Diabetes and Its Connections to Various Topics

Connor Mooney

The focus of this Biology of Disease class has been on making connections with what we’ve learned in the past and the diseases that we cover in our class. Our first disease was diabetes that has links to hundreds of different problems ranging from economic burden to coronary artery disease. This made it easy on us as students of an integrative class to connect this disease to our own lives, news stories, social issues, personal issues, and, of course, health issues. In this post, I’ll cover a few that I was able to make that really influenced how I plan to approach this illness as a future healthcare professional.

The Difficulties Associated with a Diabetic Marriage

Marriage is a difficult enough phenomenon to maintain even in perfect health. Divorce is widely prevalent, and broken families are ridiculously common. Add in a chronic condition that necessitates physical, emotional, and financial support into the mix, and that can spell disaster for some relationships.

We learned from an article in class how diabetes burdens the national economy (ADA, 2013), and if the disease can wreak havoc on such a large scale, we can safely assume the finances in the home are affected in proportionate measure with increases in insurance premiums, doctor visits, and a higher likelihood of needing emergency care.

On top of this major stressor on the relationship, add a lower libido, erectile dysfunction, and poor vaginal lubrication, because diabetes correlates with these as well (Fatemi & Taghavi, 2009). These are less likely to be looked for as symptoms, though, because of the personal nature sex has in relationships and the conservative approach our society has to sex. Discussing sex is rare and, with some individuals, completely taboo even with the person’s physician. This can lead to neglect of a completely vital aspect of many relationships and marriages. If we as healthcare professionals don’t ask questions about this aspect of life, then we may be directly responsible for the disintegration of our patients’ relationships and very lives. It’s a drastic change that I would like to be sure to make. I want to keep an open conversation with my patients.

Pathways to Diabetic Doom (or at the very least tissue damage)

There’s a lady in my town who is well known for her kindness and activity in the community despite the major handicaps that she has. She is a blind amputee. This is not unheard of in diabetics, really. With the advent of insulin, many people have been able to gain control of their illness, and live normal lives; however, a severe symptom of diabetes is blindness and poor circulation to the extremities leading to limb loss. This is terrible for those patients, and some research into these conditions gave the answer that excess glycolytic intermediates’ metabolites were to blame for the damage to the renal, retinal, and vascular tissue.

This was a good start to find what chemical mechanisms lead to this tissue necrosis. I deepened my search and discovered an article that looked into these pathways and proposed a common mechanism that lead to the problems associated with diabetes. Brownlee (2005) summarized the mechanisms and showed how the superoxide radical ion was involved. The extreme influx of glucose molecules undergoing glycolysis and the tri-carboxylic acid cycle lead to greater use of the Q-cycle that leads to oxidative stress and the forming of the superoxide ion. This radical causes damage to DNA, activating the PARP enzyme that is active in DNA repair, but also acts to inhibit GAPDH. One cool thing that they found was that PARP doesn’t leave the nucleus to inhibit GAPDH. GAPDH is a free floating glycolysis enzyme that actually enters and exits the nuclear envelope, and in that way its function can be modified by PARP. Anyway, with GAPDH out of commission or at least reduced, the aforementioned glycolytic intermediates build up and proceed into the damaging pathways that lead to cell death and tissue necrosis. This manifests as retinopathy, renal failure, and vascular epithelial cell death.

Treatment Strategies of Diabetes

The insight that the above article gave has led to the development of new strategies that are being tested for effectiveness now for the advancement of new drugs and treatment options. It’s exciting to see that treatments are beginning to target the source of tissue damage, and I am eager to see how the treatment landscape changes as I undergo my medical training.

We learned about the GSK3 pathway and targeting as a treatment for developing more and heartier beta cells in the pancreas (Mussmann, et al., 2007). Bace2 is another protein that is under study as a target for beta cell proliferation, although it’s a little different. GSK3 inhibits proliferation, and so inhibiting it is like a double negative, thus allowing the cell cycle to continue. Bace2 is a protease that shreds the proteins active in the division and development of the beta cells (Esterházy, et al., 2011). Both seem to be viable targets for the treatment of diabetes that will control the issues of the condition. However, I foresee the potential problem of unregulated growth and tumor development. So I hope that the researchers involved really know what they’re doing when they move on to human trials with inhibitors of these enzymes.

Then there’s transplantation. Two different methods have been tried: islet transplant and pancreas transplants. The most effective procedure for transplanting islets is called the Edmonton protocol where the surgeon injects a million or so islets (the equivalent to two pancreata) into the liver where they implant and begin producing the regulatory hormones needed in the patient. This seemed like it could be a cure, but the Collaborative Islet Transplant Registry showed in their 2010 report that it was usually only effective in the short term. According to Mayo Clinic Staff (2016), transplant of an entire pancreas has about a 91% survival rate after the first 5 years. The risk to the patient is greater in this procedure because they have to undergo immunosuppression therapy to prevent organ rejection, but there has been some success in patients with type 1 diabetes especially if, at the same time, the patient undergoes a kidney transplant because it may help to detect rejection with both organs being transplanted.

Diabetes: Some Final Thoughts

With the prevalence of diabetes and its connections to a variety of different problems in healthcare, the economy, and the personal lives of patients, I have found that this disease is a big issue and it’s important that we keep our fingers on the pulse of its treatment. I will definitely try to do my part to stay informed as I progress through my medical career and perhaps try to contribute to the field of knowledge gained by performing relevant research while in medical school. Really, eradication of this problem is a big step on par with curing cancer, but we, as scientists, are duty-bound to do what we can to continue to pursue the wellbeing of our species.

References

American Diabetes Association. (2013) Economic Costs of Diabetes in the U.S. in 2012. Diabetes Care, 36:1033-1046

Brownlee, M. (2005) The Pathobiology of Diabetic Complications. Diabetes, 54(6): 1615-1625. http://dx.doi.org/10.2337/diabetes.54.6.1615

Collaborative Islet Transplant Registry. (2011) Seventh Annual Report. Collaborative Islet Transplant Registry, Accessed September 23, 2016. https://web.emmes.com/study/isl//reports/01062012_7thAnnualReport.pdf

Esterházy, D., Stutzer, I., Wang, H., Rechsteiner, M.P., Beauchamp, J., Dobeli, H., . . . Stoffel, M. (2011) Bace2 is a β Cell-Enriched Protease that Regulates Pancreatic β Cell Function and Mass. Cell Metabolism, 14, 356-377. http://dx.doi.org/10.1016/j.cmet.2011.06.018

Fatemi, S.S., Taghavi, S.M. (2009) Evaluation of Sexual Function in Women with Type 2 Diabetes Mellitus. Diabetes and Vascular Disease Research, 6(1): 38-39 doi:10.3132/dvdr.2009.07

Mayo Clinic Staff. (2016) Pancreas Transplant: Procedure Details: Results. Mayo Clinic. Accessed September 23, 2016. http://www.mayoclinic.org/tests-procedures/pancreas-transplant/details/results/rsc-20203041

Mussmann, R., Geese, M., Harder, F., Kegel, S., Andag, U., Lomow, A., . . . Austen, M. (2007) Inhibition of GSK3 Promotes Replication and Survival of Pancreatic Beta Cells. The Journal of Biological Chemistry, 282(16), 12030-12037