In [House M.D.](https://m.imdb.com/title/tt0412142/), having chronic pain made Dr. House a bit arrogant. In [Breaking Bad](https://m.imdb.com/title/tt0903747/), a chemistry professor with cancer decides to become a drug lord.  We often hear about how people who have diabetes or other chronic diseases get depressed. Many chronic illness have devastating effect on our mental well being. But today, I want to talk about the opposite. How psychological stress we face throughout life sets a stage for onset of type 2 diabetes.

 ![image](https://img.esteem.ws/6oelk899hs.jpg)

<center>**Stress and altered metabolism.
 A story of mind for the body.**
[Image](https://pixabay.com/en/stress-pressure-anxiety-angst-1837384/) by johnhain | [CC0](https://pixabay.com/en/service/terms/#usage)</center>

# Previously on type 2 diabetes. 

In the [first blog](https://steemit.com/steemstem/@scienceblocks/type-2-diabetes-from-the-eyes-of-immune-cells-8aba64f95b3fb) in the series, we saw that diabetes is a disease in which the body is unable to use the glucose in the blood. We also saw that type 2 diabetes is different from type 1 diabetes in terms of insulin dependence. That is, in type 1 the pancreas fails to produce insulin(the signal which tells body's cells to take up available glucose). In type 2 diabetes, insulin is produced(at least in initial stages of the disease), however the cells are resistant and don't respond to insulin signal. The accumulation of glucose in body then leads to the known maladies, that these diabetic patients suffer with. 

In that blog we also discussed that how central mechanism to diabetes is low grade chronic inflammation in the body. We talked about, how bad diet, obesity, and known risk factors of diabetes connects to insulin resistance, via immune cells. 

In the [next blog](https://steemit.com/steemstem/@scienceblocks/type-2-diabetes-the-gut-feeling-that-youa-bacteria-654b15d1ba399) in type 2 diabetes series, we discussed the role of bacteria that live in your gut. We saw how changes in abundance of bacteria that live in your gut, changes your metabolism. We saw that these bacteria are not only sensitive to both your genes and diet, but how they also affect your gene expression and eating behaviour. 

Finally, in a separate [blog](https://steemit.com/steemstem/@scienceblocks/this-is-what-depression-is-made-of-the-biological-underpinnings-of-depressiom-ae2bc65b32b23) that I did not particularly include in the series, we focused on how psysiological state of the body leads to psychological condition such as depression. Nevertheless, can psychological stress that causes mental illness also cause physical illness? 

# The use and overuse of stress response - allostasis and allostatic load 

In his very interesting book, on role of stress, Robert Sapolsky ask a very good question, as title of the book - **"[Why Zebras don't get Ulcers](https://en.m.wikipedia.org/wiki/Why_Zebras_Don%27t_Get_Ulcers)"**. The answer seem to lie in the fact that, zebras don't lie down at night stressing about 100 ways they could die. Neither does the zebra stress about deadlines. For zebras the stress response turns on when it being chased by a predator. Its heartbeat increases, focus shifts from digesting the grass to putting all effort in their fight or flight response. This response called allostasis, which technically means altered homeostasis. 

Humans on the other hand are gifted by evolution to think themselves to allostasis. Which is fine in short term, because in a way it your brain simulating the consequences you can witness in future. But do it a lot or inability to shut it off, opens a Pandora's box of all kind of pathologies. For instance, it can make your gut favorable to a bacteria called Helicobacter pylori([Guo et al., 2009](https://www.ncbi.nlm.nih.gov/pubmed/20102319/?ncbi_mmode=std)). What does it do? It gives you peptic ulcers. So if chronic stress can change what lives in your gut, wonder what else it is changing? 

# Stress - digging your way to insulin resistance. 

The idea that chronic stress can alter metabolism and lead to type 2 diabetes is not a new one. However, we have only recently started to understand the underlying mechanisms. But before we go down that path, what is the evidence that stress is even linked to type 2 diabetes? 

# Stress as a risk factor for diabetes 

## The population studies 

A good number of studies have followed people over the course of years, and have established, the chronic stress as a predictor of type 2 diabetes. For instance, [Mommersteeg et al., in 2012](https://www.ncbi.nlm.nih.gov/pubmed/23259455?dopt=Abstract&holding=npg) published an 18 year follow up, showing psychological distress as risk factor. Another study, by [Twig et al.,](https://www.ncbi.nlm.nih.gov/pubmed/26810356?dopt=Abstract&holding=npg) linked chronic emotional distress to diabetes. Also, if stress is predictor for onset of diabetes, then people working stressful jobs should have higher incidence of diabetes. This was confirmed by a large population study in Europe by [Nyberg et al., in 2014](https://www.ncbi.nlm.nih.gov/pubmed/25061139?dopt=Abstract&holding=npg). In fact according to [Virtanen](https://www.ncbi.nlm.nih.gov/pubmed/24784831?dopt=Abstract&holding=npg), psychological distress not only predicts diabetes, but also accelerates the progression towards it. 

