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Retinopathy in Diabetes Mellitus is it due to glycosylation or lipid peroxidation?
Abstract
Aim: To know the leading cause for diabetic retinopathy using simple serological parameters.
Materials and methods: Diabetic patients of age 38-70 with retinopathy were taken as casesand age matched healthy individuals with age of 37-69 was taken as controls for this study. Fasting and postprandial blood samples were collected for analyzing BG, HbA1C, Lipid parameters, MDA and Vitamin-C. SPSS Software 17 was used for statistical analysis.
Results: The results of cases were compared with a control, shows highly significance for each parameter. Vitamin- C showed significant negative correlation with the LDL and MDA. The LDL showed a significant positive correlation with HbA1C and MDA. TC and LDL showed significant positive correlation with MDA and Significant Negative correlation with the Vitamin-C.
Conclusion: Hyperglycemia is the cause for glycosylation which independently provokes lipid peroxidation by decreasing the antioxidant status that neutralize free radicals, so it is the glycosylation and lipid peroxidation plays a main role in the development of retinopathy in diabetes mellitus.
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Non-insulin dependent diabetes mellitus (NIDDM) is the most rapidly growing chronic metabolic disorder in the world. With advancement in the age and duration of diabetes there is a gradual tendency for the level of blood sugar to rise along with a subsequent increase in the HbA1c as well as in the fasting insulin level. Whether this is an aging process or increased frequency of diabetes is still controversial. The correlation between glucose and insulin sensitivity is consistent with the idea that the degree of chronic hyperglycemia is a cause of excessive insulin resistance in type 2 diabetes, i.e. the insulin resistance which characterizes type 2 diabetes but not nondiabetic subjects matched for age, gender, family history and duration of diabetes. The study comprised a total of 76 subjects out of which 30 were normal, non-diabetic persons and the rest 46 were diabetics with different duration of time in years, after being diagnosed diabetic. Data was analyzed after dividing the subjects into four groups-Group 1 comprised of one year old diabetics, Group 2 was made up of those, who had diabetes, for the past 2-5 years, Group 3 included patients who were diabetic since more than 5 years and Group 4 included non-diabetics as the normal control group. The results obtained indicated that the HbA1c levels showed a significant increase with the duration of diabetes as well as the insulin level showed a significant correlation after adjustment for age, sex and duration of diabetes.
Patients with type 2 diabetes mellitus (DM) are subject to chronic oxidative stress. Lipid peroxidation of cellular structures is an important process in atherosclerosis and late complications of DM. Malondialdehyde (MDA) plays a major role in low-density lipoprotein modification. This study aimed to evaluate whether DM duration is an independent predictor of serum MDA levels.
A total of 120 patients with type 2 DM (60 with DM duration of 120 months or less and 60, with more than 120 months) and 45 gender- and body mass index (BMI)-matched healthy adults were studied. Fasting blood samples were obtained and the fasting plasma glucose (FPG), cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, creatinine, haemoglobin A1c (HbA1c), extracellular superoxide dismutase (EC-SOD) and MDA levels were measured.
The MDA level was significantly higher in DM patients than in controls (p is less than 0.001), and in those with DM duration more than 120 months than those with DM duration of 120 months or less (p is less than 0.001). The level of MDA was significantly correlated with DM duration (correlation coefficient 0.254, p is less than 0.01) and the EC-SOD level (correlation coefficient 0.299, p is less than 0.001). In multivariate regression analysis, the association between MDA and DM duration remained significant after adjustments were made for age, gender, BMI, FPG, HbA1c, EC-SOD, plasma creatinine and anti-diabetic medications (p is less than 0.05).
The results of this study suggest that in type 2 DM patients, DM duration is independently associated with increased levels of lipid peroxidation. Longitudinal studies are required to confirm these results.
Oxidative stress is involved in the pathophysiology of diabetes mellitus.
In the present study, 68 patients with type 2 diabetes mellitus and 31 clinically healthy individuals were evaluated. The patients were divided into two groups. Group 1 included 29 patients without diabetic complications and group 2 consisted of 39 patients with diabetic complications. Erythrocyte glutathione, superoxide dismutase, and thiobarbituric acid-reactive substance levels as well as plasma antioxidant vitamins C and E, and serum total glutathione-S-transferase, ceruloplasmin, and protein thiols were estimated by using spectro-photometer.
A significant decrease of erythrocyte glutathione was observed in group 1 when compared with the controls. Thiols decreased in group 2. An increase in glutathione-S-transferase, ceruloplasmin, superoxide dismutase, and vitamins C and E levels was noted in patients with diabetes mellitus. Thiobarbituric acid-reactive substance levels decreased in group 1 but increased in group 2 when compared with the controls.
