Reversing Type 1 Diabetes With A Patient’s Own Stem Cells

October 6, 2024 by Maya Posch 8 Comments

Type 1 diabetes is an auto-immune condition whereby the patient’s own immune system attacks the pancreatic islets, destroying them in the process. Since these islets are responsible for producing insulin in response to blood sugar (glucose) levels, the patient is thus required to externally inject insulin for the remainder of their life. That was the expected scenario, but it appears that this form of diabetes may soon be treatable, with one woman now being free of the condition for a year already, as reported in Nature, referencing an article by [Shusen Wang] et al. that describes the treatment and the one-year result.

Most notable with this study is that the researchers didn’t use the regular method to create pluripotent stem cells. These cells were extracted from the patient, to revert back to this earlier developmental stage. They were not modified using genes, but rather singular chemicals (PDF). The advantage of this is that it avoids having to modify the cell’s genomes, which could conceivably cause issues like cancer later on. This was one of the first time that this method was used in a human subject, with islet cells formed and about 1.5 million of them injected into the patient’s abdominal muscles, a novel site for this procedure.

This location made these islets easy to keep track of, and easier to remove in case of any issues compared to the usual injection site within the liver. Fortunately for this woman, no complications occurred and one year later she is still free of any diabetes symptoms. Two other patients in the trial are also seeing very positive results, leaving only the question of whether the auto-immune condition that originally caused the islet destruction still exists. Since this female patient is taking immunosuppressants for a previous liver transplant it’s a hard to thing to judge, especially since we understand the causes behind type 1 diabetes so poorly.

Regardless, this and other trials using pluripotent cells, transplanted islets and more offer the prospect of a permanent treatment for the many people who suffer from type 1 diabetes.

Featured image: “Human induced pluripotent stem cell colony” National Eye Institute/NIH

Software Bug Results In Insulin Pump Injuries, Spurs Recall

May 11, 2024 by Dan Maloney 24 Comments

Managing Type 1 diabetes is a high-stakes balancing act — too much or too little insulin is a bad thing, resulting in blood glucose levels that deviate from a narrow range with potentially dire consequences on either side. Many diabetics choose to use an insulin pump to make managing all this easier, but as a recent recall of insulin pump software by the US Food and Drug Administration shows, technology isn’t foolproof.

Thankfully, the recall is very narrow in scope. It’s targeted at users of the Tandem t:slim X2 insulin pump, and specifically the companion application running on iOS devices. The mobile app is intended to run on the user’s phone to monitor and control the pump. The pump itself is a small, rechargeable device that users often keep on their belt or tucked into a pocket that delivers a slow, steady infusion of insulin during the day, plus larger bolus doses to compensate for meals.

But version 2.7 of the t:connect mobile app can crash unexpectedly, and on iOS devices, that can lead to the OS continually relaunching it. Each time it does this, the app tries to reconnect with the pump via Bluetooth, which eventually runs down the battery in the pump. Once the battery is dead, no more insulin can be delivered, potentially leading to a condition called hyperglycemia (“hyper” meaning an excess, “gly” referring to sugar, and “emia” meaning presence in blood — excess sugar in the blood.)

Untreated hyperglycemia can progress to a much more serious state called diabetic ketoacidosis, which can lead to coma and death. Thankfully, nobody has suffered that fate from this bug, but the FDA has received over 200 reports of injuries, hence the recall. Tandem sent out a notice to all affected customers back in March to update their apps, but it’s still possible that some users didn’t get the message.

Apart from the human cost of this bug, there’s a lesson here about software design and unintended consequences. While it intuitively seems like a great idea to automatically relaunch a crashed app, especially one with a critical life-safety function, in hindsight, the better course might have been to just go into a safe mode and alert the user with an alarm. That’s a lesson we’ve learned by exploring space, and it seems to apply here as well.

