Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes
Aims/hypothesis Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by...
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| Veröffentlicht in: | Diabetologia 2021-02, Vol.64 (2), p.458-468 |
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| creator | Ziegler, Dan Strom, Alexander Straßburger, Klaus Knebel, Birgit Bönhof, Gidon J. Kotzka, Jörg Szendroedi, Julia Roden, Michael |
| description | Aims/hypothesis
Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by reduced heart rate variability (HRV), particularly in type 2 diabetes. We hypothesised that distinct lipid metabolites are associated with diminished HRV in recent-onset type 2 diabetes rather than type 1 diabetes.
Methods
We analysed 127 plasma lipid metabolites (11 acylcarnitines, 39 NEFA, 12 sphingomyelins (SMs), 56 phosphatidylcholines and nine lysophosphatidylcholines) using MS in participants from the German Diabetes Study baseline cohort recently diagnosed with type 1 (
n
= 100) and type 2 diabetes (
n
= 206). Four time-domain HRV indices (number of normal-to-normal (NN) intervals >50 ms divided by the number of all NN intervals [pNN50]; root mean square of successive differences [RMSSD]; SD of NN intervals [SDNN]; and SD of differences between adjacent NN intervals) and three frequency-domain HRV indices (very-low-frequency [VLF], low-frequency [LF] and high-frequency [HF] power spectrum) were computed from NN intervals recorded during a 3 h hyperinsulinaemic–euglycaemic clamp at baseline and in subsets of participants with type 1 (
n
= 60) and type 2 diabetes (
n
= 95) after 5 years.
Results
In participants with type 2 diabetes, after Bonferroni correction and rigorous adjustment, SDNN was inversely associated with higher levels of diacyl-phosphatidylcholine (PCaa) C32:0, PCaa C34:1, acyl-alkyl-phosphatidylcholine (PCae) C36:0, SM C16:0 and SM C16:1. SD of differences between NN intervals was inversely associated with PCaa C32:0, PCaa C34:1, PCaa C34:2, PCae C36:0 and SM C16:1, and RMSSD with PCae C36:0. For VLF power, inverse associations were found with PCaa C30:0, PCaa C32:0, PCaa C32:1, PCaa C34:2 and SM C16:1, and for LF power inverse associations were found with PCaa C32:0 and SM C16:1 (
r
= −0.242 to
r
= −0.349;
p
≤ 0.0005 for all correlations). In contrast, no associations of lipid metabolites with measures of cardiac autonomic function were noted in participants recently diagnosed with type 1 diabetes. After 5 years, HRV declined due to ageing rather than diabetes, whereby prediction analyses for lipid metabolites were hampered.
Conclusions/interpretation
Higher plasma levels of specific lipid metabolites are closely linked to cardiac au |
| doi_str_mv | 10.1007/s00125-020-05310-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_2452982430</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2476739037</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-3144d22e55feff16c1ea3ffaeed985ec14ecc9486670e55298901fdc6bdb371e3</originalsourceid><addsrcrecordid>eNqNkUuLFDEURgtRnHH0D7iQgBtBSm8eVZXaCEPjCwbcKLgLqdRNd4aqpE1SMzT-edPdY_tYiKsE7vnug1NVTym8ogDd6wRAWVMDgxoaTqFu7lXnVHBWg2DyfnW-r9dUtl_PqkcpXQMAb0T7sDrjHKToO3pefb9MKRinswueBEuMjqPThuglBx9mZ8i4S3bx5gDcurwhG7feYCQT3uCU9pntpNOsyeS2biQzZj2EyWVMxHkS0aDPdfAJM8m7LRJGyoABS_1x9cDqKeGTu_ei-vLu7efVh_rq0_uPq8ur2ohO5JpTIUbGsGksWktbQ1FzazXi2MsGDRVoTC9k23ZQINbLHqgdTTuMA-8o8ovqzbHvdhlmHPcLRT2pbXSzjjsVtFN_VrzbqHW4UZ0EyhtZGry4axDDtwVTVrNLBqdJewxLUkzspzLBoaDP_0KvwxJ9Oa9QXdvxHnhXKHakTAwpRbSnZSiovVt1dKuKW3Vwq5oSevb7GafIT5kFkEfgFodgk3HoDZ6wYr-RlEvKyg_oyuWD9FVYfC7Rl_8fLTQ_0qkQfo3x15H_2P8H0pXTHQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2476739037</pqid></control><display><type>article</type><title>Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes</title><source>MEDLINE</source><source>SpringerNature