Increased Risk of Diabetes in First-Degree Relatives of Young-Onset Type 2 Diabetic Patients Compared With Relatives of Those Diagnosed Later

We were pleased to see an article focusing on the features of young-onset type 2 diabetes (YT2D), which is diagnosed between 18 and 44 years of age (1). The importance of studying this group is illustrated by reports of rapid increases in the prevalence of diabetes in young adults in both the U.S. (2) and U.K. (3).

We describe another feature of YT2D subjects not highlighted in the study by Hillier and Pedula (1): the increased rate of diabetes in first-degree relatives. Patients with YT2D may present earlier because of a greater genetic predisposition. We hypothesized that the risk of diabetes for relatives of patients with YT2D would be higher than the risk to relatives of those diagnosed later.

To test this hypothesis, we surveyed the family history of diabetes in 4,770 patients with type 2 diabetes (99% U.K. Caucasian) in Devon, U.K. Patients were defined as type 2 diabetic if they had been diagnosed at >25 years of age and were not treated with insulin for a year after diagnosis. Family history of diabetes was compared in those diagnosed before (n=568) or after (n=4,202) 45 years of age. Despite the YT2D subjects being younger at the time of sampling (median age 53 vs. 72 years, P < 0.001), the prevalence of diabetes was higher in the parents of young-onset patients. An affected mother or father was reported in 26.9 and 15.1% of the YT2D group, respectively, compared with 15.2 and 7.6% of those diagnosed at >45 years of age (P < 0.001 for both). Biparental diabetes was also significantly increased (2.5 vs. 0.6%, P < 0.001) in the YT2D group. The rates of diabetes in siblings (21.0 vs. 21.2%, P=0.91) and children (3.7 vs. 4.6%, P=0.35) were similar in the two groups, suggesting that young age of diabetes onset clusters in these families. Similar ages of onset among affected family members have been previously observed in Mexican-American and Jewish populations (4,5).

To eliminate the effects of present age and sex on the prevalence of diabetes in relatives, 344 patients diagnosed before 45 years of age were individually matched with patients diagnosed after 45 years of age for these factors (median age of group 59.5 years, 66% male). The prevalence of diabetes in siblings was nonsignificantly higher when the proband was diagnosed before 45 years of age (23.6 vs. 16.9%, P=0.075). The higher rate in parents (35.8 vs. 25.5%, P=0.03) was confirmed. These results support a 40% increased relative risk of diabetes in relatives of YT2D compared with relatives of later-onset subjects.

We conclude that first-degree relatives of young-onset type 2 patients (diagnosed at <45 years of age) have a higher rate of diabetes when compared with relatives of diabetic patients diagnosed after 45 years of age. YT2D clusters in families; therefore, parents and siblings who will still be comparatively young are at high risk. Because this is most marked in parents, particularly mothers, nondiabetic parents should be screened when their child is first diagnosed with YT2D and on an annual basis thereafter. Parents and siblings of YT2D are an important group for all screening programs for diabetes.