Different relationship between ANGPTL3 and HDL components in female non-diabetic subjects and type-2 diabetic patients.
Angiopoietin-like protein 3 (ANGPTL3) is a major lipoprotein regulator and shows positive correlation with high-density lipoprotein-cholesterol (HDL-c) in population studies and ANGPTL3 mutated subjects. However, no study has looked its correlation with HDL components nor with HDL function in patients with type 2 diabetes mellitus (T2DM).



We studied 298 non-diabetic subjects and 300 T2DM patients who were randomly recruited in the tertiary referral centre. Plasma levels of ANGPTL3 were quantified by ELISA. Plasma samples were fractionated to obtain HDLs. HDL components including apolipoprotein A-I (apoA-I), triglyceride, serum amyloid A (SAA), phospholipid and Sphingosine-1-phosphate were measured. HDLs were isolated from female controls and T2DM patients by ultracentrifugation to assess cholesterol efflux against HDLs. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, body mass index and lipid lowering drugs were performed in male or female non-diabetic participants or diabetic patients, respectively.



We demonstrated that plasma level of ANGPTL3 was lower in female T2DM patients than female controls although no difference of ANGPTL3 levels was detected between male controls and T2DM patients. After adjusting for confounding factors, one SD increase of ANGPTL3 (164.6 ng/ml) associated with increase of 2.57 mg/dL cholesterol and 1.14 μg/mL apoA-I but decrease of 47.07 μg/L of SAA in HDL particles of non-diabetic females (p < 0.05 for cholesterol and SAA; p < 0.0001 for apoA-I). By contrast, 1-SD increase of ANGPTL3 (159.9 ng/ml) associated with increase of 1.69 mg/dl cholesterol and 1.25 μg/mL apoA-I but decrease of 11.70 μg/L of SAA in HDL particles of female diabetic patients (p < 0.05 for cholesterol; p < 0.0001 for apoA-I; p = 0.676 for SAA). Moreover, one SD increase of ANGPTL3 associated with increase of 2.11 % cholesterol efflux against HDLs in non-diabetic females (p = 0.071) but decrease of 1.46 % in female T2DM patients (p = 0.13) after adjusting for confounding factors.



ANGPTL3 is specifically correlated with HDL-c, apoA-I, SAA and HDL function in female non-diabetic participants. The decrease of ANGPTL3 level in female T2DM patients might contribute to its weak association to HDL components and function. ANGPTL3 could be considered as a novel therapeutic target for HDL metabolism for treating diabetes.
Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China.
Dong
D
Zhao
Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China.
Long-Yan
LY
Yang
Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China.
Xu-Hong
XH
Wang
Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China.
Sha-Sha
SS
Yuan
Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China.
Cai-Guo
CG
Yu
Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China.
Zong-Wei
ZW
Wang
Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China.
Jia-Nan
JN
Lang
Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China. yingmeif13@sina.com.|Stem Cell Institute, University of Leuven, 3000, Louvain, Belgium. yingmeif13@sina.com.
Ying-Mei
YM
Feng
D000328:Adult; D000367:Age Factors; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000097:blood*; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D004195:Disease Models, Animal; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D016014:Linear Models; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D015999:Multivariate Analysis; D000685:Serum Amyloid A Protein / Q000032:analysis; D012737:Sex Factors; D062606:Tertiary Care Centers
C479896:ANGPTL3 protein, human; C505693:APOA1 protein, human; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C404495:Angptl3 protein, mouse; D016632:Apolipoprotein A-I; D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D000685:Serum Amyloid A Protein
Angiopoietin-like protein; Apolipoproteins; Cholesterol efflux; Diabetes; High-density lipoproteins; Serum amyloid A