Fructosamine Levels Research Articles

Methanolic Extract of Dill Leaves Inhibits AGEs Formation and Shows Potential Hepatoprotective Effects in CCl4 Induced Liver Toxicity in Rat.

The research was aimed at evaluating the antiglycation, antioxidant, and hepatoprotective properties of methanolic extract of Anethum graveolens (dill). The antioxidant properties, photochemical characteristics, and antiglycation effects of dill extract were measured. Carbon tetrachloride-induced hepatotoxic rats were used to show the hepatoprotective activity of dill leaves. Different concentration of dill extract (0.032, 0.065, 0.125, 0.25, 0.5, and 1 mg/mL) showed potential antioxidant ability. The extract of dill leaves significantly reduced AGEs formation and also fructosamine and protein carbonyl levels in rats' liver. Thiol groups' oxidation, amyloid cross-β, and protein fragmentation (P < 0.001) significantly reduced in treated rats. Liver damage markers significantly reduced in dill-treated animals (P < 0.05). Dill with potential antioxidant, antiglycation, and hepatoprotective effects can be suggested for treatment of diabetes complications.

Cinnamaldehyde potentially attenuates gestational hyperglycemia in rats through modulation of PPARγ, proinflammatory cytokines and oxidative stress

Cinnamon has a history of use for medicinal purposes and its major benefits have been linked to cinnamaldehyde. The present study aimed to investigate the hypoglycemic action of cinnamaldehyde against fatty-sucrosed diet/streptozotocin (FSD/STZ)-rat model of gestational diabetes. Female albino rats were divided into three groups. Group I fed with normal diet (ND) while group II and III were fed with FSD for eight weeks (five weeks pre-gestational and three weeks gestational). Rats of group III were administered with a daily oral dose of 20mg/kg cinnamaldehyde one week before mating onward. At the 7th day of gestation, FSD-fed rats were injected intraperitoneally with STZ (25mg/kg b.wt.) to induce gestational diabetes. Pre-mating treatment of cinnamaldehyde controls hyperphagia and glucose intolerance during the gestational period than in diabetic rats. It also reduced levels of fructosamine, total cholesterols, triglycerides, leptin, tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA) and nitric oxide (NO), while it significantly increased levels of high-density lipoprotein (HDL)-cholesterol, adiponectin, liver glycogen, reduced glutathione (GSH) and catalase activity at term pregnancy. In addition, cinnamaldehyde administration up-regulated the mRNA expression of peroxisome proliferated activated receptor-gamma (PPARγ) and also ameliorated the number of viable fetuses, implantation loss sites, fetal glucose and insulin levels. In conclusion, cinnamaldehyde has safe hypoglycemic action on gestational diabetes by potentiating insulin secretion and sensitivity through activating the antioxidant defense system, suppressing pro-inflammatory cytokines production, upregulating PPARγ gene expression and alleviating the reproductive performance.

Effects of butanol fraction of Ziziphus mucronata root ethanol extract on glucose homeostasis, serum insulin and other diabetes-related parameters in a murine model for type 2 diabetes

Context: Ziziphus mucronata Willd (Rhamnaceae) is currently used in Nigerian traditional treatment of diabetes mellitus. However, detailed information on the antidiabetic potential of the plant parts is presently unknown. Objectives: The present study investigated the antidiabetic effects of the butanol fraction of Z. mucronata root (ZMBF) in a type 2 diabetes (T2D) model of rats. Materials and methods: T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by an intraperitoneal injection of streptozotocin (40 mg/kg bw) and the animals were orally treated with ZMBF 150 or 300 mg/kg bw for five days a week for four weeks. Food and fluid intake, body weight changes and blood glucose levels were monitored during the experiment while other blood and organ specific diabetes-associated parameters were measured at the end of the experiment. Results: After four-week treatment, significantly (p < 0.05) lower blood glucose (19.24 vs 28.96 mmol/L), improved glucose tolerance ability (21.26 vs 28.56 mmol/L), higher serum insulin (131.37 vs 64.20 pmol/L) and liver glycogen (2.40 vs 1.54 mg/g tissue) were observed in the 300 mg/kg ZMBF ingested group compared with the diabetic control group. However, food and fluid intake, body weight gain, HOMA-β, HOMA-IR, serum fructosamine level, hepatic and renal function tests were not significantly (p > 0.05) affected by the treatment of ZMBF. Conclusion: Results of this study suggest that ZMBF treatment, at 300 mg/kg bw, possess antidiabetic activity, but could not ameliorate some diabetes-related parameters in type 2 diabetic rats.

