Non-fasting Conditions Research Articles

Blood Metabolites and Profiling Stored Adipose Tissue Reveal the Differential Migratory Strategies of Eurasian Reed and Sedge Warblers

The overall speed of bird migration is limited by the amount of fuel stores acquired during the initial phases of migration. The ability to mobilize fat is crucial for migratory birds that can exhibit different migratory strategies. Birds mobilize triglycerides during nocturnal flight thus increasing circulating fatty acids and glycerol to meet the metabolic demands of flight. Eurasian Reed (Acrocephalus scirpaceus) and Sedge (Acrocephalus schoenobaenus) Warblers were captured at Portuguese stopover sites during spring and autumn migration. These species were selected based on their different migration strategies and dietary preferences during migration. Blood metabolites and fat composition were analyzed to determine their nutritional states. Sedge Warblers had higher blood triglyceride and glycerol levels during post-flight fasting than in non-fasting periods. Furthermore, Sedge Warblers had higher triglyceride and glycerol levels than Eurasian Reed Warblers in both post-flight fasting and non-fasting condition. The differences found may reflect distinct approaches in re-feeding activity (e.g., feeding intensely) associated with the number of stopovers during migratory cycle. Dietary preferences affect the fat composition available for oxidation during long-term exercise in migratory flight. Nuclear magnetic resonance analysis of subcutaneous fat composition revealed that Sedge Warblers presented higher levels of polyunsaturated fatty acid levels than Eurasian Reed Warblers. The distinct lipidic profiles observed and differences in feeding ecology may explain the different migration strategies of these species. Overall and despite their ecological similarity, our study species showed pronounced differences in blood metabolites levels and subcutaneous fatty acids composition, likely attributed to the migratory strategy and foraging preferences during their migratory cycle.

Pharmacokinetic study of high-dose oral rifampicin in critically Ill patients with multidrug-resistant Acinetobacter baumannii infection.

Although rifampicin (RIF) is used as a synergistic agent for multidrug-resistant Acinetobacter baumannii (MDR-AB) infection, the optimal pharmacokinetic (PK) indices of this medication have not been studied in the intensive care unit (ICU) settings. This study aimed to evaluate the PK of high dose oral RIF following fasting versus fed conditions in terms of achieving the therapeutic goals in critically ill patients with MDR-AB infections. 29 critically ill patients were included in this study. Under fasting and non-fasting conditions, RIF was given at 1200mg once daily through a nasogastric tube. Blood samples were obtained at seven time points: exactly before administration of the drug, and at 1, 2, 4, 8, 12, and 24h after RIF ingestion. To quantify RIF in serum samples, high-performance liquid chromatography (HPLC) was used. The MONOLIX Software and the Monte Carlo simulations were employed to estimate the PK parameters and describe the population PK model. The mean area under the curve over the last 24-h (AUC0-24) value and accuracy (mean ± standard deviation) in the fasting and fed states were 220.24 ± 119.15 and 290.55 ± 276.20μg × h/mL, respectively. There was no significant difference among AUCs following fasting and non-fasting conditions (P > 0.05). The probability of reaching the therapeutic goals at the minimum inhibitory concentration (MIC) of 4mg/L, was only 1.6%. In critically ill patients with MDR-AB infections, neither fasting nor non-fasting administrations of high-dose oral RIF achieve the therapeutic aims. More research is needed in larger populations and with measuring the amount of protein-unbound RIF levels.

Screening and Management for Dyslipidemia in Korean Children and Adolescents

Cardiovascular disease (CVD) is the most common cause of death worldwide, and dyslipidemia is a major risk factor. Atherosclerosis can begin in childhood and continue into adulthood, thereby contributing to CVD development. Obesity is the most common cause of dyslipidemia, and the prevalence of childhood obesity and dyslipidemia is increasing worldwide, making it a public health concern. As clinical evidence has accumulated, guidelines for dyslipidemia in children have been continuously revised since 1992. The limitations of screening tests for individuals with a family history of dyslipidemia emphasize the necessity of universal screening, and non-HDL cholesterol assessment is recommended as a screening test for dyslipidemia in children. The guidelines for dyslipidemia in Korean children and adolescents published in 2017 recommend that non-HDL cholesterol screening tests be performed in non-fasting conditions at 9–11 years and 17–21 years of age. The main purpose of this article is to describe the history and rationale of lipid screening recommendations in children and adolescents and to review the currently recommended screening methods and treatments for dyslipidemia. (Ewha Med J 2022;45(3):e4)

