Fructosamine Levels Research Articles

1446-P: A1C and Glycated Albumin Combined Improves Detection of Abnormal Glucose Tolerance in Africans

In nonwhite populations the prevalence of abnormal glucose tolerance (Abnl-GT) is increasing in the nonobese. However, the prevalence of Abnl-GT in African-born blacks is unknown. As BMI correlates positively with A1C and negatively with glycated albumin (GA) and fructosamine (FA), BMI may influence the diagnostic sensitivity of nonfasting markers of glycemia. Working with Africans, our goals were to determine: a) by BMI category the prevalence of Abnl-GT; and b) the diagnostic value of nonfasting markers of glycemia, individually and combined. In 416 African-born blacks living in America (male: 66%; age: 39±10 (mean±SD), range 20 to 65y, BMI: 27.7±4.5, range 18.2-42.4 kg/m2) OGTT were performed. A1C, GA and FA levels were measured. A1C, GA and FA levels were repeated 11±7 days later in 136 participants. Abnl-GT was defined by glucose: 0h ≥100 and/or 2h ≥140 mg/dL. Thresholds for A1C, GA and FA were defined by the cut-off at the upper quartile for the population (5.7%, 14.2%, 234 µM/L, resp). Analytic tools were κ-statistic, Spearman correlations and the McNemar test. In short, Abnl-GT occurred in 36% (152/416). Of the individuals with Abnl-GT, 68% (104/152) were nonobese. Reproducibility of A1C and GA were excellent (both κ≥0.8) but only moderate for FA (κ=0.6). For this reason, results focus on A1C and GA. BMI positively correlated with A1C (r= 0.18) and negatively with GA (r=-0.18) (both P<0.01). The diagnostic sensitivities of A1C, GA and the combined tests were: 43%, 34% and 61%, resp (P<0.01 compared to A1C alone). By test, 66 people with Abnl-GT were detected by A1C or A1C and GA; whereas 25 people were detected by GA alone. People with Abnl-GT detected by GA only had lower BMI than those detected by A1C (26.8±2.4 vs. 30.4±4, P<0.01). Overall, two-thirds of African-born blacks with Abnl-GT are nonobese. As GA detects Abnl-GT in nonobese individuals not detected by A1C, using both tests could improve screening and lead to earlier intervention. Disclosure A.E. Sumner: None. A.F. Hobabagabo: None. E.M. Shoup: None. T. Hormenu: None. N.H. Osei-Tutu: None. C. DuBose: None. L. Mabundo: None. S.T. Chung: None. D.B. Sacks: Other Relationship; Self; Sebia, Trinity Biotech plc.

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 (> 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 >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)

Free Fructose Intake Decreases Soluble RAGE Receptor (sRAGE) and Glyoxal and Methylglyoxal Urinary Excretion on Healthy Volunteers

Abstract Objectives Free fructose but not total fructose intake could contribute to the formation of advanced glycation end products (AGEs) and Maillard reaction products in the intestinal lumen. Therefore, the aim of this study was to compare serum levels of fructosamine, soluble receptor for AGEs (sRAGE), and urinary levels of glyoxal and methylglyoxal after free fructose and total fructose intake. Methods This is a randomized crossover study, approved by the Institutional Committee of Bioethics in Research of the University of Guanajuato (CIBIUG). Twelve clinically healthy subjects, 20–30 years old, were recruited. During the first visit, participants were randomly assigned to one of two treatments, an oral load of fructose (40 g) or total fructose (40 g fructose and 40 g glucose), in addition to their assigned treatment subjects received 25 g of hydrolyzed protein (Nature Best Isopure®) After a washing period (one week), participants were crossed over to receive the other treatment. Blood and urine samples were collected at baseline and after three hours of the oral load of each treatment. Glucose, creatinine, and lipids serum levels were measured with commercial kits. Insulin, fructosamine, and sRAGE serum levels were determined with ELISA commercial kits. Glyoxal and methylglyoxal urine levels were quantified by HPLC. Data analysis was completed using STATISTICA 10 and IBM SPSS Statistics 24.0 software. The results were considered significant with a value of P < 0.05. Results After free Fructose intake, participants had a significant decrease in sRAGE (1327 pg/L vs 1282 pg/L, P = 0.028), and in urine levels of glyoxal (0.63 ng/mg vs 0.24 ng/mg P = 0.028) and methylglyoxal (0.42 ng/mg vs 0.13 ng/mg P = 0.002). After Fructose and glucose intake, participants only had a significant decreased in serum sRAGE (1256 pg/L vs 1199 pg/L, P = 0.015). Fructosamine did not showed a difference after either intervention. Conclusions The consumption of free fructose decreased serum sRAGE levels, as well as urinary excretion of glyoxal and methylglyoxal. These results may suggest a possible in vivo formation of AGEs by consuming free fructose. Nevertheless, more studies are necessary to assess the formation of methylglyoxal derived AGEs. Funding Sources This project was supported by the University of Guanajuato through the Research and Postgraduate Support Department (DAIP).

