Clinical Significance of Determining Plasma MicroRNA33b in Type 2 Diabetic Patients with Dyslipidemia.
OBJECTIVE
Sterol regulatory element-binding protein (SREBP)-1c is the dominant liver insulin-stimulated isoform and strongly correlates with diabetic dyslipidemia characterized by hyperinsulinemia [i.e., high-density lipoprotein cholesterol (HDL-C) levels and hypertriglyceridemia]. MicroRNA (miRNA) 33b is harbored in the intron of SREBP-1c and represses ATP-binding cassette, sub-family A, and member 1 (ABCA1) expression, essential for HDL formation. We measured plasma miRNA33b levels as possible biomarkers for diabetic dyslipidemia in patients with type 2 diabetes mellitus (T2DM) showing insulin resistance.


METHODS
The participants included 50 patients with T2DM (M/F 31/19) enrolled in an educational program for controlling blood glucose levels at Hirosaki University Hospital. HbA1c, fasting plasma glucose, insulin, and lipid levels were determined. Plasma miRNA33b, miRNA33a and miRNA148a were quantified using a TaqMan®MicroRNA Assay, and values were corrected with reference to miRNA16.


RESULTS
Mean BMI of participants were 28.2±6.6 (kg/m2) and the Homeostasis Model Assessment of Insulin Resistance was 4.3±2.7. Patients' laboratory findings indicated diabetic dyslipidemia with insulin resistance. Plasma miRNA33b/16 levels revealed a positive correlation with plasma insulin level (r=0.326, P=0.021), serum C-peptide (r=0.280, P=0.049), and triglyceride (r=0.351, P=0.012), but no association with HDL-C (r=-0.210, P=0.143). The blood level of miRNA33a was approximately 1/150th of that of miRNA33b and was not correlated with the above parameters.


CONCLUSIONS
We postulated that plasma miRNA33b may be useful as a new metabolic biomarker of dyslipidemia in patients with T2DM as well as metabolic syndrome via an insulin/SREBP-1c/miRNA33b/ABCA1 pathway.
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine.
Yuki
Y
Kimura
Naoki
N
Tamasawa
Koki
K
Matsumura
Hiroshi
H
Murakami
Maki
M
Yamashita
Kota
K
Matsuki
Jutaro
J
Tanabe
Hiroshi
H
Murakami
Jun
J
Matsui
Makoto
M
Daimon
D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000032:analysis; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors
D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D008055:Lipids; D035683:MicroRNAs; C550416:MIRN33a microRNA, human; C517652:hemoglobin A1c protein, human