In the present study, tendency of most of the antioxidants to rise in diabetes could probably be due to an adaptive response to the pro-oxidant milieu of the diabetic state. Hence, we suggest that supplementation with dietary antioxidants especially antioxidant vitamins accompanied by change in lifestyle might help to reduce damage brought about by free radical toxicity in diabetes mellitus.
Vitamin C exists in two major forms. The charged form, ascorbic acid (AA), is taken up into cells via sodium-dependent facilitated transport. The uncharged form, dehydroascorbate (DHA), enters cells via glucose transporters (GLUT) and is then converted back to AA within these cells. Cell types such as certain endothelial and epithelial cells as well as neurons that are particularly prone to damage during diabetes tend to be those that appear to be dependent on GLUT transport of DHA rather than sodium-dependent AA uptake. We hypothesize that diabetic neuropathies, nephropathies and retinopathies develop in part by exclusion of DHA uptake by GLUT transporters when blood glucose levels rise above normal. AA plays a central role in the antioxidant defense system. Exclusion of DHA from cells by hyperglycemia would deprive the cells of the central antioxidant, worsening the hyperglycemia-induced oxidative stress level. Moreover, AA participates in many cellular oxidation-reduction reactions including hydroxylation of polypeptide lysine and proline residues and dopamine that are required for collagen production and metabolism and storage of catecholamines in neurons. Increase in the oxidative stress level and metabolic perturbations can be expected in any tissue or cell type that relies exclusively or mainly on GLUT for co-transport of glucose and DHA including neurons, epithelial cells, and vascular tissues. On the other hand, since DHA represents a significant proportion of total serum ascorbate, by increasing total plasma ascorbate concentrations during hyperglycemia, it should be possible to correct the increase in the oxidative stress level and metabolic perturbations, thereby sparing diabetic patients many of their complications.
Increased oxidative stress might play an important role in the initiation and progression of diabetic complications. The present study has been undertaken to investigate whether there is any relationship between retinopathy degree and leukocyte superoxide dismutase (SOD) and catalase (CAT) activities and lipid peroxidation (LPO) in diabetic individuals with type 2 diabetic retinopathy. Patients were groupped with respect to the degree of retinopathy. Leukocyte malondialdehyde (MDA) levels, and SOD and CAT activities were measured in patients with type 2 diabetes mellitus (n=41) and nondiabetic healthy controls (n=23). Leukocyte LPO of the type 2 diabetic patients with retinopathy was significantly increased (p < 0.001), whereas SOD and CAT activities were decreased (p<0.001 and p<0.001, respectively) compared to those of controls. MDA concentrations rose while SOD and CAT activities fell with increasing severity of diabetic retinopathy, altough there was no significant difference in comprasion of the parameters mentioned above between the diabetic patients with and without retinopathy. Our results show that leukocytes in patients with type 2 diabetic retinopathy are affected by oxidative stress which might be contribute to pathogenesis of diabetic retinopathy. Prospective studies are needed to evaulate the relationship between the leukocyte antioxidants status and DR.
Observation shows diabetic patients to be more prone to oxidative stress because of hyperglycemia. The elevation of free radical production by this hyperglycemic production may exacerbate cardiovascular complication in diabetes. This study aims to investigate the oxidative stress related parameters in type 2 DM. Since the effects of glycemic control and cardiovascular complications in DM on these parameters has been not fully determined, the comparison between plasma MDA (malondialdehyde) and antioxidant nutrients with their age-matched normal healthy group may be used to determine the susceptibility of oxidative stress in this type of DM.
MDA and antioxidant nutrients (vitamin A, C, E and beta-carotene) were analyzed in plasma of 19 subjects with poorly controlled type 2 DM (fasting plasma glucose [FPG] > 180 mg/dl), 26 subjects with fairly controlled type 2 DM (FPG < or = 180 mg/dl), and 20 subjects with type 2 DM complicated coronary heart disease (CHD) who were matched for age and gender. Twenty healthy subjects with normal plasma glucose level (FPG < 110 mg/dl) and matched for age and gender served as a control group. In all groups of DM these oxidative stress parameters were compared to a normal group.
