Cohort study of predictive value of urinary albumin excretion for atherosclerotic vascular disease in patients with insulin dependent diabetes.

OBJECTIVE: To examine whether slightly elevated urinary albumin excretion precedes development of atherosclerotic vascular disease in patients with insulin dependent diabetes independently of conventional atherogenic risk factors and of diabetic nephropathy. DESIGN: Cohort study with 11 year follow up. SETTING: Diabetes centre in Denmark. SUBJECTS: 259 patients aged 19-51 with insulin dependent diabetes of 6-34 years'' duration and without atherosclerotic vascular disease or diabetic nephropathy at baseline. MAIN OUTCOME MEASURES: Baseline variables: urinary albumin excretion, blood pressure, smoking habits, and serum concentrations of total cholesterol, high density lipoprotein cholesterol, sialic acid, and von Willebrand factor. End point: atherosclerotic vascular disease assessed by death certificates, mailed questionnaires, and hospital records. RESULTS: Thirty patients developed atherosclerotic vascular disease during follow up of 2457 person year. Elevated urinary albumin excretion was significantly predictive of atherosclerotic vascular disease (hazard ratio 1.06 (95% confidence interval 1.02 to 1.18) per 5 mg increase in 24 hour urinary albumin excretion, P = 0.002). Predictive effect was independent of age; sex; blood pressure; smoking; serum concentrations of total cholesterol, high density lipoprotein cholesterol, sialic acid, and von Willebrand factor; level of haemoglobin A(lc); insulin dose, duration of diabetes, and diabetic nephropathy (hazard ratio 1.04 (1.01 to 1.08) per 5 mg increase     

Proliferative diabetic retinopathy is associated with a low level of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor. a pilot study.

Retinopathy is the most common microvascular diabetes complication and represents a major threat to the eyesight. The aim of this study was to address the role of pro- and anti-angiogenic molecules in diabetic retinopathy in the aqueous humor of the eye. Aqueous humor was collected at cataract surgery from 19 diabetic patients and from 13 age- and sex-matched normoglycemic controls. Levels of pro-angiogenic vascular endothelial growth factor (VEGF) and angiogenic inhibitor pigment epithelium-derived factor (PEDF) were determined. Angiogenic activity of the aqueous humor was quantified by measuring its effect on the migration of capillary endothelial cells. In the aqueous fluid, VEGF levels were increased in diabetics (mean values: 501 vs. 367 pg/ml; p = 0.05), compared to controls. PEDF was found to be decreased in diabetics (mean values: 2080 vs. 5780 ng/ml; p = 0.04) compared to controls. In seven diabetic patients with proliferative retinopathy, the most profound finding was a significant decrease of the PEDF level (mean value: 237 ng/ml), whereas VEGF levels were comparable to diabetic patients without proliferation (mean value: 3153; p = 0.003). Angiogenic activity in samples of patients from the control group was generally inhibitory due to PEDF, and inhibition was blocked by neutralizing antibodies to PEDF. Likewise, in diabetics without proliferation, angiogenic activity was also blocked by antibodies to PEDF. We will demonstrate here that the level of the natural ocular anti-angiogenic agent PEDF is inversely associated with proliferative retinopathy. PEDF is an important negative regulator of angiogenic activity of aqueous humor. Our data may have implications for the development of novel regimens for diabetic retinopathy.     

Platelet spreading in diabetes mellitus

In 162 test persons divided into healthy control persons and diabetics of type I and type II the thrombocyte spreading was investigated according to the method of Breddin. Age, sex, degree of seriousness of retinopathy, duration of diseases, present level of blood sugar and HbA1 concentration were taken into account. Spread thrombocyte forms were increasingly found in old age, in diabetics of both types and a close relation to the extent of retinopathy was evident. As diabetic retinopathy became evident and with growing degree of seriousness, spread forms of thrombocytes were increasingly found, so that the increased spreading capacity may be interpreted as a disturbed metabolic and blood vessel situation in diabetes mellitus.     

