糖尿病并发症与载脂蛋白、自由基的关系

为了解糖尿病血管病变与载脂蛋白（Apo)含量及超氧化物歧化酶（SOD）活性、过氧化脂质（Lpo)的关系。对48例Ⅱ型糖尿病患者和60例同龄的对照组进行检测分析，得知Ⅱ型糖尿病患者的ApoA-1、T-SOD、CuZn-SOD、Mn-SOD明显降低，ApoB、Lpo显著增高，Ⅱ型糖尿病并发症的发生率与ApoA-1水平、ApoB水平、Lpo含量有关。提示Ⅱ型糖尿病时机体存在脂质过氧化作用增强可能是引起并发症的重要原因之一。     

Study of lipid peroxide and lipid profile in diabetes mellitus

The study was designed to find out the correlation between lipid peroxidation, lipoprotein levels to severity and complication of diabetes mellitus. Degree of lipid peroxidation was measured in terms of malondialdehyde (MDA) along with lipid profile and blood glucose in diabetes mellitus. It is categorised into insulin dependent diabetes mellitus (IDDM), non insulin dependent diabetes mellitus (NIDDM) and diabetes mellitus(DM) with complication. Total 112 known diabetic patients and 52 non-diabetic controls were studied. These patients were grouped as per the concentration of fasting blood glucose level i.e. controlled, poorly controlled, and uncontrolled group. There are significant increase in the lipid peroxide (MDA) and lipid profile except HDL cholesterol which is decreased, has been found in all groups as compared to controls In NIDDM group lipid peroxidation was markedly increased than IDDM group and it was higher in DM with complications. Other finding observed was that the level of lipid peroxide increased as per the increase in concentration of blood glucose. The increase lipid peroxidation in the hyperglycemic condition may be explained, as the superoxide dismutase enzyme which is antioxidant becomes inactive due the formation of superoxide radical within the cell. Maximum lipid peroxidation leads to the damage of the tissue and organs which results into complication in diabetic patients. High levels of total cholesterol appear due to increased cholesterol synthesis. The triglyceride levels changes according to the glycemic, control. The increase may be due to overproduction of VLDL-TG. It is concluded that good metabolic control of hyperglycemia will prevent in alteration in peroxidation and the lipid metabolism, which may help in good prognosis and preventing manifestation of vascular and secondary complication in diabetes mellitus.     

Efficacy of topical honey therapy against silver sulphadiazine treatment in burns: A biochemical study

Thermal injury is associated with biochemical changes. The present study was undertaken to investigate relation of oxidative free radical generation and related biochemical parameters in burn trauma. The specific aim was to compare the levels of serum lipid peroxide, Ceruloplasmin and Uric Acid in burn patients during treatment with Silver Sulfadiazine Cream and honey therapy. It is a single blind prospective controlled study involving comparison of biochemical changes after treatment with silver sulfadiazine and honey treatment in burn injury. In burn trauma, there is excessive activity of free radicals at the site of injury. This is reflected in elevated blood levels of Lipid peroxide, Ceruloplasmin & Uric Acid. Honey therapy was was shown to decline the levels of serum Lipid peroxide, while there was mild increments in serum Ceruloplasmin levels whereas there was no significant effect on serum Uric Acid levels as compared to silver sulfadiazine treatment. Honey therapy seems to accelerate the process of healing. It has positive effect in reducing oxidative stressful state in burn trauma than the silver sulfadiazine treatment that results in rapid wound healing.     

老年期痴呆患者血中氧自由基反应的相关指标

为探讨氧自由基与老年痴呆发生发展的关系,分别测定了２７例阿尔采默型霉年期痴呆,２７例多发梗塞性痴呆患者和３７例同龄的健康老年人血清中超氧化物歧化酶及其同功酶活性和ＬＰＯ含量。结果显示：ＳＤＡＴ和ＭＩＤ患者的Ｔ－ＳＯＤ,ＣｕＺｎ－ＳＯＤ活性和ＬＰＯ含量均显著高于同龄的对照组,其中ＣｕＺｎ－ＳＯＤ的异常阳性率最高,达５９．３％;Ｔ－ＳＯＤ,ＣｕＺｎ－ＳＯＤ在不同病程的三组间有显著差异。     

Effect of insulin on serum lipids in relation to nutritional status in diabetics

Serum levels of cholesterol, triglyceride, free fatty acid (FFA) and high density lipoprotein (HDL) cholesterol were studied in 10 undernourished and 10 better nourished diabetic patients at different periods of insulin treatment and in non-diabetic controls. Serum concentrations of cholesterol, triglyceride and FFA were significantly higher in untreated diabetic patients than in control but the elevated lipid levels gradually shifted towards normal on insulin treatment. The HDL cholesterol, on the other hand, was significantly lower in untreated diabetic subjects than those in controls and the HDL cholesterol also gradually modified on insulin therapy. However, the improvement of all the lipid parameters on insulin treatment was somewhat delayed in undernourished compared to those of better nourished diabetics. These results, therefore, suggest that malnutrition interferes with the serum lipid improvement in diabetics on insulin treatment and may make them more prone to develop vascular complications.     

