Aims/hypothesisBetatrophin 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.MethodsCirculating 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.ResultsBetatrophin 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/interpretationCirculating 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.

Background: Sex hormones are believed to play an important role in development and progression of cardiovascular disease. However, the gender gap in onset and mortality is not yet completely understood. Transsexuals undergoing hormone therapy are a promising collective for analysing the effects of sex hormones on cardiometabolic disease. Methods: Aim of this study is to identify gender specific cardiovascular changes attributed to high-dose cross-sex hormone therapy (HT) in male-to-female (MtF) and female to male (FtM) transgender patients by performing an oral glucose tolerance test (OGTT) and 3 Tesla magnet resonance spectroscopy for hepatic (HCL) and myocardial (MYCL) lipid content analysis. The control group (CON) is conducted by age, sex and BMI matched healthy individuals. Results: Until now we included 26 MtF,14 FtM patients and 12 age and BMI matched healthy controls. The mean age was comparable in all 3 groups (MtF 30.12±2.31, FtM 29.72±1,91, CON 30,23±1.22 as well as BMI (22.59±3.81, 21.62±2.53, 21.33±1.20 kg/m2, p=ns, respectively). The mean hormone therapy duration was similar in both groups (MtF 4.58±1.20 vs FtM 2.35±0,95, p=0,29). HOMA Index did not significantly differ between the groups (MtF 1,78±0,92 vs FtM 1,96±1.22 vs CON 1,8±1.01, p=0,3 vs 0,4 vs 0,3 respectively). HCL was significantly higher in MtF than FtM (1,50±0,41 % vs 0.54±0,33 %, p=0,022, respectively). We also found a significant correlation between ejection fraction (EF) and Testosterone levels (Spearmans Rho 0,80, p=0.002). Conclusio: These preliminary data could indicate a positive effect of Testosterone therapy on heart function. Contradictory to current data we found a higher HCL in MtF than FtM suggesting a not so protective estrogen effect when looking at the liver. Long-term studies are warranted to assess whether cross-sex HT results in different outcomes regarding cardiovascular disease.