The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy

Leif Østergaard, Nanna B Finnerup, Astrid J Terkelsen, Rasmus A Olesen, Kim R Drasbek, Lone Knudsen, Sune N Jespersen, Jan Frystyk, Morten Charles, Reimar W Thomsen, Jens S Christiansen, Henning Beck-Nielsen, Troels S Jensen, Henning Andersen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Diabetic neuropathy is associated with disturbances in endoneurial metabolism and microvascular morphology, but the roles of these factors in the aetiopathogenesis of diabetic neuropathy remain unclear. Changes in endoneurial capillary morphology and vascular reactivity apparently predate the development of diabetic neuropathy in humans, and in manifest neuropathy, reductions in nerve conduction velocity correlate with the level of endoneurial hypoxia. The idea that microvascular changes cause diabetic neuropathy is contradicted, however, by reports of elevated endoneurial blood flow in early experimental diabetes, and of unaffected blood flow when early histological signs of neuropathy first develop in humans. We recently showed that disturbances in capillary flow patterns, so-called capillary dysfunction, can reduce the amount of oxygen and glucose that can be extracted by the tissue for a given blood flow. In fact, tissue blood flow must be adjusted to ensure sufficient oxygen extraction as capillary dysfunction becomes more severe, thereby changing the normal relationship between tissue oxygenation and blood flow. This review examines the evidence of capillary dysfunction in diabetic neuropathy, and whether the observed relation between endoneurial blood flow and nerve function is consistent with increasingly disturbed capillary flow patterns. The analysis suggests testable relations between capillary dysfunction, tissue hypoxia, aldose reductase activity, oxidative stress, tissue inflammation and glucose clearance from blood. We discuss the implications of these predictions in relation to the prevention and management of diabetic complications in type 1 and type 2 diabetes, and suggest ways of testing these hypotheses in experimental and clinical settings.

OriginalsprogEngelsk
TidsskriftDiabetologia
Vol/bind58
Udgave nummer4
Sider (fra-til)666-677
ISSN0012-186X
DOI
StatusUdgivet - 2015

Fingeraftryk

Diabetic Neuropathies
Oxygen
Aldehyde Reductase
Diabetes Complications
Type 2 Diabetes Mellitus

Citer dette

Østergaard, L., Finnerup, N. B., Terkelsen, A. J., Olesen, R. A., Drasbek, K. R., Knudsen, L., ... Andersen, H. (2015). The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy. Diabetologia, 58(4), 666-677. https://doi.org/10.1007/s00125-014-3461-z
Østergaard, Leif ; Finnerup, Nanna B ; Terkelsen, Astrid J ; Olesen, Rasmus A ; Drasbek, Kim R ; Knudsen, Lone ; Jespersen, Sune N ; Frystyk, Jan ; Charles, Morten ; Thomsen, Reimar W ; Christiansen, Jens S ; Beck-Nielsen, Henning ; Jensen, Troels S ; Andersen, Henning. / The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy. I: Diabetologia. 2015 ; Bind 58, Nr. 4. s. 666-677.
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title = "The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy",
abstract = "Diabetic neuropathy is associated with disturbances in endoneurial metabolism and microvascular morphology, but the roles of these factors in the aetiopathogenesis of diabetic neuropathy remain unclear. Changes in endoneurial capillary morphology and vascular reactivity apparently predate the development of diabetic neuropathy in humans, and in manifest neuropathy, reductions in nerve conduction velocity correlate with the level of endoneurial hypoxia. The idea that microvascular changes cause diabetic neuropathy is contradicted, however, by reports of elevated endoneurial blood flow in early experimental diabetes, and of unaffected blood flow when early histological signs of neuropathy first develop in humans. We recently showed that disturbances in capillary flow patterns, so-called capillary dysfunction, can reduce the amount of oxygen and glucose that can be extracted by the tissue for a given blood flow. In fact, tissue blood flow must be adjusted to ensure sufficient oxygen extraction as capillary dysfunction becomes more severe, thereby changing the normal relationship between tissue oxygenation and blood flow. This review examines the evidence of capillary dysfunction in diabetic neuropathy, and whether the observed relation between endoneurial blood flow and nerve function is consistent with increasingly disturbed capillary flow patterns. The analysis suggests testable relations between capillary dysfunction, tissue hypoxia, aldose reductase activity, oxidative stress, tissue inflammation and glucose clearance from blood. We discuss the implications of these predictions in relation to the prevention and management of diabetic complications in type 1 and type 2 diabetes, and suggest ways of testing these hypotheses in experimental and clinical settings.",
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Østergaard, L, Finnerup, NB, Terkelsen, AJ, Olesen, RA, Drasbek, KR, Knudsen, L, Jespersen, SN, Frystyk, J, Charles, M, Thomsen, RW, Christiansen, JS, Beck-Nielsen, H, Jensen, TS & Andersen, H 2015, 'The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy', Diabetologia, bind 58, nr. 4, s. 666-677. https://doi.org/10.1007/s00125-014-3461-z

The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy. / Østergaard, Leif; Finnerup, Nanna B; Terkelsen, Astrid J; Olesen, Rasmus A; Drasbek, Kim R; Knudsen, Lone; Jespersen, Sune N; Frystyk, Jan; Charles, Morten; Thomsen, Reimar W; Christiansen, Jens S; Beck-Nielsen, Henning; Jensen, Troels S; Andersen, Henning.

