Lack of associations between betatrophin/ANGPTL8 level and C-peptide in type 2 diabetic subjects

Abstract

BackgroundBetatrophin 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.MethodsThis study was designed to examine the association between plasma betatrophin level and C-peptide in 749 T2D and non-diabetics.ResultsBetatrophin 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].ConclusionIncreased 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.

ANGPTL8 (betatrophin) role in diabetes and metabolic diseases

“…Our results suggested that the increased ANGPTL8 level in people with T2D was not effective in increasing insulin production and was not affecting plasma glucose level . This conclusion was further supported by the finding that ANGPTL8 was not associated with C‐peptide level in the people with T2D unlike the non‐diabetic people in whom ANGPTL8 was positively associated with the C‐peptide level …”

“…We found an association between ANGPTL8 and C‐peptide in an attempt to understand whether the increase in ANGPTL8 production will have an impact on the endogenous insulin production as measured by plasma C‐peptide. Comparing ANGPTL8 level in 535 non‐diabetic and 214 T2D people ANGPTL8 was significantly associated with C‐peptide level in the non‐diabetic group only . The lack of such association in the T2D group suggested that the increased ANGPTL8 level observed in people with T2D was not due to increased C‐peptide production .…”

“…In addition to its association with ANGPTL3 and insulin, the association of ANGPTL8 with other metabolic markers such as high sensitivity C‐reactive protein (hsCRP), C‐peptide, and irisin has been investigated . We found an association between ANGPTL8 and C‐peptide in an attempt to understand whether the increase in ANGPTL8 production will have an impact on the endogenous insulin production as measured by plasma C‐peptide.…”

ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients

“…Data concerning the role of ANGPTL8 in diabetes and obesity are conflicting. In mice, ANGPTL8 has been proposed to improve glucose tolerance [43], but increased ANGPTL8 levels in diabetic patients have not been correlated with glucose or insulin levels [44,45]. Taken together, only ANGPTL4 has been demonstrated to be associated with CV events [46], and none of the ANGPTL family members has been demonstrated to be associated with all-cause death.…”

Serum Concentrations of Betatrophin and Its Association with Indirect Indices of Insulin Resistance and Beta Cell Function in Women with Polycystic Ovary Syndrome

“…However, this observation was not present in T2D patients [15]. In other studies, serum betatrophin concentrations inversely correlated with the increment of C-peptide in the glucagon stimulation test in T2D patients [21].…”