type 2 diabetes is associated with higher serum levels of circulating adenylyl cyclase 8: a novel biomarker of the disease

Aim: A prospective study to evaluate the functional relevance of circulating adenylyl cyclase’s (ADCY), specifically ADCY1, 3 and 8 in patients with type 2 diabetes (T2D) vs. controls. Method: A total of 188 individuals, 92 T2D and 96 nondiabetic (ND) were recruited. Specific enzyme-linked immunosorbent assay kits were used to quantify the levels of circulating plasma ADCY and its end product cyclic AMP (cAMP) in our study population. Results: Plasma levels of ADCY1, 3 and 8 were measured. We observed significantly increased measures of plasma levels of ADCY8 in T2D compared to ND (mean ± SEM: 12.645 ± 0.179 vs. 12.056 ± 0.167 ng/mL, p= 0.017). Increased ADCY-8 levels exhibited a positive correlation with the prevailing Hb1Ac levels (r = 0.188, p= 0.012). T2D patients who are obese (12.941 ± 0.207) showed increased levels of ADCY8 relative to non-obese (12.142 ± 0.317, p= 0.039). No significant differences were observed between the plasma concentrations of ADCY -1 or -3 relative to T2D or obesity. The functional relevance of this increased circulating ADCY levels were investigated. Hence, significantly higher levels of plasma cAMP were observed in T2D compared to ND (p< 0.001); irrespective of their obesity status. Higher levels of cAMP positively correlated with fasting plasma glucose levels (r= 0.266, p= 0.026). Conclusion: Heightened state of ADCY8 and cAMP possibly reflects its potential as a biomarker for disease progression and development of complications in T2D. Disclosure A. Al Madhoun: None. F. Al-Mulla: None. Funding Kuwait Foundation for the Advancement of Science; Dasman Diabetes Institute