Plasma Fructosamine Research Articles

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.

Fructosamine in llamas (Lama glama) is associated with sex, body condition score, and hematologic and serum parameters.

The objective of this study was to provide orientation values for fructosamine in adult llamas and to characterize relationships with other laboratory and clinical parameters. Data from 22 healthy adult llamas of both sexes. A retrospective study was conducted with the findings of a veterinary herd visit from August 2022. Fructosamine measured from plasma samples was characterized, and its relationships with clinical and laboratory diagnostic data was analyzed using descriptive statistics and correlation analysis. Fructosamine was 311 ± 34 µmol/L (mean ± SD), with a range of 254.8 to 409.2 µmol/L. Males showed significantly higher plasma fructosamine levels than females (P < .05). Plasma fructosamine revealed significant positive correlations with glucose, total protein, and albumin and also with PCV, hemoglobin, calcium, sodium, and selenium. Female llamas revealed further positive correlations with body condition scoring. The results of this study can be used as orientation values for fructosamine in llamas. Fructosamine is used to distinguish acute hyperglycemia caused by stress from chronic hyperglycemia in other species, which might be caused by disorders of the glucose metabolism.

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

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. 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. 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. 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.

Predicting the HbA1c level following glucose-lowering interventions in individuals with HbA1c-defined prediabetes: a post-hoc analysis from the randomized controlled PRE-D trial.

To investigate whether the prediction of post-treatment HbA1c levels can be improved by adding an additional biomarker of the glucose metabolism in addition to baseline HbA1c. We performed an exploratory analysis based on data from 112 individuals with prediabetes (HbA1c 39-47 mmol) and overweight/obesity (BMI ≥ 25 kg/m2), who completed 13 weeks of glucose-lowering interventions (exercise, dapagliflozin, or metformin) or control (habitual living) in the PRE-D trial. Seven prediction models were tested; one basic model with baseline HbA1c as the sole glucometabolic marker and six models each containing one additional glucometabolic biomarker in addition to baseline HbA1c. The additional glucometabolic biomarkers included: 1) plasma fructosamine, 2) fasting plasma glucose, 3) fasting plasma glucose × fasting serum insulin, 4) mean glucose during a 6-day free-living period measured by a continuous glucose monitor 5) mean glucose during an oral glucose tolerance test, and 6) mean plasma glucose × mean serum insulin during the oral glucose tolerance test. The primary outcome was overall goodness of fit (R2) from the internal validation step in bootstrap-based analysis using general linear models. The prediction models explained 46-50% of the variation (R2) in post-treatment HbA1c with standard deviations of the estimates of ~2 mmol/mol. R2 was not statistically significantly different in the models containing an additional glucometabolic biomarker when compared to the basic model. Adding an additional biomarker of the glucose metabolism did not improve the prediction of post-treatment HbA1c in individuals with HbA1c-defined prediabetes.

Metabolic and inflammatory responses reveal different adaptation to the transition period challenges in Holstein, Brown Swiss, and Simmental dairy cows

Twelve Holstein (HOL), 9 Brown Swiss (BRO), and 9 Simmental (SIM) dairy cows raised in the same barn and managed identically were enrolled to characterise the responses to the transition period. From −21 to 28 d from calving (DFC), body condition score (BCS) and milk yield were measured, and blood samples were collected to assess plasma biomarkers of metabolism, minerals, liver function, inflammation, and oxidative status. Compared with SIM, HOL and BRO had higher milk yield during the first week of lactation. HOL had the highest milk yield from the second to the fourth week and the lowest BCS at 28 DFC. SIM had the highest BCS and the highest plasma creatinine and P, reflecting a greater attitude to gain muscle mass. Compared with SIM, BRO and HOL had lower plasma fructosamine, indicating reduced glucose availability driven by lactose synthesis. SIM had the mildest acute phase response at the onset of lactation, as suggested by the lowest ceruloplasmin concentration. HOL had the highest cholesterol and paraoxonase concentrations, and the greatest interleukin-1β production by leukocytes following ex-vivo stimulation, suggesting that they had the quickest resolution of the acute phase response due to the fastest immune cell activation. BRO had the highest concentration of reactive oxygen metabolites, ceruloplasmin, bilirubin, glutamate-oxaloacetate transaminase, γ-glutamyl transferase, and β-hydroxybutyrate, and the lowest concentration of paraoxonase, reflecting the strongest activation of leukocytes and the most severe acute phase response. Together, these results highlight different metabolic and inflammatory conditions around calving in the three explored breeds. HIGHLIGHTS Holstein, Brown Swiss, and Simmental are dairy breeds selected for different purposes. These three breeds have different productivity, and metabolic and inflammatory responses during the transition period. Understanding the differences among breeds might improve their management, nutrition, and productivity in commercial dairy farms.

Nanocurcumin combined with insulin alleviates diabetic kidney disease through P38/P53 signaling axis.

Treatments for diabetic kidney disease (DKD) mainly focus on managing hyperglycemia and hypertension, but emerging evidence suggests that inflammation also plays a role in the pathogenesis of DKD. This 10-week study evaluated the efficacy of daily oral nanoparticulate-curcumin (nCUR) together with long-acting insulin (INS) to treat DKD in a rodent model. Diabetic rats were dosed with unformulated CUR alone, nCUR alone or together with INS, or INS alone. The progression of diabetes was reflected by increases in plasma fructosamine, blood urea nitrogen, creatinine, bilirubin, ALP, and decrease in albumin and globulins. These aberrancies were remedied by nCUR+INS or INS but not by CUR or nCUR. Kidney histopathological results revealed additional abnormalities characteristic of DKD, such as basement membrane thickening, tubular atrophy, and podocyte cytoskeletal impairment. nCUR and nCUR+INS mitigated these lesions, while CUR and INS alone were far less effective, if not ineffective. To elucidate how our treatments modulated inflammatory signaling in the liver and kidney, we identified hyperactivation of P38 (MAPK) and P53 with INS and CUR, whereas nCUR and nCUR+INS deactivated both targets. Similarly, the latter interventions led to significant downregulation of renal NLRP3, IL-1β, NF-ĸB, Casp3, and MAPK8 mRNA, indicating a normalization of inflammasome and apoptotic pathways. Thus, we show therapies that reduce both hyperglycemia and inflammation may offer better management of diabetes and its complications.

Behavioral and Proteomic Studies Reveal Methylglyoxal Activate Pathways Associated with Alzheimer's Disease.

Diabetes is one of the major risk factors for Alzheimer's disease (AD) development. The role of elevated levels of glucose, methylglyoxal (MGO), and advanced glycation end products (AGEs) in the pathogenesis of AD is not well understood. In this pursuit, we studied the role of methylglyoxal in the pathogenesis of AD in rat models. The elevated plus-maze (EPM) behavioral study indicated that MGO induces anxiety. Treatment of telmisartan (RAGE expression inhibitor) and aminoguanidine (MGO quencher) attenuated MGO induced anxiety. Further, hippocampal proteomics demonstrated that MGO treated rats differentially regulate proteins involved in calcium homeostasis, mitochondrial functioning, and apoptosis, which may affect neurotransmission and neuronal plasticity. The hippocampal tau phosphorylation level was increased in MGO treated rats, which was reduced in the presence of aminoguanidine and telmisartan. The plasma fructosamine level was increased upon MGO treatment. Hippocampal histochemistry showed vascular degeneration and neuronal loss upon MGO treatment. This study provides mechanistic insight into the role of MGO in the diabetes-associated development of AD.

Effect of Maternal Dietary Condensed Tannins from Sainfoin (Onobrychis viciifolia) on Gut Health and Antioxidant-Immune Crosstalk in Suckling Lambs

Ewes fed sainfoin (a source of condensed tannins “CT”) may influence the homeostasis of the gastrointestinal tract of suckling lambs. This study investigated the effects of CT from sainfoin in the maternal diet on plasma fructosamine, faecal coccidian excretion, and gene expression of immune and antioxidant markers in jejunum and ileum of suckling lambs. Twelve Rasa Aragonesa lambs with their dams were selected. The maternal diet was based on fresh sainfoin (SAINFOIN, n = 6) and sainfoin + polyethylene-glycol (SAINFOIN + PEG, as a CT-binder, n = 6) plus a daily supplement of 200 g barley in both groups. A lower percentage of lambs that shed more than 10 oocysts/g faeces was observed in SAINFOIN compared to the SAINFOIN + PEG group (p = 0.07). Jejunal gene expression of transforming growth factor-β1, tumour necrosis factor-α, and glutathione peroxidase (GPX) 1 and 4 were lower in the SAINFOIN group (p &lt; 0.05). In contrast, ileal catalase and GPX2 expression were increased in the SAINFOIN group (p &lt; 0.05). Overall, the results suggest that the presence of CT in the dams’ diets has a positive effect on reducing excreted coccidian oocysts and favours antioxidant-immune crosstalk at gut level in suckling lambs.

