Diabetes-Related Complications and Mortality in Patients With Young-Onset Latent Autoimmune Diabetes: A 14-Year Analysis of the Prospective Hong Kong Diabetes Register

Abstract

Objective: Young-onset diabetes is heterogeneous in etiology and disease progression. We compared the incidence of diabetes-related complications and mortality in patients with young-onset type 2 diabetes with or without anti-GAD antibodies and patients with type 1 diabetes. We determined changes in glycemic control before and after commencement of insulin therapy stratified by antibody status.

Research design and methods: Between 1994 and 2012, 1,504 consecutively enrolled patients with type 2 diabetes who had received a diagnosis at <40 years of age and had available anti-GAD antibody status and 251 patients with type 1 diabetes from the Hong Kong Diabetes Register were followed for incident cardiovascular disease (CVD), end-stage renal disease (ESRD), severe hypoglycemia, and all-cause mortality until June 2015. Information on insulin use and HbA_1c levels during follow-up was obtained.

Results: Anti-GAD antibodies were positive in 8.1% of patients with type 2 diabetes (GAD⁺). By multivariate Cox regression, patients with GAD⁺ had a lower hazard of CVD (hazard ratio [HR] 0.43, P = 0.048), a higher hazard of severe hypoglycemia (HR 1.63, P = 0.032), and a similar hazard of ESRD and mortality compared with counterparts without anti-GAD antibodies (GAD^-). Compared with patients with type 1 diabetes, ESRD was more likely to develop (HR 2.91, P = 0.043) in patients with GAD⁺, but no differences were detected in the hazards of severe hypoglycemia, CVD, and mortality. Among new insulin users (n = 304), patients with GAD⁺ had larger reductions in HbA_1c than patients with GAD^-after 12 months of insulin use (-2.30 ± 3.80% [25 ± 42 mmol/mol] vs -0.72 ± 1.86% [8 ± 20 mmol/mol], P = 0.05).

Conclusions: Anti-GAD positivity identifies a group of patients with a different prognosis compared with patients without antibodies and those with type 1 diabetes. Patients with GAD⁺ responded differently to insulin compared with patients with GAD^-.