Insulin Therapy

Because deficient action of insulin is one of the hallmarks of diabetes mellitus, insulin therapy was for a long time considered one of the principal treatments of both type 1 and type 2 diabetes. Nowadays this notion is somewhat less predominant. In type 1 diabetes the focus has switched to preventing or curing the auto-immune processes that destruct the patients' own insulin producing capacity, while in type 2 diabetes (relative or absolute) insulin deficiency is considered just one of the myriad factors involved in its pathogenesis and hence in its adequate treatment. Nonetheless, as a glucose-lowering treatment insulin is still unsurpassed and virtually all patients with type 1 diabetes, and up to 40% of those with type 2 diabetes are treated with insulin. The beneficial effects of intensive insulin therapy on complications in type 1 diabetes have been well established. Although its benefits are somewhat less clear in type 2 diabetes, insulin therapy is generally considered the safe and reasonable next treatment step once metformin and sulfonylurea derivatives fail to maintain glycaemic control.

History of insulin

The history of insulin is closely interwoven with the history of biomedical development in the 20th Century itself ; a fact that is perhaps best illustrated by the five Nobel prizes that have been awarded for work related to, or inspired by insulin.[1] But more importantly, of course, the discovery of insulin has had dramatic, life-saving consequences for millions of people worldwide. This prompted Elliot Joslin to reverently call the period right after 1922 the Banting era, to honour the man who discovered insulin. As Joslin recalls, "I measured the length of life of my first diabetic children in days.....by the last Banting era children almost ceased to die".[2]

Evidence for efficacy of insulin

While Joslin's evidence in type 1 is hard to beat, the use of insulin in type 2 diabetes is more controversial. Being introduced before the randomised clinical trials had entered the stage, formal testing of the effect of insulin on hard endpoints such as mortality or on microvascular endpoints such as retinopathy is scarce. Judging the value of insulin in type 2 diabetes becomes even more difficult because it is usually used in the later stages of the disease, and then mostly in combination with many other drugs.

Insulin regimens

Once insulin was available, defining which insulin regimen in which setting produced the best results became the topic of much research and debate. However, the key concept is that treatment individualisation matters most. Many factors that are unrelated to the objective qualities of the insulin regimens influence which regimen will serve the needs of a specific patient best. Thus, while the insulin analogues may offer some benefits compared to conventional insulins, the excessive cost of these insulins argues strongly against their use in resource-poor countries[3]. And while most would agree that in independent, cooperative and pro-active patients a basal-bolus regimen will give the best glycaemic control, impracticalities will often limit the use of this multiple-injection regimen, e.g. in those who lead more dependent lives such as children and nursing home residents.

Pharmacokinetics and -dynamics

To understand how different regimens might work out, a basic understanding of the behaviour of the various insulins after injection, and the various factors influencing this behaviour, is helpful. For the last few decades the so-called euglycaemic clamp study has been the method of choice to delineate the properties of specific insulins.

Conventional insulins and insulin analogues

However, the objective properties of insulins in experimental settings may not always translate to clinical differences. Nor are clinical differences the only factors deciding the popularity of certain insulins. Despite having served the diabetes community very well for the best part of the 20th century, the animal insulins have been almost completely replaced by bioengineered human insulins and insulin analogues. And despite the fact that the insulin analogues thusfar offer only limited benefits over human insulins, the major companies involved put significant effort in pushing the far cheaper human insulin out of the market. However, for many patients and countries, the conventional insulins still offer the best chance of affordable and effective insulin therapy.

Insulin administration

Life is full of options, and so is insulin therapy. Apart from insulin types and insulin regimens, we can choose from various injection devices, needle types etcetera. While often irrelevant for objective clinical parameters, many of these choices impact on patient comfort and quality of life. Particularly when trying to empower patients to take control of their own disease, these factors are worth considering.

Insulin pump therapy

In this respect, insulin pump therapy is especially important. Not only does this offer more comfort to patients; due to the specific pharmacokinetics and -dynamics associated with continuous insulin administration, pump therapy can often yield better clinical results than injection therapy. Pump therapy however, is costly and not a feasible option for all patients. Much research effort is put into the so-called artificial pancreas: the coupling of insulin pump devices to continuous glucose sensors, to 'close the loop' of a feedback system where insulin affects glucose, and the change in glucose in turn affects the insulin administration.

References

  1. ^ Tattersall R. Diabetes. The Biography. Oxford University Press 2009. ISBN 978-0-19-954136-2

  2. ^ Joslin EP et al. The treatment of diabetes mellitus. Lea & Febiger, Philadelphia. 8th Edition, 1946, page 316-317.

  3. ^ Gill GV et al. Diabetologia 2011;54(1):19-24

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