Filaggrin proteins are located in the skin and prevent epidermal water loss and impede the entry of micro-organisms, allergens and chemicals. Filaggrin null mutations are strongly associated with ichthyosis vulgaris and atopic dermatitis.
The authors aimed to investigate the association between filaggrin null mutations, atopic dermatitis and diabetes.
A random sample of 3335 adults from the general population in Denmark was filaggrin-genotyped for R501X and 2282del4 null-mutations and questioned about atopic dermatitis and diabetes. Furthermore, two independent study populations of patients with type 1 (n=104) or 2 (n=774) diabetes were genotyped.
In a crude data analysis, a positive association was detected between the filaggrin null genotype and, respectively, subjects from the general population who reported diabetes (p=0.04) and patients with established type 2 diabetes (p=0.073). Adjustment for age and gender resulted in significant associations for patients with type 2 diabetes (p=0.048) and subjects with self-reported diabetes (p=0.032).
Adult Danes with a filaggrin null genotype had a significantly increased prevalence of self-reported diabetes. This finding was replicated when an independent sample of Danish patients with established type 2 diabetes was compared with control subjects from the general population.
A few studies have suggested the existence of an inverse association between atopic dermatitis and type 1 diabetes.
The existence of a specific endotype of asthma that is not driven by sensitisation but rather driven by skin barrier dysfunction was recently suggested.
It is unknown whether a putative impairment of the skin barrier may increase the propensity to low-grade inflammation in other organs as well.
Data from a general population study suggested that the prevalence of filaggrin null mutations was higher in adult Danes who reported diabetes than in non-diabetics.
This finding was replicated when an independent sample of Danish patients with type 2 diabetes was compared with participants from the general population who did not report diabetes and who had normal fasting plasma-glucose and glycated haemoglobin (HbA1c) levels.
Strengths and limitations of this study
Two independent samples were investigated and showed similar results.
The question on self-reported diabetes was not validated in the general population allowing for misclassification.