The Artificial Pancreas

Abstract

The discovery of insulin was lifesaving. However, it converted type 1 diabetes, which had been an acute and lethal disease, into a chronic disease, with its attendant complications. It had long been considered—and was clearly demonstrated in the Diabetes Control and Complications Trial (1)—that microvascular complications such as retinopathy, nephropathy, and neuropathy (as well as micro- and macrovascular legacy effects) were improved with intensive glucose control—that is, when circulating glucose levels were closer to those seen in the nondiabetic state. This entailed increased involvement on the part of a person with diabetes in their management: glucose monitoring, frequent insulin injections, or continuous subcutaneous insulin infusion (CSII). It also increased the risk of hypoglycemia. The mitigation of this trade-off, as well as controlling “brittle” diabetes, improving the quality of life of the person with diabetes, and the availability of the necessary technology, has motivated the evolution of self-managed intensive control into automated control. Indeed, the artificial pancreas has been a major goal of research in type 1 diabetes since exogenous insulin became available. Articles on the automated control of glycemia in the absence of endogenous insulin (2,3) were published on (almost) the 50th anniversary of the discovery of insulin. This early version of the artificial pancreas depended on very frequent, automated measurements of blood glucose and an intravenous delivery of insulin. It was also bulky. Nevertheless, over the short term, it could maintain near normoglycemia. Initial versions operated using versions of a proportional (P) controller (4):![Graphic][1] where uP is the insulin infusion rate, g(t) the blood glucose concentration, gtarget the target concentration, and K 1 the proportionality constant. Subsequent versions incorporated derivative (D) control:![Graphic][2] Essentially, this allows improved projections of glucose values into the future and thus better control of these future values. Albisser et al. … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif