Circulating Oxidative Stress Biomarkers in Clinical Studies on Type 2 Diabetes and Its Complications

Table 2

Selected clinical retrospective studies on circulating oxidative stress markers in T2DM with and without complications. All the studies included in this table were categorized under the class of evidence C, retrospective studies.

Disease and population	Sample	Markers	Observation	Information on medication or supplements	Reference
T2DM (); T2DM with micro- and macrovascular complications (); Controls ()	Plasma and erythrocytes	Protein carbonyl; TBARS; FRAP; GSH; CAT	↑ protein carbonyls in T2DM and T2DM with complications compared to controls and in T2DM with complications compared to T2DM without; ↑ TBARS higher in T2DM and T2DM with complications compared to controls and in T2DM with complications compared to T2DM without; ↓ FRAP, GSH, and CAT in T2DM and T2DM with complications compared to controls; ↓ GSH in T2DM and T2DM with complications compared to controls and in T2DM with complications compared to T2DM without	No antioxidants	[62]
T2DM with complications (); T2DM without complications (); Controls ()	Plasma	MDA; AOPP	↑ MDA and AOPP in T2DM compared to controls; ↑ MDA and AOPP in T2DM with complications compared to T2DM without complications	4% of T2DM without complications and 42% of T2DM with complications were on insulin treatment; 96% of T2DM without complications and 58% of T2DM with complications were on oral hypoglycaemic drug treatment	[65]
T2DM with poor glycaemic control without complications (); T2DM with poor glycaemic control with complications ()	Plasma	MDA; Protein carbonyl; FRAP; SOD	↑ SOD and FRAP in patients with complications; ↑ MDA in females with complications compared to those without; No differences in carbonyl residues between males and females	Multiregression analysis: Statin treatment was associated with SOD in females; Metformin treatment was inversely associated with MDA	[68]
T2DM with good glycaemic control without complications (); T2DM with poor glycaemic control without complications (); T2DM with poor glycaemic control with micro- and macrovascular complications ()	Plasma	MDA; Protein carbonyl; FRAP; SOD	↑ MDA and carbonyl residues in T2DM with poor glycaemic control with and without complications compared to poorly controlled; ↓ FRAP in poorly controlled without complications compared to well controlled without complications; ↑ SOD in T2DM with poor glycaemic control with complications compared to well controlled	Medications (nonexclusive): sulphonylureas (), biguanides (), insulin (), thiazolidinediones (), meglitinides (), statins (), and antihypertensive drugs (); Multiregression analysis indicated no confounding effect of statin or metformin	[63]
T2DM with nephropathy (); T2DM without nephropathy (); Controls ()	Plasma	MDA; FRAP; GSH	↑ MDA in T2DM with nephropathy compared to those without and controls; ↓ FRAP and GSH in T2DM with and without nephropathy compared to controls	Patients on inhibitors of the renin-angiotensin-aldosterone system, aspirin, and vitamin D analogues were advised to stop these drugs for one week before inclusion in the study	[71]
T2DM with nephropathy (); T2DM without nephropathy (); Controls ()	Urine	8-OHdG	↑ 8-OHdG in T2DM with and without nephropathy compared to controls; No differences between T2DM with and without nephropathy	Not provided	[90]
T2DM patients with good glycaemic control (); T2DM patients with poor glycaemic control (); Controls ()	Serum	MDA	↑ MDA in T2DM with poor glycaemic control vs. good glycaemic control and healthy volunteers	No antioxidants supplementation in the previous two months	[66]
T2DM female patients with good glycaemic control (); T2DM female patients with poor glycaemic control ()	Serum, plasma, PBMC	MDA; F2-isoprostanes; FRAP; GSH/GSSG; SOD; CAT; GPx	No differences	Similar distribution of metformin, insulin, and other antidiabetic medications in the two groups	[69]
T2DM without nephropathy (); T2DM with mild nephropathy (); T2DM with severe nephropathy ()	Plasma and RBC	AGEs; MDA; 8-OHdG; Vitamin C; TAS; GSH; GPx; CAT; SOD	↑ 8-OHdG in T2DM with micro- and macroalbuminuria compared to normoalbuminuric patients; ↓ vitamin C in T2DM; with micro- and macroalbuminuria compared to normoalbuminuric patients; No differences in AGE, MDA, TAS, GSH, GPx, CAT, and SOD	Distributions were comparable in the three groups for aspirin and drugs for diabetes control (four kinds of medications); A lower percentage of T2DM without nephropathy used insulin and antihyperlipidemic drugs than T2DM with severe nephropathy; A higher percentage of T2DM with mild nephropathy used metformin than the other two groups	[73]
