The Oncogenic Action of NRF2 Depends on De-glycation by Fructosamine-3-Kinase.

The NRF2 transcription factor controls a cell stress program that is implicated in cancer and there is great interest in targeting NRF2 for therapy. We show that NRF2 activity depends on Fructosamine-3-kinase (FN3K)-a kinase that triggers protein de-glycation. In its absence, NRF2 is extensively glycated, unstable, and defective at binding to small MAF proteins and transcriptional activation. Moreover, the development of hepatocellular carcinoma triggered by MYC and Keap1 inactivation depends on FN3K in vivo. N-acetyl cysteine treatment partially rescues the effects of FN3K loss on NRF2 driven tumor phenotypes indicating a key role for NRF2-mediated redox balance. Mass spectrometry reveals that other proteins undergo FN3K-sensitive glycation, including translation factors, heat shock proteins, and histones. How glycation affects their functions remains to be defined. In summary, our study reveals a surprising role for the glycation of cellular proteins and implicates FN3K as targetable modulator of NRF2 activity in cancer.

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.

Early pregnancy triglycerides and not fructosamine are associated with birth weight (with foetal sexual dimorphism).

BACKGROUND: We evaluated whether maternal triglycerides (TGs) or fructosamine (measured in early pregnancy) predominantly contribute to birth weight (BW), in a foetal sexual dimorphism. METHODS: Analysis of data from the Amsterdam Born Children and their Development cohort study (total n = 3514). Maternal nonfasting TGs and fructosamine were determined in early gestation (median 13 weeks). Multivariable linear regression analysis was used to determine whether maternal TGs or fructosamine was associated with BW-small for gestational age (SGA)-large for gestational age (LGA) and whether it was sex-dependent. RESULTS: With each 1 mmol/L increase in TGs, BW increased significantly by 81.7 g. This increase was larger with boys (107.3 g; 95% CI 66-148) than girls (60.5 g; 95% CI 23.6-97.4). No association was found with fructosamine. When including different covariates (gestational age at blood sampling, total duration of pregnancy, maternal height, age, parity, ethnicity, educational level, smoking, alcohol, and pre-pregnancy BMI), 29% of the variance in BW can be explained. Adding fructosamine to this model gave no added value in predicting BW, in contrast to adding TGs (R2 raised from 0.292 to 0.299, p < .001). The odds of a newborn LGA with higher maternal TG were increased (OR 1.6, 95% CI 1.3-2.0), in contrast to fructosamine. CONCLUSIONS: Maternal TGs were more dominant (compared to fructosamine) in its association with BW (measured in early physiological pregnancy) and more prominently present when carrying a male foetus. These remarkable observations warrant more future research, especially in obese patients at risk for gestational diabetes.

Enzymatic Deglycation of Damaged Skin by Means of Combined Treatment of Fructosamine-3-Kinase and Fructosyl-Amino Acid Oxidase.

The consensus in aging is that inflammation, cellular senescence, free radicals, and epigenetics are contributing factors. Skin glycation through advanced glycation end products (AGEs) has a crucial role in aging. Additionally, it has been suggested that their presence in scars leads to elasticity loss. This manuscript reports fructosamine-3-kinase (FN3K) and fructosyl-amino acid oxidase (FAOD) in counteracting skin glycation by AGEs. Skin specimens were obtained (n = 19) and incubated with glycolaldehyde (GA) for AGE induction. FN3K and FAOD were used as monotherapy or combination therapy. Negative and positive controls were treated with phosphate-buffered saline and aminoguanidine, respectively. Autofluorescence (AF) was used to measure deglycation. An excised hypertrophic scar tissue (HTS) (n = 1) was treated. Changes in chemical bonds and elasticity were evaluated using mid-infrared spectroscopy (MIR) and skin elongation, respectively. Specimens treated with FN3K and FAOD in monotherapy achieved an average decrease of 31% and 33% in AF values, respectively. When treatments were combined, a decrease of 43% was achieved. The positive control decreased by 28%, whilst the negative control showed no difference. Elongation testing of HTS showed a significant elasticity improvement after FN3K treatment. ATR-IR spectra demonstrated differences in chemical bounds pre- versus post-treatment. FN3K and FAOD can achieve deglycation and the effects are most optimal when combined in one treatment.

FRUCTOSAMINE VALUES IN MONITORING COMPENSATION AND EFFICACY OF DIABETES MELLITUS TREATMENT.