Oxidants and antioxidants in hypoxic ischaemic encephalopathy

In the present study, the role of serum lipid peroxide and serum nitric oxide as oxidants and erythrocytic superoxide dismutase & serum vitamin E as antioxidants were determined in the 50 neonates with hypoxic ischaemic encephalopathy. (HIE) as against 25 healthy neonates as controls 50 patients of HIE were further divided into two groups i. e. mild and moderate HIE patients. All subjects were in the age group of 37–41 weeks of gestation. The levels of serum lipid peroxide, serum nitric oxide and erythrocytic superoxide dismutase were significantly elevated in both groups of neonates with HIE than those of controls (P<0.001), whereas serum vitamin E levels were significantly decreased in both groups of HIE patients than those of controls (P<0.001). A positive correlation was obtained between serum lipid peroxide and erythrocytic superoxide dismutase (r=+0.86). Alterations in the status of oxidants and antioxidants indicate role of free radicals in the development of HIE.     

Altered Kinetics Properties of Erythrocyte Lactate Dehydrogenase in Type II Diabetic Patients and Its Implications for Lactic Acidosis

Recent studies have been noted that the erythrocytes from Type II diabetic patients show significantly altered structural and functional characteristics along with the changed intracellular concentrations of glycolytic intermediates. More recent studies from our laboratory have shown that the activities of enzymes of glycolytic pathway changed significantly in RBCs from Type II diabetic patients. In particular the levels of lactate dehydrogenase (LDH) increased significantly. Lactic acidosis is an established feature of diabetes and LDH plays a crucial role in conversion of pyruvate to lactate and reportedly, the levels of lactate are significantly high which is consistent with our observation on increased levels of LDH. Owing to this background, we examined the role of erythrocyte LDH in lactic acidosis by studying its kinetics properties in Type II diabetic patients. Km, Vmax and apparent catalytic efficiency were determined using pyruvate and NADH as the substrates. With pyruvate as the substrate the Km values were comparable but Vmax increased significantly in the diabetic group. With NADH as the substrate the enzyme activity of the diabetic group resolved in two components as against a single component in the controls. The Apparent Kcat and Kcat/Km values for pyruvate increased in the diabetic group. The Ki for pyruvate increased by two fold for the enzyme from diabetic group with a marginal decrease in Ki for NADH. The observed changes in catalytic attributes are conducive to enable the enzyme to carry the reaction in forward direction towards conversion of pyruvate to lactate leading to lactic acidosis.     

Non enzymatic glycosylation of IgG and their urinary excretion in patients with diabetic nephropathy

Diabetic nephropathy is a major cause of end stage renal disease. Increased excretion of albumin has widely been recognized as an early manifestation of diabetic nephropathy particularly in subjects with diabetes mellitus. However, certain other proteins besides albumin may be excreted in high amount during early phase of diabetic nephropathy. The serum and urinary IgG, Glycosylated hemoglobin, fructosamine and glycosylated IgG were evaluated in the present study. Thirty-two patients of Type 2 Diabetes without any complications, thirty-one patients of Type 2 Diabetes with nephropathy, twenty-six patients of non-diabetic nephropathy and forty normal healthy individuals were enrolled in this study. Subjects were grouped based on their serum creatinine level. Serum IgG, glycosylation of IgG and urinary IgG excretion were increased significantly in diabetic patients compared to healthy controls, which were further increased significantly in chronic renal failure patients with respect to the clinical stage of nephropathy. A positive correlation was observed between glycosylation of IgG and IgG excretion (R²=0.5995, 0.7114 respectively) in diabetic patients without any complications and diabetic nephropathy patients only, suggesting a significant role of IgG glycosylation in the vascular clearances of IgG during diabetic nephropathy.     

