Anti-diabetic and anti-oxidant effects of Zingiber Officinale on alloxan-induced and insulin-resistant diabetic male rats

This study was designed to investigate the hypoglycaemic and anti-oxidant effects of Zingiber officinale on experimentally induced diabetes mellitus using alloxan and insulin resistance. Aqueous extracts of raw ginger was administered orally at a chosen dose of 500mg/ml for a period of 4 weeks to alloxan-induced diabetic and insulin resistant diabetic rats. The experimental rats exhibited hyperglycaemia accompanied with weight loss to confirm their diabetic state. Ginger effectively reduced fasting blood glucose and malonydealdehyde levels in alloxan-induced diabetic and insulin resistant diabetic rats compared to control and ginger only treated rats. Furthermore, ginger increased serum insulin level and also enhanced insulin sensitivity in alloxan-induced diabetic and insulin resistant diabetic rats compared to control and ginger only treated rats. The results of the study clearly show that dietary ginger has hypoglycaemic effect, enhances insulin synthesis in male rats and has high antioxidant activity. One of the likely mechanisms is the action of malonydealdehyde, which acts as a scavenger of oxygen radicals. Keywords: Diabetes mellitus, Insulin resistance, Zingiber officinale, Malonydealdehyde.     

Serum fructosamine concentration as measure of blood glucose control in type I (insulin dependent) diabetes mellitus.

Serum fructosamine activity was studied in 42 patients with type I (insulin dependent) diabetes mellitus and 30 non-diabetic volunteers as an index of blood glucose control. There was a significant correlation both between fructosamine and glycosylated haemoglobin values (r = 0.82) and between fructosamine and the fasting C peptide concentration (r = -0.81). Test results in 14 of the diabetics reflected the mean plasma glucose concentration calculated from 25 serial estimations in a single 24 hour period (r = 0.75; p less than 0.01) but not the mean amplitude of glycaemic excursion (r = 0.23; p greater than 0.05). Fructosamine concentrations measured in these multiple blood specimens did not change significantly throughout the day (mean coefficient of variation 4.1%) despite wide variability of the respective plasma glucose concentrations (mean coefficient of variation 36.2%). It is concluded that a single random serum sample analysed for fructosamine concentration provides a simple and reliable assessment of glucose homoeostasis in patients with type I diabetes mellitus.     

Anti-Insulin Immune Responses Are Detectable in Dogs with Spontaneous Diabetes

Diabetes mellitus occurs spontaneously in dogs. Although canine diabetes shares many features with human type-1 diabetes, there are differences that have cast doubt on the immunologic origin of the canine disease. In this study, we examined whether peripheral immune responses directed against islet antigens were present in dogs with diabetes. Routine diagnostics were used to confirm diabetic status, and serum samples from dogs with (N = 15) and without (N = 15) diabetes were analyzed for the presence of antibodies against islet antigens (insulin, glutamic acid decarboxylase, insulinoma-associated protein tyrosine phosphatase, and islet beta-cell zinc cation efflux transporter) using standard radioassays. Interferon-γ production from peripheral blood T cells stimulated by porcine insulin and by human insulin was tested using Elispot assays. Anti-insulin antibodies were detectable in a subset of diabetic dogs receiving insulin therapy. Pre-activated T cells and incipient insulin-reactive T cells in response to porcine or human insulin were identified in non-diabetic dogs and in dogs with diabetes. The data show that humoral and cellular anti-insulin immune responses are detectable in dogs with diabetes. This in turn provides support for the potential to ethically use dogs with diabetes to study the therapeutic potential of antigen-specific tolerance.     

Pilot Study to Evaluate the Effect of Short-Term Improvement in Vitamin D Status on Glucose Tolerance in Patients With Type 2 Diabetes Mellitus

