Fructosamine Concentrations Research Articles

Study of the activity of lipolysis and gluconeognesis in new-child cows with subclinical and clinical ketosis

The article discusses the results of a study of markers of lipolysis and gluconeogenesis in new-calf cows against the background of subclinical and clinical ketosis. The indicator of beta-hydroxybutyric acid in blood serum was chosen as a marker for the formation of groups based on the presence of ketosis and its form. Cows with an indicator of up to 1.0 mmol/l were considered healthy, the presence of subclinical ketosis was determined at a level of beta-hydroxybutyrate from 1.1 to 1.5 mmol/l, clinical ketosis - over 1.6 mmol/l. Cows were bled 3-7 days after calving and a study was made of the concentration of beta-hydroxybutyric acid, glucose, fructosamine, non-esterified fatty acids, cortisol and ALT activity. The results of the study revealed a significant increase in the concentration of non-esterified fatty acids in cows with moderate ketonemia by 46.9%, and in cows with a pronounced increase in the content of beta-hydrosibutyrate in the blood - by 79.8%. When considering the concentration of glucose in cows with different levels of beta-hydroxybutyrate in the blood, there is a slight increase in the indicator by 14.5% (P> 0.05) in cows with subclinical ketosis, but in animals with severe ketonemia, a significant decrease in glucose by 38.3 %. Cows in subclinical and clinical ketosis had significantly higher levels of cortisol (1.9 and 2.4 times, respectively) than cows with low blood levels of betahydroxybutyric acid. At the same time, cows with clinical ketosis showed a significant increase in the concentration of fructosamine by 22.3%. Subclinical ketosis, manifested by a moderate increase in the concentration of beta-hydroxybutyric acid in the blood (1.1 - 1.5 mmol / l), causes adaptive reactions in the body aimed at maintaining glucose homeostasis and extracting lipids from the depot that compensate for a temporary energy deficit. Clinical ketosis is accompanied by dissociation of the regulatory mechanisms of anabolic and catabolic processes in the body of a freshly calved cow.

Role of glycemic control in elective percutaneous coronary interventions in patients with type 2 diabetes

Aim. To assess the association of glycemic control (achievement of an individual target glycated hemoglobin level) with the outcomes of elective percutaneous coronary interventions in patients with type 2 diabetes (T2D).Material and methods.This cohort observational study included 74 patients with a median age of 61 (57; 64) years. There were 49% of men with a previously established T2D, who had indications for elective primary percutaneous coronary intervention (PCI) for stable coronary artery disease. At inclusion in the study and after 1 month, the concentration of fasting blood glucose, glycated hemoglobin (HbA1c), fructosamine, and serum creatinine were determined. Plasma glucose levels were determined using the hexokinase method. HbA1clevel was determined by immunoturbidimetry on a Konelab 30i chemistry analyzer. The concentration of fructosamine was determined by the kinetic colorimetric assay on a Konelab 30i chemistry analyzer. Statistical processing was carried out using the Statistica 10.0 program from StatSoft, Inc. (USA).Results.At the time of enrollment, 31% of participants had not achieved the target glycated hemoglobin level against the background of nonoptimal hypoglycemic therapy in most cases. A total of 18 (25%) following adverse cardiovascular events were registered within 12 months after PCI: 11 (15%) patients developed acute coronary syndrome; among them, 6 (8%) patients had stent restenosis according to coronary angiography, 4 (6%) patients — progression of atherosclerosis, which required repeated PCI with stenting of another vessel, 2 (3%) patients — cerebrovascular accident, and 3 (4%) patients were hospitalized due to de compensated heart failure. According to multivariate logistic regression, only the HbA1clevel was a predictor of adverse outcomes during the year after PCI — a 1% increase in HbA1clevel increased the risk of adverse outcomes by 1,79 times (odds ratio, 1,79, 95% confidence interval, 1,06-3,02, p=0,028). Poor glycemic control 1 month before PCI increased the risk of cardiovascular events by 4,04 times over the next year, while non-target HbA1clevel immediately before PCI increased the risk of adverse outcomes by 4,7 times, and 5 months after PCI, by 7,34 times.Conclusion.The significance of non-target glycated hemoglobin level for adverse outcomes during the year after elective PCI against the background of T2D was established with an increase in the negative effect as long-term (after myocardial revascularization) maintenance of poor glycemic control.

