Diabetes Care, Vol 19, Issue 9 915-919, Copyright © 1996 by American Diabetes Association

ARTICLES

Diabetes complications in NIDDM kindreds linked to the MODY3 locus on chromosome 12q

G Velho, M Vaxillaire, V Boccio, G Charpentier and P Froguel
Institute Nacional de la Sante et de la Recherche Medicale U-358, Hopital Saint-Louis, Paris, France.

OBJECTIVE: To assess the prevalence of diabetes complications and the severity of diabetes in kindreds with NIDDM linked to the MODY3 locus (chromosome 12q) and to compare these parameters with data obtained in glucokinase (GCK)-deficient and other-MODY (unlinked to any of the three known loci) families, as well as with data from families with a late age of onset of NIDDM. RESEARCH DESIGN AND METHODS: Clinical and biological data were obtained from 667 affected members of 7 MODY3, 25 GCK-deficient, 6 other-MODY, and 81 NIDDM families. Severity of diabetes (glucose tolerance status and insulin secretion) was assessed by an oral glucose tolerance test. Neurological examination and eye fundus examination were performed in 349 and 251 subjects, respectively, and proteinuria was tested with strips in 282 family members. RESULTS: A higher prevalence of proliferative retinopathy was observed in MODY3 (21%) and NIDDM subjects (23%) than in GCK-deficient (3%) and other-MODY subjects (8%; P = 0.004). Proteinuria was detected in 19, 7, 5, and 0% (P = 0.07) of subjects, respectively. Prevalence of neuropathy was higher in NIDDM (17%; P = 0.005) than in MODY3 (4%), GCK-deficient (5%) and other-MODY (0%) subjects. MODY3 and NIDDM subjects had significantly higher fasting glucose levels than subjects in the other groups. Glucose levels after 2 h were significantly higher, and the ratios of insulin to glucose levels were significantly lower in MODY3 subjects than in the other three groups. CONCLUSIONS: The MODY3 subtype of NIDDM is characterized by a severe insulin secretory defect and by major hyperglycemia that progresses rapidly to overt diabetes. Microvascular complications of diabetes were frequently observed in the MODY3 subjects and the subjects with a late age of onset of NIDDM in this cohort. Both the duration and the severity of diabetes were independently associated with these complications.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. H. Arar, B. I. Freedman, S. G. Adler, S. K. Iyengar, E. Y. Chew, M. D. Davis, S. G. Satko, D. W. Bowden, R. Duggirala, R. C. Elston, et al. Heritability of the Severity of Diabetic Retinopathy: The FIND-Eye Study Invest. Ophthalmol. Vis. Sci., September 1, 2008; 49(9): 3839 - 3845. [Abstract] [Full Text] [PDF]

				L. Bjorkhaug, J. V. Sagen, P. Thorsby, O. Sovik, A. Molven, and P. R. Njolstad Hepatocyte Nuclear Factor-1{alpha} Gene Mutations and Diabetes in Norway J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 920 - 931. [Abstract] [Full Text] [PDF]

				S. S. Fajans, G. I. Bell, and K. S. Polonsky Molecular Mechanisms and Clinical Pathophysiology of Maturity-Onset Diabetes of the Young N. Engl. J. Med., September 27, 2001; 345(13): 971 - 980. [Full Text] [PDF]

				C. Bingham, S. Ellard, A. J. Nicholls, C. A. Pennock, J. Allen, A. J. James, S. C. Satchell, M. B. Salzmann, and A. T. Hattersley The Generalized Aminoaciduria Seen in Patients With Hepatocyte Nuclear Factor-1{alpha} Mutations Is a Feature of All Patients With Diabetes and Is Associated With Glucosuria Diabetes, September 1, 2001; 50(9): 2047 - 2052. [Abstract] [Full Text] [PDF]

				E. Kawasaki, Y. Sera, K. Yamakawa, T. Abe, M. Ozaki, S. Uotani, N. Ohtsu, H. Takino, H. Yamasaki, Y. Yamaguchi, et al. Identification and Functional Analysis of Mutations in the Hepatocyte Nuclear Factor-1{alpha} Gene in Anti-Islet Autoantibody-Negative Japanese Patients with Type 1 Diabetes J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 331 - 335. [Abstract] [Full Text]

				M. Vaxillaire, A. Abderrahmani, P. Boutin, B. Bailleul, P. Froguel, M. Yaniv, and M. Pontoglio Anatomy of a Homeoprotein Revealed by the Analysis of Human MODY3 Mutations J. Biol. Chem., December 10, 1999; 274(50): 35639 - 35646. [Abstract] [Full Text] [PDF]

				E. A. Cabanas Maturity-Onset Diabetes of the Young: Recent Findings Indicate Insulin Resistance/Obesity Are Not Factors The Diabetes Educator, January 1, 1998; 24(4): 477 - 480. [PDF]