Apolipoprotein B and Glycemic Dysregulation: New Predictors of Type 2 Diabetes in High-Cardiovascular-Risk Populations

Abstract

Background: Apolipoprotein B (ApoB), a key component of atherogenic lipoproteins, has been increasingly implicated in cardiometabolic disorders beyond dyslipidemia. However, its role in glycemic dysregulation remains unclear. This study aimed to investigate the association between ApoB levels and glycemic parameters, including fasting glucose, insulin resistance, and glycated hemoglobin (HbA1c), in individuals without diagnosed diabetes. Methods: This study was conducted at the National Research Cardiac Surgery Center (Kazakhstan) over the period between 2023 and 2024 as a cross-sectional analysis. Adults aged ≥ 20 years without diagnosed diabetes and with complete data on their ApoB and glycemic markers were included. Associations between ApoB and fasting plasma glucose (FPG), HbA1c, and HOMA-IR were assessed using multivariable linear and logistic regression models adjusted for demographic, lifestyle, and metabolic covariates. Results: Higher ApoB levels were significantly associated with increased fasting glucose (β = 2.07 mg/dL per 1-SD increase in ApoB, p < 0.001), higher HbA1c (β = 0.06%, p < 0.001), and elevated HOMA-IR (β = 0.54, p < 0.001). Participants in the highest ApoB quartile had 53% higher odds of prediabetes (adjusted OR = 1.53; 95% CI: 1.22-1.91; p < 0.001) compared to the lowest quartile. These associations remained significant after adjusting for BMI, lipid levels, and other confounders. Conclusions: Elevated ApoB is independently associated with adverse glycemic profiles in nondiabetic individuals, suggesting its potential role in early glucose metabolism disturbances.

Keywords: apolipoprotein B; cardiovascular risk; glycemic profile; lipid profile; lipoprotein(a); type 2 diabetes mellitus.

Figure 1

The scheme of the methodology of the clinical trial.

Figure 2

Frequency of occurrence of various levels of Lp(a) in a small group of very high-risk patients.

Figure 3

Frequency of occurrence of various levels of Lp(a) in the small control group.

Figure 4

Comparison of ApoB levels between the control group and the very high-risk patient group. This Figure displays a boxplot comparison of the Apolipoprotein B (ApoB) levels between two groups: the control group (low-risk patients) and the high-risk group (very high-risk patients). The central box represents the interquartile range (IQR) where 50% of the data points are located, while the line inside the box represents the median ApoB level. The whiskers extend to the minimum and maximum values, excluding outliers, which are represented as individual points. This analysis used the Mann–Whitney U test to assess differences between the groups, with no statistically significant difference observed (U-statistic: 5798.0, p-value: 0.83).

Figure 5

Quartile distribution of Lp(a) levels in patients with type 2 diabetes. The strip plot illustrates the quartile distribution of Lp(a) levels in patients with type 2 diabetes. The x-axis represents the Lp(a) quartiles (Q1–Q4), while the y-axis shows the Lp(a) values. Red dots indicate patients with type 2 diabetes, and blue dots represent patients without diabetes. The plot highlights the higher concentration of Lp(a) levels in the third and fourth quartiles for patients with type 2 diabetes.

Figure 6

Spearman’s rank correlation coefficients for lipid and glycemic profiles.