title: Time lag of glucose from intravascular to interstitial compartment in type 1 diabetes.
abstract: The premise of effective closed-loop insulin therapy for type 1 diabetes (T1D) relies on the accuracy of continuous interstitial fluid glucose sensing that represents the crucial afferent arm of such a system. An important determinant of sensor accuracy is the physiological time lag of glucose transport from the vascular to the interstitial space. The purpose of current studies was to determine the physiological time lag of glucose transport from the vascular to the abdominal subcutaneous interstitial space in T1D. Four microdialysis catheters were inserted into the abdominal subcutaneous space in 6 T1D subjects under overnight fasted conditions. Plasma glucose was maintained at 113.7 ± 6.3 mg/dl using a continuous intravenous insulin infusion. After sequential intravenous bolus administrations of glucose isotopes, timed plasma and interstitial fluid samples were collected chronologically and analyzed for tracer enrichments. We observed a median (range) time lag of tracer appearance (time to detection) into the interstitial space after intravenous bolus of 6.8 (4.8-9.8) minutes, with all participants having detectable values by 9.8 minutes. We conclude that in the overnight fasted state in T1D adults, the delay of glucose appearance from the vascular to the interstitial space is less than 10 minutes, thereby implying that this minimal physiological time lag should not be a major impediment to the development of an effective closed-loop control system for T1D.
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ananda
authors.initials: A
authors.lastname: Basu
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA.
authors.forename: Simmi
authors.initials: S
authors.lastname: Dube
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sona
authors.initials: S
authors.lastname: Veettil
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Slama
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA.
authors.forename: Yogish C
authors.initials: YC
authors.lastname: Kudva
authors.affiliation: IDDM Consulting, San Diego, CA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Peyser
authors.affiliation: Department of Health Sciences Research, Mayo College of Medicine, Rochester, MN, USA.
authors.forename: Rickey E
authors.initials: RE
authors.lastname: Carter
authors.affiliation: Department of Information Engineering, University of Padova, Padova, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA basu.rita@mayo.edu.
authors.forename: Rita
authors.initials: R
authors.lastname: Basu
mesh_terms: D000005:Abdomen; D000328:Adult; D001692:Biological Transport; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D015190:Blood Glucose Self-Monitoring / Q000295:instrumentation / Q000592:standards; D001808:Blood Vessels / Q000737:chemistry / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D045604:Extracellular Fluid / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D007332:Insulin Infusion Systems / Q000592:standards; D008297:Male; D008875:Middle Aged; D065566:Subcutaneous Absorption; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose
keywords: continuous glucose monitors; interstitial glucose concentration; microdialysis; subcutaneous glucose transport; type 1 diabetes