PSUN176 Fructosamine as a screening test for gestational diabetes

Abstract Background All organizations use variable glucose criteria for diagnosis of gestational diabetes (GDM). However all involve OGTT. American college of Obstetrics and Gynecology (ACOG) and American Diabetes Association (ADA) recommend 2 step testing; 1) 1 hour glucose level on 50 gm glucose ingestion at any time during the day (1 hour OGTT) and 2) 3 hour OGTT with 100 gm glucose ingestion after overnight fast in pregnant women with glucose > 140 mg/dl during 1 hour. OGTTs require preparation with least daily intake of carbohydrate 150 gm for 3 days before testing. Many women are hesitant getting tested because of nausea, vomiting on glucose ingestion. Thus, none of the tests is convenient. Objective We examined utility of serum Fructosamine level as a screening test for diagnosis of GDM. Methods Random serum glucose and Fructosamine (mcM/l) levels as well as HbA1c (%) were determined at 24-30 weeks in 206 pregnant women, ages 24-40 years along with 1 hour OGTT and then again with 3 hour OGTT in 46 pregnant women with abnormal 1 hour OGTT and 21 age matched non-pregnant women. Continuous glucose monitoring (CGM) for 2 weeks was performed in 5 pregnant women with abnormal 3 hour OGTT and 7 non-pregnant women. Results Fructosamine levels (192± 4) were significantly lower (p<0.01) in nondiabetic pregnant women when compared with age matched non-pregnant women (224 ± 5). Cutoff serum Fructosamine concentration between groups was 205. Glucose and HbA1c were not significantly different amongst groups. Serum Fructosamine levels in 26 pregnant with abnormal 1 hour but normal 3 hour OGTT were <205, similar to nondiabetic pregnant women. Serum Fructosamine concentrations in women with abnormal 3 hour OGTT and normal CGM e.g, 70-140 mg /dl matched levels in nondiabetic pregnant women. Conclusion CGM may be the most accurate test for diagnosis of GDM. Random serum Fructosamine level may be as accurate as CGM and more accurate than both OGTTs. Importantly, it is a simple and convenient test without requiring fast, glucose ingestion or preparation. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

BIOCHEMICAL ENERGY AND HEMATOLOGICAL PROFILE OF SHEEP SUPPLEMENTED WITH SOY MOLASSES

Soy molasses is a by-product of the soy industry, with low commercial cost and rich in carbohydrates and proteins. Despite the great variety of by-products and being potentially beneÞ cial, it is not fully understood how the interaction between the nutrients in this product and the physiological changes in sheep occurs. Thus, the objective was to evaluate the effects of supplementation levels with soy molasses on the energy metabolites and hematological parameters of sheep. The treatments consisted of 0, 3, 6, 9, and 12% of inclusion of soy molasses in dry matter basis for a basal diet of corn silage, which met the nutritional needs of the sheep in maintenance, distributed in a 5 × 5 Latin square design. The energy metabolites evaluated were: cholesterol, triglycerides, very-low-density lipoproteins (VLDL), and fructosamine. The hematological parameters were: red blood cells, hemoglobin, hematocrits, and platelets, in addition to leukocytes, rods, neutrophils, eosinophils, monocytes, and lymphocytes. Supplementation with soy molasses did not signiÞ cantly alter (P> 0.05) the serum concentrations of cholesterol, triglycerides, VLDL, and fructosamine. There was no signiÞ cant difference in the blood cell, hemoglobin, hematocrit, and platelet concentrations in sheep receiving soy molasses supplementation (P> 0.05), which may indicate that the level of inclusion was sufÞ cient to meet the nutritional needs of the animals, without damage. Leukocyte, rod, neutrophil, eosinophil, monocyte, and lymphocyte concentrations did not change (P> 0.05) with the inclusion of soy molasses in the sheep’s diet, indicating the absence of intoxication, diseases, and infections. It can be concluded that supplementation with soy molasses does not alter the energy metabolites and hematological parameters of sheep in maintenance.

Evaluation of Candida spp. and Other Fungi in Feces from Dogs with Naturally Occurring Diabetes Mellitus.

