5993
document
Physiologic modeling of the intravenous glucose tolerance test in type 2 diabetes : a new approach to the insulin compartment . The minimal model of Bergman et al has been used to yield estimates of insulin sensitivity ( Si ) and glucose effectiveness ( Sg ) in type 2 diabetes by incorporating exogenous insulin protocols into the regular intravenous glucose tolerance test ( IVGTT ) . These estimates , however , are influenced by the degree to which the dose of exogenous insulin is greater than the physiologic response to a glucose load . Moreover , most studies have related to type 2 diabetes subjects whose diabetes was relatively mild in terms of therapeutic requirements . To develop a " minimal disturbance " approach in estimating Si and Sg in type 2 diabetes , we have used a reduced glucose load ( 200 mg/kg ) and a " physiologic " insulin infusion throughout the IVGTT in a series of 8 patients , 5 of whom were insulin-requiring . Data from this approach were analyzed using the modelling program CONSAM to apply the Bergman model , either unmodified ( BMM ) , or incorporating an additional delay element between the plasma and " remote " insulin compartments ( MMD ) . Application of the MMD and extension of the IVGTT from 3 to 5 hours improved successful resolution of Si and Sg from 37.5 % ( BMM , 3-hour IVGTT ) to 100 % ( MMD , 5-hour IVGTT ) . Si was reduced in these type 2 diabetes patients compared with normal subjects ( 1.86 +/- 0.60 v. 8.65 +/- 2.27 min ( -1 ) x microU ( -1 ) x mL x 10 ( 4 ) P < .01 ) . The results were validated in the type 2 diabetes group using a 2-stage euglycemic clamp ( ( Si ) CLAMP = 2.02 +/- 0.42 min ( -1 ) x microU ( -1 ) x mL x 10 ( 4 ) P > .4 ) . Sg was not significantly reduced ( 2.00 +/- 0.25 type 2 diabetes v. 1.55 +/- 0.26 normal min ( -1 ) x 10 ( 2 ) ) . Data from a group of normal nondiabetic subjects was then analyzed using the MMD , but this approach did not enhance the fit of the model compared with the BMM . This result indicates that the delay in insulin action in type 2 diabetes represents an abnormality whereby the onset of insulin action can not be described as a single phase in the transfer of insulin from plasma to the remote compartment . It is postulated that the physiologic basis for this delayed action may relate to transcapillary endothelial transfer of insulin , this process limiting the rate of onset of insulin action .
5994
Intervention_Pharmacological
exogenous insulin protocols
5995
Intervention_Pharmacological
exogenous insulin
5996
Intervention_Pharmacological
reduced glucose load
5997
Intervention_Pharmacological
" physiologic " insulin infusion
5998
Outcome_Physical
intravenous glucose tolerance test
5999
Outcome_Physical
insulin sensitivity ( Si )
6000
Outcome_Physical
glucose effectiveness ( Sg )
6001
Outcome_Physical
Si
6002
Outcome_Physical
Sg
6003
Outcome_Physical
resolution of Si and Sg
6004
Outcome_Physical
Si
6005
Outcome_Physical
Sg
6006
Participant_Condition
type 2 diabetes :
6007
Participant_Condition
type 2 diabetes subjects