Analysis of RGB range value on fingernail image for detecting diabetes mellitus risk

Introduction: Fingernail has various colors related to the organ’s body condition, such as the pancreas, indicated by diabetes mellitus. The study aims to determine and compare the RGB range value on the fingernail image to detect diabetes mellitus risk in fasting and non-fasting conditions. Methods: The study was a true experimental study using fasting and non-fasting respondents. Data were obtained by blood glucose level testing and fingernail image capturing. The result of blood glucose levels was classified into normal, prediabetes, or diabetes, and fingernail images were followed according to their categories. The histogram determined the RGB values of fingernail images, and calculated the maximum value of color intensity based on the height peak appeared. The distribution frequency of each group was used to get a range of RGB fingernail images in each category. Results: Based on the results, it showed a comparison of RGB range value between fasting and non-fasting condition, including range value differences in red and blue, but any slightly overlapped in green range value. In a future study, we will use ordinal logistic regression to determine the prediction program of diabetes mellitus risk. Furthermore, we will develop a program by adding some features to improve the analysis system of the fingernail image for diabetes mellitus risk detection. Conclusion: There was a comparison of RGB range value on fingernail image between fasting and non-fasting condition.

Challenges in Hemoglobin A1C Measurement in 183 Patients with Diabetes having Hemoglobin Variants and Chemically Modified Derivatives

Diabetes is considered as one of the most common metabolic disorder. It has challenged in terms of diagnosis,monitoring and management in the patients with type-2 diabetes. Glycosylated Hemoglobin (HbA1c) hasrecently been validated for the diagnosis diabetes in non-fasting condition, long term blood glycose monitoringand also predicting its complications in the patients. National Glycohemoglobin Standardization Program andInternational Federation of Clinical chemistry have been collaborating for the harmonization of HbA1cmethods and directing the laboratories to maintain strict quality goals. However, standardization of variousHbA1c methods being used worldwide still needs consideration especially in diabetic patients havinghemoglobin variants. The main objectives are to review HbA1c methods and address challenges in itsmeasurement methodology for the patients with diabetes mellitus having hemoglobin variants or chemicallymodified derivatives. Thus, to provide guidance to the clinical pathologist for selection of appropriate methodfor their laboratories.

Diurnal variation of magnesium and the mineral metabolism in patients with chronic kidney disease

Increasing levels of magnesium in blood are associated with reduced risk of cardiovascular disease in chronic kidney disease (CKD). Magnesium supplementation may reduce the progression of vascular calcification in CKD. The diurnal pattern and effect of fasting on magnesium in blood and urine in CKD is unknown, and knowledge of this may influence management of magnesium supplementation.We included ten patients with CKD stage four without diabetes mellitus and ten healthy controls. Participants were admitted to our hospital ward for a 24-h study period. Blood and urine samples were collected in a non-fasting state at 8 o'clock in the morning and every third hour hereafter until the final samples in a fasting state at 8 o'clock the following morning.We found no diurnal variation in plasma magnesium (p = 0.097) in either group, but a significant diurnal variation in urinary excretion of magnesium (p = 0.044) in both CKD and healthy controls with no significant interaction between the two groups, and thus no suggestion that CKD affects diurnal variation of plasma magnesium or urinary magnesium excretion. The levels of plasma magnesium were not significantly different in fasting and non-fasting conditions.Magnesium in plasma does not display a significant diurnal variation and can be measured at any time of day and in both fasting and non-fasting conditions. Urinary magnesium excretion displays diurnal variation, which is likely related to increased uptake of magnesium during meals and helps maintain a stable concentration of magnesium in blood.