ObjectiveTo study the effect of improvement in vitamin D status on glucose tolerance in Asian Indian patients with moderately controlled type 2 diabetes mellitus (T2DM).MethodsThis randomized, double-blind, placebocontrolled pilot study was conducted in 28 Asian Indian patients with T2DM. Study participants were randomly assigned to a vitamin D-treated group (group D) or a placebo group (group P). Serum 25-hydroxyvitamin D, hemoglobin A1c, and serum fructosamine levels were measured, and an oral glucose tolerance test (OGTT) was performed in all patients at baseline and 4 weeks after intervention. During the OGTT, plasma glucose and serum insulin levels were measured at 0, 30, 60, 90, and 120 minutes. The unpaired t test was used to compare the groups at baseline and to compare the differences in changes from baseline to 4 weeks between the 2 study groups.ResultsGroup D and group P were similar with respect to their fasting plasma glucose and serum insulin concentrations, post-OGTT plasma glucose and serum insulin levels, and hemoglobin A1c and fructosamine values at baseline. Serum 25-hydroxyvitamin D levels increased significantly in group D at 4 weeks. No significant differences were found between the groups at baseline and 4 weeks with respect to serum fructosamine, fasting plasma glucose and serum insulin, post-OGTT plasma glucose and serum insulin levels, and homeostasis model assessment of insulin resistance.ConclusionIn this study, short-term improvement in vitamin D status was not associated with improvement in glucose tolerance, insulin secretion, or insulin sensitivity in Asian Indian patients with moderately controlled T2DM.(Endocr Pract. 2010;16:600-608)     

Value of determining fructosamine levels in serum of pregnant patients with diabetes to evaluate the level of compensation for glycemia]

The results in 16 pregnant women with diabetes mellitus are analysed. All patients were treated with an intensive insulin-therapy at the Voivodeship Clinic for Diabetic Patients in Zabrze. Multipoint glycaemia profiles made by the treated patients as a self control were compared with serum fructosamine and HbAlC concentrations. A significant correlation of fructosamine levels with glycaemia and HbAlC levels was noted. No significant dependence of fructosamine and glycaemia fasting levels, incidence of hyperglycaemia and Schlichtkrull's Mw index was noted. Results suggest, that the fructosamine serum concentration is a useful marker of metabolic compensation in pregnant women with diabetes mellitus. It enables less frequent performance of the daily profiles of glycaemia by the patients.     

Timing of pre-breakfast insulin injection and postprandial metabolic control in diabetic children

A peak period of hyperglycaemia in insulin-dependent diabetics occurs after breakfast. A randomised crossover study was performed on nine diabetic children at home to study the effect of varying the time of their morning mixed injection of Monotard and Actrapid insulin on this hyperglycaemic peak. Performing the study at home minimised the children''s stress.After diabetic control had been improved children injected their insulin 30 minutes (early injection) or five minutes (late injection) before breakfast on two consecutive Saturday mornings. Blood samples were taken at 30-minute intervals over 3½ hours and analysed for concentrations of glucose, insulin, C-peptide, pyruvate, lactate, alanine, and ketones. Diet, insulin dose, and exercise were kept the same on both test days.The mean blood glucose concentration at breakfast (0 minutes) was 11 mmol/l after the early injection and 10 mmol/l after the late injection. Subsequent concentrations were consistently lower with the early injection regimen than the late regimen. The greatest difference between values in the two groups was 3·7 mmol/l at 150 minutes. Mean plasma insulin concentrations were lower in the children on the early regimen than in those on the late regimen at 30 minutes before breakfast but higher at 0 minutes and thereafter. There were no significant differences in mean concentration of intermediary metabolites between the two injection regimens. These were mainly within the normal range for healthy young adults except for the ketone concentrations, which were raised with both injection regimens until 180 minutes after breakfast.These results suggest that the timing of the morning injection of insulin is important in the control of postprandial hyperglycaemia in diabetic children.     

White coat hyperglycaemia: disparity between diabetes clinic and home blood glucose concentrations.

OBJECTIVES--To identify patients with discrepantly high clinic blood glucose concentrations compared with self reported values and to assess whether such patients have errors in self monitoring technique. To determine whether, in patients with good technique, the discrepancy is a transient phenomenon related to clinic attendance. DESIGN--Prospective study of diabetes clinic patients recruited over six months. SETTING--Outpatient diabetes clinic of a teaching hospital. SUBJECTS--34 consecutive patients with non-insulin dependent diabetes who had had at least two consecutive clinic blood glucose concentrations more than 5 mmol/l higher than the mean self reported concentration. MAIN OUTCOME MEASURES--Assessment of monitoring technique; presence of cognitive or physical impairment; serum fructosamine concentration; home and clinic blood glucose concentrations. RESULTS--15 of 34 patients had errors in monitoring technique, 12 of whom had cognitive or physical impairment. In the remaining 19, the mean (SD) blood glucose concentrations of capillary and venous samples taken at home (10.2 (0.6) and 12.2 (1.1) mmol/l respectively) were significantly lower than in those taken at the clinic (16.8 (1.6) mmol/l, p < 0.0002). The fructosamine concentration was significantly higher in patients with monitoring errors than those without (2.4 (0.4) v 1.8 (0.4) mmol/l, p < 0.0001). CONCLUSIONS--"White coat" hyperglycaemia was detected in about half the patients but errors in technique accounted for the rest of the discrepancies. Patients'' ability should be assessed before teaching self monitoring and the technique checked regularly.     

