ANGIOTENSIN-CONVERTING ENZYME INSERTION DELETION POLYMORPHISM AND DIABETIC ALBUMINURIA IN PATIENTS WITH NIDDM FOLLOWED UP FOR 9 YEARS/

Nephropathy is a major cause of premature morbidity and mortality in p atients with non-insulin-dependent diabetes mellitus (NIDDM). The inse rtion/deletion (I/D) polymorphism of angiotensin-converting enzyme (AC E) is a genetic determinant of plasma ACE levels. Recent studies have found I/D polymorphism of the ACE gene to be associated with nephropat hy in NIDDM. This association has not been evaluated in prospective st udies. We, therefore, studied the relationship between ACE gene I/D po lymorphism and diabetic albuminuria and glomerular filtration rate (GF R) in 83 NIDDM patients followed up for 9 years. At baseline, 29% (24 of 83) of the diabetic patients had an increased (>30 mg/24 h) urinary albumin excretion rate (UAER) and the prevalence of albuminuria at th e 9-year examination was 35% (29 of 83). During the follow-up period, systolic blood pressure (p = 0.044), prevalence of hypertension (p < 0 .01), and fasting blood glucose levels (p < 0.01) increased, while hig h-density lipoprotein cholesterol (p < 0.01) decreased. The declines o f GFR during the follow-up period were 8.5, 14.1, and 16.3% within gen otype groups of II, ID, and DD, respectively (13 values for decreases: NS for II, <0.001 for ID, and <0.001 for DD). Patients with the DD ge notype tended to have a steeper decrease of GFR, but the change was no t statistically significant between the genotype groups. The increases of UAER during the follow-up period were 35.1, 8.3, and 122.4% within genotype groups of II, ID, and CID, respectively, but p values for al l increases were not significant. Parallel to GFR, patients with the D D genotype tended to have a steeper increase of UAER, but the change w as not statistically significant between the genotype groups. There we re no differences in the ACE genotype distribution and allele frequenc ies between the patients with or without albuminuria either at follow- up, or in cross-sectional settings. In conclusion, this 9-year follow- up study does not support the hypothesis that the ACE I/D polymorphism is a major genetic marker of diabetic nephropathy in NIDDM patients.