COVID19_31

So my posts over the weekend were all about age and coronavirus outcomes. The older we are, the more at risk we are. In this elsewhere politically correct world, SARS CoV2 bucks that trend and appears to be out-and-out ageist.

But what if? What if, rather than being the maker of a poor outcome, age is just a marker?

Fragments of evidence are appearing, and indeed have been since the first more considered papers started to emerge from China, that the metabolic health of the patient is very much correlated to the COVID19 outcome. Your isolation over the last six weeks must have been pretty extreme if you have not yet heard the word ‘co-morbidity’.

A premier league of COVID-19 co-morbidities has been forming: Hypertension, type II diabetes (T2DM), heart disease, cancer and obesity are each vying for the top spot in this somewhat macabre league.

The stats vary depending how and where the analysis was performed, but the message is strong and clear: Have one or more of these co-morbidities and your chances of a poorer COVID-19 outcome increase. And maybe age is indeed as much a maker as a marker as the older you are, the more likely you are to have more of these co-morbidities.

But do these players in the premier league have anything in common, other than their impact on COVID-19? Well, yes, actually they do. Two things in fact:

Hyperglycaemia and compensatory hyperinsulinaemia.

And yesterday I saw the first paper on COVID outcomes that started to join the dots.

Let me however start with an explanation of Type II diabetes (T2DM): Proteins, fats and carbohydrates are the three macro-nutrients that make-up the food we eat. A prime steak is (apart from its water content) mostly protein, olive oil is pure fat and potatoes and rice mostly carbohydrate. Refined sugar is 100% carbohydrate.

I will stay with carbohydrate. When you eat carbohydrate your body uses digestive enzymes to break down this macro-nutrient into molecules small enough to be absorbed into our blood. Glucose and fructose are the two most common of these small carbohydrate molecules – think of them as like Lego building blocks and the carbohydrate in potato as being long chains of these Lego blocks.

Once the glucose molecules from the potato have been freed-up, they will be absorbed into your blood, raising your ‘blood sugar level’ or more correctly termed your blood glucose level. The problem is, too much glucose in your blood is a bad thing. Yes, we can ‘burn’ glucose for energy (but not without issues), however un-checked rampant blood glucose starts attaching itself to protein molecules. This is bad news for your proteins and therefore bad news for you.

Of course we have an evolved system to protect ourselves against such damage. When your blood glucose level rises, the pancreas releases the hormone insulin into circulation to put things back in order. The insulin does many things but chief amongst these it tells your body to start squirrelling away the excess glucose. It tells our muscles to stock-up on glycogen (a starch made from lots of the glucose lego bricks – making glycogen is like digestion in reverse) and if there is any glucose left over, insulin tells the fat storage cells in your body and the liver to convert it to triglycerides and tuck those away as fat under your skin and around your vital organs. The liver also, under normal circumstances, makes glucose from excess protein and fat in the diet. Insulin switches off this process: Why continue to make your own glucose if there is plenty coming from your diet?

All perfectly under control.

But, what if you bombard your blood with glucose all the time and in excess? Well, your insulin system starts to creak under the strain. Too much insulin triggered by eating too much glucose too often, starts to dull the message of insulin. In particular, the liver gets a little deaf when it comes to insulin. The liver becomes a little less effective at making glycogen out of the excess glucose and doesn’t quite get the message to stop making its own glucose. So our pancreas has to release a bit more inulin to get its message across and get our blood glucose back under control.

The process of becoming deaf to insulin is a descending spiral. Get a bit deaf and that leads to a bit more deafness. Eventually, the liver is so deaf your pancreas just cannot produce enough insulin to get your blood sugar under control. That is Type II diabetes. Your body has lots of insulin in the blood but also lots of glucose as the insulin just is not keeping it under control.

Remember the words hyperglycaemia (raised glucose) and hyperinsulinaemia (raised insulin)? Well now we have a metabolic mechanism.

And did you notice a few things of interest on that journey? Raised insulin is telling your body to plump-up its fat cells: A mechanism for obesity. Also do you recall the liver’s role in producing triglycerides when there is excess glucose? Well (and this is something to save for another day) triglycerides are actually the form of fat correlated with heart disease – not your HDL or your LDLs – and so prolonged and repeated raised glucose and insulin will lead to raised heart disease risk.

A couple of other things about insulin I have not yet mentioned. Insulin triggers vasoconstriction (contraction of the muscular wall of blood vessels) and also stimulates the kidney to retrieve more sodium, increasing blood volume. Both these actions increase your blood pressure. And insulin is what we call an anabolic hormone, stimulating cell division and tissue growth. Sustained high levels of insulin will therefore be contributory to hypertension and pre-dispose tissues to potentially cancerous tumour development.

