title: Interstitial glucose kinetics in subjects with type 1 diabetes under physiologic conditions.
abstract: We investigated the dynamic relationship between interstitial glucose (IG) in the subcutaneous adipose tissue and plasma glucose (PG) during physiologic conditions in type 1 diabetes mellitus (T1DM). Nine subjects with T1DM (5/4 M/F; age, 33 +/- 13 years; body mass index, 26.6 +/- 4.3 kg/m(2); glycosylated hemoglobin [HbA(1c)], 8.6% +/- 0.9%; mean +/- SD) treated by continuous subcutaneous insulin infusion (CSII) with insulin lispro were studied over 12 hours after a standard meal (40 g carbohydrate [CHO]) and prandial insulin. IG was measured by open flow microperfusion. Nine compartment models were postulated to account for temporal variations in the IG/PG ratio. The models differed in the inclusion of physiologically motivated alterations of pathways entering/leaving the IG compartment in the adipose tissue. The best model included zero order (constant) glucose disposal from the interstitial fluid (ISF) and insulin-stimulated glucose transfer from plasma to the ISF. The former effect is expressed by a positive association between the IG/PG ratio and PG, eg, a decrease in PG from 9 to 3.3 mmol/L lowers the IG/PG ratio by 0.1. The latter effect results in the IG/PG ratio to be increased by 0.03 per 10 mU/L of plasma insulin. We were not able to detect the stimulatory effect of insulin on glucose disappearance from the ISF. In conclusion, we developed and quantified a model of IG kinetics in the adipose tissue applicable to physiologic conditions in subjects with T1DM.
authors.affiliation: Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
authors.forename: Malgorzata E
authors.initials: ME
authors.lastname: Wilinska
authors.forename: Manfred
authors.initials: M
authors.lastname: Bodenlenz
authors.forename: Ludovic J
authors.initials: LJ
authors.lastname: Chassin
authors.forename: Helga C
authors.initials: HC
authors.lastname: Schaller
authors.forename: Lukas A
authors.initials: LA
authors.lastname: Schaupp
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.forename: Roman
authors.initials: R
authors.lastname: Hovorka
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D061268:Insulin Lispro; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical
chemical_list: D001786:Blood Glucose; D005947:Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro