Two sisters 15 Yrs & 16 Yrs with medical and family history. They are exposed to severe acute distress because of gunshot near their home, after which they started to be Diabetic on insulin therapy. One of sisters died because she developed DKA with shortage of therapy.
What is the pathogenisis?
1. Stress increases oxygen consumption leading to increase production of H2O2.
2. Glutathione is required to reduced H2O2 to H2O by glutathione peroxidase in doing so two molecule of glutathione is converted into one molecule of glutathione disulphide.
3. NADPH is required by glutathione reductase to reconversion of glutathione disulphide to glutathione for reused.
4. NADPH is generated by Pentose phosphate pathways which is a highly reduced in diabetic patients.
5. Therefore accumulation of H2O2 is higher in diabetic patients.
6. As H202 is freely permeable and is also mother of free radical generation through The Haber-Weise reaction or Fenton reaction. It can generate havoc in our body.
7. So diabetic patients have higher sensitivity of free radical attack.
8. 8. Therefore acute stress will worsen diabetic patient body.
"DKA with shortage of therapy.
What is the pathogenisis? "
Inadequate treatment with insulin, possibly hypokalemia during DKA.
Acute stress due to pathogenisis, In this regard,if we want to improve the result,simply change the place ,ie change the patient location at least hundred kilometer away from their parental location ,change of environment ,ethnic,food,water ,temp will give improvised result .In India we tried and we got the result, thank you.
Dear respected Dr.
Greetings
Stress either the stressful event itself, or the physiological or psychological response to the stressor were blamed in the development of diabetes mellitus especially during the first two years of life, the effects are mediated through the autonomic nervous system, neuroendocrine, or the immune system. Removal of the stimulus or modifying the response could be very helpful.
All types of stress do not lead to worsening of diabetes. Stress is usually associated with increase oxygen consumption usually known as respiratory burst. Pathogenesis as mention by Dr. Arangawamy, can induced respiratory burst. Under such situation NADPH oxidase as well as inducible nitric oxide synthase of macrophages were highly activated leading to high accumulation of H2O2 and NO. H2O2 is used by macrophages to produced hypochloric acid (HOCl) which is stong oxidizing and halogenating agent. H2O2 when react with supeoxide or in presence of iron can generate hydroxyl radical. Further NO in high concentration can generate large number of nitrogen containing reactive oxygen species. Such high concentration of toxin not only killed the infecting pathogens but also damage the tissue in it vicinity. Therefore uncontrolled infection can lead to whole lot damage not only to diabetes person but also normal person. However diabetes person have greater degree of damage because it its decrease reduction of H2O2 as well as it provide higher degree microbe survivality due to higher sugar in the blood.
Oxygen consumption also increases during exercise but is usually couple with beta-oxidation and increases rate of metabolism, increases health condition and reduced obesity. And there high degree of correlation that suggest that obesity lead to diabetes.
Oxygen consumption also increases during over non physical-workload, anxiety and anger leading to lot of health issue like headache, lethargy and many because such thing do not contribute to our body metabolism.
Another silence self inflected stress is the used of psychoactive drugs that increases dopamine level in the brain. Inactivation of dopamine required monoamine oxidase resulting in the increases production of H2O2 so the increases production of free radical in the brain. Such event lead to gradual development many heath issue including Parkinson disease. Therefore drug that inhibit monoamine oxidase have been used during early onset of Parkinson disease. And there is higher frequency of Parkinson disease among diabetes.
Therefore to my mind the diabetes person undergoing insulin therapy should
have:
1. Regular exercise to reduce obesity.
2. Living in clean environment including clean air breathing, good sanitation good food choice.
3. Reduced non-physical work load and should have proper anger management.
4. Reduced used of any psychoactive drugs that are known to increase excessive buildup of dopamine in the brain.
All the well-meaning general advices are not necessarily incorrect but the question is specifically related to the death of person - this was the result of uncontrolled diabetes leading to catastrophic ketoacidosis, in the absence of proper medical care. Stress induced by hearing a gun-shot can only have so much effect, in hardly be considered as the source of ultimate result.
It is intriguing to see that how the distinction in seeing the whole forest is overlooked by focussing so acutely on individual leaves.
To Tausif Alam, Yah I recognize the condition of death of one child that can be attributed to what you say. But why one why not both. The underlying mechanism can be far more complicated. But my answer is purely directed to the title of question (as biochemical point of view but not as medical adviser).
