A higher glycemic response to oral glucose is associated with higher plasma apolipoprotein C3 independently of BMI in healthy twins

Abstract

Background and aims: Plasma apolipoprotein C3 (ApoC3) is associated with higher plasma triglyceride and type 2 diabetes incidence. We evaluated whether body mass index (BMI) or glucose metabolism were associated with ApoC3 in healthy monozygotic (MZ) twins. Methods and Results: Forty-seven MZ twin-pairs (20 man, 27 women), aged 23e42 years, were divided in subgroups according to discordance or concordance for (a) BMI (within-pair difference (D) in BMI!3.0 or<3.0 kg/m 2 ), or (b) 2-h glucose iAUC, during oral glucose tolerance test (DGlucose iAUC !97.5 or<97.5 mmol  120 minutes). Within these discordant or concordant subgroups, we tested (Wilcoxon signed-rank test) co-twin differences in ApoC3, adiposity measures, insulin-resistance and beta-cell function indices, and plasma and lipoprotein lipids.In BMI-Discordant (p Z 0.92) or BMI-Concordant (p Z 0.99) subgroups, ApoC3 did not differ between leaner and heavier co-twins. In the GlucoseeDiscordant subgroup, ApoC3 was significantly higher in twins with higher Glucose iAUC than in their co-twins with the lower Glucose iAUC (10.03 AE 0.78 vs. 8.48 AE 0.52 mg/dl; M AE SE; p Z 0.032). Co-twins with higher Glucose iAUC also had higher waist circumference, body fat percentage, liver fat content, worse insulin-sensitivity and beta-cell function and higher cholesterol and triglyceride in plasma VLDL, IDL, and LDL. In GlucoseeConcordant twin-pairs, no significant differences were observed in the explored variables. In all twin-pairs, DApoC3 correlated with D in lipids and glucose metabolism variables, the closest relationship being between DApoC3 and DVLDL triglyceride (r Z 0.74, p < 0.0001). Conclusions: While ApoC3 was not related to acquired differences in BMI, it associated with early dysregulation of glucose metabolism independently of obesity and genetic background.

ApoCIII: A multifaceted protein in cardiometabolic disease

“…Recently, Bozzetto et al (115) evaluated if ApoCIII concentrations associate with differences in body mass index (BMI) or glycemic response during oral glucose tolerance test in young and healthy monozygotic (MZ) twins. Despite they did not find any relation between ApoCIII and acquired differences in BMI, they showed that ApoCIII levels were associated with early dysregulation of glucose metabolism independently of obesity and genetics.…”