The measurement of plasma fructosamine as a diagnostic tool to improve the interpretation of plasma glucose and proteins in alpacas (Vicugna pacos).

This study assesses the use of fructosamine as a diagnostic tool for hyperglycemia in alpacas in view of their sensitivity to stress and susceptibility to conditions like lipid mobilization syndrome. Plasma fructosamine, like in diagnosing diabetes in cats and dogs, can reveal long-term blood glucose trends, differentiating stress-induced spikes from persistent diabetic hyperglycemia. In 125 alpacas presented as patients of a veterinary clinic, plasma glucose and fructosamine concentrations were compared for correlations with findings of the general clinical examination, laboratory parameters, demographic data, and a behavioral stress assessment processed by using principal component analysis. Hyperglycemia was observed on admission of 71% (89/125) of the animals. This was significantly associated with a higher concentration of serum cortisol and a higher behavioral stress scoring. Fructosamine above the reference limit was detected in only 15% (13/89) of the hyperglycemic individuals. In addition to a positive correlation of fructosamine to glucose concentration, positive relationships with different plasma proteins were detected. A relationship to stress parameters was not observed. These findings underscore stress as a significant trigger for hyperglycemia in alpacas and suggest fructosamine as a valuable parameter for distinguishing between stress-induced and diabetic hyperglycemia. However, the dependence of fructosamine formation on total plasma protein concentration should be considered to avoid misinterpretation.

4 vs 7 points self-monitoring blood glucose in gestational diabetes mellitus on diet modification: randomised clinical trial in a single tertiary centre in Malaysia.

PURPOSE: There is no standardized best method on monitoring of patients with gestational diabetes on diet modification in the country. This study aims to investigate the optimum method of self-monitoring blood glucose. METHODS: This is a randomized clinical trial in a single tertiary centre involving patients with gestational diabetes mellitus (GDM) diagnosed based on NICE guideline on diet modification. The patients are randomized in 1:1 ratio to 4 or 7 points self-monitoring blood glucose. The monitoring was required to be done monthly with ultrasound for fetal growth. Blood was taken at recruitment for measurement of serum HbA1c and fructosamine. RESULTS: A total of 200 patients were recruited. There were significantly more Malay patients in the 7 points group (88.9% vs 78.2%, p = 0.033). Multiparous patients were significantly more in the 4 points group (82.2% vs 68.7%, p = 0.033). Both groups were similar in clinical characteristics. There was no statistical difference in the neonatal outcome particularly fetal macrosomia and admission to neonatal intensive care unit. CONCLUSIONS: In patients with GDM on diet modification, self-blood glucose monitoring using either 4 or 7 points resulted in similar maternal and perinatal outcomes. The research was registered under ClinicalTrials.gov (NCT04101396) on 17/9/2019 ( https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S00098EN&selectaction=Edit&uid=U0004RD4&ts=2&cx=-qlk1w2 ).

The association between serum fructosamine and random spot urine fructose levels with the severity of non-alcoholic fatty liver disease - an analytical cross-sectional study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) in South Africa and Africa at large is considered a hidden threat. Our local population is burdened with increased metabolic risk factors for NAFLD. Our setting requires a reasonable approach to screen for and aid the diagnosis of NAFLD. OBJECTIVES: To investigate serum fructosamine and random spot urine fructose levels as biomarkers for the screening, diagnosis and monitoring of NAFLD. The primary objective of this study was to compare serum fructosamine and random spot urine fructose levels between groups with different levels of NAFLD severity as measured by ultrasound. A secondary objective was to determine the association, if any, between serum transaminases, the aspartate aminotransferase (AST) to platelet ratio index (APRI) score, serum fructosamine and urine fructose in different groups with steatosis. METHODS: Using a cross-sectional study design, 65 patients with three different levels of NAFLD, as detected by imaging, were enrolled. The primary exposures measured were serum fructosamine with random spot urine fructose, and secondary exposures were the serum transaminases (AST and alanine aminotransferase (ALT)) and the APRI score. Patients identified at the departments of gastroenterology, general internal medicine and diagnostic radiology were invited to participate. RESULTS: There were 38, 17 and 10 patients with mild, moderate and severe steatosis, respectively. There was no significant difference between the groups regarding serum fructosamine, measured as median (interquartile range): mild 257 (241 - 286) µmol/L, moderate 239 (230 - 280) µmol/L and severe 260 (221 - 341) µmol/L, p=0.5; or random spot urine fructose: mild 0.86 (0.51 - 1.30) mmol/L, moderate 0.84 (0.51 - 2.62) mmol/L and severe 0.71 (0.58 - 1.09) mmol/L, p = 0.8. ALT (U/L) differed between groups: mild 19 (12 - 27), moderate 27 (22 - 33), severe 27 (21 - 56), p=0.03, but not AST (U/L) (p=0.7) nor APRI (p=0.9). Urine fructose and ALT were correlated in the moderate to severe steatosis group (R=0.490, p<0.05), but not in the mild steatosis group. Serum fructosamine was associated with age in the mild steatosis group but not the moderate-severe steatosis group (R=0.42, p<0.01). CONCLUSION: Serum fructosamine and random spot urine fructose did not vary with the severity of NAFLD, indicating that they would not be useful biomarkers in this condition.

Phloroglucinol inhibited glycation via entrapping carbonyl intermediates.

Advanced glycation end products (AGEs) play an important role in the pathogenesis of age-linked disorders and diabetes mellitus. The aim of this study was to assess the repurposing potential of Phloroglucinol (PHL the antispasmodic drug), as an anti-glycation agent using Fructose-BSA model. The ability of PHL to inhibit AGE formation was evaluated using AGEs formation (Intrinsic fluorescence), fructosamine adduct (NBT) and free lysine availability (TNBSA) assays. The BSA protein conformation was assessed through Thioflavin-T, Congo-Red and Circular Dichroism assays. The lysine blockade and carbonyl entrapment were explored as possible mode of action. Our data showed that PHL significantly decreased the formation of AGEs with an IC50 value of 0.3mM. The fructosamine adducts and free lysine load was found to be reduced. Additionally, the BSA conformation was preserved by PHL. Mechanistic assays did not reveal involvement of lysine blockade as underlying reason for reduction in AGEs load. This was also supported by computational data whereby PHL failed to engage any catalytic residue involved in early fructose-BSA interaction. However, it was found to entrap the carbonyl moieties. In conclusion, the PHL demonstrated anti-glycation potential, which can be attributed to its ability to entrap carbonyl intermediates. Hence, the clinically available antispasmodic drug, presents itself as a promising candidate to be repurposed as anti-glycation agent.

Protein glycation products associate with progression of kidney disease and incident cardiovascular events in individuals with type 1 diabetes.

