Key result
Diet-induced obesity in rats delayed subcutaneous insulin absorption (p<0.001), correlating with smaller injection depots and slower depot disappearance compared to low-fat diet controls.
Why the study?
Obesity is associated with delayed insulin absorption upon subcutaneous dosing in humans, but whether alterations in subcutaneous depot structure and kinetics contribute to this delay was unknown.
Does diet-induced obesity alter subcutaneous depot kinetics and delay insulin absorption in rats?
Does diet-induced obesity alter subcutaneous depot kinetics and delay insulin absorption in rats?
p-value: p=<0.001
Diet-induced obesity in rats alters subcutaneous injection depot structure and kinetics, which contributes to delayed insulin absorption.
May warrant caution in obese patients' insulin dosing; hypothesis-generating for human pharmacokinetic studies.
Summary Objective Obesity is associated with delayed insulin absorption upon subcutaneous (s.c.) dosing in humans. The aim of this study was to investigate whether alterations in depot structure and kinetics of the s.c. injection depot contribute to this delay. Methods Rats fed a high‐fat diet (HFD) and low‐fat diet (LFD) were included in a series of insulin pharmacokinetic and imaging studies. Injection depots were visualized with micro X‐ray computed tomography imaging upon s.c. administration of insulin aspart mixed with the contrast agent iomeprol, and insulin aspart exposure was measured by means of luminescent oxygen channelling immunoassay. Results Body weight and fat mass were increased in rats fed an HFD vs. LFD ( p < 0.05), whereas the lean mass was not. The HFD group exhibited delayed insulin absorption from the s.c. tissue ( p < 0.001). This delay was associated with smaller injection depots upon s.c. dosing ( p < 0.05) and correlated with a slower depot disappearance from the s.c. tissue ( p < 0.05) compared with the LFD group. Depot disappearance from the s.c. tissue was inversely correlated with body fat mass ( p < 0.05). Conclusions Alterations in s.c. injection depot structure and kinetics may play a role in the obesity‐associated delay in insulin absorption.
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Gradel et al. (2018) studied Diet-induced obesity. Subcutaneous insulin aspart vs. Low-fat diet (LFD) was evaluated on Insulin absorption from the subcutaneous tissue (p=<0.001). Diet-induced obesity in rats delayed subcutaneous insulin absorption (p<0.001), correlating with smaller injection depots and slower depot disappearance compared to low-fat diet controls.
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