Following the Fate of the Failing β-Cell: New Insights From First-Phase Insulin Responses

  1. Anna E. Long2
  1. 1School of Clinical Sciences, University of Bristol, Bristol, U.K.
  2. 2Translational Research, Benaroya Research Institute at Virginia Mason, Seattle, Washington
  1. Corresponding author: Alistair J.K. Williams, a.j.k.williams{at}bristol.ac.uk.

The benefits of residual endogenous insulin secretion in improving metabolic control and reducing complications in patients with type 1 diabetes (T1D) (1) have highlighted the need for early intervention to preserve β-cell mass. However, the time course of β-cell destruction in T1D is still poorly understood (2). Islet autoantibodies indicative of ongoing autoimmunity often appear in early infancy and may be present for many years before diabetes develops (3). Thus, autoantibodies are very useful for identifying individuals at high risk of progression but do not provide precise estimates of time to diabetes onset. Current tests of T-cell activity are poor guides to the rate of progression. Imaging methods for tracking β-cell loss are in development, but are unlikely to be available for several years (4). Metabolic testing is therefore the best approach for monitoring the decline in β-cell capacity (5,6) (Fig. 1).

FIG. 1.

Schematic showing potentially informative tests for tracking the loss of β-cell mass and function. Deterioration of FPIR in the IVGTT and of OGTT responses are currently the best indicators of impending diabetes. Imaging methods for monitoring β-cell mass are still in development. Little is known about the pattern of insulitis and decline in β-cell mass in humans during the prediabetic prodrome. PI/C-peptide, proinsulin-to-C-peptide ratio; Teff, effector T cells.

Several tests have been used to assess β-cell function. These vary in complexity and differ in what …

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