Simple SummaryDiabetes mellitus is a common endocrine disorder in dogs that is similar to type 1 diabetes mellitus (T1DM) in humans. Candida spp. is a common non-pathogenic fungi that is identified more commonly and in higher amounts in humans with T1DM, including the gastrointestinal tract. This change to the distribution of microorganisms that inhabit the intestine has potential to affect glycemic control and even spread to other organs and cause severe illness. There are no studies that have investigated whether diabetic dogs, like humans, have alterations to the intestinal mycobiome. Therefore, our study sought to determine whether differences exist in the types of fungi cultured from feces in diabetic dogs and non-diabetic healthy control dogs. In addition, we wanted to find out if there were variables associated with fungi colonization. Diabetic dogs had more quantitative fungal growth than controls and females were more likely to yield growth than males. Diabetic dogs were also more likely to have Candida spp. colonized from feces. Glycemic control was also seemingly associated with growth of Candida spp. in diabetic dogs. Our results indicate that the intestinal mycobiome is altered in diabetic dogs with increased prevalence of Candida spp. and quantitative growth of fungi.Diabetes mellitus is a common endocrinopathy in dogs and in most cases is analogous to type 1 diabetes mellitus (T1DM) in humans. Candida spp. is a common commensal fungi with higher prevalence and magnitude of growth in humans with T1DM. There is currently no published information about the fungal microbiome in diabetic dogs. Therefore, the objectives of this study were to (i) determine whether diabetic dogs were more likely to have Candida spp. or other types of fungi from feces compared to non-diabetic controls, and (ii) identify variables associated with fungi colonization. Fourteen diabetic dogs and 14 age, sex, and breed matched non-diabetic healthy control dogs were included in this prospective case–control study. Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used for fungal identification. Diabetic dogs had greater quantitative fungal growth compared to controls (p = 0.004). Moreover, female dogs were more likely to have fungi colonization than males (p = 0.02). All instances of Candida spp. and Aspergillus spp. colonization were exclusively identified in diabetic dogs. Serum fructosamine concentration was higher in diabetic dogs with fecal colonization of Candida spp. compared to diabetic dogs without growth (p = 0.03). Our results indicate that the fungal microbiome in feces is altered in diabetic dogs, which seem to favor an increased prevalence of Candida spp. and higher quantitative fungal growth. Moreover, female sex and glycemic control could affect the intestinal mycobiome.

Trimester-Specific Serum Fructosamine in Association with Abdominal Adiposity, Insulin Resistance, and Inflammation in Healthy Pregnant Individuals.

This study aimed to (1) characterize the variations in serum fructosamine across trimesters and according to pre-pregnancy BMI (ppBMI), and (2) examine associations between fructosamine and adiposity/metabolic markers (ppBMI, first-trimester adiposity, leptin, glucose homeostasis, and inflammation measurements) during pregnancy. Serum fructosamine, albumin, fasting glucose and insulin, leptin, adiponectin, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were measured at each trimester. In the first trimester, subcutaneous (SAT) and visceral (VAT) adipose tissue thicknesses were estimated by ultrasound. In the 101 healthy pregnant individuals included (age: 32.2 ± 3.5 y.o.; ppBMI: 25.5 ± 5.5 kg/m2), fructosamine concentrations decreased during pregnancy whereas albumin-corrected fructosamine concentrations increased (p < 0.0001 for both). Notably, fructosamine concentrations were inversely associated with ppBMI, first-trimester SAT, VAT, and leptin (r = −0.55, r = −0.61, r = −0.48, r = −0.47, respectively; p < 0.0001 for all), first-trimester fasting insulin and HOMA-IR (r = −0.46, r = −0.46; p < 0.0001 for both), and first-trimester IL-6 (r = −0.38, p < 0.01). However, once corrected for albumin, most of the correlations lost strength. Once adjusted for ppBMI, fructosamine concentrations were positively associated with third-trimester fasting glucose and CRP (r = 0.24, r = 0.27; p < 0.05 for both). In conclusion, serum fructosamine is inversely associated with adiposity before and during pregnancy, with markers of glucose homeostasis and inflammation, but the latter associations are partially influenced by albumin concentrations and ppBMI.

Longitudinal analysis of the rectal microbiome in dogs with diabetes mellitus after initiation of insulin therapy.

There have been numerous studies in humans and rodents substantiating the role of the gastrointestinal microbiome in the pathogenesis and progression of both type 1 and type 2 diabetes mellitus. Diabetes mellitus is a common endocrinopathy in dogs; however, little is known about the composition of the gut microbiome during the development and treatment of diabetes in this species. The objective of this pilot study was to characterize the gastrointestinal microbiome of dogs with diabetes mellitus at the time of diagnosis and over the first 12 weeks of insulin therapy and identify associations with glycemic control. Rectal swabs and serum for fructosamine measurement were collected from 6 newly diagnosed diabetic dogs at 2-week intervals for 12 weeks. Rectal samples were sequenced using 16S, ITS, and archaeal primers. Measures of alpha and beta diversity were assessed for changes over time; associations between absolute sequence variant (ASV) relative abundances and time and fructosamine concentration were identified using a microbiome-specific, multivariate linear effects model. No statistically significant changes over time were noted in alpha diversity and samples significantly grouped by dog rather than by time in the beta diversity analysis. However, multiple ASVs were negatively (Clostridium sensu stricto 1, Romboutsia, Collinsella) and positively (Streptococcus, Bacteroides, Ruminococcus gauveauii, Peptoclostridium) associated with time and two ASVs were positively associated with fructosamine (Enterococcus, Escherichia-Shigella). These changes in gastrointestinal microbial composition warrant further investigation of how they may relate to diabetes mellitus progression or control in dogs.

