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.

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.

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.

Droplet-based µChopper device with a 3D-printed pneumatic valving layer and a simple photometer for absorbance based fructosamine quantification in human serum.

The development of microfluidic systems for biological assays presents challenges, particularly in adapting traditional optical absorbance assays to smaller volumes or to microfluidic formats. This often requires assay modification or translation to a fluorescence version, which can be impractical. To address this issue, our group has developed the µChopper device, which uses microfluidic droplet formation as a surrogate for an optical beam chopper, allowing for lock-in analysis and improved limits of detection with both absorbance and fluorescence optics without modifying the optical path length. Here, we have adapted the µChopper to low-cost optics using a light-emitting diode (LED) source and photodiode detector, and we have fabricated the pnuematically valved devices entirely by 3D printing instead of traditional photolithography. Using a hybrid device structure, fluidic channels were made in polydimethylsiloxane (PDMS) by moulding onto a 3D-printed master then bonding to a prefabricated thin layer, and the pneumatic layer was directly made of 3D-printed resin. This hybrid structure allowed an optical slit to be fabricated directly under fluidic channels, with the LED interfaced closely above the channel. Vacuum-operated, normally closed valves provided precise temporal control of droplet formation from 0.6 to 2.0 Hz. The system was validated against the standard plate reader format using a colorimetric fructosamine assay and by quantifying fructosamine in human serum from normal and diabetic patients, where strong correlation was shown. Showing a standard benefit of microfluidics in analysis, the device required 6.4-fold less serum volume for each assay. This µChopper device and lower cost optical system should be applicable to various absorbance based assays in low volumes, and the reliance on inexpensive 3D printers makes it more accessible to users without cleanroom facilities.

Association of time to metritis diagnosis with circulating concentration of metabolites, minerals, and haptoglobin in Jersey cows.

Our objective was to investigate the association of early metritis [EMET, diagnosed at <5 d in milk (DIM)] and late metritis (LMET, diagnosed at ≥5 DIM) with circulating concentrations of energy metabolites, minerals, and haptoglobin (Hp) throughout the first 14 d postpartum. A total of 379 purebred Jersey cows were enrolled in a prospective cohort study from a single herd in west Texas. Cows were examined for metritis using the Metricheck device (Simcro Ltd.) at 4, 7, and 10 DIM. Cows identified by farm employees as possible metritis cases were also evaluated for metritis. Blood samples were collected for analysis of concentrations of Ca, Mg, and glucose at DIM 1 through 5, 7, 10, and 14. Albumin, urea, fructosamine, free fatty acids (FFA), creatinine, and ß-hydroxybutyrate (BHB) were analyzed at DIM 3, 5, 7, 10, and 14, and Hp at DIM 1 through 5 and 7. Data were analyzed using the MIXED and PHREG procedures of SAS (SAS Institute Inc.). A series of mixed general linear models accounting for repeated measures were fitted to the data. The independent variables metritis [no metritis (NMET), EMET, and LMET], DIM of analyte assessment, and parity were forced in all models. Multivariable Cox proportional hazard models were built to assess the risk of pregnancy and culling within 150 DIM. The overall metritis incidence was 26.9% (EMET = 49; LMET = 53; NMET = 277). Average concentrations of glucose, Mg, and urea were not associated with metritis. The associations of Ca, creatinine, BHB, and fructosamine with metritis were dependent on the DIM of analyte assessment. Cows categorized as EMET and LMET had, on average, lower albumin and fructosamine compared with NMET cows. Both EMET and LMET cows had, on average, greater BHB than NMET cows. A greater FFA concentration was only observed in cows diagnosed with EMET compared with NMET cows (EMET = 0.58, LMET = 0.52, NMET = 0.48 mmol/L). Additionally, circulating Hp concentration was greater for LMET and EMET compared with NMET cows, and EMET cows had greater Hp compared with LMET cows (EMET = 1.15; LMET = 1.00; NMET = 0.84). In conclusion, several blood biomarkers were temporally associated with early versus late metritis diagnosis in postpartum Jersey cows. No meaningful differences were observed in production, reproduction, or culling between EMET and LMET cows. These results suggest that cows with EMET undergo a more severe degree of inflammation and negative energy balance compared with NMET cows.

Effect of Epstein-Barr Virus Infection on Selected Immunological Parameters in Children with Type 1 Diabetes.