Red blood cell deformability index in diabetic retinopathy

In order to investigate the relationship between haemorheological disturbances and diabetic microangiopathy we have studied the red blood cell deformability index (RBCD-index) by means of a filtration technique in 69 diabetics, aged 49-83 years, and in 40 non diabetic healthy controls (group A) of respective age and sex. The diabetics were classified into the following groups, according to the findings of a thorough clinical and laboratory investigation. Twenty patients (group B) were free of vascular complications, whereas 9 (group C) suffered from background retinopathy, 27 (group D) background retinopathy and ischaemic cardiopathy or peripheral arterial occlusive disease and 13 (group E) of proliferative retinopathy with diffuse micro- and macroangiopathy. The RBCD-index was significantly (P less than 0.001) decreased in diabetics with retinopathy compared to the diabetic and non diabetic controls. The lowest RBCD-index was observed in diabetics with proliferative retinopathy and in those with diffuse micro- and macrovascular complications (RBCD-index, means +/- SDM ml/min: A 0.68 +/- 0.15; B 0.64 +/- 0.08; C 0.60 +/- 0.08; D 0.49 +/- 0.09; E 0.48 +/- 0.09). These findings suggest that the RBCD is impaired in diabetics with retinopathy, especially in those with severe vascular complications, and that this abnormal rheological behavior of erythrocytes can be found even in the early stages of diabetic microangiopathy.     

Advanced glycation end-products and the progress of diabetic vascular complications

Epidemiological studies have confirmed that hyperglycemia is the most important factor in the onset and progress of vascular complications, both in Type 1 and 2 diabetes mellitus. The formation of advanced glycation end-products (AGEs) correlates with glycemic control. The AGE hypothesis proposes that accelerated chemical modification of proteins by glucose during hyperglycemia contributes to the pathogenesis of diabetic complications including nephropathy, retinopathy, neuropathy and atherosclerosis. Recent studies have shown that increased formation of serum AGEs exists in diabetic children and adolescents with or without vascular complications. Furthermore, the presence of diabetic complications in children correlates with elevated serum AGEs. The level of serum AGEs could be considered as a marker of later developments of vascular complications in children with Type 1 and 2 diabetes mellitus. The careful metabolic monitoring of young diabetics together with monitoring of serum AGEs can provide useful information about impending AGE-related diabetic complications. It is becoming clear that anti-AGE strategies may play an important role in the treatment of young and older diabetic patients. Several potential drug candidates such as AGE inhibitors have been reported recently.     

Low phospholipid arachidonic acid values in diabetic platelets.

Platelet aggregation is enhanced in diabetes mellitus, and platelets may be implicated in the pathogenesis of diabetic angiopathy. Increased platelet aggregation is probably mediated by the production of the proaggregatory prostaglandin thromboxane, which is synthesised from arachidonic acid (C20:4) by the action of the platelet enzymes cyclo-oxygenase and thromboxane synthetase. The fatty acid composition of platelet phospholipid was measured in 20 normal controls, 10 insulin-treated diabetics with no or minimal retinopathy, and 10 insulin-treated diabetics with proliferative retinopathy. The percentage of arachidonic acid was significantly higher in controls (mean 22.6%) than in the diabetics with no or minimal retinopathy (mean 18.5%; p less than 0.025) and the diabetics with proliferative retinopathy (mean 14.6%; p less than 0.001). The percentage of linoleic acid was lower in controls (mean 8.9%) than in the diabetics with no or minimal retinopathy (mean 12.6%; p less than 0.01) and diabetics with proliferative retinopathy (mean 13.1%; p less than 0.001). The mean percentage of linolenic acid was significantly lower in the diabetics with proliferative retinopathy (2.7%) than in the normal control group (4.4%; p less than 0.01). A significant negative correlation was found between the percentages of arachidonic acid and glycosylated haemoglobin (Rs = -0.58; p less than 0.001). A significant positive correlation was found between linoleic acid and the percentage of glycosylated haemoglobin (Rs = 0.51; p less than 0.01). The reciprocal correlation between percentages of arachidonic acid and glycosylated haemoglobin suggests that diabetic control may influence thromboxane release and platelet activity directly and that low percentages of arachidonic acid reflect the increased degree of in-vivo activation.     