Antidyslipidemic Effect of Ocimum sanctum Leaf Extract in Streptozotocin Induced Diabetic Rats

The antidyslipidemic activity of Ocimum sanctum leaf extract was studied in streptozotocin induced diabetic rats. In this model, there was significant increase in plasma markers of diabetic-dyslipidemia following diminution of lipid metabolizing enzymes. Oral administration of leaf extract (500 mg/kg b.w.p.o.) for 15 days resulted in significant decrease in diabetogenic and dyslipidemia parameters; namely blood glucose, glycosylated hemoglobin, lipid peroxide, free fatty acids, small dense low density lipoprotein, lipid and protein components of plasma lipoproteins, adipose and liver. The regulation of lipids was accompanied by stimulation of postheparin lipolytic activity, reactivation of lecithin cholesterol acyl transferase and hepatic lipoprotein lipase enzymes. The results of the present study demonstrated antidyslipidemic and antioxidant activities in leaf extract of O. sanctum which could be used in prevention of diabetic-dyslipidemia and related complications.     

Malabsorption,Orocecal Transit Time and Small Intestinal Bacterial Overgrowth in Type 2 Diabetic Patients: A Connection

Type 2 diabetes mellitus consists of dysfunctions characterized by hyperglycemia and resulting from combination of resistance to insulin action and inadequate insulin secretion. Most of diabetic patients report significant gastrointestinal symptoms. Entire GI tract can be affected by diabetes from oral cavity to large bowel and anorectal region. Proteins, carbohydrates, fats, and most fluids are absorbed in small intestine. Malabsorption may occurs when proper absorption of nutrients does not take place due to bacterial overgrowth or altered gut motility. The present study was planned to measure various malabsorption parameters in type 2 diabetic patients. 175 patients and 175 age and sex matched healthy controls attending Endocrinology Clinic in PGI, Chandigarh were enrolled. Lactose intolerance was measured by using non-invasive lactose hydrogen breath test. Urinary d-xylose and fecal fat were estimated using standard methods. Orocecal transit time and small intestinal bacterial overgrowth were measured using non-invasive lactulose and glucose breath test respectively. Out of 175 diabetic patients enrolled, 87 were males while among 175 healthy subjects 88 were males. SIBO was observed in 14.8 % type 2 diabetic patients and in 2.8 % of controls. There was statistically significant increase (p < 0.002) in OCTT in type 2 diabetic patients compared with controls. OCTT was observed to be more delayed (p < 0.003) in patients who were found to have SIBO than in patients without SIBO. Lactose intolerance was observed in 60 % diabetic patients and 39.4 % in controls. Urinary d-xylose levels were also lower in case of diabetic patients but no significant difference was found in 72 h fecal fat excretion among diabetic patients and controls. Urinary d-xylose and lactose intolerance in SIBO positive type 2 diabetic patients was more severe as compared to SIBO negative diabetic patients. From this study we can conclude that delayed OCTT may have led to SIBO which may have instigated the process of malabsorption among type 2 diabetic patients.     

Effect of herbal hypoglycemic agents on oxidative stress and antioxidant status in diabetic rats

In the present study the antioxidative potential ofMomordica charantia, Azadirachta indica, Allium sativum andOcimum sanctum was assessed in streptozotocin induced diabetic rats. Lipid peroxide levels were also measured in normal, diabetic and treated animals. Malondialdehyde (MDA) levels were significantly higher and antioxidant activity was found low in diabetic groups as compared to the control groups, and significant alteration in both the MDA levels and antioxidant activity was also observed when the above herbal hypoglycemic agents were given to diabetic rats. On the basis of our results we conclude thatM. charantia, A. indica, A. sativum andO. sanctum are not only useful in controlling the lipid peroxide levels but are also helpful in further strengthening the antioxidant potential.     

Dyslipidaemia Associated with Type 2 Diabetics with Micro and Macrovascular Complications among Ghanaians

In this study, differences in lipid levels amongst diabetics with and without complications were assessed to determine lipid disorders that are associated with diabetic complications other than cardiovascular diseases. A Cross sectional study design was employed. The study included 288 diabetics and 108 non diabetics with different types of complications such as hypertension, nephropathy, neuropathy, and retinopathy. The mean serum total cholesterol was higher in patients with complications compared to those without complications and the non-diabetic controls. The normotensive diabetic patients had the lowest total cholesterol among the diabetic patients’ groups (4.65 ± 0.17 mmol/l) compared to the diabetics with hypertension (6.051 ± 0.20 mmol/l), retinopathy (6.26 ± 0.29 mmol/l), neuropathy (5.80 ± 0.17 mmol/l) and nephropathy patients 5.74 ± 0.26 mmol/l (P < 0.05). The prevalence of dyslipidaemia among diabetic subjects was between 19.2 and 84.0%. The study shows that, in addition to macrovascular complications, dyslipidaemia is common in type 2 diabetes mellitus patients with microvascular complications.     