Implications of Low Zinc and Copper Levels As Well As Altered Iron Trafficking Proteins on Oxidant Stress in Patients with Transfusion Dependant Thalassemia

Introduction:Patients with transfusion dependent thalassemia (TDT) have a genetic anemia that causes incomplete erythropoiesis and iron overload. Plasma zinc deficiency is also seen in roughly 25% of patients with TDT. Iron overload is thought to be related to a number of secondary complications in TDT including cardiomyopathy and diabetes. However, in TDT the effects of altered Zn status are not as well characterized and the effects of low copper (Cu) are even less well known. One possible cause of these complications is oxidative damage to tissues. This oxidative stress can be caused by labile plasma iron (LPI), a component of the non-transferrin bound iron pool, which is often seen in individuals suffering from iron overload. LPI is both redox-active and chelatable and is the likely culprit distributing iron to extra-hepatic tissues. Through reactive Fenton chemistry, LPI, can also cause lipid peroxidation releasing malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which are damage-associated molecular patterns and markers of oxidative tissue damage that activate the immune system to induce inflammation. Incomplete erythropoiesis as well as transfusional iron overload are responsible for an increase in the amount of poorly handled, redox active LPI in TDT. Thus, we hypothesized that changes in the levels of key iron trafficking proteins (such as soluble transferrin receptor (sTfR) or hemopexin) would affect oxidative stress levels in TDT. We also hypothesized that metal dyshomeostasis, such as a functional Zn or Cu deficiency would affect oxidative stress.Aims: The purpose of this pilot project is to 1) Determine the state of circulating levels of oxidative stress markers and iron trafficking proteins in TDT patients and 2) Explore the relationship between the markers and proteins measured in (1)and the Zn and Cu status of TDT patients.Methods:39 subjects with informed consent were enrolled (29 patients with TDT and 10 controls). Liver iron concentration (LIC) was measured by a superconducting quantum interference device (SQUID™). LPI was measured using dihydrorhodamine 123. Both MDA and MDA + 4-HNE were measured using N-methyl-2-phenylindole. The iron trafficking proteins sTfR, transferrin, haptoglobin and hemopexin were measured by immunoassay isolation followed by multiplex multiple reaction monitoring mass spectrometry. Zn and Cu were assessed by inductively coupled plasma atomic emission spectroscopy. Fructosamine was measured by quantitative spectrophotometry.Results: Patients with TDT had elevated LIC levels of 2681 ± 2424 ug iron/g wet weight. Plasma levels of the iron trafficking proteins, transferrin, hemopexin and haptoglobin were all decreased in TDT patients (P<0.001) with a corresponding increase in soluble transferrin receptor (StfR) and the LPI (P<0.001). Serum Zn was significantly reduced in TDT patients (p = 0.028) and urinary Zn was significantly elevated (p =0.024). Serum Cu was also significantly reduced in TDT patients (p =0.026). Reduced Zn levels in TDT patients correlated with elevated MDA levels (p = 0.0195, R = -0.382) as were serum Cu levels (p = 0.0158, R = -0.394). Reduced levels of plasma iron trafficking proteins (haptoglobin, hemopexin, and transferrin) were correlated with elevated levels of MDA and LPI (all p-values < 0.05). Plasma MDA was also correlated with fructosamine levels (p < 0.001, R= 0.57).Conclusion: Metal dyshomeostasis involving Zn and Cu may be important contributors to oxidative stress and iron injury in TDT. We confirm previous findings in TDT of elevated levels of LPI as well as the oxidative stress markers MDA and 4-HNE. We expand previous findings of reduced transferrin levels in TDT to show a similar reduction in both haptoglobin and hemopexin. StfR levels were elevated in TDT patients, possibly due to a strong erythropoietic drive. Both reduced haptoglobin and hemopexin as well as decreased Zn and Cu levels and increased Zn excretion appear to be present in TDT. These preliminary findings suggest that low levels of Zn, Cu, haptoglobin and hemopexin may be related to increased oxidative stress and LPI in TDT, which could be important contributors to secondary complications of TDT. DisclosuresWalter:Apopharma: Research Funding.

