© 2012 CIM.Purpose: Hyperglycemia is the major risk factor for microvascular complications in type 2 diabetes mellitus (T2DM) patients. This randomized controlled clinical trial aimed to investigate T2DM patients with microvascular complications with regard to possible relations among serum clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4) activities. Methods: Subject groups were defined as follows: T2DM without complications (n=25, F/M=9/16, age 53.9±11.1 years); T2DM+Retinopathy (n=25, F/M=13/12, age 63.8±7.1 years); T2DM+Nephropathy (n=25, F/M=13/12, age 58.7±14.4 years); T2DM+Neuropathy (n=25, F/M=15/10, age 63.2±9.6 years); and healthy control subjects (HC) (n=25). CLU, amylin, SFRP-4, DPP-4 and GLP-1 (total and active) activities were measured and compared in blood samples from type 2 diabetic patients with and without microvascular complications. Results: Significantly lower levels of DPP-4 and GLP-1total (P < 0.005 and P < 0.001, respectively) and higher levels of SFRP-4 were measured in subjects with T2DM in comparison with HC (P < 0.05). Serum CLU, amylin and GLP-1active levels were similar between HC and T2DM patients. Patients with T2DM+microvascular complications had significantly higher DPP-4 and GLP-1total levels when compared with T2DM patients without complications (P < 0.05 and P < 0.001, respectively). Regardless of the other features, in all patients with T2DM-associated microvascular complications, a positive correlation was evident between DPP-4 activity and GLP-1total (r=0.290; P < 0.01). Conclusions: DPP-4 activity and GLP-1total levels were higher in patients with microvascular complications associated with T2DM. Contrary to expectations, no negative correlation was seen between GLP-1 and DDP-4 levels. This result suggests the possible inefficacy of DDP-4 activity as a marker to predict in vivo degradation of endogenous GLP-1.