Diabetes mellitus is a group of metabolic disorders with different etiologies, pathogeneses and clinical pictures, characterized by chronic hyperglycemia due to abnormal insulin secretion or action. Type 1 diabetes mellitus is the most common type of diabetes mellitus in children and adolescents, accounting for about 90% of diabetes in the population under the age of 18. The etiopathogenesis of type 1 diabetes is multifactorial. The disease occurs as a result of the interaction of three factors: genetic predisposition, environmental factors and the immune response. Research in recent years has focused on the involvement of Epstein-Barr virus (EBV) in the pathogenesis of type I diabetes. The goals of treating type 1 diabetes include maintaining blood-glucose, fructosamine and glycated hemoglobin (HbA1c) levels; therefore, the main purpose of this study was to evaluate the effect of EBV infection on the activation of selected immune cells, fructosamine levels and HbA1c levels in children with type I diabetes. Based on our study, we found a lower percentage of CD8+ T lymphocytes with expression of the CD69 molecule in patients with anti-VCA antibodies in the IgG class, and a lower percentage of CD8+ T lymphocytes with expression of the CD25+ molecule in patients with anti-EBNA-1 antibodies in the IgG class, which may indicate limited control of the immune system during EBV infection in patients. There was a lower percentage of CD3+CD4+ T lymphocytes secreting IL-4 in the study group, indicating that a deficiency in IL-4 production may be related to the development of type 1 diabetes. There was an increase in the percentage of CD4+CD3+IL-10 lymphocytes in the study group with anti-VCA antibodies present in the IgG class and anti-EBNA-1 antibodies in the IgG class compared to the patients without antibodies. In addition, there was a significant increase in fructosamine levels and higher glycated hemoglobin levels in the study group with antibodies to EBV antigens. In addition, an increase in the percentage of T lymphocytes with a CD4+CD3+IL-17+ phenotype in the patients with anti-VCA IgG antibodies was confirmed, and higher HbA1c levels may suggest that EBV infection is accompanied by an increase in IL-17 secretion.

Association between Hyperglycemia and Canine Serum Pancreatic Lipase Immunoreactivity Concentration in Diabetic Dogs.

It has been reported that hypertriglyceridemia can partially mediate between diabetes mellitus (DM) and pancreatitis in dogs, implying that another mediator, such as chronic hyperglycemia, might exist. Therefore, this study aimed to evaluate the relationship between hyperglycemia and serum canine pancreatic lipase immunoreactivity (cPLI) concentration in diabetic dogs. This retrospective cohort study included 26 client-owned diabetic dogs, divided according to their serum fructosamine levels (<500 µmol/L = well-controlled DM group; ≥500 µmol/L = untreated or poorly controlled DM group). Five of the 26 DM dogs (19.2%) had serum cPLI concentrations consistent with pancreatitis, among which two showed ultrasonographic evidence of pancreatitis without clinical signs. The serum cPLI concentrations (median [interquartile range]) were significantly higher in the untreated or poorly controlled group (520 µg/L [179.76-1000 µg/L]) than in the well-controlled group (77 µg/L [32.22-244.6 µg/L], P = 0.0147). The serum fructosamine concentration was positively correlated with the serum cPLI concentration (r = 0.4816; P = 0.0127). Multivariate analysis revealed serum triglyceride and fructosamine concentrations were associated with the serum cPLI concentration. In conclusion, this study suggests that chronic hyperglycemia may induce pancreatic inflammation in diabetic dogs; however, the clinical significance of increased cPLI concentration is unknown.

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.

[Modern approaches to developing a system of valid methods for monitoring individual health and maintaining active longevity]. / Sovremennye podkhody k razrabotke sistemy validnykh metodov monitoringa individual'nogo zdorov'ya i podderzhaniya aktivnogo dolgoletiya.