Does Ramadan Fasting Affect the Blood Coagulation System through A Session Soccer Match

Introduction: Fasting during Ramadan is associated with modifications in athletes' metabolic, physiological, and psychological responses that may affect physical performance. The current study aimed to assess the changes in some risk factors of thrombosis in trained men following one soccer session in non-fasting and fasting conditions. Method: The 11 amateur soccer players (age: 42 ± 16 years) and (body mass index:26.49 ± 2.86) played soccer matched (~100 min: 10 min warm-up, 90 min soccer match) on two occasions: 1 week before and on the fourth day of Ramadan. The blood samples were taken before and after the soccer game. Fibrinogen and D-dimer were analyzed by the Clauss clotting method and the turbid metric assay, respectively; plasminogen and alpha 2 anti-plasmin were analyzed by spectrophotometry, and Homocysteine was analyzed by the ELISA method. The Shapiro-Wilk, independent t-test, and dependent t-test were used to analyze the findings. (P ≤0.05). Result: The results demonstrated that one session soccer match increased homocysteine in both fasting (p = 0.006) and non-fasting (p = 0.042), Alpha 2-antiplasmin decreased in fasting (p = 0.031 and non-fasting (p = 0.001) and plasminogen decreased in non-fasting (p = 0.012). one session soccer match had not a Significant Impact on Fibrinogen and D-dimer in both condition and plasminogen in fasting(p≥0.05). Also, there was no significant difference between fasting and non-fasting conditions in Homocysteine, Alpha 2-antiplasmin, Fibrinogen, Plasminogen, and D-dimer in response to one session soccer match (p≥0.05). Conclusions: Amazingly, one session soccer match throughout the fasting condition is parallel with the non-fasting state, and fasting did not produce adverse consequences in the coagulation system.

Influence of pregnancy and non-fasting conditions on the plasma metabolome in a rat prenatal toxicity study.

The current parameters for determining maternal toxicity (e.g. clinical signs, food consumption, body weight development) lack specificity and may underestimate the extent of effects of test compounds on the dams. Previous reports have highlighted the use of plasma metabolomics for an improved and mechanism-based identification of maternal toxicity. To establish metabolite profiles of healthy pregnancies and evaluate the influence of food consumption as a confounding factor, metabolite profiling of rat plasma was performed by gas- and liquid-chromatography-tandem mass spectrometry techniques. Metabolite changes in response to pregnancy, food consumption prior to blood sampling (non-fasting) as well as the interaction of both conditions were studied. In dams, both conditions, non-fasting and pregnancy, had a marked influence on the plasma metabolome and resulted in distinct individual patterns of changed metabolites. Non-fasting was characterized by increased plasma concentrations of amino acids and diet related compounds and lower levels of ketone bodies. The metabolic profile of pregnant rats was characterized by lower amino acids and glucose levels and higher concentrations of plasma fatty acids, triglycerides and hormones, capturing the normal biochemical changes undergone during pregnancy. The establishment of metabolic profiles of pregnant non-fasted rats serves as a baseline to create metabolic fingerprints for prenatal and maternal toxicity studies.

Brain activations show association with subsequent endocrine responses to oral glucose challenge in a satiation-level dependent manner

AimsThe communication between brain and peripheral homeostatic systems is a central element of ingestive control. We set out to explore which parts of the brain have strong functional connections to peripheral signalling molecules in a physiological context. It was hypothesised that associations can be found between endocrine response to glucose ingestion and preceding brain activity in dependence of the nutritional status of the body. Materials and methodsYoung, healthy male participants underwent both a 38 ​h fasting and a control condition with standardized meals. On the second day of the experiment, participants underwent fMRI scanning followed by ingestion of glucose solution in both conditions. Subsequent endocrine responses relevant to energy metabolism were assessed. Associations between preceding brain activation and endocrine responses were examined. ResultsIn both fasting and non-fasting conditions, brain activity was associated with subsequent endocrine responses after glucose administration, but relevant brain areas differed substantially between the conditions. In the fasting condition relations between the caudate nucleus and the orbitofrontal regions with insulin and C-peptide were prevailing, whereas in the non-fasting condition associations between various brain regions and adiponectin and cortisol were the predominant significant outcome. ConclusionConnections between endocrine response following a glucose challenge and prior brain activity suggests that the brain is playing an active role in the networks regulating food intake and associated endocrine signals. Further studies are needed to demonstrate causation.

