Glucose infusion rate

This is the fundamental relation for the glucose clamp. The value of GIR depends then on the changes in Jupt and HGO after insulin stimulation and the clamped value of the glucose concentration. Introducing the uptake from Eq. (29) gives  

In a typical setup, insulin is given subcutaneously and absorbed with a given plasma profile and a somewhat delayed interstitial profile. More rarely, insulin is infused to a constant insulin concentration. The interstitial insulin stimulates the 

G LUT4 translocation that - with a further delay - gives a variation in Vq hjt At the same time, the insulin inhibits HGO - at least for some time. 

Typically, the clamp is initiated after an overnight fast, i.e. 10-12 h without food. During the clamp, the untreated group typically needs no or very little GIR [131], so with a 24 h clamp, the patient may have fasted for 36 h. At the other end of the scale, a large insulin concentration may require a GIR of 10 mg kg-1 min-1 or more. This is 2.5 times the energy expenditure and a very massive overfeeding. Continuing this for, say, 24 h has a dramatic influence on all the body s metabolic processes. 

Between these extremes exists an interval where there is an interplay between the insulin given, the GIR and the fate of the infused glucose, and the movements and oxidation of the previously stored nutrients. Also, there is a yet unknown participation of the nervous part of the control system. The effect of all this is that each clamp must be viewed in its own context. 

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Extent and duration of action of various types of insulin as indicated by the glucose infusion rates (mg/kg/min) required to maintain a constant glucose concentration. The durations of action shown are typical of an average dose of 0.2-0.3 U/kg. The durations of regular and NPH insulin increase considerably when... 

A composition based on diketopiperazine derivatives (3,6-bis (N-fumaryl-N-(n-butyl) amino-2, 5-diketopiperazine) has been investigated as a pulmonary drug delivery system, termed Technospheres (Pharmaceutical Discovery Corp., Elmsford, NY) (Pohl et al. 2000 Steiner et al. 2002). The diketopiperazine derivatives self-assemble into microparticles at low pH with a mean diameter of approximately 2 pm. During self-assembly, diketopiperazine derivatives microencapsulate peptides present in the solution. Insulin incorporated in diketopiperazine derivatives (TI) was administered to five healthy humans by the use of a capsule-based inhaler with a passive powder deagglomeration mechanism. Relative and absolute bioavailability of TI in the first 3 hours (0-180 min) were 26 12% and 15 5%, and for 6 hours (0-360 min) 16 8% and 16 6%, respectively (Steiner et al. 2002). The time to peak action for glucose infusion rates was shorter with both IV (14 6 min) injection and inhalation (39 36 min), as compared to SC administration (163 25 min). This rapid absorption of insulin would be beneficial for diabetic patients who need to rapidly affect their glucose levels. 

Fig. 9.7 Dose-response ofAERx iDMS inhaled and injected insulin. (A) Glucose infusion rates (GIR) over 10 h after administration of the different treatments. (B) Dose-response relationship of the AUC-GI Ro no h f°r inhaled insulin vertical bars indicate 95% confidence intervals. (Reproduced with permission from [64]).

A first experiment to test the model predictions could be to replace the constant glucose infusion rate GIRq by a harmonically oscillating infusion rate [10] ... 

Fig. 6.20 Relation between the fluxes and insulin concentration during a glucose clamp. The glucose infusion rate, GIR, is calculated according to Eq. (46).

Whole-body insulin sensitivity is calculated as the mean glucose infusion rate (GIR) during the last 60 min of the clamp study. 

FIGURE 3.4 Measured plasma concentrations of insulin in compartment 1 (intravascular space) after intravenous injection of a 25-mU/kg dose, and computer-derived estimates of insulin concentration in presumed splanchnic (compartment 2) and somatic (compartment 3) components of interstitial fluid space. The bar graph indicates the glucose infusion rate needed to maintain blood glucose concentrations at the basal level. (Reproduced with permission from ShenA in RS, Kramer KJ, Tobin JD, Insel PA, Liljenquist JE, Berman M, Andres R. J Clin Invest 1974 53 1481-92.)... 

Fig. 4.5 Dose-ranging study in type 1 diabetes patients. Mean glucose infusion rate (GIR mg kg min ) after subcutaneous injection (0.1 unit kg ) and 5, 10, or 20 puffs of Oralin " spray.

Determine the amount of formula required to provide a glucose infusion rate of 8-10 mg/kg/min over a 24 h period (see Box 27.2). 

Appendix K. Calculation of Glucose Infusion Rate and Cornstarch Dosing for Patients with Glycogen Storage Disease... 

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