Life expectancy In Russia in 2023, according to preliminary data, exceeded 73 years, returning to the pre-pandemic level. The increase in life expectancy is associated both with an improvement in the quality of medical care In Russia and with a more responsible attitude towards the health of citizens, which is confirmed by an improvement in the quality of nutrition, a decrease in alcohol consumption and an increase in the number of people involved in sports. At the same time, there are many signs of aging, both cellular and molecular, some of the main ones are genome stability, telomere shortening, epigenetic alterations, impaired proteostasis and nutrient recognition, mitochondrial dysfunction, depletion of the stem cell pool and changes in intercellular interactions, extracellular matrix rigidity, as well as retrotransposon activation and chronic inflammation. For these reasons, in modern healthcare, the tasks of preventing premature aging and treating age-related diseases are becoming priorities. MATERIAL AND METHODS: In total, at the first stage of work (in 2023), we examined 80 people, whose average age was 59.6±0.7 years. When analyzing and assessing data, the study adopted a division into age groups (WHO). The following indicators were studied: HbA1, fructosamine, HDL cholesterol, LDL cholesterol, insulin, homocysteine, C-peptide, TSH, free T4, prolactin, total testosterone, cortisol, arginine, asymmetric dimethylarginine, leptin, TNF-a, ferritin, interleukin 1 and 6, telomere length, creatinine, uric acid and urea. RESULTS: As a result of the study, it was revealed that the aging process of the body affects many indicators, while the main markers that changed in men aged 18 to 44 years were total testosterone, leptin and telomere length; aged 44 to 60 years - HbA1, fructosamine, HDL cholesterol, homocysteine, C-peptide, total testosterone, leptin and telomere length; from 60 to 75 years - fructosamine, HDL cholesterol and telomere length and for 75-90 years - HbA1, HDL cholesterol, insulin, total testosterone, leptin and telomere length, interleukin 6 and uric acid. In women aged 18 to 44 years, only an increase in leptin was observed against the background of shortening telomere length; at the age of 44 to 60 years, the main markers that changed were total testosterone, leptin and telomere length; for the age group 60-75 years - indicators of HbA1, homocysteine, C-peptide, prolactin, total testosterone and leptin, interleukin 6 and uric acid, telomere length was shorter by only 2%; in the age group of 75-90 years, the main markers that changed were insulin, total testosterone, leptin, interleukin 6, while the indicators of uric acid, urea and telomere length differed from the reference values by 2-4%. Shortening of telomere length in all age groups, both men and women, indicates the presence of signs of premature aging. In an individual analysis, data were obtained on a more dramatic shortening of telomeres in 16 subjects in the presence of impaired glucose tolerance and insulin secretion, especially in comparison with healthy subjects, which was confirmed by the data of glycated hemoglobin (HbA1c), while, with shortening of telomere length, the HbA1 indicator was significantly higher (6.8±0.5) than in individuals with long telomeres and no chronic pathology (5.1±0.4). CONCLUSION: A system of highly valid methods and panels of markers has been developed that indicate the presence of aging processes, taking into account gender and age characteristics, which can be used to identify premature aging processes, monitor individual health and maintain active longevity, as well as for the prevention of age-associated diseases.

Metabolic programming in the offspring after gestational overfeeding in the mother: toward neonatal rescuing with metformin in a swine model.

OBJECTIVES: Maternal overfeeding during gestation may lead to adverse metabolic programming in the offspring mediated by epigenetic alterations. Potential reversal, in early life, of these alterations may help in the prevention of future cardio-metabolic conditions. In this context, our aims were: (1) to study the effects of maternal overfeeding on the metabolic and epigenetic programming of offspring's adipose tissue; and (2) to test the potential of postnatal metformin treatment to reverse these changes. METHODS: We used a swine animal model where commercial production sows were either overfed or kept under standard diet during gestation, and piglets at birth were randomly assigned to metformin (n = 16 per group) or vehicle treatment during lactation (n = 16 per group). RESULTS: Piglets born to overfed sows showed a worse metabolic profile (higher weight, weight gain from birth and abdominal circumference; all p < 0.05) together with altered serological markers (increased HOMA-IR, fructosamine, total cholesterol, C-Reactive Protein and lower HMW adiponectin; all p < 0.05). The visceral adipose tissue also showed altered morphology (increased adipocyte area, perimeter and diameter; all p < 0.05), as well as changes in gene expression (higher CCL2 and INSR, lower DLK1; all p < 0.05), and in DNA methylation (96 hypermethylated and 99 hypomethylated CpG sites; FDR < 0.05). Metformin treatment significantly ameliorated the abnormal metabolic profile, decreasing piglets' weight, weight gain from birth, abdominal circumference and fructosamine (all p < 0.05) and reduced adipocyte area, perimeter, and diameter in visceral adipose tissue (all p < 0.05). In addition, metformin treatment potentiated several associations between gene expression in visceral adipose tissue and the altered metabolic markers. CONCLUSIONS: Maternal overfeeding during gestation leads to metabolic abnormalities in the offspring, including adipose tissue alterations. Early metformin treatment mitigates these effects and could help rescue the offspring's metabolic health.