BACKGROUND: Despite improved glycemic treatment, the impact of glycation on pathological consequences may persist and contribute to adverse clinical outcomes in diabetes. In the present study we investigated the association between serum protein glycation products and progression of kidney disease as well as incident major adverse cardiovascular events (MACE) in type 1 diabetes. METHODS: Fructosamine, advanced glycation end products (AGEs), and methylglyoxal-modified hydro-imidazolone (MG-H1) were measured from baseline serum samples in the FinnDiane study (n = 575). Kidney disease progression was defined as steep eGFR decline (> 3 mL/min/1.73 m2/year) or progression of albuminuria (from lower to higher stage of albuminuria). MACE was defined as acute myocardial infarction, coronary revascularization, cerebrovascular event (stroke), and cardiovascular death. RESULTS: Fructosamine was independently associated with steep eGFR decline (OR 2.15 [95% CI 1.16-4.01], p = 0.016) in the fully adjusted model (age, sex, baseline eGFR). AGEs were associated with steep eGFR decline (OR 1.58 per 1 unit of SD [95% CI 1.07-2.32], p = 0.02), progression to end-stage kidney disease (ESKD) (HR 2.09 per 1 unit of SD [95% CI 1.43-3.05], p < 0.001), and pooled progression (to any stage of albuminuria) (HR 2.72 per 1 unit of SD [95% CI 2.04-3.62], p < 0.001). AGEs (HR 1.57 per 1 unit of SD [95% CI 1.23-2.00], p < 0.001) and MG-H1 (HR 4.99 [95% CI 0.98-25.55], p = 0.054) were associated with incident MACE. MG-H1 was also associated with pooled progression (HR 4.19 [95% CI 1.11-15.89], p = 0.035). Most AGEs and MG-H1 associations were no more significant after adjusting for baseline eGFR. CONCLUSIONS: Overall, these findings suggest that protein glycation products are an important risk factor for target organ damage in type 1 diabetes. The data provide further support to investigate a potential causal role of serum protein glycation in the progression of diabetes complications.

Characterizing Common and Rare Variations in Nontraditional Glycemic Biomarkers Using Multivariate Approaches on Multiancestry ARIC Study.

Genetic studies of nontraditional glycemic biomarkers, glycated albumin and fructosamine, can shed light on unknown aspects of type 2 diabetes genetics and biology. We performed a multiphenotype genome-wide association study of glycated albumin and fructosamine from 7,395 White and 2,016 Black participants in the Atherosclerosis Risk in Communities (ARIC) study on common variants from genotyped/imputed data. We discovered two genome-wide significant loci, one mapping to a known type 2 diabetes gene (ARAP1/STARD10) and another mapping to a novel region (UGT1A complex of genes), using multiomics gene-mapping strategies in diabetes-relevant tissues. We identified additional loci that were ancestry- and sex-specific (e.g., PRKCA in African ancestry, FCGRT in European ancestry, TEX29 in males). Further, we implemented multiphenotype gene-burden tests on whole-exome sequence data from 6,590 White and 2,309 Black ARIC participants. Ten variant sets annotated to genes across different variant aggregation strategies were exome-wide significant only in multiancestry analysis, of which CD1D, EGFL7/AGPAT2, and MIR126 had notable enrichment of rare predicted loss of function variants in African ancestry despite smaller sample sizes. Overall, 8 of 14 discovered loci and genes were implicated to influence these biomarkers via glycemic pathways, and most of them were not previously implicated in studies of type 2 diabetes. This study illustrates improved locus discovery and potential effector gene discovery by leveraging joint patterns of related biomarkers across the entire allele frequency spectrum in multiancestry analysis. Future investigation of the loci and genes potentially acting through glycemic pathways may help us better understand the risk of developing type 2 diabetes.

Fructosamine and HbA1c: A Correlational Study in a Southeast Asian Population.

Objectives: Fructosamine correlates well with glycated haemoglobin (HbA1c) in Caucasians. This study investigates this correlation and whether fructosamine can reliably estimate glycated haemoglobin in Southeast Asians. Methods: We recruited 193 participants based on 4 HbA1c bands (<6.0%; 6.0 - 7.9%; 8.0- 9.9%; ≥10%) from a secondary hospital in Singapore between August 2017 and December 2021. Blood samples for fructosamine, glycated haemoglobin, albumin, haemoglobin, thyroid stimulating hormone and creatinine were drawn in a single setting for all participants. Scatter plot was used to explore correlation between fructosamine and glycated haemoglobin. Strength of linear correlation was reported using Pearson's correlation coefficient. Simple linear regression was used to examine the relationship between fructosamine and glycated haemoglobin. Results: We performed simple linear regression to study the relationship between fructosamine and HbA1c in the research participants (R2 = 0.756, p<0.01). Further analysis with natural logarithmic transformation of fructosamine demonstrated a stronger correlation between HbA1c and fructosamine (R2 = 0.792, p<0.01). Conclusions: Fructosamine is reliably correlated with HbA1c for the monitoring of glycaemic control in Southeast Asians.

