Econstudentlog

Diabetes: The Biography

“When I retired from clinical practice in 1998, my intention was (and still is) to write a definitive, exhaustively referenced, history of diabetes, which would be of interest primarily to doctors. However, I jumped at the suggestion of the editors of this series at Oxford University Press that I should write a biography of diabetes that would be about a tenth of the length of a full history with a minimum of references, for a wide general readership.”

This book is the result. As I pointed out on goodreads, this book is really great. The book is not particularly technical compared to other books about diabetes which I’ve read in the past, however this semi-critical review does make the point that the coverage is occasionally implicitly ‘asking too much’ even from diabetic readers (“There were parts of all this that lost my interest or that I lacked the background to appreciate”). Whereas the reviewer was apparently to some extent getting lost in the details, so was I – but in a completely different way; I was simply amazed at the amount of small details and interesting observations included in the book that I did not know, and I loved every single chapter of the book. The author of the other review incidentally also states that: “I don’t recommend that anyone read this who is not already familiar with diabetes, either by having it or knowing someone with it.” I’d note that I’m not sure I agree with this recommendation, to the extent that it’s even ‘relevant’ – these days such people who don’t even know anyone with diabetes might well be a bit hard to find, on account of the fact that diabetes has become a quite common illness. Presumably a significant proportion of the people who assume they don’t know anyone with the disease might well do so anyway, because a very large number of people have type 2 diabetes without knowing it. I think a reader would get more out of the book if he or she has diabetes or knows someone with diabetes, but a lot of people who do not would also benefit from knowing the stuff in this book. Not only in a ‘and now you know how bad type 2 is and why you should get checked out if you think you’re at risk’-sense (there’s incidentally also a lot of stuff about type 1), but also in the ‘the history of diabetes is really quite fascinating’-sense. I do think it is.

Have a look at this image. The book included a similar picture (not exactly the same one, but it’s of the same patient and the ‘before’ picture is obviously taken at the same time this one was), which is of Billy Leroy, a type 1 diabetic, before and after he started insulin. He was one of the first patients treated with insulin (the first human treated with insulin was Leonard Thompson, in 1922). Billy Leroy’s weight in the first picture, where he was 3 years old, was 6.8 kg (the 5 % (underweight) CDC body weight cutoff at the age of 3 is 12 kg) – during the three months after he started on insulin, his weight doubled. The author argues in the beginning of the book that: “When people are asked to rank diseases in order of seriousness, diabetes is usually at the mild end of the spectrum.” This may or may not be true, but the picture to which I link above certainly adds a detail which is important to keep in mind but easy to forget when evaluating ‘the severity’ of the disease today – type 1 diabetes in particular is not much fun if you don’t have access to insulin, and until the early 1920s people with this disease simply died, most of them quite fast. (They all still do – like all other humans – but they live a lot longer before they die…)

The author knows his stuff and the book has a lot of content, making it hard to know what to pick out and mention in particular in a review like this – however below I have added a few quotes from the book and some observations made along the way. The content covering the late nineteenth century and the first couple of decades of the twentieth century, before it was discovered that insulin could save the lives of a lot of sick children, would in my opinion on its own be a strong reason for reading the book; but the chapters covering the periods that came after are wonderful as well. When insulin was discovered a religiously inclined mind might well be tempted to think of the effects on young type 1 diabetic children as almost miraculous; but gradually doctors treating diabetics came to realize (the patients never knew, because they were not told – it is pointed out in the book that the fact that it might make a lot of sense to give patients with a disease like diabetes some discretion in terms of how to treat their illness is a in a historical context very new idea; active patient involvement in medical decision-making is one of the cornerstones of current treatment regimes, for good reason, and I found it really surprising and frustrating to learn how this disease was treated in the past) that things might be more complicated than they had initially been assumed to be. Type 2 diabetics had suffered from late stage complications like blindness and kidney failure for centuries, but such complications had never before been observed in type type 1 diabetics before insulin, because diabetes presenting in children were pre-insulin universally fatal. It turned out that many of the children who were initially ‘saved’ by insulin in the early 1920s ended up suffering from severe complications just a couple of decades later, and many of them died early from these complications:

“After the Second World War it became clear that [diabetic] kidney disease could also affect the young, and there were increasingly frequent reports of diabetics who had been saved by insulin as children only to succumb to kidney failure in their 20s and 30s. Fifty of Joslin’s child patients who had started insulin before 1929 were followed up in 1949, when a third had died at an average age of 25, after having had diabetes for an average of 17.6 years. One half had died of kidney failure and the other half of tuberculosis and other infections. […] In the experience of the Joslin group, only 2 per cent of deaths of young diabetic patients before 1937 were due to kidney disease, but, of those who died between 1944 and 1950, more than half had advanced kidney disease. Results in Europe were equally bad. In 1955 all of eighty-seven Swiss children had signs of kidney disease after sixteen years of diabetes, and after twenty-one years all had died. Most young people with diabetic kidney disease also had severe retinopathy and many became blind—by the mid 1950s diabetes was the commonest cause of new blindness in people under the age of 50. […] Such devastating cases were being increasingly reported in the medical literature in the late 1940s and early 1950s, but they were not publicized in the lay press, presumably to avoid spreading despair and despondency and puncturing the myth that insulin had solved the problem of diabetes […] The British Diabetic Association (founded in 1935) produced a quarterly Diabetic Journal for its lay members, but no issue from 1940 to 1960 mentions complications”.

