Correlation of Parkinson’s disease with diabetes mellitus, obesity, dyslipidemia and their association with severity of disease

Introduction . The present study aimed to investigate Parkinson’s disease with diabetes, obesity, dyslipidemia and their relationship with disease severity. Methods . In this case-control study, all patients referred to Rouhani Hospital in Babol with clinical diagnosis of Parkinson’s disease were excluded in the case study and the control group was selected from the patients of the clinic and neurology ward. Parkinson’s disease diagnosis was based on common criteria and the four classic sign (symptoms) of the disease. Results . Obesity in patients with Parkinson’s disease was 65.4%, which was higher than the control group with 34.6%. The association between obesity and Parkinson’s disease was significant (OR = 2.14 and p = 0.01). Diabetes was 59.7% in pa - tients with Parkinson’s disease and was 40.3% in patients in the control group that diabetes is also associated with the incidence of Parkinson’s disease (OR = 2.59 and p <0.001). 59.6% of patients with Parkinson’s disease had anemia, while 40.4% of the control group had anemia, and the relationship between anemia and Parkinson’s disease was significant (OR = 1.78 and p = 0.02). 55.5% of patients with Parkinson’s disease had dyslipidemia, while 44.5% of the control group had dyslipidemia, and the relationship between dyslipidemia and Parkinson’s disease was significant (OR = 2.09 and p = 0.004). Conclusion . In summary, this study showed that Parkinson’s is associated with obesity, diabetes, anemia and dyslipidem - ia. The above cases were effective as risk factors for Parkinson’s disease and how it requires further research in this area.


IntroduCtIon
Neurological diseases are among the most im por tant causes of disability, especially in the elderly, and neurodegenerative disorders are among the most important causes of these diseases [1]. Parkinson's disease is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons in the Pars Compacta in Substantia Nigra. The disease includes a wide range of movement disorders (slow ness of movement, resting tremor, muscle stiffness) and nonmovement (autonomic problems, pain, depression, dementia, gastrointestinal problems, and sleep disorders) [2]. Parkinson's disease is the most common degenerative brain disease after Alzheimer's disease. Due to its increasing incidence in old age and considering the increasing ageing rate in society, this disease is one of the most common causes of physical and mental disabilities in the elderly. The prevalence of Parkinson's disease and the number of cases of disability and the resulting mortality rate are also increasing rapidly [1]. The main cause of this disease is unknown, but many studies are underway to find the causes of this disease or the factors affecting its occurrence or exacerbation or the existence of concomitant or associated diseases [3]. The preva lence of Parkinson's disease is 12 per 1000, and its global prevalence is about 10 million people [3,4]. Parkinson's disease's global prevalence increases steadily and uniformly with age, rising from 40 per 100,000 to 1,900 per 100,000 over 80 for those aged 4049 [5]. Also, the number of Parkinson's patients is expected to increase steadily in the future, and it is estimated that by 2030, approximately 9million people worldwide will suffer from the disease [6]. In Iran (Tehran), the standardized prevalence based on age and sex distribution was 222.9 per 100,000 people and based on the standard population of the World Health Organization, it was estimated at 285 per 100,000 people, which is considered a moderate to high prevalence [7]. However, the main clinical manifestations of Parkinson's disease, the most im por tant of which are movement disorders, including tremor, hyperkinesia, rigidity, and impaired postural stability and gait [8]. However, these symptoms usual ly occur in the late stages of the disease. After the destruction of 80% of the dopaminergic neurons of the substantia nigra in the midbrain and the accumulation of alphasynuclein, the main consti tuent of Lewis, the main pathological indicator of the disease [9]. The main group manifestations are non motile symptoms in Parkinson's disease, which mani fest earlier than motor manifestations and cause more disability in these patients [10]. Another critical issue is the association of other diseases with this disease, which may be effective in developing Parkinson's disease, or these diseases may play a role in the development of Parkinson's disease. Anemia [11,12] and diabetes [13,14], obesity [15,16] and dyslipidemia [17,18] are important disorders that have been reported in Parkinson's disease. Despite much research on Parkinson's disease, the disease's root cause is still unknown, but much research is still underway to find the cause or causes of the disease or the factors influencing its occurrence or exa cer bation or to identify comorbidities. Because the types of diseases and their extent (due to the differences in the epidemiology of Parkinson's disease and these diseases in our region) can differ from these studies' results, this study was designed. If the prevalence of comorbidities is confirmed, other causes should be studied in other studies. However, if these cases are identified, the information obtained can be used to prevent or treat Parkinson's disease or comorbidities.

MAtErIALS And MEtHodS
The study was a case control study.