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.

Indicators of glucose dysregulation and the relationship with iron overload in Chinese children with beta thalassemia major.

INTRODUCTION: Patients with beta thalassemia major (TM) have a higher risk of diabetes and an abnormal oral glucose tolerance test (OGTT), but there is no single agree monitoring parameter that reflects glycemic status. The possible mechanisms include iron overload and blood transfusion, but they require further investigation. PURPOSE: This study explored the role of glycated hemoglobin A1c (HbA1c), fructosamine, and glycated albumin (GA) in evaluating the glucose dysregulation and to determine the potential relationship between iron deposition and glucose metabolism disorder in beta TM. METHODS: A cross-sectional study was performed on 118 patients with beta TM and the control group consisted of 33 healthy children with no statistical differences in age, sex, and body mass index (BMI). Fast plasma glucose (FPG), fast insulin (FINS), insulin resistance index (HOMA-IRI), and insulin sensitivity index (HOMA-ISI) were compared between the patient and control groups. HbA1c, GA, fructosamine, and serum ferritin (SF) were measured in the patient group. OGTT, as well as heart and liver magnetic resonance imaging (MRI) T2*, was performed. For all statistical analyses, SPSS 21.0 was used and p < 0.05 was accepted as statistically significant. RESULTS: FPG, FINS, and HOMA-IRI were significantly increased while HOMA-ISI decreased in the beta TM patients when compared with those in the control group. In patients with beta TM, 17 (14.41%) of patients had been diagnosed with diabetes, while 48 (40.68%) had both impaired fasting glucose and impaired glucose tolerance. HbA1c, GA, and fructosamine were increased according to the degree of abnormal glucose metabolism. Statistically significant differences were found in age, SF, and cardiac T2* between the abnormal and normal OGTT groups. CONCLUSION: HbA1c may be used as a significant measure for monitoring glycemic levels in patients with beta TM. Furthermore, GA and fructosamine were alternative indicators of glucose status. Patients with heart iron deposition or an SF > 4000 µg/L were prone to abnormal glucose metabolism, so chelation therapy should be reinforced.

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.

Does Preoperative Glycemic Control Restore Immune Defense Against Implant-related Infection in Mice With Diabetes?

