Lack of associations between betatrophin/ANGPTL8 level and C-peptide in type 2 diabetic subjects.
BACKGROUND
Betatrophin has been suggested as an inducer of β-cell proliferation in mice in addition to its function in regulating triglyceride. Recent data showed that betatrophin was increased in Type 2 Diabetes (T2D), however, its ability to induce insulin production has been questioned. We hypothesized that the increased betatrophin in T2D is not affecting insulin production from β-cells. To test this hypothesis, we investigated the association between betatrophin and C-peptide level in humans, which acts as a measure of endogenous insulin production from β-cells.


METHODS
This study was designed to examine the association between plasma betatrophin level and C-peptide in 749 T2D and non-diabetics.


RESULTS
Betatrophin and C-peptide levels were higher in T2D subjects compared with non-diabetics subjects. Betatrophin showed strong correlation with C-peptide in non-diabetics subjects (r = 0.28, p = < 0.0001). No association between betatrophin and C-peptide were observed in T2D subjects (r = 0.07, p = 0.3366). Dividing obese and non-obese subjects into tertiles according to betatrophin level showed significantly higher C-peptide levels at higher tertiles of betatrophin in obese non-diabetics subjects P-trend = 0.0046. On the other hand, C-peptide level was significantly higher in subject with higher betatrophin level in non-diabetics subjects across all age groups but not in T2D subjects. Multiple logistic regression models adjusted for age, BMI, gender, ethnicity as well as C-peptide level showed that subjects in the highest tertiles of betatrophin had higher odds of having T2D [odd ratio (OR) = 7.3, 95% confidence interval (CI) 4.0-13.3].


CONCLUSIONS
Increased betatrophin level in obese subjects is correlated with an increase in C-peptide level; which is possibly caused by the increased insulin resistance. On the other hand, no correlation is observed between increased betatrophin level and C-peptide in T2D subjects. In conclusion, the increased betatrophin in T2D subject does not cause any increase in insulin production as indicated by C-peptide level.
Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, P.O. Box 1180, Dasman, 15462, Kuwait City, Kuwait. mohamed.abufarha@dasmaninstitute.org.
Mohamed
M
Abu-Farha
Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, P.O. Box 1180, Dasman, 15462, Kuwait City, Kuwait. JEHAD.ABUBAKR@dasmaninstitute.org.
Jehad
J
Abubaker
Dasman Diabetes Institute, P.O. Box 1180, Dasman, 15462, Kuwait City, Kuwait. fiona.noronha@dasmaninstitute.org.
Fiona
F
Noronha
Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, P.O. Box 1180, Dasman, 15462, Kuwait City, Kuwait. irina.alkhairi@dasmaninstitute.org.
Irina
I
Al-Khairi
Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, P.O. Box 1180, Dasman, 15462, Kuwait City, Kuwait. preethi.cherian@dasmaninstitute.org.
Preethi
P
Cherian
Dasman Diabetes Institute, P.O. Box 1180, Dasman, 15462, Kuwait City, Kuwait. monira.arouj@dasmaninstitute.org.
Monira
M
Alarouj
Dasman Diabetes Institute, P.O. Box 1180, Dasman, 15462, Kuwait City, Kuwait. abdullah.bennakhi@dasmaninstitute.org.
Abdullah
A
Bennakhi
Clinical Epidemiology, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar. nelkum@hotmail.com.
Naser
N
Elkum
D000328:Adult; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D018912:Arabs; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology; D005260:Female; D006801:Humans; D007194:India / Q000208:ethnology; D007333:Insulin Resistance / Q000208:ethnology; D007730:Kuwait / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000175:diagnosis / Q000208:ethnology; D010154:Pakistan / Q000208:ethnology; D036361:Peptide Hormones / Q000097:blood*; D015854:Up-Regulation
C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D015415:Biomarkers; D002096:C-Peptide; D036361:Peptide Hormones