Interstitial glucose kinetics in subjects with type 1 diabetes under physiologic conditions

• Published in: Metabolism, clinical and experimental clinical and experimental, 2004-11, Vol.53 (11), p.1484-1491
• Main Authors: WILINSKA, Malgorzata E, BODENLENZ, Manfred, CHASSIN, Ludovic J, SCHALLER, Helga C, SCHAUPP, Lukas A, PIEBER, Thomas R, HOVORKA, Roman
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Adult; Associated diseases and complications; Biological and medical sciences; Blood Glucose - metabolism; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; Diabetes. Impaired glucose tolerance; Drug Delivery Systems; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Glucose - metabolism; Glycated Hemoglobin A - metabolism; Humans; Hypoglycemic Agents - administration & dosage; Injections, Subcutaneous; Insulin - administration & dosage; Insulin - analogs & derivatives; Insulin Lispro; Kinetics; Male; Medical sciences; Middle Aged; Models, Theoretical
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2004.05.014

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.