Relationship of Cytokines and Age Products in Diabetic and Non-Diabetic Patients with Cataract

Cytokines are important mediators of inflammatory and immune responses. The aim of this study was to investigate the changes in cytokines concentration (IL-6, IL-8 and TNF-α) and serum advanced glycation end products (sAGEs) in senile diabetics with or without cataract and non-diabetic patients with cataract. The study included 124 subjects (sixty or over sixty years age), distributed as four groups thirty senile diabetic patients with cataract (Group I) (16 female and 14 male), thirty senile non-diabetic patients with cataract (Group II) (15 female and 15 male), thirty three senile diabetic patients without any complication (Group III) (16 female and 17 male), thirty one apparently normal healthy individuals (Group IV) (16 female and 15 male), age, sex and weight matched with senile control subjects were investigated. Patients were selected on clinical grounds from Eye Ward Jinnah Postgraduate Medical Centre. Interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) levels were significantly increased (P < 0.001) in Group I and III as compared to Group II and IV. Fasting blood glucose, glycosylated hemoglobin, serum fructosamine, malondialdehyde (MDA), sAGEs, IL-6, IL-8 and TNF-α levels were significantly increased (P < 0.001) in Group I as compared to Group II and the levels were almost same in Group II and IV. There was a significant decrease in serum vitamin E and total antioxidant status (p< 0.001) in Group I and Group III as compared to Group II and Group IV. The results of the present study thus demonstrated that levels increased in both condition but are more severe in diabetic patients with cataract that may be a predictor for cataractogenesis and the levels were almost same in Group II and IV.

Glucose and lipid profile of obese dogs fed with different starchy sources

ABSTRACT: Among the health disorders caused by obesity in dogs stand out hyperglycemia and hyperlipidemia. Glycemic responses are directly related to the amount and type of starch. Thus, this study aimed to evaluate the effect of different sources of starch on glycemic and lipid levels in obese dogs. These dogs were distributed in a completely randomized design in a factorial 3x2x2 (three sources starchy - corn (60%), sorghum (60%) and corn: sorghum (30:30%), two breeds - Beagle and Dachshund and males and females. After 28 days of experiment, dogs fed with corn had higher amounts of glucose (93.79A mg dL-1) (P&lt;0.05) compared with diets containing sorghum (88.00Bmg dL-1) and corn: sorghum (88.75B mg dL-1) (P&gt;0.05). Thus, dogs that consumed corn had a higher glycemic peak in a shorter time compared with dogs that ingested sorghum. Furthermore, the dogs fed with diet containing sorghum showed lower levels of fructosamine that dogs that ingested corn diet (P&lt;0.05) demonstrating that the diet containing sorghum maintained blood glucose over a longer time period that reduces the fluctuation of glucose in dogs. At 56 and 112 days of the experiment, a positive correlation between glucose levels and body weight (P&lt;0.05) was also observed. At 28, 56, 84 and 112 days, Beagle dogs showed higher serum concentrations of total cholesterol compared with Dachshund dogs (P&lt;0.05). It was concluded that the starchy source and breed can interfere with metabolic rates of obese dogs.

Comparison of high- and low-dose intra-articular triamcinolone acetonide injection for treatment of primary shoulder stiffness: a prospective randomized trial

Intra-articular corticosteroid injection has a proven effect for shoulder stiffness, yet the optimal dose is still controversial. The purpose of the study was to compare the outcomes of intra-articular triamcinolone acetonide injection at 2 different doses in patients with shoulder stiffness. Intra-articular injection of 40 mg (group I, n = 76) or 20 mg (group II, n = 71) of triamcinolone acetonide was performed in patients with shoulder stiffness. The outcome measures including range of motion (ROM), American Shoulder and Elbow Surgeons score, visual analog scale for pain score, and Simple Shoulder Test score were evaluated at 3 weeks, 6 weeks, 12 weeks, 6 months, 12 months, and the last follow-up. Among the patients with controlled diabetes, the levels of blood glucose, fructosamine, and HbA1c were measured to evaluate systemic serologic changes induced by injection. There were significant improvements in ROM and functional scores in both groups at the last follow-up. However, there was no significant difference between the groups in any of the parameters at each time point. None of the diabetic patients in either group had a significant increase in blood glucose, fructosamine, and HbA1c levels compared with levels before injection. However, those in group I showed significantly higher blood glucose levels at 6 weeks after injection compared with those in group II (P = .01). Intra-articular injection of triamcinolone is an effective method for improving ROM and clinical function in patients with shoulder stiffness. However, there was no significant difference in regard to different doses. In diabetic patients, a lower dose is recommended as short-term glucose levels may increase with a high dose of corticosteroid.