OBJECTIVE: Aim: The relevance of the study is determined by the objective of finding an optimal type of diagnostics of carbohydrate metabolism, that would assess the condition of a diabetic patient undergoing treatment. The purpose of the study is to create a model for monitoring the efficacy of diabetes mellitus treatment by determining the fructosamine levels. PATIENTS AND METHODS: Materials and Methods: The methods for investigating the highlighted issue are clinical examination and laboratory diagnosis of diabetic patients to measure the state of carbon metabolism using ion-exchange chromatography to determine glycated haemoglobin levels and an automatic colorimetric method to determine fructosamine levels. RESULTS: Results: The study presents certain values of fructosamine over the level of changes in the state of patients with diabetes mellitus, reflecting the progress from the treatment in the compensation of carbohydrate metabolism, which allows creating a model of diagnostic values of the fructosamine levels, according to which the efficacy of treatment of diabetes mellitus, the state of progress of the disease in its compensation or decompensation are determined at a qualitative level. CONCLUSION: Conclusions: This allows for the timely adaptive corrective therapeutic and preventive measures to be carried out by medical personnel, who, using values, will monitor the efficacy of treatment in each patient once every three weeks, as this will determine the influence of the type of conducted treatment or other factors aimed at compensating for pathogenetic and clinical manifestations of the disease, which makes the identified fructosamine criteria an important component in the treatment of diabetes mellitus, and indirectly allows to improve the life quality of this patient population, thus bringing a practical solution to the challenge facing the healthcare sector.

Assessment of glycemia in chronic kidney disease.

Reliable assessment of glycemia is central to the management of diabetes. The kidneys play a vital role in maintaining glucose homeostasis through glucose filtration, reabsorption, consumption, and generation. This review article highlights the role of the kidneys in glucose metabolism and discusses the benefits, pitfalls, and evidence behind the glycemic markers in patients with chronic kidney disease. We specifically highlight the role of continuous glucose monitoring as an emerging minimally invasive technique for glycemic assessment.

Proteomics profiles of blood glucose-related proteins involved in a Chinese longevity cohort.

BACKGROUND: High blood glucose level is one of the main characteristics of diabetes mellitus. Based on previous studies, it is speculated longevity families may have certain advantages in blood glucose regulation. However, limited information on these items has been reported. The purpose of this study was to profile differences of plasma proteomics between longevity subjects (with normal fructosamine (FUN) level) and non-longevity area participants (with exceeding standard FUN level). METHODS: In this study, a TMT-based proteomics analysis was used to profile differences of plasma proteomics between longevity subjects (with normal FUN level) and non-longevity area participants (with exceeding standard FUN level). Results were validated by Luminex detection. RESULTS: A total of 155 differentially expressed proteins (DEPs) were identified between these two groups. The DEPs related to blood glucose regulation were mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism and propanoate metabolism, and most of the DEPs were contained in carbohydrate metabolism, PI3K-Akt pathway, glucagon signaling pathway and inflammatory response. Validation by Luminex detection confirmed that CD163 was down-regulated, and SPARC, PARK 7 and IGFBP-1 were up-regulated in longevity participants. CONCLUSIONS: This study not only highlighted carbohydrate metabolism, PI3K-Akt pathway, glucagon signaling pathway and inflammatory response may play important roles in blood glucose regulation, but also indicated that YWHAZ, YWHAB, YWHAG, YWHAE, CALM3, CRP, SAA2, PARK 7, IGFBP1 and VNN1 may serve as potential biomarkers for predicting abnormal blood glucose levels.

Metabolic changes associated with two endocrine abnormalities in dogs: elevated fructosamine and low thyroxine.

INTRODUCTION: Metabolomics studies in canine endocrine abnormalities are sparse and basic information on these abnormalities must be generated. OBJECTIVES: To characterize the metabolic changes associated with elevated fructosamine, reflecting poor glycemic control, and low thyroxine, a thyroid hormone controlling metabolism. METHODS: Leftovers of clinical serum samples; 25 controls, 79 high fructosamine, and 47 low thyroxine, were analyzed using 1H NMR and differences were evaluated using Firth logistic regression. RESULTS: Both high fructosamine and low thyroxine were associated with changes in concentrations of multiple metabolites, including glycoprotein acetyls and lipids. CONCLUSION: These findings suggest promising makers for further research and clinical validation.

Clinicopathologic characteristics of pancreatic islet amyloidosis in the rhesus macaque (Macaca mulatta) and sooty mangabey (Cercocebus atys).