Changes in Salivary Amylase and Glucose in Diabetes: A Scoping Review.

Background and Objective: Diabetes mellitus (DM) is a common long-term disease which can be related with salivary amylase levels. DM has recently been associated with salivary amylase diagnostics that could further impair diagnoses in the diabetic population, as well as being an interesting alternative to traditional methods of determine glucose levels. The main advantage of this method is related to the fact that it is a fast diagnostic method. The DM population experiences changes to their metabolism which affects their salivary parameters, making this an alternative procedure for diagnosis and follow-up of the illness due to the non-invasive nature of salivary analyzes. The objective of this review is to summarize the evidence regarding the changes in salivary amylase and glucose levels, and their relationship with blood markers of glycemic control used in clinical settings such as blood glucose and glycated hemoglobin. The differences in salivary amylase levels depending on the method of saliva collection under fasting or non-fasting conditions. The changes in salivary amylase depends on the type of diabetes, the type of insulin treatment or the quality of glycemic control. Conclusions: Salivary amylase concentration is increased in diabetic patients in most of the studies and salivary glucose concentration in all studies in both fasting and non-fasting (post-prandial) conditions. Salivary amylase and glucose concentration represent potential non-invasive biomarkers to evaluate glycemic control and clinical management of diabetic patients, although it is necessary to evaluate the influence of potential modulating factors such as age, duration diseases, sex and the effects of pharmacological treatments in these outcomes which remained to be elucidated.

Bayesian parameter estimation in the oral minimal model of glucose dynamics from non-fasting conditions using a new function of glucose appearance

Background and objectiveThe oral minimal model (OMM) of glucose dynamics is a prominent method for assessing postprandial glucose metabolism. The model yields estimates of insulin sensitivity and the meal-related appearance of glucose from insulin and glucose data after an oral glucose challenge. Despite its success, the OMM approach has several weaknesses that this paper addresses. MethodsA novel procedure introducing three methodological adaptations to the OMM approach is proposed. These are: (1) the use of a fully Bayesian and efficient method for parameter estimation, (2) the model identification from non-fasting conditions using a generalised model formulation and (3) the introduction of a novel function to represent the meal-related glucose appearance based on two superimposed components utilising a modified structure of the log-normal distribution. The proposed modelling procedure is applied to glucose and insulin data from subjects with normal glucose tolerance consuming three consecutive meals in intervals of four hours. ResultsIt is shown that the glucose effectiveness parameter of the OMM is, contrary to previous results, structurally globally identifiable. In comparison to results from existing studies that use the conventional identification procedure, the proposed approach yields an equivalent level of model fit and a similar precision of insulin sensitivity estimates. Furthermore, the new procedure shows no deterioration of model fit when data from non-fasting conditions are used. In comparison to the conventional, piecewise linear function of glucose appearance, the novel log-normally based function provides an improved model fit in the first 30 min of the response and thus a more realistic estimation of glucose appearance during this period. The identification procedure is implemented in freely accesible MATLAB and Python software packages. ConclusionsWe propose an improved and freely available method for the identification of the OMM which could become the future standardard for the oral minimal modelling method of glucose dynamics.

Pharmacogenetic and safety analysis of cinacalcet hydrochloride in healthy Chinese subjects.

