Sclerostin - A Biomarker for Vascular Risk in Diabetes

Type 2 Diabetes Mellitus (T2DM) and Cardiovascular (CV) diseases

Patients with T2DM have an elevated risk of developing CV diseases due to multiple factors. Chronic hyperglycemia, or elevated blood sugar levels, can cause damage to blood vessels promoting the development of atherosclerosis (1). Insulin resistance, a hallmark of T2DM, contributes to abnormal lipid profiles, such as increased triglycerides and low HDL cholesterol, both of which are risk factors for cardiovascular disease. Additionally, high blood sugar levels impair endothelial function, reducing the blood vessels’ ability to dilate properly and increasing the likelihood of plaque formation. T2DM is also associated with increased systemic inflammation, which accelerates the process of atherosclerosis. Moreover, patients with T2DM often develop increased arterial stiffness, further elevating cardiovascular risk (2).

Measuring Arterial Stiffness

Arterial stiffness is commonly measured using several non-invasive techniques, including Pulse Wave Velocity (PWV). PWV it the most widely used and regarded as the gold standard. It measures the speed at which the blood pressure pulse propagates through the arteries. A higher PWV indicates increased arterial stiffness. In patients with T2DM, arterial stiffness has been demonstrated to predict cardiovascular events independently of traditional risk factors, including glycemic control and 24-hour ambulatory blood pressure (3).

Sclerostin – A Biomarker for Vascular Risk in Diabetes

Sclerostin and DKK-1 in Type 2 Diabetes Mellitus (T2DM)

Sclerostin and DKK-1 are proteins that act as inhibitors of the Wnt signaling pathway, which is crucial for bone formation and remodeling (4).

In cardiovascular diseases, elevated levels of these proteins are associated with increased vascular calcification and atherosclerosis (5, 6). They influence the functioning of vascular cells and contribute to the development and progression of vascular damage.

In a recent study, researchers investigated the relationship of the biomarkers Sclerostin and DKK-1with peripheral arterial stiffness in patients with Type 2 Diabetes Mellitus (T2DM) (7). Sclerostin and DKK-1 were both successfully measured in serum samples using the ELISA assays from BIOMEDICA.

Key findings:

• Sclerostin, but not DKK-1 is independently associated with increased arterial stiffness in T2DM patients. 
• Circulating sclerostin may represent a potential biomarker of arterial stiffness in this population

 

The study highlights the potential of sclerostin as a biomarker for arterial stiffness and cardiovascular risk in diabetes.

SCLEROSTIN ELISA Assay | BI-20492

• most referenced in over 340 publications
• full validation package
• 20µl sample/well – serum and plasma – sample volume: 20µl / well

 

DKK-1 ELISA Assay | BI-20413

• highly cited in over 180 publications 
• full validation package
• 20µl sample/well – for serum  – sample volume: 20µl / well
• no sample pre-dilution – direct measurment

 

 

Positive Correlates of Sclerostin and Association with Peripheral Arterial Stiffness in Patients with Type 2 Diabetes Mellitus. Hsu B-G et al., Medicina. 2026

Abstract

Background and Objectives: Sclerostin or dickkopf-1 (DKK1) inhibits the canonical Wnt/β-catenin signaling pathway, which regulates vascular calcification and may contribute to the development of arterial stiffness. The brachial–ankle pulse wave velocity (baPWV) measures peripheral arterial stiffness (PAS). This study aimed to investigate the correlation between sclerostin and DKK1 levels and PAS in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Biochemical data and sclerostin and DKK1 levels were analyzed in the fasting blood samples of 125 patients with T2DM. baPWV measurements using the VaSera VS-1000 automatic pulse wave analyzer classified patients with values > 18.0 m/s on either side into the PAS group. Results: Among patients with T2DM, 47 (37.6%) were classified as having PAS. These patients exhibited higher hypertension prevalence (p = 0.002); greater age (p < 0.001); elevated systolic (p < 0.001) and diastolic blood (p = 0.012) pressures; and increased fasting glucose (p = 0.001), glycated hemoglobin (p = 0.008), triglyceride (p = 0.001), blood urea nitrogen (p < 0.001), and creatinine (p = 0.001) levels, urine albumin-to-creatinine ratio (p = 0.039), and C-reactive protein (p = 0.024) and serum sclerostin (p < 0.001) levels, but decreased estimated glomerular filtration rate (p < 0.001). Multivariate logistic regression analysis identified serum sclerostin level (odds ratio, 1.127; 95% confidence interval, 1.058–1.200; p < 0.001) as an independent PAS predictor in patients with T2DM. Serum log-transformed sclerostin levels were positively correlated with left (p = 0.005) and right (p = 0.001) baPWV via Spearman’s rank-order correlation coefficient analysis. Conclusions: Serum sclerostin levels, but not DKK1 levels, are positively correlated with PAS in patients with T2DM.

Literature

1. 2-Fold More Cardiovascular Disease Events Decades Before Type 2 Diabetes Diagnosis: A Nationwide Registry Study. Gyldenkerne C, Kahlert J, Thrane PG, Olesen KKW, Mortensen MB, Sørensen HT, Thomsen RW, Maeng M.J Am Coll Cardiol. 2024 Dec 3;84(23):2251-2259. doi: 10.1016/j.jacc.2024.06.050. PMID: 39603746.
2. The Interplay Between Diabetes, Cardiovascular Disease, and Kidney Disease. Usman MS, Khan MS, Butler J. In: Chronic Kidney Disease and Type 2 Diabetes. Arlington (VA): American Diabetes
3. Association; 2021 Jun. PMID: 34279879.Prognostic impact of aortic stiffness in high-risk type 2 diabetic patients: the Rio deJaneiro Type 2 Diabetes Cohort Study. Diabetes Care. Cardoso CR, Ferreira MT, Leite NC, Salles GF. 2013 Nov;36(11):3772-8. doi: 10.2337/dc13-0506. Epub 2013 Jul 22. PMID: 23877987; PMCID: PMC3816863.
4. Wnt signaling pathway inhibitors, sclerostin and DKK-1, correlate with pain and bone pathology in patients with Gaucher disease. Ivanova MM, Dao J, Kasaci N, Friedman A, Noll L, Goker-Alpan O.Front Endocrinol (Lausanne). 2022 Nov 24;13:1029130. doi: 10.3389/fendo.2022.1029130. PMID: 36506070; PMCID: PMC9730525.
5. Sclerostin and Cardiovascular Disease. Tobias JH.Curr Osteoporos Rep. 2023 Oct;21(5):519-526. doi: 10.1007/s11914-023-00810-w. Epub 2023 Jul 25. PMID: 37490188; PMCID: PMC10543142.
6. Dickkopf-1, a potential target for heart disease. Xu P, Cao Y, Zhang S, Liu X, Zhang M, Zhang C.Int J Cardiol. 2024 Aug 1;408:132146. doi: 10.1016/j.ijcard.2024.132146. Epub 2024 May 9. PMID: 38729311.
7. Positive Correlates of Sclerostin and Association with Peripheral Arterial Stiffness in Patients with Type 2 Diabetes Mellitus. Hsu B-G, Li J-C, Wu D-A, Chen M-C. Medicina. 2026; 62(4):643.