Journals</source><source>Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><creator>Ziegler, Dan ; Strom, Alexander ; Straßburger, Klaus ; Knebel, Birgit ; Bönhof, Gidon J. ; Kotzka, Jörg ; Szendroedi, Julia ; Roden, Michael</creator><creatorcontrib>Ziegler, Dan ; Strom, Alexander ; Straßburger, Klaus ; Knebel, Birgit ; Bönhof, Gidon J. ; Kotzka, Jörg ; Szendroedi, Julia ; Roden, Michael ; German Diabet Study Grp ; German Diabetes Study group ; for the German Diabetes Study group</creatorcontrib><description>Aims/hypothesis
Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by reduced heart rate variability (HRV), particularly in type 2 diabetes. We hypothesised that distinct lipid metabolites are associated with diminished HRV in recent-onset type 2 diabetes rather than type 1 diabetes.
Methods
We analysed 127 plasma lipid metabolites (11 acylcarnitines, 39 NEFA, 12 sphingomyelins (SMs), 56 phosphatidylcholines and nine lysophosphatidylcholines) using MS in participants from the German Diabetes Study baseline cohort recently diagnosed with type 1 (
n
= 100) and type 2 diabetes (
n
= 206). Four time-domain HRV indices (number of normal-to-normal (NN) intervals >50 ms divided by the number of all NN intervals [pNN50]; root mean square of successive differences [RMSSD]; SD of NN intervals [SDNN]; and SD of differences between adjacent NN intervals) and three frequency-domain HRV indices (very-low-frequency [VLF], low-frequency [LF] and high-frequency [HF] power spectrum) were computed from NN intervals recorded during a 3 h hyperinsulinaemic–euglycaemic clamp at baseline and in subsets of participants with type 1 (
n
= 60) and type 2 diabetes (
n
= 95) after 5 years.
Results
In participants with type 2 diabetes, after Bonferroni correction and rigorous adjustment, SDNN was inversely associated with higher levels of diacyl-phosphatidylcholine (PCaa) C32:0, PCaa C34:1, acyl-alkyl-phosphatidylcholine (PCae) C36:0, SM C16:0 and SM C16:1. SD of differences between NN intervals was inversely associated with PCaa C32:0, PCaa C34:1, PCaa C34:2, PCae C36:0 and SM C16:1, and RMSSD with PCae C36:0. For VLF power, inverse associations were found with PCaa C30:0, PCaa C32:0, PCaa C32:1, PCaa C34:2 and SM C16:1, and for LF power inverse associations were found with PCaa C32:0 and SM C16:1 (
r
= −0.242 to
r
= −0.349;
p
≤ 0.0005 for all correlations). In contrast, no associations of lipid metabolites with measures of cardiac autonomic function were noted in participants recently diagnosed with type 1 diabetes. After 5 years, HRV declined due to ageing rather than diabetes, whereby prediction analyses for lipid metabolites were hampered.
Conclusions/interpretation
Higher plasma levels of specific lipid metabolites are closely linked to cardiac autonomic dysfunction in recent-onset type 2 diabetes but not type 1 diabetes, suggesting a role for perturbed lipid metabolism in the early development of CAN in type 2 diabetes.