Correlation between Seminal Fructosamine and Glycosylation Gap and Some Sex Hormones in the Young Infertile Male in Mosul City

Infertility represents a growing health problem in Mosul city and worldwide. Infertility defined as a failure to induce pregnancy after unprotected sexual intercourse for more than 12 months. Infertility in male is a multifactorial complex pathology that leads to different types of problems. This work try to explore the correlation between glycosylation gap and seminal fructosamine and another parameter in the young male patient in Mosul city. The study included 50 subjects with age range 19-29 year with BMI 18-26. The infertility group include 25 patients newly diagnosed with infertility before starting any treatment; have no infection and no structural abnormality. The control group included 25 healthy subjects. HbA1c, fructosamine, Serum and seminal Testosterone, estradiol and Testosterone/ estradiol. Plasma trace element as K, Mg and Zn also measured. There was a significant elevation in the glycosylation profile in the infertile male in compare to control (p&lt;0.05). There was a significant elevation in glycosylation gap in the infertile group (p&lt;0.01). Testosterone and Testosterone/ Estradiol ratio significantly reduced in the infertile group in comparison to control group (p&lt; 0.0004 and 0.0002 respectively). Serum and Seminal plasma Testosterone/ Estradiol ratio showed no significant changes between the two groups (p&gt;0.05). In conclusion, there was a significant positive correlation seminal plasma fructosamine and glycosylation gap in infertile male group.

Diurnal glycemic pattern on inclusion of sucrose in daily meals in type 2 diabetes: Reflection of antecedent glycemic control

Background: Inclusion of sucrose in diabetic diets is not recommended in subjects with diabetes since effects of such diets on glycemic indices are not established. Some studies have documented lapse in metabolic control on consumption of these diets type 2 diabetes. However, most studies examined plasma glucose only for a few hours after ingestion of a single meal containing sucrose after an overnight fast whereas others recommended increasing insulin dose prior to the meal. None of these studies examined influence of inclusion of sucrose in daily meals in subjects with new onset diabetes at diagnosis and again after achieving desirable glycemic control. Objective : Study was conducted to assess glycemic responses to ingestion of all meals containing sucrose constituting 50% of carbohydrate calories. Methods: 12 subjects with new onset type 2 diabetes participated. They were administered the following isocaloric diets for 4 days each prior to and after achieving desirable glycemic control; Diet 1- Diabetic diet recommended by American Diabetes Association (ADA), diet 2- test diet containing sucrose, diet 3- ADA diet. Glycemic control was assessed by diurnal glycemia (average of pre-prandial, postprandial and bedtime blood glucose), fasting plasma glucose, HbA1c and fructosamine on 4th day of each dietary period. Results: All glycemic indices deteriorated after consumption of sucrose containing meals prior to initiation of treatment and remained worsened on return to ingestion of ADA diet. Glycemic responses after all meals improved markedly on achieving desirable glycemic control. Moreover, glycemic indices remained unaltered on consumption of sucrose containing meals after attaining and maintaining desirable glycemic control. Conclusion: Diurnal glycemic responses deteriorate on ingestion of daily meals containing sucrose in subjects with new onset uncontrolled type 2 diabetes. In contrast, diurnal glycemic pattern is unaltered following consumption of daily meals containing sucrose after attaining and maintaining desirable glycemic control.

