Diabetes Or Depression Which One Comes First?

12/4/2020 8:56:45 PM

Diabetes or Depression, Which One Comes First?

Diabetes and depression share an inflammatory pathology, one in the pancreas, and the other in the nervous system (1). Patients with diabetes mellitus (DM) have a higher risk of major depressive disorder. Conversely, depression increases the risk for both type 1, 2 DM (1, 2).

Let's look at a few potential mechanisms for this interaction: 

   1)Common environmental risk factors: Low socioeconomic level, physical activity, sleep disorders, stress, etc. Stress through the hypothalamic-pituitary-adrenal (HPA) axis releases cortisol, a hormone that helps you to face stressful conditions. Cortisol induces the immune system to release inflammatory cytokines, and so in a long time, it causes chronic inflammation (1).

   2)HPA axis gene variants: Cortisol again, but how? In a physiologic condition, when cortisol levels increase, it has a negative effect on the HPA axis. Still, in type 2 DM and depression, the HPA axis is not inhibited by cortisol, and CRH and ACTH levels are more than a physiologic condition; there is an interesting hypothesis to justify this: HPA axis hyperactivation, but how this happens? It's because of HPA axis receptors' self-stimulation, like ACTH and CRH receptors, and that goes back to their coding genes (2).

  3)Oxidative stress: the imbalance between reactive oxygen species (ROS) and anti-oxidant defenses. This imbalance can be harmful to cells like neurons and B cells of the pancreas, tissue, protein, DNA and etc. It can result in pathological effects such as DM and depression (3).

Some studies have evaluated the effects of anti-inflammatory and anti-oxidant drugs and agents on diabetes-induced depression, like Zeaxanthin (an anti-oxidant), but it needs more research (4).

By Elham Khalili


1- Bădescu S, Tătaru C, Kobylinska L, Georgescu E, Zahiu D, Zăgrean A, et al. The association between diabetes mellitus and depression. Journal of medicine and life. 2016;9(2):120.

2- Gragnoli C. Hypothesis of the neuroendocrine cortisol pathway gene role in the comorbidity of depression, type 2 diabetes, and metabolic syndrome. Appl Clin Genet. 2014;7:43-53

3- Reus GZ, Carlessi AS, Silva RH, Ceretta LB, Quevedo J. Relationship of Oxidative Stress as a Link between Diabetes Mellitus and Major depressive disorder. Oxid Med Cell Longev. 2019;2019:8637970

4- Zhou X, Gan T, Fang G, Wang S, Mao Y, Ying C. Zeaxanthin improved diabetes-induced anxiety and depression through inhibiting inflammation in hippocampus. Metab Brain Dis. 2018; 33(3):705-11


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