Type 2 Diabetes (T2D) is one of the most common diseases worldwide affecting about 9% of the world population. (1) As a complex disease, it affects the function of many organs, which implies the possible connection it has with many other diseases.(2–4) Obesity and cardiovascular disease (CVD) which are in the context of this study, are two of the most well-known examples of these connections with confirmed links to diabetes.(5–7)
Obesity is a leading cause of insulin resistance thus, it is considered as one of the major risk factors for diabetes. Moreover, it is generally accepted that CVD is the leading cause of mortality among T2D patients, which arise from several abnormalities in cellular metabolism and energy homeostasis. Since the connection among these conditions is becoming more and more evident through recent studies, identifying the possible molecules and the their underlying mechanism seem to be important in this regard.(8)
Adipose tissue plays a major role in regulating the overall metabolism of the body by using, secreting a wide range of adipocytes. Adiponectin and their parallogues, the family of C1q/TNF-related proteins (CTRPs), seems to be the crucial molecules in the cross-talk among metabolic disorders.(9)
There is growing evidence that adiponectins levels are inversely associated with insulin resistance. Adiponectin acts as an anti-inflammatory agent in the adipose tissue and can improve insulin sensitivity in peripheral tissues.(10, 11) More importantly, accumulating evidence points toward the association between hypoadiponectinemia and increased risk of cardiovascular problems.(12, 13)
The family of CTRPs has 15 protein members that plays key roles in physiological and pathological metabolic conditions.(14, 15) The alteration in circulating levels of CTRPs has been reported in various metabolic diseases such as T2D, obesity, CVD, fatty liver disease and metabolic syndrome.(16–19)
CTRP1 is expressed in various tissues including adipose tissue, liver, muscles, kidneys, and heart.(14) Muscles are primary targets for CTRP1 as it activates AMPK and MAPK signaling pathways and promotes glucose uptake, ameliorates insulin resistance and increases fat oxidation.(20) Studies have shown increased levels of CTRP1 in T2D, prediabetes, coronary artery disease, congestive heart failure and atherosclerosis.(21, 22) Although there is evidence on the protective role of CTRP1 in murine heart injuries, the exact role of CTRP1 in these conditions is still not fully understood and requires further studies.(23)
CTRP5, another member of CTRPs family also expressed in a wide range of tissues including adipose tissue, eye, testis, skeletal muscle, brain, spleen, uterus, and ciliary epithelium but like CTRP1, adipose tissue is considered as the main secretor.(21) CTRP5 increases glucose uptake via stimulating plasma membrane incorporation of the glucose transporter 4 (GLUT4) into plasma membrane by a mechanism dependent on AMPK phosphorylation. In addition, Phosphorylation of acetyl-CoA carboxylase (ACC) is mediated by CTRP5 that results in fatty acid oxidation in rat myocytes. (14, 24, 25) According to recent studies, decreased levels of CTRP5 have been observed in metabolic syndrome, and T2D and increased levels were reported in coronary artery disease. Studies about the exact association between CTRP5 and metabolic disorders are rare with contradicting results, either suggesting a role against insulin resistant or a role promoting insulin resistance and atherosclerosis.
Given the importance of CVD as one of the most common cause of death in T2D patients as well as a close association among T2D, obesity and an increased occurrence of CVD risk factors, it has been of great importance to detect the possible molecules which links between aforementioned conditions.
Up to date, there is no study to evaluate CTRP1 and CTRP5 correlation with various obesity indices including body mass index (BMI), waist, hip, waist-to-hip ratio (WHR), visceral adipose tissue (VAT), and visceral adiposity index (VAI) in T2D patients compared to healthy group. In this study, we intended to address the association of circulating CTRP1 and CTRP5 with obesity indices and carotid intima-media thickness (cIMT) in patients with T2D and healthy subjects.