Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes
Introduction Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality.Research design and methods In adults with type 1 diabetes, 49 metabolites previously associated with either DR o...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024-04-01
|
| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/12/2/e003973.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846100662882926592 |
|---|---|
| author | Peter Rossing Simone Theilade Christian Stevns Hansen Marie Frimodt-Moller Viktor Rotbain Curovic Tine W Hansen Cristina Legido-Quigley Nete Tofte Tarunveer S Ahluwalia Ismo Matias Mattila Brede A Sørland Siddhi Y Jain Karolina Sulek Kajetan Trost Signe Abitz Winther |
| author_facet | Peter Rossing Simone Theilade Christian Stevns Hansen Marie Frimodt-Moller Viktor Rotbain Curovic Tine W Hansen Cristina Legido-Quigley Nete Tofte Tarunveer S Ahluwalia Ismo Matias Mattila Brede A Sørland Siddhi Y Jain Karolina Sulek Kajetan Trost Signe Abitz Winther |
| author_sort | Peter Rossing |
| collection | DOAJ |
| description | Introduction Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality.Research design and methods In adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications—ie, presence of DKD±DR±DSPN) using linear regression models. Subsequently, the same metabolites were assessed with progression to endpoints: soft microvascular events (progression in albuminuria grade, ≥30% estimated glomerular filtration rate (eGFR) decline, or any progression in DR grade), hard microvascular events (progression to proliferative DR, chronic kidney failure, or ≥40% eGFR decline), and hard microvascular or macrovascular events (hard microvascular events, cardiovascular events (myocardial infarction, stroke, or arterial interventions), or cardiovascular mortality), using Cox models. All models were adjusted for sex, baseline age, diabetes duration, systolic blood pressure, HbA1c, body mass index, total cholesterol, smoking, and statin treatment.Results The full cohort investigated consisted of 487 participants. Mean (SD) follow-up was 4.8 (2.9, 5.7) years. Baseline biothesiometry was available in 202 participants, comprising the cross-sectional cohort. Eight metabolites were significantly associated with presence of DR, DKD, and DSPN, and six with additive microvascular burden severity. In the full cohort longitudinal analysis, higher levels of 3,4-dihydroxybutanoic acid (DHBA), 2,4-DHBA, ribonic acid, glycine, and ribitol were associated with development of events in both crude and adjusted models. Adding 3,4-DHBA, ribonic acid, and glycine to a traditional risk factor model improved the discrimination of hard microvascular events.Conclusions While prospective studies directly assessing the predictive ability of these markers are needed, our results strengthen the role of clinical metabolomics in relation to risk assessment of diabetic complications in chronic type 1 diabetes. |
| format | Article |
| id | doaj-art-1af062286c6c4c5eac1dbe7151d7f537 |
| institution | Kabale University |
| issn | 2052-4897 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj-art-1af062286c6c4c5eac1dbe7151d7f5372024-12-29T17:20:10ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972024-04-0112210.1136/bmjdrc-2023-003973Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetesPeter Rossing0Simone Theilade1Christian Stevns Hansen2Marie Frimodt-Moller3Viktor Rotbain Curovic4Tine W Hansen5Cristina Legido-Quigley6Nete Tofte7Tarunveer S Ahluwalia8Ismo Matias Mattila9Brede A Sørland10Siddhi Y Jain11Karolina Sulek12Kajetan Trost13Signe Abitz Winther14Department of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkDepartment of Complication Research, Steno Diabetes Center Copenhagen, Gentofte, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Gentofte, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkIntroduction Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality.Research design and methods In adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications—ie, presence of DKD±DR±DSPN) using linear regression models. Subsequently, the same metabolites were assessed with progression to endpoints: soft microvascular events (progression in albuminuria grade, ≥30% estimated glomerular filtration rate (eGFR) decline, or any progression in DR grade), hard microvascular events (progression to proliferative DR, chronic kidney failure, or ≥40% eGFR decline), and hard microvascular or macrovascular events (hard microvascular events, cardiovascular events (myocardial infarction, stroke, or arterial interventions), or cardiovascular mortality), using Cox models. All models were adjusted for sex, baseline age, diabetes duration, systolic blood pressure, HbA1c, body mass index, total cholesterol, smoking, and statin treatment.Results The full cohort investigated consisted of 487 participants. Mean (SD) follow-up was 4.8 (2.9, 5.7) years. Baseline biothesiometry was available in 202 participants, comprising the cross-sectional cohort. Eight metabolites were significantly associated with presence of DR, DKD, and DSPN, and six with additive microvascular burden severity. In the full cohort longitudinal analysis, higher levels of 3,4-dihydroxybutanoic acid (DHBA), 2,4-DHBA, ribonic acid, glycine, and ribitol were associated with development of events in both crude and adjusted models. Adding 3,4-DHBA, ribonic acid, and glycine to a traditional risk factor model improved the discrimination of hard microvascular events.Conclusions While prospective studies directly assessing the predictive ability of these markers are needed, our results strengthen the role of clinical metabolomics in relation to risk assessment of diabetic complications in chronic type 1 diabetes.https://drc.bmj.com/content/12/2/e003973.full |
| spellingShingle | Peter Rossing Simone Theilade Christian Stevns Hansen Marie Frimodt-Moller Viktor Rotbain Curovic Tine W Hansen Cristina Legido-Quigley Nete Tofte Tarunveer S Ahluwalia Ismo Matias Mattila Brede A Sørland Siddhi Y Jain Karolina Sulek Kajetan Trost Signe Abitz Winther Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes BMJ Open Diabetes Research & Care |
| title | Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes |
| title_full | Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes |
| title_fullStr | Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes |
| title_full_unstemmed | Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes |
| title_short | Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes |
| title_sort | circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes |
| url | https://drc.bmj.com/content/12/2/e003973.full |
| work_keys_str_mv | AT peterrossing circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT simonetheilade circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT christianstevnshansen circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT mariefrimodtmoller circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT viktorrotbaincurovic circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT tinewhansen circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT cristinalegidoquigley circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT netetofte circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT tarunveersahluwalia circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT ismomatiasmattila circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT bredeasørland circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT siddhiyjain circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT karolinasulek circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT kajetantrost circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes AT signeabitzwinther circulatingmetabolomicmarkersinassociationwithoverallburdenofmicrovascularcomplicationsintype1diabetes |