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Wednesday, April 6, 2016

Progress in Artificial Pancreas Development

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A clinical trial at the Massachusetts General Hospital in Boston has found that a glucagon pump can reduce incidents of dangerously low blood sugar levels for diabetics on an insulin pump or taking multiple injections per day. While this is an important step for the development of an artificial pancreas, it's also an example of a treatment that poorly matched with the disease.





All type 1 and some type 2 diabetics take injections of insulin to lower blood sugars. The advantage of insulin over every other treatment for diabetes is that, at some dosage, it will always work. The disadvantage that insulin shares with other treatments for diabetes that at some dosages it will work too well, lowering blood sugars to unsafe levels.

The body has a natural system for dealing with this possibility. A healthy pancreas releases not just insulin to lower blood sugar levels but also glucagon to raise them, by stimulating the conversion of glycogen stored in the liver into glucose. Releasing tiny amounts of glucagon keeps blood sugars from falling too low when the body underestimates that amount of sugar about to enter the bloodstream. When you eat a large, bulky meal, for example, stretch receptors in your small intestine send a signal to your pancreas that a large amount of digested sugar is on the way. This signal causes a healthy pancreas to release both insulin to keep blood sugars from going too high and glucagon to keep blood sugars from going too low.

In diabetics, the pancreas doesn't release enough insulin but still can produce glucagon. This causes blood sugar levels to surge after meals. Many diabetics struggle far more with high blood sugar levels than with low blood sugar levels. In a few diabetics, however, glucagon production is also impaired, so that insulin overdose is a constant problem. When diabetics also have nerve damage (or take beta-blockers) that keep them from sensing imminent danger of low blood sugar levels so that they take corrective action (taking glucose tablets, eating a snack, or injecting glucagon), hypoglycemia is a frequent danger.

A research team led by Dr. Laya Ekhlaspour at Massachusetts General recruited 22 volunteers with type 1 diabetes. Everyone in the study either had an insulin pump or took multiple injections of insulin daily. Everyone in the study had at least two incidents of hypoglycemia (sugars below 50 mg/dl) on average at least twice a week, but because their symptoms were inconsistent, they did not always know to take corrective measures.  The volunteers were fitted with a pump that could release small amounts of glucagon or a placebo. They were fitted with a continuous glucose monitor that measured blood sugar levels every 5 minutes and sent the readings to an iPhone that had an app to detect falling blood sugar levels. The app then sent a signal to the glucagon pump to release glucagon if sugars were falling too low. The glucagon pump delivered either glucagon or a placebo, each participant getting either the glucagon or the placebo for seven days in a row, then switching.

The doctors found that when the pump was set to deliver glucagon, there was a 91% reduction in time at night with blood sugar levels below 60 mg/dl, and a 50% reduction in episodes of hypoglycemia with blood sugar levels of 50 mg/dl or lower.

Patients had more nausea when their pumps were set to deliver glucagon instead of a placebo, but most participants in the trial were not able to guess which days they were receiving glucagon and which days they were receiving a placebo.

These findings indicate that a glucagon pump for preventing hypoglycemia can work. There's just one drawback to this system. Wouldn't it be simpler just to reduce the dosage of insulin in the first place?

A glucagon pump will be an important part of a truly artificial pancreas. The artificial pancreas system has to be able to deal with "oopsies." But a stand-alone glucagon pump seems a lot less practical than simply allowing blood sugars to run in the 80's, instead of keeping them in the 70's. Lower is not always better, even with blood sugar and HbA1C.

As a general rule for diabetics, small inputs lead to small errors. I'd like to claim that saying as my own, but I came across it in a book by Dr. Richard Bernstein. If you have a problem with your blood sugars going too low, try using less insulin, which may require eating smaller portions and also cutting short some of your resistance exercise sessions (which tend to raise blood sugar before they lower it). Try small changes before making drastic changes, like having yourself hooked up to a glucagon pump.


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