Beta-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial

Lancet. 2001 Nov 24;358(9295):1749-53. doi: 10.1016/S0140-6736(01)06801-5.


Background: Type 1 diabetes results from autoimmune destruction of insulin-producing pancreatic beta cells. The 60 kDa heat-shock protein (hsp60) is one of the known target self antigens. An immunomodulatory peptide from hsp60, p277, arrested beta-cell destruction and maintained insulin production in newly diabetic NOD mice. We did a randomised, double-blind, phase II study of peptide treatment in patients with newly diagnosed (<6 months) type 1 diabetes.

Methods: 35 patients with type 1 diabetes and basal C-peptide concentrations above 0.1 nmol/L were assigned subcutaneous injections of 1 mg p277 and 40 mg mannitol in vegetable oil (DiaPep277; n=18) at entry, 1 month, and 6 months, or three placebo injections (mannitol in vehicle; placebo; n=17). The primary endpoint was glucagon-stimulated C-peptide production. Secondary endpoints were metabolic control and T-cell autoimmunity to hsp60 and to p277 (assayed by cytokine secretion). 31 patients completed 10 months of follow-up and were included in the intention-to-treat analysis.

Findings: At 10 months, mean C-peptide concentrations had fallen in the placebo group (n=16) but were maintained in the DiaPep277 group (n=15; 0.26 [SD 0.11] vs 0.93 [0.35] nmol/L; p=0.039). Need for exogenous insulin was higher in the placebo than in the DiaPep277 group (0.67 [0.33] vs 0.43 [0.17] U/kg; p=0.042). Haemoglobin A1c concentrations were low (around 7%) in both groups. T-cell reactivity to hsp60 and p277 in the DiaPep277 group showed an enhanced T-helper-2 cytokine phenotype. No adverse effects were noted.

Interpretation: Although this study was small, treatment of newly diagnosed type 1 diabetes with DiaPep277 seems to preserve endogenous insulin production, perhaps through induction of a shift from T-helper-1 to T-helper-2 cytokines produced by the autoimmune T cells.

Publication types

  • Clinical Trial
  • Legal Case
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • C-Peptide / biosynthesis
  • Chaperonin 60
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Double-Blind Method
  • Heat-Shock Proteins / therapeutic use*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / metabolism
  • Insulin Secretion
  • Interleukins / biosynthesis
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Male
  • Peptide Fragments / therapeutic use*
  • Treatment Outcome


  • C-Peptide
  • Chaperonin 60
  • Heat-Shock Proteins
  • Hypoglycemic Agents
  • Insulin
  • Interleukins
  • Peptide Fragments
  • peptide 277, heat shock protein 60