Serum Levels of Activin A: Predictor of Insulin Resistance and Atherosclerosis in Prediabetics

ABSTRACT

Background: Pathological effects of dysglycemia and insulin resistance on atherosclerosis and cardiac remodeling starts as early as in the prediabetic state before the onset of overt diabetes. Activin A is a molecule with multiple functions, including an important part in glucose homeostatic mechanisms as well as inflammatory processes and is therefore being researched as a useful novel biomarker for prompt recognition of the risk of cardiovascular disease (CVD) in prediabetic individuals, thereby helping in disease prognostication and early institution of therapeutic measures. Objective: The study aimed to measure serum levels of activin A in prediabetic patients and evaluate them in comparison to normoglycemic controls. The association of activin A with carotid intima media thickness (CIMT), left ventricular diastolic dysfunction (LVDD), and homeostatic assessment of insulin resistance (HOMA-IR) was also studied. Materials and methods: A total of 60 prediabetic cases and 60 normoglycemic control subjects [matched as per age, gender, and body mass index (BMI)] were recruited. Measurement of serum glucose levels (fasting and postprandial) and fasting insulin levels and glycated hemoglobin (HbA1c) levels were done in all the subjects. The values of HOMA-IR were computed using established formulae. Enzyme-linked immunosorbent assay (ELISA) kits were used for the evaluation of serum levels of activin A in both groups. Parameters for the two groups were compared. In the cases, CIMT (using B-mode ultrasound) and LVDD (using two-dimensional (2D) echocardiography) were measured and correlated with activin A levels. Results: Serum fasting insulin (mIU/L) was considerably higher in cases than in the controls (p < 0.001). HOMA-IR median [interquartile range (IQR)] was 4 (3.25–4.93) in some cases, and that in the control group was 1.2 (0.88–1.5) (p < 0.001). Serum activin A levels in the cases group had a median (IQR) of 263.55 (227.1–279.5) ng/mL, which was substantially greater as compared to the control group 159.9 (150.7–178.7) ng/mL (p < 0.001). A significant positive association of serum activin A levels with HOMA-IR (? = 0.75, p < 0.001) and CIMT (? = 0.50, p < 0.001) was found. In LVDD grade I and II groups, the serum levels of activin A were 257.86 (219.3–271.2) ng/mL and 269 (244.19–291.5) ng/mL, respectively (p = 0.12). Conclusion: A substantial proportion of morbidity and mortality related to dysglycemic states can be attributed to cardiovascular complications. Elevated levels of activin A in prediabetes can act as an indicator of subclinical CVD leading to early diagnosis and intervention.