Coffee leaf extract inhibits advanced glycation end products and their precursors: A mechanistic study.

Excessive accumulation of advanced glycation end products (AGEs) in the body is associated with diabetes and its complications. In this study, we aimed to explore the potential and mechanism of coffee leaf extract (CLE) in inhibiting the generation of AGEs and their precursors in an in vitro glycation model using bovine serum albumin and glucose (BSA-Glu) for the first time. High-performance liquid chromatography analysis revealed that CLE prepared with ultrasound pretreatment (CLE-U) contained higher levels of trigonelline, mangiferin, 3,5-dicaffeoylquinic acid, and γ-aminobutyric acid than CLE without ultrasound pretreatment (CLE-NU). The concentrations of these components, along with caffeine and rutin, were dramatically decreased when CLE-U or CLE-NU was incubated with BSA-Glu reaction mixture. Both CLE-U and CLE-NU exhibited a dose-dependent inhibition of fluorescent AGEs, carboxymethyllysine, fructosamine, 5-hydroxymethylfurfural, 3-deoxyglucosone, glyoxal, as well as protein oxidation products. Notably, CLE-U exhibited a higher inhibitory capacity compared to CLE-NU. CLE-U effectively quenched fluorescence intensity and increased the α-helix structure of the BSA-Glu complex. Molecular docking results suggested that the key bioactive compounds present in CLE-U interacted with the arginine residues of BSA, thereby preventing its glycation. Overall, this research sheds light on the possible application of CLE as a functional ingredient in combating diabetes by inhibiting the generation of AGEs.

Association of Fructosamine Levels With Glycemic Management in Children With Type 1 Diabetes as Determined by Continuous Glucose Monitoring: Results From the CGM TIME Trial.

OBJECTIVE: Our aim in this study was to determine the correlation between serum fructosamine and average blood glucose, as measured by continuous glucose monitoring (CGM) in children with type 1 diabetes. METHODS: Ninety-seven blood samples were collected from 70 participants in the Timing of Initiation of continuous glucose Monitoring in Established pediatric diabetes (CGM TIME) Trial. Each eligible participant had 3 weeks of CGM data with at least 60% CGM adherence before blood collection. Ordinary least-squares linear regression incorporating restricted cubic splines was used to determine the association between fructosamine levels and mean blood glucose. RESULTS: An association was found between fructosamine and mean blood glucose, with an F statistic of 9.543 (p<0.001). Data were used to create a formula and conversion chart for calculating mean blood glucose from fructosamine levels for clinical use. CONCLUSIONS: There is a complex relationship between average blood glucose, as determined by CGM and fructosamine. Fructosamine levels may be clinically useful for assessing short-term glycemic management when CGM is not available.

Gastric emptying of a glucose drink is predictive of the glycaemic response to oral glucose and mixed meals, but unrelated to antecedent glycaemic control, in type 2 diabetes.

BACKGROUND: Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes (T2D). However, it is uncertain whether GE of a carbohydrate-containing liquid meal is predictive of the glycaemic response to physiological meals, and whether antecedent hyperglycaemia influences GE in T2D. We evaluated the relationships of (i) the glycaemic response to both a glucose drink and mixed meals with GE of a 75 g glucose drink, and (ii) GE of a glucose drink with antecedent glycaemic control, in T2D. METHODS: Fifty-five treatment-naive Chinese adults with newly diagnosed T2D consumed standardised meals at breakfast, lunch and dinner with continuous interstitial glucose monitoring. On the subsequent day, a 75 g glucose drink containing 150 mg 13C-acetate was ingested to assess GE (breath test) and plasma glucose response. Serum fructosamine and HbA1c were also measured. RESULTS: Plasma glucose incremental area under the curve (iAUC) within 2 hours after oral glucose was related inversely to the gastric half-emptying time (T50) (r = -0.34, P = 0.012). The iAUCs for interstitial glucose within 2 hours after breakfast (r = -0.34, P = 0.012) and dinner (r = -0.28, P = 0.040) were also related inversely to the T50 of oral glucose. The latter, however, was unrelated to antecedent fasting plasma glucose, 24-hour mean interstitial glucose, serum fructosamine, or HbA1c. CONCLUSIONS: In newly diagnosed, treatment-naive, Chinese with T2D, GE of a 75 g glucose drink predicts the glycaemic response to both a glucose drink and mixed meals, but is not influenced by spontaneous short-, medium- or longer-term elevation in glycaemia.