I: Diabetologia, Bind 58, Nr. 4, 2015, s. 666-677.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy

AU - Østergaard, Leif

AU - Finnerup, Nanna B

AU - Terkelsen, Astrid J

AU - Olesen, Rasmus A

AU - Drasbek, Kim R

AU - Knudsen, Lone

AU - Jespersen, Sune N

AU - Frystyk, Jan

AU - Charles, Morten

AU - Thomsen, Reimar W

AU - Christiansen, Jens S

AU - Beck-Nielsen, Henning

AU - Jensen, Troels S

AU - Andersen, Henning

PY - 2015

Y1 - 2015

N2 - Diabetic neuropathy is associated with disturbances in endoneurial metabolism and microvascular morphology, but the roles of these factors in the aetiopathogenesis of diabetic neuropathy remain unclear. Changes in endoneurial capillary morphology and vascular reactivity apparently predate the development of diabetic neuropathy in humans, and in manifest neuropathy, reductions in nerve conduction velocity correlate with the level of endoneurial hypoxia. The idea that microvascular changes cause diabetic neuropathy is contradicted, however, by reports of elevated endoneurial blood flow in early experimental diabetes, and of unaffected blood flow when early histological signs of neuropathy first develop in humans. We recently showed that disturbances in capillary flow patterns, so-called capillary dysfunction, can reduce the amount of oxygen and glucose that can be extracted by the tissue for a given blood flow. In fact, tissue blood flow must be adjusted to ensure sufficient oxygen extraction as capillary dysfunction becomes more severe, thereby changing the normal relationship between tissue oxygenation and blood flow. This review examines the evidence of capillary dysfunction in diabetic neuropathy, and whether the observed relation between endoneurial blood flow and nerve function is consistent with increasingly disturbed capillary flow patterns. The analysis suggests testable relations between capillary dysfunction, tissue hypoxia, aldose reductase activity, oxidative stress, tissue inflammation and glucose clearance from blood. We discuss the implications of these predictions in relation to the prevention and management of diabetic complications in type 1 and type 2 diabetes, and suggest ways of testing these hypotheses in experimental and clinical settings.

AB - Diabetic neuropathy is associated with disturbances in endoneurial metabolism and microvascular morphology, but the roles of these factors in the aetiopathogenesis of diabetic neuropathy remain unclear. Changes in endoneurial capillary morphology and vascular reactivity apparently predate the development of diabetic neuropathy in humans, and in manifest neuropathy, reductions in nerve conduction velocity correlate with the level of endoneurial hypoxia. The idea that microvascular changes cause diabetic neuropathy is contradicted, however, by reports of elevated endoneurial blood flow in early experimental diabetes, and of unaffected blood flow when early histological signs of neuropathy first develop in humans. We recently showed that disturbances in capillary flow patterns, so-called capillary dysfunction, can reduce the amount of oxygen and glucose that can be extracted by the tissue for a given blood flow. In fact, tissue blood flow must be adjusted to ensure sufficient oxygen extraction as capillary dysfunction becomes more severe, thereby changing the normal relationship between tissue oxygenation and blood flow. This review examines the evidence of capillary dysfunction in diabetic neuropathy, and whether the observed relation between endoneurial blood flow and nerve function is consistent with increasingly disturbed capillary flow patterns. The analysis suggests testable relations between capillary dysfunction, tissue hypoxia, aldose reductase activity, oxidative stress, tissue inflammation and glucose clearance from blood. We discuss the implications of these predictions in relation to the prevention and management of diabetic complications in type 1 and type 2 diabetes, and suggest ways of testing these hypotheses in experimental and clinical settings.

U2 - 10.1007/s00125-014-3461-z

DO - 10.1007/s00125-014-3461-z

M3 - Journal article

C2 - 25512003

VL - 58

SP - 666

EP - 677

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 4

ER -

Østergaard L, Finnerup NB, Terkelsen AJ, Olesen RA, Drasbek KR, Knudsen L et al. The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy. Diabetologia. 2015;58(4):666-677. https://doi.org/10.1007/s00125-014-3461-z