Research community
According to the formula inclusion criteria (having a diagnosis of Parkinson's disease), and exclusion (patients with Parkinson's syndrome due to neuroleptics or Parkinson's syn drome with specific causes that were not part of pri mary idiopathic Parkinson's disease, Parkinson's patients with renal failure and liver failure and drug supplementation as well as patient dissatisfac tion) were selected. Sampling was by census method and 150 patients referred to Ayatollah Rouhani Hos pital in Babol with a confirmed clinical diagnosis of Parkinson's disease were included in the case group, and 150 healthy patients were included in the study as a control group. The mean age of patients was 68.91±10.07 years (minimum age 43 and maximum age 99 years). Out of 300 subjects, 195 (65.0%) were male and 105 (35.0%) were female.

Data collection method
The definitive diagnosis of Parkinson's disease and its varying degrees of severity was made by the neurologist who performed the project. At the time of examination, the priority of each of the four clin ical symptoms was determined. The control group was selected from the clinic and neurology ward pa tients who were not diagnosed with Parkinson's dis ease in the history and clinical examination. Parkin son's patients and the control group were divided into three age groups: under 60, between 6080, and over 80 years. Diagnosis of anemia, diabetes, obesity and dyslipidemia in Parkinson's patients who en tered the project was performed by an internal medicine specialist based on common and classic criteria for these diseases. The weight of the people was measured using the Seka digital scale with the least clothes and without shoes and with an accura cy of one tenth of a kilogram and their height was measured with the help of a height meter with an accuracy of five tenths of a centimeter. Calculation of BMI was obtained through height (square meter to the power of 2) divided by weight (kg). In this study, a BMI above 30 was considered obesity. To de termine the concentration of serum lipids and lipo proteins and fasting blood sugar in patients and controls, after 12 hours of fasting, first from the an terior vein of the arm, blood samples in the same conditions in terms of environment and time (7:30 to 9:30 in the morning (to separate the serum, the samples were immediately centrifuged and imme diately transferred to the laboratory of the hospital (Ayatollah Rouhani) in Babol. Measurement of glu cose, cholesterol and triglyceride, with enzymatic methods and measurement of dense lipoprotein based on serum deposition with dextran sulfate and using Pars test kit, made in Iran. Diagnosis of diabe tes with fasting glucose ≥7.0 mmol/L (126 mg/dL) or with glucose level two hours after feeding ≥11.1 mmol/L (200 mg/dL) HbA1C ≥6.5%. Diagnosis of dys lipidemia based on plasma triglyceride level above 200 mg/dL and total cholesterol above 200 mg/dL and high density cholesterol less than 40 mg/dL 10 low density cholesterol above 150 mg/dL has been deciliters. Regarding laboratory criteria for diagnos ing anemia in this study, the amount of hemoglobin was 16±2 g/l, and hematocrit was 47.6±6% in men and hemoglobin was 14.2±2 g/l hematocrit was 42 ± 6% in women and was considered normal.

Data analysis method
Data were analyzed using SPSS V.22 software. Chisquare and Mann Whitney tests and logistic re gression were used. Pvalue less than 0.05 were con sidered significant.
Scientific accuracy and validity of data Data were carefully collected and recorded. Sev eral trained individuals examined the validity of the measurement tool in this study (checklist).

rESuLtS
Examining the relationship between baseline cha racteristics in patients with and without Parkinson's disease, it was found that obesity in patients with Parkinson's disease was 65.4%, which was higher than the control group with 34.6%. The relationship between obesity and Parkinson's disease was sig nificant (OR = 2.14 and p = 0.01). Diabetes was 59.7% in patients with Parkinson's disease and 40.3% in the control group. Diabetes is also associated with Parkinson's disease (OR = 2.59 and p <0.001). 59.6% of patients with Parkinson's disease had anemia, while 40.4% of the control group had anemia, and the relationship between anemia and Parkinson's disease was significant (OR = 1.78 and p = 0.02). 55.5% of patients with Parkinson's disease had dyslipidemia, while 44.5% of the control group had dyslipidemia, and the relationship between dyslipidemia and Parkinson's disease was significant(OR = 2.09 and p = 0.004) ( Table 1).
Based on Table 2, the studied quantitative vari ables were compared between Parkinson's patients and healthy individuals. So that body mass index, fasting blood sugar, glycosylated hemoglobin, triglyc eride, cholesterol and low density lipoprotein were significantly higher in patients with Parkinson's dis ease. Also, hemoglobin, hematocrit and high density lipoprotein were lower in patients with Parkinson's  disease, and this significant difference was reported ( Table 2). The Table 3 shows the multivariate logistic regres sion analysis results based on which the obesity of patients was a risk factor for Parkinson's disease (OR = 2.25 and p = 0.01). In the case of diabetes, based on the odds ratio, which is more than one, shows that diabetes is also a risk factor for Parkinson's disease (OR = 2.84 and p <0.001). Anemia is also a risk factor for Parkinson's disease (OR = 2.10 and p = 0.006). Mul tivariate analysis results showed that dyslipidemia is also a risk factor for Parkinson's disease (OR = 1.88 and p = 0.02).
In the study of Parkinson's disease severity based on Hoehn and Yahr staging scale in 150 patients in the case group, 4 patients (2.7%) Stage 1, 19 patients (12.7%) stage 1.5, 43 patients (28.7%) stage 2, 28 (18.7%) were stage 2.5, 37 (24.7%) were stage 3, 17 (11.3%) were stage 4 and 2 (1.3%) were stage 5 ( Figure 1). were moderate to severe, and two patients (1.3%) were in the severe disease group (Figure 2).  The subjects' age was divided into three age groups under 60, 60 and 80 and more than 80 years to increase the analysis's accuracy. In general, 60 people (0.20%) in the age group under 60 years, 207 people (69.0%) in the age group between 60 to 80 years and 33 people (0.11%) in the age group more than They were 80 years old (Figure 3). There was no significant relationship between obesity, diabetes, anemia and dyslipidemia with different Parkinson's disease (Table 4).