The Shepherds’ Tale: A Genome-Wide Study across 9 Dog Breeds Implicates Two Loci in the Regulation of Fructosamine Serum Concentration in Belgian Shepherds

Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (p_corrected ≈ 1:68 × 10^-6) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (p = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus.     

Dysfunction of soluble guanylyl cyclase in aorta and kidney of Goto-Kakizaki rats: influence of age and diabetic state.

Type 2 diabetes mellitus is frequently associated with arterial hypertension. The mechanisms involved in this association are not known in detail, but endothelial dysfunction and a blunted vascular response to endogenous vasodilators are thought to play a role. In the present study we investigated the in vitro activity of vascular and renal soluble guanylyl cyclase in type 2 diabetic Goto-Kakizaki rats aged 5, 15, and 30 weeks, in comparison with age-matched Wistar controls. Blood pressure was monitored by radiotelemetry, and serum glucose and insulin concentrations were measured by standard assays. Goto-Kakizaki rats of all age groups had serum glucose concentrations significantly higher than those of corresponding Wistar controls. Serum insulin was unchanged until 15 weeks of age and was elevated in the 30-week-old diabetic rats. Blood pressure in Goto-Kakizaki rats was significantly higher than that in Wistar controls, and heart rate was significantly lower. Mesenteric arteries of diabetic rats showed a blunted relaxation in response to acetylcholine and sodium nitroprusside. In aortic tissue from Wistar rats an age-dependent increase was found in nitric oxide-stimulated cGMP formation, which was absent in the diabetic animals. Moreover, the maximum activity of soluble guanylyl cyclase was significantly lower in Goto-Kakizaki rats in all age groups studied. In renal tissue no differences were found between diabetic and control rats, except at 30 weeks of age when Goto-Kakizaki rats showed a significant reduction in basal and stimulated guanylyl cyclase activity. In conclusion, the present study shows a persistent reduction in vascular nitric oxide-sensitive guanylyl cyclase in Goto-Kakizaki rats, which occurred shortly after weaning and may contribute to the elevation in blood pressure in this strain of genetically diabetic rats.     

Clinical usefulness of estimation of serum fructosamine concentration as a screening test for diabetes mellitus.

Fructosamine, a putative measure of serum glycosylated proteins, was measured in 74 subjects referred for oral glucose tolerance tests. A normal range (mean (2 SD] of 1.6 (0.4) mmol/l (40(10) mg/100 ml) derive from results obtained in 83 healthy non-diabetic volunteers permitted the detection of 15 out of 17 (88%) subjects with proved diabetes and yielded only five (9%) false positive diagnoses. Fructosamine concentrations correlated significantly (p less than 0.001) with fasting plasma glucose concentrations (r = 0.76) and glycosylated haemoglobin concentrations (r = 0.70). A longitudinal study suggested that fructosamine concentration was an index of intermediate term (one to three weeks) blood glucose control. Fructosamine concentration was not related to uraemia and did not depend on albumin or total protein concentrations, provided that serum albumin concentrations remained above 30 g/l. Estimation of fructosamine concentrations is a fully automated procedure and may provide a simple means of screening for diabetes mellitus.     

Carrier solutions for low-level intravenous insulin infusion.

In the use of low-level intravenous insulin infusion for treating diabetic hyperglycaemia and ketoacidosis adsorption of insulin to containers or plastic infusion apparatus results in significant losses of 60-80% of insulin in dilute physiological saline solution (40 U/l). It is therefore necessary to add protein to the carrier solution to minimize losses and maintain a constant delivery rate. Recovery studies showed that 3.5% w/v polygeline solution (polymer of degraded gelatin) was a suitable medium for this purpose, offering some advantages over human serum albumin. A minimum concentration of 0.5% polygeline was required to ensure adequate delivery of insulin to the patient.     

