Does Age at Diagnosis in Familial Diabetes Affect Type 2 Risk?

Mar 27, 2021 Editor: David L. Joffe, BSPharm, CDE, FACA
Author: Mit Suthar, PharmD. Candidate, LECOM School of Pharmacy 

Study of the Danish national register suggests that family members’ age at onset of diabetes could be an essential factor that is overlooked in determining type 2 risk. 

A family history of diabetes is a risk factor that is widely used in screening and predicting which patients are at increased risk of developing diabetes. Family history is a practical and conveniently identifiable risk factor that provides insight into the genetic and social/behavioral contributing factors of diabetes. The familial risk depends on the number of family members affected with diabetes and the type of family relationship. However, the strongest determinants of developing type 2 diabetes are the social and behavioral elements: “obesity, physical inactivity, diet, and low socioeconomic status.”  

There has been progress in understanding the connection between the etiology of type 2 diabetes and family history. Still, there is a lack of information about the effect of family members’ age at diabetes diagnosis and its relation to a patient’s risk of diabetes and their likely age of onset. The study hypothesized that “in addition to the type of family relationship and the number of family members affected with diabetes, their age at diagnosis would be associated with overall familial diabetes risk.” In a nutshell, they were trying to ascertain the effect that family members’ age at diabetes diagnosis had on an individual’s risk of developing diabetes and developing diabetes. This hypothesis was studied by using a national register that covered the total Danish population.  

A national register-based open cohort study of patients living in Denmark between 1995 and 2012 was performed. The study population consisted of individuals 30 years old or older without a diabetes diagnosis but who had access to their parent’s identity and information. The open cohort design allowed the addition of patients who turned 30 years old during the observation period. These specific criteria meant that most individuals included in the study were born between 1960 and 1982. This population was followed from January 1, 1995 (or the date of cohort entry) until they emigrated, or death, or until December 31, 2012.

After the inclusion and exclusion criteria were implemented, the study population comprised 2,000,552 individuals in 1,107,915 families, with the median age at entry into the study being 30 years old. These individuals were followed for a median of 14 years, and 76,633 new cases of type 2 diabetes were observed. They found that men and women had similar sociodemographic backgrounds and familial diabetes indicators. Still, a more significant proportion of women (42%) had completed more than 15 years of education than men (31%).  

Furthermore, and more importantly, they found that: “Compared with individuals of the same age and sex who did not have a parent or full sibling with diabetes, the highest risk of developing type 2 diabetes was observed in individuals with family members diagnosed at an early age.“ The IRR was also increasingly lower when family members had diabetes diagnosed at a later age. “3.9 vs. 1.4 for those with a parental age at diagnosis of 50 or 80 years, respectively; and 3.3 vs. 2.0 for those with a full sibling‘s age at diagnosis of 30 or 60 years, respectively.“  

The data collected from the national registers of Denmark illuminated how different combinations of exposure to familial diabetes can increase an individual’s risk of developing type 2 diabetes.  The researchers found that individuals with a family member who was diagnosed with diabetes at an earlier age are more likely to develop diabetes and unfortunately also develop it at an earlier age, compared to individuals with family members who developed diabetes at a later age.  

These findings are significant as they highlight the importance of understanding the complex interactions between “genetic diabetes determinants and the social, behavioral and environmental diabetes determinants,” which follow families across generations. There is a strong argument for the inclusion of recording an age of onset of diabetes for those family members we include in the family history when trying to screen for and predict the risk of developing type 2 diabetes in patients. The relative ease with which such data can be obtained and the highly relevant nature of the findings can significantly improve individuals’ identification, especially those at a higher risk of developing diabetes at a younger age vs. those who are more likely to develop diabetes later in life. This information can benefit many family members and not just the patient who is being screened.  

Practice Pearls: 

• Family history is a vital independent risk factor for developing type 2 diabetes. Right now, the familial risk depends on the number of family members affected by the disease and the nature of the family relationship, but the age of onset of diabetes could be an essential factor that is overlooked. 
• The nationwide open cohort found that patients with a family member who was diagnosed with diabetes earlier in life are more likely to develop diabetes, and also at an earlier age, than those patients whose family members developed diabetes at a later age. 
• The benefits of obtaining the age of diagnosis of family members mean that it should become part of recording the diabetes family history. These individuals with family members who developed diagnosis at an earlier age could benefit from a more detailed risk factor assessment as well as individualized prevention strategies. 

Schwarz, et al. “Effect of Familial Diabetes Status and Age at Diagnosis on Type 2 Diabetes Risk: a Nationwide Register-Based Study from Denmark.“ Diabetologia, 19 Feb. 2020, link.springer.com/article/10.1007/s00125-020-05113-8.  

Mit Suthar, PharmD. Candidate, LECOM School of Pharmacy  

My comment: Although it seems common sense that the younger age at diagnosis and the number of relatives affected with type 2 diabetes, the higher a persons individual risk seems, this is the study that nails it.