Background: Few data exist as to whether dipeptidyl peptidase (DPP)-4 inhibitors affect cardio-renal interaction, which is a strong independent prognostic factor for cardiovascular disease (CVD), in diabetic patients. We evaluated the effects of a DPP-4 inhibitor on atherogenic low-density lipoprotein (LDL) heterogeneity and albuminuria in diabetics as an indicator of the severity of diabetic nephropathy.
Methods: Type 2 diabetes patients (n = 47) inadequately controlled with diabetes therapy were treated with vildagliptin 50 mg bid for 8 weeks. LDL heterogeneity was evaluated on the basis of the patients' small dense (sd) LDL levels and sd-LDL proportion (sd-LDL/LDL cholesterol [LDL-C]). The level of albuminuria was evaluated on the basis of the urinary albumin-to-creatinine ratio (UACR).
Results: After 8 weeks of treatment, there was no significant change in serum LDL-C level, but the serum sd-LDL level had decreased significantly by 8.8 %, and the UACR had also decreased significantly by 44.6 %. Triglyceride (TG)-metabolism-related markers (TG, remnant-like particle cholesterol, apolipoprotein [apo] B, apoC-2, and apoC-3) had decreased significantly. The Δ (absolute change from baseline) sd-LDL values correlated positively with ΔTG-metabolism-related markers, but not with the Δ hemoglobin (Hb) A1c or Δ fasting blood sugar (ΔFBS). Furthermore, multivariate regression analysis revealed that Δsd-LDL proportion, but not ΔHbA1c or ΔFBS, was an independent predictor of ΔUACR (β = 0.292, p = 0.0016).
Conclusions: Although this was a single-arm study, treatment of type 2 diabetes with vildagliptin might prevent the progression of CVD complicating diabetes by improving LDL heterogeneity, and it might improve renal function by decreasing albuminuria. A randomized controlled trial is warranted.