Progression of diabetic retinopathy and changes in serum insulin-like growth factor I (IGF I) during continuous subcutaneous insulin infusion (CSII)

The rise in serum IGF I concentration during continuous subcutaneous insulin infusion (CSII) may be a contributory factor in the deterioration of diabetic retinopathy that sometimes occurs during this treatment but the relation of serum levels to the severity of retinopathy has not been previously studied. In twelve non-obese insulin dependent diabetics (age range: 22-41 yrs) with mean +/- SD duration of diabetes: 14.8 +/- 4.7 yrs, serum IGF I concentration, HbA1 and retinopathy score were estimated prospectively over twelve months following the institution of CSII therapy. After four months of treatment, eight patients showed deterioration of retinopathy by at least one level of severity. Serum IGF I concentration rose from a mean +/- SEM of 155 +/- 17.7 micrograms/l at entry to 199 +/- 23.1 micrograms/l at four months and by twelve months had returned to near initial values 163 +/- 17.4 micrograms/l. There was however, no significant correlation between retinopathy score and serum IGF I level by analysis of variance for the whole group, or in the group of diabetics whose retinopathy deteriorated. The rise in IGF I concentration over the first four months and subsequent decline in IGF I values over the next eight months was inversely related to HbA1 concentration (r = -0.58; P less than 0.05). One patient with early ischaemic retinopathy on entry, experienced a marked rise in serum IGF I corresponding to a rapid tightening of glycaemic control. At four months she developed florid proliferative changes requiring panretinal laser therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between thromboxane/prostacyclin ratio and diabetic vascular complications.

To elucidate the relationship between the thromboxane A2/prostacyclin (TXA2/PGI2) ratio and diabetic complications, the levels of 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1alpha, the urinary metabolites of thromboxane A2 and prostacyclin, were measured in diabetics by gas chromatography/selected ion monitoring. We compared the TXA2/PGI2 ratio in healthy volunteers and diabetics. The TXA2/PGI2 ratio of diabetics was significantly higher than that of healthy volunteers and we could reconfirm the hypercoagulable condition in diabetics. We also investigated the difference of TXA2/PGI2 levels in diabetics with retinopathy and neuropathy. The TXA2/PGI2 ratio of diabetics with retinopathy showed significantly higher level than without retinopathy. However, the TXA2/PGI2 ratio of diabetics with neuropathy was the same as without neuropathy. These results suggest that the TXA2/PGI2 ratio reflects the pathological conditions of diabetes, especially the change of vasculature. The monitoring and improvement of TXA2/PGI2 ratio could be useful for the prevention of diabetic vascular complications.     

Serum sialic acid levels and selected mineral status in patients with type 2 diabetes mellitus

The aim of the present study was to investigate whether altered serum total sialic acid (TSA), lipid-associated sialic acid (LSA), copper (Cu), manganese (Mn), zinc (Zn), chromium (Cr), iron (Fe), and magnesium (Mg) levels had an interactive connection with diabetes and also whether they were correlated with each other in diabetic patients. Two study groups (control and type 2 diabetic subjects) were included. Two hundred patients (108 female and 92 male), diagnosed and treated for type 2 diabetes in the Yuzuncu Yil University Hospital (Van, Turkey), were selected consecutively to represent type 2 diabetic patients. Fifty healthy individuals (29 female and 21 male) served as the control group matched for age, sex, body mass index, and smoking status were selected from hospital staff and other outpatient clinics. All participants had not taken vitamin or mineral supplements for at least 2 wk before sampling. Blood samples were drawn after an overnight fasting in both groups for the determination of serum glucose, TSA, LSA, Cu, Zn, Mn, Cr, Fe, and Mg. It was found that diabetics had higher TSA, LSA, Fe, Mn, Fe/Zn, and Cu/Zn levels, and lower Zn and Mg levels than those of controls. Although, Cu levels were higher, and Cr levels were lower in total and male diabetic patients, they were not different in female diabetic patients than in controls. The Cu/Fe ratio was lower in total and female diabetic patients, but not different in male diabetic patients than controls. The Zn/Cr ratio, on the other hand, was not different in diabetics than in controls. There was only a positive correlation between Fe-Mn levels in male diabetic patients. There was a negative correlation in LSA-Mn, Fe-Cu, Cu-Fe/Zn, and Mn-Cu/Zn levels in total diabetic patients. There was a positive correlation in TSA-Cr, TSA-Mg, LSA-Cu/Fe, LSA-Zn/Cr levels, and a negative correlation in TSA-Cu/Zn, LSA-Mn, Fe-Cu, Mn-Cu, Cu-Fe/Zn, Fe-cholesterol, and Cr-cholesterol in female diabetic patients. Our results showed that TSA, LSA, and selected minerals have interactive connections with diabetes mellitus (DM). There are also many sex-related positive or negative correlations between the altered parameters in diabetic patients. These parameters might be used as diagnostic index in patients with DM.     

