Skip to main content
Top
Published in: Diabetologia 1/2014

Open Access 01-01-2014 | Short Communication

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

Authors: Daniel Espes, Joey Lau, Per-Ola Carlsson

Published in: Diabetologia | Issue 1/2014

Login to get access

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.
Literature
1.
go back to reference Wang L, Lovejoy NF, Faustman DL (2012) Persistence of prolonged C-peptide production in type 1 diabetes as measured with an ultrasensitive C-peptide assay. Diabetes Care 35:465–470PubMedCrossRef Wang L, Lovejoy NF, Faustman DL (2012) Persistence of prolonged C-peptide production in type 1 diabetes as measured with an ultrasensitive C-peptide assay. Diabetes Care 35:465–470PubMedCrossRef
2.
go back to reference Keenan HA, Sun JK, Levine J et al (2010) Residual insulin production and pancreatic ss-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes 59:2846–2853PubMedCrossRef Keenan HA, Sun JK, Levine J et al (2010) Residual insulin production and pancreatic ss-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes 59:2846–2853PubMedCrossRef
3.
go back to reference Yi P, Park JS, Melton DA (2013) Betatrophin: a hormone that controls pancreatic beta cell proliferation. Cell 153:747–758PubMedCrossRef Yi P, Park JS, Melton DA (2013) Betatrophin: a hormone that controls pancreatic beta cell proliferation. Cell 153:747–758PubMedCrossRef
4.
go back to reference Cleland SJ, Fisher BM, Colhoun HM, Sattar N, Petrie JR (2013) Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks? Diabetologia 56:1462–1470PubMedCrossRef Cleland SJ, Fisher BM, Colhoun HM, Sattar N, Petrie JR (2013) Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks? Diabetologia 56:1462–1470PubMedCrossRef
5.
go back to reference Williams KV, Erbey JR, Becker D, Arslanian S, Orchard TJ (2000) Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes 49:626–632PubMedCrossRef Williams KV, Erbey JR, Becker D, Arslanian S, Orchard TJ (2000) Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes 49:626–632PubMedCrossRef
6.
go back to reference Zhang R (2012) Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun 424:786–792PubMedCrossRef Zhang R (2012) Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun 424:786–792PubMedCrossRef
7.
go back to reference Quagliarini F, Wang Y, Kozlitina J et al (2012) Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci U S A 109:19751–19756PubMedCrossRef Quagliarini F, Wang Y, Kozlitina J et al (2012) Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci U S A 109:19751–19756PubMedCrossRef
8.
go back to reference Dong XY, Pang XW, Yu ST et al (2004) Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method. Int J Cancer 112:239–248PubMedCrossRef Dong XY, Pang XW, Yu ST et al (2004) Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method. Int J Cancer 112:239–248PubMedCrossRef
9.
go back to reference Butler AE, Galasso R, Meier JJ, Basu R, Rizza RA, Butler PC (2007) Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of diabetic ketoacidosis. Diabetologia 50:2323–2331PubMedCrossRef Butler AE, Galasso R, Meier JJ, Basu R, Rizza RA, Butler PC (2007) Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of diabetic ketoacidosis. Diabetologia 50:2323–2331PubMedCrossRef
10.
go back to reference Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG (2010) Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes. Diabetologia 53:2020–2028PubMedCrossRef Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG (2010) Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes. Diabetologia 53:2020–2028PubMedCrossRef
Metadata
Title
Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes
Authors
Daniel Espes
Joey Lau
Per-Ola Carlsson
Publication date
01-01-2014
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 1/2014
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-013-3071-1

Other articles of this Issue 1/2014

Diabetologia 1/2014 Go to the issue