Momordica charantia fruit reduces plasma fructosamine whereas stems and leaves increase plasma insulin in adult mildly diabetic obese Göttingen Minipigs.

BACKGROUND: Traditionally Momordica charantia (Bitter gourd) is known for its blood glucose lowering potential. This has been validated by many previous studies based on rodent models but human trials are less convincing and the physiological mechanisms underlying the bioactivity of Bitter gourd are still unclear. The present study compared the effects of whole fruit or stems-leaves from five different Bitter gourd cultivars on metabolic control in adult diabetic obese Göttingen Minipigs. METHODS: Twenty streptozotocin-induced diabetic (D) obese Minipigs (body weight ~85 kg) were subdivided in mildly and overtly D pigs and fed 500 g of obesogenic diet per day for a period of three weeks, supplemented with 20 g dried powdered Bitter gourd or 20 g dried powdered grass as isoenergetic control in a cross-over, within-subject design. RESULTS: Bitter gourd fruit from the cultivars "Palee" and "Good healthy" reduced plasma fructosamine concentrations in all pigs combined (from 450±48 to 423±53 and 490±50 to 404±48 µmol/L, both p<0.03, respectively) indicating improved glycemic control by 6% and 17%. These effects were statistically confirmed in mildly D pigs but not in overtly D pigs. In mildly D pigs, the other three cultivars of fruit showed consistent numerical but no significant improvements in glycemic control. The composition of Bitter gourd fruit was studied by metabolomics profiling and analysis identified three metabolites from the class of triterpenoids (Xuedanoside H, Acutoside A, Karaviloside IX) that were increased in the cultivars "Palee" (>3.9-fold) and "Good healthy" (>8.9-fold) compared to the mean of the other three cultivars. Bitter gourd stems and leaves from the cultivar "Bilai" increased plasma insulin concentrations in all pigs combined by 28% (from 53±6 to 67±9 pmol/L, p<0.03). The other two cultivars of stems and leaves showed consistent numerical but no significant increases in plasma insulin concentrations. The effects on plasma insulin concentrations were confirmed in mildly D pigs but not in overtly D pigs. CONCLUSIONS: Fruits of Bitter gourd improve glycemic control and stems-leaves of Bitter gourd increase plasma insulin concentrations in an obese pig model for mild diabetes. The effects of Bitter gourd fruit on glycemic control seem consistent but relatively small and cultivar specific which may explain the varying results of human trials reported in the literature.

Primary care diabetes assessment when HbA1c and other measures of glycemia disagree.