BACKGROUND: Diabetes mellitus type 2 has been linked to pancreatic islet amyloid deposition in humans and nonhuman primates. The authors hypothesized that diabetic primates would have significant differences in pathology than non-diabetic groups. METHODS: This retrospective study used histopathology and immunohistochemistry to characterize and compare pancreatic islet amyloidosis in 58 diabetic and non-diabetic rhesus macaque (RM) and sooty mangabeys (SM). RESULTS: The pancreatic tissues from diabetic RM and SM showed higher histopathology scores for islet amyloid deposit distribution, severity, and calcification deposits compared to their respective non-diabetic cohorts. Further, these tissues from RM and SM with amyloid deposits showed immunoreactivity to insulin, glucagon, islet amyloid polypeptide, serum amyloid P, and glucagon-like peptide 1. CONCLUSIONS: Histopathology results showed that the defined amyloid characteristics are associated with clinical diabetes in both species. The immunohistochemistry results collectively suggest differences in pancreatic hormones and islet amyloid components among both species and diabetic status.

Maternal serum fructosamine levels and stillbirth: a case-control study of the Stillbirth Collaborative Research Network.

OBJECTIVE: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth. DESIGN: Secondary analysis of a case-control study. SETTING: Multicentre study of five geographic catchment areas in the USA. POPULATION: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls. MAIN OUTCOME MEASURES: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth. RESULTS: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 µmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 µmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 µmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605-0.663) overall, 0.713 (0.624-0.802) with diabetes and 0.625 (0.595-0.656) with no diabetes. CONCLUSIONS: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth. TWEETABLE ABSTRACT: Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes.

The Accuracy of Hemoglobin A1c and Fructosamine Evaluated by Long-Term Continuous Glucose Monitoring in Patients with Type 2 Diabetes Undergoing Hemodialysis.

INTRODUCTION: The accuracy of hemoglobin A1c (HbA1c) as a glycemic marker in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with T2D receiving HD. METHODS: Thirty patients in the HD group and 36 patients in the control group (T2D and an estimated glomerular filtration rate >60 mL/min/1.73 m2) completed the study period of 17 weeks. CGM (Ipro2®, Medtronic) was performed 5 times for periods of up to 7 days (with 4-week intervals) during a 16-week period. HbA1c (mmol/mol), the estimated mean plasma glucose from HbA1c (eMPGA1c [mmol/L]) and fructosamine (µmol/L) was measured at week 17 and compared with mean sensor glucose levels from CGM. FINDINGS: In the HD group, mean sensor glucose was 1.4 mmol/L (95% confidence interval [CI]: 1.0-1.8) higher than the eMPGA1c, whereas the difference for controls was 0.1 mmol/L (95% CI: -0.1-[0.4]; p < 0.001). Adjusted for mean sensor glucose, HbA1c was lower in the HD group (-7.3 mmol/mol, 95% CI: -10.0-[-4.7]) than in the control group (p < 0.001), with no difference detected for fructosamine (p = 0.64). DISCUSSION: HbA1c evaluated by CGM underestimates plasma glucose levels in patients receiving HD. The underestimation represents a clinical challenge in optimizing glycemic control in the HD population. Fructosamine is unaffected by the factors affecting HbA1c and appears to be more accurate for glycemic monitoring. CGM or fructosamine could thus complement HbA1c in obtaining more accurate glycemic control in this patient group.

Evaluation of metabolic and oxidative profile in ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of disease.

This study was conducted on ewes with pregnancy toxemia (PT) with an attempt to evaluate metabolic and oxidative profile in subclinical and clinical ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of the disease. A total of 20 ewes having beta-hydroxy butyric acid (ß-HBA) > 2.5 mmol/L and proven clinical sings of PT, categorized as clinical PT (CPT); 12 ewes having ß-HBA 0.8-2.5 mmol/L and no clinical signs of PT, categorized at subclinical PT (SPT); and 10 ewes having ß-HBA ≤ 0.8 mmol/L, categorized as healthy control (CON) were enrolled. Among 20 CPT ewes, 11 had negative outcomes (non-survivors), six ewes had positive outcomes (survivors), and three were lost during follow-up. A significant increase in non-esterified fatty acid, ß-HBA, triglycerides, gamma-glutamyl transferase, lactate dehydrogenase, and malondialdehyde levels and a significant decrease in fructosamine were observed in CPT and SPT compared to CON. A significant increase in cholesterol, aspartate amino transferase, and creatinine kinase and a significant decrease in albumin, potassium, calcium, superoxide dismutase, and catalase were observed in CPT only. Glucose was significantly decreased in SPT only. The highest area under the curve (AUC) was observed for fructosamine (89.7% and 87.5% for CPT and SPT, respectively) with the optimum cutoff point calculated on the basis of maximum sensitivity (SE) and specificity (SP) being 0.607 mmol/L (SE: 89.3% and SP: 72.2%) and 1.005 mmol/L (SE: 90.0% and SP: 75.3%) for CPT and SPT, respectively. At the cutoff limit of 0.607 mmol/L and 1.005 mmol/L, the odds ratio was 10.8 and 8.0 for CPT and SPT, respectively. A significant decrease in fructosamine and potassium and a significant increase in creatinine, lactate dehydrogenase, and malondialdehyde were observed in non-survivors compared to survivors. It was thus concluded that fructosamine was the best diagnostic indicator of both CPT and SPT followed by non-esterified fatty acid. Fructosamine, creatinine, potassium, lactate dehydrogenase, and malondialdehyde were the best prognostic indicators of PT.

