# RKS: DIABETES AFTER COVID? - Do Not Be Surprised!
# RKS: DIABETES AFTER COVID?
- DO NOT BE SURPRISED!
POST-COVID DIABETES?
BE GRATEFUL TO YOUR LADY LUCK IF HAVE ESCAPED
Dear Reader,
It is general knowledge that when diabetics having COVID-19 infection they are more likely to suffer from graver consequences. However, what is more startling is the revelation that infection with novel coronavirus (nCoV-2 / SARS-CoV-2) itself can cause type 2 or even type 1 diabetes mellitus (T2DM / T1DM)!!
There are 2 unfavourable outcomes post the COVID-19 disease:
- Post-Acute Sequelae of SARS-CoV-2 or PASC: A label for those who suffer from symptoms after COVID-19 and leading to a longer period of recovery.
- Post-COVID-19 Conditions.
Post–COVID-19 conditions are defined as new, returning, or ongoing health problems occurring ≥4 weeks after being infected with SARS-CoV-2. Since India is labelled as the 'World Capital of Diabetes' it is discerning to have a situation wherein the COVID-19 pandemic has been reported to contribute to the increase in incidence of T2DM.
T2DM INCIDENCE POST-COVID-19 SPELL
14.4% of newly diagnosed T2DM patients have had a previous history of novel coronavirus infection - meta-analysis of 3,700 COVID-19 patients. [Diabetes Obes Metab 2021; 23(3): 870-874] In India, an increased incidence of 59% has been documented with respect to developing T2DM (in previous non-diabetics) post the acute phase of COVID-19 infection!! [Prim Care Diabetes 2022; 16(4): 591-593]
HOW T2DM DEVELOPS DUE TO SARS-CoV-2 INFECTION?
It is now a widely known fact that the SARS-CoV-2 gains entry within human body by first and foremost attacking the ACE2 receptors present in various cells of the body. It is now general knowledge that these devil entry points are present in the respiratory system, but even the cardiovascular system, urogenital system, nervous system, gastrointestinal tract, as well as in the liver, gallbladder and pancreas have these ACE2 receptors. Hence, the PASC or post-COVID-19 Conditions (long-term) could impact any of these parts of the body - the insulin-producing pancreas included.
New onset of T2DM, related to pancreatic affection, is the most prevalent post-COVID-19 complication amongst all the disturbances in blood sugar levels documented due to infection by SARS-CoV-2 -
- precipitating diabetes in pre-diabetics.
- worsening blood sugar control in existent diabetics.
- causing grave complications in diabetics during COVID-19 infection period .
- even initiating T1DM status!
It would be but intriguing to know how suffering from COVID-19 can be the cause of one getting diagnosed as a new diabetes patient.
COVID-19 - T2DM - RAAS
The renin-angiotensin-aldosterone system (RAAS) exerts a major control for blood pressure and sodium levels in the body.
There is a protein angiotensinogen (Agt) that is secreted by the liver. Agt is ultimately converted to a hormone-like substance called angiotensin (Ang) II by an enzyme called angiotensin converting enzyme (ACE).
ACE enzymes are of 2 types: [Int J Mol Sci 2017; 18(3): 563]
- ACE: Present in lung, heart, liver and blood. ACE breaks down Ang I to Ang II.
- ACE2: Present in pancreas, liver and blood. ACE2 breaks down Ang II to generate Ang1-7.
There are 2 functions of this Ang II:
- Constrict blood vessels (vasoconstriction): Ang II keeps up the pressure in blood flowing through the arteries - maintains blood pressure.
- Maintain sodium concentrations and ensure fluid balance (more sodium means more water retention and swelling caused thereby): Ang II stimulates the liberation of a hormone called aldosterone from the adrenal glands (lying above each kidney). Aldosterone, in turn, facilitates re-uptake of sodium from the urine as it is being filtered by the kidneys.
Ang1-7 is found in heart and kidneys and is responsible for dilating the arteries so that the blood pressure is not unduly increased due to the vasoconstrictive action of Ang II - a balancing effect.
ACE vs ACE2
God with his wisdom has always provided checks and counterchecks - corrective factors and balancing factors in our body and one can cite umpteen such examples:
- Opposite nature of blood vessels: Arteries carry pure blood whilst veins drain away the impure blood.
- Inhalation and exhalation: Oxygen being supplied to body in inspired air and the waste carbon dioxide driven away into atmosphere in the opposite act of expiration.
