High Prevalence of Undiagnosed Insulin Resistance in Non-Diabetic Subjects with Parkinson's Disease.

BACKGROUND: Reduced glucose tolerance has been long recognized as a potential risk factor for Parkinson's disease (PD), and increasing scrutiny is currently being placed on insulin resistance (IR) as a pathologic driver of neurodegeneration. However, the prevalence of IR in PD is unknown. OBJECTIVE: To determine IR prevalence in non-diabetic patients with PD and to correlate IR with other metabolic indicators, motor and non-motor symptoms (NMS) of PD, and quality of life (QoL). METHODS: Non-diabetic patients with a diagnosis of PD were identified and tested for fasting insulin, fasting glucose, and HbA1c. Patients were also offered to take a battery of clinical tests (MoCA, NMSQ, and PDQ-39) and had their PD medications, height, weight, and other demographic features recorded. IR was defined as HOMA-IR≥2.0 and/or HbA1c≥5.7. IR abnormalities were correlated with BMI and demographic features, in addition to motor and NMS. RESULTS: 154 subjects (109 M, 45F, mean age 67.7±10.5) were included in this study. Mean HOMA-IR was 2.3±1.8. Ninety out of 154 (58.4%) subjects had abnormal IR. IR was more frequent in overweight and obese subjects (61.1% and 82.8% respectively) than normal weight subjects (41.5%). Multivariate analysis showed that BMI was the only significant predictor of IR (p < 0.0001). There was no significant correlation between HOMA-IR and MoCA, PDQ-39, and NMSQ scores. CONCLUSIONS: IR is prevalent in PD and it correlates with BMI. A correlation between IR with cognitive and QoL measures cannot be determined on the basis of this sample.

Constipation is reduced by beta-blockers and increased by dopaminergic medications in Parkinson's disease.

BACKGROUND: Constipation is one of most frequent non-motor symptoms of Parkinson's disease (PD) and it may precede the clinical diagnosis of PD by years, with negative effects on quality of life. In contrast to motor features, levodopa is ineffective and possibly detrimental on constipation. Treatment of constipation in PD is non-specific and frequently unsuccessful. Stemming from a clinical observation of unexpected relief of bothersome constipation, abdominal bloating and pain after treatment with the beta-blocker carvedilol in one patient, we have evaluated the association between the use of beta-blockers and the presence of constipation in a large, unselected PD cohort. METHODS: Retrospective review of the medical records of every patient with a diagnosis of PD seen in the Movement Disorders clinic at Cedars-Sinai Medical Center from October 2010 to April 2014. RESULTS: 341 medical records with a primary diagnosis of PD were reviewed, 336 of which contained information about constipation. Overall, 205/336 patients (61%) reported constipation. Among the 66 subjects treated with beta-blockers at the time of the encounter of record, only 28 (42.4%) reported constipation. By comparison, among the 270 subjects not treated with beta-blockers, 177 (65.5%) had constipation (χ(2) test p value = 0.001). Multivariate logistic analysis showed an odds ratio (OR) of 0.293 for beta-blockers (95% C.I. 0.161-0.535, p = 0.0001), 2.287 for levodopa (95% C.I. 1.271-4.117, p = 0.006) and 1.805 for dopamine agonists (95% C.I. 1.039-3.136, p = 0.036). CONCLUSIONS: Beta-blockers are associated with a lower risk of constipation, while dopaminergic treatments appear to increase risk of constipation.