Let’s go back to our premier league of co-morbidities: hypertension, heart disease, type II diabetes, cancer and the like. It turns out that the appearance of these players in the league is not coincidence at all as they have the same management team – excess glucose and excess insulin.

So do we have evidence that hyperglycaemia and hyperinsulinaemia are implicated in COVID-19 outcomes. We do now. Whilst there are many studies linking type II diabetes to worsened COVID outcomes, for a mechanistic explanation I wanted to see if anyone had actually looked at glucose and insulin management in COVID patients.

Two studies published a few days ago did just that. If you want to skip the detail, please jump to the ‘CONCLUSIONS’ heading.

Before I dive into the detail, I need to explain first what a ‘HbA1c’ score is. Remember how I said that having sustained raised levels of glucose in the blood was bad news because the glucose would attach itself to proteins? Well one of the proteins in the front-line of that glucose attack is haemoglobin (Hb), the oxygen carrying protein in your red blood cells. When it gets ‘attacked’ by glucose it transforms into HbA1c. The so-called HbA1c test measures what proportion of your haemoglobin has been converted into this glucose-attacked form. If your HbA1c score is low, it means you have managed to keep your blood glucose under control; a higher score means there has been sustained higher levels of glucose in your blood.

HbA1c is a therefore a measure of how well you have controlled your blood sugar levels. It is actually a 90 day insight into that glucose management as haemoglobin molecules are recycled after 90 days.

The first study I cite was of 1,122 hospitalised COVID-19 patients between 1 March and 6 April to whom CGM monitors (continuous glucose monitors) had been attached.

451 of the patients were either:

• previously diagnosed as type II diabetic (T2DM)

• • measured to have a HbA1c score of 6.5% or higher (the clinical measure for T2DM but testing at admission ensured that all diabetic patients – previously diagnosed or not – could be included in the study)

• hyperglycaemic (they had two consecutive blood glucose readings above 180mg/dl in a 24 hour period during their hospital admission).

The study compared the outcomes of these 451 with the remaining cohort of 671.

• The 451 with measures of T2DM/hyperglycaemia were nearly five times more likely to die of COVID-19 than those who did not. Mortality rate in the 451 was 29%; in the 671 it was just 6%.
• Of greater concern, those patients from within the 451 who were not diabetic but had at least one hyperglycaemic event in hospital (raised blood glucose levels) had a 42% chance of dying from COVID-19. This is seven times higher than the non-hyperglycaemic/non-diabetic 671.
• Of those patients that recovered, patients with the T2DM/hyperglycaemic indicators had on average longer hospital stays than those who did not.

This is the first study I have seen that shows that acutely hyperglycaemic patients hospitalised with COVID-19, irrespective of T2DM diagnosis, are significantly more likely to die than patients without hyperglycaemia.

The second study published at the same time looked at 7,336 COVID-19 patients in China. 952 of these had been previously diagnosed with T2DM. In this study those with T2DM had a greater need of medical intervention, had a morality rate three times higher than those without T2DM and were more prone to multiple organ injury than non-diabetic patients.

What was interesting in this study, and unlike the majority of studies reported to date, is that they also continuously measured the blood glucose levels in the T2DM group. The researchers noticed that within this group, those who kept their blood glucose level within a good range of control were eight times less likely to die than those diabetics who had severe hyperglycaemic events whilst hospitalised.

CONCLUSIONS

Blood glucose levels matter.

There is hope for Type II diabetics here. If you have T2DM, then, as previous studies have shown, your risk of a poorer COVID-19 outcome is increased. BUT, these most recent studies show that you can significantly mitigate that risk with better blood glucose management: Reduce your hyperglycaemia. And that is in your hands: Reduce your consumption of carbohydrate.

The latest studies also though give us a veiled warning: Just because you have not been diagnosed with T2DM does not mean that the risk does not apply to you. If you have any of the other premier league of co-morbidities that are under the same ‘management team’ as type II diabetes, then you could be at greater risk of severe COVID-19 outcome as they could be the signs that your insulin and blood glucose mechanisms are deteriorating. Being obese (or over-weight), having a history of heart disease, or having hypertension might be indicators of this. You could also look like the ‘otherwise healthy’ but the downward spiral of insulin deafness might have already started for you. These might be the hidden risks for COVID-19 severity. Fortunately for you too, the same mitigation applies – get your blood glucose levels under control and you have reduced your risk.

And you can start getting your blood glucose under control today……..