Plasma non-cholesterol sterols in patients with non-insulin dependent diabetes mellitus.

Plasma plant sterol concentrations (an index of cholesterol absorption efficiency) and plasma lathosterol concentration (an index of cholesterol synthesis rate) were measured in 52 patients with non-insulin dependent diabetes mellitus (NIDDM) and 36 non-diabetic controls. Plasma plant sterol concentrations were significantly (P less than 0.01) lower in diabetic patients (campesterol: men -36%, women -48%; betasitosterol: men -35%, women -42%). Fasting serum insulin levels were inversely correlated with plasma plant sterol concentrations in diabetic patients (campesterol: r = -0.347, P = 0.012; betasitosterol: r = -0.345, P = 0.012) and in non-diabetic men (campesterol: r = -0.578, P = 0.039; betasitosterol: r = -0.702, P = 0.008). Serum insulin levels were also correlated significantly with plasma lathosterol concentration in diabetic patients (r = 0.295, P = 0.034). The results of this study suggest that absorption of plant sterols and possibly cholesterol from the diet may be reduced in hyperinsulinemic diabetics.     

Renal transplantation in diabetics nephropathy.

Forty diabetics who had developed end-stage renal failure from diabetic nephropathy and underwent renal transplantation have been followed up from one to six years. After one and two years 63% and 42% survived (45% and 33% respectively with functioning kidneys). Older patients, those with coronary and peripheral vascular disease, and those with severe neuropathy are prone to higher postoperative morbidity and mortality. The presence of advanced retinopathy, on the other hand, does not appear to influence the outcome.     

A comparison of the levels of hepatocyte growth factor in serum in patients with type 1 diabetes mellitus with different stages of diabetic retinopathy

INTRODUCTION: The aim of this study was to evaluate the blood concentration of hepatocyte growth factor (HGF) in patients at various stages of retinopathy. We hypothesised that the high level of HGF found in diabetic patients may be an important marker of retinopathy progression and that HGF level may be an index of the risk of proliferative retinopathy. MATERIAL AND METHODS: The participants in the study were 76 patients with type 1 diabetes mellitus. Of these, 35 patients were without retinopathy and formed Group 1. Of the remaining 41 patients with retinopathy, 20 patients had non-proliferative diabetic retinopathy (NPDR) and formed Group 2, while 21 patients had proliferative diabetic retinopathy (PDR) and formed Group 3. We evaluated the concentration of HGF In the peripheral blood by an enzyme-linked immunosorbent assay. RESULTS: Mean serum concentrations of HGF in the control group were significantly lower than in the type 1 diabetic patients. We found a significant increase in HGF serum concentrations in diabetic patients with PDR compared with the control group. Mean serum HGF concentrations were significantly higher in diabetic subjects with PDR than in diabetic patients without retinopathy. CONCLUSION: HGF concentration is increased in patients with type 1 diabetes mellitus with proliferative retinopathy, and concentrations increase with the progression of retinopathy, suggesting that HGF plays a role in the pathogenesis of proliferative diabetic retinopathy.     

Polymorphisms of interleukin-8 and -18 genes and diabetic retinopathy

We evaluated possible roles of interleukin-8 gene polymorphisms (1633T/C-rs2227543, 251A/T-rs4073) and interleukin-18 gene polymorphisms (-607C/A-rs1946518, -137G/C-rs187238) in the development of diabetic retinopathy (DR) in Caucasians with type 2 diabetes. 271 patients with DR and 113 without diabetic retinopathy were enrolled in this cross-sectional study. We did not observe an association between either interleukin-8 gene polymorphisms (1633T/C, 251A/T) or interleukin-18 gene polymorphisms (-607C/A, -137G/C) and diabetic retinopathy in Caucasians with type 2 diabetes. We did not find statistically significant differences in interleukin-8 serum levels between diabetics with the TT and AA genotype and those with other genotypes. The interleukin-18 serum levels between diabetics with the CC genotype of the -607C/A polymorphism and those with other genotypes (AA, AC) were not significantly different. Moreover, we did not observe a statistically significant effect of the tested polymorphisms of either interleukin-8 or interleukin-18 genes on serum levels in diabetics. In conclusion, our study indicates that the examined polymorphisms of interleukin-8 (1633T/C, 251A/T) and interleukin-18 (-607C/A or the -137G/C) genes are not genetic risk factors for diabetic retinopathy. Therefore, they may not be used as genetic markers for diabetic retinopathy in Caucasians with type 2 diabetes.     