Graphical abstract</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-020-05310-5</identifier><identifier>PMID: 33084971</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aging ; Autonomic nervous system ; Autonomic Nervous System Diseases - blood ; Autonomic Nervous System Diseases - etiology ; Autonomic Nervous System Diseases - physiopathology ; Carnitine - analogs & derivatives ; Carnitine - blood ; Diabetes ; Diabetes mellitus (insulin dependent) ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 1 - blood ; Diabetes Mellitus, Type 1 - complications ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - complications ; Diabetic Neuropathies - blood ; Diabetic Neuropathies - etiology ; Diabetic Neuropathies - physiopathology ; Diabetic neuropathy ; Dysautonomia ; Dyslipidemia ; Dyslipidemias - blood ; Endocrinology & Metabolism ; Fatty Acids, Nonesterified - blood ; Female ; Glucose Clamp Technique ; Heart Rate ; Human Physiology ; Humans ; Hyperglycemia ; Insulin ; Insulin Resistance ; Internal Medicine ; Lecithin ; Life Sciences & Biomedicine ; Lipid Metabolism ; Lipidomics ; Lipids ; Lysophosphatidylcholines - blood ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolites ; Middle Aged ; Obesity - blood ; Phosphatidylcholine ; Phosphatidylcholines - blood ; Plasma levels ; Science & Technology ; Sphingomyelins - blood ; Young Adult</subject><ispartof>Diabetologia, 2021-02, Vol.64 (2), p.458-468</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>23</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000581381200001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c474t-3144d22e55feff16c1ea3ffaeed985ec14ecc9486670e55298901fdc6bdb371e3</citedby><cites>FETCH-LOGICAL-c474t-3144d22e55feff16c1ea3ffaeed985ec14ecc9486670e55298901fdc6bdb371e3</cites><orcidid>0000-0001-8200-6382 ; 0000-0001-9896-1106 ; 0000-0003-1446-6592 ; 0000-0001-8956-3552 ; 0000-0003-1173-9372</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-020-05310-5$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-020-05310-5$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,27929,27930,39263,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33084971$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ziegler, Dan</creatorcontrib><creatorcontrib>Strom, Alexander</creatorcontrib><creatorcontrib>Straßburger, Klaus</creatorcontrib><creatorcontrib>Knebel, Birgit</creatorcontrib><creatorcontrib>Bönhof, Gidon J.</creatorcontrib><creatorcontrib>Kotzka, Jörg</creatorcontrib><creatorcontrib>Szendroedi, Julia</creatorcontrib><creatorcontrib>Roden, Michael</creatorcontrib><creatorcontrib>German Diabet Study Grp</creatorcontrib><creatorcontrib>German Diabetes Study group</creatorcontrib><creatorcontrib>for the German Diabetes Study group</creatorcontrib><title>Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>DIABETOLOGIA</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by reduced heart rate variability (HRV), particularly in type 2 diabetes. We hypothesised that distinct lipid metabolites are associated with diminished HRV in recent-onset type 2 diabetes rather than type 1 diabetes.
Methods
We analysed 127 plasma lipid metabolites (11 acylcarnitines, 39 NEFA, 12 sphingomyelins (SMs), 56 phosphatidylcholines and nine lysophosphatidylcholines) using MS in participants from the German Diabetes Study baseline cohort recently diagnosed with type 1 (
n
= 100) and type 2 diabetes (
n
= 206). Four time-domain HRV indices (number of normal-to-normal (NN) intervals >50 ms divided by the number of all NN intervals [pNN50]; root mean square of successive differences [RMSSD]; SD of NN intervals [SDNN]; and SD of differences between adjacent NN intervals) and three frequency-domain HRV indices (very-low-frequency [VLF], low-frequency [LF] and high-frequency [HF] power spectrum) were computed from NN intervals recorded during a 3 h hyperinsulinaemic–euglycaemic clamp at baseline and in subsets of participants with type 1 (
n
= 60) and type 2 diabetes (
n
= 95) after 5 years.
