Background
Angiopoietin-like 3 (Angptl3) is a regulator of lipoprotein metabolism at least by inhibiting lipoprotein lipase activity. Loss-of-function mutations in ANGPTL3 cause familial combined hypolipidemia and ANGPTL3 deficiency, in both mice and humans, has been associated with measures of increased insulin sensitivity.
Methods 
112 subjects have been studied for insulin sensitivity by glucose tolerance tests (OGTT). Results in carriers of the S17X loss-of-function mutation in ANGPTL3 and non-carrier controls have been compared.
Results
Fasting glucose and insulin were not different between genotypes. In an adjusted model for BMI, gender and age, we have shown significantly lower homeostatic model assessment of insulin resistance (HOMA-IR) and higher insulin sensitivity index (ISI) in S17X homozygotes as compared with the other genotypes (respectively P=0.011 and P=0.05).
Conclusions
In this study we have confirmed the results on HOMA-IR. The observation of an increase insulin-sensitivity in ANGPTL3 deficiency was further strengthen by the higher ISI levels in S17X homozygotes as compared to heterozygotes and wild type. The mechanism by which reduced ANGPTL3 levels lead to improved insulin sensitivity is not known so that further studies are needed to clarify this point. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism confirm its role as a potential therapeutic target.

04 - EVALUATION OF INDICES OF GLUCOSE AND INSULIN METABOLISM IN A COORT PATIENTS WITH ANGPTL3 DEFICIENCY