Impact of triglycerides and waist circumference on insulin resistance and ß-cell function in non-diabetic first-degree relatives of type 2 diabetes.

BACKGROUND: Although there is abundant evidence indicating the relative contribution of insulin resistance (HOMA-IR) and ß-cell dysfunction (HOMA-ß) among first-degree relatives (FDRs) of Type 2 DM patients, few studies reported the association between HOMA-IR and HOMA-ß with metabolic syndrome. Our objective was to evaluate the impact of metabolic syndrome factors on HOMA-IR, HOMA-ß and glycoproteins in non-diabetic FDRs. METHODS: In this study, 103 Yemeni male subjects aged 25-42 years, with BMI < 25 kg/m2 were examined, 39 of whom were normal subjects with no family history of diabetes served as control and 64 subjects were non-diabetic FDRs of Type 2 DM patients. RESULTS: Both glycoproteins, glycated haemoglobin (HbA1c) and fructosamine as well as insulin, HOMA-IR and HOMA-ß were significantly (p = 4.9 × 10-9; 6.0 × 10-8; 6.6 × 10-12; 1.3 × 10-7; 5.5 × 10-12, respectively) higher in non-diabetic FDRs as compared to control group. Fasting plasma glucose, though within normal range, were significantly (p = 0.026) higher in non-diabetic FDRs. Linear regression analysis showed that both TG and WC are the main metabolic syndrome factors that significantly increased HOMA-IR (B = 0.334, p = 1.97 × 10-6; B = 0.024, p = 1.05 × 10-5), HOMA-ß (B = 16.8, p = 6.8 × 10-5; B = 0.95, p = 0.004), insulin (B = 16.5, p = 1.2 × 10-6; B = 1.19, p = 8.3 × 10-6) and HbA1c (B = 0.001, p = 0.034; B = 0.007, p = 0.037). CONCLUSION: Triglyceride and WC are the important metabolic syndrome factors associated with insulin resistance, basal ß-cell function and insulin levels in non-diabetic FDR men of Type 2 DM patients. Moreover, FDRs showed insulin resistance with compensatory ß-cell function (hyperinsulinaemia) suggesting that insulin resistance precede the development of pancreatic ß-cell dysfunction in individuals at risk of Type 2 DM.

Use of large scale EHR data to evaluate A1c utilization among sickle cell disease patients.

BACKGROUND: The glycated hemoglobin (A1c) test is not recommended for sickle cell disease (SCD) patients. We examine ordering patterns of diabetes-related tests for SCD patients to explore misutilization of tests among this underserved population. METHODS: We used de-identified electronic health record (EHR) data in the Cerner Health Facts™ (HF) data warehouse to evaluate the frequency of A1c and fructosamine tests during 2010 to 2016, for 37,151 SCD patients from 393 healthcare facilities across the United States. After excluding facilities with no A1c data, we defined three groups of facilities based on the prevalence of SCD patients with A1c test(s): adherent facilities (no SCD patients with A1c test(s)), minor non-adherent facilities, major non-adherent facilities. RESULTS: We determined that 11% of SCD patients (3927 patients) treated at 393 facilities in the US received orders for at least one A1c test. Of the 3927 SCD patients with an A1c test, only 89 patients (2.3%) received an order for a fructosamine test. At the minor non-adherent facilities, 5% of the SCD patients received an A1c test while 58% of the SCD patients at the least adherent facilities had at least one A1c test. Overall, the percent of A1c tests ordered for SCD patients between 2010 and 2016 remained similar. CONCLUSIONS: Inappropriate A1c test orders among a sickle cell population is a significant quality gap. Interventions to advance adoption of professional recommendations that advocate for alternate tests, such as fructosamine, can guide clinicians in test selection to reduce this quality gap are discussed. The informatics strategy used in this work can inform other largescale analyses of lab test utilization using de-identified EHR data.