Prolonged, low-grade inflammation in the first week of lactation: Associations with mineral, protein, and energy balance markers, and milk yield, in a clinically healthy Jersey cow cohort

Our objectives were to perform a proof-of-concept study to assess the association of a prolonged inflammatory state (based on a continually elevated haptoglobin concentration at the end of the first week after parturition) with mineral, protein, and energy balance markers in the first 2 wk after parturition, and milk production in the first 60 d of lactation in clinically healthy cows. We conducted a cohort study in 1 herd in west Texas that was milking Jersey and Jersey-Holstein crosses. Only multiparous Jersey cows were eligible for enrollment. Cows were classified as having or not having elevated haptoglobin concentrations based on plasma concentrations evaluated on d 4 and 7 postpartum. We used median concentrations of haptoglobin in the reference population (i.e., before the exclusion of cows diagnosed with clinical diseases) as the limits for categorizing cows into 2 groups: cows with plasma haptoglobin concentrations greater than the median values on both d 4 (0.49 g/L) and 7 (0.35 g/L) had continually elevated haptoglobin (with eHp); and cows with plasma haptoglobin concentrations lower than or equal to the median values of the reference population on d 4 or 7 did not have continually elevated haptoglobin (without eHp). Next, cows with clinical diseases in the first 2 wk of the postpartum period were excluded, so that 233 cows remained for the final analyses. Evaluated outcomes were average daily milk production across the first 60 d of lactation, plasma Ca, Mg, and glucose concentrations on d 1, 2, 3, 4, 5, 7, 10, and 14 postpartum, and β-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), fructosamine, albumin, urea, and creatinine concentrations on d 3, 5, 7, 10, and 14 postpartum. Rectal temperatures measured on d 4, 7, and 10 postpartum were also analyzed. We performed statistical analyses using linear mixed models while accounting for the repeated effect of sampling time (plasma analytes and rectal temperature models) and weekly milk test (milk production model). Cows with eHp had lower plasma Ca concentrations in the first 2 wk after calving, but no differences in Mg, BHB, NEFA, glucose, or rectal temperatures compared to cows without eHp. Cows with eHp had lower plasma fructosamine, albumin, and urea concentrations in a time-dependent manner. They also had lower milk production (2.3 kg/d less than cows without eHp in the first 60 DIM). Our study demonstrated that 25% of cows without clinical disorders in the first 2 wk after parturition had continually elevated haptoglobin concentrations at d 7 after parturition relative to d 4, suggestive of a prolonged, low-grade systemic inflammatory state. More observational studies are needed to more fully characterize the duration of prolonged postpartum subclinical inflammation in cows without clinical diseases, as well as its long-term effects, and to evaluate the use of other potential markers of systemic inflammation to describe this disorder.

Novel GLP-1 analog supaglutide improves glucose homeostasis in diabetic monkeys.

Glucagon-like peptide 1 (GLP-1) is an insulinotropic hormone and plays an important role in regulating glucose homeostasis. GLP-1 has a short half-life (t1/2 < 2 min) due to degrading enzyme dipeptidyl peptidase-IV and rapid kidney clearance, which limits its clinical application as a therapeutic reagent. We demonstrated recently that supaglutide, a novel GLP-1 mimetic generated by recombinant fusion protein techniques, exerted hypoglycemic and β-cell trophic effects in type 2 diabetes db/db mice. In the present study, we examined supaglutide's therapeutic efficacy and pharmacokinetics in diabetic rhesus monkeys. We found that a single subcutaneous injection of supaglutide of tested doses transiently and significantly reduced blood glucose levels in a dose-dependent fashion in the diabetic monkeys. During a 4-week intervention period, treatment of supaglutide of weekly dosing dose-dependently decreased fasting and random blood glucose levels. This was associated with significantly declined plasma fructosamine levels. The repeated administration of supaglutide remarkably also decreased body weight in a dose-dependent fashion accompanied by decreased food intake. Intravenous glucose tolerance test results showed that supaglutide improved glucose tolerance. The intervention also showed enhanced glucose-stimulated insulin secretion and improved lipid profile in diabetic rhesus monkeys. These results reveal that supaglutide exerts beneficial effects in regulating blood glucose and lipid homeostasis in diabetic rhesus monkeys.