Longterm Neuroendocrine and Metabolic Effects of Physical Training in Intermittent Claudication

Twenty-five elderly patients with peripheral vascular disease and intermittent claudication were prospectively followed during a six-month session of physical training. Neuroendocrine and metabolic patterns as well as effects on walking performance were assessed during the training period. At the initial evaluation there was an inverse association between walking distance and serum cortisol and blood glucose levels. The walking distance increased during the training period. A positive effect on glucose homeostatis was seen with decreased basal fructosamine levels after training. During physical exercise a decrease in insulin and an increase in growth hormone was seen. Changes in growth hormone were, in contrast to insulin, more related to the pain level perceived than to the work load imposed. Apart from the marked effects on physical performance the results of the study suggest an improvement of hormonal and metabolic balance after physical training. This regularly applied exercise program improved the health status of rather old people.

SAT-664 Fluctuating Blood Glucose in an Infant with Newly Diagnosed IPEX Syndrome

Background: In the IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome, Type 1 diabetes mellitus is the most common endocrine complication and usually occurs with a variable presentation from immediately at birth to within the first few months of life.Clinical case: A four-month-old male presented for evaluation of failure to thrive, eczema, and diarrhea. In the ED, his glucose value was 246 mg/dL with beta-hydroxybutyrate of 0.29 mmol/L (0.00-0.30). Within eight hours and without insulin, he became hypoglycemic and required dextrose-containing fluids to maintain euglycemia; he was quickly made NPO and started on TPN due to excessive stool output. For nearly two weeks he required no insulin while receiving 84g of dextrose per day (21 g/kg/day) in TPN. He developed bloody stools on the day that he started receiving Tacrolimus and IVIG and required transfer to the ICU, and an insulin need of 1 unit/kg/day developed with this worsening of his systemic illness. After the bloody stools resolved, immunosuppression with Rituximab was initiated. Once bowel function improved, Pedialyte and formula were slowly reintroduced and for three weeks his insulin requirement varied from 0.2-0.4 units/kg/day. In his seventh week of hospitalization his insulin was discontinued due to hypoglycemia, and at the time of discharge he had been without insulin for ten days on ad lib formula feeding.Hemoglobin A1c on admission was 10.2%, and repeat was 10.3%. A fructosamine level was obtained to evaluate the discrepancy between the initial HgbA1c and being euglycemic. It was 269 umol/L (190-270), equivalent to an approximate HgbA1c of 6.5%, suggesting that hyperglycemia resulting in an elevated HgbA1c occurred early in his life and had improved in the days to weeks prior to admission. Further testing revealed an elevated GAD-65 antibody of >250 IU/mL (<5) but normal ICA 512 and insulin autoantibody.His clinical picture was consistent with IPEX syndrome, confirmed with rapid whole genome sequencing showed a pathogenic hemizygous c.1010G>A p.Arg337Gln variant in the FOXP3 gene.A HgbA1c performed prior to discharge, eight weeks after the initial, was 6.6%. This spontaneous resolution of hyperglycemia in IPEX, with insulin needs developing only when he had worsening systemic illness as demonstrated by bloody stools, has yet to be described.Conclusion: Hyperglycemia fluctuated in the first few months of life in a patient with IPEX syndrome, likely related to severity of systemic illness and control of enteropathy.