Repeated Low-Dose Streptozotocin and Alloxan Induced Long-Term and Stable Type 1 Diabetes Model in Beagle Dogs.

Type 1 diabetes mellitus (T1DM) is a chronic disease represented by insulin-causing pancreatic β-cell disruption and hyperglycemia. Therefore, it is necessary to establish a variety of animal models of diabetes to study the pathogenesis and pathophysiology of it. However, there are few reports on the use of beagle dogs to establish an animal model of type 1 diabetes. This study aimed to explore a simple and feasible modeling method to establish a long-term and stable type 1 diabetes model in beagle dogs. Forty adult beagle dogs were randomly divided into control group and model group. After 24 h of fasting, streptozotocin (20 mg/kg) and alloxan (20 mg/kg) were injected through the cephalic vein. The second intravenous injection was given on the 4th day after the first injection. Insulin release testing was performed on the 7th day after the last intravenous injection. Fasting blood glucose and body weight were recorded monthly. Four months after the last injection, the serum fructosamine content and the ratio of glycated hemoglobin were detected. Then, the pancreatic tissue was harvested for histopathological examination. The results showed that the level of fasting blood glucose of the 16 dogs in the model group was consistently higher than 11.1 mmol/L for 4 consecutive months. Moreover, compared with the control group, the insulin release curve of the model group was flat with no increase. The body weight of the model group was significantly reduced, and the ratios of blood glucose, fructosamine, and glycosylated hemoglobin were significantly higher than those in the control group. Meanwhile, histopathological examination of the pancreas showed that the islet beta cells appeared to have vacuoles or even necrosis. In the model group, pancreatic β-cells were damaged and insulin release was reduced. These results suggest that the above modeling methods can induce long-term and stable type 1 diabetes models in beagle dogs.

Fructosylation of human insulin causes AGEs formation, structural perturbations and morphological changes: an in silico and multispectroscopic study

Fructosylation of proteins results in the formation of advanced glycation end-products (AGEs). A diet rich in fructose along with hyperglycemia can cause fructose mediated glycation (fructosylation) of proteins, which results in AGEs formation. Insulin is a peptide hormone that is glycated when exposed to carbohydrates such as glucose. In this study, we have analysed the interaction of insulin with fructose and biophysically characterized fructose modified insulin. In silico studies performed through molecular docking and molecular dynamics simulation revealed that fructose binds to insulin with strong affinity resulting in the formation of insulin-fructose complex. Fructosylation of insulin caused hyperchromicity, loss of intrinsic fluorescence, gain in AGEs specific fluorescence and elevated the carbonyl and fructosamine content. Enhanced thioflavin T fluorescence suggested the presence of fibrillar structures at higher concentrations of fructose. Electron microscopy revealed the formation of characteristic amorphous and amyloid like aggregates at lower and higher concentrations of fructose, respectively. These findings show that fructosylation of insulin causes AGEs production, aggregation and alters its gross structural integrity. These changes may reduce the biological activity of insulin that can aggravate conditions like type II diabetes mellitus. Communicated by Ramaswamy H. Sarma

Binding Studies of Caffeic and p-Coumaric Acid with α-Amylase: Multispectroscopic and Computational Approaches Deciphering the Effect on Advanced Glycation End Products (AGEs).

Alpha-amylase (α-amylase) is a key player in the management of diabetes and its related complications. This study was intended to have an insight into the binding of caffeic acid and coumaric acid with α-amylase and analyze the effect of these compounds on the formation of advanced glycation end-products (AGEs). Fluorescence quenching studies suggested that both the compounds showed an appreciable binding affinity towards α-amylase. The evaluation of thermodynamic parameters (ΔH and ΔS) suggested that the α-amylase-caffeic/coumaric acid complex formation is driven by van der Waals force and hydrogen bonding, and thus complexation process is seemingly specific. Moreover, glycation and oxidation studies were also performed to explore the multitarget to manage diabetes complications. Caffeic and coumaric acid both inhibited fructosamine content and AGE fluorescence, suggesting their role in the inhibition of early and advanced glycation end-products (AGEs). However, the glycation inhibitory potential of caffeic acid was more in comparison to p-coumaric acid. This high antiglycative potential can be attributed to its additional –OH group and high antioxidant activity. There was a significant recovery of 84.5% in free thiol groups in the presence of caffeic acid, while coumaric attenuated the slow recovery of 29.4% of thiol groups. In vitro studies were further entrenched by in silico studies. Molecular docking studies revealed that caffeic acid formed six hydrogen bonds (Trp 59, Gln 63, Arg 195, Arg 195, Asp 197 and Asp 197) while coumaric acid formed four H-bonds with Trp 59, Gln 63, Arg 195 and Asp 300. Our studies highlighted the role of hydrogen bonding, and the ligands such as caffeic or coumaric acid could be exploited to design antidiabetic drugs.