Effects of High and Low Molecular Weight Chitosan on Plasma Cholesterol, Glucose and Adipocytokines in Diabetic Rats Induced by Streptozotocin and Nicotinamide

Chitosan is known for its lipid-lowering effect. To investigate the comparative effects of low (LCS) and high molecular weight chitosan (HCS) on plasma glucose, cholesterol and adipocytokines, male Sprague-Dawley rats were divided into four groups: normal control, diabetic, and diabetic fed the HCS or LCS diet for seven weeks. Diabetes was induced by subcutaneous injection of nicotinamide and streptozotocin. Results showed that diabetic rats fed the HCS diet had reduced liver weight and perirenal adipose weight, compared to those that were fed the control diet. Higher fecal triglyceride and cholesterol excretion and lower hepatic cholesterol and triglyceride contents were found in diabetic rats fed with both chitosan diets. These observations were more significant in the HCS group than in the LCS group. HCS, but not LCS diet, significantly reduced plasma fructosamine, leptin, total cholesterol and lowered the insulin resistance index (homeostasis model assessment; HOMA) in diabetic rats. A lower intestinal dissaccharidase activity including sucrase and lactase was found in diabetic rats fed the HCS dict. Moreover, plasma tumor necrosis factor-alpha and plasminogen activator inhibitor-1 concentrations were significantly reduced by both chitosan supplementations. The results suggested that HCS feeding may reduce insulin resistance by the suppression of lipid accumulation in liver and adipose tissue and amelioration of chronic inflammation in diabetic rats. HCS may improve glucose and lipid metabolism more significantly than LCS in diabetic rats.

Effect of shengmai san on insulin resistance, tumor necrosis factor-alpha and oxidative stress in rats fed on a high-fat diet

Shengmai San (SMS) is a well-known traditional Chinese medicine formula prescribed for patients with coronary heart disease (CHD). Insulin resistance is the most likely explanation for the development and progression of this disease. To investigate the effect of SMS on high-fat diet-induced insulin resistance, inflammatory cytokine production and oxidative stress, male Wistar rats were fed with low-fat control diet, high-fat diet and high-fat diet supplemented with 4% SMS for eight weeks. An oral glucose tolerance test was conducted in the seventh week. Rats fed the SMS diet had significantly lower plasma fructosamine concentration (p < 0.05) and tended to have lower (p < 0.1) AUC values of plasma glucose and insulin concentrations after glucose challenge, compared to those fed the high-fat diet. Moreover, SMS reduced TNF-α and lipid peroxidation levels in the liver and heart. However, SMS had no effect on fasting plasma concentrations of glucose, insulin, triglyceride, non-esterified fatty acids, total cholesterol, HDL-cholesterol and insulin resistance index (homeostasis model assessment; HOMA) in rats. Our results show that SMS may have little or no significant effect on reducing insulin resistance, but display anti-oxidative and anti-inflammatory properties.

Abstract C077: The association between diabetes, plasma fructosamine, and risk of mortality after invasive breast cancer among Hispanic and non-Hispanic white women

Abstract Background: Epidemiologic studies primarily conducted in non-Hispanic white (NHW) women have found that elevated insulin levels, hyperinsulinemia, and chronic hyperglycemia (measured by hemoglobin A1c) are associated with poor prognosis in women diagnosed with breast cancer (BC). Only one study to date has included US Hispanic women, in whom diabetes is highly prevalent. Objective: We examined the associations between plasma fructosamine, a biomarker of hyperglycemia and glycemic control, self-reported diabetes, and risk of BC-specific and all-cause mortality among Hispanic and NHW women diagnosed with BC (stages I-IIIa) from the New Mexico Health, Eating, Activity, and Lifestyle (HEAL) Study. Methods: A total of 399 BC survivors (96 Hispanic, 303 NHW) contributed baseline data and plasma samples. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazards regression models. Models were adjusted for age at diagnosis, ethnicity, body size, education, BC stage and treatment. Results: After a median follow-up time of 13 years from baseline interview to death, a total of 134 deaths occurred, of which 56 deaths were attributed to BC. Approximately 38% of women with diabetes had clinically high fructosamine (&amp;gt; 285 μmol/L). While more Hispanic women had diabetes (11.5%) compared to NHW women (7.6%), significant differences by ethnicity for fructosamine levels were not observed (Hispanic mean= 236 μmol/L; NWH mean=238 μmol/L). Hispanics, however, had larger body size measures at baseline interview compared to NHW survivors. Diabetes was associated with increased BC mortality (HR, 2.89; 95% CI 1.27-6.60) and all-cause mortality (HR, 2.10; 95% CI 1.24-3.55). As a continuous measure, fructosamine was positively associated with BC-specific mortality (p=0.01) and with all-cause mortality, independent of diabetes history (p=0.001). Associations were strongest among women with clinically high fructosamine levels (BC: HR, 4.25; 95% CI 1.67-10.80; all-cause: HR, 2.32; 95% CI 1.30-4.14) compared to women with normal levels (≤285 μmol/L). Significant statistical interactions for associations by ethnicity were not observed. Conclusions: Our findings suggest that diabetes and fructosamine are significantly associated with increased risk of BC-specific and all-cause mortality among Hispanic and NHW women with invasive BC, even &amp;gt;10 years post diagnosis. Interventions to reduce BC mortality among ethnically diverse BC survivors should also consider methods to improve glycemic control among women with diabetes. Citation Format: Avonne E. Connor, Kala Visvanathan, Stephanie D. Boone, Kathy B. Baumgartner, Richard N. Baumgartner. The association between diabetes, plasma fructosamine, and risk of mortality after invasive breast cancer among Hispanic and non-Hispanic white women [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C077.

