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The Second Greatest Advance in Diabetes Technology

February 28th, 2011

In less than a hundred years autoimmune diabetes has gone from a death sentence to a manageable disease, albeit requiring 24/7 management. What advances in medical technology made this possible?

Clearly the premier advance was the discovery, characterization and commercial manufacturing of insulin. We know much about insulin, enough that we can molecular engineer it to tweak its therapeutic properties. But without its chemical structure we would know nothing but its existence. All other advances at root help deliver insulin.

For the coveted Best Supporting Medical Technology, I nominate personal glucose monitoring.

Insulin has a rapid effect on blood sugar and a short half-life in the blood. So to keep blood sugar steady the insulin level needs to be adjusted hourly. And you can only do that if you know you blood sugar hour-to-hour.

Right now with a glance at my belt I can see my blood sugar as of fifteen minutes ago (CGM, Continuous Glucose Monitoring). I am astonished to recall that in 1979 I visited my doctor in New York, and he said, “your blood sugar is 220, you need to work harder.” I would get my blood sugar every three months! Since I now get it every five minutes, the sampling frequency has gone up by a factor of 25,000. Would you like to fly from New York to San Francisco based on one altitude measurement?

In fact with today’s quality of information from CGM the limiting factor has returned to the insulin. With a sensor and a pump one no longer needs any long acting insulin. But each pump injection of a bolus means that you will have insulin on board for something like three hours. An insulin that worked for 1/2 hour only would mean that tight control would be much easier. Of course, it would also mean you are only a hour from ketosis if your pump failed.

Early BG Meter

I fondly remember my many blood sugar meters over the years. My first from Boehringer was a revelation at the time but in retrospect was pretty clunky. It plugged into the wall, was the size of a shoe box, and took a few minutes to warm up. You had to calibrate it, saturate the surface of the strip with blood, wash it in a sink, dry it, wait, then turn a knob (young readers: a knob was used in he pre-digital era to set a continuous parameter like voltage) to zero on a volt meter. The blood glucose was read from the edge of the knob.

In addition to pocket sized meter, the best advance was when the strips internalized the blood and you no longer made a bloody mess.

For decades glucose was measure by chemical reactions that produced a color that could be measured. All the early meters simply measured the depth of this color. Starting in the ’70′s meters began to depend on the enzyme glucose oxidase coupled with an electrode. The enzyme makes peroxide from glucose, and the electrode can measure peroxide in real time.

The ultimate in sophisticated blood sugar measurement is the beta cell. It is very accurate, and produces a rapid burst of insulin secretion when blood sugar rises above 5 mM. It is both meter and insulin pump and does both jobs better. Those of us working to make cell therapy practical and affordable know that islets are the best insulin delivery system because islets not only make their own insulin but also detect the need for insulin.

I believe that there are many small steps to the cure, but three big ones: insulin, personal glucose measurement, and islet implants. Two of the three big steps are behind us.

Diabetes Technology.
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2 Responses to “The Second Greatest Advance in Diabetes Technology”

  1. JP Marat says:

    You hit the nail on the head when you suggest that having a device to ensure rapid response to changing glucose levels requires an equally rapidly acting and quickly disappearing form of insulin to go with it, since otherwise the capacity for focused intervention is not matched by a correspondingly focused duration of the intervention. It has recently been demonstrated that all forms of current insulin replacement therapy are non-physiologic in type 1 diabetics, since hyperinsulinemia has to be generated in the periphery of the body in order to achieve normal insulin levels in the liver. This unavoidable mismatch causes both hypoglycemia and elevated postprandial glucose levels. (H. Lebovitz, “Adjunct Therapy for Type 1 Diabetes Mellitus,” Nature Reviews Endocrinology, vol. 6, p. 326 (2010)) Since hyperinsulinemia has an angiogenic effect, it is easy to see what this is doing to promote the neovascularization of the diabetic retina (P. Silva, et al, “Effect of Systemic Medications on Onset and Progression of Diabetic Retinopathy,” Nature Reviews Endocrinology, vol. 6, p. 494 (2010), and the effect of excess circulating insulin on macroangiopathy is well-known from insulin resistance in type 2 diabetics.

    But even if dosing problems could be perfectly tailored to requirements throughout the body in type 1 diabetics, the question always has to be, at what cost? ‘Dis-ease,’ as the name suggests, is essentially the discomfort of the patient, and being hooked up to a variety of machines to allow monitoring blood sugar levels all day and half the night so as to inject repeated bolus doses of insulin as needed is a profoundly uncomfortable way to live. To regard this as a solution, as many in the diabetes community now seem to, is like saying what is wrong with living your entire life in an iron lung as long as it manages to normalize respiration, or spending nearly all your life on hemodialysis — as many of the advocates of daily home hemodialysis are now recommending — as long as the fluid and electrolyte levels are optimized.

  2. Scott King says:

    JP, I am currently on Dexcom CGM and Omnipod insulin pump. It is cumbersome. But within 4 days of starting the pump (two weeks ago) it seemed worth the inconvenience. I was close to satisfied with injected insulin but now I view Lantus as too crude. To each his own.

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