The establishment of biological reference intervals of nontraditional glycemic markers in a Chinese population.

We established the reference intervals for glycated albumin (GA), fructosamine (FA), and 1,5-anhydroglucitol (1,5-AG) in a Chinese healthy population. This study enrolled a total of 458 eligible reference individuals, consisted of 226 men and 232 women, aged from 20~79years (median age 43years), who attending routine healthy checks. We stratified the subjects according to gender (males and females) and age (20-39, 40-59, and 60-79years), and combined statistical methods with Lahti algorithm, as well as appropriate clinical consideration, to judge whether partitioning for data was needed. Glycated albumin levels between males and females were statistically different (P<.001), but the absolute difference between the upper reference limits was only 0.31%, which was too small to be clinically relevant. GA levels across the three age groups were statistically different (P<.001), and Lahti algorithm suggested partitioning for 20-59 and 60-79years, which reference intervals were 10.38%-13.89% and 10.23%-14.79%, respectively. 1,5-AG levels in males were significant higher than females (P<.001), and absolute difference was 51μmol/L (8.5μg/mL) in mean level. Thus, partitioning for gender was needed. Reference intervals for 1,5-AG were 107-367μmol/L for males and 79-306μmol/L for females. The absolute difference of the lower reference limits for FA was only 7μmol/L between males and females. FA levels across the three age groups were not statistically different (P>.05). The reference interval for FA was 220-298μmol/L. New reference intervals for nontraditional glycemic markers were established based on a Chinese population.

Methylglyoxal treatment in lactating mothers leads to type 2 diabetes phenotype in male rat offspring at adulthood.

Environmental and nutritional disorders during perinatal period cause metabolic dysfunction in the progeny and impair human health. Advanced glycation end products (AGEs) are primarily produced during metabolism of excess blood glucose, which is observed in diabetes. Methylglyoxal (MG) is a precursor for the generation of endogenous AGEs, which disturbs the metabolism. This work aimed to investigate whether the maternal MG treatment during lactation programs the progeny to metabolic dysfunction later in life. Female Wistar rats were divided into two groups: control group (C) treated with saline and MG group treated with MG (60mg/kg/day) by gavage throughout the lactation period. Both mothers and offspring were fed a standard chow. At weaning, breast milk composition was analyzed and mothers euthanized for blood and tissue sample collections. At 90 days of age, offspring were submitted to glucose tolerance test (ivGTT) and euthanized for blood and tissue samples collection. MG mothers showed increase in glucose and fructosamine levels; however, they showed low insulin levels and failure in β-cell function (p<0.05). MG mothers also showed dyslipidemia (p<0.05). Moreover, breast milk had elevated levels of glucose, triglycerides, cholesterol and fructosamine and low insulin (p<0.05). Interestingly, MG offspring had increased body weight and adipose tissue at adulthood, and they also showed glucose intolerance and failure in β-cell function (p<0.05). Besides, MG offspring showed dyslipidemia (p<0.05) increasing cardiovascular diseases risk. Maternal MG treatment negatively affects the male rat offspring, leading to type 2 diabetes and dyslipidemia in later life, possibly by changes in breast milk composition.

Zinc oxide nanoparticles and a standard antidiabetic drug restore the function and structure of beta cells in Type-2 diabetes.

