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[Limits of chromatographic determination of glycated hemoglobin (Hb A1c) in diabetes mellitus in presence of abnormal hemoglobins].

The content of glycated hemoglobin (Hb A1c) evaluated by high pressure chromatography on a VARIANT analyzer using Hb A1c software correlated with the mean daily blood glucose level in the majority of diabetics with types 1 and 2 disease and helped evaluate the compensation of diabetes mellitus during the latest 2-3 months of observation. Low Hb A1c values in combination with an extra hemoglobin fraction, unidentified by the software we used, were detected in 3 Russian women suffering from type 2 diabetes mellitus, with high blood glucose levels. Application of Hemoglobinopathy software showed an abnormal spectrum of hemoglobin fractions in the blood of all 3 patients: appearance of hemoglobin D paralleled by decrease of Hb A0. The presence of abnormal hemoglobin D in these patients was confirmed by the results of electrophoresis on cellulose acetate films and a negative test for sickle erythrocytes. Abnormal hemoglobins are responsible for discoordination between glucose content and Hb A1c in the blood of diabetics. Measurement of serum fructosamine is recommended for evaluation of diabetes compensation in patients with hemoglobinopathies.

Chromatography, Ion Exchange↗

[Regulation of natriuresis in diabetic nephropathy].

The aim of this study was to determine the influence of metabolic control of diabetes on natriuresis, the effect of natriuretic peptides and renal kallikrein on the kidney and the participation of proximal and distal tubules in natriuresis. The study was done in 41 individuals: 27 IDDM patients and 14 healthy controls. The patients were on insulin only, had normal blood pressure, and were prescribed a standard diabetic diet without sodium or protein restriction. Diabetic patients were assigned to subgroups, depending on the stage of nephropathy and level of metabolic control. Urine collection was done three times daily in all participants. The first collection was done after 500 mg lithium carbonate (p.o.) and was followed by 10 mg amilorid (Midamor, Thomas Morson Pharmaceuticals). The third collection of urine was used to evaluate excretion of cGMP. In addition to sodium, lithium, potassium and creatinine clearances, excretion of renal kallikrein, and levels of microalbuminuria, fructosamine and glycated hemoglobin were also determined. Lithium clearance was used to evaluate tubular sodium transport. The influence of diuretic peptides--ANP and urodilatin, on natriuresis was reflected by urinary cGMP excretion. Function of the kallikrein-kinin system was studied on the basis of excretion of kallikrein. Amilorid was used to test the effect of blocking amiloride-sensitive sodium channels in distal tubules on natriuresis (Tab. 1). A statistically significant decrease in mean lithium clearance was observed in IDDM patients as compared to healthy controls. Creatinine clearance was the same in both groups (Tab. 2). Lower lithium clearance was observed in the subgroup of diabetic patients with "silent" nephropathy. Diabetic patients with "silent" and early nephropathy had significantly higher levels of fractional sodium reabsorption in the proximal tubule when compared with controls (Tab. 3). Moreover, lower daily excretion of kallikrein was observed in patients with stage II nephropathy in comparison to the control group (Tab. 4). Amilorid uptake had no influence on urinary kallikrein. However, natriuresis after amilorid was significantly higher in diabetic patients than in controls. In conclusion, reabsorption in the proximal tubule is increased in patients with "silent" diabetic nephropathy, as revealed by decreased lithium clearance and unchanged creatinine clearance. Hyperactivity of the proximal tubule in stage II and III of diabetic nephropathy results in increased sodium reabsorption in the proximal tubule, as reflected by the increase in fractional sodium reabsorption in this tubule. Amilorid, a distal tubule blocker, reduces distal tubule activity independently of urinary kallikrein excretion. Elevated natriuresis was observed after amilorid without any change in urinary kallikrein excretion.

Cyclic GMP↗

Serum levels of advanced glycation end products in poorly metabolically controlled children with diabetes mellitus: relation to HbA1c.

Serum levels of advanced glycation end products (s-AGEs) were investigated in children with poorly metabolically controlled diabetes to determine whether they may be correlated with HbA1c, fructosamine, glycaemia, albumin excretion rate, duration of diabetes and age. In this study, 17 children with Type 1 diabetes mellitus (age range 9 to 18 yr) and 8 healthy children (age range 7 to 17 yr) served as subjects. S-AGEs were found to be increased in poorly metabolically controlled children with diabetes (HbA1c>9%). A significant correlation (r=0.65;p<0.01) was found between s-AGEs and HbA1c in the group of diabetic children. In poorly metabolically controlled children with diabetes of pre-pubertal and pubertal age, the level of s-AGEs should be monitored as the risk of microvascular complications may be already present at this early stage of life.

