Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes

Abstract

Aims/hypothesis: The hormone betatrophin was recently described as a potent stimulator of beta cell proliferation in mice. Insulin resistance, but not insulin deficiency, caused upregulation of betatrophin expression. If these findings were found to be fully applicable in humans, this would open up the possibility of future betatrophin treatment in type 1 diabetes. The present study measured for the first time betatrophin concentrations in humans and tested the hypothesis that there would be no difference in circulating betatrophin concentrations between patients with type 1 diabetes and healthy individuals.

Methods: Betatrophin concentrations in plasma of 33 patients with type 1 diabetes and 24 age-matched healthy controls were measured by ELISA. The study participants were characterised for blood lipids, BMI, plasma glucose and HbA1c, and, for the diabetic patients, their insulin requirements and any residual C-peptide concentrations.

Results: Plasma betatrophin concentrations were normally ~300 pg/ml, but were approximately doubled in patients with type 1 diabetes. In the patients, there were no correlations between betatrophin and age, blood lipids, BMI, glucose control or insulin requirement, whereas in controls betatrophin levels increased with age. BMI, blood pressure and triacylglycerol, LDL-cholesterol and HDL-cholesterol levels were similar in patients and healthy controls.

Conclusions/interpretation: Circulating concentrations of betatrophin are increased in type 1 diabetes in contrast with what was recently described in an insulin-deficient mouse model. However, increased betatrophin concentrations do not protect against loss of C-peptide. Betatrophin treatment in type 1 diabetes would therefore probably not be successful without the use of supraphysiological doses or a combination with immune regulatory treatment.

Figures

Fig. 1

Increased fasting plasma levels of betatrophin in patients with type 1 diabetes. (a) Plasma concentrations of betatrophin in healthy controls (HC, n = 24) and patients with type 1 diabetes (T1D, n = 33) shown as mean ± SEM. (b) Scatter plot of the individual betatrophin concentrations with mean ± SEM. (c) Correlation of betatrophin levels obtained by western immunoblot with those obtained by ELISA in 13 of the samples (six HC and seven patients with T1D) showing an r2 value of 0.69 (p = 0.0004). Samples were normalised for total protein content, values are arbitrary units (AU). *p < 0.05