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Impaired circadian blood pressure (BP) variation (i.e. lack of nocturnal BP fall by at least 10% of daytime values; 'non-dipping') is associated with increased risk of cardiovascular events. Blunted circadian BP profile is common in hypertension and autonomic neuropathy as well as in patients with renal function impairment. However, pathophysiology of non-dipping phenomenon in normotensive diabetes subjects with normal autonomic function and without nephropathy is unclear. We studied whether angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism, known for its role in BP regulation, may play a role in 24-hour BP rhythm control. The study group comprised 34 normotensive normoalbuminuric type 2 diabetes patients with no signs of autonomic neuropathy (18 women, 16 men, mean [±SD] age 594±9 years, BMI 29.24-3.4 kg/m², diabetes duration 7.9±5.1 years, HbA[sub 1c] 8.6±1.4%) with impaired BP variation, the controls were 49 normotensive normoalbuminuric type 2 diabetes subjects (28 women, 21 men, age 624±10 years, BM1 30.3±3.9 kg/m², diabetes duration 8.5±3.1 years, HbA[sub 1c] 8.2±1.1%) with normal 24-hour BP rhythm. ACE I/D polymorphism as well as endothelial function and subclinical inflammation parameters (endothelin-1, sE-selectin, soluble intercellular (sICAM) and vascular (sVCAM) cell adhesion molecules, tumor necrosis factor-α (TNF-α) were assessed with ELISA in all the subjects. ACE DD genotype was found in 24 (71%) and ID in 10 (29%) study group subjects; 3 (6%) control subjects had DD, 32 (65%) - ID, and 14 (29%) - II genotype p<0.001). In the study and control group subjects fasting serum endothelin-1 was 7.9±:1.4 and 6.3±0.8 pg/ml (p<0.05), sE-selectin 28.9±12.2 and 18.2±12.7 ng/ml (p<0.05), ICAM 1569±732 and 755±473 ng/ml (p<0.01), VCAM 1932±556 and 1173±701 ng/ml (p<0.05), respectively. No statistically significant difference was found in serum TNF-α (85.7±83.3 and 82.8±73.3 pg/ml, p>0.05) between the groups. In conclusion, impaired circadian BP variation in normotensive normoalbuminuric type 2 diabetes patients is strongly associated with ACE DD genotype and marked endothelial dysfunction when compared to the subjects with normal BP rhythm. These findings may offer plausible explanation for the non-dipping phenomenon in normotensive normoalbuminuric type 2 diabetes patients. [ABSTRACT FROM AUTHOR]