Islet autoantibody positivity in overweight and obese adults with type 2 diabetes

Abstract

Islet autoantibodies are typically associated with type 1 diabetes, but have been found in patients diagnosed with type 2 diabetes in whom they are associated with lower adiposity. The significance of autoantibody positivity in overweight and obese patients is not well understood. The aim of this study was to determine the prevalence and clinical significance of islet autoantibodies in overweight/obese adults diagnosed with type 2 diabetes. This study includes 204 participants at one site of the multicenter Look AHEAD (Action for Health in Diabetes) trial (ClinicalTrials.gov identifier: NCT00017953) which randomized overweight/obese adults diagnosed with type 2 diabetes to an intensive lifestyle intervention or diabetes support and education. We measured antibodies to glutamic acid decarboxylase, insulinoma antigen-2, and zinc transporter 8. Participants with and without autoantibodies were compared with respect to baseline clinical features, and longitudinal changes in weight, hemoglobin A1c, and antihyperglycemic medications. We found that 13 participants (6.4%) were autoantibody positive, including six of 47 participants (12.8%) with BMI ≥40 kg/m². At baseline, autoantibody positive participants had higher HDL cholesterol (1.27 vs. 1.09 mmol/L, p = .034) and lower fasting C-peptide (0.32 vs. 0.57 nmol/L, p = .049). Over four years, autoantibody positive participants lost 5.1 kg more weight than autoantibody negative participants (p = .056). Longitudinal changes in hemoglobin A1c did not differ by autoantibody status, though autoantibody positive participants were more likely to increase the number of antihyperglycemic medications or initiate insulin (p = .011). In conclusion, islet autoantibodies were present in 6.4% of overweight/obese adults with type 2 diabetes including those with severe obesity, and were associated with distinct clinical features. The effect of autoantibody positivity on weight loss interventions requires further study.

Keywords:

• Type 2 diabetes
• autoantibodies
• islet cell antibody
• autoimmunity
• obesity
• weight loss

Acknowledgements

The authors would like to thank James Potter and the Translational Research Enhancement Core of the Hopkins Conte Digestive Diseases Basic and Translational Research Development Center for the processing, storage, and shipment of specimens. We would also like to thank Dr. Santica Marcovina of the University of Washington and the Northwest Lipid Research Laboratories in Seattle, Washington, for assistance with islet autoantibody assays.

Disclosure statement

The authors report no conflicts of interest in this work.

Additional information

Funding

This research was funded in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). S.J.P. was supported by NIH training grant 5T32HL007180-40. A.B. was supported by NIH/NIDDK grant U01DK057177-18. D.M.N. was supported by NIH/NIDDK grant U01DK057154-18. X.P. was supported by NIH/NIDDK grant U01DK057178-18. J.M.C. and N.M.M. were supported by NIH/NIDDK grant U01DK057149-17. The study was also funded by National Heart, Lung, and Blood Institute.