A novel indicator of widespread endothelial damage and ischemia in diabetic patients: ischemia-modified albumin

Abstract

Ischemia-modified albumin (IMA) is a novel marker of tissue ischemia. Nowadays, IMA is accepted as a marker of oxidative stress. In this study, we aimed at establishing an association between IMA and hyperglycemia, blood pressure, lipid parameters, microvascular complications, hsCRP, and microalbuminuria in type 2 diabetes patients without overt macrovascular disease and acute ischemia. Fifty type 2 diabetes mellitus patients without a history of macrovascular disease or end-stage renal disease were enrolled into the study. Age-matched 30 healthy individuals were also included in the study as a control group. Plasma IMA (0.329 ± 0.046 and 0.265 ± 0.045 AbsU; P < 0.0001) and hsCRP levels (0.51 ± 0.36 and 0.32 ± 0.17 mg/dl; P < 0.0001) were significantly higher in the diabetic group compared to healthy controls. IMA level was significantly correlated with hsCRP (r = 0.76; P < 0.0001), HbA1c (r = 0.72; P < 0.0001), microalbuminuria (r = 0.40; P = 0.004), systolic blood pressure (r = 0.28; P = 0.049), diastolic blood pressure (r = 0.44; P = 0.005), and HOMA-IR (r = 0.42; P = 0.005) levels in the entire diabetic subjects. In the diabetic patients group, presence of microalbuminuria was associated with a higher plasma IMA level (0.355 ± 0.035 and 0.265 ± 0.0045 AbsU; P < 0.0001, patients with microalbuminuria and control subjects, respectively). In the type 2 diabetes patients with nephropathy, IMA level (0.355 ± 0.035 and 0.311 ± 0.046 AbsU; P = 0.002) was determined higher compared to the diabetes patients without nephropathy. Diabetic patients without an overt cardiovascular disease still have a higher serum IMA level compared to healthy controls. The correlation of high plasma IMA levels with high hsCRP and microalbuminuria levels in diabetic subjects indicates the presence of a chronic ischemic process. Therefore, elevated IMA levels may indicate an underlying subclinical vascular disease in type 2 diabetes mellitus patients.

Associations of FPG, A1C and disease duration with protein markers of oxidative damage and antioxidative defense in type 2 diabetes and diabetic retinopathy

“…Our findings are in accordance with previous studies in DM [17][18][19][20][21] and DR patients. 11 However, we could not find reports on both IMA and GSH simultaneously in DM and DR patients.…”

“…18,19 IMA has been well accepted in the literature as a marker of OS, and its elevation has been associated with endothelial dysfunction, inflammation, and hyperglycemia in different types of diabetes with and without complications. [17][18][19][30][31][32][33][34] Hyperglycemia in DM is linked to OS, and retinal exposure to hyperglycemia activates multiple enzymes/ pathways accelerating OS and development of DR. [9][10][11]35 Hyperglycemia promotes increased IMA formation probably owing to mechanisms of hypoxia and OS. [17][18][19] Interestingly, it was reported that increased glycosylation of hemoglobin increases its affinity for oxygen, therefore, preventing its release at the tissue inducing hypoxia and OS.…”

“…[17][18][19][30][31][32][33][34] Hyperglycemia in DM is linked to OS, and retinal exposure to hyperglycemia activates multiple enzymes/ pathways accelerating OS and development of DR. [9][10][11]35 Hyperglycemia promotes increased IMA formation probably owing to mechanisms of hypoxia and OS. [17][18][19] Interestingly, it was reported that increased glycosylation of hemoglobin increases its affinity for oxygen, therefore, preventing its release at the tissue inducing hypoxia and OS. 25,36 Positive associations of IMA with FPG and A1C in our patient groups (Table 2) may be owing to the role of hyperglycemia and A1C as an OS inducer.…”

“…Although multiple reports [13][14][15] including ours 12 showed increased lipid peroxidation and impaired antioxidant status in diabetes and DR, little published data on protein markers of OS in both diabetes and DR patients are available. 11,16 Although ischemia modified albumin (IMA) has been demonstrated as a novel marker of ischemia, OS and endothelial dysfunction in diabetes [17][18][19] studies on IMA in DR patients are very scarce. To the best of our knowledge, there is only one study in the literature on IMA levels in human DR patients.…”

Serum Ischemia-Modified Albumin in Preterm Babies with Respiratory Distress Syndrome

“…Therefore, infants with RDS expose to severe hypoxia [4]. Current studies have determined that cord blood levels of IMA are higher in perinatal asfixia and complicated deliveries associated with fetal distress, hypoxia, and oxidative stress in newborns [11,12,19,20], and IMA has been declared to be a good marker for diagnosis of asphyxia. RDS is known a severe disease that leads to severe hypoxia and further deleterious neurodevelopmental outcomes of preterm infants and mortality without appropriate respiratory support and surfactant therapy.…”