BackgroundOur study aims to explore the effect of genetics on the pharmacodynamics (PD) and pharmacokinetics (PK) of cinacalcet in healthy Chinese subjects; to investigate the effect of dietary factors on cinacalcet, and to evaluate the safety of cinacalcet under fasting and non-fasting conditions using a bioequivalence trial.MethodsWe investigated the relationship of cinacalcet PK with single nucleotide polymorphisms (SNPs) of CYP3A4, CYP1A2 and CYP2D6, and of cinacalcet PD with SNPs of calcium-sensitive receptors (CASR) and vitamin D receptors (VDR) in 65 healthy Chinese subjects recruited to participate in this study. Our study was a phase I, open-label, randomized, two-period, two-sequence crossover, a single-center clinical study designed under both fasting and non-fasting conditions to investigate the effect of dietary factors on cinacalcet. Plasma cinacalcet concentrations were analyzed using a validated HPLC-MS/MS assay. Clinical laboratory tests evaluated safety. Thirteen SNPs of CASR, VDR, and CYP genes were selected for pharmacogenetic analysis.ResultsCYP3A4 rs4646437 was found to be associated with the PK of cinacalcet under fasting conditions (P<0.01). Subjects carrying T alleles of rs4646437 appeared to metabolize cinacalcet poorly. The Cmax and AUC of subjects in the non-fasting group were significantly higher (P<0.0001) than those in the fasting group. The Tmax, CL/F, and Vd/F in the fasting group were significantly higher (P<0.0001) than those in the non-fasting group. In the fasting group, the geometric least square mean ratios (T/R) of the Cmax and AUC0-t were 109.89% and 105.33%, and the corresponding 90% CIs were 98.36–122.79% and 98.04–113.15%, respectively. In the non-fasting group, the T/R of the Cmax and AUC0-t were 100.74% and 99.09%, and the corresponding 90% CIs were 92.65–109.54% and 94.79–103.58%, respectively. All adverse events (AEs) were mild, and no serious adverse events (SAEs) occurred during the bioequivalence trial.ConclusionsFollowing our investigation, we reached the following conclusions: CYP3A4 rs4646437 may affect cinacalcet PK; the reference and test preparations of cinacalcet were bioequivalent under fasting and non-fasting conditions and were safe to use; and dietary factors had a significant effect on the PK of cinacalcet, in that exposure to the drug increased when cinacalcet was taken after eating.

Ramadan Fasting and Kidney Stones: A Systematic Review.

Ramadan fasting in Muslims may contain several hours of abstaining from food and drinking in any kind. This can potentially increase the risk of urinary stone disease. Current literature on possible effects of Ramadan fasting on urolithiasis is rather limited. Having the gap in scientific background, we decided to evaluate the available comparative information in this systematic review. We included all studies comparing fasting and non-fasting conditions, studies evaluating stone formation and clinical manifestations of kidney stone disease. All the English studies published from January 1980 to the end of 2019 were included. The exclusion criteria were as followed: fasting out of Ramadan, non-comparative studies, animal studies, patients with bladder stones, and studies evaluating conditions that are only indirectly related to the stone formation or clinical manifestations of it. Applying the Joanna Briggs Institute (JBI) methodology for systematic review showed the quality of included studies was not high. Only five studies remained after exclusion. Meta-analysis was not applicable due to the diversity in methods and evaluated population. Main trend of the included studies is toward showing no difference between fasting and non-fasting conditions in terms of renal stone formation. However, generalization of the findings to greater populations should be applied carefully considering the heterogeneity of results and quality of studies.

Fasting Status and Circadian Variation Must be Considered When Performing AUC-based Therapeutic Drug Monitoring of Tacrolimus in Renal Transplant Recipients.

Therapeutic drug monitoring (TDM) is mandatory for the immunosuppressive drug tacrolimus (Tac). For clinical applicability, TDM is performed using morning trough concentrations. With recent developments making tacrolimus concentration determination possible in capillary microsamples and Bayesian estimator predicted area under the concentration curve (AUC), AUC‐guided TDM may now be clinically applicable. Tac circadian variation has, however, been reported, with lower systemic exposure following the evening dose. The aim of the present study was to investigate tacrolimus pharmacokinetic (PK) after morning and evening administrations of twice‐daily tacrolimus in a real‐life setting without restrictions regarding food and concomitant drug timing. Two 12 hour tacrolimus investigations were performed; after the morning dose and the following evening dose, respectively, in 31 renal transplant recipients early after transplantation both in a fasting‐state and under real‐life nonfasting conditions (14 patients repeated the investigation). We observed circadian variation under fasting‐conditions: 45% higher peak‐concentration and 20% higher AUC following the morning dose. In the real‐life nonfasting setting, the PK‐profiles were flat but comparable after the morning and evening doses, showing slower absorption rate and lower AUC compared with the fasting‐state. Limited sampling strategies using concentrations at 0, 1, and 3 hours predicted AUC after fasting morning administration, and samples obtained at 1, 3, and 6 hours predicted AUC for the other conditions (evening and real‐life nonfasting). In conclusion, circadian variation of tacrolimus is present when performed in patients who are in the fasting‐state, whereas flatter PK‐profiles and no circadian variation was present in a real‐life, nonfasting setting.