Suppression of GLUT1; A new strategy to prevent diabetic complications

High blood glucose results in high glucose levels in retina, because GLUT1, the sole glucose transporter between blood and retina, transports more glucose when blood glucose is high. This is the ultimate cause of diabetic retinopathy. Knockdown of GLUT1 by intraocular injections of a pool of siRNAs directed against SLC2A1 mRNA which codes for GLUT1 significantly reduced mean retinal glucose levels in diabetic mice. Systemic treatment of diabetic mice with forskolin or genistein, which bind GLUT1 and inhibit glucose transport, significantly reduced retinal glucose to the same levels seen in non‐diabetics. 1,9‐Dideoxyforskolin, which binds GLUT1 but does not stimulate adenylate cyclase had an equivalent effect to that of forskolin regarding lowering retinal glucose in diabetics indicating that cyclic AMP is noncontributory. GLUT1 inhibitors also reduced glucose and glycohemoglobin levels in red blood cells providing a peripheral biomarker for the effect. In contrast, brain glucose levels were not increased in diabetics and not reduced by forskolin. Treatment of diabetics with forskolin prevented early biomarkers of diabetic retinopathy, including elevation of superoxide radicals, increased expression of the chaperone protein β2 crystallin, and increased expression of vascular endothelial growth factor (VEGF). These data identify GLUT1 as a promising therapeutic target for prevention of diabetic retinopathy. J. Cell. Physiol. 228: 251–257, 2013. © 2012 Wiley Periodicals, Inc.     

Effectiveness of nifedipine in the treatment of arterial hypertension in various types of diabetes mellitus

Selection of indications and the general tactics of nifedipine monotherapy of hypertension in diabetic subjects is not clearly established, as yet. It refers specifically to different forms and phases of diabetes mellitus. This was the reason to carry out a respective study. In 4 groups of hypertension: 1) in diabetics without vascular complications, 2) in diabetic nephropathy, 3) in diabetics type II without nephropathy, and 4) in comparative group of subjects without diabetes mellitus, a 6-week controlled, open trial was performed. Before, during and after nifedipine (3 X 10-20 mg p.d.), the following parameters were monitored: 1) systolic, diastolic and mean blood pressures, 2) glycaemic indices of diabetes control, 3) serum cholesterol: total, HDL, LDL, triglycerides, 4) daily albuminuria and GFR, 5) adverse reactions to nifedipine. It could be concluded that nifedipine therapy was relatively most effective and safe in hypertensive diabetics type II without nephropathy. It was less effective in diabetics type I without nephropathy and failed in diabetics type I with nephropathy.     

Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy.

Clinical studies have shown a relationship between diabetic retinopathy and vascular endothelial growth factor (VEGF) levels in ocular fluid. Advanced glycation end products (AGEs) have been implicated in diabetes complications, including diabetic retinopathy. Nepsilon-(carboxymethyl) lysine (CML) is a glycoxidation product that may be a marker of oxidative stress. In this study, we used enzyme-linked immunosorbent assays to determine the levels of VEGF, non-CML AGE and CML in the aqueous humor and serum of 82 Japanese patients with type 2 diabetes and 60 non-diabetic subjects. VEGF, non-CML AGE, and CML concentrations in aqueous humor and serum were then compared with the severity of diabetic retinopathy. Immunohistochemical detection analysis of non-CML AGE and CML was also performed using retinal tissues from patients with progressive diabetic retinopathy. Aqueous levels of VEGF, non-CML AGE and CML increased along with the progression of diabetic retinopathy compared to age-matched controls. After coagulation therapy, the VEGF, non-CML AGE, and CML levels were significantly reduced. Immunostaining showed diffuse co-localization of non-CML AGE and CML around microvessels and in the glial cells of proliferative membranes from patients with progressive diabetic retinopathy. These findings suggest that glycation and glycoxidation reactions (or oxidation, as revealed by CML) may contribute to both the onset and progression of diabetic retinopathy.     