BACKGROUND: The presence of Type II diabetes is a well-established risk factor for bone and joint infection, especially in patients with poor glycemic control. However, few studies have investigated the effect of the duration of preoperative glycemic intervention. For patients with poor glycemic control, the effect of the duration of preoperative glycemic intervention remains unknown. Many glycemic biomarkers including hemoglobin A1c (HbA1c), fructosamine, and 1,5-anhydroglucitol have different response rates to glycemic change. It is unclear which biomarker is more closely related to the decrease in infection proportion after preoperative glycemic intervention. QUESTIONS/PURPOSES: (1) Is there an effect of the duration of preoperative insulin therapy in mice with diabetes receiving an experimental intra-articular implant? (2) Of the three commonly used biomolecules for monitoring blood glucose levels (HbA1c, fructosamine, and 1,5-anhydroglucitol), is one more closely related to decrease in infection proportion after presurgical insulin therapy? METHODS: With a well-established protocol, Type II diabetes was modeled in female 10-week-old C57BL/6 mice by maintaining them on a high-fat diet (60% fat) for 8 months; control mice without diabetes received a normal low-fat diet (10% fat). Mice with Type II diabetes were randomized into groups to receive preoperative glycemic intervention with insulin for 0, 1, 3, 5, 7, 14, or 28 days, and investigators were blinded to the randomization. Mice with and without diabetes then received a surgically inserted wire into the femoral canal in a retrograde fashion and received a local or systemic challenge with Staphylococcus aureus or Escherichia coli (n = 20 for each bacteria challenge [systemic or local]/timepoint). The proportion of culture-positive joint samples was calculated. An additional 10 mice with Type II diabetes were treated with insulin for 28 days and the HbA1c, fructosamine, and 1,5-anhydroglucitol levels were consecutively monitored. Fisher exact tests and nonparametric Wilcoxon rank sum tests were used to analyze the different between different groups, with p < 0.05 taken as significant. RESULTS: When insulin therapy was administered, the proportion of bone and joint infections decreased in mice with Type II diabetes, reaching asymptotic levels after 3 days of treatment for the systemic (S. aureus: 7 of 20 mice with diabetes on 3-day therapy, p < 0.001; 8 of 20 on 5-day, p = 0.002; 10 of 20 on 7-day, p = 0.01; 9 of 20 on 14-day, p = 0.006; and 8 of 20 on 28-day, p = 0.002 versus 18 of 20 in the no insulin therapy group; E. coli: 6 of 20 on 3-day therapy, p = 0.004; 7 of 20 on 5-day, p = 0.01; 7 of 20 on 7-day, p = 0.01; 6 of 20 on 14-day, p = 0.004; and 7 of 20 on 28-day, p = 0.01 versus 16 of 20 in the no insulin therapy group) or local bacterial challenge (S. aureus: 11 of 20 on 3-day therapy, p = 0.001; 12 of 20 on 5-day, p = 0.003; 10 of 20 on 7-day, p < 0.001; 12 of 20 on 14-day, p = 0.003; and 13 of 20 on 28-day, p = 0.008 versus 20 of 20 in the no insulin therapy group; E. coli: 10 of 20 on 3-day therapy, p = 0.003; 10 of 20 on 5-day, p = 0.003; 9 of 20 on 7-day, p = 0.001; 11 of 20 on 14-day, p = 0.008; and 10 of 20 on 28-day, p = 0.003 versus 19 of 20 in no insulin therapy group). Even after 28 days of insulin therapy, the proportion of bone and joint infections was still higher (statistically insignificant with large absolute difference, except for one instance) in mice with diabetes than in control mice without diabetes after systemic (S. aureus: 8 of 10 mice with diabetes on 28-day therapy versus 4 of 20 mice without diabetes, p = 0.30; E. coli: 7 of 20 on 28-day therapy versus 1 of 20 mice without diabetes, p = 0.04) or local challenge (S. aureus: 13 of 20 mice on 28-day therapy versus 8 of 20 mice without diabetes, p = 0.21; E. coli: 10 of 20 on 28-day therapy versus 5 of 20 mice without diabetes, p = 0.19). HbA1c and fructosamine levels were lagging indicators of the decrease in infection proportion after insulin treatment. In contrast, the 1,5-anhydroglucitol level increased quickly (reflecting lower blood glucose levels) in response to short-term glycemic control. Moreover, the time required for changes in 1,5-anhydroglucitol levels to be detected was no more than 3 days (3 days insulin therapy 1.86 ± 0.20 [95% CI -1.27 to -0.45]; p˂0.001 versus no insulin therapy 1.00 ± 0.11). CONCLUSION: In a model of mice with Type II diabetes, prolonged preoperative glycemic intervention did not further reduce the proportion of bone and joint infections compared with that achieved with short-term intervention of 3 days. CLINICAL RELEVANCE: Compared with HbA1c and fructosamine, 1,5-anhydroglucitol might be a better indicator for risk stratification and guiding the timing for elective surgery. Comparative study of these three biomarkers based on patient samples is warranted to further confirm this conclusion.

Protective effect of nimbolide against streptozotocin induced gestational diabetes mellitus in rats via alteration of inflammatory reaction, oxidative stress, and gut microbiota.

