Protective Effects of Sitagliptin on β Cell Function in Patients With Adult-onset Latent Autoimmune Diabetes (LADA)
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The aim of this study is to investigate the protective effects of sitagliptin on β cell
      function in patients with adult-onset latent autoimmune diabetes (LADA) and its mechanisms.
    

Detailed description: 
      Adult-onset latent autoimmune diabetes (LADA), etiologically belongs to type 1 diabetes
      (T1D), is characterized by the presence of islet autoantibodies, such as islet cell antibody
      (ICA) and glutamic acid decarboxylase antibody (GADA), and is prone to develop β-cell
      failure. The goals of treatment for LADA are suppression of autoimmune β cell destruction,
      preservation of islet function and prevention of diabetic complications. Recently two classes
      of compounds have been approved by the FDA as type 2 diabetes (T2D) therapeutics: the
      glucagon-like peptide-1 (GLP-1) receptor agonist (incretin mimetic) exenatide (Byetta) and
      the dipeptidyl peptidase IV (DPP-IV) inhibitor sitagliptin (Januvia) and vildagliptin
      (Galvus). They have been shown to reduce HbA1c, fasting glucose and to improve β cell
      function in T2D patients, as a mono-therapy or in combination with metformin or
      thiazolidinediones. Besides, in vitro studies showed incretin-based therapy can stimulate
      β-cell proliferation and survival, increase β cell insulin content and inhibit apoptosis.
      Moreover, several short-term pilot studies suggest GLP-1 may also have the potential for
      treating T1D. Several findings suggest that Ex-4 may also act as a regulator of the immune
      response in addition to its potential effects on β cell proliferation. Therefore, we
      hypothesized DPP-IV inhibitors might provide therapeutic advantages in T1D though no study
      has been reported. Besides the β cell function, another important target is insulin
      sensitivity. As for DPP-IV inhibitor, clinical trials demonstrated their beneficial effects
      on insulin sensitivity in subjects with T2D and impaired fasting glucose (IFG) and in
      diabetic rat model. We'd like to further explore the possible effect of sitagliptin on
      insulin sensitivity in LADA patients by homeostasis model assessment for insulin resistance
      (HOMA-IR) index and euglycemic clamp technique. In addition, the systemic inflammation
      associated with a wide array of plasma proteins and pro-inflammatory cytokines (i.e., C
      reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6) play an additional
      role in the pathogenesis of insulin resistance in diabetes. It will be of interest to
      investigate the adipokines and proinflammatory cytokines after the sitagliptin therapy in the
      study. Hence, we aim to explore the effects of sitagliptin plus insulin on β cell function,
      insulin sensitivity, pro-inflammatory cytokines and immune regulation including Teff and Treg
      frequency, and function in patients with LADA.
    

Intervention name(s): sitagliptin; Insulin
Intervention type(s): Drug; Drug
Intervention description(s): sitagliptin tablet,100 mg p.o. qd,2 year
Other intervention name(s): Januvia
Intervention MeSH terms: Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: sitagliptin; LADA; C-Peptide; Flow Cytometry; ELISPOT