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Islet Autoimmunity is Highly Prevalent and Associated With Diminished β-Cell Function in Patients With Type 2 Diabetes in the Grade Study
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posted on 2022-01-21, 15:51 authored by Barbara Brooks-Worrell, Christiane S. Hampe, Erica G. Hattery, Brenda Palomino, Sahar Z. Zangeneh, Kristina Utzschneider, Steven E. Kahn, Mary E. Larkin, Mary L. Johnson, Kieren J. Mather, Naji Younes, Neda Rasouli, Cyrus Desouza, Robert M. Cohen, Jean Y. Park, Hermes J. Florez, Willy Marcos Valencia, GRADE Beta-cell Ancillary Study Network, Ali Shojaie, Jerry P. Palmer, Ashok Balasubramanyam, GRADE Research GroupIslet autoimmunity may contribute to β-cell dysfunction in type 2
diabetes (T2D). Its prevalence and clinical significance have not been
rigorously determined. In this ancillary study to the Glycemia Reduction
Approaches in Diabetes-A Comparative Effectiveness (GRADE) Study, we
investigated the prevalence of cellular and humoral islet autoimmunity
in patients with T2D duration 4·0±3·0 y, HbA1c 7·5±0·5% on metformin
alone. We measured T cell autoreactivity against islet proteins, islet
autoantibodies against GAD65, IA2, ZnT8, and β-cell function.
Cellular islet autoimmunity was present in 41·3%, humoral islet autoimmunity in 13·5%, and both in 5·3%. β-cell function calculated as iAUC-CG and ∆C-peptide(0– 30)/∆glucose(0–30) from an oral glucose tolerance test was lower among T cell-positives (T+) than T cell-negatives (T-) using two different adjustments for insulin sensitivity (iAUC-CG: 13·2% [95% CI 0·3, 24·4%] or 11·4% [95% CI 0·4, 21·2%] lower; ∆C-peptide(0–30)/∆glucose(0–30)) 19% [95% CI 3·1, 32·3%] or 17·7% [95% CI 2·6, 30·5%] lower). T+ patients had 17% higher HbA1c (95% CI 0·07, 0·28) and 7·7 mg/dL higher fasting plasma glucose levels (95% CI 0·2,15·3) than T- patients.
We conclude that islet autoimmunity is much more prevalent in T2D patients than previously reported. T cell-mediated autoimmunity is associated with diminished β-cell function and worse glycemic control.
Cellular islet autoimmunity was present in 41·3%, humoral islet autoimmunity in 13·5%, and both in 5·3%. β-cell function calculated as iAUC-CG and ∆C-peptide(0– 30)/∆glucose(0–30) from an oral glucose tolerance test was lower among T cell-positives (T+) than T cell-negatives (T-) using two different adjustments for insulin sensitivity (iAUC-CG: 13·2% [95% CI 0·3, 24·4%] or 11·4% [95% CI 0·4, 21·2%] lower; ∆C-peptide(0–30)/∆glucose(0–30)) 19% [95% CI 3·1, 32·3%] or 17·7% [95% CI 2·6, 30·5%] lower). T+ patients had 17% higher HbA1c (95% CI 0·07, 0·28) and 7·7 mg/dL higher fasting plasma glucose levels (95% CI 0·2,15·3) than T- patients.
We conclude that islet autoimmunity is much more prevalent in T2D patients than previously reported. T cell-mediated autoimmunity is associated with diminished β-cell function and worse glycemic control.