Resveratrol Inhibits Metabolism and Affects Blood Platelet Function in Type 2 Diabetes.

Chronic hyperglycemia contributes to vascular complications in diabetes. Resveratrol exerts anti-diabetic and anti-platelet action. This study aimed to evaluate the effects of resveratrol on metabolism and the function of blood platelets under static and in in vitro flow conditions in patients with type 2 diabetes. Blood obtained from 8 healthy volunteers and 10 patients with type 2 diabetes was incubated with resveratrol and perfused over collagen-coated capillaries. Isolated blood platelets were incubated with resveratrol and activated by collagen to assess platelet function, metabolism, ATP release, TXA2 production, lipid peroxidation, and gluthatione content. In the type 2 diabetes group, plasma glucose and fructosamine concentrations were significantly higher than in the healthy group. In in vitro studies, collagen-induced thrombi formation in the blood of diabetic patients was 33% higher than in the healthy group. Resveratrol reduced thrombi by over 50% in the blood of healthy and diabetic patients. TXA2 production was 47% higher in diabetic platelets than in the healthy group. Resveratrol reduced TXA2 release by 38% in healthy platelets and by 79% in diabetic platelets. Resveratrol also reduced the activities of enzymes responsible for glycolysis and oxidative metabolism in the platelets of both groups. These data indicate that the resveratrol-induced inhibition of platelet metabolism and TXA2 release may lead to a reduction of platelet function and thrombus formation in patients with type 2 diabetes. Therefore, resveratrol may be beneficial to prevent vascular complications as a future complementary treatment in aspirin-resistant diabetic patients.

Relationship between HbA1c, fructosamine and clinical assessment of glycemic control in dogs.

BackgroundSerum fructosamine is a routine test used for clinical monitoring of diabetes mellitus (DM) but the usefulness of HbA1c for this purpose has not been extensively studied.HypothesisThe study aimed to compare the ability of blood HbA1c and serum fructosamine tests to correctly classify DM control determined using a clinically-based assessment.Animals28 client-owned dogs with naturally-occurring diabetes mellitus.MethodsCross-sectional observational study. Ability of fructosamine and HbA1c tests to classify diabetes control in dogs was determined.ResultsClinical assessment classified 50% of dogs as having good diabetic control and 82% as having acceptable diabetic control. Analysis using Cohen’s kappa test showed that agreements between fructosamine and HbA1c results and the clinical assessment ranged from poor to fair. Fructosamine and HbA1c results from each dog showed a moderate correlation. Overall, the HbA1c test showed the best agreement with the clinical assessment when diabetes control was considered either acceptable or unacceptable, although the strength of agreement was considered fair (kappa = 0.27).Conclusions and clinical importanceThe HbA1c concentration was found to be more consistent with clinical evaluation of diabetes control than was the serum fructosamine concentration. The HbA1c level is a useful tool for assessment of glycemic status in diabetic dogs but should be used alongside other tests for outpatient monitoring of clinically stable diabetic dogs.

Cabergoline treatment in cats with diabetes mellitus and hypersomatotropism.