A randomized trial on the effect of oral combined estradiol and drospirenone on glucose and insulin metabolism in healthy menopausal women with a normal oral glucose tolerance test

BackgroundMenopause is often associated with a central accumulation of body fat. This provokes insulin resistance. The resulting hyperinsulinemia may increase the risk of diabetes, cardiovascular disease and breast cancer. Long-term studies indicate that menopausal hormone therapy (MHT) reduces insulin resistance. To broaden knowledge of the mechanisms behind the influence of MHT on glucose homeostasis we focused on the direct short-term effects of MHT with oral combined estradiol and drospirenone on glucose and insulin metabolism in healthy postmenopausal women. MethodsThis randomized, placebo-controlled study recruited 80 healthy postmenopausal women. Women were randomized to treatment with estradiol 1 mg continuously combined with drospirenone 2 mg or placebo for 6–8 weeks. All participants underwent an oral glucose tolerance test (OGTT) before and after the treatment period. Glucose, insulin, fructosamine and C-peptide levels were measured in serum before and 30, 60, 90, 120 and 150 min after a 75-gram oral glucose challenge. ResultsAfter intervention, significantly higher glucose levels at 120 min (p < 0.024) and 150 min (p < 0.030) were observed in the MHT group compared with the placebo group. These glucose levels remained within the normal range.A significantly lower insulin peak serum level (p < 0.040) and a non-significantly smaller area under the curve (AUC) for insulin levels (p = 0.192) was observed in the MHT group at the end of the study period relative to baseline. No significant change in the insulin AUC in the placebo group was observed. There were no significant differences in fructosamine, HOMA-IR and C-peptide levels between the MHT group and the placebo group. ConclusionThis double-blind randomized study (EC/2008/694) indicates that treating healthy, postmenopausal women with 1 mg estradiol continuously combined with 2 mg drospirenone significantly decreases peak insulin levels and increases peak glucose levels during an OGTT compared to placebo. These glucose levels remained within the normal range.

Glycemic effect of post-meal walking compared to one prandial insulin injection in type 2 diabetic patients treated with basal insulin: A randomized controlled cross-over study.

Studies demonstrate that post-meal walking decreases postprandial hyperglycemia in type 2 diabetic patients but it has never been tested with the active treatment comparator. The objective of this study was to determine the effect of post-meal walking on glycemic control compared with one prandial insulin in type 2 diabetic patients who failed basal insulin. A randomized controlled cross-over study of post-meal walking or one prandial insulin was done in type 2 diabetic patients who were being treated with basal insulin between May 2017 and March 2018. In post-meal walking group, patients walked after meal for 15-20 minutes one meal a day every day for 6 weeks. In prandial insulin (basal plus) group, one prandial insulin was injected before breakfast or main meal with rapid-acting insulin. The primary outcome was a difference in HbA1c reduction in post-meal walking compared with basal plus groups. Fourteen patients completed the study. By intention-to-treat analysis, HbA1c was reduced by -0.05(range:-1.08 to 0.74) and -0.19(range:-0.8 to 0.56) % in post-meal walking and basal plus groups respectively. By per-protocol analysis, post-meal walking and basal plus groups decreased HbA1c by 0.13(range:-0.74 to 1.08) and 0.2(range:-0.56 to 0.8) %, respectively. There was were no significant differences in HbA1c reduction from baseline in each group and between groups in both intention-to-treat and per-protocol analysis. Fructosamine levels were decreased by 17.5(-59 to 43) and 10(-15 to 40) μmol/L, respectively at 3 and 6 weeks in post-meal walking group whereas the respective changes in basal plus group were 12.5(-17 to 64) and 17.5(-28 to 38) μmol/L and there were no significant differences in fructosamine reduction from baseline in each group and between groups. In conclusion, although post-meal walking might be as effective as one prandial insulin to improve glycemic control in type 2 diabetic patients who failed basal insulin but the magnitude of reduction was small. A longer-term study with a larger sample size or with a different walking protocol is required.

Patterns of Glucose Fluctuation are Challenging in Patients Treated for Non-Hodgkin's Lymphoma.

PurposeThis cohort study aimed to determine patterns of glycemic fluctuation and changes in metabolic parameters during and after corticosteroid administration in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP chemotherapy.Patients and MethodsThe study was performed in 20 patients of whom 11 had diabetes and 9 were nondiabetics. Anthropometric parameters were collected, and blood samples were taken four times during the study to analyze metabolic parameters. Capillary glucose was measured seven times a day (fasting, before mean meals, postprandial, and before bedtime) to evaluate the glycemic profile.ResultsIn all 20 patients, acute glucocorticoid administration resulted in the elevation of average glucose levels, dominantly postprandial in the afternoon which correlates with corticosteroid peak action. In 7 out of 11 diabetics, prandial insulin was started during corticosteroid administration and discontinued afterward. Although none of our nondiabetic patients met diabetes criteria, evident is the elevation in average glycemia levels six weeks after corticosteroid administration. Potentially, even transient corticosteroid administration reduces insulin sensitivity and contributes to later glycemic disturbances. HbA1c levels were higher at the end of the study while fructosamine levels were higher during the study.ConclusionPatients and health-care professionals need to be aware of corticosteroid-induced hyperglycemia. We recommend identifying risk factors, measuring glycemia before, during, and after corticosteroid administration, and starting the adequate therapy as soon as possible.

