This observational study reveals important long-term trends of type 1 diabetes in regard to kidney function & end stage renal disease (ESRD). Subjects were followed for up to 42 years:
Rates of ESRD are lower when children are diagnosed with DM1 before age 10 than during puberty. Kidney disease is less prevalent in females than males. Diabetic nephropathy peaks at 25 years after diagnosis and remains stable subsequently.
These findings could be shared with parents at the time of child's type 1 diabetes diagnosis.
End-stage renal disease (ESRD) is one of the most severe complications in type 1 diabetes. We aimed to estimate the cumulative incidence of ESRD in individuals with childhood-onset type 1 diabetes followed for up to 42 years.
Data were based on the nationwide, population-based Norwegian Childhood Diabetes Registry and included case patients with new-onset type 1 diabetes (age <15 years) who had received a diagnosis during the periods 1973–1982 and 1989–2012. Follow-up took place until the development of ESRD, death, emigration, or 30 November 2015. We estimated the cumulative incidence of ESRD by linking to the Norwegian Renal Registry.
Among the 7,871 patients, representing 147,714 person-years of follow-up, ESRD developed in 103 individuals (1.3%). The mean time from the diagnosis of diabetes to the development of ESRD was 25.9 years.
The cumulative incidence of ESRD was 0.7% at 20 years’ diabetes duration, 2.9% at 30 years’ duration, and 5.3% at 40 years’ duration.
The risk of the development of ESRD was lower in women than in men (hazard ratio [HR] 0.61) and higher in individuals in whom diabetes had been diagnosed at 10–14 years of age compared with those in whom it was diagnosed before 10 years of age (HR 1.29)
We did not identify any significant difference in the risk of the development of ESRD between those in whom diabetes was diagnosed in 1973–1982 and in 1989–2012 (HR 0.80)
We report a very low incidence of ESRD among patients with childhood-onset diabetes in Norway. The risk was lower in women compared with men and in individuals in whom diabetes was diagnosed at a younger age.
More from the publication:
Diabetic nephropathy is one of the most serious complications of type 1 diabetes, and the presence and severity of kidney disease is closely linked to mortality. The incidence of end-stage renal disease (ESRD), defined as the need to start renal replacement therapy due to chronic renal failure, has been reported from several regions, and there seem to be substantial geographic variations. Studies from Finland and Sweden have indicated a lower incidence of ESRD among children in whom diabetes was diagnosed before age 5 years or 10 years compared with those in whom it was diagnosed up to age 34 years. Receiving a diagnosis in the pubertal years might give a higher risk of the development of ESRD. A declining incidence of ESRD in individuals with type 1 diabetes by more recent year of diagnosis has been reported in studies comparing the incidence in cohorts of individuals with childhood-onset type 1 diabetes in previous decades compared with cohorts in which it was diagnosed more recently. This is in line with improved diabetes care, including better renoprotective treatment during the last 3 decades
In Norway, the incidence of childhood-onset type 1 diabetes is high, but the incidence of ESRD in childhood-onset type 1 diabetes has not yet been assessed. To our knowledge, few studies have assessed the incidence of ESRD in nationwide cohorts with type 1 diabetes that were followed for >40 years. Therefore, the aim of this study was to estimate the cumulative incidence of ESRD by sex, age at diagnosis, and year of diagnosis of diabetes in individuals with up to 42 years of follow-up.
In this study, we found that the incidence of ESRD in individuals with childhood-onset type 1 diabetes in Norway was low: 0.7% at 20 years after diagnosis, 2.9% at 30 years, and 5.3% at 40 years. The risk of the development of ESRD was lower in women compared with men and in those in whom type 1 diabetes had been diagnosed at a younger age.
We have shown earlier that all-cause mortality in these cohorts was elevated 3.6 times compared with the general population in Norway. The cumulative mortality at 35 years after the diagnosis of diabetes was 9.1%. Acute complications were the leading cause of death before 30 years of age; after 30 years of age, cardiovascular death was predominant.
