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

To investigate the frequency, clinical phenotype, inflammatory cytokine levels and genetics of glutamic acid decarboxylase autoantibody (GADA)-positive phenotypic youth-onset type 2 diabetes. This nationwide, multicentre, cross-sectional study included 5324 newly diagnosed subjects with phenotypic type 2 diabetes aged 15 years or older 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, lipocalin 2, high-sensitivity C-reactive protein, adiponectin and human leukocyte antigen (HLA) genotyping in subjects with LADY, age- and sex-matched GADA-negative type 2 diabetes, type 1 diabetes and controls. Twenty-nine of the 248 subjects (11.7%) were GADA positive. Compared with subjects with type 2 diabetes, subjects with LADY were less probable to have metabolic syndrome (27.6% vs. 59.4%; p=.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] vs. 0.47 [0.29-0.77] nmol/L; p=.11). The cytokine levels of subjects with LADY were indistinguishable from subjects with type 1 diabetes, but subjects with LADY presented increased adiponectin levels compared with subjects with type 2 diabetes after adjusting for age, sex and body mass index (7.19 [4.05-11.66] vs. 3.42 [2.35-5.74] μg/mL; p < .05). The frequency of total susceptible HLA genotypes (DR3/3, -3/9 and -9/9) in subjects with LADY and type 1 diabetes were similarly higher than controls (LADY and type 1 diabetes vs. controls: 21.4% and 30.8% vs. 2.6%, respectively; p < .001). A high GADA positivity was observed in youth-onset type 2 diabetes subjects in China. As subjects with LADY had an increased susceptible HLA genetic load and different cytokine levels compared with subjects with type 2 diabetes, differentiating LADY from phenotypic type 2 diabetes subjects is important.