BACKGROUND: Gestational diabetes mellitus (GDM) is a significant pregnancy-related condition, which showed effect on the development of fetal. Anti-inflammatory and antioxidant therapy commonly used for the treatment of GDM. Nimbolide already confirmed their anti-inflammatory and anti-oxidant effect against various animal disease model. Our objective in this research is to investigate the protective effect of nimbolide against STZ induced GDM and elucidate the mechanism. METHODS: In this experimental study, pregnant female Wistar rats were used and STZ (40 mg/kg) was used to induce the GDM. Blood glucose level (BGL), body weight and plasma insulin were assessed at regular time (gestational day 0, 9, and 18). Water intake, food intake, fecal and urine output were also estimated. In the female rats, hemoglobin (Hb), glycalated hemoglobin (HbA1c), hepatic glycogen, fructosamine, adiponectin, leptin, lipid, antioxidant and inflammatory cytokines parameters were estimated. In the fetuses, the fetues weight, implementation loss, and fetal weight were estimated. At the completion of the protocol, biochemical parameters were calculated. Gut microbiota was estimated in end of the study. RESULTS: Nimbolide treatment significantly (p < .001) improved the fetuses level and suppressed the fetal weight and implantation loss. Nimbolide treatment significantly (p < .001) suppressed the BGL and enhanced the body weight, insulin level. Nimbolide treatment suppressed the water intake, food intake, urinary and fecal output. Nimbolide significantly (p < .001) suppressed the fructosamine, leptin and enhanced the adiponectin level. Nimbolide treatment significantly (p < .001) decreased the malonaldehyde (MDA) level and boosted the total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and catalase (CAT); suppressed the level of TNF-α, IL-1ß, IL-6, and boosted the level of IL-10. Furthermore, nimbolide treatment reversed the gut microbiota alteration induced via STZ in female rats. At the phylum level, the Firmicutes and Bacteroidetes relative abundance was altered via nimbolide treatment. The ratio of F/B boosted in GDM group and nimbolide treatment significantly (p < .001) suppressed. Nimbolide considerably suppressed the firmicutes and enhanced the Bacteroidetes, CAG-352, Lacnospirace. CONCLUSION: Based on the findings, we may conclude that nimbolide protects the pregnant rats from GDM via alteration of inflammation, oxidative stress, and gut microbiota.

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.

Glycaemic markers and all-cause mortality in older adults with and without diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: There is controversy regarding the performance of HbA1c in old age. We evaluated the prognostic value of HbA1c and other glycaemic markers (fructosamine, glycated albumin, fasting glucose) with mortality risk in older adults (66-90 years). METHODS: This was a prospective analysis of 5636 participants (31% with diagnosed diabetes, mean age 76, 58% female, 21% black) in the Atherosclerosis Risk in Communities (ARIC) study, baseline 2011-2013. We used Cox regression to examine associations of glycaemic markers (modelled in categories) with mortality risk, stratified by diagnosed diabetes status. RESULTS: During a median of 6 years of follow-up, 983 deaths occurred. Among older adults with diabetes, 30% had low HbA1c (<42 mmol/mol [<6.0%]) and 10% had high HbA1c (≥64 mmol/mol [≥8.0%]); low (HR 1.32 [95% CI 1.04, 1.68]) and high (HR 1.86 [95% CI 1.32, 2.62]) HbA1c were associated with mortality risk vs HbA1c 42-52 mmol/mol (6.0-6.9%) after demographic adjustment. Low fructosamine and glycated albumin were not associated with mortality risk. Both low and high fasting glucose were associated with mortality risk. After further adjustment for lifestyle and clinical risk factors, high HbA1c (HR 1.81 [95% CI 1.28, 2.56]), fructosamine (HR 1.96 [95% CI 1.43-2.69]), glycated albumin (HR 1.81 [95% CI 1.33-2.47]) and fasting glucose (HR 1.81 [95% CI 1.24, 2.66]) were associated with mortality risk. Low HbA1c and fasting glucose were no longer significantly associated with mortality risk. Among participants without diabetes, associations of glycaemic markers with mortality risk were less robust. CONCLUSIONS/INTERPRETATION: Elevated HbA1c, fructosamine, glycated albumin and fasting glucose were associated with risk of mortality in older adults with diabetes. Low HbA1c and fasting glucose may be markers of poor prognosis but are possibly confounded by health status. Our findings support the clinical use of HbA1c in older adults with diabetes. Graphical abstract.

Association Among Glycemic Biomarkers in Korean Adults: Hemoglobin A1c, Fructosamine, and Glycated Albumin.

BACKGROUND: We aimed to investigate the associations between glycemic biomarkers (hemoglobin A1c [HbA1c], fructosamine, and glycated albumin [GA]) in Korean adults. METHODS: We retrospectively reviewed data for HbA1c, fructosamine, and glycated albumin between August 28, 2017, and June 30, 2020, to investigate the association between HbA1c and fructosamine and between HbA1c and GA. RESULTS: Overall, 961 fructosamine and 142 GA tests concurrently measured HbA1c. The equations were HbA1c (%) = 0.0175 x fructosamine (µmol/L) + 1.6255 and HbA1c (%) = 0.2029 x GA + 2.8102, respectively. The absolute difference between estimated and measured HbA1c ranged from -3.4% to 2.1% HbA1c with the fructosamine equation and -3.2% to 2.8% HbA1c with the GA equation. CONCLUSIONS: Fructosamine and GA may be useful adjuncts to HbA1c in Korean patients.

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.