dISCuSSIon
Personal and environmental factors influence the development of Parkinson's disease [27].Some of these factors, such as obesity, diabetes, anemia, and dyslipidemia were investigated in the present study. The most important finding of the present study, which is the main purpose of this study, was that Parkinson's disease is associated with diabetes, obesity, anemia and dyslipidemia. Each of the above variables is examined separately with Parkinson's incidence in both crude and multivariate analysis. The results showed that the association between diabetes and Parkinson's was 2.5 times higher than the control group. Yang et al. Reported in their study that diabetes increased the chance of developing Parkinson's by at least 1.36 compared to the control group [22]. In a similar study, Sun et al. Found that the overall incidence of Parkinson's disease was 3.59 per 10,000 in the diabetic group, compared with 2.15 in the control group [19]. Yue [21]. Early diagnosis and intervention of Parkinson's disease are closely related to improving the quality of life and reducing these patients' mortality. In a systematic review and meta analysis, Noyce et al. Reported that diabetes mel litus was not associated with Parkinson's disease [28]. Another finding of this study was that obesity with a body mass index of more than 30 kg/m 2 was more associated with Parkinson's than the control group. Bousquet et al. found that obesity under a highfat diet increased the risk of Parkinson's disease as a neurodegenerative disease [20]. Because the pa tients studied were elderly and with Parkinson's disease with clinical manifestations of Brady Keynesian, gait disorders and tremors, so the possibility of physical activity and mobility was not enough for them. Hence, their body mass index was high, and in the analysis, it is considered a risk factor. In the present study, anemia was also observed as one of the diseases associated with Parkinson's. Savica et al. Also found that among 196 Parkinson patients with a history of anemia in their previous history, there was an association between anemia and Parkinson's disease [24].
Regarding the relationship between anemia and Parkinson's, Pichler et al. concluded that increased blood iron levels were associated with a decrease in Parkinson's disease [23]. People with dyslipidemia were 1.88 times more likely to have Parkinson's disease than patients without dyslipidemia. Haung et al. Concluded in their study that higher levels of total cholesterol were associated with an accelerated progression of Parkinson's clinical symptoms [25]. However, in the study of Schlep et al., It was reported that there was no association between metabolic syndrome and the risk of Parkinson's disease related dementia [26]. Parkinson's disease is usually idiopathic, but external and individual factors are important in its occurrence. The multifactorial hypothesis of Parkinson's disease is also a combi nation of environmental and hereditary factors. In the study of Parkinson's disease severity based on the Hoehn and Yahr staging scale, stage 2 and stage 3, respectively, with a frequency of 28.7% and 24.7%, respectively, had the most common severity. In the study, Leopald et al. Used the Hoehn and Yahr sta g ing scale to assess the severity of the disease in patients with Parkinson's disease and divided the patients into two groups of mild/moderate disease severity and advanced disease [29]. One of the streng ths of the present study was that the rela tionship between diabetes, obesity, anemia and dys li pidemia with the severity of Parkinson's disease was investigated, although there was no rela tionship between these cases and the severity of the disease. Ineffectiveness of Parkinson's disease severity based on the Hoehn and Yahr scale with the above in patients in this study was one of the most significant possible results. Since our patients were mostly in the pre2.5 stage and had a mild illness, this could explain the lack of association between the severity of the illness and the above.

ConCLuSIon
Overall, this study showed that Parkinson's is associated with obesity, diabetes, anemia and dyslipidemia. The above can be effective as risk factors for Parkinson's disease, but how they are related and their impact requires further research in this area. Using the results of this study, it is possible to prevent Parkinson's disease and modify its risk factors.

Limitations
Failure to study other underlying diseases such as hypertension, cardiovascular disease.

Suggestions for further research
It is recommended that a study be conducted to examine some personal and environmental factors such as family history, occupation, and smoking in the incidence of Parkinson's disease.