Long term correction of hyperglycaemia and progression of renal failure in insulin dependent diabetes

The effect of long term correction of hyperglycaemia on the rate of deterioration of renal function was studied in six insulin dependent diabetics with proteinuria due to diabetic nephropathy. After a planned run in observation period of 10 to 24 months patients entered a programme of continuous subcutaneous insulin infusion for up to 24 months. Glycaemic control was promptly and significantly improved and optimal glycaemic values sustained throughout the study. Blood pressure was maintained stable. A control group of six nephropathic diabetics was studied receiving conventional insulin injection treatment but also with blood pressure control over the same period.Despite greatly improved metabolic control in the infusion treated group no significant change in the rate of decline of glomerular filtration rate could be shown, the plasma creatinine concentrations continued to increase, and the fractional clearance of albumin and IgG rose progressively, indicating progression of glomerular damage. The conventionally treated control group behaved similarly. In a single patient receiving the continuous infusion the rate of decline of the glomerular filtration rate slowed considerably, suggesting that the response to strict diabetic control may differ in some patients.These findings suggest that by the time glomerular function has started to fail in diabetic nephropathy the process culminating in end stage renal failure has become self perpetuating and is little influenced by the degree of metabolic control. A new definition of potential clinical diabetic nephropathy is proposed that will permit identification of patients at risk and earlier intervention by glycaemic correction in an attempt to arrest diabetic renal disease.     

Superoxide-forming NADPH oxidase preparation of pig polymorphonuclear leucocyte.

The effect of corticosterone on myofibrillar protein breakdown in diabetic rats was investigated in order to assess the possible counteracting effects of the secondary rise in plasma insulin concentrations which normally accompanies such treatment. N^τ-Methylhistidine excretion, an index of myofibrillar protein breakdown, was compared before and after corticosterone treatment (4.0 mg/100 g body wt. per day) of normal control, adrenalectomized, 10-day-streptozotocin-diabetic and adrenalectomized diabetic rats. Diabetic rats received 1.5 units of insulin/100 g body wt. per day throughout the experiment and showed marked hyperglycaemia and glucosuria during corticosterone treatment, whereas non-diabetic rats had only mild hyperglycaemia but elevated insulin concentrations. Corticosterone treatment increased the average rate of myofibrillar protein breakdown by 68% and 95% respectively in non-diabetic and diabetic rats. Net loss of muscle non-collagen protein for the same 7-day period was greater in diabetic than in non-diabetic animals (4.15 versus 2.84% per day), and the calculated average synthesis rates were lowest in diabetic rats. Adrenalectomy had little effect except to decrease slightly the rate of muscle protein breakdown. These results show that the rise in plasma insulin concentrations that accompanies exogenous corticosterone administration to non-diabetic rats diminishes the catabolic effect of this glucocorticoid on muscle. Insulin appears to antagonize the effects of the glucocorticoid by attenuating the increased rates of myofibrillar protein breakdown and, to a lesser extent, by limiting the decrease in synthesis rates.     

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.     

Action of pelargonidin on hyperglycemia and oxidative damage in diabetic rats: implication for glycation-induced hemoglobin modification

Glycation-modified hemoglobin in diabetes mellitus has been suggested to be a source of enhanced catalytic iron and free radicals causing pathological complications. The present study aims to verify this idea in experimental diabetes. Pelargonidin, an anthocyanidin, has been tested for its antidiabetic potential with emphasis on its role against pathological oxidative stress including hemoglobin-mediated free radical reactions. Male wistar rats were grouped as normal control, streptozotocin-induced diabetic control, normal treated with pelargonidin and diabetic treated with pelargonidin. Pelargonidin-treated rats received one time i.p injection of the flavonoid (3 mg/kg bodyweight). Biochemical parameters were assayed in blood samples of different groups of rats. Liver was used for histological examinations. Pelargonidin treatment normalized elevated blood glucose levels and improved serum insulin levels in diabetic rats. Glucose tolerance test appeared normal after treatment. Decreased serum levels of SOD and catalase, and increased levels of malondialdehyde and fructosamine in diabetic rats were reverted to their respective normal values after pelargonidin administration. Extents of hemoglobin glycation, hemoglobin-mediated iron release, iron-mediated free radical reactions and carbonyl formation in hemoglobin were pronounced in diabetic rats, indicating association between hemoglobin glycation and oxidative stress in diabetes. Pelargonidin counteracts hemoglobin glycation, iron release from the heme protein and iron-mediated oxidative damages, confirming glycated hemoglobin-associated oxidative stress in diabetes.     