T2DM with complications (); T2DM without complications (); Controls ()	Urine	8-OHdG; 8-oxoGuo	↑ 8-OHdG and; 8-oxoGuo in T2DM compared to controls; ↑ 8-oxoGuo in T2DM with macrovascular complications compared to those without complications	Not provided	[91]
T2DM with microvascular complications (); T2DM without complications (); Controls ()	Urine	8-OHdG	↑ 8-OHdG in T2DM with microvascular complications than those without complications	Not provided	[93]
T2DM with microvascular complications (); T2DM with macrovascular complications (); T2DM without complications ()	Serum	AGEs; Protein carbonyl; MDA; AOPP	↑ MDA, protein carbonyl, AOPP, and AGE in T2DM with micro- and macrovascular complications compared to T2DM without complications	Not provided	[64]
T2DM with micro-and macrovascular complications (); T2DM without complications (); Controls ()	Plasma	AGEs; AOPPs	↑ AGE and AOPPs in T2DM compared to controls; ↑ AGE in T2DM with complications compared to those without	No antioxidant supplements; Lipid- or triglyceride-lowering drugs: 62% of T2DM without complications and 73% with complications	[76]
T2DM (); Controls ()	Plasma	AOPP	↑ AOPP in T2DM with albuminuria compared to those without; AOPP was better than IMA in distinguishing patients with micro- and macroalbuminuria	Not provided	[85]
Newly diagnosed T2DM without albuminuria (); Newly diagnosed T2DM with albuminuria (); Controls ()	Plasma	AOPP	↑ AOPP in T2DM with albuminuria compared to those without and to controls	No hypoglycaemic or antihypertensive drugs, lipid-lowering agents, or antioxidants (vitamin C, vitamin E, or lipoic acid)	[86]
Poorly controlled T2DM with vascular complication (); Poorly controlled T2DM without vascular complication (); Controls ()	Plasma	AGE	↑ AGE in T2DM with complications compared to those without	Not provided	[77]
T2DM with nephropathy (); T2DM without nephropathy (); Controls ()	Serum and erythrocytes	MDA; SOD	↑ MDA in T2DM compared to controls; No changes in MDA and SOD in T2DM with and without nephropathy	Distributions were comparable in the groups with and without nephropathy for antihypertensives, statins, metformin, sulfonylureas, and insulin	[72]
T2DM with stable ischemic heart disease (); T2DM without stable ischemic heart disease ()	Plasma and serum	Protein carbonyl; MDA	↑ MDA in T2DM with stable ischemic heart disease; No differences in protein carbonyl	No antioxidants; Distributions were comparable in the groups with and without ischemic heart disease for Ca channel blockers, beta blockers, ACE inhibitors/ARB, statins, and acetylsalicylic acid	[70]
T2DM with retinopathy (); T2DM without retinopathy (); Controls ()	Red blood cells	Protein carbonyl	↑ protein carbonyl in T2DM with retinopathy compared to those without and to controls	No vitamin E or C supplementation	[87]
T2DM with normoalbuminuria (); T2DM with microalbuminuria (); T2DM with macroalbuminuria (); Controls ()	Urine	HO1	↑ HO1/creatinine in T2DM with microalbuminuria and macroalbuminuria compared to those with normoalbuminuria and control; ↑ HO1/creatinine in T2DM with normoalbuminuria than controls	Not provided	[111]
T2DM with retinopathy (); T2DM without retinopathy (); Healthy control ()	Serum	PON1	↑ PON1 in controls compared to T2DM; ↑ PON1 in T2DM without retinopathy compared to T2DM with retinopathy	No patient under lipid-lowering therapy; No patient was taking vitamin or mineral supplements or food fortified with vitamins	[105]
T2DM with macrovascular complications (); T2DM without complications (); Controls (); Ethnicity: Indians	Serum	PON1; AGEs	↑ PON1 in controls compared to T2DM; ↑ PON1 in T2DM without complications compared to T2DM with macrovascular complications; ↑ AGE in T2DM compared to controls; ↑ AGE in T2DM with complications compared to those without	No antioxidants; Distribution of antihypertensive and lipid-lowering drugs not provided	[106]

8-iso-PGF2α: 8-iso- prostaglandin F2α ; 8-OHdG: 8-hydroxy-2-deoxyguanosine; 8-oxoGuo: 8-oxo-7,8-dihydroguanosine; AGEs: advanced glycation end products; AOPP: advanced oxidation protein products ;CAT: catalase; FRAP: ferric reducing ability of plasma; GSH: reduced glutathione; GSSG: oxidized glutathione; GPx: glutathione peroxidase; GR: glutathione reductase; HNE: 4-hydroxy-2-nonenal; HO1: heme oxygenase; MDA: malondialdehyde; PON1: paraoxonase 1; SOD: superoxide dismutase; TBARS: thiobarbituric acid reactive substances; TAS: total antioxidant status.