Relation of high-density lipoprotein cholesterol concentration to type of diabetes and its control.

Serum cholesterol and high-density lipoprotein (HDL) cholesterol concentrations were measured in 192 diabetics (94 with juvenile-onset and 98 with maturity-onset diabetes) and 177 non-diabetic controls. Hb A1C, an index of blood sugar control, was also measured in the diabetics. Serum cholesterol concentrations were similar in all the diabetics and controls, but HDL cholesterol concentrations were lower in patients with maturity-onset diabetes than in those with juvenile-onset diabetes and controls. There was no correlation in diabetics between HDL cholesterol and Hb A1C. We conclude that HDL cholesterol concentrations are abnormally low in patients with maturity-onset diabetes but essentially normal in those with juvenile-onset diabetes. They are not related to diabetic control.     

Impact of cardiovascular risk factors on coronary heart disease and mortality among middle aged diabetic men: a general population study.

OBJECTIVE--To investigate the effect of cardiovascular risk factors on coronary heart disease and all cause mortality in middle aged diabetic men. DESIGN--Prospective population study based on data collected from second screening (from 1974 to 1977) in the multifactor primary prevention trial and follow up until March 1983. SETTING--Gothenburg, Sweden. SUBJECTS--6897 Men aged 51 to 59, of whom 232 were self reported diabetics and 6665 were non-diabetic; none had a history of myocardial infarction. MAIN OUTCOME MEASURES--Incidences of coronary heart disease and mortality from all causes. RESULTS--Diabetic men with a serum cholesterol concentration greater than 7.3 mmol/l had a significantly higher incidence of coronary heart disease during follow up than those with a concentration less than or equal to 5.5 mmol/l (28.3% v 5.4%; p = 0.020); corresponding figures for non-diabetic men were 9.4% and 2.4% respectively. In multivariate logistic regression analyses serum cholesterol concentration and smoking habit were independent predictors of coronary heart disease (odds ratio serum cholesterol concentration 6.1 (95% confidence interval 2.1 to 17.6) current smoking 2.9 (1.1 to 7.5)) and of all cause mortality (3.2 (1.3 to 7.9), 3.0 (1.4 to 6.7) respectively) in diabetic men whereas systolic blood pressure, body mass index, family history, marital state, and alcohol abuse were not. Low occupational class was an independent predictor of mortality (2.4 (1.01 to 5.5)), but not of coronary heart disease, in diabetic men. CONCLUSIONS--Middle aged diabetic men with hypercholesterolaemia are at very high risk of developing coronary heart disease and of dying prematurely. Lowering serum cholesterol concentration in such subjects seems to be warranted.     

Influence of proteinuria on vascular disease,blood pressure,and lipoproteins in insulin dependent diabetes mellitus.

Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.     

Effects of chard (Beta vulgaris L. var cicla) on the liver of the diabetic rats: a morphological and biochemical study

Chard (Beta vulgaris L. var cicla) is one of the medicinal herbs used by diabetics in Turkey. It has been reported to reduce blood glucose. We have investigated the effect of chard extracts on the liver by biochemical and morphological investigation. The plant extract was administered by the gavage technique to rats at a dose of 2 g/kg every d for 28 d, 14 d after experimental animals were made diabetic. In the diabetic group, some degenerative changes were observed by light and electron microscope examination, but degenerative changes decreased or were not observed in the diabetic group given chard. In the diabetic group, blood glucose levels, serum alanine, aspartate transaminase, alkaline phosphatase activities, total lipids, sialic and uric acid levels, liver lipid peroxidation (LPO), and nonenzymatic glycosylation (NEG) levels increased, while blood glutathione, body weight, and liver glutathione (GSH) levels decreased. The diabetic group given chard, serum alanine, aspartate transaminase, alkaline phosphatase activities, total lipid level, sialic and uric acid levels, blood glucose levels, and liver LPO and NEG levels decreased, but the other values increased. As a result of all the morphological and biochemical findings obtained, it was concluded that the extract of this plant has a protective effect on the liver in diabetes mellitus.