A Potential Role for Fructosamine-3-Kinase in Cataract Treatment.

Cataracts are the major cause of blindness worldwide, largely resulting from aging and diabetes mellitus. Advanced glycation end products (AGEs) have been identified as major contributors in cataract formation because they alter lens protein structure and stability and induce covalent cross-linking, aggregation, and insolubilization of lens crystallins. We investigated the potential of the deglycating enzyme fructosamine-3-kinase (FN3K) in the disruption of AGEs in cataractous lenses. Macroscopic changes of equine lenses were evaluated after ex vivo intravitreal FN3K injection. The mechanical properties of an equine lens pair were evaluated after treatment with saline and FN3K. AGE-type autofluorescence (AF) was measured to assess the time-dependent effects of FN3K on glycolaldehyde-induced AGE-modified porcine lens fragments and to evaluate its actions on intact lenses after in vivo intravitreal FN3K injection of murine eyes. A potential immune response after injection was evaluated by analysis of IL-2, TNFα, and IFNγ using an ELISA kit. Dose- and time-dependent AF kinetics were analyzed on pooled human lens fragments. Furthermore, AF measurements and a time-lapse of macroscopic changes were performed on intact cataractous human eye lenses after incubation with an FN3K solution. At last, AF measurements were performed on cataractous human eyes after crossover topical treatment with either saline- or FN3K-containing drops. While the lenses of the equine FN3K-treated eyes appeared to be clear, the saline-treated lenses had a yellowish-brown color. Following FN3K treatment, color restoration could be observed within 30 min. The extension rate of the equine FN3K-treated lens was more than twice the extension rate of the saline-treated lens. FN3K treatment induced significant time-dependent decreases in AGE-related AF values in the AGE-modified porcine lens fragments. Furthermore, in vivo intravitreal FN3K injection of murine eyes significantly reduced AF values of the lenses. Treatment did not provoke a systemic immune response in mice. AF kinetics of FN3K-treated cataractous human lens suspensions revealed dose- and time-dependent decreases. Incubation of cataractous human eye lenses with FN3K resulted in a macroscopic lighter color of the cortex and a decrease in AF values. At last, crossover topical treatment of intact human eyes revealed a decrease in AF values during FN3K treatment, while showing no notable changes with saline. Our study suggests, for the first time, a potential additional role of FN3K as an alternative treatment for AGE-related cataracts.

Heritability analysis of nontraditional glycemic biomarkers in the Atherosclerosis Risk in Communities Study.

Nontraditional glycemic biomarkers, including fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG) are potential alternatives or complement to traditional measures of hyperglycemia. Genetic variants are associated with these biomarkers, but the heritability, or extent to which genetics control their variation, is not known. We estimated pedigree-based, SNP-based, and bivariate heritabilities for traditional glycemic biomarkers (fasting glucose, HbA1c), and nontraditional biomarkers (fructosamine, glycated albumin, 1,5-AG) among white participants in the Atherosclerosis Risk in Communities (ARIC) Study (N = 400 first-degree relatives from sibships, N = 5,575 unrelated individuals). Pedigree-based heritabilities (representing heritability from the entire genome) for nontraditional biomarkers were substantial (0.44-0.55) and comparable to HbA1c (0.34); the fasting glucose estimate was nonsignificant. SNP-based heritabilities (representing heritability from common variants) were lower than pedigree-based heritabilities for all biomarkers. Bivariate heritabilities showed shared genetics between fructosamine and glycated albumin (0.46 pedigree-based, 1.00 SNP-based) and glycated albumin and 1,5-AG (0.50 pedigree-based, 0.47 SNP-based). Genetic factors contribute to a considerable proportion of the variance of fructosamine, glycated albumin, and 1,5-AG and a portion of this heritability likely comes from common variants.

Hemoglobin A1c and fructosamine correlate in a patient with sickle cell disease and diabetes on chronic transfusion therapy.

