Fibulin-1 Is a Marker for Arterial Extracellular Matrix Alterations in Type 2 Diabetes

Cangemi, Claudia; Skov, Vibe; Poulsen, Mikael Kjær; Funder, Jonas Amstrup; Twal, Waleed O.; Gall, Mari-Anne; Hjortdal, Vibeke E.; Jespersen, Marie Louise; Kruse, Torben A.; Aagard, Jan; Parving, Hans‐Henrik; Knudsen, Steen; Høilund-Carlsen, Poul Fl.; Rossing, Peter; Henriksen, Jan Erik; Argraves, W. Scott; Rasmussen, Lars Melholt

doi:10.1373/clinchem.2011.162966

Cited by 67 publications

(123 citation statements)

References 43 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…We found a significant fibulin-1-lowering effect of metformin, but not of rosiglitazone. This finding is in accordance with results from a previous observational study where we observed lower plasma fibulin-1 concentrations among metformin-treated T2D patients (18). We find that the metformin-induced effect on plasma fibulin-1 is probably not mediated by improved glycemic status, since no effect on fibulin-1 was observed after rosiglitazone treatment even though HbA 1c was reduced to the same level in the metformin-only group, and no additional effect on plasma fibulin-1 was observed when HbA 1c was further reduced by rosiglitazone and metformin combination treatment.…”

Section: Discussionsupporting

confidence: 93%

“…The fibulin-1 protein amounts were also higher in arterial tissue from patients with T2D. These results are in agreement with previous findings of arterial ECM modulations in T2D (18). Fibulin-1 is also present at high levels in plasma, and in our previous study, we also found higher circulating amounts of fibulin-1 in patients with T2D.…”

Section: Discussionsupporting

confidence: 93%

“…In the initial presentation, we found higher amounts of fibulin-1 protein both in the arterial wall and in the circulation among patients with T2D. Moreover, we demonstrated an association between increased levels of plasma fibulin-1 and arterial stiffness, blood pressure, and glycemic status in a cohort of 305 welldescribed patients with T2D (18). These results, concerning relations between plasma fibulin-1, glycemic status, and hypertension, have been confirmed in three subsequent studies (19)(20)(21).…”

supporting

confidence: 76%

“…These results, concerning relations between plasma fibulin-1, glycemic status, and hypertension, have been confirmed in three subsequent studies (19)(20)(21). In the initial paper, we also presented a 15-year follow-up study, showing that high plasma fibulin-1 concentrations among patients with T2D were independently predictive of mortality in T2D with a hazard ratio similar to that of plasma cholesterol (18). In the initially investigated diabetic patients, we observed that individuals treated with metformin had reduced fibulin-1 levels (18).…”

supporting

confidence: 65%

“…Total cholesterol, LDL, HDL, and triglycerides were measured on a Modular Analytics P instrument (Roche Diagnostics, Basel, Switzerland) according to the manufacturer's instructions. Plasma fibulin-1 was measured with a sandwich immunoassay as previously described (18). The plasma concentration of metformin was determined by a validated high-performance liquid chromatography method (28).…”

Section: Clinical and Biochemical Measurementsmentioning

confidence: 99%

See 4 more Smart Citations

Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes

et al. 2014

Self Cite

View full text Add to dashboard Cite

OBJECTIVEThe extracellular matrix protein fibulin-1 is upregulated in the arterial wall in type 2 diabetes (T2D) and circulates in increased concentrations in diabetes. Metformin is an antidiabetic drug with beneficial cardiovascular disease effects in diabetes. We hypothesized that metformin would influence the increased level of plasma fibulin-1 in diabetes. RESEARCH DESIGN AND METHODSAfter a 4-week run-in period, 371 eligible patients with T2D were randomized to treatment groups in a factorial design including insulin alone (control), +metfor-min, +rosiglitazone, or +both metformin and rosiglitazone. Plasma fibulin-1 was analyzed at the beginning of the study and after 18 and 24 months. RESULTSPlasma fibulin-1 increased in all groups throughout the 2-year period; however, the increase was strongly attenuated among patients treated with metformin. A highly significant difference was observed when the mean change in plasma fibulin-1 was compared between metformin-and non-metformin-treated individuals both at 18 and 24 months of treatment, but rosiglitazone had no effect. Metformin and rosiglitazone alone reduced the HbA 1c levels to comparable levels and in combination even further. CONCLUSIONSMetformin attenuates the increase in plasma fibulin-1 concentrations in T2D, independently of glycemic effects. Changes in fibulin-1 may reflect an important element in diabetic arteriopathy that can be influenced by metformin. Increased mortality and morbidity owing to a higher incidence of cardiovascular diseases (CVDs) is a major clinical challenge in type 2 diabetes (T2D) (1,2). Several studies have demonstrated that management of hypertension, LDL cholesterol, and other major CVD risk factors have reduced micro-and macrovascular complications in patients with T2D; however, optimal risk reduction is still not achieved when these important risk factors are controlled, indicating that further attempts are needed to control the CVD risk burden (3-5). One assumption is that improvement

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

supporting

confidence: 76%

supporting

confidence: 65%

Section: Clinical and Biochemical Measurementsmentioning

confidence: 99%

See 3 more Smart Citations

Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

Total and isoform‐specific quantitative assessment of circulating fibulin‐1 using selected reaction monitoring MS and time‐resolved immunofluorometry

Overgaard

Cangemi

Jensen

et al. 2015

Proteomics Clinical Apps

Self Cite

View full text Add to dashboard Cite

show abstract

Important options available — from start to finish — for translating proteomics results to clinical chemistry

Heegaard

Østergaard

Bahl

et al. 2015

Proteomics Clinical Apps

Self Cite

View full text Add to dashboard Cite

In the realm of clinical chemistry, the field of clinical proteomics, that is, the application of proteomic methods for understanding mechanisms and enabling diagnosis, prediction, measurement of activity, and treatment response in disease, is first and foremost a discovery and research tool that feeds assay development downstream. Putative new assay candidates generated by proteomics discovery projects compete with well-established assays with known indications, well-described performance, and of known value in specific clinical settings. Careful attention to the many options available in the design, execution, and interpretation of clinical proteomics studies is thus necessary for translation into clinical practice. We here review and discuss important options associated with clinical proteomics endeavors stretching from the planning phases to the final use in clinical chemistry.

show abstract

Fibulin-1 Is a Marker for Arterial Extracellular Matrix Alterations in Type 2 Diabetes

Abstract: BACKGROUND: Extracellular matrix alterations are important elements in the arterial changes seen in diabetes, being associated with increased vascular stiffness and the development of cardiovascular diseases. However, no biomarkers for diabetes-related arterial changes have been defined.

Cited by 67 publications

References 43 publications

Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes

Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes

Total and isoform‐specific quantitative assessment of circulating fibulin‐1 using selected reaction monitoring MS and time‐resolved immunofluorometry

Important options available — from start to finish — for translating proteomics results to clinical chemistry

Contact Info

Product

Resources

About