Pre-diabetes (PD) and type 2 diabetes (T2D) are rising rapidly in China due to aging and lifestyle changes, currently affecting over 50% of adults. Individuals with PD have a 3-10 times higher risk of developing diabetes. Small dense low-density lipoprotein cholesterol (sdLDL-C) is a highly atherogenic lipid. It is emerging as a key cardiovascular risk factor, but its role in glucose metabolism and diabetes remains under investigation. This relationship was well explained in a recent study published in the scientific reports. This study focused on PD, newly diagnosed T2D (NT2D), and normal Chinese adults, aiming to support early detection and prevention of diabetes through a better understanding of lipid profile changes.
A cross-sectional study was conducted between May 26 to September 17, 2022, in permanent residents of Zhejiang Province, China, who participated in a community health examination. Participants aged 30-69 years, who were able to complete questionnaires independently, conscious, and without any mental disorders, were included in this study. Individuals who were bedridden, pregnant, lactating, or diagnosed with dementia or schizophrenia were excluded.
Three blood samples were collected from each participant and analyzed for fasting blood glucose (FBG), sdLDL-C, and glycated hemoglobin A1c (HbA1c). The impact of sdLDL-C level on NT2D and PD were detected by using binary logistic regression analysis. Additionally, this effect modification through gender and age (>55 and ≤55 years) on NT2D and PD was measured using subgroup analysis. All statistical analysis were conducted using SAS software and R version 4.3.0.
A total of 3570 individuals (median age = 58 [52, 64], male = 41.3%, female = 58.7%) were included in this survey study. These individuals were categorized into 3 groups: the normal blood glucose group (control group; n = 1330), the PD group (n = 1913), and the NT2D group (n = 327). The prevalence of PD was higher in females (61.4%) compared to the remaining 2 groups (control = 54.9% and NT2D = 59%). The median level of sdLDL-C was found to be 0.939 mmol/L.
Logistic regression analysis found that the risk of PD increased by 3.4% (odds ratio [OR] = 1.034, 95% confidence interval [CI]:1.002–1.067), and the risk of NT2D increased by 5.7% (OR = 1.157, 95%CI:1.097–1.220) for every 0.1 mmol/L raise in the concentration of sdLDL-C after confounding various variables such as gender, age, ethnicity, drinking, education level, diastolic blood pressure (DBP), body mass index (BMI), hypertension, low-density lipoprotein cholesterol (LDL-C), smoking, systolic blood pressure (SBP), waist circumference (WC) and regular physical activity.
Restricted cubic spline (RCS) curves demonstrated that increasing sdLDL-C levels were associated with a higher risk of both PD (P = 0.037) and NT2D (P < 0.001). However, no significant nonlinear dose-response relationship was observed between sdLDL-C and PD (non-linearity P = 0.142) or NT2D (non-linearity P = 0.227). Sub-group analysis found a significant interaction between sdLDL-C concentration and age (≤55 years versus >55 years), whereas no significant interaction with gender for PD. A significant association was observed with gender and a non-significant association with age for NT2D. Â
In conclusion, this study investigated that the risk of NT2D and PD increased with the increase of sdLDL-C concentration. This study supports sdLDL-C as a promising independent risk factor for PD and NT2D, regardless of LDL-C levels. Combining sdLDL-C assessment with routine lipid monitoring holds significant potential for lipid-lowering therapy, early prevention, and improving the prognosis of NT2D and PD.
Reference: He Q, Wang L, Fang Y, et al. Relationship of small dense low-density lipoprotein cholesterol level with pre-diabetes and newly detected type 2 diabetes. Sci Rep. 2025;15:19500. doi:10.1038/s41598-025-03133-1