Results
In participants with type 2 diabetes, after Bonferroni correction and rigorous adjustment, SDNN was inversely associated with higher levels of diacyl-phosphatidylcholine (PCaa) C32:0, PCaa C34:1, acyl-alkyl-phosphatidylcholine (PCae) C36:0, SM C16:0 and SM C16:1. SD of differences between NN intervals was inversely associated with PCaa C32:0, PCaa C34:1, PCaa C34:2, PCae C36:0 and SM C16:1, and RMSSD with PCae C36:0. For VLF power, inverse associations were found with PCaa C30:0, PCaa C32:0, PCaa C32:1, PCaa C34:2 and SM C16:1, and for LF power inverse associations were found with PCaa C32:0 and SM C16:1 (
r
= −0.242 to
r
= −0.349;
p
≤ 0.0005 for all correlations). In contrast, no associations of lipid metabolites with measures of cardiac autonomic function were noted in participants recently diagnosed with type 1 diabetes. After 5 years, HRV declined due to ageing rather than diabetes, whereby prediction analyses for lipid metabolites were hampered.
Conclusions/interpretation
Higher plasma levels of specific lipid metabolites are closely linked to cardiac autonomic dysfunction in recent-onset type 2 diabetes but not type 1 diabetes, suggesting a role for perturbed lipid metabolism in the early development of CAN in type 2 diabetes.
Graphical abstract</description><subject>Adult</subject><subject>Aging</subject><subject>Autonomic nervous system</subject><subject>Autonomic Nervous System Diseases - blood</subject><subject>Autonomic Nervous System Diseases - etiology</subject><subject>Autonomic Nervous System Diseases - physiopathology</subject><subject>Carnitine - analogs & derivatives</subject><subject>Carnitine - blood</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 1 - blood</subject><subject>Diabetes Mellitus, Type 1 - complications</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetic Neuropathies - blood</subject><subject>Diabetic Neuropathies - etiology</subject><subject>Diabetic Neuropathies - physiopathology</subject><subject>Diabetic neuropathy</subject><subject>Dysautonomia</subject><subject>Dyslipidemia</subject><subject>Dyslipidemias - blood</subject><subject>Endocrinology & Metabolism</subject><subject>Fatty Acids, Nonesterified - blood</subject><subject>Female</subject><subject>Glucose Clamp Technique</subject><subject>Heart Rate</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Internal Medicine</subject><subject>Lecithin</subject><subject>Life Sciences & Biomedicine</subject><subject>Lipid Metabolism</subject><subject>Lipidomics</subject><subject>Lipids</subject><subject>Lysophosphatidylcholines - blood</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Metabolites</subject><subject>Middle Aged</subject><subject>Obesity - blood</subject><subject>Phosphatidylcholine</subject><subject>Phosphatidylcholines - blood</subject><subject>Plasma levels</subject><subject>Science & Technology</subject><subject>Sphingomyelins - blood</subject><subject>Young Adult</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkUuLFDEURgtRnHH0D7iQgBtBSm8eVZXaCEPjCwbcKLgLqdRNd4aqpE1SMzT-edPdY_tYiKsE7vnug1NVTym8ogDd6wRAWVMDgxoaTqFu7lXnVHBWg2DyfnW-r9dUtl_PqkcpXQMAb0T7sDrjHKToO3pefb9MKRinswueBEuMjqPThuglBx9mZ8i4S3bx5gDcurwhG7feYCQT3uCU9pntpNOsyeS2biQzZj2EyWVMxHkS0aDPdfAJM8m7LRJGyoABS_1x9cDqKeGTu_ei-vLu7efVh_rq0_uPq8ur2ohO5JpTIUbGsGksWktbQ1FzazXi2MsGDRVoTC9k23ZQINbLHqgdTTuMA-8o8ovqzbHvdhlmHPcLRT2pbXSzjjsVtFN_VrzbqHW4UZ0EyhtZGry4axDDtwVTVrNLBqdJewxLUkzspzLBoaDP_0KvwxJ9Oa9QXdvxHnhXKHakTAwpRbSnZSiovVt1dKuKW3Vwq5oSevb7GafIT5kFkEfgFodgk3HoDZ6wYr-RlEvKyg_oyuWD9FVYfC7Rl_8fLTQ_0qkQfo3x15H_2P8H0pXTHQ</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Ziegler, Dan</creator><creator>Strom, Alexander</creator><creator>Straßburger, Klaus</creator><creator>Knebel, Birgit</creator><creator>Bönhof, Gidon J.