- Sleep and awake cycles: One works when awake and rests whilst asleep.
- Digestion and excretion: Ability of small intestine to liberate digestive juices for breakdown of food and facilitate passage of nutrients into the blood and large intestine to throw out all the unwanted junk eaten as waste matter in stools.
- Opposing nervous systems: Sympathetic nervous system, like pressing an accelerator, stimulates the heart to beat, lungs to breathe and intestines to propel further undigested food - the parallel parasympathetic nervous system is like a brake which slows down each of these three functions. The resultant simultaneous interplay of both sympathetic / parasympathetic nervous systems (combined referred to as autonomic nervous system) ensures one has a normal pulse rate of 70-80 beats per minute, breaths 16-18 times a minute and pass stools once or twice in a day.
So also is the same in the case of blood pressure which is under the dual control of both ACE and ACE2.
- ACE-mediated Ang II formed stimulates AT1 receptor to increase blood pressure and stimulate release of aldosterone. Aldosterone facilitates sodium retention and a rise in blood pressure as well.
- ACE2-mediated Ang1-7 generated activates MAS (name derived from the first three alphabets of surname of a cancer patient from whose genes the receptor was identified) receptors present in brain, kidneys and blood vessels to counter Ang II and prevent an excessive rise in blood pressure.
ACE2 activates ACE2 receptors to produce Ang1-7. When SARS-CoV-2 strikes it blocks the ACE2 receptor and hence, there is inadequate manufacturing of Ang1-7; as a result, the vasodilation is compromised and blood pressure can rise unchecked due to Ang II.
INSULIN RESISTANCE & T2DM
Insulin is produced by pancreas to drive the extra food-derived glucose in blood into the muscles for its utilization as energy. T2DM is all because of the insulin produced not being able to execute its glucose-pushing function. In normal individuals, the insulin released after food hand-holds the glucose and takes it to the muscles; thereafter, the insulin by itself goes and sits inside insulin receptors present on the muscle cell and this initiates and transmits message to the nucleus to accept the glucose. If this communication is disrupted - called as insulin resistance (and a hallmark of T2DM) - the glucose cannot get inside the muscles and remains in blood to result in high blood sugar levels - hyperglycemia.
Within muscles there are special proteins known as Insulin Receptor Substrate-1 (IRS-1). When the insulin combines with insulin receptors, the IRS-1 is activated and signals the nucleus of muscle cell to accept glucose; as a result, special doors (GLUT-4 receptor) open up in surface of muscle cell from wherein the glucose entry occurs. Aldosterone lowers the response of IRS-1 (downregulates) to insulin binding with its receptor. This is called insulin resistance. [Hypertension 2007; 50: 750-755]
As a result of insulin resistance, glucose entry into the muscles is compromised, blood glucose levels rise and T2DM is precipitated. Thus, insulin resistance causes T2DM - the resultant outcome of excess aldosterone levels following infection with SARS-CoV-2 virus.
SUMMARIZING
Within four months post-infection with SARS-CoV-2 virus the risk of developing a new diabetes status is 1.5 times more than those who do not have COVID-19, and this risk enhances to being 2.5 times greater by 6 months post the acute phase of disease. [Diabetologia 2022; 65: 949-954]
Why?
Viral persistence post the acute phase of infection is a prime reason for not only developing new diabetes post-COVID-19 episode, but also for the PASC! [eLife 2022; 11: e78200]
The most surprising outcome of post-COVID-19 complication is developing new T1DM in adults! Usually T1DM constitutes only 10% of diabetes incidence, is detected in small children and has a genetic origin. But since SARS-CoV-2 can block ACE2 in pancreas, the insulin-manufacturing beta cells can all be destroyed with resultant dramatic decrease in the production of the blood glucose lowering (insulin) hormone - T1DM status.
The COVID-19 long-term complications should be a lesson-in-learning not only for those with PASC or Post-Covid-19 conditions, but for all. Do not take diseases like infection with SARS-CoV-2 lightly. Being symptomatically free does not mean ‘all is well’. There could have occurred many unknown body health concerns that could have occurred if the cause has not been emphatically addressed. Adopting the ostrich philosophy can cost one dear.
DR R K SANGHAVI
Prophesied Enabler
Experience & Expertise: Clinician & Healthcare Industry Adviser
So, this explains the higher occurrence of Diabetes in those inflicted by Covid. Any thing that can be done to prevent this from happening?
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