Abstract P129: Biomarkers of Hyperglycemia With All-cause Mortality in Older Adults With and Without Diagnosed Diabetes

Introduction: HbA1c is central to diagnosis and management of diabetes. However, our understanding of the associations of HbA1c with clinical outcomes is based primarily on studies of middle-aged adults. Objective: To characterize the associations between HbA1c and mortality among older adults with and without diabetes. We compared the HbA1c-mortality associations with those for alternative glycemic markers (fructosamine and glycated albumin). Methods: We conducted a prospective cohort analysis of 6370 participants (32% with diagnosed diabetes, mean age 76, 59% female, 23% black) in the Atherosclerosis Risk in Communities (ARIC) Study, baseline visit 5 (2011-13). We used Cox regression models to examine the association of each glycemic biomarker (modeled as a linear spline) with all-cause mortality through 2017, stratified by diagnosed diabetes. Model discrimination was tested using c-statistics. Results: There were 1022 deaths over 6 years of follow-up. In persons with diabetes, there was a J-shaped association between HbA1c and mortality ( Figure ). Associations were largely similar for fructosamine and glycated albumin. Among persons without diabetes, HbA1c was not strongly associated with mortality, but confidence intervals were wide for HbA1c &lt;5.0% and ≥6.5% (undiagnosed diabetes); whereas, higher levels of fructosamine and glycated albumin were associated with an elevated mortality risk. Associations were similar before and after adjustment for cardiovascular risk factors. The addition of individual glycemic markers to the models modestly improved discrimination in both persons with and without diabetes. C-statistics were similar when the glycemic markers were added individually to the diabetes-stratified models (Figure). Conclusions: Among older adults, HbA1c and other glycemic markers tend to have similar associations with mortality. HbA1c, fructosamine, and glycated albumin, including low levels, may reflect common markers of risk in older adults, particularly in those with diabetes.

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

BackgroundTo 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.MethodsCKD 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.ResultsOf 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).ConclusionOur 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.

Inhibition of pyruvate dehydrogenase complex activity by 3-bromopyruvate affects blood platelets responses in type 2 diabetes.

Hyperactivation of blood platelets is an essential factor in the pathomechanism of diabetes-evoked angiopathies. The aim of this work was to investigate whether blood platelets hyperactivation resulting from type 2 diabetic hyperglycaemia-increased pyruvate dehydrogenase complex activity and excessive acetyl-CoA accumulation may be brought to the normal range by the enzyme inhibitors. Platelets were isolated from the blood of 9 type 2 diabetic patients and 10 healthy donors. Effects of 3-bromopyruvate and 3-nitropropionate on pyruvate dehydrogenase complex (PDHC) and succinate dehydrogenase activities, as well as levels of acetyl-CoA, ATP, thiobarbituric acid reactive species and aggregation were assessed in non-activated and thrombin-activated platelets. In type 2 diabetic patients fasting plasma glucose and fructosamine levels were 61 and 64% higher, respectively, than in the healthy group (p < 0.001). In non-activated diabetic platelets PDHC activity, PDHC-E2, acetyl-CoA and ATP levels were 66, 70, 68 and 60%, higher, respectively, than in platelets from healthy controls (p < 0.01). 3-bromopyruvate (0.1mM) decreased pyruvate dehydrogenase activity in healthy and diabetic platelets by 42% and 59%, respectively. Similar inhibitory effects were observed for acetyl-CoA and ATP levels, aggregation and TBARS accumulation rates. Succinate dehydrogenase activity was inhibited by 3-nitropropionate (10mM) to 38 and 41% of control values in healthy and diabetic platelets, respectively, but affected neither function nor acetyl-CoA metabolism in platelets of both groups. These data indicate that inhibition of pyruvate dehydrogenase excessive activity in diabetic platelets by 3-bromopyruvate may normalise their functional parameters through adjustment of acetyl-CoA/ATP levels to control values. Platelets from blood of diabetic patients display higher activities of pyruvate dehydrogenase complex (PDHC), higher levels of dihydrolipoate transacetylase (DLAT, E2 subunit of PDHC) as well as higher levels of acetyl-CoA yielding greater ATP/ADP accumulation than in platelets of normoglycemic subjects. Therefore, in diabetic platelets, thrombin caused higher release of ATP/ADP triggering excessive production of reactive oxygen species (ROS) and stronger aggregation compared to control platelets. In diabetic platelets, relative excess of DLAT in PDHC made them highly susceptible to 3-bromopyruvate (3BrP) inhibition. Resulting limitation of acetyl-CoA provision by 3-BrP normalised activity of diabetic platelets.