The plasma MDA levels were significantly higher in all types of DM compared to age-matched normal control. Plasma antioxidant vitamin C and E significantly lower only in poorly controlled and CHD complicated type 2 DM, respectively. The mean of plasma vitamin E level was lowest in type 2 DM complicated with CHD. No significant differences in both plasma vitamin A and beta-carotene were noted between any types of DM and age-matched normal healthy group. The positive correlation between MDA and FPG was demonstrated in most group of patients with their normal subjects except in fairly controlled type 2 DM and negative correlation between vitamin E and FPG was also demonstrated in type 2 DM with CHD.
These findings suggested that diabetic patients were susceptible to oxidative stress and higher plasma glucose level had an association with free radical-mediated lipid peroxidation. The lowest level of vitamin E in type 2 DM complicated with CHD indicated that oxidative stress played an important role in cardiovascular complication and vitamin E supplementation may be necessary for treatment and prevention in this group of diabetics.
In diabetic patients, persistence of hyperglycemia has been reported as a cause of increased production of oxy- gen free radicals. Hyperglycemia could induce oxidative stress and become the main factor for predisposing the complica- tions in diabetes. The study is being aimed to find out the status of lipid peroxidation product i.e. malondialdehyde (MDA) and antioxidant enzymes (AOEs) such as glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) which might be helpful in risk assessment of various complications of diabetes mellitus. The study included 300 subjects (50-70yrs) out of which 150 patients were non insulin dependent diabetes mellitus (NIDDM) with micro vascular complications and 150 age matched healthy controls. The status of fasting blood sugar (FBS), reduced glutathione (GSH), GPx, GR, CAT, SOD and MDA were determined. Our results showed significant increase (p< 0.001) in FBS, CAT and MDA while GSH, GPx, GR and SOD were found decreased significantly (p< 0.001). The data suggest that alteration in antioxidant status and MDA may help to predict the risk of various micro vascular complications of diabetes mellitus.
SUMMARY The oxidation process is one of the most important natural processes. Oxidative change in retina is believed to be an important process in the pathogenesis of diabetic retinopathy. In the present study, the oxidation flux change was assessed in such cases. The simulation test to determine the oxidation flux change based on nanomedicine technique was used. Of interest, no flux change could be detected. The main pathogenesis should be direct injury of membrane structure by other processes. Therefore, study results support the concept according to which the oxidation flux change in basement membrane does not exist.
Hyperglycemia and dyslipidemia in diabetes mellitus induce increased lipid peroxidation and peroxyl radical formation, an important mechanism in genesis of microangiopathy. We took up a study on oxidative stress, measured by plasma MDA and antioxidant vitamin status in type - 2 DM patients with and without retinopathy and compared them with a control non-diabetic group. Lipid peroxidation marker MDA was significantly elevated (p < 0.001) in both the diabetic groups whereas, serum vitamin E and vitamin C registered a significant fall (p<0.001) as compared to controls. Our correlation study revealed a significant positive association between plasma MDA with both fasting and 2hr post prandial plasma glucose (r=0.81, p < 0.001, r=0.92, p <0.001) suggesting the role of hyperglycemia in free radical production. Plasma MDA also depicted significant positive relation (p< 0.001) with all lipid parameters except serum HDLc pointing the role of dyslipidemia towards lipid peroxidation. Plasma MDA level was also found to be negatively correlated with both the vitamins (p<0.001, p<0.001) in the study group explaining their protective consumption in the oxidative process prevailing in diabetic retinopathy.
Advanced age is associated with an accumulation of free radical damage, which leads to physiological and clinical modifications. Age related changes resulting from free radical reactions include increasing levels of lipid peroxides, alterations in enzyme activities and greater osmotic fragility. The present study was conducted to estimate the level of lipid peroxidation product-Malondialdehyde and antioxidants Catalase and Glutathione in elderly people. An increase in lipid peroxidation and decrease in antioxidants was observed in normal elderly people. Highly significant increase in MDA and decrease in antioxidants was observed in elderly people when complicated with diabetes and hypertension. Supplementation of antioxidants may prevent further oxidative injury in elderly people.
Patients with type II Diabetes Mellitus (NIDDM) are more prone to Ischaemic Heart Disease (IHD). Although, oxygen free radicals are known to contribute to the development of IHD, conflicting reports are available regarding the antioxidant status in patients of NIDDM complicated with IHD. This study was undertaken to investigate the oxidative status in patients of NIDDM and to assess their correlation with plasma glucose, glycosylated haemoglobin and duration of diabetes. The levels of malondialdehyde were significantly increased where as levels of superoxide dismutase, Glutathione peroxidase and vitamin C were significantly decreased in diabetics without complications and non-diabetics with IHD when compared with the controls. The levels of malondialdehyde and Glutathione peroxidase were significantly increased where as levels of superoxide dismutase and vitamin C were significantly decreased in diabetics with IHD when compared with diabetics without complications and non-diabetics with IHD. The implications of the results are discussed.
