For this analysis, Warner and colleagues linked English national Hospital Episode Statistics and mortality data from 1999 to 2011. The team constructed a cohort of patients who were admitted for hospital care with a coded diagnosis of type 2 diabetes, comparing them with a reference group of people who did not have a diabetes diagnosis. Excluded were people diagnosed with cerebrovascular disease, vascular parkinsonism, drug-induced parkinsonism, and normal pressure hydrocephalus.
The researchers searched the records of 2,017,115 individuals in the type 2 diabetes group and 6,173,208 people in the reference group for any later hospital admission with a diagnosis of PD. Patients in the diabetes cohort were more likely to have a subsequent PD diagnosis (HR 1.32, 95% CI 1.29-1.35; P< 0.001) than patients in the reference cohort. The relative increase was greater among patients with complicated type 2 diabetes (HR 1.49, 95% CI 1.42-1.56) and rose substantially among younger people with diabetes (HR 3.81, 95% CI 2.84-5.11 for the age group 25–44).
The greater magnitude of risk in young people may occur when genetic factors might exert more of an effect, the researchers noted; more than 400 genes identified through genome-wide association studies have been linked to both conditions. The association in elderly patients may stem from disrupted insulin signaling secondary to lifestyle and environmental factors that result in cumulative pathogenic brain changes, the researchers added.
“Whether attributable to genetic predisposition, environmental factors, or both, disrupted brain insulin signaling could lead to shared dysregulated cellular pathways including neuroinflammation (microglia activation, production of pro-inflammatory cytokines), mitochondrial dysfunction, and increased oxidative stress ultimately promoting synuclein aggregation and contributing to the development of PD.”