## Childhood experience and diabetes - spanking your kids is never a good idea. 

Chronic stress at any point in life is usually bad. But worst are the stressors in early childhood. [Medei et al.,](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641896/) reported in 2013, that how physical abuse during childhood, is correlated with metabolic syndrome in adult women. This was in agreement with [Claudia Thomas's](http://pediatrics.aappublications.org/content/121/5/e1240) previous report that childhood experiences can predict the onset of both obesity and diabetes in adulthood. And if you are thinking that it is only story of humans so there are a lot of other variables, well it has been seen in rats as well. Early life stress does indeed modify, how an adult individuals even responds to high-fat and sucrose diet([Paternain et al., 2012](https://www.ncbi.nlm.nih.gov/pubmed/22773756?dopt=Abstract&holding=npg)).

So stress may make you fat, and fat may cause diabetes. Or stress may cause diabetes directly. However, irrespective of child maltreatment being direct or indirect cause of diabetes, it is best idea to not be tough on your kids. 

## Mental illness as predictor for diabetes. 

Some people may debate about stress affecting physical health. Nevertheless, stress and mental health are strongly linked. Given the above information and this knowledge, I would predict that people with a mental condition - PTSD, depression, anxiety, etc are also at higher risk of developing diabetes. So I checked if I could find literature supporting my hypothesis. 

In this regard, [Engum, 2007](https://www.ncbi.nlm.nih.gov/pubmed/17188118?dopt=Abstract&holding=npg) published that symptoms of depression and anxiety preceded diabetes onset. Even more surprising for me, was the fact, that lifestyle choices of depressed and anxious, in some studies, only partially explained diabetes([Atlantis et al., 2012](https://www.ncbi.nlm.nih.gov/pubmed/23062854?dopt=Abstract&holding=npg)). In fact PTSD, a pathology that develops in people who underwent traumatic stress, is also highly correlated with onset of diabetes([Vancampfort et al., 2016](https://www.ncbi.nlm.nih.gov/pubmed/26867081?dopt=Abstract&holding=npg)).

Another mental illness highly correlated with childhood stressors is schizophrenia. And guess what! The onset of schizophrenia is followed by onset of diabetes in many if not all schizophrenia pateints([Mamakou et al., 2018](https://www.ncbi.nlm.nih.gov/m/pubmed/29754122/)). In fact even the mood disorders such Bipolar is not free of type 2 diabetes risk([Calkin et al,. 2013](https://www.ncbi.nlm.nih.gov/m/pubmed/22621171/)).

However, all I have mentioned up until now are correlational studies. There exists a clear correlation between mental and physical well being. But then again correlation doesn't define causation. So in next part of this article I am going to talk about the mechanisms that link the two. Like do mental illnesses and metabolic disorder share common pathogenesis? 

# Stress hormones and insulin resistance. 

Corticosteroids are set of hormones released by adrenal gland in response to stress(apart from adrenaline and noradrenaline). But guess what, apart from regulating stress response, corticosteroids has role in regulating our metabolism. In 1993, [Dallman et al.,](https://www.ncbi.nlm.nih.gov/pubmed/8258378?dopt=Abstract&holding=npg) showed, how these hormones interact with insulin and metabolism as part of diurnal rhythms and stress response. So technically, if our hypothesis derived from observed correlations is correct then, we should be able to test it in mice. So what happens to insulin sensitivity if I inject mice or rats with high levels of corticosteroids? 

Well, rats given high corticosteroids, along with high fat diet shows severe insulin resistance([Shpilberg et al., 2012](https://www.ncbi.nlm.nih.gov/pubmed/22184636?dopt=Abstract&holding=npg)). In support of this, removing the adrenal gland from the rats improved the insulin sensitivity in the brain.([Chavez et al., 1997](https://www.ncbi.nlm.nih.gov/pubmed/9272675?dopt=Abstract&holding=npg)). 

So until this point we can see that stress hormones can explain the correlation observed between stress and diabetes. But story is far from complete. I would love to discuss the underlying mechanisms, in detail. Nonetheless, in respect of your attention span I will do that next week. 