Images: AdobeStock, Tandem Diabetes

DIY Chemistry Points The Way To Open Source Blood Glucose Testing

January 4, 2024 by Dan Maloney 16 Comments

Every diabetic knows that one of the major burdens of the disease is managing supplies. From insulin to alcohol wipes, diabetes is a resource-intensive disease, and running out of anything has the potential for disaster. This is especially true for glucose test trips, the little electrochemical dongles that plug into a meter and read the amount of glucose in a single drop of blood.

As you might expect, glucose test strips are highly proprietary, tightly regulated, and very expensive. But the chemistry that makes them work is pretty simple, which led [Markus Bindhammer] to these experiments with open source glucose testing. It’s all part of a larger effort at developing an open Arduino glucometer, a project that has been going on since 2016 but stalled in part thanks to supply chain difficulties on the chemistry side, mainly in procuring glucose oxidase, an enzyme that oxidizes glucose. The reaction creates hydrogen peroxide, which can be measured to determine the amount of glucose present.

With glucose oxidase once again readily available — from bakery and wine-making suppliers — [Markus] started playing with the chemistry. The first reaction in the video below demonstrates how iodine and starch can be used as a reagent to detect peroxide. A tiny drop of glucose solution turns the iodine-starch suspension a deep blue color in the presence of glucose oxidase.

While lovely, colorimetric reactions such as these aren’t optimal for analyzing blood, so reaction number two uses electrochemistry to detect glucose. Platinum electrodes are bathed in a solution of glucose oxidase and connected to a multimeter. When glucose is added to the solution, the peroxide produced lowers the resistance across the electrodes. This is essentially what’s going on in commercial glucose test strips, as well as in continuous glucose monitors.

Hats off to [Markus] for working so diligently on this project. We’re keenly interested in this project, and we’ll be following developments closely. Continue reading “DIY Chemistry Points The Way To Open Source Blood Glucose Testing” →

An Insulin Injection That Lasts For Days: A New Hope For Diabetics

December 27, 2023 by Maya Posch 12 Comments

A major challenge for people who have a form of diabetes is the need to regulate the glucose levels in their body. Normally this is where the body’s insulin-producing cells would respond to glucose with a matching amount of insulin, but in absence of this response it is up to the patient to manually inject insulin. Yet recent research offers the hope that these daily injections might be replaced with weekly injections, using insulin-binding substances that provide a glucose-response rather like the natural one. One such approach was tested by Juan Zhang and colleagues, with the results detailed in Nature Biomedical Engineering.

In this study, the researchers injected a group of diabetic (type 1) mice and minipigs with the formulation, consisting out of gluconic acid-modified recombinant human insulin bound to a glucose-responsive phenylboronic acid-diol complex. The phenylboronic acid element binds more easily to glucose, which results in the insulin being released, with no significant hypoglycemia observed in this small non-human test group. A major advantage of this mechanism is that it is fully self-regulating through the amount of glucose present in the blood.

This study is similar to work by Sijie Xian and colleagues published in Advanced Materials (ChemRxiv preprint) where a similar complex of glucose-sensitive, bound insulin complex was studied, albeit in vitro. With non-human animal testing showing good results for this method, human trials may not be far off, which could mean the end to daily glucose and insulin management for millions in the US alone.

(Top image: Chemical structures of the insulin-DiPBA complex and its functioning. Credit: Sijie Xian et al., 2023)

Implant Fights Diabetes By Making Insulin And Oxygen

October 10, 2023 by Dan Maloney 13 Comments

Type 1 diabetes remains a problem despite having an apparently simple solution: since T1D patients have lost the cells that produce insulin, it should be possible to transplant those cells into their bodies and restore normal function. Unfortunately, it’s not actually that simple, and it’s all thanks to the immune system, which would attack and destroy transplanted pancreas cells, whether from a donor or grown from the patient’s own stem cells.