The book makes it clear that patients were for many years basically to some extent kept in the dark about the severity of their condition, but in all fairness for a long time the doctors treating them frankly didn’t know enough to give them good information on a lot of topics anyway. The book has some really interesting observations included about how medical men of the times thought about various aspects of the illness and treatment, and how many of the things we know today, some of which ‘seem obvious’, really were not to people at the time. Many attempts have been made over time to explain why people got diabetes, and especially type 1 was really quite hard to pin down – type 2 was somewhat easier because the lifestyle component was hard to miss; however it was natural to explain the disease in terms of the symptoms it caused, and some of those symptoms in type 2 diabetics were complications which are best considered secondary to the ‘true’ disease process. For example because many type 2 diabetics suffered from disorders of the nervous system, neuropathy, the nervous system was for a while assumed to be implicated in causing diabetes – but although disorders of the nervous system can and often do present in long-standing diabetes, they are not why type 2 diabetics get sick. Kidney problems were thought to be “part and parcel of diabetes in the 19th century.” Oskar Minkowsky made it clear in 1889 that removal of the pancreas caused severe (‘type 1-like’) diabetes in dogs – but despite this discovery it still took a long time for people to figure out how it worked. This wasn’t because people at the time were stupid. One problem faced at the time was that the pancreas actually looked quite normal in people who died from diabetes – the islet cells which are implicated in the disease weigh around 1-1.5 grams altogether, and make up only a very small proportion of the pancreas (1% or so). Many doctors found it hard to imagine that the islets cells could be reponsible for controlling carbohydrate metabolism (and other aspects of metabolism as well – “It is important to realize that diabetes is not just a glucose disease. There are also abnormalities of fat metabolism”). The pancreas wasn’t the only organ that looked normal – despite the excessive urination the kidneys did as well, and so did other organs, to the naked eye. All major features of diabetic retinopathy (diabetic eye disease) had been described by the year 1890 with the aid of the ophthalmoscope, so people knew the eyes of people with long-standing diabetes looked different; how to interpret these findings was however not clear at the time – some argued the eye damage found in diabetics was not different from eye damage caused by hypertension, and treatment options were non-existent anyway.

Many of the treatment options discussed among medical men before insulin were diets, and although dietary considerations are important in the treatment context today, it’s probably fair to say that not all of the supposed dietary remedies of the past were equally sensible: “One diet that had a short vogue in the 1850s was sugar feeding, brainchild of the well-known but eccentric French physician Pierre Piorry (1794–1879). He thought that diabetics lost weight and felt so weak because of the amount of sugar they lost in the urine and that replacing it should restore their strength”. (Aargh!). For the curious (or desperate) man, though, there were alternatives to diets: “A US government publication in 1894 listed no less than forty-two anti-diabetic remedies including bromides, uranium nitrate, and arsenic.” Relatedly, “in England until 1925, any drug could be advertised and marketed as a cure for any disease, even if it was completely ineffective”. Whether or not diets ‘worked’ depended in part on what those proposed diets included (see above..), whether people followed them, and whether people who presented were thin or fat. In the book Tattersall mentions that already from the middle of the nineteenth century many physicians thought that there were two different types of diabetes (there are more than two, but…). The thin young people presenting with symptoms were by many for decades considered hopeless cases (that they were hopeless cases was even noted in medical textbooks at the time), because they had this annoying habit of dying no matter what you did.

It should be noted that the book indirectly provides some insights into the general state of medical research and medical treatment options over time; for an example of the former it is mentioned that the first clinical trial (with really poor randomization/selection mechanisms, it seems from the description in the book) dealing with diabetes was undertaken in the 1960es: “the FDA demanded randomized controlled trials for the first time in 1962, and [the University Group Diabetes Program (UGDP)] was the first in diabetes. Before 1962 the evidence in support of therapeutic efficacy put to the FDA was often just ‘testimonials’ from physicians who casually tested experimental drugs on their patients and were paid for doing so.” See also this link. An example of the latter would be the observation made in the book that: “until the 1970s treatment for a heart attack was bed rest for five or six weeks, while nature took its course.” Diabetics were not the only sick people who had a tough time in the past.