</creator><creator>Kotzka, Jörg</creator><creator>Szendroedi, Julia</creator><creator>Roden, Michael</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8200-6382</orcidid><orcidid>https://orcid.org/0000-0001-9896-1106</orcidid><orcidid>https://orcid.org/0000-0003-1446-6592</orcidid><orcidid>https://orcid.org/0000-0001-8956-3552</orcidid><orcidid>https://orcid.org/0000-0003-1173-9372</orcidid></search><sort><creationdate>20210201</creationdate><title>Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes</title><author>Ziegler, Dan ; Strom, Alexander ; Straßburger, Klaus ; Knebel, Birgit ; Bönhof, Gidon J. ; Kotzka, Jörg ; Szendroedi, Julia ; Roden, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-3144d22e55feff16c1ea3ffaeed985ec14ecc9486670e55298901fdc6bdb371e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aging</topic><topic>Autonomic nervous system</topic><topic>Autonomic Nervous System Diseases - blood</topic><topic>Autonomic Nervous System Diseases - etiology</topic><topic>Autonomic Nervous System Diseases - physiopathology</topic><topic>Carnitine - analogs & derivatives</topic><topic>Carnitine - blood</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 1 - blood</topic><topic>Diabetes Mellitus, Type 1 - complications</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetic Neuropathies - blood</topic><topic>Diabetic Neuropathies - etiology</topic><topic>Diabetic Neuropathies - physiopathology</topic><topic>Diabetic neuropathy</topic><topic>Dysautonomia</topic><topic>Dyslipidemia</topic><topic>Dyslipidemias - blood</topic><topic>Endocrinology & Metabolism</topic><topic>Fatty Acids, Nonesterified - blood</topic><topic>Female</topic><topic>Glucose Clamp Technique</topic><topic>Heart Rate</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Hyperglycemia</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Internal Medicine</topic><topic>Lecithin</topic><topic>Life Sciences & Biomedicine</topic><topic>Lipid Metabolism</topic><topic>Lipidomics</topic><topic>Lipids</topic><topic>Lysophosphatidylcholines - blood</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Metabolites</topic><topic>Middle Aged</topic><topic>Obesity - blood</topic><topic>Phosphatidylcholine</topic><topic>Phosphatidylcholines - blood</topic><topic>Plasma levels</topic><topic>Science & Technology</topic><topic>Sphingomyelins - blood</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ziegler, Dan</creatorcontrib><creatorcontrib>Strom, Alexander</creatorcontrib><creatorcontrib>Straßburger, Klaus</creatorcontrib><creatorcontrib>Knebel, Birgit</creatorcontrib><creatorcontrib>Bönhof, Gidon J.</creatorcontrib><creatorcontrib>Kotzka, Jörg</creatorcontrib><creatorcontrib>Szendroedi, Julia</creatorcontrib><creatorcontrib>Roden, Michael</creatorcontrib><creatorcontrib>German Diabet Study Grp</creatorcontrib><creatorcontrib>German Diabetes Study group</creatorcontrib><creatorcontrib>for the German Diabetes Study group</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ziegler, Dan</au><au>Strom, Alexander</au><au>Straßburger, Klaus</au><au>Knebel, Birgit</au><au>Bönhof, Gidon J.</au><au>Kotzka, Jörg</au><au>Szendroedi, Julia</au><au>Roden, Michael</au><aucorp>German Diabet Study Grp</aucorp><aucorp>German Diabetes Study group</aucorp><aucorp>for the German Diabetes Study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><stitle>DIABETOLOGIA</stitle><addtitle>Diabetologia</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>64</volume><issue>2</issue><spage>458</spage><epage>468</epage><pages>458-468</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by reduced heart rate variability (HRV), particularly in type 2 diabetes. We hypothesised that distinct lipid metabolites are associated with diminished HRV in recent-onset type 2 diabetes rather than type 1 diabetes.
