The Impact of Sitagliptin as an Add on Therapy With Closed Loop Control in Adolescents With Diabetic Nephropathy

Overview

Diabetic nephropathy (DN) is one of the most frequent microvascular complications of diabetes mellitus, affecting 25 to 40% of patients with type 1 diabetes (T1DM). Early diagnosis, appropriate patient follow-up and treatment are essential to improve the outcomes. There is a need for improvements in insulin therapy for people with T1DM as the majority of patients are struggling to achieve glycemic targets. Technological advancements and oral adjuncts to insulin therapies are starting to be licensed for the use of people with T1DM. Dipeptidyl peptidase-4 (DPP-4), a multifunctional serine protease with a dual function (regulatory protease and binding protein), can modulate inflammation and immune cell-mediated β-cell destruction. DPP-4 degrades the peptide hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP). Several studies have suggested that the upregulated DPP-4 activity is correlated with T1DM pathophysiology.

Evidence from preclinical investigation suggests that DPP-4 inhibition may have beneficial effects on various metabolic indicators in diabetes. DPP-4 inhibitors, such as sitagliptin, have been widely used as outstanding blood glucose-dependent antidiabetic agents for patients with type 2 diabetes(T2DM). DPP-4 inhibitors have a lowering effect on the glycemic level and were not associated with increasing incidence of adverse events. The reno-protective effects of DPP-4 inhibition in diabetic nephropathy could be a consequence of the antidiabetic actions of DPP-4 inhibitors. A second-generation advanced hybrid closed loop ( AHCL) system has been developed to further improve glycemic control and usability, with adjustable target glucose and automated correction boluses. This system provides proportional integral derivate (PID) algorithm with insulin feedback with adaptive insulin limits and model based auto-corrections located on the pump. Sitagliptin demonstrated an overall decrease in blood glucose concentrations in adults with T1DM when used as an adjunct therapy with an insulin only closed loop (CL) system. Stromal cell-derived factor-1 (SDF-1) is ubiquitously expressed in diverse organs and has multiple functions. SDF-1 is cleaved and inactivated by the DPP-4 enzyme. The DPP-4 enzyme is highly expressed in the kidney. It has been suggested that renal SDF-1 upregulation by DPP-4 inhibition produces multiple protective actions on the diabetic kidney. In view of these data, the investigators assessed the impact of sitagliptin as add on therapy with closed loop control in adolescents with T1DM on glycemic control, diabetic nephropathy and SDF-1 as a marker for nephropathy.