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Abstract

Aims

The aim was to evaluate the impact of family history of diabetes on the phenotype of patients diagnosed with Type 2 diabetes and the frequency of susceptibility genotypes.

Methods

Patients with Type 2 diabetes with family history for both Type 1 and Type 2 diabetes (FHMIX, n = 196) or Type 2 diabetes only (FHT2, n = 139) matched for age, sex, BMI and age at diagnosis, underwent an oral glucose tolerance test and a combined glucagon test and insulin tolerance test. Glutamic acid decarboxylase (GAD) antibodies and major Type 1 and Type 2 diabetes susceptibility gene variants were analysed. Patients were stratified into groups according to family history or GAD antibody positivity (GADA+, GADA–) or a combination of these (GADA+/FHMIX, GADA+/FHT2, GADA–/FHMIX, GADA–/FHT2).

Results

Compared with other patients, those with FHMIX more often had GAD antibodies (14.3 vs. 4.3%, P = 0.003), and those with both FHMIX and GAD antibodies had the highest frequency of insulin deficiency (stimulated serum C-peptide < 0.7 nmol/l, GADA+/FHMIX 46.4% vs. GADA–/FHMIX 9.5% (P < 0.00001), GADA–/FHT2 4.5% (P < 0.00001), GADA+/FHT2 0%). Patients with GADA+/FHMIX more often had HLA-DQB1 risk genotypes compared with patients with GADA–/FHMIX or GADA–/FHT2D (47 vs. 23 or 14%, P = 0.05 and P < 0.00001, respectively). In logistic regression analyses, FHMIX, GAD antibody positivity and HLA risk genotypes were independently associated with insulin deficiency.

Conclusion

A family history for both type 1 and type 2 diabetes was associated with higher prevalence of GAD antibodies and HLA-DQB1 risk genotypes than a family history of type 2 diabetes only, and was associated with earlier and more severe development of insulin deficiency, which was only partially explained by GAD antibodies and HLA.