Diabetes Tied to Parkinson’s Risk, More Rapid Disease Progression

Diabetes mellitus (DM) is associated with Parkinson’s disease (PD) development, as well as more severe symptoms and more rapid disease progression, new research suggests.

In a systematic review, patients with type 2 diabetes were 34% more likely to develop PD than those without comorbid DM. In addition, patients with both conditions had significantly worse scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) and worse cognitive performance.

Together, the results suggest that “DM may be a facilitating factor of neurodegeneration,” investigators led by Gennaro Pagano, MD, PhD, expert medical director at Roche Pharma Research and Early Development, in Basel, Switzerland, write.

The findings were published in a recent issue of the Journal of Parkinson’s Disease.

Unanswered Questions

Researchers have long proposed a potential relationship between diabetes and PD. However, case-control studies have yielded conflicting results about this relationship ― and previous systematic reviews have failed to clarify the question.

In the current systematic review and meta-analysis, investigators identified relevant studies in databases such as MEDLINE/PubMed, Cochrane CENTRAL, and Scopus.

Eligible studies reported prevalence of DM in patients with PD, reported incidence of PD in those with and those without DM, and analyzed Parkinson’s phenotype and progression in those with and those without DM.

The researchers identified 3829 articles in their initial search, evaluated 90 articles in detail, and included 43 studies in their analysis. Study quality was judged to be moderate or good, and the investigators did not find significant publication bias.

Twenty-one studies that encompassed 11,396 patients were examined to determine prevalence of DM in PD. This prevalence was calculated to be 10.02%, which is similar to the global prevalence of 9.3% reported in 2019.

The researchers also analyzed 12 cohort studies that included 17,797,221 patients to calculate risk for PD in patients with comorbid diabetes. The pooled summary odds ratio (OR) for incident PD among patients with type 2 diabetes was 1.34.

The evaluation of the effect of diabetes on PD severity was based on 10 studies that included 603 patients with both diseases. Because data on motor symptoms were not available for all studies, the researchers considered Hoehn and Yahr stage, UPDRS score, and cognitive impairment.

Patients with both conditions had a worse Hoehn and Yahr stage (standardized mean difference [SMD], 0.36; P < .001), and higher UPDRS score (SMD, 0.60; P < .001). In seven of the 10 studies, diabetes was associated with worse cognitive performance in patients with PD.

Mechanisms Uncertain

The mechanisms of the effect of diabetes on risk for and severity of PD are uncertain, but the researchers have developed hypotheses.

“Overlapping mechanisms between insulin resistance, mitochondrial disfunction, oxidative stress, and alpha-synuclein expression could influence the development of the neurodegeneration process,” they write.

Because the current analysis demonstrated a trend toward more pronounced cognitive decline in patients with the comorbidities, clinicians should pay particular attention to the progression of motor and cognitive symptoms in patients with these diseases, the investigators note.

“[A]dditional studies are needed in order to better define the clinical phenotype of PD-DM patients and explore the role of antidiabetic drugs on PD progression,” they write.

They add that future studies also are needed to evaluate whether antidiabetic drugs might reduce risk for PD in these patients.

The investigators note several limitations of their research. In many of the studies they examined, for example, diagnostic criteria of type 2 diabetes and PD were based only on medical records or self-reported health questionnaires. The diagnoses were rarely confirmed.

In addition, not all studies clearly stated that their populations presented with type 2 diabetes. Finally, patients with diabetes may be at increased risk for cardiovascular death, which could affect follow-up related to the development of PD, the investigators note.

Pagano is an employee of F. Hoffmann-La Roche.

J Parkinsons Dis. 2021;11:1585-1596. Abstract

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