Protein markers and risk of type 2 diabetes and prediabetes: a targeted proteomics approach in the KORA F4/FF4 study

The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the city of Rotterdam, The Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. The study focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1700 research articles and reports. This article provides an update on the rationale and design of the study. It also presents a summary of the major findings from the preceding 3 years and outlines developments for the coming period.

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“…For additional EJE references please see [197][198][199][200][201][202][203][204][205][206][207][208].…”

Section: Future Perspectivesmentioning

confidence: 99%

Objectives, design and main findings until 2020 from the Rotterdam Study

et al. 2020

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“…All participants without known diabetes received the OGTT. 28 The OGTT was performed after an overnight fast of at least 8 hours. During the fast only drinking water was allowed.…”

Section: Methodsmentioning

confidence: 99%

“…The Siemens insulin data were calibrated using a formula developed from 194 FF4 samples, which were measured with both instruments. 28 …”

Section: Methodsmentioning

confidence: 99%

Association of endothelial dysfunction with incident prediabetes, type 2 diabetes and related traits: the KORA F4/FF4 study

Huemer¹,

Huth²,

Schederecker

et al. 2020

BMJ Open Diab Res Care

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IntroductionPeripheral arterial tonometry (PAT) is an operator-independent and non-invasive measurement method to assess microvascular endothelial function in the fingertips. PAT-derived measures of endothelial function were associated with type 2 diabetes in cross-sectional studies. However, longitudinal studies are lacking. The study aims to investigate the association of two PAT-derived endothelial function parameters reactive hyperemia index (RHI) and mean baseline amplitude (MBA) with follow-up glucose and insulin parameters and the development of (pre)diabetes and type 2 diabetes.Research design and methodsThe study included 673 participants initially without diabetes (328 men and 345 women) aged 52–71 years from the prospective population-based Cooperative Health Research in the Region of Augsburg F4/FF4 cohort study conducted in Southern Germany (baseline examination F4: 2006–2008; follow-up FF4: 2013–2014). An oral glucose tolerance test was performed at baseline and follow-up to define type 2 diabetes, prediabetes, fasting glucose, fasting insulin, 2-hour glucose, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of beta-cell function and hemoglobin A1c.ResultsIn multivariable adjusted logistic/linear regression models, a 1 SD increase in baseline RHI was inversely associated with incident type 2 diabetes (OR 0.69 (95% CI 0.48 to 0.97)) as well as with fasting insulin (β −0.069 (95% CI −0.131 to −0.007)) and HOMA-IR (β −0.072 (95% CI −0.133 to −0.010)) at follow-up in participants with initial normoglycemia. A 1 SD increase in baseline MBA was positively associated with incident (pre)diabetes (OR 1.62 (95% CI 1.25 to 2.11)) and fasting glucose (β 0.096 (95% CI 0.047 to 0.146)) at follow-up in participants with initial normoglycemia.ConclusionsMicrovascular endothelial dysfunction seems to be involved in the development of early derangements in glucose metabolism and insulin resistance and could thereby trigger the development of prediabetes and type 2 diabetes.

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“…The study was approved by the Ethics committee of the Bavarian Chamber of Physicians (17). Plasma samples from 90 men and 83 women KORA F4 participants within the age range of 62-74 years were randomly selected from a subset of KORA F4 participants with deep phenotyping data (18)(19)(20).…”

Section: Samplesmentioning

confidence: 99%

Multi-platforms approach for plasma proteomics: complementarity of Olink PEA technology to mass spectrometry-based protein profiling

Petrera¹,

Toerne²,

Behler³

et al. 2020

Preprint

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The plasma proteome is the ultimate target for biomarker discovery. It stores an endless amount of information on the pathophysiological status of a living organism, which is however still difficult to comprehensively access. The high structural complexity of the plasma proteome can be addressed by either a system-wide and unbiased tool such as mass spectrometry (LC-MS/MS) or a highly sensitive targeted immunoassay such as the Proximity Extension Assays (PEA). In order to address relevant differences and important shared characteristics, we tested the performance of LC-MS/MS in data-dependent and -independent acquisition modes and PEA Olink to measure circulating plasma proteins in 173 human plasma samples from a Southern German population-based cohort. We demonstrated the measurement of more than 300 proteins with both LC-MS/MS approaches applied, mainly including high abundance plasma proteins. By the use of the PEA technology, we measured 728 plasma proteins, covering a broad dynamic range with high sensitivity down to pg/ml concentrations. In a next step, we quantified 35 overlapping proteins with all three analytical platforms, verifying the reproducibility of data distributions, measurement correlation and gender-based differential expression. Our work highlights the limitations and the advantages of both, targeted and untargeted approaches, and prove their complementary strengths. We demonstrated a significant gain in proteome coverage depth and subsequent biological insight by platforms combination – a promising approach for future biomarker and mechanistic studies.

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Protein markers and risk of type 2 diabetes and prediabetes: a targeted proteomics approach in the KORA F4/FF4 study

Cited by 40 publications

References 39 publications

Objectives, design and main findings until 2020 from the Rotterdam Study

Objectives, design and main findings until 2020 from the Rotterdam Study

Association of endothelial dysfunction with incident prediabetes, type 2 diabetes and related traits: the KORA F4/FF4 study

Multi-platforms approach for plasma proteomics: complementarity of Olink PEA technology to mass spectrometry-based protein profiling

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