Introduction & Recent studies have shown a possible role of promoter variants in uncoupling protein genes (UCPs), especially UCP2 and UCP3, as factors predisposing for diabetic polyneuropathy (DPN) [1 – 3] . There are at least two hypotheses aiming to explain the possible role of UCPs on DPN. First, enhanced neuronal expression of UCPs in mitochondria might reduce the hyperglycemia dependent increased production of reactive oxygen species (ROS) [1, 2, 4, 5] . Consistent with this hypothesis, functional polymorphisms in the UCP2 and UCP3 genes [6, 7] are associated with a reduced prevalence of DPN in Caucasian patients with type 1 diabetes [2] . On the other hand, enhanced expression, particularly of UCP2, might increase the proton leak across the inner mitochondrial membrane without oxidative phosphorylation and ATP generation. Therefore, it might lead to an energy defi ciency in the nerve, and thus contribute to DPN [3] . In accordance with this second hypothesis, an association of the common − 866G / A UCP2 polymorphism with peripheral nerve dysfunction has been described in Japanese type 2 diabetic patients [3] . Therefore, we sought to answer whether these contradictory results might refl ect different pathogenetic entities of type 1 and type 2 diabetes mellitus or are they possibly due to the different ethnic background of the respective study population? Hence, we examined the infl uence of the variants − 3826A / G in UCP1, − 866G / A in UCP2, and − 55C / T in UCP3 genes on diabetic microvascular complications in Caucasian subjects with type 2 diabetes mellitus.