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Concept: Glycation

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Clinical chemistry tests for autism spectrum disorder (ASD) are currently unavailable. The aim of this study was to explore the diagnostic utility of proteotoxic biomarkers in plasma and urine, plasma protein glycation, oxidation, and nitration adducts, and related glycated, oxidized, and nitrated amino acids (free adducts), for the clinical diagnosis of ASD.

Concepts: Amino acid, Acid, Ammonia, Nitrogen, Autism, Asperger syndrome, Autism spectrum, Glycation

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The One Drop | Mobile app supports manual and passive (via HealthKit and One Drop’s glucose meter) tracking of self-care and glycated hemoglobin A1c (HbA1c).

Concepts: Diabetes mellitus, Diabetes, Glycated hemoglobin, Glycation, Anthony Cerami

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What is the extent and effect of excessive testing for glycated hemoglobin (HbA1c) among adults with controlled type 2 diabetes?

Concepts: Diabetes mellitus, Diabetes, Glycated hemoglobin, Glycation

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Background The feasibility, safety, and efficacy of prolonged use of an artificial beta cell (closed-loop insulin-delivery system) in the home setting have not been established. Methods In two multicenter, crossover, randomized, controlled studies conducted under free-living home conditions, we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes. The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy (control) for a similar period. The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents. Results Among adults, the proportion of time that the glucose level was in the target range was 11.0 percentage points (95% confidence interval [CI], 8.1 to 13.8) greater with the use of the closed-loop system day and night than with control therapy (P<0.001). The mean glucose level was lower during the closed-loop phase than during the control phase (difference, -11 mg per deciliter; 95% CI, -17 to -6; P<0.001), as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter (39% lower; 95% CI, 24 to 51; P<0.001) and the mean glycated hemoglobin level (difference, -0.3%; 95% CI, -0.5 to -0.1; P=0.002). Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase (by 24.7 percentage points; 95% CI, 20.6 to 28.7; P<0.001), and the mean nighttime glucose level was lower (difference, -29 mg per deciliter; 95% CI, -39 to -20; P<0.001). The area under the curve for the period in which the day-and-night glucose levels were less than 63 mg per deciliter was lower by 42% (95% CI, 4 to 65; P=0.03). Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use. Conclusions Among patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 ClinicalTrials.gov numbers, NCT01961622 and NCT01778348 .).

Concepts: Insulin, Diabetes mellitus, Diabetes mellitus type 1, Diabetes, Blood sugar, Hypoglycemia, Glycated hemoglobin, Glycation

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Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.

Concepts: Genetics, Biology, Diabetes mellitus type 2, Diabetes mellitus, Diabetes, Glycated hemoglobin, Glycation, Anthony Cerami

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Glycated hemoglobin (HbA1c) has been recently adopted as a diagnostic marker of type 2 diabetes. However, its usage is currently limited to fresh blood samples. To allow retrospective HbA1c measurement in blood banks developed in large epidemic studies, here, we contribute to validate HbA1c assessment in frozen versus fresh blood samples from a cohort of diabetic/nondiabetic adult subjects. HbA1c was measured by HPLC in 237 fresh whole blood samples and on the same samples after a 12-month storage and a further 6-month-refrozen storage. Mean HbA1c ± SD in fresh, frozen, and refrozen samples was 6.9 ± 1.2, 6.6 ± 1.1, and 6.4 ± 1.0 % for the Diabetes Control and Complications Trial and 52 ± 13, 49 ± 12, and 46 ± 11 mmol/mol for the International Federation of Clinical Chemistry and Laboratory Medicine reference, respectively. A significant correlation was found between fresh/frozen and fresh/refrozen (R = 0.994 and 0.993, P < 0.001) samples. HbA1c relative error ratio (%RER) between frozen/refrozen and fresh samples significantly correlated with HbA1c and depended on fresh value range, increasing in the five HbA1c classes (<6.0, 6.0-6.5, 6.5-7, 7-8, ≥8 %, corresponding to <42, 42-48, 48-53, 53-64, ≥64 mmol/mol, P < 0.001). In particular, the 6.5 % (48 mmol/mol) HbA1c diagnostic cutoff of fresh samples identified two classes reflecting significant differences in %RER (2.8 ± 2.0 and 3.3 ± 1.7; P < 0.05) between frozen and fresh samples. In conclusion, our results demonstrate a high correlation between data from fresh and frozen samples, with a very limited %RER between the two measurements, which increases with baseline HbA1c levels. Accordingly, when analyzing biobank frozen specimens for diagnostic purpose, the effect of the HbA1c range should be taken into account.