The aim of this study was to evaluate the safety and efficacy of cabergoline to control hypersomatotropism (HST) and diabetes mellitus (DM) in cats. This was a prospective cohort study. Twenty-three cats with HST and concurrent DM were enrolled. Cats received a dose of 10 μg/kg cabergoline q48h PO for 6 months. Serum insulin-like growth factor 1 (IGF-1) and fructosamine concentrations, insulin dose and Insulin Resistance Index (IRI) were measured at the time of diagnosis of HST and at the start of cabergoline treatment (t0), and 3 months (t1) and 6 months (t2) during cabergoline treatment. A decrease and normalization of serum IGF-1 concentration was observed in 35% and 26% of cats, respectively. Median IGF-1 (t0: 1350 ng/ml [range 832-1501]; t1: 1284 ng/ml [range 365-1501]; t2: 1240 ng/ml [range 263-1501]; P = 0.016) decreased significantly. Twelve cats underwent diagnostic imaging of the pituitary area. The median pituitary height at t0 of cats that experienced an IGF-1 reduction (n = 5/12) was significantly lower compared with those that did not experience an IGF-1 reduction (n = 7/12) (3.2 mm [range 3.1-3.7] vs 6 mm [range 3.5-9.5]; P = 0.011). Median fructosamine (t0: 628 µmol/l [range 400-963]; t1: 404 µmol/l [range 249-780]; t2: 400 µmol/l [range 260-815]; P <0.0001), insulin dose (t0: 1.3 IU/kg [range 0.5-4.6]; t0: 0.5 IU/kg [range 0-2.3]; t2: 0.4 IU/kg [range 0-2.1]; P <0.0001) and IRI (t0: 800 µmolIU/kgl [range 257-2700]; t1: 300 µmolIU/kgl [range 0-1498]; t2: 250 µmolIU/kgl [range 0-1498]; P <0.0001) decreased significantly during cabergoline treatment. Eight cats achieved diabetic remission between months 1 and 6 of cabergoline treatment (median time to achieve remission: 3 months [range 1-6]). Three cats experienced asymptomatic hypoglycemia. Cabergoline was effective in normalizing IGF-1 concentration in 26% of cats. Cabergoline improved diabetes control and was associated with remission of DM in 35% of cases. Cabergoline could be a treatment option for cats with HST and DM, especially in those cases with a relatively small pituitary tumor.

Albumin-Corrected Fructosamine Predicts All-Cause and Non-CVD Mortality Among the Very Elderly Aged 80 Years or Older Without Diabetes.

Several guidelines have suggested alternative glycemic markers for hemoglobin A1c among older adults with limited life expectancy or multiple coexisting chronic illnesses. We evaluated associations between fructosamine, albumin-corrected fructosamine (AlbF), fasting plasma glucose (FPG), and mortality in the diabetic and nondiabetic subpopulations, and compared which marker better predicts mortality among participants aged 80 and older. Included were 2 238 subjects from the Healthy Ageing and Biomarkers Cohort Study (2012-2018) and 207 participants had diabetes at baseline. Multivariable Cox proportional hazards regression models investigated the associations of fructosamine, AlbF, FPG, and all-cause, cardiovascular disease (CVD), and non-CVD mortality in the diabetic and nondiabetic subpopulations. Restricted cubic splines explored potential nonlinear relations. C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) evaluated the additive value of different glycemic markers to predict mortality. Overall, 1 191 deaths were documented during 6 793 person-years of follow-up. In the linear model, per unit increases of fructosamine, AlbF, and FPG were associated with a higher risk of mortality in nondiabetic participants, with hazard ratios of 1.02 (1.00, 1.05), 1.27 (1.14, 1.42), and 1.04 (0.98, 1.11) for all-cause mortality, and 1.04 (1.00, 1.07), 1.38 (1.19, 1.59), and 1.10 (1.01, 1.19) for non-CVD mortality, respectively. Comparisons indicated that AlbF better predicts all-cause and non-CVD mortality in nondiabetic participants with significant improvement in IDI and NRI. Higher concentrations of fructosamine, AlbF, and FPG were associated with a higher risk of all-cause or non-CVD mortality among the very elderly where AlbF may constitute an alternative prospective glycemic predictor of mortality.

Influence of high-protein and high-carbohydrate diets on serum lipid and fructosamine concentrations in healthy cats.

The aim of this study was to determine whether high-protein and high-carbohydrate diets exert differential effects on serum cholesterol, triglyceride and fructosamine concentrations in healthy cats. A randomised, crossover diet trial was performed in 35 healthy shelter cats. Following baseline health assessments, cats were randomised into groups receiving either a high-protein or high-carbohydrate diet for 4 weeks. The cats were then fed a washout diet for 4 weeks before being transitioned to whichever of the two studied diets they had not yet received. Fasting serum cholesterol, triglyceride and fructosamine concentrations were determined at the end of each 4-week diet period. Cats on the high-carbohydrate diet had significantly lower serum cholesterol (P <0.001) concentrations compared with baseline measurements. Cats on the high-protein diet had significantly higher serum cholesterol (P <0.001) and triglyceride (P <0.001) concentrations, yet lower fructosamine (P <0.001) concentrations compared with baseline measurements. In contrast, overweight cats (body condition score [BCS] >5) had lower cholesterol (P = 0.007) and triglyceride (P = 0.032) concentrations on the high-protein diet than cats within other BCS groups. Diets higher in protein and lower in carbohydrates appear beneficial for short-term glucose control in healthy cats. A high-protein diet was associated with significantly elevated cholesterol and triglyceride concentrations in healthy cats, even though the increase was significantly less pronounced in cats with a BCS >5. This finding suggests that overweight cats process high-protein diets, cholesterol and triglycerides differently than leaner cats.