In patients with sickle cell disease (SCD) and diabetes mellitus (DM), hemoglobin A1c (HbA1c ) is unreliable and the American Diabetes Association recommends monitoring long-term glycemia by measuring serum glucose, but use of serum fructosamine (SF), a measurement independent of red cell lifespan, has been reported. SF as a screen for DM in SCD, however, is not standardized and its relationship to serum glucose has not been validated. Further, screening for DM was not adequately addressed in the 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines for SCD management. Blood transfusions, an important treatment for some patients with SCD, can also impact HbA1c . We present a case of a patient with SCD and cystic fibrosis-related diabetes on monthly chronic transfusions therapy (CTT) who had well-correlated "steady state" HbA1c and SF levels over time, suggesting for the first time these markers may actually be useful when following long-term glycemic control in patients with SCD on CTT programs.

The agreement between fasting glucose and markers of chronic glycaemic exposure in individuals with and without chronic kidney disease: a cross-sectional study.

BACKGROUND: To assess whether the agreement between fasting glucose and glycated proteins is affected by chronic kidney disease (CKD) in a community-based sample of 1621 mixed-ancestry South Africans. METHODS: CKD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2. Fasting plasma glucose and haemoglobin A1c (HbA1c) concentrations were measured by enzymatic hexokinase method and high-performance liquid chromatography, respectively, with fructosamine and glycated albumin measured by immunoturbidimetry and enzymatic method, respectively. RESULTS: Of those with CKD (n = 96), 79, 16 and 5% where in stages 3, 4 and 5, respectively. Those with CKD had higher levels of HbA1c (6.2 vs. 5.7%; p < 0.0001), glycated albumin (15.0 vs. 13.0%; p < 0.0001) and fructosamine levels (269.7 vs. 236.4 µmol/l; p < 0.0001), compared to those without CKD. Higher fasting glucose levels were associated with higher HbA1c, glycated albumin and fructosamine, independent of age, gender, and CKD. However, the association with HbA1c and glycated albumin differed by CKD status, at the upper concentrations of the respective markers (interaction term for both: p ≤ 0.095). CONCLUSION: Our results suggest that although HbA1c and glycated albumin perform acceptably under conditions of normoglycaemia, these markers correlate less well with blood glucose levels in people with CKD who are not on dialysis.

HbA1C as a marker of retrograde glycaemic control in diabetes patient with co-existed beta-thalassaemia: A case report and a literature review.

WHAT IS KNOWN AND OBJECTIVE: The HbA1C marker used in assessing diabetes control quality is not sufficient in diabetes patients with thalassaemia. CASE DESCRIPTION: A male diabetic patient with thalassaemia was hospitalized due to distal neuropathic pain, right toe trophic ulcer, unacceptable five-point glycaemic profile and recommended HbA1C value. After simultaneously initiated insulin therapy and management of ulcer by hyperbaric oxygen, the patient showed improved glycaemic control and ulcer healing, which led to the patient's discharge. WHAT IS NEW AND CONCLUSION: In thalassaemia and haemoglobinopathies, due to discrepancies in the five-point glycaemic profile and HbA1C values, it is necessary to measure HbA1C with a different method or to determine HbA1C and fructosamine simultaneously.

Comparison of glycaemic control and anthropometric parameters before and after Ramadan fasting in a selected cohort of patients with type 2 diabetes mellitus in Sri Lanka.

INTRODUCTION: The majority of Sri Lankan Moors fast during Ramadan. This may have an effect on their glycaemic control and anthropometric parameters. However, limited information exists about the impact of Ramadan fasting on diabetes in Sri Lanka. OBJECTIVES: The main objective of this study was to investigate the effect of Ramadan fasting on glycaemic control and anthropometric parameters in patients with type 2 diabetes mellitus (T2DM). Patients were also observed for symptoms of hypoglycaemia, timing and association with different antidiabetic agents. METHODS: One hundred and twenty Sri Lankan Moors with T2DM were recruited for this study. Biochemical investigations and anthropometric parameters were done before and after Ramadan fasting. The statistical analysis was done with paired t test to compare glycaemic control and anthropometric parameters before and after Ramadan. RESULTS: There was a significant decrease in body weight (mean body weight 66.17 to 65.52 kg; p= < 0.001) and waist circumference (93.84 to 92.16cm; p= < 0.001). However, the glycaemic control worsened in all patients during Ramadan with rise in mean fructosamine value of 354.1 to 996.9µmol/L. Out of 104 participants 43 participants experienced symptoms of hypoglycaemia. CONCLUSIONS: The current study showed an improvement in the body weight and waist circumference during Ramadan fasting, however the glycaemic control has been worsened. More follow-up studies are warranted in order to draw a conclusion on the effect of Ramadan fasting in glycaemic control and anthropometric parameters in diabetes patients.