Association of Glycated Proteins with Inflammatory Proteins and Periodontal Disease Parameters.

Periodontitis is a chronic inflammatory condition that may contribute to diabetogenesis. The aim was to investigate the levels of glycated proteins and their correlation with periodontal and systemic inflammation. Fifty-one patients with periodontitis and 20 healthy subjects underwent probing pocket depth (PPD) measurements. PPD total and PPD disease with and without tooth adjustment were used as continuous indices. Marginal bone loss (MBL) for mandibular premolars and molars was measured digitally. Body mass index (BMI) and waist circumference (WC) were also analyzed. Glycated hemoglobin (HbA1c) and fructosamine (FrAm) levels were measured in all subjects. A multiplex proximity extension assay (PEA) was used to analyze the serum samples for simultaneous measurement of 92 proteins. Both HbA1c and FrAm inversely correlated with IL-10, FGF-21, MCP-1, and TNF beta amongst 16 proteins. HbA1c correlated directly with OPG. Parameters of disease severity were consistently significant for HbA1c. Adjusted PPD total and number of missing teeth were increased in diabetes whereas levels of RANKL and RANKL to OPG ratio were the highest in nondiabetic periodontitis patients. Hyperglycemic conditions in periodontitis patients are associated with reduced levels of anti-inflammatory proteins as well as dysregulated bone resorption.

Orally deliverable nanoformulation of liraglutide against type 2 diabetic rat model

The present study was designed to evaluate the hypoglycemic effect of nanoparticle based drug delivery system of liraglutide loaded in Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) upon oral delivery in experimentally induced type 2 diabetes mellitus in Wistar rats. NPs were synthesized using double emulsion solvent evaporation method. Physiochemical characterization of NPs revealed small particle size of 159.25 ± 24.46 nm with 75 ± 7.8% liraglutide encapsulation efficiency and 7 ± 1% as liraglutide loading efficiency. The NPs were also studied for in vitro release study and stability studies in various gastrointestinal fluid pH conditions which demonstrated the stability of NPs under these conditions. In-vivo model in wistar rats induced by high fat diet (HFD) along with Streptozotocin (STZ) were treated with liraglutide NPs for 8 weeks at two doses (75 and 150 μg/kg, orally). The rats were monitored for various biochemical and physiological parameters at regular intervals i.e. baseline before initiation of the experiment, at the 1st, 5th, and 9th week of STZ administration. Further in vivo study showed alleviation of HFD-STZ induced diabetes mellitus as evident from the reduction in biochemical parameters like blood glucose (both fasting and post prandial blood glucose), HbA1c, fructosamine levels, serum triglycerides, serum total cholesterol. Physiological parameters such as body weight and food intake were also in support of the data. Moreover, liraglutide NPs demonstrated hypoglycemic activity by significantly increasing the insulin secretion in diabetic rats. To the best of our knowledge, we for the first time proposing the orally deliverable NPs of liraglutide that ameliorates HFD-STZ induced diabetes mellitus effectively as compared to conventional liraglutide.

