Plasma malondialdehyde levels and risk factors for the development of chronic complications in type 2 diabetic patients on insulin therapy.

BACKGROUND: We assessed plasma malondialdehyde (MDA) levels as a biomarker of lipid peroxidation in type 2 diabetic patients on insulin therapy. Associations among MDA levels and some risk factors for the development of chronic complications of diabetes were also evaluated. METHODS: MDA, fasting glucose, fructosamine, urinary albumin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, creatinine, uric acid, serum albumin, lactate, high sensitive C reactive protein (hsCRP), and vitamin E were measured in 53 type 2 diabetic patients and 26 healthy subjects. RESULTS: MDA levels were higher in type 2 diabetes insulin users (12.8 +/- 3.0 micromol/L) and type 2 diabetes no insulin users (10.3 +/- 2.1 micromol/L) compared to control subjects (8.2 +/- 2.1 micromol/L). Fasting glucose, fructosamine, urinary albumin, and hsCRP were higher in all type 2 diabetic patients compared to controls. Significant correlations were observed between MDA and fasting glucose (r = 0.685, p < 0.001), fructosamine (r = 0.526, p < 0.001), urinary albumin (r = 0.516, p < 0.001), and the duration of type 2 diabetes (r = 0.401, p = 0.005). CONCLUSIONS: MDA levels increased in type 2 diabetes, especially in patients on insulin therapy. Chronic hyperglycemia and other biomarkers, such as urinary albumin, were correlated with MDA levels, suggesting the involvement of lipid peroxidation in the pathogenesis of diabetes complications.

Hba(1c) as a tool for the diagnosis of type 2 diabetes: comparison with fasting glucose.

BACKGROUND: Glycated hemoglobin (HbA(1c)) has been proposed for the diagnosis of diabetes. However, several countries have not incorporated its use for this purpose yet and there is no consensus on a suitable cut-off point of HbA(1c) for the diagnosis of diabetes. Thus, the aim of this study was to evaluate the diagnostic characteristics of HbA(1c) and fasting plasma glucose (FPG) for the assessment of type 2 diabetes. METHODS: FPG, HbA(1c), and creatinine levels were assessed in 47 patients with type 2 diabetes and 46 healthy controls. RESULTS: The areas under the curve for HbA(1c) > or = 6.5% and FPG > or = 7.0 mmol/L were 0.97 and 0.92, respectively. HbA(1c). has a slightly higher ability to discriminate type 2 diabetes compared with FPG. The association between HbA(1c) and type 2 diabetes was independent of gender, age, hypertension, smoking, and body mass index. CONCLUSIONS: HbA(1c) was able to be used for the diagnosis of type 2 diabetes.

Association between DNA strand breakage and oxidative, inflammatory and endothelial biomarkers in type 2 diabetes.

Evidence has been presented recently that type 2 diabetes patients have an increased level of DNA damage. This DNA damage could be associated with oxidative, inflammatory, and endothelial biomarkers and could represent a possible indication of injury in the endothelium and induction of inflammation in type 2 diabetes. To confirm this possible association, DNA strand breakage was evaluated by use of the comet assay and its association with oxidative, inflammatory, and endothelial biomarkers in type 2 diabetes patients. A case-control study (30 healthy controls and 32 subjects with type 2 diabetes) was performed to evaluate the association between DNA damage and NOx (nitrate/nitrite), interleukin-6 (IL-6), urinary albumin, fasting glucose, and glycated hemoglobin (HbA(1c)) levels. Type 2 diabetes patients presented higher DNA damage than control subjects, higher levels of IL-6 and urinary albumin, and lower NOx. Significant correlations between DNA damage and NOx (r=-0.303, p=0.016), IL-6 (r=0.845, p<0.001), urinary albumin (r=0.496, p<0.001), fasting glucose (r=0.449, p<0.001), and HbA(1c) (r=0.575, p<0.001) were reported. Our findings showed an increase of DNA damage in type 2 diabetes especially in those patients with poor glycemic control and associations among NOx, IL-6 and urinary albumin levels with DNA damage.

Assessment of urinary γ-glutamyltransferase and alkaline phosphatase for diagnosis of diabetic nephropathy.

