The Impact of Type 2 Diabetes in Parkinson's Disease

Abstract

A BS TRACT: Background: Type 2 diabetes (T2DM) is an established risk factor for developing Parkinson's disease (PD), but its effect on disease progression is not well understood. Objective: The aim of this study was to investigate the influence of T2DM on aspects of disease progression in PD. Methods: We analyzed data from the Tracking Parkinson's study to examine the effects of comorbid T2DM on PD progression and quality of life by comparing symptom severity scores assessing a range of motor and nonmotor symptoms. Results: We identified 167 (8.7%) patients with PD and T2DM (PD + T2DM) and 1763 (91.3%) patients with PD without T2DM (PD). After controlling for confounders, patients with T2DM had more severe motor symptoms, as assessed by Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III (25.8 [0.9] vs. 22.5 [0.3] P = 0.002), and nonmotor symptoms, as assessed by Non-Motor Symptoms Scale total (38.4 [2.5] vs. 31.8 [0.7] P < 0.001), and were significantly more likely to report loss of independence (odds ratio, 2.08; 95% confidence interval [CI]: 1.34-3.25; P = 0.001) and depression (odds ratio, 1.62; CI: 1.10-2.39; P = 0.015). Furthermore, over time, patients with T2DM had significantly faster motor symptom progression (P = 0.012), developed worse mood symptoms (P = 0.041), and were more likely to develop substantial gait impairment (hazard ratio, 1.55; CI: 1.07-2.23; P = 0.020) and mild cognitive impairment (hazard ratio, 1.7; CI: 1.24-2.51; P = 0.002) compared with the PD group. Conclusions: In the largest study to date, T2DM is associated with faster disease progression in Parkinson's, highlighting an interaction between these two diseases. Because it is a potentially modifiable metabolic state, with multiple peripheral and central targets for intervention, it may represent a target for alleviating parkinsonian symptoms and slowing progression to disability and dementia.

Type 2 Diabetes and Parkinson's Disease: A Focused Review of Current Concepts

“…45 The most recent and largest study included 167 patients with PD and T2D from the Tracking Parkinson's study, and after controlling for confounders, it was observed that they were more likely to report loss of independence (OR: 2.08) and depression (OR: 1.62) and develop substantial gait impairment (HR: 1.55) and mild cognitive impairment (HR: 1.7). 46 Those with T2D also had worse nonmotor symptom scores, largely driven by sleep, mood, and memory issues. 46 In addition, survival from diagnosis was markedly reduced in a cohort of neuropathologically confirmed PD cases in whom T2D preceded the onset of motor symptoms.…”

“…46 Those with T2D also had worse nonmotor symptom scores, largely driven by sleep, mood, and memory issues. 46 In addition, survival from diagnosis was markedly reduced in a cohort of neuropathologically confirmed PD cases in whom T2D preceded the onset of motor symptoms. 47 Although vascular complications of T2D such as neuropathy and ischemic heart disease may exacerbate motor impairment in PD, biomarker studies have shown that PD patients with comorbid diabetes have higher serum neurofilament light chain levels independent of age, BMI, and other vascular risk factors, as well as lower striatal dopamine transporter binding and higher CSF tau levels, 41,48,49 suggesting that increased neuroaxonal damage is the substrate for faster PD progression in those with T2D.…”

“…178 These findings suggest that hyperglycemia may directly contribute to the more severe clinical phenotype and higher L-dopa doses observed in PD patients with T2D. 38,46 Hyperglycemia also promotes glycation, which is a nonenzymatic series of reactions between reducing sugars and macromolecules, leading to the formation of advanced glycation end products (AGEs). Different amino acids such as lysine and arginine can be glycated, changing the chemical properties of the protein.…”

“…206 Given that depression is also associated with reduced serum BDNF, 207 this may contribute to the increased rates of depression observed in PD patients with T2D. 46 Physical activity may also mitigate against T2D-associated inflammation as it has been shown to reduce circulating inflammatory cytokines, including CRP, IL6, and TNF-α, in older people. 208…”

Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders

“…T2DM is also linked to another common neurodegenerative disorder, Parkinson’s disease (PD) [ 9 , 10 ]. Epidemiological studies have shown that patients with T2DM have a higher risk of PD and faster progression of PD symptoms [ 11 , 12 ]. In addition to neurodegenerative disorders, T2DM is associated with psychiatric disorders, too.…”