Friday, November 30, 2012

Question from Megan - Causes of death

Has there been any papers published about the illness that caused the death of Arthur Tudor, Henry FitzRoy, Edward VI, and Henry Brandon, Earl of Lincoln. I can't remember where I read it, but diabetes could have been the genetic cause of death, thanks


PhD Historian said...

Since I am both a Registered Nurse and an academic research historian, I would like to weigh in here. And the first thing I have to say is that Megan raises a wonderfully interesting question!

Type I diabetes, sometimes called juvenile diabetes, can have an age of onset at any point during childhood and adolescence. In the absence of insulin replacement therapy, it is eventually fatal, though death from diabetes itself is less common than from the complications caused by the presence of diabetes.

Instead, death often results from a secondary condition known as diabetic ketoacidosis (DKA). In this condition, any other physical illness, such as an infection, increases the body's need for the basic sugar glucose, from which energy is produced by the individual cells of the body. Insulin helps move the glucose out of the bloodstream and into the cells. Diabetes impairs insulin production, yet during an illness the body will still increase glucose production. Without the necessary insulin to move that glucose into the cells, the blood glucose level can become extremely high. The individual cells, starved of glucose, turn instead to fat for producing energy. The by-products of unusual and extremely rapid fat metabolism, called ketones, then accumulate in the blood, since the body is not accustomed to disposing of such high levels. This then leads to the blood becoming more acidic than normal. The tiniest of changes in the pH (relative acidity- alkalinity) of the blood can have catastrophic effects on other body systems and lead quickly to death. The key word here is "quickly". Death from DKA usually occurs in a matter of hours or days, depending on the severity of the underlying infection. DKA and death can also occur in the absence of infection if the Type I diabetes progresses to the point of zero insulin production.

Type I diabetes does appear to have a genetic component, but is not itself 100% genetic. That is, it does tend to run in families, but factors other than genetics also play a role in whether or not someone actually develops Type I diabetes. It would be a little unusual for a cluster of people as closely related as Arthur Tudor, Henry Fitzroy, Edward VI, and Henry Brandon (all sons or grandsons of Henry VII) to be ALL affected. And Megan’s premise (and that of others who have suggested this inherited-diabetes scenario) seems to hinge largely on the supposition that Henry VIII had diabetes. Henry was, after all, Arthur’s brother, Fitzroy’s and Edward’s father, and Brandon’s uncle. IF Henry VIII had diabetes (see below), he had Type II (adult onset), not Type I. Type I and Type II diabetes are distinctly different disease entities and do not appear to have the same root cause or genetic predisposition. That is, people with Type II diabetes are NOT more likely to have relatives with Type I diabetes.

The modern prevalence of Type 1 (juvenile) diabetes is 0.02%. That is extremely low. Assuming the rate was similar in the first half of the sixteenth century, the statistical likelihood that any specific child of the Tudor bloodline had Type 1 diabetes is about 1 in 5000. In the same era, the statistical likelihood that any person would die before reaching adulthood was as much as 1 in 4 or 1 in 3. The far greater statistical probability, therefore, is that a child of the Tudor bloodline is hundreds of times more likely to have died from any of the “normal” fatal illnesses common in the period than to have died from Type I diabetes specifically.

(Word length limits required me to cut this in half ...)

PhD Historian said...

Arthur Tudor certainly died from some type of infection, since his wife Katherine of Aragon was also ill (but recovered). And his death was relatively sudden. But whether Arthur’s death was hastened by the presence of Type I diabetes cannot be determined since there is not sufficiently thorough description of his symptoms to make even a tentative diagnosis possible.

Henry Fitzroy’s final illness seems to have been a bit more protracted, though he seems to have died within a month of becoming ill. But as with Arthur, there is simply not enough documentation of his symptoms available either to include or exclude Type I diabetes as a contributing factor.

Henry Brandon’s illness was a protracted one of several months. This is not generally consistent with complications from Type I diabetes. And as with Arthur and Fitzroy, there is not sufficient record of his symptoms to make it possible to formulate a tentative diagnosis.

Edward VI certainly did not have Type I diabetes. Edward was extremely ill with a pulmonary infection for at least a month prior to his death. Had he actually had Type I diabetes, the pulmonary infection would have led to DKA almost immediately (within hours), and he would have died within hours or days.

Lastly, we come to Henry VIII himself, whose well-documented illnesses have led to much of the speculation about diabetes as a genetic disorder among the Tudors. Henry famously suffered from a non-healing ulcer on his leg throughout the last years of his life, and he was markedly obese. Obesity is a strong contributing factor in modern Type II (adult) diabetes, and leg ulcers are a common complication. However, Henry’s leg ulcer can be traced with greater reliability to injuries he is known to have sustained during his jousting days. The greater likelihood is that he suffered from chronic osteomyelitis, an infection of the bone that creates an ulcer and fails to heal. Osteomyelitis can and does occur in persons who do not have diabetes. Even in this modern medical era of IV antibiotics, it can be a very difficult condition to cure, even when the sufferer is otherwise healthy. Had Henry VIII’s leg ulcer been the result of Type II diabetes, he would certainly have died much earlier than 1547 and much closer to the time the ulcer was first reported.

Apologies for the very lengthy response, but I did want to be thorough.

Marilyn R said...

Very interesting stuff.I often wonder about the sudden death of Edward IV, who seems to have expired as a result of an excess of good living.

Bearing in mind the fashions of the day and Henry VIII's pride in his (apparently) splendid manly calves, how well could the dressings and bandages have been camouflaged under tight-fitting hose? Also, would there have been a bad odour coming from the ulcers? Does anyone have any ideas?

