Abstract 18157: Impact of Betatrophin (ANGPTL8) R59W Mutation for Future Diabetes, and Minimal Modification of Circulating Betatrophin With Strong Statins
Betatrophin (ANGPTL8), also known as “Lipasin” (lipoprotein lipase inhibitor), has been reported as a dual-regulator of glucose and lipid metabolism. Functional variant R59W in betatrophin gene is common in Japanese (minor allele 25%) compared with Caucasian (5%). Little is known about long-term impact of this gene variant, and also about the effect of lipid-lowering drugs on this hormone.
Methods: A total of 205 cases with dyslipidemia evaluated with baseline 75gOGTT, and post-heparin lipoprotein lipase activities were registered as a long-term cohort. As lipid-lowering trial, a total of 44 patients (Male 21, Age 65±11 ys) with primary dyslipidemia, and 18 genetically confirmed heterozygous familial hypercholesterolemia (FH) (Male 12, Age 65±10 ys,) were analyzed. Non-FH dyslipidemia was treated with 10mg Atorvastatin, and FH was treated with 20mg Rosuvastatin for 8 weeks. Plasma TG and betatrophin levels were log-transformed for statistical analysis.
Results: In long-term cohort, 57 cases already showed diabetic pattern at baseline, 148 cases (Male 82, age 56±15 ys, hetero-FH 48 cases, mean follow-up period 10±3 ys) without diabetes at baseline were finally analyzed. Sixty-two cases (42%) developed newly diabetes mellitus during the follow-up, significantly fewer in FH than non-FH (25% vs. 50%, p<0.005). No differences in BMI, fasting glucose, HbA1c in baseline with R59W genotype. In low LPL activity group (n=31), W carriers showed significant increase in HbA1c compared with RR (2.1±0.5 vs. 0.9±0.4 %, p<0.05), but no differences in normal LPL group.
In lipid lowering trial, baseline betatrophin levels were lower in FH group (19±13 vs. 13±6 ng/mL, p<0.05), but no difference with/without R59W variant. Statin treatment slightly decreased betatrophin in dyslipidemia group (-4%, p<0.01) and in FH group (-5%, p<0.01). Changes in betatrophin were positively correlated with changes in LDL-C with statins in both groups.
Conclusion: Betatrophin R59W variant was a susceptibility factor of future diabetes mellitus with low LPL activity. Baseline betatrophin levels were lower in FH group than other primary dyslipidemia in lipid-lowering trial. Strong statin treatments slightly decreased betatrophin levels, but effect sizes were minimal.
Author Disclosures: A. Nohara: Research Grant; Modest; Aegerion, Astellas Pharma, AstraZeneca, Kowa, Shionogi, Takeda, Synageva BioPharma. Research Grant; Significant; Keiai-Kai Medical Corp., MSD, Sanofi. M. Kawashiri: None. H. Hattori: None. T. Iwasaki: None. J. Liu: None. K. Yagi: None. M. Yoshida: None. M. Mori: None. C. Nakanishi: None. H. Tada: None. A. Inazu: None. T. Kobayashi: None. M. Yamagishi: None. H. Mabuchi: None.
- © 2015 by American Heart Association, Inc.