That may be changing, though, at least if this implantable insulin-producing bioreactor proves successful. The device comes from MIT’s Department of Chemical Engineering, and like earlier implants, it relies on encapsulating islet cells, which are the insulin-producing cells within the pancreas, inside a semipermeable membrane. This allows the insulin they produce to diffuse out into the blood, and for glucose, which controls insulin production in islet cells, to diffuse in. The problem with this arrangement is that the resource-intensive islet cells are starved of oxygen inside their capsule, which is obviously a problem for the viability of the implant.

The solution: electrolysis. The O₂-Macrodevice, as the implant is called, uses a tiny power-harvesting circuit to generate oxygen for the islet cells directly from the patient’s own interstitial water. The circuit applies a current across a proton-exchange membrane, which breaks water molecules into molecular oxygen for the islet cells. The hydrogen is said to diffuse harmlessly away; it seems like that might cause an acid-base imbalance locally, but there are plenty of metabolic pathways to take care of that sort of thing.

The implant looks promising; it kept the blood glucose levels of diabetic mice under control, while mice who received an implant with the oxygen-generating cell disabled started getting hyperglycemic after two weeks. What’s really intriguing is that the study authors seem to be thinking ahead to commercial production, since they show various methods for mass production of the cell chamber from standard 150-mm silicon wafers using photolithography.

Type 1 diabetics have been down the “artificial pancreas” road before, so a wait-and-see approach is clearly wise here. But it looks like treating diabetes less like a medical problem and more like an engineering problem might just pay dividends.

The New-Phone Blues: A Reminder That Hackers Shouldn’t Settle

March 22, 2022 by Dan Maloney 67 Comments

For all the convenience and indispensability of having access to the sum total of human knowledge in the palm of your hand, the actual process of acquiring and configuring a smartphone can be an incredibly frustrating experience. Standing in those endless queues at the cell phone store, jumping through the administrative hoops, and staring in sticker shock at a device that’s likely to end its life dunked in a toilet all contribute to the frustration.

But for my money, the real trouble starts once you get past all that stuff and start trying to set up the new phone just right. Sure, most phone manufacturers make it fairly easy to clone your old phone onto the new one, but there are always hiccups. And for something that gets as tightly integrated into the workflows of your daily life as cell phones do, that can be a real bummer. Especially when you find out that your shiny new phone can’t do something you absolutely depend on.

Continue reading “The New-Phone Blues: A Reminder That Hackers Shouldn’t Settle” →

Tech In Plain Sight: Glucose Meters

October 20, 2021 by Al Williams 27 Comments

If you or someone you know is diabetic, it is a good bet that a glucose meter is a regular fixture in your life. They are cheap and plentiful, but they are actually reasonably high tech — well, at least parts of them are.

The meters themselves don’t seem like much, but that’s misleading. A battery, a few parts, a display, and enough of a controller to do things like remember readings appears to cover it all. You wouldn’t be surprised, of course, that you can get the whole affair “on a chip.” But it turns out, the real magic is in the test strip and getting a good reading from a strip requires more metrology than you would think. A common meter requires a precise current measurement down to 10nA. The reading has to be adjusted for temperature, too. The device is surprisingly complex for something that looks like a near-disposable piece of consumer gear.

Of course, there are announcements all the time about new technology that won’t require a needle stick. So far, none of those have really caught on for one reason or another, but that, of course, could change. GlucoWatch G2, for example, was a watch that could read blood glucose, but — apparently — was unable to cope with perspiration.

Even the meters that continuously monitor still work in more or less the same way as the cheap meters. As Hackaday’s Dan Maloney detailed a few years back, continuous glucose monitors leave a tiny sensor under your skin and measure fluid in your body, not necessarily blood. But the way the sensor works is usually the same.

For the purposes of this article, I’m only going to talk about the traditional meter: you insert a test strip, prick your finger, and let the test strip soak up a little bit of blood.

Continue reading “Tech In Plain Sight: Glucose Meters” →