Do you know how our understanding and treatment of diabetes has changed through history?
Oooh good question, anon!
As you may guess, diabetes mellitus is not new.
We've known about it since at least the Ebers Papyrus (1550 BCE) when the disease and a treatment was first described. This treatment was: "a liquid extract of bones, grain, grit, wheat, green lead and earth." I did not look these up, but I would guess they did not do a whole lot for the treatment of diabetes.
Later during the 6th century BCE it was first given a name when it was described by Hindu physician Sushruta as madhumeh or "honey urine."
Honey urine is a very apt descriptor for diabetes. In any type, one of the most measurable symptoms is that the person urinates a lot, and the urine tastes sweet (or, if one didn't feel like tasting, that it ferments, or that it attracts ants). This was also the first test for diabetes.
The reason for the sweetness of the urine (as well as a lot of other general info about diabetes) is spelled out more clearly in my "Don't Be That Guy Who Wrote Hansel and Gretel: Witch Hunters" post.
A Greek physician Apolonius of Memphis named it Diabetes, meaning "to siphon" (referring to the large amount of urine lost).
Roman physician Aretaeus later made the first precise description of diabetes. This included the classic symptoms of incessant thirst, copious urination, and constant hunger leading to emaciation and death. He also notes that if deprived of water, the patient will continue to urinate until they become so dehydrated that they die.
The term "Mellitus" was not added until the 1600s by an English physician Thomas Willis. This was again due to the sweetness of the expressed urine. Willis prescribed a diet of "slimy vegetables, rice, and white starch. He also suggested a milk drink which was distilled with cypress tops and egg whites, two powders (a mixture of gum arabic and gum dragant), rhubarb and cinnamon". Supposedly his patients improved if they kept to this diet, though few managed it long term. I honestly don't know how it would have worked, even temporarily.
A major breakthrough came in 1889 when it was discovered that if you removed the pancreas from a dog, the dog would become diabetic (particularly, that it would urinate large quantities of sweet urine). Up until this point it was thought that diabetes stemmed from the kidneys and bladder, or perhaps the lungs. This was the first time it had been shown experimentally that the pancreas was the problem.
Speaking of this, this was also part of a series of experiments where an English physician named Merkowski implanted a small amount of pancreas in the pancreas-less dog's fat, which reversed the diabetes temporarily. This proved that the pancreas was making something that helped regulate blood (and thus urine) sugar.
What this was wasn't figured out until 1921, when Canadian scientists Banting and Best (with help from McLeod and Collip) isolated something they called insletin (after the islets of langerhans, where the substance was being produced). It's important to note that all of these scientists hated each other so much they almost refused a Nobel Prize over it. Later, Collip would refine the substance and McLeod would rename it insulin.
Prior to insulin existing there was basically 1 vaguely useful treatment for diabetes. Unfortunately, that was starvation. So you could either die a slow and painful death by diabetes or you could die a slightly less slow but still painful death due to eating about 500 calories per day. Either way, diabetes was fatal, usually within a couple of years of diagnosis.
By 1923, the first commercial insulin product, Iletin, had been developed. Iletin was a U10 insulin (10 units per 1 milliliter- less potent than today's U100 and U500 insulins) and was made from pork pancreases. It took nearly a ton of pork pancreas to make 1oz of insulin. Fortunately, as a byproduct of the meat industry, pancreases were readily available.
Now, you might be thinking- no one has mentioned type 1 or type 2 yet in this entire post!
Well, you would be right, because diabetes wouldn't be split into 2 forms (insulin-dependent and non-insulin dependent) until 1979, and wouldn't be classified as types 1 and 2 until 1995. That's right- some of you were alive when there was only one kind of diabetes out there.
Now, there's more about the types in the Hansel and Gretel post, but essentially type 1 diabetes occurs when the pancreas itself stops producing insulin, usually in childhood. When this happens, the body stops being able to use sugar (insulin, a hormone, acts as a "key" to let sugar into cells for use). Without replacing that insulin, the person dies because their cells starve.
Type 2 diabetes occurs when the pancreas still produces insulin, but the cells stop responding to it correctly. This causes high sugar levels in the blood, which causes longer-term complications (infections, ulcers, blindness, neuropathy, heart and kidney disease, hyperosmolar syndrome, etc..) which eventually lead to death.
We started discovering oral drugs that worked on what would later become type 2 in the 1950s. Particularly those that worked by increasing the insulin output of the pancreas, but only when the pancreas was still producing some insulin.
Predicting which diabetics would benefit from oral therapies was challenging, but it was recognized that when the onset of diabetes was slow and came on in adulthood, the oral agents would work, while if it came on suddenly in childhood, the oral agents wouldn't. Terms like "adult onset" and "maturity onset" were common:
(Side note: if you have ever read Alas, Babylon (1955) there is a diabetic character who by today's standards clearly has type 1 diabetes, but wants to switch to the "new oral pill" (called "orinase" in the book, though they are likely referring to diabinese pictured above).)
From 1923 into the 1980s, insulin was given once or twice per day, and not particularly titrated to blood sugar. This was probably just because we didn't have a great way to measure blood sugar in real time. Pre-1970s, there was no way to test blood sugar outside of a lab setting.
Urine testing was common starting in the 1940s, but was cumbersome as it required a flame for heating the urine. By the 1950s, a test had been developed that didn't require a flame, but was still not practical for home use. In the 1960s, paper strips were developed that changed color for different amounts of sugar in the urine. The problem with this was that the strips couldn't change color until there was sugar in the urine- a blood sugar level of over 200 by today's measurements. Low blood sugar readings were impossible at this time, and had to be treated based on symptoms.
In the 1970s, blood sugar could finally be measured by putting a drop of blood on a test strip, wiping it off, and matching the color of the test strip to a chart. While less cumbersome than urine tests, this was still something that would generally only be done at a doctor's office.
In 1983, the first home blood glucometer is developed. Finally, it was practical to take one's sugar multiple times per day, and it becomes possible to experiment with "sliding scale" insulin injections that keep tighter control of blood sugar. By the late 90s, continuous glucose monitors became available- though unlike today's CGMs that allow readings in real time on a smartphone or monitor, these had to be downloaded to a computer at regular intervals.
The 1980s were the first decade where insulin pumps become widely available. The very first pump was large and had to be carried in a backpack, but it represented a huge step forward in glucose control, as it more closely mimicked the function of a working pancreas than once-daily injections.
For the next 30 or so years you really had to work to qualify for an insulin pump, but recently it's been found that pumps greatly improve compliance with blood glucose control whether or not the person had good compliance before getting the pumps, and insurance has gotten better about covering them (though CGMs are still a pain to get insurance to cover).
The 1980s was also the decade that recombinant human insulin (insulin made by genetically modified bacteria) was first used. Up until that point the only insulins were pork and beef insulins, which some people had allergic reactions to. Recombinant insulin was closer to regular human insulin than beef or pork, and represented a big change in how insulin was made.
Today for people who take insulin to manage their diabetes, insulin is usually given as a single injection of a long-acting basal insulin, coupled with smaller doses of ultra-short-acting insulins with meals or snacks. This is the closest we've gotten to mimicking the way a pancreas would work in the wild, and keeps very tight control of blood sugar. This can be done by fingerstick blood sugar tests and individual injections of insulin, or it can be done with a CGM and pump- it just depends on the resources available to the person and their personal preference.
110 notes
·
View notes