Glucose Sensing in the Peritoneal Space Offers Faster Kinetics Than Sensing in the Subcutaneous Space

The paramount goal in the treatment of type 1 diabetes is the maintenance of normoglycemia. Continuous glucose monitoring (CGM) technologies enable frequent sensing of glucose to inform exogenous insulin delivery timing and dosages. The most commonly available CGMs are limited by the physiology of the subcutaneous space in which they reside. The very same advantages of this minimally invasive approach are disadvantages with respect to speed. Because subcutaneous blood flow is sensitive to local fluctuations (e.g., temperature, mechanical pressure), subcutaneous sensing can be slow and variable. We propose the use of a more central, physiologically stable body space for CGM: the intraperitoneal space. We compared the temporal response characteristics of simultaneously placed subcutaneous and intraperitoneal sensors during intravenous glucose tolerance tests in eight swine. Using compartmental modeling based on simultaneous intravenous sensing, blood draws, and intraarterial sensing, we found that intraperitoneal kinetics were more than twice as fast as subcutaneous kinetics (mean time constant of 5.6 min for intraperitoneal vs. 12.4 min for subcutaneous). Combined with the known faster kinetics of intraperitoneal insulin delivery over subcutaneous delivery, our findings suggest that artificial pancreas technologies may be optimized by sensing glucose and delivering insulin in the intraperitoneal space.     

A comment on the importance of numerical evaluation of analytic solutions involving approximations

An analytic solution proposed by Senn (1) for removing the effects of covariate imbalance in controlled clinical trials was subjected to Monte Carlo evaluation. For practical applications of his derivation, Senn proposed substitution of sample statistics for parameters of the bivariate normal model. Unfortunately, that substitution produces severe distortion in the size of tests of significance for treatment effects when covariate imbalance is present. Numerical-verification of proposed substitutions into analytic models is recommended as a prudent approach.     

Metabolism of deltamethrin and cis- and trans-permethrin by rat and human liver microsomes,liver cytosol and plasma preparations

1. The metabolism of deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in liver microsomes, liver cytosol and plasma from male Sprague–Dawley rats aged 15, 21 and 90 days and from adult humans.

2. DLM and CPM were metabolised by rat hepatic microsomal cytochrome P450 (CYP) enzymes and to a lesser extent by microsomal and cytosolic carboxylesterase (CES) enzymes, whereas TPM was metabolised to a greater extent by CES enzymes.

3. In human liver, DLM and TPM were mainly metabolised by CES enzymes, whereas CPM was metabolised by CYP and CES enzymes.

4. The metabolism of pyrethroids by cytosolic CES enzymes contributes to the overall hepatic clearance of these compounds.

5. DLM, CPM and TPM were metabolised by rat, but not human, plasma CES enzymes.

6. This study demonstrates that the ability of male rats to metabolise DLM, CPM and TPM by hepatic CYP and CES enzymes and plasma CES enzymes increases with age. In all instances, apparent intrinsic clearance values were lower in 15 than in 90?day old rats. As pyrethroid-induced neurotoxicity is due to the parent compound, these results suggest that DLM, CPM and TPM may be more neurotoxic to juvenile than to adult rats.