Sensitive RIA for the Specific Determination of Insulin Lispro

Bowsher, Ronald R.; Lynch, Renee; Brown‐Augsburger, Patricia; Santa, Paula F.; Legan, William E.; Woodworth, James R.; Chance, Ronald E.

doi:10.1093/clinchem/45.1.104

Cited by 48 publications

(13 citation statements)

References 22 publications

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“…A conversion factor of 1 was applied between insulin measurements to achieve this common concentration expression if a compound‐specific assay, such as for insulin glargine and insulin lispro, was utilized. The discussion of the relationship between total insulin‐ and insulin‐lispro specific assays has been previously published …”

Section: Methodsmentioning

confidence: 99%

Modeling Pharmacokinetic Profiles of Insulin Regimens to Enhance Understanding of Subcutaneous Insulin Regimens

Tham

Schneck

Ertekin³

et al. 2017

The Journal of Clinical Pharmacology

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Insulin pharmacokinetics following subcutaneous administration were modeled, simulated, and displayed through an interactive and user‐friendly interface to illustrate the time course of administered insulins frequently prescribed, providing a simple tool for clinicians through a straightforward visualization of insulin regimens. Pharmacokinetic data of insulin formulations with different onset and duration of action from several clinical studies, including insulin glargine, regular insulin, neutral protamine Hagedorn (NPH), insulin lispro, and premixed preparations of NPH with regular insulin (Mix 70/30), and insulin lispro protamine suspension with insulin lispro (Mix 50/50, Mix 75/25), were used to develop a predictive population pharmacokinetic model of insulins with consideration of factors such as insulin formulation, weight‐based dosing, body‐weight effect on volume of distribution, and administration time relative to meals, on the insulin time‐action profile. The model‐predicted insulin profile of each insulin was validated and confirmed to be comparable to observed data via an external validation method. Model‐based simulations of clinically relevant insulin‐dosing scenarios to cater to specific initial patient and prescribing conditions were then implemented with differential equations using the R statistical program (version 3.2.2). The R package Shiny was subsequently applied to build a web browser interface to execute and visualize the model simulation outputs. The application of insulin pharmacokinetic modeling enabled informative visualization of insulin time‐action profiles and provided an efficient and intuitive educational tool to quickly convey and interactively explore many insulin time‐action profiles to ease the understanding of insulin formulations in clinical practice.

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Section: Methodsmentioning

confidence: 99%

Modeling Pharmacokinetic Profiles of Insulin Regimens to Enhance Understanding of Subcutaneous Insulin Regimens

Tham

Schneck

Ertekin³

et al. 2017

The Journal of Clinical Pharmacology

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“…Direct measurement of peripheral insulin may be more sensitive to detect low levels of autonomous insulin secretion in small insulinomas. The parallel determination of serum insulin and serum concentration of lispro-insulin can be recommend (Bowsher et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Modified hyperinsulinaemic, eu- and hypoglycaemic clamp technique using lispro-insulin for insulinoma diagnostic

Roudovitch

Nauck²,

Schatz³

et al. 2001

Exp Clin Endocrinol Diabetes

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Characterization of metabolically inadequate insulin secretion is essential for insulinoma diagnostics. Hyperinsulinaemic, eu- and hypoglycaemic clamp procedures have been used to suppress endogenous insulin secretion in healthy subjects. The use of exogenous insulin precluded the use of insulin as a parameter to be measured. We now suggest to use exogenous insulin lispro and an insulin-specific ELISA not cross reacting with insulin lispro. Thus, determination of insulin by ELISA in this experimental setting reflects endogenous insulin. A 39-year-old man with a surgically confirmed pancreatic insulinoma was studied under hyperinsulinaemic [lispro insulin 40 mU x m(-2) body surface x min(-1)] clamp conditions. Euglycaemia was achieved (3.8 +/- 0.5 mmol/L) for 1 h and hypoglycaemia (2.36 +/- 0.49 mmol/L) was achieved for another 30 min. Insulin was evaluated by ELISA (cross-reaction with lispro insulin < 0.006%, C-peptide < 0.01%, proinsulin < 0.001%) and by a nonselective RIA (cross-reaction with proinsulin 40%). In control subjects the euglycaemic hyperinsulinaemia suppressed C-peptide to 0.36 +/- 0.03 ng/ml and hypoglycaemic hyperinsulinaemia to 0.29 +/- 0.03 ng/ml. Endogenous insulin was suppressed to 2.8 +/- 0.03 mU/L under euglycaemia and to 2.6 +/- 0.03 mU/L under hypoglycaemia in control subjects. In the insulinoma patient apparently irregular but small changes in both C-peptide (1.43 +/- 0.1 ng/ml) and more pronounced changes in endogenous insulin concentrations 4.41 +/- 0.1 mU/l under euglycaemia and 5.35 +/- 0.3 mU/l under hypoglycaemic conditions, were observed. The basal level of insulin (ELISA insulin 4.6 mU/L) and C-peptide (1.7 ng/ml) were not markedly elevated. Determination of insulin allowed better characterization of irregular pulses because of the shorter half-life of insulin relative to C-peptide. The new modification of sequential eu- and hypoglycaemic clamp procedures should also be useful in pharmacological studies of insulinotropic substances. Direct measurement of peripheral insulin may be more sensitive than C-peptide to detect low levels of autonomous insulin secretion in small insulinomas.

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“…FIRI levels were measured using a double‐antibody radioimmunoassay technique (Diagnostic Products Corp., Los Angeles, CA, USA). A separate double‐antibody radioimmunoassay method specific for LP was used to measure free LP [7]. A lower limit of quantification of 43.0 pmol/l was established for this assay.…”

Section: Methodsmentioning

confidence: 99%

A 75% insulin lispro/25% NPL mixture provides a longer duration of insulin activity compared with insulin lispro alone in patients with Type 1 diabetes

Roach

Woodworth

Gudat³

et al. 2003

Diabetic Medicine

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Sensitive RIA for the Specific Determination of Insulin Lispro

Cited by 48 publications

References 22 publications

Modeling Pharmacokinetic Profiles of Insulin Regimens to Enhance Understanding of Subcutaneous Insulin Regimens

Modeling Pharmacokinetic Profiles of Insulin Regimens to Enhance Understanding of Subcutaneous Insulin Regimens

Modified hyperinsulinaemic, eu- and hypoglycaemic clamp technique using lispro-insulin for insulinoma diagnostic

A 75% insulin lispro/25% NPL mixture provides a longer duration of insulin activity compared with insulin lispro alone in patients with Type 1 diabetes

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