Evidence That Differences in Fructosamine-3-Kinase Activity May Be Associated With the Glycation Gap in Human Diabetes

Dunmore, Simon; Alderawi, Amr Saleh; Nayak, Ananth; Narshi, Aruna; Nevill, Alan M.; Hellwig, Anne; Majebi, Andrew; Kirkham, Paul; Brown, James E.; Singh, Baldev

doi:10.2337/db17-0441

Cited by 23 publications

(16 citation statements)

References 32 publications

(40 reference statements)

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“…The latter are unstable and spontaneously decompose into inorganic phosphate and 3-deoxyglucosone, regenerating the unglycated amine (Gugliucci, 2005). The presence of proteins related to fructosamine 3-kinase in many prokaryotic and eukaryotic genomes implies that this ‘deglycation’ process is not restricted to erythrocytes nor to just mammals (Collard et al, 2004; Dunmore et al, 2018; Van Schaftingen et al, 2007; Szwergold et al, 2011). …”

Section: The Maillard Reaction: Initiators Propagators and Chemistrymentioning

confidence: 99%

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

et al. 2018

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Accumulation of advanced glycation end products (AGEs) on nucleotides, lipids, and peptides/proteins are an inevitable component of the aging process in all eukaryotic organisms, including humans. To date, a substantial body of evidence shows that AGEs and their functionally compromised adducts are linked to and perhaps responsible for changes seen during aging and for the development of many age-related morbidities. However, much remains to be learned about the biology of AGE formation, causal nature of these associations, and whether new interventions might be developed that will prevent or reduce the negative impact of AGEs-related damage. To facilitate achieving these latter ends, we show how invertebrate models, notably Drosophila melanogaster and Caenorhabditis elegans, can be used to explore AGE-related pathways in depth and to identify and assess drugs that will mitigate against the detrimental effects of AGE-adduct development.

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Section: The Maillard Reaction: Initiators Propagators and Chemistrymentioning

confidence: 99%

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

et al. 2018

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“…FN3K is highly expressed in erythrocytes with a documented role in HbA1c variation independent of glucose levels [16]. It was reported that FN3K enzyme activity and protein levels were both significantly higher in patients with a negative glycation gap (lower HbA1c levels than would be expected from average glycemia) [16]. The HGI calculated using MBG levels was strongly correlated with the HGI calculated using only pre-breakfast glucose (r=0.867) or FBG (r=0.687) levels.…”

Section: Discussionmentioning

confidence: 99%

“…If an individual has a measured HbA1c that is higher than expected from MBG levels (i.e., a high HGI), higher measured HbA1c levels than would be expected from MBG levels is likely to continue during repeated comparisons over time. Such individuals likely have a relatively long red blood cell (RBC) life span (i.e., a slow RBC turnover rate), a relatively high RBC glycation rate, or a variation in another yet undefined biological or genetic factor [15,16]. Genetic variations could influence HbA1c levels through nonglycemic pathways and contribute to HbA1c/glycemia discordance.…”

Section: Discussionmentioning

confidence: 99%

“…A potential mechanism for variation in glycation may be a fructosamine-3-kinase (FN3K)related glycation/deglycation shift through the deglycation of intracellular proteins, such as hemoglobin. FN3K is highly expressed in erythrocytes with a documented role in HbA1c variation independent of glucose levels [16]. It was reported that FN3K enzyme activity and protein levels were both significantly higher in patients with a negative glycation gap (lower HbA1c levels than would be expected from average glycemia) [16].…”

Section: Discussionmentioning

confidence: 99%

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Consistency of the Glycation Gap with the Hemoglobin Glycation Index Derived from a Continuous Glucose Monitoring System

Joung¹,

Kwon²,

Baek³

et al. 2020

Endocrinol Metab

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Background: Discordances between glycated hemoglobin (HbA1c) levels and glycemic control are common in clinical practice. We aimed to investigate the consistency of the glycation gap with the hemoglobin glycation index (HGI). Methods: From 2016 to 2019, 36 patients with type 2 diabetes were enrolled. HbA1c, glycated albumin (GA), and fasting blood glucose levels were simultaneously measured and 72-hour continuous glucose monitoring (CGM) was performed on the same day. Repeated tests were performed at baseline and 1 month later, without changing patients' diabetes management. The HGI was calculated as the difference between the measured HbA1c and the predicted HbA1c that was derived from CGM. The glycation gap was calculated as the difference between the measured and GA-based predicted HbA1c levels. Results: Strong correlations were found between the mean blood glucose (MBG)-based HGI and the prebreakfast glucose-based HGI (r=0.867, P<0.001) and between the glycation gap and the MBG-based HGI (r=0.810, P<0.001). A close correlation was found between the MBG-based HGI at baseline and that after 1 month (r=0.729, P<0.001), with a y-intercept of 0 and a positive slope. Conclusion: The HGI and glycation gap were highly reproducible, and the magnitudes of repeated determinations were closely correlated. Patients with similar mean glucose levels may have significantly different HbA1c levels.

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“…49 The enzyme fructosamine-3-kinase is highly expressed in erythrocytes and promotes deglycation of proteins and is one of the mechanisms contributing to changes in HbA1c not related to glucose levels. 51 Several reports have shown that Black individuals have systematically higher HbA1c levels than Whites. Furthermore, HbA1c has been associated with the imprecise classification of T2DM in the Black population than in Whites.…”

Section: Hba1cmentioning

confidence: 99%

<p>The Oral Glucose Tolerance Test: 100 Years Later</p>

Jagannathan¹,

Neves²,

Dorcely³

et al. 2020

DMSO

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For over 100 years, the oral glucose tolerance test (OGTT) has been the cornerstone for detecting prediabetes and type 2 diabetes (T2DM). In recent decades, controversies have arisen identifying internationally acceptable cut points using fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and/or HbA1c for defining intermediate hyperglycemia (prediabetes). Despite this, there has been a steadfast global consensus of the 2-h PG for defining dysglycemic states during the OGTT. This article reviews the history of the OGTT and recent advances in its application, including the glucose challenge test and mathematical modeling for determining the shape of the glucose curve. Pitfalls of the FPG, 2-h PG during the OGTT, and HbA1c are considered as well. Finally, the associations between the 30-minute and 1-hour plasma glucose (1-h PG) levels derived from the OGTT and incidence of diabetes and its complications will be reviewed. The considerable evidence base supports modifying current screening and diagnostic recommendations with the use of the 1-h PG. Measurement of the 1-h PG level could increase the likelihood of identifying high-risk individuals when the pancreatic ß-cell function is substantially more intact with the added practical advantage of potentially replacing the conventional 2-h OGTT making it more acceptable in the clinical setting.

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Evidence That Differences in Fructosamine-3-Kinase Activity May Be Associated With the Glycation Gap in Human Diabetes

Cited by 23 publications

References 32 publications

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

Consistency of the Glycation Gap with the Hemoglobin Glycation Index Derived from a Continuous Glucose Monitoring System

<p>The Oral Glucose Tolerance Test: 100 Years Later</p>

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