Diabetes Drug May Help Prevent Parkinson's, Study Shows
Drugs used to treat type 2 diabetes, belonging to a class called glitazones (GTZs) may reduce the risk of Parkinson’s by as much as 28 percent, a study suggests. It was a large scale study done by analyzing more than 100 million prescriptions.
Parkinson’s is a sporadic neurodegenerative disease characterized by movement disorders. This differs from type 2 diabetes, however, as it is a metabolic disorder characterized by insulin resistance and later insulin deficit. Both Parkinson’s and diabetes have a few things in common, like they are still not fully understood, and neither the mechanism nor the causes are realized till the end. Further, it seems that both of these disorders are triggered due to a combination of reasons, and have multiple pathological pathways. Both diseases are more or less related to lifestyle. As evident from the fact that those who have diabetes are also at a slightly higher risk of developing Parkinson’s when compared to general population.
In type 2 diabetes, insulin resistance is more of a problem in the initial phase, as compared to insulin deficit. So, some drugs used to treat diabetes increase insulin sensitivity. At this moment, two of the leading drugs that are known to help improve sensitivity to insulin are metformin and GTZs.
In most cases, treatment of type 2 diabetes would start with lifestyle modification and prescription of metformin, though in some cases it could be started with GTZs.
In a study, Brakedal et al. reported the earlier, little-known benefit of GTZs in preventing Parkinson’s, and the report was published in a journal called Movement Disorders.
This study was provoked by the contradicting results reported in many other studies on similar lines. Thus, in one of the studies published in PLOS medicine prescription of GTZs was found to decrease the incidence of Parkinson’s. While in another study, no such benefit was found. Hence, till date studies have been inconclusive about whether GTZs would help to prevent Parkinson’s or not.
GTZs may help to cut down prevalence of Parkinson’s
To gain deeper insight into the subject, researchers decided to analyze the Norwegian prescription data of antidiabetic drugs. Reason for choosing Norwegian data was the availability of better information, as data provided information about complete information on medicines dispensed in all pharmacies across Norway, along with medical records of the patients.
Researchers decided to compare the link between thedevelopment of Parkinson’s and prescription of GTZs, for comparison they also analyzed the data for metformin, as metformin is a much more widely prescribed medication. Further, such comparison would help to identify whether theneuroprotective effect was specific to GTZs or it was achieved merely due to better control of diabetes.
Researchers combed the 10-year data between the year 2005 and 2014, and they found 94,349 users of metformin and 8,393 users of GTZs that met the study criteria.
A study by Brakedal et al. demonstrated that patients who took GTZs were at 28 percent lower risk of developing Parkinson’s, as compared to those on Metformin.
However, researchers failed to explain the underlying mechanism. They think that it is entirely possible that neuroprotective action of GTZs could be due to their effect on mitochondria. Mitochondria are small organelles that are responsible for the production of energy in cells; they are called powerhouse of cells.
Many specialists have earlier proposed that mitochondrial dysfunction could be the cause of Parkinson’s. It has been suggested that in Parkinson’s there is a reduction in energy production by mitochondria, a mutation in mitochondrial DNA, changes in the way mitochondria work. Hence, it is entirely possible that the beneficial effect of GTZs in Parkinson’s may be due to an increase in mitochondrial mass and synthesis.
However, Brakedal and team agree that it is too early to conclude about the underlying mechanism. It is also entirely possible that we could be missing something. Especially considering that very little is known about the pathology of Parkinson’s.
One more step towards preventing Parkinson’s
Though no doubt that this study is one more positive step toward finding a preventive measure for Parkinson’s disease, researchers agree that there are certain limitations to their findings. Like, for instance, there was no data regarding the dosage of GTZs and its relationship to Parkinson’s disease prevention. Hence, it cannot be said that whether such protecting effect is dose-related or not.
Further, investigators noted that there was lack of information regarding the stage and seriousness of diabetes in each patient. However, researchers noted that since diabetes is only a minor risk factor in Parkinson’s, it is unlikely that severity of diabetes and its treatment would have distorted their findings.
Another drawback of the study is that it only compared the prevention rate of GTZs in those living with diabetes, it means that these results would still not be entirely applicable to the general population.
Researchers also noted that earlier large-scale trials done in the US could have failed to show the beneficial effect of GTZs in diabetes prevention, as they were carried out in much older people. From pathological studies, it is well known that Parkinson’s has an extended sub-clinical period. Thus, it is entirely possible that in the older population Parkinson’s was already there in sub-clinical forms.
If we combine the results from earlier studies, we can see that GTZs would probably not help in old age group and they will not change the course of Parkinson’s. However, they may have a preventive effect if taken over an extended period of time. Considering that Parkinson’s cannot be adequately treated with modern drug therapy, any success in prevention would hold great practical value.
References
1. Hu G, Jousilahti P, Bidel S, Antikainen R, Tuomilehto J. Type 2 Diabetes and the Risk of Parkinson’s Disease. Diabetes Care. 2007;30(4):842-847. doi:10.2337/dc06-2011
2. Brakedal B, Flønes I, Reiter SF, et al. Glitazone use associated with reduced risk of Parkinson’s disease. Mov Disord. 2017;32(11):1594-1599. doi:10.1002/mds.27128
3. Brauer R, Bhaskaran K, Chaturvedi N, Dexter DT, Smeeth L, Douglas I. Glitazone Treatment and Incidence of Parkinson’s Disease among People with Diabetes: A Retrospective Cohort Study. PLOS Med. 2015;12(7):e1001854. doi:10.1371/journal.pmed.1001854
4. Connolly JG, Bykov K, Gagne JJ. Thiazolidinediones and Parkinson Disease: A Cohort Study. Am J Epidemiol. 2015;182(11):936-944. doi:10.1093/aje/kwv109
5. Bose A, Beal MF. Mitochondrial dysfunction in Parkinson’s disease. J Neurochem. 2016;139 Suppl 1:216-231. doi:10.1111/jnc.13731