Estimated Creatinine Clearance, Homocysteine and High Sensitivity-C-Reactive Protein Levels Determination for Early Prediction of Nephropathy and Atherosclerosis Risk In Type 2 Diabetic Patients

Type 2 diabetes mellitus (T2D) patients are increased risk for cardiovascular disease (CVD) and chronic kidney disease (CKD). Many studies had demonstrated that CKD is significantly associated with CVD. We aim to indicate the using estimated creatinine clearance (eCrCl), homocysteine (tHcy), and high sensitivity-C-reactive protein (hs-CRP) levels, may have an impact on the interpretation risk for nephropathy and CVD. eCrCl was using the Cockroft-Gault formula, eCrCl levels were stratified according to the Kidney Disease Outcome Quality Initiative definition. We measured serum tHcy, hs-CRP, and the other biochemical variables in 54 T2D patients compared with 40 age matched healthy controls (NDM). T2D patients were significantly lower eCrCl than NDM (P < 0.05). T2D patients also showed significantly higher in tHcy, hs-CRP, and MDA levels than NDM subjects (P < 0.05). The eCrCl was significantly correlated with tHcy and hs-CRP levels in T2D patients (r = −0.504, P < 0.001; r = −0.282, P = 0.047). eCrCl had an impact on interpretation for CKD, especially in T2D patients. Decrease eCrCl concomitant with increased in tHcy, hs-CRP, and MDA levels may present a higher risk for future diabetic nephropathy and CVD.     

Effect of corticosteroids on elevated intracellular sodium, plasma lipid peroxide levels and reduced Na+, K+-ATPase activity in patients of bronchial asthma

In view of several reports that there is a lack of balance in free radicals in case of bronchial asthma (1) the effect of free radicals on cell membrane was studied by estimating the membrane bound protein Na⁺, K⁺-ATPase activity and the intracellular sodium level in patients of bronchial asthma before and after a short course (one week) of oral corticosteroid (prednisolone 0.75–1mg/kg body weight) therapy. Results showed that there is a definite statistically significant rise in free radical level and intracellular sodium level and a significant lowering of Na⁺, K⁺-ATPase activity in case of untreated bronchial asthma. After short course of therapy with oral corticosteroids, the free radical level and intracellular sodium level decreased significantly, together with a significant rise of the Na⁺, K⁺-ATPase activity. Also, a significant negative correlation (r=−0.74) between the lipid peroxide level and the Na⁺,-K⁺-ATPase activity was found in these cases.     

Hypoglycemic, lipid lowering and antioxidant activities in root extract of Anthocephalus indicus in alloxan induced diabetic rats

The present study was carried out to evaluate the hypoglycemic, lipid lowering and antioxidant activities in root extract of Anthocephalus indicus (A indicus) in alloxan inducd diabetic rats. Oral administration of ethanol extract of root (500mg/ kg body weight) for 21 days resulted in significant decrease in the levels of blood glucose, triglycerides, total cholesterol, phospholipid and free fatty acids. Furthermore, the root extract (100–400μg) inhibited the generation of superoxide anions and hydroxyl radicals, in both enzymic and non-enzymic systems, in vitro. The result of the present study demonstrated hypoglycemic, lipid lowering and antioxidant activities in root extract of A indicus, which could help in prevention of diabetic dyslipidemia and related diseases.     

Free radical generation and lipid peroxidation among the dry cell industry workers exposed to carbon

A total of 75 healthy male dry cell industry workers exposed to carbon for 5, 8 and 10 years were compared with 48 controls matched for age and economic status with respect to free radical generation, lipid peroxidation and antioxidant levels. Lymphocytes were seperated from the whole blood and used for estimation of free radicals and antioxidants. Plasma lipid peroxidation products were estimated in the form of thiobarbituric acid reactive substances. Significant increase in free radical generation and lipid peroxidation products were observed in carbon exposed population than controls, and the increase was found to be significant with increase in the period of exposure. The levels of antioxidants i.e., superoxide dismutase (SOD) and catalase were found to decrease with the increase in exposure to carbon in industrial workers. These results suggest that exposure to carbon augments free radical generation, lipid peroxidation and promotes decline in antioxidant enzymes.     

