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ESRD in Type 1 Diabetes: What Has Changed?

Feb 17, 2018
 

Although the risk of end-stage renal disease remains high for individuals with type 1 diabetes, lifetime likelihood of ESRD has substantially decreased over the last 50 years.

Owing to better treatment options and more stringent monitoring overall, nowadays the risk of diabetic nephropathy is smaller than what it once has been. Currently, there is contradictory evidence of how gender is related to ESRD. Some studies claim that male gender carries a higher risk of renal disease, such as the study conducted by A. Andersen et al. While other studies, such as a study by V.Harjutsalo and colleagues, report the risk to be equal between the genders in instances where diabetes is diagnosed during childhood, yet in instances were diabetes is developed after puberty, male sex still bares a higher risk. Investigators in Finland focused on determining how the trends of end-stage renal disease have changed over the last 50 years, and in addition, they focused on evaluating the effect of age, sex, and time of diabetes diagnosis on life-long incidence of ESRD. The results of their nationwide population-based study are presented below.

Diabetes in Finland Study (FinDM) and nationwide registry of entitlements were utilized to identify subjects with type 1 diabetes for enrollment into the study. All individuals with diabetes in Finland receive a full reimbursement for insulin prescriptions; therefore, the registries contain a complete list of patients with diabetes. In order to distinguish between type 1 and type 2 diabetes, researchers utilized Finnish Social Insurance Institution prescription database. All subjects who used an oral medication within 1 year of insulin therapy were labeled to have type 2 diabetes and were excluded from the study. Individuals were followed from commencement of insulin therapy until the start of renal replacement therapy at which point they were considered to have developed ESRD, until death, or until end of follow-up.

The study enrolled close to 30,000 individuals below the age of 30 with T1D from 1965 until 2012.  Out of these, 58% were males. For patients who were diagnosed between the years of 1965 and 1969, the trend of ESRD increased 15 to 25 years following the diagnosis, after which it stayed consistent. As years passed, the incidence of ESRD decreased. Researchers reported the cumulative ESRD risk for all patients in the cohort to be 2.2% 20 years following the diagnosis and 7% 30-years post-diagnosis. However, when they excluded patients who were diagnosed with diabetes prior to 1980, the cumulative risk decreased to 1.3% and 4.4% 20 and 30 years following the diagnosis, respectively. Men were more likely to develop ESRD than females, 7.7% vs. 6%.  Incidence of ESRD was lowest for individuals diagnosed with diabetes before they were five years of age; similar results were seen even after excluding individuals diagnosed with diabetes prior to 1980. Nonetheless, patients who were diagnosed with diabetes between the ages of 25 and 29 had incidence of diabetes as 3.5% for males and 2.1% for females, while these numbers were significantly higher for individuals diagnosed from birth to 24 years of age, 12.1% in males and 13.2% in females.

Strong clinical evidence is available that shows the optimized glucose control, better blood pressure regulation and treatment of dyslipidemia decrease the risk of renal disease, and therefore, the risk of ESRD. So, the investigators concluded the the trend of ESRD is declining over the years and has occurred mostly due to changed insulin regiment (i.e. multiple injections per day), use of RAS inhibitors, and guideline-directed statin therapy. Moreover, they report the risk of ESRD to be lowest in females and in those who are diagnosed with diabetes before the age of 5. Cumulative incidence of ESRD has a potential to decrease even further due to advances in medicine that have been occurring for the last 20 years.

Practice Pearls:

  • ESRD incidence has decreased over the last 50 years.
  • Men are more likely to develop ESRD than women, 7.7% vs. 6%.
  • Patients who are diagnosed with diabetes before age of 5 are least likely to have ESRD.
  • Both males and females diagnosed with DM between the ages of 25 and 29 have the highest chances of developing ESRD.

References:

Jaakko Helve, Reijo Sund, Martti Arffman, et al. “Incidence of End-Stage Renal Disease in Patients With Type 1 Diabetes.” Diabetes Care. 2017. http://care.diabetesjournals.org/content/early/2017/12/19/dc17-2364.long.  Accessed Jan 2018.

A Andersen, J Christiansen, et al. “Abstract: Diabetic nephropathy in Type 1 (insulin-dependent) diabetes: An epidemiological study.” Diabetologia 1983. https://www.ncbi.nlm.nih.gov/pubmed/6363177.  Accessed Jan 2018.

V Harjutsalo, C Maric, C Forsblom, et al. “Sex- related differences in the long-term risk of microvascular complications by age at onset of type 1 diabetes.” Diabetologia 2011.  https://link.springer.com/article/10.1007/s00125-011-2144-2. Accessed Jan 2018.

Lamija Zimic, PharmD(c), University of South Florida, College of Pharmacy