Immune Biomarkers of Residual Beta-cell Mass in Type 1 Diabetes

Summary

There is currently no imaging technique allowing to directly visualize and measure pancreatic beta-cell mass. Consequently, the best parameter to estimate this mass is the insulin (and its C-peptide byproduct) that residual beta cells are able to produce. This insulin secretion is measured during a meal test, before and at different times after drinking a standardized quantity of nutrients. However, this test is cumbersome (lasting 3 h, with blood samples taken every 30 minutes) and it holds poor sensitivity, probably insufficient to detect very few residual beta cells. Nevertheless, these few residual cells can improve glycemic control and can be instrumental for the clinical efficacy of immune and/or regenerative therapies.

We hypothesize that residual beta cells may not only represent the remaining insulin secretory capacity, but also the antigenic load capable of stimulating beta-cell-reactive T lymphocytes. The disappearance of these T lymphocytes from circulating blood over time may thus be correlated with beta-cell loss. Measuring beta-cell-reactive T-cell responses may therefore provide simple and sensitive immune surrogate markers of residual insulin secretion. Other surrogate markers may be obtained by measuring urinary C peptide or residual secretion of the counter-regulatory hormone glucagon.

The main objectives of this study are:

1. To evaluate the correlation between beta-cell-reactive T-cell responses and residual insulin secretion.
2. To evaluate the correlation between the residual insulin secretion measured by serum C peptide and by urinary C peptide.
3. To evaluate the correlation between the residual insulin and glucagon secretion.

Conditions

• Type 1 Diabetes

Interventions

OTHER

Meal Test

Insulin secretion is stimulated by a standardized meal test. Blood and urine samples are collected in order to measure serum and urinary C peptide, glucagon and T-lymphocyte responses against selected beta-cell antigens. The meal test is performed at 0, 6, 12, 18, 24 and 30 months.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France

  collaborator OTHER_GOV

• URC-CIC Paris Descartes Necker Cochin

  collaborator OTHER

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Etienne LARGER, MD, PhD · Service de Diabétologie, Hôtel Dieu, AP-HP, Paris

• Roberto MALLONE, MD, PhD · INSERM , AP-HP

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

6 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-11-15

Primary Completion

2017-05-30

Completion

2017-05-30

Countries

• France

Study Locations