The aim of this study was to use Zinc oxide nanoparticles and a standard antidiabetic drug to restore the function and structure of beta cells in a rat model of Type-2 diabetes and compare the effects of a DPP-IV inhibitor with or without zinc oxide nanoparticles (ZnONPs) using a model of type 2 diabetes (rats fed a high fat diet that was treated with a low dose of streptozotocin). Ninety male Wistar rats were randomly divided into three groups 10days after the induction of diabetes: group I: non-diabetic animals that received only the chow diet plus 2ml of 0.5% carboxymethyl cellulose sodium; group II: diabetic animals that received only the chow diet plus 2ml of 0.5% carboxymethyl cellulose sodium; group III: diabetic animals were subdivided into 7 equal subgroups; one subgroup was administered Vildagliptin (10mg/kg/day p.o.); three subgroups were administered ZnONPs at doses of 1, 3 and 10mg/kg/day p.o.; and three subgroups were administered ZnONPs in different doses plus Vildagliptin for seven weeks. The DPP-IV inhibitor (Vildagliptin) and ZnONPs alone or in combination significantly decreased microRNA-103 and microRNA-143 expression compared to the diabetic group, indicating antidiabetic effects. ZnONPs improved many of the indices of diabetic dysfunction (glucose tolerance, weight loss, insulin levels, fructosamine levels, pancreatic SOD activity, and pancreas histology), but the addition of the DPP-IV further improved these indices. ZnONPs alone resulted in significant antidiabetic effects, whereas the addition of Vildagliptin resulted in a synergistic effect on the therapy of diabetes.

Higher glucose level and systemic oxidative stress decrease the mean velocity index of the retinal artery during flickering light stimulation in type 1 diabetes.

AimTo determine whether higher glucose level and systemic oxidative stress decrease mean velocity (MV) index of the central retinal artery (CRA) during flickering light stimulation in type 1 diabetes (T1D).MethodsThe study was performed in the period from 2008 to 2015 at the University Eye Clinic in Ljubljana. 41 patients with T1D and 37 participants without diabetes were included. MV in the CRA was measured using Doppler ultrasound diagnostics in basal conditions and during 8 Hz flickering light irritation. The plasma levels of glucose, fructosamine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), triglycerides, cholesterol, and low-density lipoprotein (LDL) were measured.ResultsPatients with T1D had significantly higher levels of blood glucose (P < 0.001), fructosamine (P < 0.001), and 8-OHdG (P < 0.001), but there were no significant differences in triglycerides (P = 0.108), cholesterol (P = 0.531), and LDL (P = 0.645) between the groups. Patients with T1D also had a significantly lower MV index in the CRA (1.11 ± 0.15 vs 1.24 ± 0.23; P = 0.010). In the T1D group, a significant negative correlation was found between the level of glucose (r = −0.58; P < 0.001), fructosamine (r = −0.46; P = 0.003), 8-OHdG (r = −0.48; P = 0.002) and the MV index in the CRA. At the same time, in this group fructosamine and 8-OHdG levels had a separate effect on the MV index (adjusted R2 = 0.38, P < 0.001).ConclusionHigher glucose levels, the medium-term glucose level, and systemic oxidative stress could importantly reduce retinal vasodilatation during flickering light irritation in patients with T1D.

PARP-1 inhibition alleviates diabetic cardiac complications in experimental animals

Cardiovascular complications are the major causes of mortality among diabetic population. Poly(ADP-ribose) polymerase-1 enzyme (PARP-1) is activated by oxidative stress leading to cellular damage. We investigated the implication of PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for ten weeks after diabetes induction. At the end of study, surface ECG, blood pressure and vascular reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin, and tumor necrosis factor alpha (TNF-α) levels were measured in serum. Finally, histological examination and collagen deposition detection in rat ventricular and aortic sections were carried out.Hearts isolated from diabetic animals showed increased PARP-1 enzyme activity compared to control animals while significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP-1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced by histopathological changes. In addition, 4-AB administration improved the elevated blood pressure and the associated exaggerated vascular contractility, endothelial destruction and vascular inflammation seen in diabetic animals. Moreover, PARP-1 inhibition decreased serum levels of TNF-α and cardiac nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1 inhibition did not significantly affect the developed hyperglycemia.Our findings prove that PARP-1 enzyme plays an important role in diabetic cardiac complications through combining inflammation, oxidative stress, and fibrosis mechanisms.

Low fructosamine and mortality – A long term follow-up of 215,011 non-diabetic subjects in the Swedish AMORIS study