Non-nutritive sweeteners are in concomitant with the formation of endogenous and exogenous advanced glycation end-products

This study investigated the role of non-nutritive sweeteners in the formation of advanced glycation end-products (AGEs) and their reactive intermediates using endogenous and exogenous models. In the endogenous model, xylitol and sorbitol formed similar levels of reactive intermediates compared to sucralose. Protein-bound fluorescent AGEs, Nε-carboxymethyllysine (CML), and Nε-carboxyethyllysine (CEL) levels in the xylitol and sorbitol treatment were significantly higher compared to the sucralose treatment. In the exogenous model, sucralose treatment showed significantly higher glyoxal and fructosamine levels compared to xylitol and sorbitol, respectively. However, protein-bound fluorescent AGEs, CML, and CEL were lower in the sucralose treatment compared to other sugar treatments. The data suggest that the structure of sugar alcohols which are similar to reducing sugars may contribute to the formation of AGEs and their reactive intermediates in the endogenous model. The long-term effects of non-nutritive sweeteners consumption on AGEs formation and health implications should be verified with population studies.

Diagnostic orientation values for ACTH and other parameters for clinically healthy donkeys and mules (insulin, triglycerides, glucose, fructosamines, and ɣ-GT).

Pituitary pars intermedia dysfunction is the most prevalent endocrine disease in horses. Although donkeys and mules may also be affected, only a few data have been published. Reference values for diagnostic parameters, such as adrenocorticotropic hormone (ACTH), are especially scarce or even lacking. Therefore, in the present study, available data from the literature have been verified and completed to facilitate a reliable diagnosis. Clinical inspections and haematological and biochemical examinations were carried out four times in a three-month interval (February to November) in 44 donkeys and 31 mules. Data from clinically healthy animals were used as an orientation. Plasma ACTH concentrations showed seasonal changes in both animal groups. However, it was generally higher in donkeys than mules. Although blood glucose (EDTA plasma) showed no difference between groups, serum insulin concentrations were consistently higher in donkeys. Serum fructosamine levels were slightly higher in mules, whereas, in some cases, serum triglyceride levels were considerably higher in donkeys. Serum gamma-glutamyltransferase showed a striking peak in mules in August, whereas the remaining gamma-glutamyltransferase values were lower compared to donkeys. By comparing donkeys and mules, the present work reveals differences in various blood parameters which should be considered for diagnoses and future studies.

Favorable outcome of pheochromocytoma in a dog with atypical Cushing\u2019s syndrome and diabetes mellitus following medical treatment: a case report

BackgroundPheochromocytoma (PCC) has poor prognosis and adrenalectomy is hard to be performed, in case of caudal vena cava invasion. The long-term administration of phenoxybenzamine in PCC has not been reported in dogs.Case presentationA 14-year-old castrated male Poodle dog presented with an abdominal mass. On physical examination, hypertension, increased lens opacity, calcinosis cutis, generalized alopecia, and systolic murmur were observed. Serum chemistry and urinalysis profiles revealed hyperglycemia, hypercholesterolemia, elevated liver enzymes, and glucosuria. Abdominal ultrasonography showed a right adrenal mass with invasion of the caudal vena cava, which was cytologically diagnosed as suspected PCC. An adrenal mass (width × height × length, 28 × 26 × 48 mm3) was found on computed tomography and diagnosed as PCC with increased plasma metanephrines and normetanephrines. An adrenocorticotropin hormone stimulation test showed elevated adrenal hormones (androstenedione, estradiol, progesterone, and 17-OH progesterone) with normal cortisol, compatible with atypical Cushing’s syndrome. The dog was managed with trilostane, phenoxybenzamine, and insulin therapy. Glycosylated hemoglobin and fructosamine levels gradually decreased, and hypertension resolved. In the 10-month follow-up period, the liver enzymes levels gradually decreased, and the clinical signs of the dog were well-controlled without deterioration.ConclusionsThis case report describes long-term medical management without adrenalectomy of PCC complicated with atypical Cushing’s syndrome and DM.

Antiglycation and Antioxidant Properties of Ficus deltoidea Varieties.

The present study aimed to evaluate the potential of standardized methanolic extracts from seven Ficus deltoidea varieties in inhibiting the formation of AGEs, protein oxidation, and their antioxidant effects. The antiglycation activity was analyzed based on the inhibition of AGEs, fructosamine, and thiol groups level followed by the inhibition of protein carbonyl formation. The antioxidant activity (DPPH radical scavenging activity and reducing power assay) and total phenolic contents were evaluated. After 28 days of induction, all varieties of Ficus deltoidea extracts significantly restrained the formation of fluorescence AGEs by 4.55–5.14 fold. The extracts also reduced the fructosamine levels by 47.0–86.5%, increased the thiol group levels by 64.3–83.7%, and inhibited the formation of protein carbonyl by 1.36–1.76 fold. DPPH radical scavenging activity showed an IC50 value of 66.81–288.04 μg/ml and reducing power activity depicted at 0.02–0.24 μg/ml. The extent of phenolic compounds present in the extracts ranged from 70.90 to 299.78 mg·GAE/g. Apart from that, correlation studies between the activities were observed. This study revealed that seven varieties of Ficus deltoidea have the potential to inhibit AGEs formation and possess antioxidant activity that might be attributed to the presence of phenolic compounds.

