Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity

Abstract

BackgroundDipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents.MethodsFasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects.ResultsADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean±standard error, 23.1±0.6 U/L vs. 18.6±0.8 U/L; P<0.05). ADA activity was correlated with fasting plasma glucose (r=0.258, P<0.05), HbA1c (r=0.208, P<0.05), aspartate aminotransferase (r=0.325, P<0.05), and alanine aminotransferase (r=0.248, P<0.05). Compared with the well-controlled T2DM patients (HbA1c<7%), the poorly controlled group (HbA1c>9%) showed significantly increased ADA activity (21.1±0.8 U/L vs. 25.4±1.6 U/L; P<0.05). The effect of DPP4I on ADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9±1.0 U/L vs. 28.1±2.8 U/L; P<0.05) compared with that of those on sulfonylurea monotherapy.ConclusionOur results show that ADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect.

Elevated levels of serum adenosine deaminase in type 2 diabetes mellitus patients

“…Inosine and 2'-deoxyinosine are converted to hypoxanthine, xanthine and finally to uric acid. 5,6 Highest ADA activity is observed in the lymphoid and fatty tissues, liver, skeletal muscle, and heart, although the activity is widely distributed in most organs. 7 An increase in ADA activity in T2DM patients has been reported by several researchers.…”

“…8,9 Elevated ADA levels are also found in obesity, metabolic syndrome, liver cirrhosis and hepatoma, TB, brucellosis, typhoid fever, hypoxic states and cell mediated immune responses. 6,10,11 However, it is difficult to conclude whether changes in ADA activity are the cause or result of actual insulin resistance. [12][13][14][15] In the present study, we measured serum ADA activity in T2DM patients to evaluate the relationship between serum ADA activity with glycemic status and various metabolic parameters in T2DM patients.…”

Role of Adenosine Deaminase and Insulin in Type 2 Diabetes Mellitus in Eastern India

“…Few studies have reported an increased serum ADA levels and also correlated with glycemic control in T2DM patients [30,31] . Moreover, higher serum ADA have also been seen in nonobese T2DM cases and correlated with fasting plasma glucose [7] .…”

“…As adenosine causes apoptosis and inhibits differentiation of T lymphocytes by activating P1 adenosine receptors, interface of ADA with DPP-4 may lead to T cell proliferation and increased cytokine production which can interfere with insulin signalling [22][23][24][25] . Cytokines stimulate the acute-phase proteins.…”

Cyclic AMP and PKA: How can a Lot of Good Come from the Potentially Bad?

“…However, less information is available regarding cardio-protective effects of the DPP4 inhibitors. In addition to preventing the deactivation of endogenous GLP-1, DPP4 inhibitors also have anti-inflammatory properties and can bind adenosine deaminase, thereby elevating extracellular adenosine levels [9].…”