Background and aimsBoth high and low fasting glucose has been associated with an increased mortality among individuals without diabetes. This J-shaped association has also been shown for HbA1c in relation to all-cause mortality. High fructosamine is associated with increased mortality. In this study we aim to evaluate if low fructosamine is also associated with increased mortality in non-diabetic subjects. Methods and resultsWe included 215,011 subjects from the AMORIS cohort undergoing occupational health screening or primary care in Stockholm, Sweden. Cause specific mortality was obtained from the Swedish Cause-of-Death Register by record linkage.Hazard ratios for the lowest decile of fructosamine were estimated by Cox regression for all-cause (n = 41,388 deaths) and cause-specific mortality during 25 years of follow-up.We observed gradually increased mortality with lower fructosamine in a large segment of the population. In the lowest decile of fructosamine the sex, age, social class and calendar adjusted hazard ratio was 1.20 (95% CI; 1.18–1.27) compared to deciles 2–9. This increased mortality was attenuated after adjustment for six other biomarkers (HR = 1.11 (95% CI; 1.07–1.15)). Haptoglobin, an indicator of chronic inflammation, made the greatest difference in the point estimate. In sensitivity analyses we found an association between low fructosamine and smoking and adjustment for smoking further attenuated the association between low fructosamine and mortality. ConclusionLow levels of fructosamine in individuals without diabetes were found to be associated with increased mortality. Smoking and chronic inflammation seem to at least partially explain this association but an independent contribution by low fructosamine cannot be excluded.

Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA‐Ramadan): a randomized trial

AimsCompare effects of liraglutide 1.8 mg and sulphonylurea, both combined with metformin, on glycaemic control in patients with type 2 diabetes (T2D) fasting during Ramadan.Materials and methodsIn this up to 33‐week, open‐label, active‐controlled, parallel‐group trial, adults [glycated haemoglobin (HbA1c) 7%‐10% (53‐86 mmol/mol); body mass index ≥20 kg/m2; intent to fast] were randomized (1:1) ≥10 weeks before Ramadan to either switch to once‐daily liraglutide (final dose 1.8 mg) or continue pre‐trial sulphonylurea at maximum tolerated dose, both with metformin. Primary endpoint: change in fructosamine, a validated marker of short‐term glycaemic control, during Ramadan.ResultsSimilar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide (−12.8 µmol/L); sulphonylurea (−16.4 µmol/L); estimated treatment difference (ETD) 3.51 µmol/L (95% CI: −5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide‐treated (2%, three subjects) versus sulphonylurea‐treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: −0.54 kg; 95% CI: −0.94;−0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: −0.59% (−6.40 mmol/mol), 95% CI: −0.79; −0.38%; −8.63; −4.17 mmol/mol; p < 0.0001].ConclusionsDespite lower fructosamine levels and body weight at the beginning of Ramadan, use of liraglutide showed similar glycaemic improvements, fewer hypoglycaemic episodes and greater body weight reduction compared with sulphonylurea. LIRA‐Ramadan provides evidence for liraglutide being safe and efficacious for management of T2D during Ramadan fasting.

A randomized, placebo-controlled, double-blind study on the effects of (−)-epicatechin on the triglyceride/HDLc ratio and cardiometabolic profile of subjects with hypertriglyceridemia: Unique in vitro effects

BackgroundCardiometabolic disruptions such as insulin resistance, obesity, high blood pressure, hyperglycemia, and dyslipidemias, are known to increase the risk for cardiovascular and metabolic diseases such as type 2 diabetes mellitus and atherosclerosis. Several screening tools for assessing cardiometabolic risk have been developed including the TG/HDLc ratio, which has been, demonstrated to possess a strong association with insulin resistance and coronary disease.Dietary modifications, together with regular moderate exercise have proven to be effective in attenuating cardiometabolic disruptions. However, they often exhibit poor long-term patient compliance. Nutraceutics, including (−)-epicatechin (EPI), have gained increasing interest as coadjuvant effective and safe therapies that are able to attenuate hypertension, hyperglycemia, hyperinsulinemia, hypertriglyceridemia and hypoalphalipoproteinemia. MethodsThe aims of this study were: 1) to compare the in vitro effect of EPI vs. (+)-catechin on fructose induced triglyceride accumulation and mitochondrial function in Hep2 cells in culture, 2) to evaluate the efficacy of EPI treatment in reducing fasting blood triglycerides and improving the TG/HDLc ratio in hypertriglyceridemic patients with a total daily dose of 100mg of EPI. Secondary clinical variables included total cholesterol, LDLc, fructosamine, glucose, insulin, and high sensitivity C-reactive protein blood levels. Results and conclusionOur results provide preliminary evidence as to favorable effects of EPI on glycemia homeostasis, lipid profile and systemic inflammation such bioactive actions are not class-effects (i.e. limited to their antioxidant potential) but instead, may result from the specific activation of associated downstream signaling pathways since catechin has no effects.

