Reduced Thalamic Volume and Metabolites in Type 1 Diabetes with Polyneuropathy

Tine M Hansen; Jens B Frøkjær; Dinesh Selvarajah; Janusiya A Muthulingam; Solomon Tesfaye; Anne Juhl; Asbjørn M Drewes; Poul E Jakobsen; Jesper Karmisholt; Birgitte Brock; Christina Brock

doi:10.1055/a-1347-2579

Reduced Thalamic Volume and Metabolites in Type 1 Diabetes with Polyneuropathy

Tine M Hansen, Jens B Frøkjær, Dinesh Selvarajah, Janusiya A Muthulingam, Solomon Tesfaye, Anne Juhl, Asbjørn M Drewes, Poul E Jakobsen, Jesper Karmisholt, Birgitte Brock, Christina Brock

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

OBJECTIVE: Thalamus is essential in processing of sensory information. This study explored the associations between thalamic volume and intra-thalamic metabolites and associations to clinical and experimental characteristics of sensory function in adults with diabetic polyneuropathy.

METHODS: 48 adults with type 1 diabetes and confirmed distal symmetric peripheral neuropathy (DPSN) and 28 healthy controls participated in a cross-sectional study and underwent a brain magnetic resonance imaging scan. Estimates for thalamic volume were extracted using voxel-based morphometry and intra-thalamic N-acetylaspartate/creatine (NAA/cre) levels were assessed by magnetic resonance spectroscopy. Associations between thalamic volume and clinical measures, quantitative sensory testing and neuropathic phenotype were explored.

RESULTS: In diabetes, reduced gray matter volume was identified including bilateral thalamus (all p≤0.001) in comparison to healthy participants. Thalamic volume estimates were positively associated to intra-thalamic NAA/cre (r=0.4; p=0.006), however not to diabetes duration (p=0.5), severity of DSPN (p=0.7), or presence of pain (p=0.3). Individuals with the lowest thalamic volume had greatest loss of protective sensation (light touch using von Frey-like filaments, p=0.037) and highest pain tolerance to electric stimulation (tetanic stimulation, p=0.008) compared to individuals with the highest thalamic volume.

CONCLUSIONS: In this cohort with type 1 diabetes and severe DSPN, thalamic atrophy was present and associated with reduced NAA/cre, indicating thalamic structural loss and dysfunction. Thalamic atrophy was associated to reduced sensory function involving large fiber neuropathy and sensation to tetanic stimulation that may reflect synaptic transmission. This may ultimately contribute to the current understanding of the pathophysiology behind the perception changes evident in DSPN.

Original language	English
Journal	Experimental and Clinical Endocrinology and Diabetes
Volume	130
Issue number	5
Pages (from-to)	327-334
Number of pages	8
ISSN	0947-7349
DOIs	https://doi.org/10.1055/a-1347-2579
Publication status	Published - May 2022

Keywords

Brain metabolites
Central nervous system
Diabetic neuropathy
Magnetic Resonance Spectroscopy
Peripheral nervous system
Thalamus

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Hansen, T. M., Frøkjær, J. B., Selvarajah, D., Muthulingam, J. A., Tesfaye, S., Juhl, A., Drewes, A. M., Jakobsen, P. E., Karmisholt, J., Brock, B., & Brock, C. (2022). Reduced Thalamic Volume and Metabolites in Type 1 Diabetes with Polyneuropathy. Experimental and Clinical Endocrinology and Diabetes, 130(5), 327-334. Advance online publication. https://doi.org/10.1055/a-1347-2579

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title = "Reduced Thalamic Volume and Metabolites in Type 1 Diabetes with Polyneuropathy",

abstract = "OBJECTIVE: Thalamus is essential in processing of sensory information. This study explored the associations between thalamic volume and intra-thalamic metabolites and associations to clinical and experimental characteristics of sensory function in adults with diabetic polyneuropathy.METHODS: 48 adults with type 1 diabetes and confirmed distal symmetric peripheral neuropathy (DPSN) and 28 healthy controls participated in a cross-sectional study and underwent a brain magnetic resonance imaging scan. Estimates for thalamic volume were extracted using voxel-based morphometry and intra-thalamic N-acetylaspartate/creatine (NAA/cre) levels were assessed by magnetic resonance spectroscopy. Associations between thalamic volume and clinical measures, quantitative sensory testing and neuropathic phenotype were explored.RESULTS: In diabetes, reduced gray matter volume was identified including bilateral thalamus (all p≤0.001) in comparison to healthy participants. Thalamic volume estimates were positively associated to intra-thalamic NAA/cre (r=0.4; p=0.006), however not to diabetes duration (p=0.5), severity of DSPN (p=0.7), or presence of pain (p=0.3). Individuals with the lowest thalamic volume had greatest loss of protective sensation (light touch using von Frey-like filaments, p=0.037) and highest pain tolerance to electric stimulation (tetanic stimulation, p=0.008) compared to individuals with the highest thalamic volume.CONCLUSIONS: In this cohort with type 1 diabetes and severe DSPN, thalamic atrophy was present and associated with reduced NAA/cre, indicating thalamic structural loss and dysfunction. Thalamic atrophy was associated to reduced sensory function involving large fiber neuropathy and sensation to tetanic stimulation that may reflect synaptic transmission. This may ultimately contribute to the current understanding of the pathophysiology behind the perception changes evident in DSPN.",