Adolescent↗

Maternal adjustment and infant outcome in medically defined high-risk pregnancy.

Biological and psychosocial risk factors in high-risk pregnancy and their relation to infant developmental outcomes were explored in a sample of 153 pregnant Israeli women who had pregestational diabetes mellitus, gestational diabetes mellitus, or were nondiabetic. Questionnaires on coping and resources as well as well-being and distress during the 2nd trimester were administered. Estimates of maternal fuels (HbAlc and fructosamine) were obtained throughout pregnancy. At 1 year, offspring were administered the Bayley Scales of Infant Development and mother-infant interactions were observed. Infants of mothers in the diabetic groups scored lower on the Bayley Scales and revealed fewer positive and more negative behaviors than did infants of mothers in the nondiabetic group. Infant outcomes in the maternal diabetic groups were associated with maternal metabolism. Maternal coping and resources differed in the 3 groups and differentially predicted infant development.

Adaptation, Psychological↗

[Food dietary supplement efficacy in complex therapy of patients with type 2 diabetes with obesity].

The dynamic of glycemia, insulin, C peptide, glycosylated hemoglobin, fructosamine, parameters of serum lipids, lipid peroxidation and system of antioxidant defense in 28 patients with diabetes mellitus type 2 associated with obesity was studied of influence of hypoglycemic hypocaloric diet. Besides favorable influence to a clinical picture of the disease universal normalizing influence of hypoglycemic hypocaloric diet with food dietary supplement "Cogent DB+" on parameters of carbohydrate, lipid and oxidative metabolism. The scheme of investigation of efficacy of food dietary supplements in complex treatment of patients with diabetes mellitus type 2 associated with obesity was offered on basis of study of influence "Cogent DB+" on mechanisms of metabolic disorders in these patients.

Adult↗

Plasma antioxidants and type 2 diabetes mellitus.

Reports indicate that some complications of diabetes mellitus are associated with increased activity of free radicals and accumulation of lipid peroxidation products. The organism's susceptibility to free radical stress and peroxidative damage is related to the balance between the free radical load and the adequacy of antioxidant defenses. In the present study, the relationship between plasma oxidants and antioxidants in diabetes mellitus was investigated. Thirty patients with type-2 diabetes mellitus were examined as well as twenty healthy controls (matched for age and sex against the diabetic patients). The plasma insulin and C-peptide levels in the diabetic group were significantly lower (p < 0.001) than that of the control group. The mean plasma fructosamine, lipid peroxide, lipids and low-density lipoprotein cholesterol (LDL-C) levels were significantly high (p < 0.001) in the diabetic group compared to the control group. There were not any significant differences in the plasma high-density lipoprotein cholesterol (HDL-C) levels between the patients and the control group (p < 0.001). The type-2 diabetes mellitus patients exhibited higher activities of plasma superoxide dismutase (SOD) than control values, whereas plasma glutathione peroxidase (GPx) activities were significantly lower. Our results suggest that there seems to be an imbalance between plasma oxidant and antioxidant systems in patients with type-2 diabetes mellitus. The estimation of plasma antioxidant levels and their replenishment by exogenous agents when necessary may be useful in the prevention of the diabetic complications.

Adult↗

[The use of highly purified glucomannan-based fibers in childhood obesity].

To evaluate the effectiveness of highly purified glucomannan in childhood obesity a study has been carried out in 23 obese children (12 boys and 11 girls, aged 5.2-15.8 years), with excess weight of 51 +/- 16%, treated with 2-3 caps twice a day of glucomannan fibres (DICOMAN 5:2-3 gr/die), and in 30 obese children (aged 5-18 years) with excess weight of 51 +/- 10%, studied as controls. After a three-days food recall, a balanced diet with adequate caloric intake was provided to all obese children. In all patients before and 2-4 months after the auxological data (weight, height, weight excess) and laboratory data (serum levels of cholesterol, HDL, triglycerides, glucose, fructosamine, glycosylated hemoglobin, RBC, WBC, hemoglobin, iron, calcium, Cu and Zn) have been determined. Excess weight and triglycerides levels were significantly decreased in treated obese patients than in obese controls 4 months after the beginning of the study. A decrease of cholesterol levels was also observed in treated obese patients, but not in controls, whereas serum iron, calcium, copper and zinc persisted unchanged. No important side-effects were observed in treated patients. On the basis of our results highly purified glucomannan fibres may be employed with effectiveness in obese and dyslipidemic children together with diet.