AIMS: Although diabetes management decisions in primary care are typically based largely on HbA1c, mismatches between HbA1c and other measures of glycemia that are increasingly more available present challenges to optimal management. This study aimed to assess a systematic approach to identify the frequency of mismatches of potential clinical significance amongst various measures of glycemia in a primary care setting. METHODS: Following screening to exclude conditions known to affect HbA1c interpretation, HbA1c, and fructosamine were obtained and repeated after ∼90 days on 53 adults with prediabetes or type 2 diabetes. A subset of 13 participants with repeat labs wore continuous glucose monitoring (CGM) for 10 days. RESULTS: As expected, HbA1c and fructosamine only modestly correlated (initial R2 = 0.768/repeat R2 = 0.655). The HbA1c/fructosamine mismatch frequency of ± 0.5% (using the following regression HbA1c = 0.015 *fructosamine + 2.994 calculated from the initial sample) was 27.0%. Of the 13 participants with CGM data, HbA1c and CGM-based Glucose Management Indicator correlated at R2 = 0.786 with a mismatch frequency of ± 0.5% at 46.2% compared to a HbA1c/fructosamine mismatch frequency of ± 0.5% at 30.8%. CONCLUSIONS: HbA1c is frequently mismatched with fructosamine and CGM data. As each of the measures has strengths and weaknesses, the utilization of multiple different measures of glycemia may be informative for diabetes assessment in the clinical setting.

Preliminary evaluation of the impact of periodontal treatment on markers of glycaemic control in dogs with diabetes mellitus: A prospective, clinical case series.

BACKGROUND: Periodontal disease (PD) can adversely affect glycaemic control in humans. However, it is unknown if a similar association exists in dogs. METHODS: Ten client-owned dogs with poorly regulated diabetes mellitus (DM) and PD were prospectively enrolled. A complete blood count, serum biochemistry, urinalysis and measurement of C-reactive protein, interleukin-6 (IL-6), tumour necrosis factor-α, haemoglobin A1c (HbA1c) and fructosamine concentrations were performed before periodontal treatment (PT) and monthly thereafter for 3 months. A periodontal disease severity score (PDSS) was determined during PT. The effects of time post-PT and PDSS on markers of inflammation and glycaemic control were determined by generalised estimating equation analysis. RESULTS: HbA1c (mean; 95% confidence interval [CI]) decreased 3 months post-PT (32.1 mmol/mol; 21.1-43.1 mmol/mol vs. 44.3 mmol/mol; 36.4-52.0; p = 0.003). PDSS at enrolment was significantly (p = 0.031) positively associated with HbA1c concentration. Due to a significant (p < 0.001) interaction between PDSS and time post-PT in the analysis of fructosamine, dogs with low (1-3) PDSS and high (7-9) PDSS were analysed separately. Fructosamine (mean; 95% CI) significantly decreased 1 month post-PT (570 µmol/L; 457-684 µmol/L vs. 624 µmol/L; 499-748; p = 0.001) in the high PDSS group but not in the low PDSS group. Fructosamine concentration upon enrolment and PDSS were correlated (r = 0.73, p = 0.017). IL-6 concentration significantly decreased 3 months post-PT (9.9 pg/mL; 8.5-11.3 pg/mL vs. 11.2 pg/mL; 9.7-12.7; p = 0.002). LIMITATIONS: Limitations of the study included the small number of dogs, the lack of a control group and the inability to assess PDSS during follow-ups. CONCLUSIONS: These findings support a potential detrimental interaction between PD and DM. The apparent beneficial effect of PT on markers of glycaemic control was most conspicuous in dogs with more severe PD.

Combination of milk variables and on-farm data as an improved diagnostic tool for metabolic status evaluation in dairy cattle during the transition period.