Elevated cardiac 3-deoxyglucosone, a highly reactive intermediate in glycation reaction, in doxorubicin-induced cardiotoxicity in rats

3-Deoxyglucosone (3-DG) is a highly reactive carbonyl intermediate in glycation reaction (also known as Maillard reaction) and plays an important role in diabetic complications. We investigated the potential involvement of 3-DG in doxorubicin (DXR)-induced cardiotoxicity. Male Crl:CD(SD) rats received intravenous injections of DXR at 2mg/kg, once weekly, for 6 weeks, with/without daily intraperitoneal treatment with 3-DG scavenging agents, i.e., aminoguanidine (AG, 25mg/kg/day) and pyridoxamine (PM, 60mg/kg/day). Cardiac levels of 3-DG, thiobarbituric acid reactive substances (TBARS), fructosamine, and pentosidine, plasma glucose levels and cardiac troponin I (cTnI), echocardiography, and histopathology were assessed at 4 and 6 weeks after treatment. Cardiac 3-DG levels were significantly increased by DXR treatment at 4 and 6 weeks. Cardiac fructosamine levels and plasma glucose were not altered by DXR; however, TBARS levels in the heart were significantly increased at 4 and 6 weeks, suggesting that the enhanced generation of 3-DG is not attributed to any abnormal glycemic status, but may be related to oxidative stress by DXR. An advanced glycation end-product, pentosidine, was significantly increased by DXR treatment at 6 weeks. Intervention by AG and PM ameliorated the DXR-induced echocardiographic abnormalities, increased cTnI in plasma, and histopathological lesion as well as normalizing the elevation of 3-DG and pentosidine levels. These results suggest that 3-DG is generated by DXR and involved, at least in part, in the pathogenesis of DXR-cardiotoxicity through glycation reaction.

Moringa oleifera aqueous leaf extract inhibits reducing monosaccharide-induced protein glycation and oxidation of bovine serum albumin.

Advanced glycation end products (AGEs) play an important factor for pathophysiology of diabetes and its complications. Moringa oleifera is one of the medicinal plants that have anti-hyperglycemic activity. However, anti-glycation property of Moringa oleifera leaf extract on the different types of reducing monosaccharides-induced protein glycation has not been investigated. Therefore, the aim of this study was to examine the protective effect of Moringa oleifera aqueous leaf extract (MOE) on reducing sugars-induced protein glycation and protein oxidation. Total phenolic content of MOE was measured using the Folin–Ciocalteu method. Bovine serum albumin was incubated with 0.5 M of reducing sugars (glucose or fructose) with or without MOE (0.5–2.0 mg/mL) for 1, 2, 3 and 4 weeks. The results found that total phenolic content was 38.56 ± 1.50 mg gallic acid equivalents/g dry extract. The formation of fluorescent and non-fluorescent AGEs [Nε-(carboxymethyl) lysine (CML)] and the level of fructosamine were determined to indicate protein glycation, whereas the level of protein carbonyl content and thiol group were examined for protein oxidation. MOE (0.5–2.0 mg/mL) significantly inhibited the formation of fluorescent, Nε-CML and markedly decreased fructosamine level (P < 0.05). Moreover, MOE significantly prevented protein oxidation manifested by reducing protein carbonyl and the depletion of protein thiol in a dose-dependent manner (P < 0.05). Thus, the findings indicated that polyphenols containing in MOE have high potential for decreasing protein glycation and protein oxidation that may delay or prevent AGE-related diabetic complications.

Molecular mechanisms of the antiglycative and cardioprotective activities of Psidium guajava leaves in the rat diabetic myocardium

