight-matched control subjects with no family history of diabetes mellitus. RESULTS--Fasting proinsulin levels (median, 25th, and 75th percentiles) were 8 pM (range 3.2-14 pM) in first-degree relatives and 1.7 pM (range 1.7-4 pM) in control subjects (P less than 0.0001). Proinsulin was significantly elevated in siblings (7.2 pM, range 3.8-15 pM; P less than 0.0001), parents (9.8 pM, range 6.4-13 pM; P less than 0.0001), and children (6.6 pM, range 1.8-12 pM, P = 0.04) compared with control subjects but without differences between these groups. Islet cell antibody positive (ICA+) IDDM relatives had significantly higher proinsulin levels than ICA- (16 pM; range 7.2-25 vs. 6.9 pM, range 3.1-12 pM; P = 0.02). There was no difference between individuals with and without insulin autoantibodies. No difference in proinsulin levels was observed if the relatives were subdivided according to HLA-DR sharing with the diabetic proband. CONCLUSIONS--Fasting proinsulin concentrations were raised not only in siblings but also in parents and children of IDDM patients. Because proinsulin is more elevated in ICA+ than in ICA- subjects, increased proinsulin levels could reflect minor beta-cell damage due to previous immunological attack.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Borjesson and C. Carlsson Altered proinsulin conversion in rat pancreatic islets exposed long-term to various glucose concentrations or interleukin-1{beta} J. Endocrinol., February 1, 2007; 192(2): 381 - 387. [Abstract] [Full Text] [PDF]

				I. Vauhkonen, L. Niskanen, M. Knip, L. M. Mykkanen, S. Haffner, M. Uusitupa, and M. Laakso Subtle hyperproinsulinaemia characterises the defective insulin secretory capacity in offspring of glutamic acid decarboxylase antibody-positive patients with latent autoimmune diabetes mellitus in adults Eur. J. Endocrinol., August 1, 2005; 153(2): 265 - 273. [Abstract] [Full Text] [PDF]

				W. Chen, I. Bergerot, J. F. Elliott, L. C. Harrison, N. Abiru, G. S. Eisenbarth, and T. L. Delovitch Evidence That a Peptide Spanning the B-C Junction of Proinsulin Is an Early Autoantigen Epitope in the Pathogenesis of Type 1 Diabetes J. Immunol., November 1, 2001; 167(9): 4926 - 4935. [Abstract] [Full Text] [PDF]

				A. Amrani, S. Durant, M. Throsby, J. Coulaud, M. Dardenne, and F. Homo-Delarche Glucose Homeostasis in the Nonobese Diabetic Mouse at the Prediabetic Stage Endocrinology, March 1, 1998; 139(3): 1115 - 1124. [Abstract] [Full Text] [PDF]