Insulin dysregulation in horses with induced obesity

ABSTRACT: Insulin deregulation (ID) is a central player in the pathophysiology of equine metabolic syndrome (EMS), which is associated with generalized and/or regional obesity. The objective of this experiment was to characterize the alterations in the hormonal profile in horses exposed to a hypercaloric diet. A total of nine Mangalarga Marchador adult horses with initial body condition score (BCS) of 2.9±1/9 (mean±SD) were submitted to a high calorie grain-rich diet for 5 months. The data was collected before the start of the experiment and every 15 days until the end of the experiment and glucose and insulin concentrations were measured in the plasma. Proxies G:I, RISQI, HOMA-IR and MIRG were calculated. The low-dose oral glucose tolerance test (OGTT) was performed and the total area under the glucose (GTA) and insulin (ITA) curves at three different timepoints (before inducing obesity, after 90 days and after 150 days) was used. Analysis of variance of the results was performed considering the time effects and the means were compared with repeated measures by the Tukey’s test (P≤0.05). The ID was observed during the first 90 days of the experiment and was characterized as a decompensated ID, showing an increase of basal glucose and insulin plasma levels, changes in all proxies and a significant increase in GTA (P&lt;0.001) and ITA (P&lt;0.05). However, a clear compensation of the ID was evident after 150 days of experiment, which was supported by data from the insulin secretory response of β cells of the pancreas that showed an increase in insulin plasma levels, after fasting or exposure to gastric glucose, with a concomitant decrease in fasting glucose and fructosamine levels, and a decrease of GTA and marked increase of ITA (P&lt;0.0001) in the dynamic test. These findings confirm the occurrence of hyperinsulinemia associated with insulin deregulation in Mangalarga Marchador horses exposed to hypercaloric diets.

Investigation of Aloe ferox leaf powder on anti-diabesity activity

Obesity and diabetes contribute largely to increased morbidity and mortality globally. However, the treatment of obesity is not well established, hence plant materials are being considered for the development of new anti-diabesity therapies. Aloe ferox has been used for different medicinal purposes, but the research on its anti-diabesity activity is limited. This study therefore aimed to investigate the anti-diabesity potential of Aloe ferox leaf powder. Sprague Dawley rats assigned into 2 groups consisting of 8 animals each were fed with either a high fat diet (HFD; control), or a high fat diet containing Aloe ferox leaf powder (HFD-AL; treatment) over a period of 12 weeks. The animals were weighed weekly and their food consumption was monitored three times a week. Blood samples were collected after 12 weeks and analysed for liver function, fructosamine level, cholesterol and triglycerides levels. Furthermore, the aqueous and 50% dichloromethane-methanol extracts of A. ferox leaf powder were also analysed for their α-amylase and α-glucosidase inhibition potential. Phytochemical analysis was done using Liquid Chromatography coupled with Mass Spectroscopy (LC-MS) to identify active compounds. Body weight gain was lower in animals on HFD-AL than HFD only. Fructosamine level was significantly lower in HFD-AL than HFD animals at p<0.05. HFD-AL animals also presented with lower cholesterol and triglycerides levels as well as less adipose tissue than animals in the control. Histology examination did not reveal any lesions due to toxic effects in any of the organs in both groups. Aloe ferox leaf extracts showed potential inhibition of α-glucosidase, with little effect on α-amylase inhibition in vitro assays. Aloe ferox leaf powder showed the presence of isoferulic acid-3-glucoronide, chrysophanol-8-O-glucoside, oleic acid and stearic acid. While Aloe ferox water extract showed the presence of isorhamnetin, cinnamic acid and caffeoylshikimic acid. Aloe ferox leaf powder showed potential to prevent weight gain and possible hypoglycaemic effect in animals fed with high fat diet. It also showed potential glucose modulation activity through inhibition of α-glucosidase enzyme activity.