Relationship between fructosamine with serum protein, albumin and glucose concentrations in dairy ewes

The aim of the study was to investigate the changes in blood fructosamine concentrations of ewes during late pregnancy and lactation. The relationship of serum fructosamine to changes in the serum glucose and blood protein and albumin concentrations were measured in 10 crossbred dairy ewes. Blood was sampled 10 days prior to lambing (D − 10), on day 10 (D + 10), day 20 (D + 20), day 90 (D + 90) and on day 130 post partum (D + 130). The concentration of serum fructosamine significantly decreased on D + 10, then significantly increased on D + 20 (p < 0.05), remaining on the same level until D + 130. The concentration of serum glucose was highest on D − 10, and gradually decreased, being significantly lower on D + 130 post partum, compared to D − 10. Similarly the serum albumin and total protein concentrations were highest on D − 10, and significantly decreased on D + 10. The concentration of both parameters increased by D + 20, but then decreased on D + 90 and D + 130. The significant decrease in fructosamine concentration observed on D + 10 probably resulted from the substantial and rapid decrease in total serum protein and albumin concentrations, also established during the same period. The results confirm that in ewes, similar to other species, the shorter serum protein life span during the transition period has an influence on the decrease in blood fructosamine concentrations. These should be considered during the interpretation of serum fructosamine concentration as part of blood biochemical findings during the pre and post partum period.     

Serum fructosamine concentrations in patients with type II (non-insulin-dependent) diabetes mellitus during changes in management.

The serum fructosamine concentration was examined as a new means to monitor metabolic control in non-insulin-dependent diabetes during changes in management. Weekly fructosamine estimations were compared with glycosylated haemoglobin (HbA1c), 24 hour urinary glucose, and fasting plasma glucose concentrations in a 17 week study entailing withdrawal and reinstitution of oral treatment. The serum fructosamine concentration was more sensitive than the other measurements in detecting a deterioration in diabetic control after stopping oral hypoglycaemic drugs. The response to reinstitution of treatment was not significant in the first three weeks (p = 0.266), despite a highly significant reduction in fasting plasma glucose (p = 0.001) and 24 hour urinary glucose concentrations (p = 0.012). Compared with HbA1c, concentrations of fructosamine appeared more useful in monitoring short term (three to six weeks) changes after alterations in management of diabetes. Additional advantages were lower cost and technical simplicity of measurement.     

Interrelation between glucose, insulin, C-peptide and 3-hydroxybutyrate in plasma and amniotic fluid in last trimester diabetic women without residual betacell function

The relationship between maternal plasma and amniotic fluid (AF) concentrations of glucose, insulin, C-peptide and 3-hydroxybutyrate (3-HB) was analysed between 45 to 140 minutes after a standardized breakfast in 8 type I diabetic women without residual betacell function and in 13 nondiabetic control women during the last trimester of gestation. AF levels of both glucose and C-peptide were slightly and AF insulin levels significantly (P less than 0.05) elevated above normal in the diabetic women. 3-HB levels in plasma and in AF were significantly (P less than 0.05) elevated in the diabetic group between 45 to 65 minutes after breakfast. AF insulin and glucose was significantly correlated in the diabetic group (r = 0.96, P less than 0.05). During the 2 hour study period AF levels of glucose, insulin and C-peptide remained essentially unchanged in both groups of women. Changes in maternal plasma 3-HB concentrations seemed to be more rapidly reflected in AF.     

Effect of Sustained Maternal Hyperglycaemia on the Fetus in Normal and Diabetic Pregnancies

The effect of prolonged maternal hyperglycaemia on fetal plasma glucose and insulin concentrations was investigated in eight normal and nine diabetic patients. It was found that under fasting conditions the fetal glucose concentration in gestational diabetic pregnancies tended to be lower than in normal pregnancies. Insulin measurements suggested that this may be due to fetal hyperinsulinism in the diabetic group. During glucose infusion, regardless of the degree of maternal hyperglycaemia, the fetal glucose concentration was limited in 12 out of 13 cases to less than 200 mg/100 ml, with only small differences between normal and diabetic pregnancies. It is proposed that the placenta prevents unlimited transport of glucose to the fetus; yet in diabetic pregnancies a sequence of increased maternal-fetal glucose transport, fetal hyperinsulinism, and fetal hypoglycaemia may contribute to the observed perinatal mortality.