keywords = "Brain metabolites, Central nervous system, Diabetic neuropathy, Magnetic Resonance Spectroscopy, Peripheral nervous system, Thalamus",

author = "Hansen, {Tine M} and Fr{\o}kj{\ae}r, {Jens B} and Dinesh Selvarajah and Muthulingam, {Janusiya A} and Solomon Tesfaye and Anne Juhl and Drewes, {Asbj{\o}rn M} and Jakobsen, {Poul E} and Jesper Karmisholt and Birgitte Brock and Christina Brock",

year = "2022",

month = may,

doi = "10.1055/a-1347-2579",

language = "English",

volume = "130",

pages = "327--334",

journal = "Experimental and Clinical Endocrinology and Diabetes",

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TY - JOUR

T1 - Reduced Thalamic Volume and Metabolites in Type 1 Diabetes with Polyneuropathy

AU - Hansen, Tine M

AU - Frøkjær, Jens B

AU - Selvarajah, Dinesh

AU - Muthulingam, Janusiya A

AU - Tesfaye, Solomon

AU - Juhl, Anne

AU - Drewes, Asbjørn M

AU - Jakobsen, Poul E

AU - Karmisholt, Jesper

AU - Brock, Birgitte

AU - Brock, Christina

PY - 2022/5

Y1 - 2022/5

N2 - OBJECTIVE: Thalamus is essential in processing of sensory information. This study explored the associations between thalamic volume and intra-thalamic metabolites and associations to clinical and experimental characteristics of sensory function in adults with diabetic polyneuropathy.METHODS: 48 adults with type 1 diabetes and confirmed distal symmetric peripheral neuropathy (DPSN) and 28 healthy controls participated in a cross-sectional study and underwent a brain magnetic resonance imaging scan. Estimates for thalamic volume were extracted using voxel-based morphometry and intra-thalamic N-acetylaspartate/creatine (NAA/cre) levels were assessed by magnetic resonance spectroscopy. Associations between thalamic volume and clinical measures, quantitative sensory testing and neuropathic phenotype were explored.RESULTS: In diabetes, reduced gray matter volume was identified including bilateral thalamus (all p≤0.001) in comparison to healthy participants. Thalamic volume estimates were positively associated to intra-thalamic NAA/cre (r=0.4; p=0.006), however not to diabetes duration (p=0.5), severity of DSPN (p=0.7), or presence of pain (p=0.3). Individuals with the lowest thalamic volume had greatest loss of protective sensation (light touch using von Frey-like filaments, p=0.037) and highest pain tolerance to electric stimulation (tetanic stimulation, p=0.008) compared to individuals with the highest thalamic volume.CONCLUSIONS: In this cohort with type 1 diabetes and severe DSPN, thalamic atrophy was present and associated with reduced NAA/cre, indicating thalamic structural loss and dysfunction. Thalamic atrophy was associated to reduced sensory function involving large fiber neuropathy and sensation to tetanic stimulation that may reflect synaptic transmission. This may ultimately contribute to the current understanding of the pathophysiology behind the perception changes evident in DSPN.

AB - OBJECTIVE: Thalamus is essential in processing of sensory information. This study explored the associations between thalamic volume and intra-thalamic metabolites and associations to clinical and experimental characteristics of sensory function in adults with diabetic polyneuropathy.METHODS: 48 adults with type 1 diabetes and confirmed distal symmetric peripheral neuropathy (DPSN) and 28 healthy controls participated in a cross-sectional study and underwent a brain magnetic resonance imaging scan. Estimates for thalamic volume were extracted using voxel-based morphometry and intra-thalamic N-acetylaspartate/creatine (NAA/cre) levels were assessed by magnetic resonance spectroscopy. Associations between thalamic volume and clinical measures, quantitative sensory testing and neuropathic phenotype were explored.RESULTS: In diabetes, reduced gray matter volume was identified including bilateral thalamus (all p≤0.001) in comparison to healthy participants. Thalamic volume estimates were positively associated to intra-thalamic NAA/cre (r=0.4; p=0.006), however not to diabetes duration (p=0.5), severity of DSPN (p=0.7), or presence of pain (p=0.3). Individuals with the lowest thalamic volume had greatest loss of protective sensation (light touch using von Frey-like filaments, p=0.037) and highest pain tolerance to electric stimulation (tetanic stimulation, p=0.008) compared to individuals with the highest thalamic volume.CONCLUSIONS: In this cohort with type 1 diabetes and severe DSPN, thalamic atrophy was present and associated with reduced NAA/cre, indicating thalamic structural loss and dysfunction. Thalamic atrophy was associated to reduced sensory function involving large fiber neuropathy and sensation to tetanic stimulation that may reflect synaptic transmission. This may ultimately contribute to the current understanding of the pathophysiology behind the perception changes evident in DSPN.

KW - Brain metabolites

KW - Central nervous system

KW - Diabetic neuropathy

KW - Magnetic Resonance Spectroscopy

KW - Peripheral nervous system

KW - Thalamus

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U2 - 10.1055/a-1347-2579

DO - 10.1055/a-1347-2579

M3 - Journal article

C2 - 33524993

SN - 0947-7349

VL - 130

SP - 327

EP - 334

JO - Experimental and Clinical Endocrinology and Diabetes

JF - Experimental and Clinical Endocrinology and Diabetes

IS - 5

ER -

Reduced Thalamic Volume and Metabolites in Type 1 Diabetes with Polyneuropathy

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