MASP1, THBS1, GPLD1 and ApoA-IV are novel biomarkers associated with prediabetes: the KORA F4 study

Toerne, Christine von; Huth, Cornelia; Gala, Tonia de las Heras; Kronenberg, Florian; Herder, Christian; Köenig, Wolfgang; Meisinger, Christa; Rathmann, Wolfgang; Waldenberger, Mélanie; Roden, Michael; Peters, Annette; Thorand, Barbara; Hauck, Stefanie M.

doi:10.1007/s00125-016-4024-2

Cited by 62 publications

(56 citation statements)

References 44 publications

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“…48 Extracellular THBS1 has been suggested to have a deleterious role in obesity and insulin resistance, and a recent report identified circulating THBS1 as a biomarker of pre-diabetes. 49 THBS1 is more abundantly expressed in visceral compared with subcutaneous fat, and it is increased by high fat feeding and obesity. 50,51 THBS1 − / − mice are protected from high-fat-diet-induced obesity and insulin resistance through increased skeletal muscle insulin sensitivity and browning of subcutaneous fat.…”

Section: Discussionmentioning

confidence: 99%

Thrombospondin 1 protects pancreatic β-cells from lipotoxicity via the PERK–NRF2 pathway

et al. 2016

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The failure of β-cells has a central role in the pathogenesis of type 2 diabetes, and the identification of novel approaches to improve functional β-cell mass is essential to prevent/revert the disease. Here we show a critical novel role for thrombospondin 1 (THBS1) in β-cell survival during lipotoxic stress in rat, mouse and human models. THBS1 acts from within the endoplasmic reticulum to activate PERK and NRF2 and induce a protective antioxidant defense response against palmitate. Prolonged palmitate exposure causes THBS1 degradation, oxidative stress, activation of JNK and upregulation of PUMA, culminating in β-cell death. These findings shed light on the mechanisms leading to β-cell failure during metabolic stress and point to THBS1 as an interesting therapeutic target to prevent oxidative stress in type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Thrombospondin 1 protects pancreatic β-cells from lipotoxicity via the PERK–NRF2 pathway

et al. 2016

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“…Processing of SRM data SRM data were processed using the Skyline software as previously described [15]. Briefly, after manual quality control, heavy to light peptide ratios were calculated on fragment levels, log 2 transformed and corrected for batch effects by linear regression, followed by averaging fragment values to peptides.…”

Section: Methodsmentioning

confidence: 99%

“…Proteomics has been used to identify biomarkers in diverse diseases such as cardiovascular diseases [11], prostrate and other cancers [12,13], Parkinson's disease [14] and metabolic disorders [11,15]. In type 1 diabetes, previous proteomic biomarker screening studies have compared patients with type 1 diabetes to autoantibody-negative control participants [16][17][18] and identified protein signatures correlated with clinical disease.…”

Section: Introductionmentioning

confidence: 99%

Peptide serum markers in islet autoantibody-positive children

et al. 2016

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Aims/hypothesis We sought to identify minimal sets of serum peptide signatures as markers for islet autoimmunity and predictors of progression rates to clinical type 1 diabetes in a case-control study. Methods A double cross-validation approach was applied to first prioritise peptides from a shotgun proteomic approach in 45 islet autoantibody-positive and -negative children from the BABYDIAB/BABYDIET birth cohorts. Targeted proteomics for 82 discriminating peptides were then applied to samples from another 140 children from these cohorts. Results A total of 41 peptides (26 proteins) enriched for the functional category lipid metabolism were significantly different between islet autoantibody-positive and autoantibodynegative children. Two peptides (from apolipoprotein M and apolipoprotein C-IV) were sufficient to discriminate autoantibody-positive from autoantibody-negative children. Hepatocyte growth factor activator, complement factor H, ceruloplasmin and age predicted progression time to type 1 diabetes with a significant improvement compared with age alone. Conclusion/interpretation Distinct peptide signatures indicate islet autoimmunity prior to the clinical manifestation of type 1 diabetes and enable refined staging of the presymptomatic disease period.

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“…The study design has been described in detail previously (32). All participants underwent standard physical and medical examinations at KORA F4, which are described in detail elsewhere (33). The studies were carried out in accordance with the Declaration of Helsinki, including written informed consent from all participants, and were approved by the ethics committee of the Bavarian Chamber of Physicians (Munich, Germany).…”

Section: Study Design Setting and Participantsmentioning

confidence: 99%

Sex hormone-binding globulin, androgens and mortality: the KORA-F4 cohort study

Schederecker

Cecil

Prehn

et al. 2020

Endocrine Connections

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Objective Sex hormone-binding globulin (SHBG) and androgens have been associated with mortality in women and men, but controversy still exists. Our objective was to investigate associations of SHBG and androgens with all-cause and cause-specific mortality in men and women. Design 1006 men and 709 peri- and postmenopausal women (age range: 45–82 years) from the German population-based KORA F4 cohort study were followed-up for a median of 8.7 years. Methods SHBG was measured with an immunoassay, total testosterone (TT) and dihydrotestosterone (DHT) with mass-spectrometry in serum samples and we calculated free testosterone (cFT). To assess associations between SHBG and androgen levels and mortality, we calculated hazard ratios (HRs) with 95% CIs using Cox proportional-hazards models. Results In the cohort, 128 men (12.7%) and 70 women (9.9%) died. In women, we observed positive associations of SHBG with all-cause (HR: 1.54, 95% CI: 1.16–2.04) and with other disease-related mortality (HR: 1.86, 95% CI: 1.08–3.20) and for DHT with all-cause mortality (HR: 1.32, 95% CI: 1.00–1.73). In men, we found a positive association of SHBG (HR: 1.24 95% CI: 1.00–1.54) and inverse associations of TT (HR: 0.87, 95% CI: 0.77–0.97) and cFT (HR: 0.84, 95% CI: 0.73–0.97) with all-cause mortality. No other associations were found for cause-specific mortality. Conclusions Higher SHBG levels were associated with increased risk of all-cause mortality in men and women. Lower TT and cFT levels in men and higher DHT levels in women were associated with increased risk of all-cause mortality. Future, well-powered population-based studies should further investigate cause-specific mortality risk.

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MASP1, THBS1, GPLD1 and ApoA-IV are novel biomarkers associated with prediabetes: the KORA F4 study

Cited by 62 publications

References 44 publications

Thrombospondin 1 protects pancreatic β-cells from lipotoxicity via the PERK–NRF2 pathway

Thrombospondin 1 protects pancreatic β-cells from lipotoxicity via the PERK–NRF2 pathway

Peptide serum markers in islet autoantibody-positive children

Sex hormone-binding globulin, androgens and mortality: the KORA-F4 cohort study

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