Gender differences in GAD antibody-positive diabetes mellitus in relation to age at onset, C-peptide and other endocrine autoimmune diseases

Abstract

Background: Females have an increased incidence of autoimmune diseases. However, no gender difference in the incidence of type 1 diabetes is found. The frequency of antibodies against glutamic acid decarboxylase (GADA) in diabetes mellitus depends on age at diagnosis and also gender. Several studies have shown that high GADA levels can predict future beta-cell failure and need for insulin treatment. The aim of this study was to investigate possible gender differences in relation to GADA levels, fasting plasma C-peptide levels and frequency of other autoimmune endocrine diseases in GADA-positive patients with different age at diabetes diagnosis.

Methods: GADA were screened in 4974 patients from a local diabetes registry, and plasma C-peptide was measured and a history of other autoimmune endocrine diseases was recorded. Of these patients, 822 were GADA positive and were further divided into four groups depending on the age at diagnosis of diabetes; Group 1: <20 years, Group 2: 20-39 years, Group 3: 40-59 years and Group 4: > or =60 years.

Results: Female patients in Group 3 had lower fasting plasma C-peptide levels (median 0.21[0.00-0-56] vs. 0.41[0.00-0.73] nmol/L, p=0.02), higher GADA levels (median 7 [4-9] vs. 5 [2-7] Arbitrary Unit (AU), p=0.0003) and higher frequency of other autoimmune endocrine diseases (22.4 vs. 5.3%, p=0.0001) than male patients. In a stepwise logistic regression analysis, diabetes duration (p<0.000001), high GADA levels (Exp (B) 3.68 CI 1.69-7.98, p=0.001) and low BMI (p=0.00002) were associated with total beta-cell failure in Group 3.

Conclusions: GADA-positive female diabetic patients with an age at diagnosis between 40 and 59 years have higher GADA levels and a more severe loss of beta-cell function than male patients with the same age at diagnosis. This could be due to the effect of sex steroids and/or GnRH on the regulation of the immune system. Female patients with high GADA levels also had a high prevalence of other autoimmune endocrine diseases, especially autoimmune thyroid disease, which further emphasises the need for screening of thyroid function in female patients with high GADA levels.