Adolescent↗

[Activity of platelet sodium-proton exchanger, microalbuminuria and insulin-dependent diabetes].

The plasma membrane Na+/H+ exchanger is a ubiquitous system which plays a role in the regulation of intracellular pH and the control of cell growth. In order to assess the potential role of this system in the pathogenesis of diabetic nephropathy, we investigate 42 normotensive insulin-dependent diabetic patients with or without microalbuminuria. We tested the platelet Na+/H+ exchange as the rate of amiloride sensitive and sodium dependent volume gain of cells suspended in sodium propionate. Urinary albumin excretion (UAE) was assayed by radioimmunoassay on a 24 h sample; the glomerular filtration rate (GFR) and the renal plasma flow were determined by 99 m Tc-DTPA and 1231 l-hippuran respectively. Thirty patients (group 1) had EUA > 30 mg/24 h (m +/- sd: 11 +/- 7 mg/24 h), 12 patients (group 2) had microalbuminuria (62 +/- 30 Mg/24 h, range from 35 to 136 mg/24 h). The platelet Na+/H+ exchange rate was significantly increased in patients of group 2: 0.34 +/- 0.01 versus 0.26 +/- 0.06 s-1 x 10(-2) (p < 0.005). There was no significant difference between these two groups regarding blood pressure (116 +/- 14/71 +/- 7 versus 119 +/- 12/73 +/- 5 mmHg), age, diabetes duration, glycated hemoglobin or fructosamine levels. On the whole population, we found a significant positive correlation between the platelet Na+/H+ exchange rate and the UAE (r = 0.57, p < 0.001) and with the glomerular filtration fraction (r = 0.43, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Determining the time of diabetes mellitus onset by the level of glycosylated keratin in hair].

The levels of glycosylated hemoglobin (HbA1c) and glycosylated keratin were studied along the hair length in 17 patients with newly detected insulin dependent diabetes mellitus (IDDM) aged 7 to 33, in 14 patients with newly detected noninsulin dependent diabetes mellitus (NIDDM) aged 46 to 73, and in 41 healthy subjects. The level of glycosylated keratin in healthy hairs along the entire length varied within 0.094-0.124 mumol of fructosamine per 100 mg of hair. In 10 of 17 patients of the IDDM group measurements of glycosylated keratin levels made it possible to determine the time of appearance of diabetes mellitus, in 13 patients of the NIDDM group these levels along the entire hair length were elevated. The determination of these levels permitted the estimation of the time of appearance of IDDM. Its manifestation followed a long period (1-2 yrs.) of latent derangements of carbohydrate metabolism. In NIDDM patients the time of appearance of disease is difficult to determine because of the limited hair length and a long latent period of disease (over 2-3 yrs.).

Adolescent↗

Hereditary spherocytosis, a pitfall in the assessment of glycaemic control.

The use of glycosylated haemoglobin in the assessment of diabetic control is ubiquitous. Hereditary spherocytosis is a haemolytic anaemia with shortened red blood cell lifespan, which can interfere with the methods of glycosylated haemoglobin measurement. We report a case of hereditary spherocytosis in a young man with type 1 diabetes, and illustrate the discrepancy in the measurements of glycosylated haemoglobin, which were inconsistent with the blood glucose profiles. Fructosamine, an alternative time-averaged indicator of blood glucose level, was advantageous in this particular situation. The awareness of the limitations of glycosylated haemoglobin is essential in the clinical care of patients with diabetes, which is a major health problem in Singapore.

Adult↗

Increased lipid peroxidation in type 2 poorly controlled diabetic patients.

An increased lipid peroxidation, due to the altered intracellular ratio between free radicals and antioxidant systems, has been recently related to diabetes. To study the possible relationship between lipid peroxidation and metabolic control, we measured the plasma concentrations of malondialdehyde (MDA), end product of the oxidation of polyunsaturated fatty acids, in poorly and well controlled Type 2 diabetic patients. A significant increase in plasma malondialdehyde concentrations was found in poorly controlled diabetics when compared to well controlled patients (p < 0.001) and to healthy normoglycaemic subjects (p < 0.001), whereas no significant difference was observed between the two latter groups. Plasma MDA/Cholesterol and MDA/triglyceride ratios were both higher in poorly controlled diabetics than in well controlled (p < 0.005) and in normal subjects (p < 0.01 and p < 0.02 for MDA/CHOL and MDA/TG respectively). In diabetic patients a positive correlation was found between plasma MDA levels and mean daily blood glucose (p < 0.01), plasma fructosamines (p < 0.001), HbA1 (p < 0.05) and plasma triglycerides (p < 0.05), while no significant correlation was shown between plasma malondialdehyde and total cholesterol. Malondialdehyde levels were followed-up for 7 days running (T1-T7) in five poorly controlled diabetics, treated with conventional insulin therapy. This group showed normalized plasma lipid peroxide values (0.486 +/- 0.13 mumol/l, T5, M +/- SEM) 72 h after the restoration of glycaemic control (145 +/- 25 mg/dl, T2, M +/- SEM). These results confirm the increase of lipid peroxidation during Type 2 diabetes. The correlation with the degree of metabolic imbalance suggests a possible role for lipid peroxidation in the occurrence of glucose-induced macromolecular changes.