Methods
We analysed 127 plasma lipid metabolites (11 acylcarnitines, 39 NEFA, 12 sphingomyelins (SMs), 56 phosphatidylcholines and nine lysophosphatidylcholines) using MS in participants from the German Diabetes Study baseline cohort recently diagnosed with type 1 (
n
= 100) and type 2 diabetes (
n
= 206). Four time-domain HRV indices (number of normal-to-normal (NN) intervals >50 ms divided by the number of all NN intervals [pNN50]; root mean square of successive differences [RMSSD]; SD of NN intervals [SDNN]; and SD of differences between adjacent NN intervals) and three frequency-domain HRV indices (very-low-frequency [VLF], low-frequency [LF] and high-frequency [HF] power spectrum) were computed from NN intervals recorded during a 3 h hyperinsulinaemic–euglycaemic clamp at baseline and in subsets of participants with type 1 (
n
= 60) and type 2 diabetes (
n
= 95) after 5 years.
Results
In participants with type 2 diabetes, after Bonferroni correction and rigorous adjustment, SDNN was inversely associated with higher levels of diacyl-phosphatidylcholine (PCaa) C32:0, PCaa C34:1, acyl-alkyl-phosphatidylcholine (PCae) C36:0, SM C16:0 and SM C16:1. SD of differences between NN intervals was inversely associated with PCaa C32:0, PCaa C34:1, PCaa C34:2, PCae C36:0 and SM C16:1, and RMSSD with PCae C36:0. For VLF power, inverse associations were found with PCaa C30:0, PCaa C32:0, PCaa C32:1, PCaa C34:2 and SM C16:1, and for LF power inverse associations were found with PCaa C32:0 and SM C16:1 (
r
= −0.242 to
r
= −0.349;
p
≤ 0.0005 for all correlations). In contrast, no associations of lipid metabolites with measures of cardiac autonomic function were noted in participants recently diagnosed with type 1 diabetes. After 5 years, HRV declined due to ageing rather than diabetes, whereby prediction analyses for lipid metabolites were hampered.
Conclusions/interpretation
Higher plasma levels of specific lipid metabolites are closely linked to cardiac autonomic dysfunction in recent-onset type 2 diabetes but not type 1 diabetes, suggesting a role for perturbed lipid metabolism in the early development of CAN in type 2 diabetes.
Graphical abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>33084971</pmid><doi>10.1007/s00125-020-05310-5</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-8200-6382</orcidid><orcidid>https://orcid.org/0000-0001-9896-1106</orcidid><orcidid>https://orcid.org/0000-0003-1446-6592</orcidid><orcidid>https://orcid.org/0000-0001-8956-3552</orcidid><orcidid>https://orcid.org/0000-0003-1173-9372</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-186X |
| ispartof | Diabetologia, 2021-02, Vol.64 (2), p.458-468 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2452982430 |
| source | MEDLINE; SpringerNature Journals; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /> |
| subjects | Adult Aging Autonomic nervous system Autonomic Nervous System Diseases - blood Autonomic Nervous System Diseases - etiology Autonomic Nervous System Diseases - physiopathology Carnitine - analogs & derivatives Carnitine - blood Diabetes Diabetes mellitus (insulin dependent) Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 1 - blood Diabetes Mellitus, Type 1 - complications Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - complications Diabetic Neuropathies - blood Diabetic Neuropathies - etiology Diabetic Neuropathies - physiopathology Diabetic neuropathy Dysautonomia Dyslipidemia Dyslipidemias - blood Endocrinology & Metabolism Fatty Acids, Nonesterified - blood Female Glucose Clamp Technique Heart Rate Human Physiology Humans Hyperglycemia Insulin Insulin Resistance Internal Medicine Lecithin Life Sciences & Biomedicine Lipid Metabolism Lipidomics Lipids Lysophosphatidylcholines - blood Male Medicine Medicine & Public Health Metabolic Diseases Metabolites Middle Aged Obesity - blood Phosphatidylcholine Phosphatidylcholines - blood Plasma levels Science & Technology Sphingomyelins - blood Young Adult |
| title | Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes |
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