Obesity is associated with an altered HDL subspecies profile among adolescents with metabolic disease

Abstract

We aimed to determine the risk factors associated with the depletion of large HDL particles and enrichment of small HDL particles observed in adolescents with T2D. Four groups of adolescents were recruited: ) lean insulin-sensitive (L-IS), normal BMI and no insulin resistance;) lean insulin-resistant (L-IR), normal BMI but insulin resistance (fasting insulin levels ≥ 25 mU/ml and homeostatic model assessment of insulin resistance ≥ 6); ) obese insulin-sensitive (O-IS), BMI ≥ 95th percentile and no insulin resistance; and) obese insulin-resistant (O-IR), BMI ≥ 95th percentile and insulin resistance. Plasma was separated by using gel-filtration chromatography to assess the HDL subspecies profile and compared with that of obese adolescents with T2D (O-T2D). Large HDL subspecies were significantly lower across groups from L-IS > L-IR > O-IS > O-IR > O-T2D ( < 0.0001); small HDL particles were higher from L-IS to O-T2D ( < 0.0001); and medium-sized particles did not differ across groups. The contributions of obesity, insulin resistance, and diabetes to HDL subspecies profile were between 23% and 28%, 1% and 10%, and 4% and 9%, respectively. Obesity is the major risk factor associated with the altered HDL subspecies profile previously reported in adolescents with T2D, with smaller contributions from insulin resistance and diabetes.

High density lipoprotein proteome is associated with cardiovascular risk factors and atherosclerosis burden as evaluated by coronary CT angiography

“…The association between HDL-C and NCB is lost after adjustment for BMI. This supports a known, but not well understood, relationship between BMI and HDL [28, 29] and is consistent with our observed influence of BMI on HDL proteome.…”

HDL Particle Subspecies and Their Association With Incident Type 2 Diabetes: The PREVEND Study

“…Of further interest, the correlation between phospholipid content of HDL subfractions separated by gel filtration chromatography and HDL subspecies as quantified by NMR spectroscopy was reported recently ( 37 , 39 ). Fractions with low phospholipid content appeared very similar to H7P and H6P, respectively, as assessed by NMR, while the fraction with high phospholipid content appeared very similar to H2P as assessed by NMR ( 37 ). Fractions with a low phospholipid content were inversely correlated with HOMA-IR ( 37 ).…”

“…A salient feature of HDL subclasses and subspecies distribution and their associations with T2D could be explained by their relationships with BMI and insulin resistance as confirmed in the current study. Insulin resistance is appreciated to be associated with fewer large HDL particles and a decrease in HDL particle size ( 15 , 16 , 37 , 38 ). Of further interest, the correlation between phospholipid content of HDL subfractions separated by gel filtration chromatography and HDL subspecies as quantified by NMR spectroscopy was reported recently ( 37 , 39 ).…”

“…Insulin resistance is appreciated to be associated with fewer large HDL particles and a decrease in HDL particle size ( 15 , 16 , 37 , 38 ). Of further interest, the correlation between phospholipid content of HDL subfractions separated by gel filtration chromatography and HDL subspecies as quantified by NMR spectroscopy was reported recently ( 37 , 39 ). Fractions with low phospholipid content appeared very similar to H7P and H6P, respectively, as assessed by NMR, while the fraction with high phospholipid content appeared very similar to H2P as assessed by NMR ( 37 ).…”

High-Density Lipoprotein Particles and Their Relationship to Posttransplantation Diabetes Mellitus in Renal Transplant Recipients

“…However, among obese people, individuals with high insulin resistance had a lower amount of H6P compared to insulin-sensitive adults. Moreover, homeostatic model assessment for insulin resistance (HOMA-IR) was strongly correlated with fraction 22 which contains H6P as the major HDL subspecies [50].…”