Milk composition, particularly milk fatty acids, has been extensively studied as an indicator of the metabolic status of dairy cows during early lactation. In addition to milk biomarkers, on-farm sensor data also hold potential in providing insights into the metabolic health status of cows. While numerous studies have explored the collection of a wide range of sensor data from cows, the combination of milk biomarkers and on-farm sensor data remains relatively underexplored. Therefore, this study aims to identify associations between metabolic blood variables, milk variables, and various on-farm sensor data. Second, it seeks to examine the supplementary or substitutive potential of these data sources. Therefore, data from 85 lactations on metabolic status and on-farm data were collected during 3 wk before calving up to 5 wk after calving. Blood samples were taken on d 3, 6, 9, and 21 after calving for determination of ß-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucose, insulin-like growth factor-1 (IGF-1), insulin, and fructosamine. Milk samples were taken during the first 3 wk in lactation and analyzed by mid-infrared for fat, protein, lactose, urea, milk fatty acids, and BHB. Walking activity, feed intake, and body condition score (BCS) were monitored throughout the study. Linear mixed effect models were used to study the association between blood variables and (1) milk variables (i.e., milk models); (2) on-farm data (i.e., on-farm models) consisting of activity and dry matter intake analyzed during the dry period ([D]) and lactation ([L]) and BCS only analyzed during the dry period ([D]); and (3) the combination of both. In addition, to assess whether milk variables can clarify unexplained variation from the on-farm model and vice versa, Pearson marginal residuals from the milk and on-farm models were extracted and related to the on-farm and milk variables, respectively. The milk models had higher coefficient of determination (R2) than the on-farm models, except for IGF-1 and fructosamine. The highest marginal R2 values were found for BHB, glucose, and NEFA (0.508, 0.427, and 0.303 vs. 0.468, 0.358, and 0.225 for the milk models and on-farm models, respectively). Combining milk and on-farm data particularly increased R2 values of models assessing blood BHB, glucose, and NEFA concentrations with the fixed effects of the milk and on-farm variables mutually having marginal R2 values of 0.608, 0.566, and 0.327, respectively. Milk C18:1 was confirmed as an important milk variable in all models, but particularly for blood NEFA prediction. On-farm data were considerably more capable of describing the IGF-1 concentration than milk data (marginal R2 of 0.192 vs. 0.086), mainly due to dry matter intake before calving. The BCS [D] was the most important on-farm variable in relation to blood BHB and NEFA and could explain additional variation in blood BHB concentration compared with models solely based on milk variables. This study has shown that on-farm data combined with milk data can provide additional information concerning the metabolic health status of dairy cows. On-farm data are of interest to be further studied in predictive modeling, particularly because early warning predictions using milk data are highly challenging or even missing.

Assessment of Glycemic Control by Continuous Glucose Monitoring, Hemoglobin A1c, Fructosamine, and Glycated Albumin in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes.

OBJECTIVE: Patients with diabetes and end-stage kidney disease (ESKD) may experience "burnt-out diabetes," defined as having an HbA1c value <6.5% without antidiabetic therapy for >6 months. We aim to assess glycemic control by continuous glucose monitoring (Dexcom G6 CGM) metrics and glycemic markers in ESKD patients on hemodialysis with burnt-out diabetes. RESEARCH DESIGN AND METHODS: In this pilot prospective study, glycemic control was assessed by continuous glucose monitoring (CGM), HbA1c measures, and glycated albumin and fructosamine measurements in patients with burnt-out diabetes (n = 20) and without a history of diabetes (n = 20). RESULTS: Patients with burnt-out diabetes had higher CGM-measured daily glucose levels, lower percent time in the range 70-180 mg/dL, higher percent time above range (>250 mg/dL), and longer duration of hyperglycemia >180 mg/dL (hours/day) compared with patients without diabetes (all P < 0.01). HbA1c and fructosamine levels were similar; however, patients with burnt-out diabetes had higher levels of glycated albumin than did patients without diabetes. CONCLUSIONS: The use of CGM demonstrated that patients with burnt-out diabetes have significant undiagnosed hyperglycemia. CGM and glycated albumin provide better assessment of glycemic control than do values of HbA1c and fructosamine in patients with ESKD.

