Treatment-induced neuropathy in diabetes (TIND) is defined by the occurrence of an
acute neuropathy within 8 weeks of an abrupt decrease in glycated hemoglobin-A1c (HbA1c). The
underlying pathogenic mechanisms are still incompletely understood with only one mouse model
being explored to date. The aim of this study was to further explore the hypothesis that an abrupt
insulin-induced fall in HbA1c may be the prime causal factor of developing TIND. BB/OKL (bio
breeding/OKL, Ottawa Karlsburg Leipzig) diabetic rats were randomized in three groups, receiving
insulin treatment by implanted subcutaneous osmotic insulin pumps for 3 months, as follows: Group
one received 2 units per day; group two 1 unit per day: and group three 1 unit per day in the first
month, followed by 2 units per day in the last two months. We serially examined blood glucose
and HbA1c levels, motor- and sensory/mixed afferent conduction velocities (mNCV and csNCV)
and peripheral nerve morphology, including intraepidermal nerve fiber density and numbers of
Iba-1 (ionized calcium binding adaptor molecule 1) positive macrophages in the sciatic nerve. Only
in BB/OKL rats of group three, with a rapid decrease in HbA1c of more than 2%, did we find a
significant decrease in mNCV in sciatic nerves (81% of initial values) after three months of treatment
as compared to those group three rats with a less marked decrease in HbA1c <2% (mNCV 106% of
initial values, p 0.01). A similar trend was observed for sensory/mixed afferent nerve conduction
velocities: csNCV were reduced in BB/OKL rats with a rapid decrease in HbA1c >2% (csNCV 90%
of initial values), compared to those rats with a mild decrease <2% (csNCV 112% of initial values,
p 0.01). Moreover, BB/OKL rats of group three with a decrease in HbA1c >2% showed significantly
greater infiltration of macrophages by about 50% (p 0.01) and a decreased amount of calcitonin
gene related peptide (CGRP) positive nerve fibers as compared to the animals with a milder decrease
in HbA1c. We conclude that a mild acute neuropathy with inflammatory components was induced in
BB/OKL rats as a consequence of an abrupt decrease in HbA1c caused by high-dose insulin treatment.
This experimentally induced neuropathy shares some features with TIND in humans and may be
further explored in studies into the pathogenesis and treatment of TIND.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89635 |
| Date | 09 February 2024 |
| Creators | Baum, Petra, Koj, Severin, Klöting, Nora, Blüher, Matthias, Classen, Joseph, Paeschke, Sabine, Gericke, Martin, Toyka, Klaus V., Nowicki, Marcin, Kosacka, Joanna |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1571 |
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