ApoC-III Levels Correlate with Insulin Resistance and HbA1c in Familial Partial Lipodystrophy—Observations from the Broaden Study

Familial Partial Lipodystrophy (FPLD) is a rare genetic disorder with selective loss of adipose tissue from the periphery with an increase in ectopic fat leading to severe hepatic insulin resistance, and hypertriglyceridemia. ApoC-III is a secreted liver glycoprotein associated with hypertriglyceridemia and insulin resistance. We inquired the relationship between lipid and other metabolic parameters with morphometric characteristics (including those of ectopic fat deposition) and circulating apoC-III levels in a cohort of FPLD patients who were screened for enrollment into the BROADEN study, a global trial to study efficacy of volanesorsen (an antisense mRNA apoC-III inhibitor). 28 patients are included in these analyses (age range, 28 to 65, mean 45 years; M/F, 7/21; all but one Caucasian). Table 1 shows the significant relationships observed using linear regression analyses between circulating ApoC-III levels and investigated parameters. These results reiterate the tight relationship between triglyceride levels and ApoC-III levels, and further demonstrate that circulating ApoC-III levels also correlate with insulin resistance, and HbA1c as well as important left ventricle morphometric parameters. It is plausible to hypothesize that a strategy to lower apoC-III levels may have additional benefits beyond lowering triglyceride levels.