Angiotensin II type 1 receptor gene polymorphism and the response to hyperglycemia in early type 1 diabetes

Recent studies suggest that there is an association between the A(1166)-->C polymorphism of the angiotensin II type 1 receptor (AGT(1)R), glycemic con trol, and the risk of diabetic nephropathy in subjects with type I diabetes . Because hypertension and renal hemodynamic function are also related to t he risk of diabetic nephropathy and because hyperglycemia can activate the renin angiotensin system, we sought to determine if there is an association between the AGT(1)R polymorphism, baseline renal and peripheral hemodynami c function, and presser response to high glucose in subjects with early unc omplicated type 1 diabetes. There were 39 diabetic subjects genotyped for t he AGT(1)R polymorphism by polymerase chain reaction and segregated into 2 groups: those with. and those without the C1166 allele (AA and AC/CC). The average age was 27 +/- 1 years, and the mean duration of diabetes was 3.6 /- 0.6 years, HbA(1c) values were <10% in all subjects and were similar in the 2 groups (8.2 +/- 0.3 vs, 9.1 +/- 0.4%). After a 7-day controlled diet; (150 mmol sodium, 1.5-2.0 g kg(-1).day(-1) protein), renal hemodynamic fun ction was assessed by inulin and para-aminohippurate clearance during clamp ed euglycemic conditions ( 4-6 mmol/l), Mean values for glomerular filtrati on rates did not differ between groups during euglycemia, In contrast, mean values for renal plasma flow and renal blood flow were significantly great er in the AC/CC group compared with the AA group, Values for mean arterial pressure were similar in the 2 groups, whereas renal vascular resistance wa s significantly reduced in the AC/CC group. In 20 subjects (10 from each ge notype subgroup), hemodynamic function was assessed on a second occasion du ring controlled clamped hyperglycemia (9-11 mmol/l) after a similar prepara tory period, In response to high glucose, plasma renin activity increased i n both genotype groups to the same extent, but a presser response was noted only in subjects with the C1166 allele, Mean arterial pressure increased s ignificantly in the AC/CC subgroup and remained unchanged in the AA subgrou p. We conclude that there is an association between the AGT(1)R A(116)6-->C polymorphism and renal hemodynamic function in early type 1 diabetes. But more importantly, the presser response to hyperglycemia is augmented in tho se diabetic patients with the C1166 allele and may represent a factor that predisposes them to renal injury during periods of inadequate glucose contr ol.