Context: Antiglycative potential of Psidium guajava L. (Myrtaceae) leaves has been established. However, the molecular basis of its antiglycative potential remains unknown.Objective: The ethyl acetate fraction of P. guajava leaves (PGEt) was evaluated to determine the cardioprotective effect and its mechanism of action compared to quercetin.Materials and methods: After the induction of diabetes by streptozotocin (55 mg/kg body weight), PGEt and quercetin (50 mg/kg body weight) was administered for 60 days. Rats were grouped as follows: Group C: Control, Group D: Diabetic, Group D + E: Diabetic rats treated with PGEt, Group D + Q: Diabetic rats treated with quercetin. The antiglycative potential was evaluated by assaying glycosylated haemoglobin, serum fructosamine and advanced glycation end product levels. The differential receptor for advanced glycation end products and nuclear factor kappa B (NFκB) protein levels was determined by western blot and the transcript level changes of connective tissue growth factor (CTGF), brain natriuretic peptide (BNP) and TGF-β1 in heart tissue were assessed by RT-PCR analysis.Results: Glycated haemoglobin and serum fructosamine levels were found to be enhanced in diabetic rats when compared with control. Administration of PGEt significantly reduced the glycated haemoglobin and fructosamine levels to a larger extent than quercetin treated diabetic rats. PGEt reduced the translocation of NFκB from cytosol to nucleus when compared with diabetic rats. Expression of TGF-β1, CTGF and BNP was downregulated in PGEt treated groups compared with diabetic controls.Discussion and conclusion: Administration of PGEt ameliorated diabetes associated changes in the myocardium to a greater extent than quercetin.

YI-11 - a-13'-OH is the main product of a-tocopherol metabolism and influences CYP4F2 and PPAR? gene expression in HepG2 human hepatocarcinoma cells

Glycine has been proposed as an immune modulator and cell protector for several pathologies. Results of several in vivo studies have shown that glycine inhibits glycation of hemoglobin; however, its role or effects on protein oxidation and formation of advanced glycation end products (AGEs) have not been studied yet. The present investigation aims to determine the effect of daily administration of glycine on the end products of glucose toxicity conformation in experimentally diabetic mice induced by streptozotocin.Four groups of mice were set as follows: Group 1, healthy controls; Group 2, diabetic controls; Group 3, diabetic and administered with aminoguanidine (0.1 g/kg/day); Group 4, diabetic and administered with glycine (0.2 g/kg/day). After treatment for 25 days, the animals were sacrificed and samples of serum, liver, and kidneys were isolated. Glycated hemoglobin (HbA1C), fructosamine, and formation of AGE of bovine serum albumin (AGE-BSA) were quantified together along with determination of liver and kidney protein oxidation. In addition, histological studies were also conducted.The experimental data demonstrate that glycine reduced glucose, HbA1C, and fructosamine levels in blood. Even more, glycine significantly reduced AGE-BSA conformation, but the reduction of protein oxidation occurred only in the kidneys. With regard to morphological studies, it was observed that diabetic mice had liver and kidney alterations such as liver steatosis and kidney glomerulosclerosis, respectively, with a diminished activity of alanine aminotransferase linked to glycine treatment.Administration of glycine prevents some glucose toxicity, suggesting prevention of development of vascular complications in mice with diabetes mellitus.

Combined therapy with metformin and insulin attenuates systemic and hepatic alterations in a model of high-fat diet-/streptozotocin-induced diabetes.

In this study we have explored the pathogenesis of the hepatic alterations which occur in diabetes and the modulation of these complications by the combination of metformin adjunct treatment and insulin monotherapy. For this purpose, diabetic rats were treated with insulin (DM+Ins) or metformin plus insulin (DM+Met+Ins). Biochemical and cardiometabolic parameters were analysed by spectrophotometry. Intravital microscopy was used to study the hepatic microcirculation. In the liver tissue, real-time PCR was used to analyse oxidative stress enzymes, inflammatory markers and receptors for advanced glycation end products (AGE) (RAGE) gene expression. Lipid peroxidation was assessed by thiobarbituric acid reactive species (TBARs) analyses. AGE deposition and RAGE protein expression were studied by fluorescence spectrophotometry and Western blot respectively. Body weight, %HbA1c , urea, total proteins and oxidative stress parameters were found to be similarly improved by insulin or Met+Ins treatments. On the other hand, Met+Ins treatment showed a more pronounced effect on fasting blood glucose level than insulin monotherapy. Fructosamine, uric acid, creatinine, albumin and amylase levels and daily insulin dose requirements were found to be only improved by the combined Met+Ins treatment. Liver, renal and pancreatic dysfunction markers were found to be more positively affected by metformin adjunct therapy when compared to insulin treatment. Liver microcirculation damage was found to be completely protected by Met+Ins treatment, while insulin monotherapy showed no effect. Our results suggest that oxidative stress, microcirculatory damage and glycated proteins could be involved in the aetiology of liver disease due to diabetes. Additionally, metformin adjunct treatment improved systemic and liver injury in induced diabetes and showed a more pronounced effect than insulin monotherapy.