In obesity, immune cells establish a systemic inflammatory state associated with development of insulin resistance and T2D. Previous studies have shown that peripheral blood mononuclear cell (PBMC) responses to islet proteins (IPs) in adults with established T2D on glucose-lowering therapies identify those patients with more severe β-cell dysfunction. Moreover, attenuation of PBMC responses to IPs in adults with established T2D improves β-cell function. However, the presence of IP reactive PBMCs, glutamic acid decarboxylase autoantibodies (GADA), and their relationship to insulin sensitivity and β-cell function has never been evaluated in IGT or Ndx T2D. We measured at baseline and after 12 months of RISE medication interventions (12 months with either metformin or liraglutide plus metformin or for 3 months with insulin glargine followed by 9 months of metformin), PBMC responses to IPs, GADA, insulin sensitivity, and β-cell function in 258 RISE participants (mean ± SD) 53.3 ± 9.2 years of age, BMI 35.1 ± 5.4 kg/m2, with IGT (n=180) or Ndx T2D (<12 months duration, n=78). At baseline, IP reactive PBMCs were present in 46% of participants with IGT and 40% of participants with Ndx T2D. However, 97% of IGT and 98% of Ndx T2D were GADA negative. There were no significant relationships between the presence of PBMC reactivity to IPs, GADA positivity and insulin sensitivity or β-cell function. RISE treatments did not alter PBMC responses to IPs, GADA, or the relationship between IP reactive PBMCs or GADA with glycemic responses.
In summary, IP reactive PBMCs are present in a large percentage of adults with very early dysglycemia, However, the presence of IP reactive PBMCs did not correlate with insulin sensitivity or early β-cell dysfunction. Further studies are needed to unravel the pathogenesis of IP reactive PBMCs and GADA and their effects on β-cell function during progression of T2D.
B. Brooks-Worrell: None. A.H. Tjaden: None. S. Edelstein: None. B.M. Palomino: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. T.A. Buchanan: None. K.J. Nadeau: None. K.M. Atkinson: None. E. Barengolts: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. J.P. Palmer: None.
National Institutes of Health (R01DK107560)