Impact of islet autoimmunity on the progressive β-cell functional decline in type 2 diabetes

Barbara M Brooks-Worrell, Edward J Boyko, Jerry P Palmer, Barbara M Brooks-Worrell, Edward J Boyko, Jerry P Palmer

Abstract

Objective: Cross-sectional studies have suggested that islet autoimmunity may be more prevalent in type 2 diabetes (T2D) than previously appreciated and may contribute to the progressive decline in β-cell function. In this study, we longitudinally evaluated the effect of islet autoimmune development on the progressive β-cell dysfunction in T2D patients.

Research design and methods: Twenty-three T2D patients negative for islet autoantibodies (GAD antibody and insulinoma-associated protein 2) and islet-specific T cells were evaluated prospectively for up to 36 months. We investigated the percentage of patients who developed islet autoantibodies (Ab+) and/or islet-reactive T cells (T+) and the effect of the islet autoimmunity on fasting and glucagon-stimulated C-peptide responses. We defined positive islet autoimmunity as Ab+ and/or T+ for at least two study visits.

Results: Of the 23 patients, 6 (26%) remained negative for islet autoimmunity (Ab-T-), 14 (61%) developed Ab+ and/or T+, and 3 (13%) were unclassifiable because they developed islet autoimmunity at only one study visit. Islet Ab+ was observed to be less stable than islet-specific T-cell responses. Development of islet autoimmunity was significantly associated with a more rapid decline in fasting (P < 0.0001) and glucagon-stimulated (P < 0.05) C-peptide responses.

Conclusions: These pilot data suggest that the development of islet autoimmunity in T2D is associated with a significantly more rapid β-cell functional decline.

© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1
Figure 1
Longitudinal islet-specific T-cell responses for six Ab−T− T2D patients (A) and seven Ab−T+ T2D patients (B). The horizontal line at three blot sections represents the cutoff for T-cell positivity.
Figure 2
Figure 2
Longitudinal islet Ab responses for two Ab+T− T2D patients. A: Both patients developed IA-2 positivity, and one patient developed both IA-2 and GADA. B: GADA results. The horizontal lines show the cutoff for positive responses.
Figure 3
Figure 3
A:Five T2D patients developed both islet-specific T-cell reactivity and islet Abs during follow-up (Ab+T+). All five patients were GADA+ (B), and one patient was also IA-2+ (C). The horizontal lines show the cutoff for positive responses.
Figure 4
Figure 4
Median percentage change in FCP levels (A) and glucagon-SCP (B) responses for the nonautoimmune patients (Ab−T−) and patients developing islet autoimmunity (Ab+T−, Ab-T+, and Ab+T+) before and after autoimmune development.

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