# Steembasicincome giveaway

However, in the meantime feel free to propose the mechanisms you can think of. It will be easy if you have read my first two blogs. Good comments will get 1 SBI share as a gift

# The type 2 Diabetes series

1. [Type 2 Diabetes - from the eyes of immune cells.](https://steemit.com/steemstem/@scienceblocks/type-2-diabetes-from-the-eyes-of-immune-cells-8aba64f95b3fb)

2. [Type 2 Diabetes - The gut feeling that you might be a bacteria](https://steemit.com/steemstem/@scienceblocks/type-2-diabetes-the-gut-feeling-that-youa-bacteria-654b15d1ba399)

3. Type 2 diabetes - how psychology changes physiology(part 1 - character introduction)

4. (Upcoming) Type 2 diabetes - mechanistic insights on how psychology changes physiology(part 2 - The plot)

**Related blog**

[This is what depression is made of! - The biological underpinnings of depression](https://steemit.com/steemstem/@scienceblocks/this-is-what-depression-is-made-of-the-biological-underpinnings-of-depressiom-ae2bc65b32b23)


# References 

1. [Why Zebra don't get Ulcers](https://en.m.wikipedia.org/wiki/Why_Zebras_Don%27t_Get_Ulcers) 

2. [Guo G, Jia KR, Shi Y, Liu XF, Liu KY, Qi W, Guo Y, Zhang WJ, Wang T, Xiao B, Zou QM. Psychological stress enhances the colonization of the stomach by
Helicobacter pylori in the BALB/c mouse. Stress. 2009 Nov;12(6):478-85. doi: 10.3109/10253890802642188. PubMed PMID: 20102319.](https://www.ncbi.nlm.nih.gov/pubmed/20102319/?ncbi_mmode=std)

3. [Mommersteeg PM, Herr R, Zijlstra WP, Schneider S, Pouwer F. Higher levels of psychological distress are associated with a higher risk of incident diabetes during 18 year follow-up: results from the British household panel survey. BMC Public Health. 2012;12:1109.](https://www.ncbi.nlm.nih.gov/pubmed/23259455?dopt=Abstract&holding=npg)

4. [Twig G, Gerstein HC, Fruchter E, Shina A, Afek A, Derazne E, Tzur D, Cukierman-Yaffe T, Amital D, Amital H, Tirosh A. Self-Perceived Emotional Distress and Diabetes Risk Among Young Men. Am J Prev Med. 2016 Jun;50(6):737-745. doi: 10.1016/j.amepre.2015.12.006. Epub 2016 Jan 22. PubMed PMID: 26810356.](https://www.ncbi.nlm.nih.gov/pubmed/26810356)

5. [Nyberg ST, Fransson EI, Heikkilä K, Ahola K, Alfredsson L, Bjorner JB, Borritz M, Burr H, Dragano N, Goldberg M, Hamer M, Jokela M, Knutsson A, Koskenvuo M, Koskinen A, Kouvonen A, Leineweber C, Madsen IE, Magnusson Hanson LL, Marmot MG, 
Nielsen ML, Nordin M, Oksanen T, Pejtersen JH, Pentti J, Rugulies R, Salo P, Siegrist J, Steptoe A, Suominen S, Theorell T, Väänänen A, Vahtera J, Virtanen M,
Westerholm PJ, Westerlund H, Zins M, Batty GD, Brunner EJ, Ferrie JE, Singh-Manoux A, Kivimäki M; IPD-Work Consortium. Job strain as a risk factor for 
type 2 diabetes: a pooled analysis of 124,808 men and women. Diabetes Care. 2014 Aug;37(8):2268-75. doi: 10.2337/dc13-2936. PubMed PMID: 25061139; PubMed Central PMCID: PMC4113178.](https://www.ncbi.nlm.nih.gov/pubmed/25061139?dopt=Abstract&holding=npg)

6. [Virtanen M, Ferrie JE, Tabak AG, Akbaraly TN, Vahtera J, Singh-Manoux A, Kivimäki M. Psychological distress and incidence of type 2 diabetes in high-risk and low-risk populations: the Whitehall II Cohort Study. Diabetes Care. 2014
Aug;37(8):2091-7. doi: 10.2337/dc13-2725. Epub 2014 May 1. PubMed PMID: 24784831; PubMed Central PMCID: PMC4113169.](https://www.ncbi.nlm.nih.gov/pubmed/24784831)

7. [Midei AJ, Matthews KA, Chang Y-F, Bromberger JT. Childhood Physical Abuse Is Associated with Incident Metabolic Syndrome in Mid-Life Women. Health psychology : official journal of the Division of Health Psychology, American Psychological Association. 2013;32(2):121-127. doi:10.1037/a0027891.](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641896/). 