Cholesterol↗

Dynamic tests in the clinical management of diabetes.

Diabetes mellitus affects carbohydrate, lipid and protein metabolism. Although remarkably complex because of the interaction between different metabolisms, diabetes can be investigated with a variety of procedures allowing a precise characterization of the metabolic dysregulation associated with the disease. The diagnostic clue is fasting hyperglycemia (> or = 7 mmol/l). As glucose homeostasis is a dynamic process, in the clinical setting different parameters are usually required to most accurately depict the situation of any individual patient. The most important dynamic tests used are the oral and iv glucose tolerance tests, and the glucagon test which is adopted to evaluate the residual beta-cell function in patients with Type 1 diabetes. For the evaluation of long-term metabolic control in the diabetic patient, glycosylated haemoglobin (HbA1c) and fructosamine are currently adopted in clinical practice. HbA1c < 7% is a target for any type of therapy in diabetic patients. Mathematical modelling and/or computer-assisted analysis of empirical data allow the derivation of dynamic parameters to investigate the functional state of beta-cells with precision and offer information to monitor disease progression in both Type 1 and Type 2 diabetes.

Blood Glucose↗

[Insulin receptor Arg1131-->Gln: a novel mutation in the catalytic loop of insulin receptor observed in insulin resistant diabetes].

A novel mutation Arg1131-->Gln in the catalytic loop of insulin receptor (IR) associated with insulin resistant diabetes was detected. A 56-year-old male with hyperinsulinemia (fasting IRI 92 microU/ml) showed moderate impairment in glucose tolerance (HbAlc 7.0%, fructosamine 258 mumol/l, fasting glucose 119 mg/dl, maximum value of blood glucose during 75 g OGTT 220 mg/dl). While insulin binding to erythrocytes IR was normal, the insulin-induced autophosphorylation of the patient's erythrocytes IR in vivo showed marked decrease, suggesting this patient had some defect in the kinase domain (exon 17-21) of IR. PCR-SSCP analysis of kinase domain with a genomic DNA obtained from the patient's leucocytes indicated the presence of some mutations in exon 19. Sequencing analysis in M13 revealed a heterozygous mutation at a position 1131 (CGG-->CAG) substituting Gln for Arg. Four people of patient's family analyzed are revealed to have an identical missense mutation at the same position with the patient.

DNA↗

[Study of the origin of hyperglycemia in acute myocardial infarct].

In order to clarify the origin of hyperglycaemia, blood glucose, glycated haemoglobin (GHb) and protein-corrected serum fructosamine (SFA) values were simultaneously determined at admission of 65 patients with acute myocardial infarction while oral glucose tolerance test was performed later at discharge. In 29 patients no alterations in carbohydrate metabolism were found (blood glucose: 5.2 +/- 0.1 mmol/l, GHb: 4.4 +/- 0.1%, SFA: 2.20 +/- 0.08 mmol/l) while in 9 patients diabetes was already recorded in the medical history (blood glucose: 11.5 +/- 1.1 mmol/l, GHb: 7.9 +/- 0.9%, SFA: 3.36 +/- 0.31 mmol/l, p < 0.001). Undiagnosed diabetes was documented in 8 patients (blood glucose: 11.8 +/- 1.3 mmol/l, GHb: 7.3 +/- 0.6%, SFA: 3.51 +/- 0.24 mmol/l) while stress-hyperglycaemia was found in 19 patients (blood glucose: 8.4 +/- 0.3 mmol/l, GHb: 4.5 +/- 0.1%, SFA: 2.55 +/- 0.17 mmol/l). Undiagnosed diabetes could be recorded in one seventh while stress-hyperglycaemia could be found in one third of non-diabetic patients with acute myocardial infarction. Due to overlapping values SFA is not suitable to distinguish between stress-hyperglycaemia and undiagnosed diabetes in patients with acute myocardial infarction.

Adult↗

[Aminoguanidine prevents peroxynitrite production and cardiac hypertrophy in streptozotocin-induced diabetic rats].

