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


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.
Tarnow
L
L
Steno Diabetes Center, Gentofte, Denmark. lise.tarnow@dadlnet.dk
Rossing
P
P
Nielsen
F S
FS
Fagerudd
J A
JA
Poirier
O
O
Parving
H H
HH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality; D003718:Denmark / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000401:mortality / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000401:mortality; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D010290:Parents; D015995:Prevalence; D015996:Survival Rate