Elevated circulating BACE2 is associated with insulin resistance and type 2 diabetes risk: evidence from a Chinese cohort study

This study investigated the role of β-site amyloid precursor protein-cleaving enzyme 2 (BACE2) in type 2 diabetes (T2D) and its relationship with insulin resistance (IR) and metabolic parameters. The results showed significantly higher serum BACE2 levels in T2D and overweight/obese individuals compared to those with normal glucose tolerance (NGT). BACE2 levels were positively correlated with glucose, insulin, HbA1c, HOMA-IR, BMI, triglycerides, and total cholesterol, with HbA1c being the strongest independent predictor. Additionally, higher BACE2 levels were associated with an increased risk of T2D. The study also found that BACE2 levels declined during an oral glucose tolerance test (OGTT), particularly in T2D patients, indicating a dynamic response to glucose fluctuations. The relationship between BACE2 and metabolic traits was non-linear, with the strongest associations observed at intermediate BACE2 levels, suggesting its potential as a dynamic biomarker for metabolic stress and T2D.

Table 1 compares clinical and laboratory characteristics between NGT and T2D participants, showing significant differences in BMI, waist-to-hip ratio, blood pressure, glucose metabolism parameters, and BACE2 levels. T2D patients exhibited higher BACE2 concentrations across multiple forms. Table 2 highlights the correlations between BACE2 and metabolic parameters, including significant positive correlations with HbA1c, FBG, HOMA-IR, BMI, and total cholesterol. After adjusting for gender, the correlation with some parameters weakened, but BACE2 remained significantly linked to HbA1c and HDL-C. Table S1 provides additional details on clinical and laboratory characteristics, including fasting and postprandial insulin levels, lipid profiles, and other metabolic markers, supporting the findings from Tables 1 and 2.

The data was collected from clinical measurements and blood tests on 74 NGT participants and 91 T2D patients. The results provide insights into the metabolic dysfunctions associated with T2D and the potential of BACE2 as a biomarker for early detection and risk stratification. The findings suggest that BACE2 could be crucial in understanding insulin resistance and glucose metabolism in T2D and may offer a useful tool for assessing metabolic stress in diabetic patients.