1786-P: The New Insulin Sensitizer MSDC-0602K Synergizes with the GLP-1 Receptor Agonist Liraglutide

First generation insulin sensitizers improve both hyperglycemia and hyperinsulinemia and can preserve beta cell mass and function. GLP-1 receptor agonists work by augmenting glucose-stimulated insulin secretion. Our objective was to assess potential additive effects of the new insulin sensitizer, MSDC-0602K (0602K) when combined with a GLP-1 receptor agonist in db/db mice. Mice were gavaged daily with 30 mg/kg 0602K or vehicle, injected subcutaneously every other day with 200 μg/kg Liraglutide (Lira) or vehicle, or received both drugs. Lira reduced glycemia and plasma fructosamine levels, while 0602K or 0602K+Lira normalized glycemia and fructosamine to lean db/+ mouse levels. Both drugs alone improved glucose tolerance compared to vehicle db/db, while the combination of 0602K+Lira further improved glucose tolerance even compared to lean db/+ mice. Vehicle treated db/db mice displayed elevated insulin and C-peptide levels, which were both reduced by 0602K treatment. C-peptide levels were lowered to a greater degree than insulin, indicating that 0602K treatment exerted a major effect on insulin secretion. In contrast, Lira increased the insulin and C-peptide levels in db/db mice, while the combination of 0602K+Lira displayed reduced levels of insulin and C-peptide similar to 0602K-alone treatment. Pancreas immunohistochemistry of vehicle treated db/db mice showed little islet insulin content, but islet insulin was significantly increased by 0602K or 0602K+Lira treatment. Isolated islets from lean, naïve mice showed no defect in glucose-stimulated insulin secretion with 0602K treatment, suggesting that the lowered insulinemia in vivo is due to corrected insulin resistance rather than direct inhibition of insulin secretion. In conclusion, the new insulin sensitizer MSDC-0602K improves insulinemia and helps to restore islet insulin content when used alone or in combination with Liraglutide. Glucose tolerance displayed additive effects with combined 0602K+Lira treatment. Disclosure K.D. Pyles: None. D. Kamm: None. J.R. Colca: Stock/Shareholder; Self; Cirius Therapeutics, Metabolic Solutions Development Company. K.S. McCommis: None. Funding National Institutes of Health (R01HL136658)

Effect of Alpha Lipoic Acid on Apoptotic Mechanisms and Oxidative Stress in Pancreatic Cells of High Fat Diet Induced Type II Diabetes Mellitus in Rats

