Preliminary evidence of genetic anticipation in type 2 diabetes mellitus

Abstract

Background: The term "anticipation" in genetic diseases refers to earlier age at onset and/or increased severity in successive generations. Several diseases with genetic anticipation include rheumatoid arthritis, Crohn's disease, Schizophrenia, Graves' disease and several other neuropsychiatric disorders. The aim of the present study was to investigate whether genetic anticipation may occur in diabetes.

Material/methods: The medical records of 485 subjects with type 2 diabetes, seen in the Diabetes Clinic were screened for subjects with a family history of diabetes and also aware of a definite date of diagnosis for both the subject and their family member. Ninety-six parent-child pairs with a known definite date of diagnosis of type 2 diabetes were identified and the age at onset of diabetes between two parent-child generations was compared.

Results: The age at diagnosis of the subjects with positive family history of diabetes was lower than those with no family history of diabetes (48.82+/-12 vs. 56.18+/-13; p<0.001). There was a significant difference in the mean age at diagnosis between the 1(st) generation and 2(nd) generation (57.39 vs. 52.03 years p<0.0001). When the age at diagnosis of the subjects with siblings was compared (38 sibling pairs), there was no significant difference noted (52.21 vs. 50.57; p=0.35).

Conclusions: Patients in the second affected generation seem to acquire the disease at an earlier time in life, indicating strong evidence of anticipation. We conclude that genetic anticipation might occur in type 2 diabetes.