Diabetes Care, Vol 23, Issue 1 30-33, Copyright © 2000 by American Diabetes Association

ARTICLES

Cardiovascular morbidity and early mortality cluster in parents of type 1 diabetic patients with diabetic nephropathy

L Tarnow, P Rossing, FS Nielsen, JA Fagerudd, O Poirier and HH Parving
Steno Diabetes Center, Gentofte, Denmark. lise.tarnow@dadlnet.dk

OBJECTIVE: A familial predisposition was proposed to be a determinant of the increased morbidity and mortality from cardiovascular disease in type 1 diabetic patients with diabetic nephropathy. The insertion allele of an insertion/deletion polymorphism in the ACE (ACE/ID) gene seems to protect against coronary heart disease in nondiabetic and diabetic subjects. The aim of the present study was to evaluate these hypotheses in parents of a large group of type 1 diabetic patients with and without diabetic nephropathy. RESEARCH DESIGN AND METHODS: We investigated cardiovascular morbidity and mortality of parents of 163 type 1 diabetic patients with nephropathy and parents of 163 sex- and age-matched normoalbuminuric patients with type 1 diabetes. RESULTS: Kaplan-Meier curves showed that total parental mortality was significantly increased in parents of type 1 diabetic patients with nephropathy (121 of 244 [ approximately 50%] ) as compared with parents of normoalbuminuric type 1 diabetic patients (119 of 269 [approximately 44%]) (P = 0.008 [log-rank test]) partially due to an increase in cardiovascular deaths (48 of 244 [approximately 20%] vs. 42 of 269 [approximately 16%], P<0.05). In addition, more patients with nephropathy, as compared with the normoalbuminuric group, had at least one parent with fatal/nonfatal cardiovascular disease (46% [95% CI 38-54] vs. 36% [28-44], P = 0.05). Fathers of patients homozygous for the I-allele of the ACE/ID polymorphism had significantly less myocardial infarction as compared with other genotypes (P = 0.03), regardless of the nephropathic state of the offspring. CONCLUSIONS: Cardiovascular morbidity and early mortality clusters in parents of type 1 diabetic patients with diabetic nephropathy The ACE/ID polymorphism helps explain the increased morbidity from cardiovascular disease.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Tarnow, P.-H. Groop, S. Hadjadj, G. Kazeem, F. Cambien, M. Marre, C. Forsblom, H.-H. Parving, D. Tregouet, A. Thevard, et al. European rational approach for the genetics of diabetic complications EURAGEDIC: patient populations and strategy Nephrol. Dial. Transplant., January 1, 2008; 23(1): 161 - 168. [Abstract] [Full Text] [PDF]

				L. M. Thorn, C. Forsblom, J. Fagerudd, K. Pettersson-Fernholm, R. Kilpikari, P.-H. Groop, and on behalf of the FinnDiane Study Group Clustering of Risk Factors in Parents of Patients With Type 1 Diabetes and Nephropathy Diabetes Care, May 1, 2007; 30(5): 1162 - 1167. [Abstract] [Full Text] [PDF]

				E. E. Tchekneva, E. M. Rinchik, D. Polosukhina, L. S. Davis, V. Kadkina, Y. Mohamed, S. R. Dunn, K. Sharma, Z. Qi, A. B. Fogo, et al. A Sensitized Screen of N-ethyl-N-nitrosourea-Mutagenized Mice Identifies Dominant Mutants Predisposed to Diabetic Nephropathy J. Am. Soc. Nephrol., January 1, 2007; 18(1): 103 - 112. [Abstract] [Full Text] [PDF]

				E. Galkina and K. Ley Leukocyte Recruitment and Vascular Injury in Diabetic Nephropathy J. Am. Soc. Nephrol., February 1, 2006; 17(2): 368 - 377. [Abstract] [Full Text] [PDF]

				B. Janssen, D. Hohenadel, P. Brinkkoetter, V. Peters, N. Rind, C. Fischer, I. Rychlik, M. Cerna, M. Romzova, E. de Heer, et al. Carnosine as a Protective Factor in Diabetic Nephropathy: Association With a Leucine Repeat of the Carnosinase Gene CNDP1 Diabetes, August 1, 2005; 54(8): 2320 - 2327. [Abstract] [Full Text] [PDF]

				M. D. Breyer, E. Bottinger, F. C. Brosius III, T. M. Coffman, R. C. Harris, C. W. Heilig, K. Sharma, and for the AMDCC Mouse Models of Diabetic Nephropathy J. Am. Soc. Nephrol., January 1, 2005; 16(1): 27 - 45. [Abstract] [Full Text] [PDF]

				S. Hadjadj, F. Pean, Y. Gallois, P. Passa, R. Aubert, L. Weekers, V. Rigalleau, B. Bauduceau, A. Bekherraz, R. Roussel, et al. Different Patterns of Insulin Resistance in Relatives of Type 1 Diabetic Patients With Retinopathy or Nephropathy: The Genesis France-Belgium Study Diabetes Care, November 1, 2004; 27(11): 2661 - 2668. [Abstract] [Full Text] [PDF]

				C. S. Arun, J. Stoddart, P. Mackin, J. M. MacLeod, J. P. New, and S. M. Marshall Significance of Microalbuminuria in Long-Duration Type 1 Diabetes Diabetes Care, July 1, 2003; 26(7): 2144 - 2149. [Abstract] [Full Text] [PDF]

				S. Fava and A. T. Hattersley The role of genetic susceptibility in diabetic nephropathy: evidence from family studies Nephrol. Dial. Transplant., September 1, 2002; 17(9): 1543 - 1546. [Full Text] [PDF]

				S. Fava, J. Azzopardi, S. Ellard, and A. T. Hattersley ACE Gene Polymorphism as a Prognostic Indicator in Patients With Type 2 Diabetes and Established Renal Disease Diabetes Care, December 1, 2001; 24(12): 2115 - 2120. [Abstract] [Full Text] [PDF]

				L. Tarnow, N. Grarup, T. Hansen, H.-H. Parving, and O. Pedersen Diabetic microvascular complications are not associated with two polymorphisms in the GLUT-1 and PC-1 genes regulating glucose metabolism in Caucasian type 1 diabetic patients Nephrol. Dial. Transplant., August 1, 2001; 16(8): 1653 - 1656. [Abstract] [Full Text] [PDF]