Concepts: Blood, Diabetes mellitus, Measurement, Diabetes, Blood plasma, Glycated hemoglobin, Glycation, Blood donation

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The glycopeptide CcTx, isolated from the venom of the piscivorous cone snail Conus consors, belongs to the κA-family of conopeptides. These toxins elicit excitotoxic responses in the prey by acting on voltage-gated sodium channels. The structure of CcTx, a first in the κA-family, has been determined by high-resolution NMR spectroscopy together with the analysis of its O-glycan at Ser7. A new type of glycopeptide O-glycan core structure, here registered as core type 9, containing two terminal L-galactose units {α-L-Galp-(1→4)-α-D-GlcpNAc-(1→6)-[α-L-Galp-(1→2)-β-D-Galp-(1→3)-]α-D-GalpNAc-(1→O)}, is highlighted. A sequence comparison to other putative members of the κA-family suggests that O-linked glycosylation might be more common than previously thought. This observation alone underlines the requirement for more careful and in-depth investigations into this type of post-translational modification in conotoxins.

Concepts: Posttranslational modification, Sodium channel, Lysine, Conotoxin, Glycation, Threonine, Conus, Conidae

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Since the discovery of the relation between increased concentrations of fast haemoglobin fractions in patients with diabetes mellitus compared to concentrations in subjects without diabetes mellitus by Samuel Rahbar and co-workers in 1969, glycated haemoglobin A1c (HbA1c) has become a “gold standard” for glucose management in patients with diabetes mellitus. Recently, HbA1c has been advocated as a diagnostic marker for diabetes mellitus, which further underlines the importance of HbA1c. There are currently more than 30 methods available on the market with an analytical performance ranging from poor to state of the art. This review describes the biochemistry of HbA1c and the concepts of analytical and biological variation with respect to the measurement of HbA1c. Subsequently, aspects regarding the discovery of HbA1c are described. In addition, an overview is given on the assays methods that are currently available for the measurement of HbA1c. Finally, recommendations for the minimally required analytical performance characteristics of the current HbA1c assays are presented.

Concepts: Insulin, Diabetes mellitus, Glucose, Diabetes, Blood sugar, Glycated hemoglobin, Glycation, Anthony Cerami

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We attempted to determine whether betanin (from natural pigments) that has antioxidant properties would be protective against fructose-induced diabetic cardiac fibrosis in Sprague-Dawley rats. Fructose water solution (30%) was accessed freely, and betanin (25 and 100mg/kg/d) was administered by intra-gastric gavage continuously for 60d. Rats were sacrificed after overnight fast. The rat blood and left ventricle were collected. In vitro antiglycation assay in bovine serum albumin/fructose system was also performed. In rats treated only with fructose, levels of plasma markers: glucose, insulin, HOMA and glycated hemoglobin rised, left ventricle collagen accumulated and cross-linked, profibrotic factor-transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF) protein expression increased, and soluble collagen decreased, compared with those in normal rats, showing fructose induces diabetic cardiac fibrosis. Treatment with betanin antagonized the changes of these parameters, demonstrating the antifibrotic role of betanin in the selected diabetic models. In further mechanistic study, betanin decreased protein glycation indicated by the decreased levels of protein glycation reactive intermediate (methylglyoxal), advanced glycation end product (N(ε)-(carboxymethyl) lysine) and receptors for advanced glycation end products (AGEs), antagonized oxidative stress and nuclear factor-κB activation elicited by fructose feeding, suggesting inhibition of glycation, oxidative stress and nuclear factor-κB activation may be involved in the antifibrotic mechanisms. Betanin also showed anitglycative effect in BSA/fructose system, which supported that anitglycation was involved in betanin’s protective roles in vivo. Taken together, the potential for using betanin as an auxillary therapy for diabetic cardiomyopathy deserves to be explored further.

Concepts: Protein, Blood, Glucose, Collagen, Heart, Vitamin C, Connective tissue, Glycation

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There is limited information from population-based investigations of the associations between sleep duration and sleep disorders and parameters of glucose homeostasis. The objective of the present study was to examine cross-sectional associations between sleep duration and sleep disordered breathing with concentrations of insulin, fasting and 2-hour glucose, and HbA1c.

Concepts: Diabetes mellitus, Glucose, Blood sugar, Sleep, Sleep disorder, Circadian rhythm, Glycation, Narcolepsy