One interesting question related to what people didn’t know in the beginning after the introduction of insulin was how the treatment might work long-term. The author notes that newspapers in the early years made people believe that insulin would be a cure; it was thought that insulin might nurse the islet cells back to health, so that they’d start producing insulin on their own again – which was actually not a completely stupid idea, as e.g. kidneys had the ability to recover after acute glomerulonephritis. The fact that diabetics often started on high doses which could then be lowered a month or two later even lent support to this idea; however it was discovered quite fast that regeneration was not taking place. Remarkably, insulin was explored as a treatment option for other diseases in the 1920s, and was actually used to stimulate appetite in tuberculosis patients and ‘in the insane refusing food’, an idea which came about because one of its most obvious effects was weight gain. This effect was also part of the reason why insulin was for a long time not considered an attractive option for type 2 diabetics, who instead were treated only with diet unless this treatment failed to reduce blood sugar levels sufficiently (these were the only two treatment options until the 1950s); most of them were already overweight and insulin caused weight gain, and besides insulin didn’t work nearly as well in them as it did in young and lean people with type 1 because of insulin resistance, which lead to the requirement of high doses of the drug.

Throughout much of the history of diabetes, diabetics did not measure their blood glucose regularly – what they did instead was measuring their urine, figuring out if it contained glucose or not (glucose in the urine indicates that the blood glucose is quite high). This meant that the only metric they had available to them to monitor their disease on a day to day basis was one which was unable to measure low blood glucose, and which could only (badly) distinguish between much too high blood glucose values and not-much-too-high values. Any type of treatment regime like the one I’m currently on would be completely impossible without regular blood tests on a daily basis, and I was very surprised about how late the idea of self-monitoring of blood glucose appeared; like the measurement of Hba1c, this innovation did not appear until the late 1970s. Few years after that, the first insulin pen revolutionized treatment regimes and made treatment regimes using multiple rejections each day much more common than they had been in the past, facilitating much better metabolic control.

The book has a lot of stuff about specific complications and the history of treatment advances – both the ones that worked and some of the ones that didn’t. If you’re a diabetic today, you tend to take a lot of stuff for granted – and reading a book like this will really make you appreciate how many ideas had to be explored, how many false starts there were, how much work by so many different people actually went into giving you the options you have today, keeping you alive, and perhaps even relatively well. One example of the type of treatment options which were considered in the past but turned out not to work was curative pancreas transplants, which were explored in the 60es and 70es: “Pancreas transplantation offered a potential cure of type 1 diabetes. The first was done in 1966 […] Worldwide in the next eleven years, fifty-seven transplants were done, but only two worked for more than a year”. Recent attempts to stop people at risk of developing type 1 diabetes from becoming sick are also discussed in the last part of the book, and in this context he makes a point I was familiar with: “[Repeated] failures [in this area] are particularly frustrating, because, in the best animal model of type 1 diabetes, the NOD mouse, over 100 different interventions can prevent diabetes.” This is one of the reasons why I tend to be skeptical about results from animal studies. Although he spends many pages on complications – which in a book like this makes a lot of sense given how common these complications were (and to some extent still are), and how important a role they have played in the lives of people suffering from diabetes throughout the ages – I have talked about many of these things before, just as I have talked about the results of various large-scale trials like the DCCT trial and the UKPDS (see e.g. this and this), so I will not discuss such topics in detail here. I do however want to briefly remind people of what kind of a disease badly managed type 2 diabetes (the by far most common of the two) is, especially if it is true as the author argues in the introduction that many people perceive of it as a relatively mild disease – so I’ll end the post with a few quotes from the book:

“I took over the diabetic clinic in Nottingham in 1975 and three years later met Lilian, an overweight 60-year-old woman who was on tablets for diabetes. She had had sugar in her urine during her last pregnancy in 1957 but was well until 1963, when genital itching (pruritus vulvae) led to a diagnosis of diabetes. She attended the clinic for two years but was then sent back to her GP with a letter that read: ‘I am discharging this lady with mild maturity onset diabetes back to your care.’ She continued to collect her tablets but had no other supervision. When I met her after she had had diabetes for eighteen years she was blind, had had a heart attack, and had had one leg amputated below the knee. The reason for the referral to me was an ulcer on her remaining foot, which would not heal. […] Someone whose course is not dissimilar to that of Lilian is Sue Townsend (b. 1946), author of the Adrian Mole books. She developed diabetes at the age of 38 and after only fifteen years was blind from retinopathy and wheelchair bound because of a Charcot foot, a condition in which the ankle disintegrates as a result of nerve damage. Neuropathy has also destroyed the nerve endings in her fingers, so that, like most other blind diabetics, she cannot read Braille. She blames her complications on the fact that she cavalierly disregarded the disease and kept her blood sugars high to avoid the inconvenience of hypoglycaemic (low-blood-sugar) attacks.”

January 25, 2015 - Posted by | books, diabetes, medicine

No comments yet.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: