RELATIONSHIP OF THE ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM TO GLUCOSE-INTOLERANCE, INSULIN-RESISTANCE, AND HYPERTENSION IN NIDDM

The deletion (D) allele of the angiotensin-converting enzyme (ACE) gen e insertion/deletion (I/D) polymorphism has been shown to be associate d with cardiovascular and renal diseases in diabetes mellitus, but the mechanism underlying this association is not known. In addition, rece nt studies of the effect of the ACE gene on blood pressure have yielde d conflicting results. Therefore, we studied the association of the AC E gene I/D polymorphism with glucose intolerance and insulin resistanc e, and the contribution of this locus to genetic susceptibility to hyp ertension in non-insulin-dependent diabetic mellitus (NIDDM). We analy sed the ACE genotype in 84 unrelated NIDDM patients with a known disea se duration of less than 1 year and in 115 age-and sex-matched control s. The I/D polymorphism was determined by the polymerase chain reactio n. There were no differences in ACE genotype distribution and allele f requencies between patients with NIDDM and nondiabetic controls. The f requencies of the D and I alleles in both groups were identical, viz., 0.65 and 0.35, respectively. The NIDDM patients with the DD genotype had significantly higher blood glucose levels in the oral glucose tole rance test than those with the other genotypes; the incremental glucos e area under the curve in the order of II, ID, and DD was 7.2 +/- 2.4, 9.2 +/- 4.0, and 10.7 +/- 2.7 mmol/l . h (II vs ID vs DD, P=0.0066 by ANOVA). No significant difference was found between the ACE genotype and serum insulin values. Similarly, there were no differences in body mass index, blood pressure, or serum lipids between the three genotyp es, Among the nondiabetic controls, there was no statistically signifi cant association of the I/D polymorphism with serum lipids, blood gluc ose levels, serum insulin concentrations, or blood pressure values. In conclusion, NIDDM patients with the DD genotype have higher blood glu cose levels and are more glucose intolerant; this may help to explain the reported association between the D allele and vascular complicatio ns in NIDDM.