The present study was undertaken in 100 subjects, 30 diabetics without complication (group I), 40 diabetics with retinopathy (group II) and 30 non diabetic as normal control group (group III). Blood sugar levels, magnesium, cholesterol and triglyceride were analyzed from plasma and serum. The results were correlated with degree of diabetic control from the levels of glycosylated hemoglobin. Serum magnesium levels in group II were found to be significantly lowered than in group I. There was also significant difference in magnesium levels of group I and group III. We found a significant correlation between the glycosylated hemoglobin and magnesium levels in our study.
The results also indicate that the patients with diabetic retinopathy showed significant rise in serum cholesterol and triglyceride. Probably hypomagnesemia and increased serum cholesterol and triglyceride levels are responsible for microvascular changes in diabetes leading to retinopathy. The purpose of this study was thus to gather information about the degree of control of diabetes and magnesium status.
The role of oxidant stress in the causation of chronic tissue damage is being increasingly recognized. Oxidant stress is usually countered by abundant supply of antioxidants. If concomitant antioxidant deficiency occurs, oxidant stress may produce tissue damage. We took up a study on antioxidant status in non-insulin dependent diabetes mellitus (NIDDM) patients with and without retinopathy and compared them with a control non-diabetic group. The levels of superoxide dismutase (SOD) were significantly reduced in all diabetic patients, i.e., those with and without retinopathy. However, the lowest levels were found in the diabetic patients with retinopathy. Vitamin E and vitamin C levels were also markedly lower in the diabetic patients. There was a paradoxical rise in the catalase and glutathione peroxidase (GPx) in the diabetic patients with retinopathy. This may be a compensatory mechanism by the body to prevent tissue damage by increasing the levels of the two alternative antioxidant enzymes.
Hyperglycemia is considered a primary cause of diabetic vascular complications and is associated with oxidative stress, impaired trace element and lipid metabolism as well as pancreatic enzyme abnormalities. The role of trace elements in some of the metabolic dysfunctions and their contributions in the development of vascular complications is not clear. Therefore, the present study investigates the relationship among diabetes mellitus, trace elements status, advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), lipid profiles, antioxidant status, nitric oxide and pancreatic amylase activity in the sera of 55 non-insulin-dependent diabetes mellitus (NIDDM; 35 with microvascular complications and 20 without vascular complications), 40 insulin-dependent diabetes mellitus (IDDM; 25 with microvascular and 15 without microvascular complications), and 20 nondiabetic healthy control subjects. The mean age of the diabetic patients was similar to that of control. The mean duration of the disease was 11.8 +/- 6.8 years (3-27 years) in IDDM and 7.1 +/- 4.7 years (1-15 years) in NIDDM.
Plasma Cu, Zn, Mg, Ca, thiobarbituric acid-reactive substance (i.e. malondialdehyde; MDA), nitric oxide (NO), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), ceruloplasmin (Cp) and amylase activities as well as AOPP were assessed spectrophotometrically whereas AGEs were estimated spectrofluorometrically in two types of diabetes mellitus (DM) as well as control subjects of matched sex and ages.
SOD, CAT and Cp activities were decreased whereas serum alpha-amylase activity was increased in two types of DM in comparison to the corresponding activities of the control subjects. The plasma levels of MDA, NO and Cu were increased but GSH, Zn, Mg and Ca levels were significantly diminished in diabetic patients as compared to the controls. The averages of total cholesterol (CHOL), triglyceride (TG) and low-density lipoprotein-cholesterol (LDLc) were higher in both types of diabetes mellitus in comparison to the control subjects. The mean value of high-density lipoprotein-cholesterol (HDLc) was lower in both types of diabetes mellitus. Further, the mean values of AGEs and AOPP were elevated in diabetic patients vs. control. These parameters are significantly higher in NIDDM patients when compared to the IDDM subjects. Slight but not significant differences in these parameters were observed in patients with diabetic complications when compared to that of without diabetic complications.
These findings may explain the role of impaired trace element status, defect of antioxidants and increased of AGE and AOPP in the pathogenesis of pancreas and the vascular complications of diabetes mellitus. Oxidative stress is increased in both types of DM, but it is more in NIDDM patients than in IDDM subjects. In addition, oxidative stress also plays an important role in the formation of AGEs and AOPP in DM.
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