Assessment of iris vasculature abnormalities in dogs with diabetes mellitus.

To identify and characterize abnormalities of iris vasculature in dogs with diabetes mellitus, compared to clinically normal, age-matched control dogs, by means of anterior segment angiography. 10 dogs with naturally occurring diabetes mellitus and 10 age-matched control dogs with no ocular or systemic disease. The day before iris vasculature abnormality (IVA) assessment, all dogs underwent complete physical and ophthalmic examinations and baseline clinicopathologic analyses. For diabetic dogs, serum fructosamine concentration and a 12-hour blood glucose concentration curve were generated. The next day, all dogs were sedated and anterior segment angiography (following IV injection of indocyanine green [1 mg/kg] and subsequently sodium fluorescein [20 mg/kg]) was performed with a full-spectrum camera and camera adapter system. Group findings were compared, and multiple linear regression analysis was performed to identify potential factor associations with IVAs. During anterior segment angiography, the arterial, capillary, and venous phases were identified in all dogs. Times to onset of all phases in diabetic dogs were significantly less than those in control dogs. Vascular disruptions within the peripupillary region (evident following sodium fluorescein administration) were common in diabetic dogs. Severity of dye leakage into the iris stroma and aqueous humor was significantly greater in diabetic dogs than in control dogs. Duration of disease, mean blood glucose concentration, and serum fructosamine concentration were significantly associated with IVAs. In diabetic dogs, anterior segment angiography revealed IVAs that were not evident in control dogs. The severity of those changes appeared to be associated with disease duration and blood glucose regulation.

An ultra-long-acting recombinant insulin for the treatment of diabetes mellitus in cats.

BackgroundTreatment of diabetes mellitus (DM) in cats typically requires insulin injections q12h‐q24h, posing a major compliance barrier for caregivers. Novel treatments enabling decreased injection frequency while maintaining safety are highly desirable. Insulin fused with feline immunoglobulin fragment crystallizable (Fc) has an ultra‐long plasma half‐life because it recycles through cells where it is protected from proteolysis.HypothesisGlycemic control can be achieved in diabetic cats with a recombinant fusion protein of a synthetic insulin and feline Fc (AKS‐267c) administered SC weekly.AnimalsFive cats with spontaneous DM.MethodsCats previously controlled using insulin glargine q12h were transitioned to once‐weekly injection of AKS‐267c. The dose of AKS‐267c was titrated weekly for 7 weeks based on continuous glucose monitoring. Clinical signs, body weight, fructosamine concentrations, and mean interstitial glucose concentrations (IG) were compared between baseline (week 0, on insulin glargine) and the last week of treatment. Data were assessed for normality and compared using parametric or nonparametric paired tests (as appropriate).ResultsAfter 7 weeks of once‐weekly injections, compared to baseline, there were no significant changes in clinical signs, body weight (median [range] gain, 0.1 kg [−0.1 to +0.7]; P = .5), fructosamine (−60 mmol/L [−338 to +206]; P = .6), and mean IG concentrations (change = −153 mmol/L [−179 to +29]; P = .3), and no adverse reactions were reported.ConclusionSuccessful control of clinical signs and maintenance of glycemia was achieved with this once‐weekly novel insulin treatment. The efficacy and safety of this novel formulation should be further assessed in a large clinical trial.

Bioflavonoid (Hesperidin) Restrains Protein Oxidation and Advanced Glycation End Product Formation by Targeting AGEs and Glycolytic Enzymes.

Alpha-amylase (α-amylase) not long ago has acquire recognition as a possible drug target for the management of diabetes. Here, we have investigated the binding and enzyme activity of α-amylase by hesperidin; a naturally occurring flavanone having wide therapeutic potential. Hesperidin exerted an inhibitory influence on α-amylase activity with an IC50 value of 16.6 µM. Hesperidin shows a significant binding toward α-amylase with a binding constant (Ka) of the order of 104 M-1. The evaluation of thermodynamic parameters (∆H and ∆S) suggested that van der Waals force and hydrogen bonding drive seemingly specific hesperidin-α-amylase complex formation. Glycation and oxidation studies were performed using human serum albumin (HSA) as ideal protein. Hesperidin inhibited fructosamine content ≈40% at 50 µM and inhibited advanced glycation end products (AGEs) formation by 71.2% at the same concentration. Moreover, significant recovery was evident in free -SH groups and carbonyl content of HSA. Additionally, molecular docking also entrenched in vitro observations and provided an insight into the important residues (Trp58, Gln63, His101, Glu233, Asp300, and His305) at the heart of hesperidin-α-amylase interaction. This study delineates mechanistic insight of hesperidin-α-amylase interaction and provides a platform for use of hesperidin to treat AGEs directed diseases.