Fructosamine and HbA1c: A correlational study in a Southeast Asian Population / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#Fructosamine correlates well with glycated haemoglobin (HbA1c) in Caucasians. This study investigates this correlation and whether fructosamine can reliably estimate glycated haemoglobin in Southeast Asians.@*Methodology@#We recruited 193 participants based on 4 HbA1c bands (<6.0%; 6.0 – 7.9%; 8.0– 9.9%; ≥10%) from a secondary hospital in Singapore between August 2017 and December 2021. Blood samples for fructosamine, glycated haemoglobin, albumin, haemoglobin, thyroid stimulating hormone and creatinine were drawn in a single setting for all participants. Scatter plot was used to explore correlation between fructosamine and glycated haemoglobin. Strength of linear correlation was reported using Pearson’s correlation coefficient. Simple linear regression was used to examine the relationship between fructosamine and glycated haemoglobin.@*Results@#We performed simple linear regression to study the relationship between fructosamine and HbA1c in the research participants (R2 = 0.756, p<0.01). Further analysis with natural logarithmic transformation of fructosamine demonstrated a stronger correlation between HbA1c and fructosamine (R2 = 0.792, p<0.01).@*Conclusions@#Fructosamine is reliably correlated with HbA1c for the monitoring of glycaemic control in Southeast Asians.

Association of vitamin D status with redox balance and insulin resistance and its predicting ability for subclinical pregnancy toxemia in pregnant sheep.

The study aimed to evaluate the role of vitamin D on redox balance, insulin resistance and its predicting value for subclinical pregnancy toxemia (SPT) in pregnant ewes. At four weeks pre-lambing, fifteen healthy pregnant ewes were divided into two groups, ewes with sufficient vitamin D (25-hydroxy-vitamin D (25VitD) (SVD, n = 9) and ewes with insufficient 25VitD (ISVD, n = 6). Blood samples were collected at 4 weeks pre-lambing using modified frequently sampled intravenous glucose tolerance test for the estimation of various metabolites. The baseline glucose, insulin, non-esterified fatty acid (NEFA), fructosamine, beta-hydroxy butyric acid (ß-BHA), calcium, phosphorus concentration and total oxidant status (TOS) did not differ significantly between the two groups, however, total antioxidant capacity (TAC) was significantly (p = 0.031) low in ISVD ewes. Area under the curve for glucose, insulin, elimination rate of glucose and peak insulin also did not differ significantly between the two groups. Correlation analysis revealed, positive association of 25VitD with fructosamine, calcium and TAC, and negative correlation with NEFA and TOS. Subsequent blood sampling at 2 weeks pre-lambing and at lambing showed significant difference in NEFA (p = 0.001), ß-HBA (p = 0.001), and fructosamine(p = 0.012) between the two groups. A significant time x group interaction was observed in NEFA (p = 0.019), ß-HBA (p = 0.031), and fructosamine (p = 0.026) concentration. The NEFA concentrations were increased and fructosamine decreased at 2 weeks pre-lambing and at lambing along with significantly increased ß-HBA at 2 weeks pre-lambing in ISVD compared to SVD. Taking 0.8 mmol/L ß-HBA as the cut off limit for SPT, ISVD ewes had higher odds of developing SPT two weeks prior to lambing (OD 16.00; p = 0.042) and at lambing (OD 10; p = 0.077). This study concludes that 25VitD significantly influence redox balance and energy profile and serves as a valuable predictor for SPT in pregnant sheep.

1-Amino-1-deoxy-d-fructose ("fructosamine") and its derivatives: An update.

1-Amino-1-deoxy-d-fructose (fructosamine, FN) derivatives are omnipresent in all living organisms, as a result of non-enzymatic condensation and Amadori rearrangement reactions between free glucose and biogenic amines such as amino acids, polypeptides, or aminophospholipids. Over decades, steady interest in fructosamine was largely sustained by its role as a key intermediate structure in the Maillard reaction that is responsible for the organoleptic and nutritional value of thermally processed foods, and for pathophysiological effects of hyperglycemia in diabetes. New trends in fructosamine research include the discovery and engineering of FN-processing enzymes, development of advanced tools for hyperglycemia monitoring, and evaluation of the therapeutic potential of both fructosamines and FN-recognizing proteins. This article covers developments in the field of fructosamine and its derivatives since 2010 and attempts to ascertain challenges in future research.