The cumulative incidence of ESRD in individuals with type 1 diabetes has been reported from several countries; for instance, it was estimated to be 9–11% at 25 years after the diagnosis of diabetes in the U.S. and 7.8% at 30 years in Finland. Compared with these studies, we report a very low cumulative incidence of ESRD. However, our estimates are in line with results from a Swedish study that included individuals in whom type 1 diabetes had been diagnosed in 1977–1995. It is known that the incidence of ESRD is lower in Western European countries compared with, for instance, the U.S. According to a Norwegian population-based study, this could not be explained by the lower prevalence of chronic kidney disease, but rather by the lower risk of ESRD among individuals with chronic kidney disease. We believe that the results we report are influenced by several factors. The effect of near-normoglycemia on diabetic nephropathy was shown in the Oslo Study in 1986 and resulted in recommendations of intensified insulin treatment at an early point in Norway.
Also, national guidelines for the use of ACE inhibitors in normotensive patients with type 1 diabetes with microalbuminuria were available in 1995, although they had been used by many clinicians at an earlier point. We also believe that the low risk of ESRD may be related to the Norwegian health care system. Equal health care is provided for all patients in Norway without extra cost, independent of socioeconomic status. A Norwegian study reported overt nephropathy in only 7.8% of individuals at 19–30 years after the diagnosis of diabetes in the cohort in whom childhood-onset type 1 diabetes was diagnosed in 1973–1982. Another important aspect is the fact that in the Norwegian and Swedish study populations no patients had received a diagnosis of type 1 diabetes before 1973 and therefore probably have profited more from modern diabetes therapy, including renoprotective treatment, than patients who had received a diagnosis in earlier decades.
Our data support the more recent reports from Sweden, Finland, and the Diabetes Control and Complications Trial showing that the peak in the incidence rate of diabetes nephropathy has been delayed compared with earlier studies from Denmark. The peak we report was at ∼25–29 years after the diagnosis of diabetes; thereafter, it seemed to remain constant up to 42 years of follow-up. Our study indicates that the peak incidence of ESRD has been delayed or was probably reached at 25–29 years after the diagnosis of diabetes.
We observed a higher risk of ESRD in men with type 1 diabetes compared with women with type 1 diabetes. The cumulative incidence curve of ESRD for men and women seemed to diverge after 20 and 25 years diabetes duration. The higher risk in men is in accordance with some studies, but not all. It has been suggested that the sex difference could be explained by modifiable risk factors like blood pressure and lifestyle or renal physiology. There might also be sex differences in the patients’ use of the health care system that may influence the development of long-term complications; for instance, women may use the available health care more frequently and be more compliant with the suggested treatment than men.
It has been indicated that young age at diagnosis of diabetes might prolong the time until the development of chronic complications. Our results support this statement. We observed a 39% lower risk of the development of ESRD if a diagnosis of diabetes had been received before 10 years of age compared with a diagnosis being received at 10–14 years of age. Both Swedish and Finnish studies have reported a lower risk of or a delay in the development of ESRD associated with being diagnosed with type 1 diabetes before 10 years of age compared with being diagnosed up to 34 years of age. We report a higher risk of ESRD if individuals had received a diagnosis of type 1 diabetes at 10–14 years of age, which might be a result of both psychological and endocrine factors that are important during the pubertal period. It is suggested that hormonal changes and poor glycemic control can accelerate the development of chronic complications. Also, receiving a diagnosis in puberty, a period in life represented by large psychological changes, might affect how well the patient adheres to diabetes treatment. This age is a particular challenge to the health care system to achieve good diabetes care in the patients.
In conclusion, we report a risk of the development of ESRD in individuals in Norway with childhood-onset type 1 diabetes that was lower than that reported in several other countries. Receiving a diagnosis of diabetes before the pubertal period seems to imply lower risk, or a delay, in the development of ESRD.