The Impact of Ketogenic Capacity on Lipid Profile in Individuals with Prediabetes or Newly Diagnosed Type 2 Diabetes

In individuals with non-adipogenic traits and enhanced ketogenic capacity, plasma triglyceride (TG) levels are typically low, while low-density lipoprotein cholesterol (LDL-C) levels often exceed the normal range, complicating cardiovascular risk assessment. We analyzed lipid profiles to better characterize cardiovascular risk in this population. Drug-naïve patients newly diagnosed with prediabetes or type 2 diabetes (T2D) were divided into two groups based on serum β-hydroxybutyrate levels: enhanced versus non-enhanced ketogenesis. Among those with enhanced ketogenesis, 27 individuals with high LDL-C (≥100 mg/dL) and low TG (<150 mg/dL) were selected. For comparison, 27 individuals with high TG (>150 mg/dL) from the non-enhanced group were included. The enhanced ketogenesis group demonstrated more favorable lipid characteristics, including a significantly larger average LDL particle size (26.8 ± 0.3 nm vs. 25.9 ± 0.6 nm, p < 0.001), a lower proportion of small dense LDL particles, and reduced oxidized LDL to LDL-C ratio. Importantly, enhanced ketogenesis remained an independent predictor of larger LDL particle size after adjusting for potential confounders including TG. Despite the potential of selection bias intentionally induced by the predefined inclusion criteria, our findings suggest that patients with T2D or prediabetes who exhibit enhanced ketogenesis, even in the presence of elevated LDL-C levels, may have a more favorable atherogenic profile and are not necessarily at increased cardiovascular risk.