Practice Therapeutics

Newer insulins in type 2 diabetes

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e4611 (Published 11 September 2012) Cite this as: BMJ 2012;345:e4611
  1. Edwin A M Gale, emeritus professor of diabetic medicine
  1. 1University of Bristol, Bristol, UK
  1. Correspondence to: Professor E A M Gale, Diabetes and Metabolism, Learning and Research, Southmead Hospital, Bristol BS10 5NB Edwin.Gale{at}bristol.ac.uk

A 68 year old woman with a body mass index (weight (kg)/(height (m))2) of 31 has a five year history of type 2 diabetes. She is reasonably active but takes treatment for hypertension, hyperlipidaemia, and angina. She has signs of early diabetic background retinopathy. Her current treatment for diabetes is with metformin 850 mg twice daily and gliclazide 160 mg daily. Her haemoglobin A1c (HbA1c) concentration has risen from 0.076 to 0.085 over the past year, and she is keen to improve her glucose control.

After review of her diabetes management, she opts for insulin as the next step in treatment. She mentions that a friend has just started a special new insulin and wonders if that is what she will be taking too. After discussion of the evidence for insulin analogues, she agrees to start taking isophane insulin rather than an analogue.

What are the insulin analogues?

In health, glucose control is achieved by feedback regulation, such that food intake is matched by sharp spikes of insulin, and the glucose concentration remains stable between meals because of regulated basal insulin secretion. By contrast, injected insulin has no feedback regulation, enters the systemic rather than the portal circulation, is delivered into subcutaneous tissue rather than the bloodstream, and diffuses variably into the circulation. Standard, short acting insulins reach the circulation more slowly than food, so blood glucose tends to swing too high after each meal and to drop too low before the next. Longer acting human insulins reach peak absorption 4-16 hours after injection, which means that insulin injected before the evening meal tends to produce a glucose dip in the middle of the night, followed by a rebound as insulin fades before breakfast. Injection therapy thus tends to produce unwanted oscillations in glucose control, with an increased risk of hypoglycaemia before …

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