Total antioxidant capacity and lipid peroxidation in liver transplantation

Liver transplantation is an accepted therapy for chronic liver disease patients. These patients generally have low levels of fat soluble vitamins, which have important antioxidant roles. Therefore, this study was undertaken to investigate whether such patients had evidence of antioxidant depletion and increased lipid peroxidation before transplant and whether the subsequent ischemia and reperfusion encountered during liver transplantation have any effect on antioxidant levels and lipid peroxidation. We assessed plasma total antioxidant capacity and serum lipid peroxide in 12 patients undergoing liver transplantation and equal numbers of healthy subjects. We found that before reperfusion, antioxidant levels were significantly decreased along with significantly elevated lipid peroxidation levels as compared with healthy controls (P<0.001). On reperfusion of the liver graft, further declined values of total antioxidant accompanied with highly elevated lipid peroxidation were seen than those of pre-reperfusion samples (P<0.001). This data shows that patients undergoing liver transplant have lowered antioxidant defenses and evidence of free radical damage, which compound the additional insult of reperfusion injury. Therefore antioxidant therapy in these patients before transplantation may ameliorate the effects of reperfusion.     

Antioxidant status in patients with acute myocardial infarction

Free radicals play an important role in the pathogenesis of tissue damage in many clinical disorders, including atherosclerosis. Antioxidants protect the body from damage caused by free radicals. In this study we investigated oxidative stress, antioxidants and inflammatory molecules in patients with acute myocardial infarction. This study has been carried out on 106 patients with acute myocardial infarction, (89 men and 17 females). The control group consisted of 50 healthy, age-matched subjects (40 men and 10 females). Levels of Glucose, lipid profile, glutathione reduced, glutathione peroxidase, Superoxide dismutase, Glycosylated hemoglobin, fibrinogen, vitamin C, vitamin E, malondialdehyde, ceruloplasmin, adenosine deaminase, lysozyme and sialic acid were measured. Malondialdehyde and ceruloplasmin levels were significantly high and antioxidants such as vitamin C, vitamin E, glutathione reduced, glutathione peroxidase and superoxide dismutase were significantly decreased in diabetic and non-diabetic AMI patients as compared with control (p<0.001). Inflammatory markers showed significant rise in diabetic patients as compared with controls. Our results clearly show increased inflammation and oxidative stress in patients with acute myocardial infarction. Depression of antioxidant system in these patients confirms this conclusion.     

Study of Common Genetic Variant S447X in Lipoprotein Lipase and Its Association with Lipids and Lipoproteins in Type 2 Diabetic Patients

Elevated plasma triglyceride and non-esterified fatty acid concentrations may cause insulin resistance and type 2 diabetes mellitus. Lipoprotein lipase (LPL) is a rate-determining enzyme in lipid metabolism. A variant in the LPL gene has been identified which alters the penultimate amino acid Serine at 447 to a stop codon (S447X), and results in a truncated LPL molecule lacking the C-terminal dipeptide Ser–Gly. The present study was designed to evaluate the frequency of S447X variant in the LPL gene and its effect on the lipid and lipoprotein levels in type 2 diabetic subjects. The genotype frequency distributions of type 2 diabetes patients and controls were in Hardy–Weinberg equilibrium. Comparison of the genotype and allelic frequencies of S447X in subjects with type 2 diabetics compared to controls demonstrated no significant difference. In subjects with type 2 diabetics having hypertriglyceridemia (TG ≥ 150 mg/dl) compared to diabetics with TG level <150 mg/dl, significant difference in genotype frequency was found among these groups, while allelic frequency of X was significantly differed. Logistic regression analysis showed the negative association of LPL S447X variant with TG and VLDL cholesterol, while no association with total cholesterol, HDL cholesterol and LDL cholesterol was found. The lipid levels except for HDL cholesterol were found to be significantly lower in carriers for S447X than wild type in diabetes group. The decreased level of TG and TG rich lipoprotein in subjects with SNP S447X in LPL, predicts anti-atherogenic activity of carriers for S447X variant in general population as well as type 2 diabetic patients.     

Antidyslipidemic and Antioxidant Activities of Hibiscus rosa sinensis Root Extract in Alloxan Induced Diabetic Rats

The antidyslipidemic activity of Hibiscus rosa sinensis (Malvaceae) root extract has been studied in alloxan induced diabetic rats. In this model, oral administration of root extract (500 mg/kg bw. p.o.) for 15 days resulted in significant decreased in the levels of blood glucose, plasma lipids and reactivated post heparin lipoprotein lipase activity in alloxan induced diabetic rats. Furthermore, the root extract (50–500 μg) when tested for its antioxidant activity, inhibited the generation of super oxide anions and hydroxyl radicals, in both enzymic and non enzymic systems in vitro. The results of the present study demonstrated antidyslipidemic and antioxidant activities in root extract of H. rosa sinensis which could be used in prevention of diabetic-dyslipidemia and related complications.