Korean patients with type 2 diabetes (T2D) who had reduced levels of estimated glomerular filtration rate and/or proteinuria, 2 hallmarks of diabetic kidney disease, had a greater risk of developing Parkinson disease.
Affecting 1 in 11 adults worlwide, T2D shares several pathophysiological similarities with PD, including mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, and altered metabolism.
Prior studies have suggested a potential association between the 2 age-related chronic diseases, in which the prevalence of diabetic kidney disease (DKD), one of the major complications of diabetes, additionally poses significant risks for PD development. An increasingly significant prevalence of DKD has been reported in Korea.
“Classically, proteinuria (PU) has been considered a hallmark of DKD, which necessarily precedes a decrease in estimated glomerular filtration rate (eGFR). However, accumulating evidence has shown that some patients with progressive renal decline have no PU,” explained the researchers. “To date, effects of PU and non-PU DKD [nonproteinuric DKD] on PD development have not been reported yet.”
Deriving data from the Korean National Health Insurance Service database, they sought to assess whether risk of PD differed among Korean adults with T2D based on PU and eGFR levels. A total of 2,217,326 patients with T2D who underwent regular health check-ups from 2009 to 2012 were included in the analysis and followed until 2018. Participants were classified into 4 groups:
For the analysis, cumulative incidence of PD was calculated using a Cumulative Incidence Competing Risk estimate, Cox proportional hazards regression analysis was performed to evaluate risk for PD depending on the DKD status, and subgroup analyses were performed according to age (< 65 vs ≥ 65 years), sex, and body mass index (BMI; < 25 kg/m2 vs ≥ 25 kg/m2).
Overall prevalence was 83.3% for no-DKD, 5.0% for PU DKD with normal eGFR, 10.1% for non-PU DKD, and 1.6% for PU DKD with reduced eGFR.
“Indicators for severe diabetes, such as duration of diabetes, proportion of insulin usage, polypharmacy, and proliferative diabetic retinopathy were the most pronounced in the PU DKD with reduced eGFR group,” said the researchers.
During a median follow-up of 7.2 years, 16,079 cases of PD were detected among the study cohort. Cumulative incidence of PD was significantly higher in the reduced eGFR group than in the normal eGFR group (P < .001), in which the PD incidence rates in patients with no-DKD, PU DKD with normal eGFR, non-PU DKD, and PU DKD with reduced eGFR were 0.88, 1.00, 1.93, and 1.94 per 1000 person-years, respectively.
Compared with patients in the no-DKD group, the risk of PD was elevated among those in the PU DKD with normal eGFR (adjusted HR [aHR], 1.10; 95% CI, 1.01-1.21; P = .0091), non-PU DKD (aHR, 1.15; 95% CI, 1.09-1.21; P < .0001), and PU DKD with reduced eGFR (aHR, 1.23; 95% CI, 1.09-1.39; P < .0001) groups, after adjusting for age, sex, social factors, and additional clinical characteristics.
Although the incidence rate of PD was higher in patients 65 years and older than in those younger than 65 years, the effect of DKD on PD development was more prominent in the latter age group (P for interaction < .0001). No significant interactions of DKD status with sex and BMI were observed regarding PD development.
“More attention should be paid to PD development in patients with DKD, even in a younger-aged population,” concluded the study authors. “Strategies to prevent the progression of DKD among T2D might help mitigate the risk of PD development.”
Lee SE, Yoo J, Choi HS, Han K, Kim KA. The risk of Parkinson’s disease according to diabetic kidney disease status. Parkinsonism Relat Disord. 2022 Jul;100:13-18. doi:10.1016/j.parkreldis.2022.05.021