Changes of Plasma Analytes Reflecting Metabolic Adaptation to the Different Stages of the Lactation Cycle in Healthy Multiparous Holstein Dairy Cows Raised in High-Welfare Conditions.

Simple SummaryThis study investigates the changes occurring in plasma analytes of healthy multiparous Holstein dairy cows during the dry, the postpartum, the early and the late lactation phases. A welfare assessment at the herd level and a retrospective subclinical diseases screening were used as blocking factors for the selection of reference individuals. Thus, this study provides measurements of the physiological variations affecting plasma analytes concentrations during the pivotal stages of the lactation cycle in a healthy, high welfare-raised subset of reference individuals and suggest an explanation for the underlying processes involved. Finally, we propose reference intervals for plasma analytes in the stages investigated.Here, we tested the changes occurring in several plasma analytes during different stages of the lactation cycle of high welfare raised multiparous Holstein cows, and provided reference intervals (RI) for plasma analytes concentrations. Eleven high-welfare farms (HWF) located in Northern Italy were selected and their herds used to recruit 361 clinically healthy cows undergoing the dry (from −30 to −10 days from real calving; DFC), the postpartum (from 3 to 7 DFC), the early lactation (from 28 to 45 DFC) and the late lactation phases (from 160 to 305 DFC). Cows affected by subclinical diseases (SCD) were retrospectively excluded, and a subset of 285 cows was selected. Data of plasma analytes underwent ANOVA testing using physiological phases as predictors. The individual effect of each phase was assessed using a pairwise t-test assuming p ≤ 0.05 as a significance limit. A bootstrap approach was used to define the reference interval (RI) for each blood analyte within physiological phases having a pairwise t-test p ≤ 0.05. The concentration of nonesterified fatty acids, albumin, cholesterol, retinol, paraoxonase and tocopherol changed throughout all the physiological phases, whereas the concentration of K, alkaline phosphatase and thiol groups remained stable. Triglycerides, Zn, and ferric ion reducing antioxidant power in the dry phase and BHB, Ca, myeloperoxidase, haptoglobin, reactive oxygen metabolites and advanced oxidation of protein product in postpartum differed compared with other physiological phases. During the dry phase, Packed cell volume, Cl, and urea concentrations were similar to during the postpartum phase. Similarly, Na, γ-glutamyl transferase and β-carotene concentrations were similar to during the early lactation phase; fructosamine and bilirubin concentrations were similar to during the late lactation phase. During the postpartum phase, fructosamine and P concentrations were similar to during the early lactation phase, and the aspartate transaminase concentration was similar to during the late lactation phase. During the early lactation phase, Mg, creatinine, total protein, globulin and ceruloplasmin concentrations were similar to during the postpartum phase, while the urea concentration was similar to during the late lactation phase. All these plasma analytes differed among the other phases. This study identifies physiological trends affecting plasma analytes concentrations during the different stages of the lactation cycle and provides a guideline for the duration and magnitude of their changes when animals are healthy and raised in optimal welfare conditions.

Evaluation of the antiglycating potential of thymoquinone and its interaction with BSA

Thymoquinone (TQ) is a bioactive component of medicinal plant, Nigella sativa. It has been identified as promising anti-inflammatory and anti-analgesic properties. In the present study, the TQ has been investigated for physiological interaction as well as binding properties with serum albumin and their thermodynamic parameters at different temperatures. Glycation process was checked with the measurement of fructosamine content, carbonyl content and total advanced glycated end products. The aggregation of amyloid β-structure was measured with Thioflavin-T and the secondary structure of BSA was observed by circular dichroism (CD) in glycated and thermal treated samples. The results indicate that the TQ showed binding interaction (both static and dynamic) with BSA (K b= 18.31 × 107 M −1 at 293 K) and suppression of glycated products. The glycation-induced and thermal aggregation were prevented and the secondary structure of BSA was maintained. Therefore, these findings suggest that TQ may be used for a therapeutic drug for antiglycation as well as anti-aggregation. Communicated by Ramaswamy H. Sarma