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Glucose levels at the site of subcutaneous insulin administration and their relationship to plasma levels.

ABSTRACT: OBJECTIVE:To examine insulin's effect on the tissue glucose concentration at the site of subcutaneous insulin administration. RESEARCH DESIGN AND METHODS:A CMA-60 microdialysis (MD) catheter and a 24-gauge microperfusion (MP) catheter were inserted into the subcutaneous adipose tissue of fasting, healthy subjects (n = 5). Both catheters were perfused with regular human insulin (100 units/ml) over a 6-h period and used for glucose sampling and simultaneous administration of insulin at sequential rates of 0.33, 0.66, and 1.00 units/h (each rate was used for 2 h). Before and after the insulin delivery period, both catheters were perfused with an insulin-free solution (5% mannitol) for 2 h and used for glucose sampling only. Blood plasma glucose was clamped at euglycemic levels during insulin delivery. RESULTS:Start of insulin delivery with MD and MP catheters resulted in a decline of the tissue glucose concentration and the tissue-to-plasma glucose ratio (TPR) for approximately 60 min (P < 0.05). However, during the rest of the 6-h period of variable insulin delivery, tissue glucose concentration paralleled the plasma glucose concentration, and the TPR for MD and MP catheters remained unchanged at 83.2 +/- 3.1 and 77.1 +/- 4.8%, respectively. After subsequent switch to insulin-free perfusate, tissue glucose concentration and TPR increased slowly and reattained preinsulin delivery levels by the end of the experiments. CONCLUSIONS:The results show the attainment of a stable TPR value at the site of insulin administration, thus indicating that insulin delivery and glucose sensing may be performed simultaneously at the same adipose tissue site.

SUBMITTER: Lindpointner S

PROVIDER: S-EPMC2845037 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Glucose levels at the site of subcutaneous insulin administration and their relationship to plasma levels.

Lindpointner Stefan S Korsatko Stefan S Köhler Gerd G Köhler Hans H Schaller Roland R Schaupp Lukas L Ellmerer Martin M Pieber Thomas R TR Regittnig Werner W

Diabetes care 20100122 4

<h4>Objective</h4>To examine insulin's effect on the tissue glucose concentration at the site of subcutaneous insulin administration.<h4>Research design and methods</h4>A CMA-60 microdialysis (MD) catheter and a 24-gauge microperfusion (MP) catheter were inserted into the subcutaneous adipose tissue of fasting, healthy subjects (n = 5). Both catheters were perfused with regular human insulin (100 units/ml) over a 6-h period and used for glucose sampling and simultaneous administration of insulin ...[more]

PMID: 20097778

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Project description:Aims/hypothesisThe small intestine plays an important role in hepatic and whole-body insulin sensitivity, as shown by bariatric surgery. Our goal was to study whether routes and dose of glucose administration have an acute impact on insulin sensitivity. The primary endpoint of this proof-of-concept study was the difference in insulin-mediated metabolic clearance rate (MCR/I) of glucose between the oral and intravenous routes of glucose administration. Secondary endpoints were differences in insulin effect on proteolysis, ketogenesis, lipolysis and glucagon levels.MethodsIn this parallel cohort study, we administered multiple oral glucose loads to 23 participants (aged between 18 and 65 years) with morbid obesity and with normal or impaired glucose tolerance or type 2 diabetes. In a different session, we administered isoglycaemic intravenous glucose infusions (IGIVI) to match the plasma glucose levels observed during the oral challenges. Glucose rate of appearance (Ra) and disappearance (Rd) and endogenous glucose production (EGP) were calculated by infusing [6,6-2H2]glucose with or without oral [U-13C6]glucose. Plasma small polar metabolites were measured by gas chromatography and time-of-flight mass spectrometry. Lipids were measured by ultra-HPLC and quadrupole mass spectrometry. Glucagon-like peptide-1, insulin, C-peptide and glucagon were also measured. Participants, caregivers, people doing measurements or examinations, and people assessing the outcomes were unblinded to group assignment.ResultsGlucose MCR/I was significantly higher during IGIVI than during oral glucose administration, independently of glycaemic status (12 ± 6 for IGIVI vs 7.4 ± 3 ml min-1 kg-1 per nmol/l for oral, p< 0.001 from paired t test). Insulin secretion was higher during oral administration than during IGIVI (p< 0.001). The disposition index was significantly lower during the oral procedure: 4260 ± 1820 vs 5000 ± 2360 (ml min-1 kg-1 (nmol/l)-1 pmol/min; p = 0.005). Insulin clearance was significantly higher when glucose was infused rather than ingested (2.53 ± 0.82 vs 2.16 ± 0.49 l/min in intravenous and oral procedure, respectively, p = 0.006). The efficacy of insulin in inhibiting lipolysis and proteolysis was decreased after oral glucose loads. A heat map diagram showed a different pattern for the metabolites between the two routes of glucose administration.Conclusions/interpretationOur study shows that insulin sensitivity depends on the route of glucose administration, the oral route leading to increased insulin secretion and compensatory insulin resistance compared with the intravenous route. The efficacy of insulin in blocking lipolysis and protein breakdown is lower after oral glucose loads vs the intravenous route. Our findings suggest that, while the glucose-mediated incretin release is followed by an increase in insulin release, the effect of the released insulin is limited by an increase in insulin resistance.Trial registrationClinicalTrials.gov NCT03223129. Graphical abstract.

Project description:Background and objectivesPatients with diabetes mellitus inject insulin in different regions of the body. This study investigated the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a new-generation once-daily basal insulin with an ultra-long duration of action, after subcutaneous (SC) administration in different injection regions.MethodsIn this study, 20 healthy subjects received single SC doses of IDeg (0.4 U/kg; separated by 13-21 days) in the thigh, abdomen and deltoid in a randomised, open-label, single-centre, single-dose, complete crossover trial. Each dose was followed by a 24-h euglycaemic clamp and 120-h pharmacokinetic blood sampling. The obtained pharmacokinetic/pharmacodynamic profiles were extrapolated to steady state by simulation using a pharmacokinetic/pharmacodynamic model.ResultsTotal IDeg exposure [area under the IDeg serum concentration-time curve 0-120 h after a single dose (AUCIDeg,0-120h,SD)] and maximum serum concentration [maximum IDeg serum concentration after a single dose (C max,IDeg,SD)] were higher (6-7 and 23-27 %, respectively) following a single SC dose in the deltoid or abdomen, compared with the thigh, as also observed with other insulin preparations. No statistical difference was observed in these measures between deltoid and abdominal administration. No pronounced differences were observed in the glucose-lowering effect of IDeg [area under the glucose infusion rate (GIR) curve 0-24 h after a single dose (AUCGIR,0-24h,SD) and maximum GIR after a single dose (GIRmax,SD)] when injected in the thigh, abdomen or deltoid (AUCGIR,0-24h,SD 2,572, 2,833 and 2,960 mg/kg, respectively). Simulated mean steady-state pharmacokinetic and pharmacodynamic profiles supported a flat and stable IDeg exposure and effect regardless of injection region, with comparable total glucose-lowering effects [area under the GIR curve at steady state (AUCGIR,τ,SS)] between the thigh, abdomen and deltoid.ConclusionsThese findings support administering IDeg SC in the thigh, upper arm or abdominal wall without affecting IDeg absorption or effect at steady state.

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Glucose levels at the site of subcutaneous insulin administration and their relationship to plasma levels.

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Glucose levels at the site of subcutaneous insulin administration and their relationship to plasma levels.

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