Mohammad:
"But why one why not both."
Do you have to ask?
Obviously, do not fully understand the pathophysiology of type 1 diabetes (most likely scenario for the age mentioned).
Even in identical twins, the concordance of T1D is not 100% and given the age difference, and poor health care, would you care to guess which of the two children succumbed to uncontrolled diabetes?
yes i dont have to ask? I ask because the problem is not so simple. There seems to be involvement of human error. Thanks you for your information of identical twins. It is much needed in my research.
Dear Mohammed ali ,Thanks for your detailed answer about the question.i appreciate ,you have given detailed explanation about stress.i hope Tausif alam clear your doubts like twin sister , I think still the question is not fullfill .the question is relation between acute stress and diabetes.
A few points that I can garner from this question
1, Did this adolescents become diabetic from severe acute distress either from one gun shotor possibly from repeated gunshots or was this a case of post traaumatic stress disorder and/or diabetes mellitus. " The effect of stress on glycemic control in people with diabetes may be related to a direct effect of stress hormones on blood glucose levels and an indirect effect of stress on patient behaviors related to diabetes treatment and monitoring, meal and exercise plans. In contrast, there is no clear evidence that stressful life events promote the development of diabetes in children or in adults. A large body of evidence supports an association between stress hyperglycemia and increased morbidity and mortality in critically ill patients. Interestingly, there is some evidence supporting a beneficial effect of insulin in reducing morbidity and mortality in patients admitted to intensive care units. Finally, stress can influence the development of type 2 diabetes indirectly by promoting obesity and metabolic syndrome.
2. Do they have a family history of diabetes mellitus,or was this type 2 DM masquerading as type I becuase of the "acute stress disorder,
Although this information was not given I would presume that with or without a family history of diabetes this adolescents may just have had diabetes mellitus diagnosed at that time, because they were undergoing evaluation for acute stress disorder or possibley their need for therapy increased due to the stressful condition. l would have appreciated if the managing physcians approached the disorders as two remotely related events probably the outomes may have been different
3. Were they being treated for the acute stress disorder and if they were, was the possibility of a antidepresant-insulin or a antidepressant-blood glucose interaction ever considered.
4. Finally was isulin theraphy opitmised, because I do not except DKA if inslin therapy is optimised
Best regards
Adejoke Onaolapo
Acute stress and development of D.M?, I seriously doubt there is a direct causal link.However, the acutely stressful event may be the tipping point for these individuals who were probably already diabetic, but undiagnosed.
Arangaswamy,
In the context of normal physiological response to acute stress a fair bit is well-known for ages. A fight or flight response does effect glucohomeostasis very significantly via directly influencing innervated alpha cells to dump glucagon, which causes breakdown of glycogen, making substantial quantities of glucose available for the task at hand - yes, this means hyperglycemia - sustained stress causes increase in glucorticoid levels, which also increases blood glucose levels. None of these conditions, however, are known to be cabable of causing lethal ketoacidosis.
Perhaps a literature review will prove beneficial to those who think that the question is unanswered.
http://www.panafrican-med-journal.com/content/article/19/328/full/#.WDNXULIrKUs
The mind-body connection is theoretically extended to suggest concrete impact of one on the other. (E.g., stress and heart disease). The specific diabetes-trauma relationship in children is less studied. The above article is a case study. I myself have noticed that children who are diabetic have had extreme trauma pre-diagnosis--but of course, one cannot say cause-effect.
Despite my strong belief in mind-body connection, I never underestimate the power of psychological dynamics. The subtle psychological underpinnings of overt expressions, be they behavioral, emotional, cognitive, or physiological, is evident to me daily in my therapeutic work. Notwithstanding scientifically evidenced outcomes, being human demands each case to be healed under its own merits. Predispositions give cues to biological causes (partially); external trauma gives cues to socio-relational causes (partially). The genius of the Orchid Children study fills in the gap in understanding predisposition and gives hope for that small group of Orchid children---who are lucky to get "good" parenting. I cannot question science, I will not fight evidence, and I will always believe in that invisible force within us which ultimately determines our drive to survive. And if a child with DM or any other "disorder" with shown genetic/biological/physiological causes, eventually gives-up, psychologically or physiologially, being alive means to honor both life and death.
I think both of them had Type 1 diabetes and that they were in prediabetes phase when stress precipitated the onset of clinical diabetes. The age at onset may be different even in concordant twins. Familial occurrence is well known in Type 1 diabetes.
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