Inverse relationship between serum adenosine deaminase levels and islet beta cell function in patients with type 2 diabetes

Abstract

Objective Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease, which characterized by islet beta cell dysfunction. Serum adenosine deaminase (ADA) is an important enzyme that regulates the biological activity of insulin, and its levels are greatly increased in inflammatory diseases with insulin resistance. The present study was designed to explore the relationship between serum ADA levels and islet beta cell function in patients with T2D. Methods This cross-sectional study recruited 1573 patients with T2D from the Endocrinology Department of the Affiliated Hospital 2 of Nantong University between 2015 and 2018. All participants were received serum ADA test and oral glucose tolerance test (OGTT). Insulin sensitivity index (assessed by Matsuda index using C-peptide, ISIM-cp), insulin secretion index (assessed by ratio of area under the C-peptide curve to glucose curve, AUCcp/glu) and islet beta cell function (assessed by insulin secretion-sensitivity index 2 using C-peptide, ISSI2cp) were derived from OGTT. And other clinical parameters, such as HbA1c, were also collected. Results It was showed that HbA1c was significantly increased, while ISIM-cp, AUCcp/glu and ISSI2cp significantly decreased, across ascending quartiles of serum ADA levels. Moreover, serum ADA levels were negatively correlated with ISSI2cp (r = − 0.267, p < 0.001). Furthermore, after adjusting for other clinical parameters by multiple linear regression analysis, serum ADA levels were still independently associated with ISSI2cp (β = − 0.125, t = − 5.397, p < 0.001, adjusted R2 = 0.459). Conclusions Serum ADA levels are independently associated with islet beta cell function in patients with T2D.

Increased levels of serum adenosine deaminase and increased risk of diabetic peripheral neuropathy in type 2 diabetes

“…In addition, patients with increased cardiometabolic risks are always characterized by elevated serum ADA levels, and these cardiometabolic risks include higher BMI ( 35 ), increased TC ( 36 ), hypertension ( 16 ), atherosclerosis ( 13 ), thrombosis ( 14 ), coronary artery calcification ( 37 ) and T2D ( 38 ). Furthermore, in our previous studies and other previous studies, elevated serum ADA levels are not only involved in impaired pancreatic β-cell function in T2D ( 39 ) but also contribute to several diabetic complications, such as diabetic retinopathy ( 40 ), diabetic nephropathy ( 41 ), and prolonged heart QT interval in T2D ( 42 ). In our present study, serum ADA levels were observed to be positively correlated with ageing, higher SBP, longer diabetes duration, and increased levels of ALT, AST, GGT, CysC and HbA1c and negatively correlated with eGFR and insulin sensitivity index (IS-CP).…”

A crucial role of adenosine deaminase in regulating gluconeogenesis in mice

“…Recent studies have known ADO nucleotide and its metabolites elevate in the blood of T2DM, and uric acid, as the end-product of ADO nucleotide metabolism, is a potential risk factor for developing diabetes ( 7 , 26 ). ADA is notably elevated in patients with T2DM, and this elevation positively correlates with fasting blood glucose, glycated hemoglobin, and insulin resistance ( 27 ). Elevated serum ADA levels not only indicate impaired β-cell function in T2DM but may also lead to several diabetic complications such as diabetic retinopathy and diabetic nephropathy ( 17 , 28 ).…”

Inflammatory protein signatures in individuals with obesity and metabolic syndrome

“…Particularly, FGF21 stimulates the release of leptin and interleukin-6 while suppressing adiponectin 36,37 . Similarly, research has shown that increased HGF levels are associated with higher waist circumference, HDL-cholesterol, elevated liver enzymes, pro-inflammatory gene activation, and insulin resistance 38,39 . Others have demonstrated a positive association between VEGF levels and abdominal obesity, dysglycemia, elevated serum triglycerides, low high-density cholesterol (HDL) as well as elevated blood pressure [40][41][42][43] .…”