Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies

The aim of the study was 1) to establish the prevalence of GAD antibodies ( GAL)ab) in a population-based study of type 2 diabetes in western Finland, 2) to genetic ally and phenotypically characterize this subgroup, and 3) to provide a definition for latent autoimmune diabetes: in adults (LADA), The prevalence of GADab was 9.3%, among 1,122 type 2 diabetic patients, 3.6% a mong 558 impaired glucose tolerance (IGT) subjects, and 4.4%, among 383 non diabetic control subjects, Islet antigen 2 antibodies (IA2ab) or islet cell antibodies were detected in only 0.5% of the GADab(-) patients. The GADab( +) patients had lower fasting C-peptide concentrations (median [interquarti le range]: 0.46 [0.45] vs. 0.62 [0.44] nmol/l, P = 0.0002) and lower Insuli n response to oral glucose compared with GADab patients, With respect to fe atures of the metabolic syndrome, the GADab(+) patients had lower systolic (140 [29.1] vs, 148 [26.0] mmHg, P = 0.009) and diastolic (79.2 [17.6] vs. 81.0 [13.1] mmHg, P = 0.030) blood pressure values, as well as lower trigly ceride concentrations (1.40 [1.18] vs, 1.75 [1.25] mmol/l, P=0.003). GADab( +) men had a lower waist-to-hip ratio compared with GADab(-) patients, Comp ared with GADab(-) patients and control subjects! the GADabi patients had a n increased frequency HLA-DQB1*0201/0302 (13 vs. 4%; P = 0.002) and other g enotypes containing the *0302 allele (22 vs. 12%; P = 0.010), However, the frequency of these high-risk genotypes was significantly lower in GADab(+) type 2 patients than in type 1 diabetes of young or adult onset (0201/0302 or 0302/X: 36 vs. 66 vs. 64%, P < 0.001). The GADab(+) type 2 group did not differ from control subjects with respect to genotypes containing the prot ective DQB1-alleles *0602 or *0603, nor with respect to the type 1 high-ris k genotype in the IDDM1 (Hph1 +/+), we conclude that AGDab(+) patients diff er from both GADab(-) type 2 diabetic patients and type I diabetic patients with respect to beta-cell function, features of the metabolic syndrome, an d type 1 diabetes susceptibility genes. Further, we propose that: LADA be d efined as GADab positivity (>5 relative units) in patients older than 35 ye ars at onset of type 2 diabetes.