Serum sclerostin level is positively associated with endothelial dysfunction measured by digital thermal monitoring in patients with type 2 diabetes: A prospective cross-sectional study

Abstract

Sclerostin and dickkopf-1 (DKK1), extracellular inhibitors of the canonical Wnt/β-catenin signaling pathway, have been associated with vascular aging and atherosclerosis. This study aimed to assess the correlation of sclerostin and DKK1 concentrations with endothelial function measured using vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples were collected from 100 patients with T2DM. Endothelial function and VRI were measured using digital thermal monitoring and circulating sclerostin and DKK1 levels by enzyme-linked immunosorbent assays. VRI values < 1.0, 1.0–1.9, and > 2.0 indicated poor, intermediate, and good vascular reactivity, respectively. Overall, 30, 38, and 32 patients had poor, intermediate, and good vascular reactivity, respectively. Older age, higher serum glycated hemoglobulin, urinary albumin-to-creatinine ratio, and sclerostin as well as lower hypertension prevalence, systolic blood pressure, and diastolic blood pressure (DBP) were associated with poor VRI. Multivariable forward stepwise linear regression analysis showed that DBP (β = 0.294, adjusted R2 change = 0.098, P < .001), log-glycated hemoglobin (β = −0.235, adjusted R2 change = 0.050, P = .002), log-urine albumin-to-creatinine ratio (β = −0.342, adjusted R2 change = 0.227, P < .001), and log-sclerostin level (β = −0.327, adjusted R2 change = 0.101, P < .001) were independently associated with VRI. Serum sclerostin, along with glycated hemoglobin and albumin-to-creatinine ratio, exhibited a negative correlation with VRI, while DBP showed a positive correlation with VRI. These factors can independently predict endothelial dysfunction in patients with T2DM.

Serum 25-Hydroxyvitamin D Level Is Positively Associated with Vascular Reactivity Index in Patients with Type 2 Diabetes Mellitus

“…Evidence indicates that vascular ED begins early in arteriosclerosis and is observable during early glucose intolerance in patients with T2DM [ 5 ]. Additionally, DM contributes to ED progression [ 5 , 11 ], and a study also reported that some classic hypoglycemic agents may ameliorate both ED and hyperglycemia [ 22 ]. Earlier studies indicate that chronic hyperglycemia induces ED through varied pathways: heightened reactive oxygen species (ROS) from hyperglycemia, elevated transforming growth factor-β and plasminogen activator inhibitor-1, and diminished NO availability impacting both macrovascular and microvascular function [ 1 ] As expected, our study found elevated fasting glucose and HbA1C level are inversely related to vascular reactivity in T2DM patients.…”

“…Waist circumference was determined by measuring the mid-point between the lower ribs and the hip bones, with the participants placing their hands on their hips. The body mass index (BMI) was computed by dividing the weight in kilograms by the square of the height in meters [ 11 , 12 ]. Blood pressure was measured in the morning after a 10 min seated rest using standard mercury sphygmomanometers.…”

“…Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded thrice at 5 min intervals and averaged for analysis. Hypertension was ≥140/90 mmHg or recent antihypertensive medication use in the preceding two weeks [ 11 , 12 ].…”

“…Post an 8 h overnight fast, around 5 mL of venous blood was drawn from the patients and promptly centrifuged at 3000× g for a duration of 10 min. Serum levels of blood urea nitrogen (BUN), creatinine, fasting glucose, glycated hemoglobin (HbA1c), total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) were assessed using a Siemens Advia 1800 autoanalyzer (Siemens Healthcare GmbH, Henkestr, Germany) [ 11 , 12 ]. A random spot urine test assessed the urinary albumin-to-creatinine ratio (UACR).…”

“…VRI, computed using VENDYS software (https://www.vendys2.com/, accessed on 14 May 2024), ranges from 0.0 to 3.5, indicating the reactive hyperemia's maximum temperature differential between the rebound and zero reactivity curves. VRI < 1.0 indicated poor reactivity, from 1.0 to 1.9 indicated intermediate reactivity, and ≥2.0 indicated good reactivity [11].…”