Young Age at diabetes diagnosis amplifies the effect of diabetes duration on risk of chronic kidney disease

Young age at diagnosis or disease aggression which increases lifetime risk of CKD in type 2 patients with diabetes

Type 2 Diabetes, once considered a disease that comes about at an older age, is now increasingly diagnosed in younger adults. The number of people between the ages of 20-39 years old diagnosed with diabetes in just 13 years from 2000 to 2013 has doubled from 23 million young adults to 63 million worldwide. As type 2 diabetes is diagnosed earlier, the risk of other complications also increases. Chronic kidney disease is one of the major complications associated with diabetes, and studies show chronic kidney disease develops in approximately 50% of people with diabetes throughout the course of life. Chronic kidney disease can go on to developing into complete kidney failure and increases the chances of other serious complications such as cardiopulmonary issues and mortality. Studies have been done highlighting the relationship between young diabetes diagnosis and chronic kidney disease. Those studies include A prospective study done in 2020 early-onset type 2 diabetes as a risk factor for end-stage renal disease in patients with diabetic kidney disease and risk of chronic kidney disease in young adults with impaired glucose tolerance/impaired fasting glucose.

It is known that a diabetes diagnosis at a younger age compared to those diagnosed at older ages, generally over 40 years old, has a higher lifetime risk of microvascular complications. What is currently unclear is if this lifetime risk is attributed to more prolonged disease exposure or the aggressive nature of young-onset diabetes.  A meta-analysis study previously reported that with each year increase in age at diabetes diagnosis, there was a 5% decreased risk of microvascular disease. These findings stressed a complex interplay between age at diabetes diagnosis, diabetes duration, and age attainment on the risk of lifetime complications. However, the correlation between the three variables is linear and therefore gives an unclear answer to the question. This study aims to test the hypothesis that “younger age at diabetes onset/diagnosis increases susceptibility to chronic kidney disease beyond the effect of longer diabetes duration. This hypothesis was tested by using data from both territory-wide population-based and hospital registry-based diabetes cohorts. Included in the study were 436,744 people with incident type 2 diabetes aged 20 years or older and had no CKD at the time of diabetes diagnosis from the Hong Kong Diabetes Surveillance database and 16,979 people with prevalent type 2 diabetes aged 20 and older with no CKD at time of enrollment from the Hong Kong Diabetes Register. Poisson models were used to predict chronic kidney disease incidence rates for men and women separately.

Results with a median follow-up of 5.3 years, 134,043 cases of chronic kidney disease were recorded in the Hong Kong Diabetes Surveillance database. The incidence ratio for chronic kidney disease comparing people of the same attained age but diagnosed with diabetes at ages five years apart was higher in people with a younger at diabetes onset/diagnosis. Still, it was decreased with increasing age at diabetes diagnosis. Results for a median follow-up of 6.3 years from the Hong Kong Diabetes Register showed 6500 people developed chronic kidney disease. The risk of chronic kidney disease with longer diabetes duration decreased with older age at diabetes diagnosis. The hazard ratio for chronic kidney disease associated with a 5-year increase in diabetes duration in participants diagnosed at 20-2 years was 1.37. In participants with a 5-year increase in diabetes diagnosis diagnoses at 70 years or older, the hazard ratio was 1.01. Male sex was reported as an independent risk factor for chronic kidney disease as the incidence rates of chronic kidney were more significant in men than women in this study.

In conclusion, the study data suggest that the higher lifetime risk of chronic kidney disease in people with younger age of onset/diagnosis is driven by more than just the prolonged duration of the disease. Therefore, young age at diagnosis is concluded to amplify the effect of increasing diabetes duration on an increased risk of chronic kidney disease. Strengths of the study include the large sample size and the longevity of the follow-up period. Weaknesses include the small population analyzed as the Chinese population is not generalized to other people and ethnicities. More studies would need to be conducted to have more of the world’s population to test this hypothesis further.

Practice Pearls:

• Chronic kidney disease is one of the major complications associated with diabetes and studies show chronic kidney disease develops in approximately 50% of people with diabetes throughout the course of life
• Young age at diagnosis amplifies the effect of increasing diabetes duration on increased risk of chronic kidney disease.
• More studies would need to be conducted to include more of the world’s population to further test this hypothesis

1. Wu, H., Lau, E.S.H., Yang, A.et al. Young age at diabetes diagnosis amplifies the effect of diabetes duration on risk of chronic kidney disease: a prospective cohort study. Diabetologia 64, 1990–2000 (2021). https://doi.org/10.1007/s00125-021-05494-4

Erica Hicks, PharmD Candidate 2022, South College School of Pharmacy