BACKGROUND: Urinary biomarkers of tubular damage can be useful for early diagnosis of diabetic nephropathy. Thus, the aim of this study was to test the diagnostic accuracy of the urinary excretion of γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) for diagnosis of diabetic nephropathy (DN). METHODS: Fasting glucose, fructosamine, serum creatinine, glomerular filtration rate (GFR), serum uric acid, serum albumin, and urinary albumin, creatinine, GGT and ALP were assessed in 74 type 2 diabetic patients without nephropathy and 38 type 2 diabetic patients with nephropathy. RESULTS: Urinary GGT and ALP were threefold higher in type 2 diabetic patients with nephropathy. Significant correlations were observed between urinary albumin and GGT (r=0.439, P<0.001) and urinary albumin and ALP (r=0.305, P<0.01). Areas under the curve for GGT and ALP were 0.7696 (P<0.001) and 0.7233 (P<0.001), respectively. At a cut-off value of 72U/g creatinine, GGT demonstrated a sensitivity of 96.0% and a specificity of 52.6%. At a cut-off value of 20U/g creatinine, ALP demonstrated a sensitivity and specificity of 83.8% and 36.8%, respectively. CONCLUSIONS: Urinary GGT and ALP have potential value in the diagnosis of nephropathy in type 2 diabetic patients, but GGT has a slightly higher ability to discriminate nephropathy than ALP.

Ischemia-modified albumin as an oxidative stress biomarker in obesity.

OBJECTIVE: We evaluated the levels of ischemia-modified albumin (IMA) and its association with body mass index (BMI) in patients who are obese. DESIGN AND METHODS: Fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, malondialdehyde, and IMA levels were assessed in 148 subjects. RESULTS: IMA, malondialdehyde, and fasting glucose levels were significantly higher while the HDL cholesterol levels were lower in obese population. CONCLUSIONS: IMA levels increase in overweight and obese subjects.

Association between ischemia modified albumin, inflammation and hyperglycemia in type 2 diabetes mellitus.

OBJECTIVES: The aim of this study was assess serum ischemia modified albumin (IMA) in type 2 diabetes patients and determine its correlation with other risk factors for chronic complications such as inflammation and hyperglycemia. DESIGN AND METHODS: Fasting glucose, glycated albumin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, creatinine, uric acid, albumin, lactic acid, high-sensitivity C-reactive protein (hs-CRP) and IMA were measured in 80 patients with type 2 diabetes and 26 controls. RESULTS: Fasting glucose, glycated albumin, triglycerides, creatinine, IMA and hs-CRP were significantly higher in patients with type 2 diabetes. Correlations were weak but significant between IMA and fasting glucose, IMA and hs-CRP, hs-CRP and HDL cholesterol and hs-CRP and fasting glucose were observed. CONCLUSIONS: We have shown higher levels of IMA and hs-CRP in type 2 diabetes. Hyperglycemia and inflammation reduces the capacity of albumin to bind cobalt, resulting in higher IMA levels.

Human erythrocyte delta-aminolevulinate dehydratase activity and oxidative stress in hemodialysis patients.

BACKGROUND: Oxidative stress is a complicating factor in chronic renal failure, especially in hemodialysis (HD) patients. Also, aluminum intoxication may occur during hemodialysis treatment. Aluminum has been shown to inhibit the sulfhydryl-containing enzyme delta-aminolevulinate dehydratase (ALA-D). Thus, the involvement of -SH oxidation in ALA-D inhibition and its relationship with serum Al levels and lipid peroxidation in HD patients were evaluated. METHODS: Blood ALA-D activity, plasma thiobarbituric acid reactive substances (TBARS), and serum aluminum levels were measured in HD patients (n=37) and healthy controls (n=20). RESULTS: TBARS and Al levels were higher in HD patients than in controls (p<0.01), while ALA-D activity was lower (p<0.05). The sulfhydryl-reducing agent dithiothreitol (DTT) reactivated ALA-D of HD patients, but activity was still lower than that of controls. ALA-D activity was negatively correlated with TBARS (r=-0.63, p<0.01) and aluminum levels (r=-0.31, p<0.05). CONCLUSIONS: Reduced ALA-D activity in HD patients was found to be related to the oxidation of -SH groups essential for enzyme activity. Our results suggest that increased oxidative stress may have contributed to enzyme inhibition in HD patients.