Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA study
Abstract Background Biomarkers may contribute to our understanding of the pathophysiology of various diseases. Type 2 diabetes (T2D) and coronary heart disease (CHD) share many clinical and lifestyle risk factors and several biomarkers are associated with both diseases. The current analysis aims to...
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-03-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12933-020-01003-w |
| _version_ | 1819050358399303680 |
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| author | Cornelia Huth Alina Bauer Astrid Zierer Julie Sudduth-Klinger Christa Meisinger Michael Roden Annette Peters Wolfgang Koenig Christian Herder Barbara Thorand |
| author_facet | Cornelia Huth Alina Bauer Astrid Zierer Julie Sudduth-Klinger Christa Meisinger Michael Roden Annette Peters Wolfgang Koenig Christian Herder Barbara Thorand |
| author_sort | Cornelia Huth |
| collection | DOAJ |
| description | Abstract Background Biomarkers may contribute to our understanding of the pathophysiology of various diseases. Type 2 diabetes (T2D) and coronary heart disease (CHD) share many clinical and lifestyle risk factors and several biomarkers are associated with both diseases. The current analysis aims to assess the relevance of biomarkers combined to pathway groups for the development of T2D and CHD in the same cohort. Methods Forty-seven serum biomarkers were measured in the MONICA/KORA case-cohort study using clinical chemistry assays and ultrasensitive molecular counting technology. The T2D (CHD) analyses included 689 (568) incident cases and 1850 (2004) non-cases from three population-based surveys. At baseline, the study participants were 35–74 years old. The median follow-up was 14 years. We computed Cox regression models for each biomarker, adjusted for age, sex, and survey. Additionally, we assigned the biomarkers to 19 etiological pathways based on information from literature. One age-, sex-, and survey-controlled average variable was built for each pathway. We used the R2 PM coefficient of determination to assess the explained disease risk. Results The associations of many biomarkers, such as several cytokines or the iron marker soluble transferrin receptor (sTfR), were similar in strength for T2D and CHD, but we also observed important differences. Lipoprotein (a) (Lp(a)) and N-terminal pro B-type natriuretic peptide (NT-proBNP) even demonstrated opposite effect directions. All pathway variables together explained 49% of the T2D risk and 21% of the CHD risk. The insulin-like growth factor binding protein 2 (IGFBP-2, IGF/IGFBP system pathway) best explained the T2D risk (about 9% explained risk, independent of all other pathway variables). For CHD, the myocardial-injury- and lipid-related-pathways were most important and both explained about 4% of the CHD risk. Conclusions The biomarker-derived pathway variables explained a higher proportion of the T2D risk compared to CHD. The ranking of the pathways differed between the two diseases, with the IGF/IGFBP-system-pathway being most strongly associated with T2D and the myocardial-injury- and lipid-related-pathways with CHD. Our results help to better understand the pathophysiology of the two diseases, with the ultimate goal of pointing out targets for lifestyle intervention and drug development to ideally prevent both T2D and CHD development. |
| first_indexed | 2024-12-21T11:46:47Z |
| format | Article |
| id | doaj.art-6fe4091a69df4c80a2360322be1d93e4 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-12-21T11:46:47Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-6fe4091a69df4c80a2360322be1d93e42022-12-21T19:05:10ZengBMCCardiovascular Diabetology1475-28402020-03-0119111410.1186/s12933-020-01003-wBiomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA studyCornelia Huth0Alina Bauer1Astrid Zierer2Julie Sudduth-Klinger3Christa Meisinger4Michael Roden5Annette Peters6Wolfgang Koenig7Christian Herder8Barbara Thorand9Institute of Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health (GmbH)Institute of Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health (GmbH)Institute of Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health (GmbH)Tethys Bioscience Inc.Chair of Epidemiology, Ludwig-Maximilians-Universität München, UNIKA-T AugsburgGerman Center for Diabetes Research (DZD)Institute of Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health (GmbH)German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart AllianceGerman Center for Diabetes Research (DZD)Institute of Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health (GmbH)Abstract Background Biomarkers may contribute to our understanding of the pathophysiology of various diseases. Type 2 diabetes (T2D) and coronary heart disease (CHD) share many clinical and lifestyle risk factors and several biomarkers are associated with both diseases. The current analysis aims to assess the relevance of biomarkers combined to pathway groups for the development of T2D and CHD in the same cohort. Methods Forty-seven serum biomarkers were measured in the MONICA/KORA case-cohort study using clinical chemistry assays and ultrasensitive molecular counting technology. The T2D (CHD) analyses included 689 (568) incident cases and 1850 (2004) non-cases from three population-based surveys. At baseline, the study participants were 35–74 years old. The median follow-up was 14 years. We computed Cox regression models for each biomarker, adjusted for age, sex, and survey. Additionally, we assigned the biomarkers to 19 etiological pathways based on information from literature. One age-, sex-, and survey-controlled average variable was built for each pathway. We used the R2 PM coefficient of determination to assess the explained disease risk. Results The associations of many biomarkers, such as several cytokines or the iron marker soluble transferrin receptor (sTfR), were similar in strength for T2D and CHD, but we also observed important differences. Lipoprotein (a) (Lp(a)) and N-terminal pro B-type natriuretic peptide (NT-proBNP) even demonstrated opposite effect directions. All pathway variables together explained 49% of the T2D risk and 21% of the CHD risk. The insulin-like growth factor binding protein 2 (IGFBP-2, IGF/IGFBP system pathway) best explained the T2D risk (about 9% explained risk, independent of all other pathway variables). For CHD, the myocardial-injury- and lipid-related-pathways were most important and both explained about 4% of the CHD risk. Conclusions The biomarker-derived pathway variables explained a higher proportion of the T2D risk compared to CHD. The ranking of the pathways differed between the two diseases, with the IGF/IGFBP-system-pathway being most strongly associated with T2D and the myocardial-injury- and lipid-related-pathways with CHD. Our results help to better understand the pathophysiology of the two diseases, with the ultimate goal of pointing out targets for lifestyle intervention and drug development to ideally prevent both T2D and CHD development.http://link.springer.com/article/10.1186/s12933-020-01003-wType 2 diabetesCoronary heart diseaseCase-cohort studyPathwaysBiomarkerFetuin-A |
| spellingShingle | Cornelia Huth Alina Bauer Astrid Zierer Julie Sudduth-Klinger Christa Meisinger Michael Roden Annette Peters Wolfgang Koenig Christian Herder Barbara Thorand Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA study Cardiovascular Diabetology Type 2 diabetes Coronary heart disease Case-cohort study Pathways Biomarker Fetuin-A |
| title | Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA study |
| title_full | Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA study |
| title_fullStr | Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA study |
| title_full_unstemmed | Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA study |
| title_short | Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA study |
| title_sort | biomarker defined pathways for incident type 2 diabetes and coronary heart disease a comparison in the monica kora study |
| topic | Type 2 diabetes Coronary heart disease Case-cohort study Pathways Biomarker Fetuin-A |
| url | http://link.springer.com/article/10.1186/s12933-020-01003-w |
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