UNLABELLED: The effect and possible mechanisms of action of aminoguanidine (a preferential iNOS inhibitor) has been studied on cardiovascular damages and overproduction of reactive nitrogen species in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: 40 rats were divided into five groups (control and diabetic, with or without aminoguanidine treatment, diabetic with insulin treatment) and oxidative stress parameters were examined. Tissue nitric oxide levels were determined by EPR spectroscopy, while peroxynitrite generation by a chemiluminescence method. Cardiac hypertrophy, blood metabolic parameters (blood glucose, HbA1c, fructosamine), as well as tissue protein carbonyl levels were also determined. RESULTS: Diabetic animals showed increased nitric oxide and peroxynitrite generation in the aorta along with a significant hypertrophy and protein carbonylation of the cardiac tissue. Both aminoguanidine and insulin treatment suppressed high levels of nitric oxide and peroxynitrite in the vasculature, but only aminoguanidine was able to prevent hypertrophic alterations and to reduce protein carbonylation in the heart. CONCLUSIONS: The results show that (1) aminoguanidine reduces nitric oxide production and prevents cardiac hypertrophy, (2) insulin therapy improves carbohydrate metabolism, reduces nitrosative stress but has no effect on cardiac hypertrophy. Cardiac hypertrophy in diabetes is strongly correlated with non-enzymatic glycation. Aminoguanidine prevented hypertrophy by blocking the formation of advanced glycation end products rather than via other mechanisms.

Animals↗

[Evaluation of the efficacy of metformin-glibenclamide treatment in overweight non-insulin dependent diabetics].

The authors evaluated the efficacy of treatment with the metformin-glibenclamide combination in 30 non-insulin dependent overweight diabetic patients in poor metabolic control during sulfonylurea treatment. After three months' therapy, a significant reduction of glycaemia, insulinaemia and fructosamine were found. Therefore, the addition of biguanides in those patients, was able to reduce blood glucose levels and to improve insulin resistance. In addition the metformin glibenclamide combination never produced relevant side effects of lactic acidosis, which is the most dangerous event during biguanide treatment.

Adult↗

Oxidative stress and protein glycation in patients with chronic obstructive pulmonary disease.

Several studies have indicated the presence of increased oxidative stress as a critical feature in the pathogenesis of chronic obstructive pulmonary disease (COPD). Another biochemical complication leading to pathogenesis is protein glycation. The nexus between oxidative stress and protein glycation in various pathological conditions is being unraveled. Increased oxidative stress can lead to enhanced protein glycation by a process of auto-oxidative glycation. No information is available in the literature regarding protein glycation among COPD patients. Eleven non-diabetic COPD patients were included in the study and equal number of age and sex-matched healthy individuals were enrolled as controls. The whole-blood reduced glutathione was found to be less among the patients while lipid peroxides and fructosamine were elevated in comparison to control. The present study confirmed oxidative stress and enhanced protein glycation among the COPD patients. Antioxidant therapy may be considered as part of the treatment regimen for COPD patients.

Female↗

On the clinical chemistry of the Bennett's wallaby (Macropus rufogriseus rufogriseus).

The following parameters were determined in blood serum of apparently healthy Bennett's wallabies (Macropus rufogriseus) using the Hitachi 917 (Roche Diagnostics, Mannheim, Germany) and/or the Vettest 8008 (IDEXX-GmbH, Woerrstadt, Germany): alkaline phosphatase, alanine aminotransferase, ammonia, alpha-amylase, aspartate aminotransferase, Ca, Cl, cholesterol, cholinesterase, creatine kinase, creatinine, gammaglutamyltransferase, glucose, iron, lactate dehydrogenase, magnesium, phosphate, potassium, protein, sodium, total bilirubin, triglyceride, and urea. The results for cholesterol, glucose, total protein, triglyceride and for the enzymes alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyltransferase and lactate dehydrogenase differed significantly between both methods (P < 0.05). There is a negative correlation between the age of the Bennett's wallabies and the activity of the alkaline phosphatase. Five protein fractions could be separated on cellulose acetate electrophoresis. The mean concentrations of fructosamine and beta-hydroxybutyrate were 447.3 micromol/L and 0.27 mmol/L, respectively. The estimated vitamin A intake had no influence on the vitamin A concentration in serum. The serum vitamin E concentration was in general low and vitamin E was below the detection limit of 0.82 micromol/L in 29 out of 42 serum samples. The use of these analytes is discussed concerning the knowledge about the physiology, nutrition and diseases of macropods.

Aging↗