Frequency, clinical features, inflammatory cytokines and genetic background of latent autoimmune diabetes in youth in youth‐onset type 2 diabetes: Results from a nationwide, multicentre, clinic‐based, cross‐sectional study (LADA China)

Abstract

Aims We aimed to study the frequency, clinical phenotype, inflammatory cytokine levels and genetics of the glutamic acid decarboxylase autoantibody (GADA)‐positive phenotypic youth‐onset type 2 diabetes. Materials and Methods This nationwide, multicenter, cross‐sectional study included 5,324 newly diagnosed subjects with phenotypic type 2 diabetes aged ≥ 15 years enrolled in the LADA China study. GADA was screened in 248 subjects with youth‐onset type 2 diabetes aged 15‐29 years. Subjects who presented as GADA‐positive were defined as having latent autoimmune diabetes in youth (LADY). We added subjects with LADY, type 1 diabetes, type 2 diabetes and controls from the Diabetes Center of Central South University, and measured serum concentrations of interleukin‐6 (IL‐6), lipocalin 2 (LCN2), high‐sensitivity C‐reactive protein (hs‐CRP), adiponectin and human leukocyte antigen (HLA) genotyping in LADY, age‐ and sex‐matched GADA‐negative type 2 diabetes, type 1 diabetes and controls. Results Twenty‐nine of the 248 subjects (11.7%) were GADA positive. Compared with subjects with type 2 diabetes, subjects with LADY were less likely to have metabolic syndrome (27.6 vs. 59.4%, P=0.001). The fasting C‐peptide levels tended to be lower in subjects with LADY than in subjects with type 2 diabetes, but the difference was not statistically significant (LADY vs. type 2 diabetes: 0.21 [0.17‐0.64] nmol/L vs. 0.47 [0.29‐0.77] nmol/L, P=0.11). The cytokine levels of LADY subjects were indistinguishable from subjects with type 1 diabetes, but LADY presented increased adiponectin levels compared with type 2 diabetes after adjusting for age, sex and BMI (7.19 [4.05‐11.66] vs. 3.42 [2.35‐5.74] μg/mL, PP<0.001). Conclusions A high GADA positivity was observed in youth‐onset type 2 diabetes subjects in China. As LADY had an increased susceptible HLA genetic load and different cytokine levels compared with type 2 diabetes, differentiating LADY from phenotypic type 2 diabetes subjects is important.