8. [Claudia Thomas, Elina Hyppönen, Chris Power(2008), Obesity and Type 2 Diabetes Risk in Midadult Life: The Role of Childhood Adversity](http://pediatrics.aappublications.org/content/121/5/e1240)

9. [Paternain L, Martisova E, Milagro FI, Ramírez MJ, Martínez JA, Campión J. Postnatal maternal separation modifies the response to an obesogenic diet in adulthood in rats. Dis Model Mech. 2012 Sep;5(5):691-7. doi: 10.1242/dmm.009043. Epub 2012 Jul 5. PubMed PMID: 22773756; PubMed Central PMCID: PMC3424467.](https://www.ncbi.nlm.nih.gov/pubmed/22773756)

10. [Engum A. The role of depression and anxiety in onset of diabetes in a large population-based study. J Psychosom Res. 2007 Jan;62(1):31-8. PubMed PMID:
17188118.](https://www.ncbi.nlm.nih.gov/pubmed/17188118)

11. [Atlantis E, Vogelzangs N, Cashman K, Penninx BJ. Common mental disorders associated with 2-year diabetes incidence: the Netherlands Study of Depression and Anxiety (NESDA). J Affect Disord. 2012 Oct;142 Suppl:S30-5. doi:10.1016/S0165-0327(12)70006-X. PubMed PMID: 23062854.](https://www.ncbi.nlm.nih.gov/pubmed/23062854.)

12. [Vancampfort D, Rosenbaum S, Ward PB, Steel Z, Lederman O, Lamwaka AV, Richards JW, Stubbs B. Type 2 Diabetes Among People With Posttraumatic Stress Disorder: Systematic Review and Meta-Analysis. Psychosom Med. 2016 May;78(4):465-73. doi:10.1097/PSY.0000000000000297. Review. PubMed PMID: 26867081.](https://www.ncbi.nlm.nih.gov/pubmed/26867081?dopt=Abstract&holding=npg)

13. [Mamakou V, Thanopoulou A, Gonidakis F, Tentolouris N, Kontaxakis V. Schizophrenia and type 2 diabetes mellitus. Psychiatriki. 2018 Jan-Mar;29(1):64-73. doi: 10.22365/jpsych.2018.291.64. PubMed PMID: 29754122.](https://www.ncbi.nlm.nih.gov/pubmed/29754122/?ncbi_mmode=std)

14. [Calkin CV, Gardner DM, Ransom T, Alda M. The relationship between bipolar disorder and type 2 diabetes: more than just co-morbid disorders. Ann Med. 2013 Mar;45(2):171-81. doi:10.3109/07853890.2012.687835. Epub 2012 May 24. Review. PubMed PMID: 22621171.](https://www.ncbi.nlm.nih.gov/pubmed/22621171/?ncbi_mmode=std)

15.  [Dallman MF, Strack AM, Akana SF, Bradbury MJ, Hanson ES, Scribner KA, Smith M. Feast and famine: critical role of glucocorticoids with insulin in daily energy flow. Front Neuroendocrinol. 1993 Oct;14(4):303-47. Review. PubMed PMID: 8258378.](https://www.ncbi.nlm.nih.gov/pubmed/8258378?dopt=Abstract&holding=npg)

16. [Shpilberg Y, Beaudry JL, D'Souza A, Campbell JE, Peckett A, Riddell MC. A rodent model of rapid-onset diabetes induced by glucocorticoids and high-fat
feeding. Dis Model Mech. 2012 Sep;5(5):671-80. doi: 10.1242/dmm.008912. Epub 2011 Dec 19. PubMed PMID: 22184636; PubMed Central PMCID: PMC3424464.](https://www.ncbi.nlm.nih.gov/pubmed/22184636?dopt=Abstract&holding=npg)

17. [Chavez M, Seeley RJ, Green PK, Wilkinson CW, Schwartz MW, Woods SC. Adrenalectomy increases sensitivity to central insulin. Physiol Behav. 1997 Sep;62(3):631-4. PubMed PMID: 9272675.](https://www.ncbi.nlm.nih.gov/pubmed/9272675?dopt=Abstract&holding=npg)

<hr>

*See you on part 2 - __The plot__*

Signing off
@scienceblocks