Stepped hypoglycaemic clamp

Stepped clamps are used to create a slow fall in plasma glucose so that the glucose concentration at which any given response begins can be identified (Figure 5.6).

Responses are influenced by the duration of exposure to hypoglycaemia but this is standardised in the stepped clamp procedure. In these clamps, the glucose is held at predetermined plateaus for a fixed duration. The first part of the plateau is used for stabilisation of glucose and the second for measurement of symptoms, cognitive function and counterregulatory hormones, before lowering the glucose to the next plateau. Each plateau must be long enough to allow the plasma glucose to stabilise and the stabilisation of the response, as well as completion of any other measures that the investigator requires. It takes at least 20 minutes for the responses to hypoglycaemia to approach stability (Evans et al. 2000). If a battery of cognitive function tests are being carried out, they will require about 20 minutes to compete, so each plateau will be for about 40 minutes.

Intravenous insulin infusion

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Figure 5.6 Schematic showing the major elements of a stepped hypoglycaemic clamp. A primed continuous intravenous insulin infusion is started (black box) to raise circulating insulin concentrations (black line) rapidly to target. The resultant fall in plasma glucose (grey line) is controlled by a variable rate infusion of glucose solution (hatched bars).

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Figure 5.6 Schematic showing the major elements of a stepped hypoglycaemic clamp. A primed continuous intravenous insulin infusion is started (black box) to raise circulating insulin concentrations (black line) rapidly to target. The resultant fall in plasma glucose (grey line) is controlled by a variable rate infusion of glucose solution (hatched bars).

If sophisticated measurements are to be made, these studies usually require at least three team members. Cognitive function tests should be carried out in peaceful surroundings in a reproducible way by an experienced investigator. Blood samples taken for hormone analysis need to be handled with care, often requiring rapid centrifugation, accurate removal of plasma and immediate freezing using dry ice. Teamwork is crucial, with different members completing different parts of the study.

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