AbstractBackground: Type 2 Diabetes Mellitus (T2DM) is a worldwide health problem with significant morbidity and mortality. b-cell failure is a main contributor to the develop-ment of T2DM. Oxidative stress and enhanced apoptosis play a critical role in pathogenesis of b-cell failure. Recently, Alpha Lipoic Acid (ALA), a universal antioxidant, has been shown to exert anti-apoptotic actions.Aim of Study: The present study was aimed to evaluate the possible ameliorative effect of ALA against pancreatic tissue oxidative stress and apoptotic mechanisms in a rat model of High Fat Diet (HFD)-induced T2DM.Material and Methods: Eighty albino rats were included, 20 rats received a standard diet and served as normal control group (Group I) and 60 rats were fed a homemade HFD for 6 months for induction of T2DM, only diabetics (40 rats) were included and divided into 2 groups; 20 continued to receive HFD for further 21 days, served as diabetic untreated group (Group II); 20 received ALA (50mg/kg i.p) for 21 days and served as ALA-treated group (Group III). Thioredoxin Interacting Protein (TXNIP) and cyclic Adenosine Monophos-phate (cAMP) were immunoassayed in addition to determina-tion of levels of plasma fructosamine, fasting blood glucose (FBG) and pancreatic tissue Malondialdehyde (MDA) along with pancreatic catalase and Superoxide Dismutase (SOD) activities.Results: ALA treatment showed significant improvement in fructosamine and FBG levels, decreased MDA level and increased catalase and SOD activities, in addition to increased cAMP level and decreased TXNIP level.Conclusion: We concluded that ALA has the ability to interfere with b-cell dysfunction associated with HFD-induced T2DM possibly by improving redox status, rescuing cAMP signaling and decreasing the level of TXNIP.

Green Tea Ameliorates Hyperglycemia by Promoting the Translocation of Glucose Transporter 4 in the Skeletal Muscle of Diabetic Rodents.

It is known that green tea helps prevent obesity and diabetes mellitus. In this study, we aimed to determine whether green tea ameliorates hyperglycemia and the mechanism involved in diabetic rodents. Green tea consumption reduced blood glucose and ameliorated glucose intolerance, which was assessed using an oral glucose tolerance test in both streptozotocin-induced type 1 diabetic rats and type 2 diabetic KK-Ay mice. Green tea also reduced the plasma fructosamine and glycated hemoglobin concentrations in both models. Furthermore, it increased glucose uptake into the skeletal muscle of both model animals, which was accompanied by greater translocation of glucose transporter 4 (GLUT4). Moreover, epigallocatechin gallate (EGCG), the principal catechin in green tea, also ameliorated glucose intolerance in high-fat diet-induced obese and diabetic mice. These results suggest that green tea can ameliorate hyperglycemia in diabetic rodents by stimulating GLUT4-mediated glucose uptake in skeletal muscle, and that EGCG is one of the effective compounds that mediate this effect.

Mid-Pregnancy Fructosamine Measurement-Predictive Value for Gestational Diabetes and Association with Postpartum Glycemic Indices.

Screening for gestational diabetes mellitus (GDM) during pregnancy is cumbersome. Measurement of plasma fructosamine may help simplify the first step of detecting GDM. We aimed to assess the predictive value of mid-pregnancy fructosamine for GDM, and its association with postpartum glycemic indices. Among 1488 women from Project Viva (mean ± SD: 32.1 ± 5.0 years old; pre-pregnancy body mass index 24.7 ± 5.3 kg/m2), we measured second trimester fructosamine and assessed gestational glucose tolerance with a 50 g glucose challenge test (GCT) followed, if abnormal, by a 100 g oral glucose tolerance test (OGTT). Approximately 3 years postpartum (median 3.2 years; SD 0.4 years), we measured maternal glycated hemoglobin (n = 450) and estimated insulin resistance (HOMA-IR; n = 132) from fasting blood samples. Higher glucose levels 1 h post 50 g GCT were associated with higher fructosamine levels (Pearson’s r = 0.06; p = 0.02). However, fructosamine ≥222 µmol/L (median) had a sensitivity of 54.8% and specificity of 48.6% to detect GDM (area under the receiver operating characteristic curve = 0.52); other fructosamine thresholds did not show better predictive characteristics. Fructosamine was also weakly associated with 3-year postpartum glycated hemoglobin (per 1 SD increment: adjusted β = 0.03 95% CI [0.00, 0.05] %) and HOMA-IR (per 1 SD increment: adjusted % difference 15.7, 95% CI [3.7, 29.0] %). Second trimester fructosamine is a poor predictor of gestational glucose tolerance and postpartum glycemic indices.

Abstracts from the NIH Office of Research on Women's Health 2018 Annual BIRCWH Meeting – Building Interdisciplinary Research Careers in Women's Health November 28, 2018

Abstracts from the NIH Office of Research on Women's Health 2018 Annual BIRCWH Meeting – Building Interdisciplinary Research Careers in Women's Health November 28, 2018