Sweat gland nerve fiber density and association with sudomotor function, symptoms, and risk factors in adolescents with type 1 diabetes

Vinni Faber Rasmussen; Ann Schmeichel; Mathilde Thrysøe; Jens Randel Nyengaard; Ann-Margrethe Rønholt Christensen; Esben Thyssen Vestergaard; Kurt Kristensen; Astrid Juhl Terkelsen; Páll Karlsson; Wolfgang Singer

doi:10.1007/s10286-023-00973-7

Sweat gland nerve fiber density and association with sudomotor function, symptoms, and risk factors in adolescents with type 1 diabetes

Vinni Faber Rasmussen^*, Ann Schmeichel, Mathilde Thrysøe, Jens Randel Nyengaard, Ann-Margrethe Rønholt Christensen, Esben Thyssen Vestergaard, Kurt Kristensen, Astrid Juhl Terkelsen, Páll Karlsson, Wolfgang Singer

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

PURPOSE: To quantify sweat gland nerve fiber density in adolescents with diabetes. Additionally, to investigate associations between sudomotor innervation, sweat responses, and possible risk factors for sudomotor neuropathy.

METHODS: Cross-sectional study where 60 adolescents with type 1 diabetes (duration > 5 years) and 23 control subjects were included. Clinical data, quantitative sudomotor axon reflex test, and skin biopsies were obtained. Skin tissue was immunostained and imaged by confocal microscopy. Quantification of the sweat gland volume and three-dimensional reconstruction of the nerve fibers was performed using a design-unbiased technique.

RESULTS: Adolescents with diabetes had a significant reduction of maximum and mean values of nerve fiber length and nerve fiber density in sweat glands compared to controls (p values < 0.05). No association between nerve fiber density and sweat responses was found (p = 0.21). In cases with reduced sweat gland nerve fiber length, nerve fiber density, and volume, the sweat response was reduced or absent. Height, systolic blood pressure, time in hypoglycemia, and total daily and basal/total insulin dose were positively correlated to sweat response, while low-density lipoprotein, and HbA1c were negatively correlated with sweat response (p values < 0.05). Other microvascular complications and high cholesterol levels increased the relative risk for reduced sweat gland nerve fiber density.

CONCLUSION: Our findings of reduced sweat gland innervation in a selected group of adolescents add new knowledge about the structural changes that occur in autonomic nerves due to diabetes. Evaluating both the sweat gland innervation and sweat gland volume was important for understanding the association with sweat responses. Further research is needed to understand its clinical relevance.

Original language	English
Journal	Clinical Autonomic Research
Volume	33
Issue	6
Pages (from-to)	691-703
Number of pages	13
ISSN	0959-9851
DOIs	https://doi.org/10.1007/s10286-023-00973-7
Publication status	Published - Dec 2023

Keywords

Adolescents
Neuropathy
Quantitative sudomotor axon reflex test
Sweat gland nerve fiber density
Type 1 diabetes

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Rasmussen, V. F., Schmeichel, A., Thrysøe, M., Nyengaard, J. R., Christensen, A.-M. R., Vestergaard, E. T., Kristensen, K., Terkelsen, A. J., Karlsson, P., & Singer, W. (2023). Sweat gland nerve fiber density and association with sudomotor function, symptoms, and risk factors in adolescents with type 1 diabetes. Clinical Autonomic Research, 33(6), 691-703. https://doi.org/10.1007/s10286-023-00973-7

@article{192de435b1bf411787b4f5884ea123ab,

title = "Sweat gland nerve fiber density and association with sudomotor function, symptoms, and risk factors in adolescents with type 1 diabetes",

abstract = "PURPOSE: To quantify sweat gland nerve fiber density in adolescents with diabetes. Additionally, to investigate associations between sudomotor innervation, sweat responses, and possible risk factors for sudomotor neuropathy.METHODS: Cross-sectional study where 60 adolescents with type 1 diabetes (duration > 5 years) and 23 control subjects were included. Clinical data, quantitative sudomotor axon reflex test, and skin biopsies were obtained. Skin tissue was immunostained and imaged by confocal microscopy. Quantification of the sweat gland volume and three-dimensional reconstruction of the nerve fibers was performed using a design-unbiased technique.RESULTS: Adolescents with diabetes had a significant reduction of maximum and mean values of nerve fiber length and nerve fiber density in sweat glands compared to controls (p values < 0.05). No association between nerve fiber density and sweat responses was found (p = 0.21). In cases with reduced sweat gland nerve fiber length, nerve fiber density, and volume, the sweat response was reduced or absent. Height, systolic blood pressure, time in hypoglycemia, and total daily and basal/total insulin dose were positively correlated to sweat response, while low-density lipoprotein, and HbA1c were negatively correlated with sweat response (p values < 0.05). Other microvascular complications and high cholesterol levels increased the relative risk for reduced sweat gland nerve fiber density.CONCLUSION: Our findings of reduced sweat gland innervation in a selected group of adolescents add new knowledge about the structural changes that occur in autonomic nerves due to diabetes. Evaluating both the sweat gland innervation and sweat gland volume was important for understanding the association with sweat responses. Further research is needed to understand its clinical relevance.",

keywords = "Adolescents, Neuropathy, Quantitative sudomotor axon reflex test, Sweat gland nerve fiber density, Type 1 diabetes",

author = "Rasmussen, {Vinni Faber} and Ann Schmeichel and Mathilde Thrys{\o}e and Nyengaard, {Jens Randel} and Christensen, {Ann-Margrethe R{\o}nholt} and Vestergaard, {Esben Thyssen} and Kurt Kristensen and Terkelsen, {Astrid Juhl} and P{\'a}ll Karlsson and Wolfgang Singer",