(At the coronation of George IV, who for some strange reason chose a Tudor fashion theme for himself and his male attendants, the writer Sir Walter Scott commented that as a group the effect wasn't too bad, but seen individually, with varicose veins, wrinkled stockings and the rest, the effect in many cases was awful.)

Laura said...

PhD Historian, I'm a mom of a Type 1 child, so I know a bit about it as well, and by and large agree with what you say here. The likelihood of H VIII's Type 2 diabetes has no bearing on the possibility of Type 1 for anyone in the Tudor bloodline.

However, I've always considered Type 1 as a possible contributing factor for Arthur Tudor's death. As you undoubtedly know, Type 1 is usually triggered by a viral illness...the suspicion is that the virus is what triggers the autoimmune process that leads to the destruction of islet cells in the pancreas, which is what causes Type 1 diabetes. The genetic predisposition means little if the autoimmune process isn't triggered. However, given the frequency of contagion in the Tudor era, with the lack of proper medical treatment, it seems very likely that most children with the genetic predisposition would face viruses which could trigger the autoimmune process, so it's possible that the incidence of Type 1 diabetes was more common in the medieval era.

Frequently, children with Type 1 diabetes have months of high blood sugars before diagnosis, that do not result in DKA due to the fact that the pancreas still produces insulin in decreasing amounts. Diagnosis usually occurs when the diabetes advances to the point of very low to nonexistent insulin production, which is when the child starts experiencing the common symptoms of excessive thirst and urination. The diet of medieval children would probably contribute to a longer process as well. While bread and pastries were a large part of the medieval diet, whole grain flour, which was the only flour available at the time, does not cause as many high blood sugars as the common flour of today due to the higher protein and fiber content.

Prior to the introduction of insulin, many children of Type 1 diabetes died of starvation before DKA had a chance to kill them. This is due to the fact that blood cells can't access the sugar in the blood stream, causing gradual starvation over a period of time, despite the increased food intake caused by the increased hunger the body feels when it cannot convert the glucose in the blood stream to energy. This is why extreme weight losses are also typical before diagnosis. That weight loss also makes children vulnerable to death from infections, which means that flu viruses and other infections are more likely to kill these children than children without Type 1 diabetes

My theory has always been that perhaps the illness that Arthur and Katherine of Aragon suffered, combined with the the possibility of early stage Type 1 diabetes could have been the cause of Arthur succumbing to the illness from which Katherine of Aragon recovered. Arthur was never a robust boy, and the starvation of early stage Type 1 diabetes would have made him even weaker.

Ultimately, we'll never discover the reason for any of the deaths of the young men, but it is fun and fascinating to debate.

PhD Historian said...

Laura, I do hope your child is coping with with his or her condition. Care and treatment for diabetics of both types has advanced remarkably since I got my nursing license 32 years ago!

I would not argue that Arthur Tudor did NOT have Type I diabetes. I simply argue that there is not sufficient discussion in the original (primary source) historical record of his symptoms to make any determination one way or the other. With Edward VI, I believe the contemporary descriptions of the course of his illness are sufficiently detailed to allow exclusion of Type I diabetes. For the others (Arthur, Fitzroy, Brandon), the evidence is just too sketchy and inconclusive.

Marilyn R, there was an excellent show on History Channel called "Inside the Body of Henry VIII" that dealt very specifically (and reasonably accurately, for a television show) with Henry's health conditions, including the leg ulcers and their causes. I do not recall that it addressed the issue of hiding them, however. Still, my understanding is that the ulcers were at their worst only later in life, after about 1540. By that point, he was markedly obese and less vain about his appearance, including his legs. How vain can you be when you weigh 28 stone (almost 400 pounds)?!? And yes, by that time the ulcers were indeed malodorous. But did they smell any worse than all the other unwashed bodies of dozens of courtiers crammed into rooms with poor ventilation, excrement (both human and animal) on the floors, etc? I think we too often underestimate the degree to which Tudor persons and households simply "stunk to high heaven"!

tudor princess said...

I have wondered why Henry was depicted wearing red hose, rather than white, in his later portraits eg the Barber Surgeon picture by Holbein. I have a suspicion that the reason is it's easier to disguise marks eg blood on red hose from his ulcers.

Actually, I think it must have been hell for such a pernickety person as Henry (he's the one that complained that Anne of Cleves smelt!) to suffer those ulcers. He must have been acutely aware of the smell. Elizabeth seems to have inherited her father's sense of smell so doubtless she suffered from living in what was a very smelly age.

It's interesting that you mention the coronation of George IV, Marilyn. When I went to the Gold Exhibition, they had one of the "Tudor" doublets on show, worn by one of the pages. It was extremely over the top!

Unknown said...

I'm confused by the mentions of Henry VIII's ulcer and hose. I was under the impression the ulcer was on his thigh, where it would have been concealed by breeches, and not on his calf...?

reptilegrrl said...

PhD Historian: surely you have heard of LADA (Latent Autoimmune Diabetes in Adults)? And are you aware that people with family histories of Type 1 diabetes are at increased risk of developing Type 2 diabetes?

reptilegrrl said...

Also WRT to wound healing and Type 2 diabetes: slow wound healing is actually also a symptom of Insulin Resistance, which when untreated leads to Type 2 diabetes and is also a greater risk factor for heart disease. It is possible that Henry became gradually more IR, and upon developing full-blown diabetes, went downhill rapidly.

As for the association between Type 1 and Type 2, I've had that information from multiple endocrinologists. In my family we have both Type 1 diabetes and a hereditary form of hypoglycemia that can lead to Type 2 if untreated.