Circulating Betatrophin Is Strongly Increased in Pregnancy and Gestational Diabetes Mellitus.
OBJECTIVE
Betatrophin has recently been introduced as a novel hormone and promotor of beta cell proliferation and improved glucose tolerance in mouse models of insulin resistance. In obese and diabetic humans altered levels were reported and a role in pathophysiology of metabolic diseases was therefore hypothesized. However its release and regulation in women with gestational diabetes mellitus (GDM), as well as its associations with markers of obesity, glucose and lipid metabolism during pregnancy still remain unclear.


METHODS
Circulating betatrophin was quantified in 21 women with GDM and 19 pregnant body mass index-matched women with normal glucose tolerance (NGT) as well as 10 healthy age-matched non-pregnant women by enzyme-linked immunosorbent assay. Additionally we performed radioimmunassay (RIA) to confirm the results.


RESULTS
Betatrophin concentrations measured by ELISA were significantly higher in GDM than in NGT (29.3±4.4 ng/ml vs. 18.1±8.7 ng/ml, p<0.001) which was confirmed by RIA. Betatrophin did not correlate with BMI or insulin resistance but showed a weak association with leptin levels in pregnancy and negative relationship with fasting C-peptide levels in all women. Moreover it correlated significantly with lipid parameters including triglycerides and total cholesterol in pregnancy, as well as estrogen, progesteron and birth weight.


CONCLUSIONS
Circulating betatrophin concentrations are dramatically increased in pregnancy and are significantly higher in GDM versus pregnant NGT. In the light of the previously reported role in lipid metabolism, betatrophin may represent a novel endocrine regulator of lipid alterations in pregnancy. However additional studies are needed to elucidate whether hormonal factors, such as estrogen, control the production of betatrophin and if targeting betatrophin could hold promise in the fight against metabolic disease.
Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Gender Medicine Unit, Medical University of Vienna, Vienna, Austria.
Lana Kosi
LK
Trebotic
Section for Science of Complex Systems, CEMSIIS, Medical University of Vienna, Spitalgasse 23, Vienna, Austria.
Peter
P
Klimek
Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Gender Medicine Unit, Medical University of Vienna, Vienna, Austria.
Anita
A
Thomas
Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Gender Medicine Unit, Medical University of Vienna, Vienna, Austria.
Anna
A
Fenzl
Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Gender Medicine Unit, Medical University of Vienna, Vienna, Austria.
Karoline
K
Leitner
Clinical Division of Gynaecology and Obstretics, Medical University of Vienna, Vienna, Austria.
Stefanie
S
Springer
Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Gender Medicine Unit, Medical University of Vienna, Vienna, Austria.
Florian W
FW
Kiefer
Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Gender Medicine Unit, Medical University of Vienna, Vienna, Austria.
Alexandra
A
Kautzky-Willer
D000328:Adult; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D015992:Body Mass Index; D016022:Case-Control Studies; D016640:Diabetes, Gestational / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D036361:Peptide Hormones / Q000097:blood*; D011247:Pregnancy / Q000097:blood*; D011863:Radioimmunoassay
C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D036361:Peptide Hormones