note = "{\textcopyright} 2023. The Author(s).",

year = "2023",

month = dec,

doi = "10.1007/s10286-023-00973-7",

language = "English",

volume = "33",

pages = "691--703",

journal = "Clinical Autonomic Research",

issn = "0959-9851",

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Rasmussen, VF, Schmeichel, A, Thrysøe, M, Nyengaard, JR, Christensen, A-MR, Vestergaard, ET , Kristensen, K , Terkelsen, AJ , Karlsson, P & Singer, W 2023, 'Sweat gland nerve fiber density and association with sudomotor function, symptoms, and risk factors in adolescents with type 1 diabetes', Clinical Autonomic Research, vol. 33, no. 6, pp. 691-703. https://doi.org/10.1007/s10286-023-00973-7

Sweat gland nerve fiber density and association with sudomotor function, symptoms, and risk factors in adolescents with type 1 diabetes. / Rasmussen, Vinni Faber; Schmeichel, Ann; Thrysøe, Mathilde et al.
In: Clinical Autonomic Research, Vol. 33, No. 6, 12.2023, p. 691-703.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Sweat gland nerve fiber density and association with sudomotor function, symptoms, and risk factors in adolescents with type 1 diabetes

AU - Rasmussen, Vinni Faber

AU - Schmeichel, Ann

AU - Thrysøe, Mathilde

AU - Nyengaard, Jens Randel

AU - Christensen, Ann-Margrethe Rønholt

AU - Vestergaard, Esben Thyssen

AU - Kristensen, Kurt

AU - Terkelsen, Astrid Juhl

AU - Karlsson, Páll

AU - Singer, Wolfgang

PY - 2023/12

Y1 - 2023/12

N2 - PURPOSE: To quantify sweat gland nerve fiber density in adolescents with diabetes. Additionally, to investigate associations between sudomotor innervation, sweat responses, and possible risk factors for sudomotor neuropathy.METHODS: Cross-sectional study where 60 adolescents with type 1 diabetes (duration > 5 years) and 23 control subjects were included. Clinical data, quantitative sudomotor axon reflex test, and skin biopsies were obtained. Skin tissue was immunostained and imaged by confocal microscopy. Quantification of the sweat gland volume and three-dimensional reconstruction of the nerve fibers was performed using a design-unbiased technique.RESULTS: Adolescents with diabetes had a significant reduction of maximum and mean values of nerve fiber length and nerve fiber density in sweat glands compared to controls (p values < 0.05). No association between nerve fiber density and sweat responses was found (p = 0.21). In cases with reduced sweat gland nerve fiber length, nerve fiber density, and volume, the sweat response was reduced or absent. Height, systolic blood pressure, time in hypoglycemia, and total daily and basal/total insulin dose were positively correlated to sweat response, while low-density lipoprotein, and HbA1c were negatively correlated with sweat response (p values < 0.05). Other microvascular complications and high cholesterol levels increased the relative risk for reduced sweat gland nerve fiber density.CONCLUSION: Our findings of reduced sweat gland innervation in a selected group of adolescents add new knowledge about the structural changes that occur in autonomic nerves due to diabetes. Evaluating both the sweat gland innervation and sweat gland volume was important for understanding the association with sweat responses. Further research is needed to understand its clinical relevance.

AB - PURPOSE: To quantify sweat gland nerve fiber density in adolescents with diabetes. Additionally, to investigate associations between sudomotor innervation, sweat responses, and possible risk factors for sudomotor neuropathy.METHODS: Cross-sectional study where 60 adolescents with type 1 diabetes (duration > 5 years) and 23 control subjects were included. Clinical data, quantitative sudomotor axon reflex test, and skin biopsies were obtained. Skin tissue was immunostained and imaged by confocal microscopy. Quantification of the sweat gland volume and three-dimensional reconstruction of the nerve fibers was performed using a design-unbiased technique.RESULTS: Adolescents with diabetes had a significant reduction of maximum and mean values of nerve fiber length and nerve fiber density in sweat glands compared to controls (p values < 0.05). No association between nerve fiber density and sweat responses was found (p = 0.21). In cases with reduced sweat gland nerve fiber length, nerve fiber density, and volume, the sweat response was reduced or absent. Height, systolic blood pressure, time in hypoglycemia, and total daily and basal/total insulin dose were positively correlated to sweat response, while low-density lipoprotein, and HbA1c were negatively correlated with sweat response (p values < 0.05). Other microvascular complications and high cholesterol levels increased the relative risk for reduced sweat gland nerve fiber density.CONCLUSION: Our findings of reduced sweat gland innervation in a selected group of adolescents add new knowledge about the structural changes that occur in autonomic nerves due to diabetes. Evaluating both the sweat gland innervation and sweat gland volume was important for understanding the association with sweat responses. Further research is needed to understand its clinical relevance.

KW - Adolescents

KW - Neuropathy

KW - Quantitative sudomotor axon reflex test

KW - Sweat gland nerve fiber density

KW - Type 1 diabetes

U2 - 10.1007/s10286-023-00973-7

DO - 10.1007/s10286-023-00973-7

M3 - Journal article

C2 - 37682387

SN - 0959-9851

VL - 33

SP - 691

EP - 703

JO - Clinical Autonomic Research

JF - Clinical Autonomic Research

IS - 6

ER -

Sweat gland nerve fiber density and association with sudomotor function, symptoms, and risk factors in adolescents with type 1 diabetes

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Keywords

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