Effects of Prolonged Whey Protein Supplementation and Resistance Training on Biomarkers of Vitamin B12 Status: A 1-Year Randomized Intervention in Healthy Older Adults (the CALM Study).

We investigated the effect of long-term whey supplementation on biomarkers of B12 status in healthy older adults subjected to different schemes of supplements and exercise. The total study population examined at baseline consisted of 167 healthy older adults (age ≥ 65 year) who were randomized to 1-y intervention with two daily supplements of (1) whey protein (3.1 µg B12/day) (WHEY-ALL), (2) collagen (1.3 µg B12/day) (COLL), or (3) maltodextrin (0.3 µg B12/day) (CARB). WHEY-ALL was comprised of three groups, who performed heavy resistance training (HRTW), light resistance training (LITW), or no training (WHEY). Dietary intake was assessed through 3-d dietary records. For the longitudinal part of the study, we included only the participants (n = 110), who met the criteria of ≥ 50% compliance to the nutritional intervention and ≥ 66% and ≥ 75% compliance to the heavy and light training, respectively. Fasting blood samples collected at baseline and 12 months and non-fasting samples collected at 6 and 18 months were examined for methylmalonic acid, B12 and holotranscobalamin. At baseline, the study population (n = 167) had an overall adequate dietary B12 intake of median (range) 5.3 (0.7–65) µg/day and median B12 biomarker values within reference intervals. The whey intervention (WHEY-ALL) caused an increase in B12 (P < 0.0001) and holotranscobalamin (P < 0.0001). In addition, methylmalonic acid decreased in the LITW group (P = 0.04). No change in B12 biomarkers was observed during the intervention with collagen or carbohydrate, and the training schedules induced no changes. In conclusion, longer-term daily whey intake increased plasma B12 and holotranscobalamin in older individuals. No effect of intervention with collagen or carbohydrate or different training regimes was observed. Interestingly, the biomarkers of B12 status appeared to be affected by fasting vs. non-fasting conditions during sample collection.

Comparison of fasting and non-fasting lipid profile in healthy adult population

Lipid profile is done in fasting blood specimen commonly, the reasons being: 1. Triglycerides remain elevated for several hours in postprandial state, 2. Reference range are established for fasting serum lipid profile.This study was proposed to compare the lipid profiles obtained in fasting and non-fasting conditions. If a reliable correlation between fasting and non-fasting lipid profile will be obtained, assay for lipids in non-fasting state may be adopted for clinical evaluation. This might help in reducing the difficulties faced in obtaining the sample in fasting state. This was a cross-sectional study, conducted from October 2011 to October 2013. Total of 200 subjects were included in the study. Two Samples were collected from each individual, one sample after 8-12 hours fasting and second sample in non-fasting state (random sample). Total cholesterol, Triglycerides, HDL-cholesterol were analyzed by standard methods and, LDL-cholesterol was calculated using Friedewald’s formula. Significant increase was observed in non-fasting Triglyceride and VLDL-C as compared to fasting samples in total population, but we observed significant difference in total cholesterol and LDL-C in total population. Significant reduction was observed in HDL-C in non-fasting state as compared to fasting state. Positive correlation was observed between fasting and non-fasting total cholesterol triglyceride, VLDL-C, HDL-C and LDL-C in the total population. Non-fasting sample can be used to measure Total cholesterol and HDL-C. Non-fasting sample can be used to measure triglyceride, VLDL-C and LDL-C provided reference intervals are established in non-fasting state for the same in larger population.

Sciadonic acid derived from pine nuts as a food component to reduce plasma triglycerides by inhibiting the rat hepatic \u03949-desaturase

Sciadonic acid (Scia) is a Δ5-olefinic fatty acid that is particularly abundant in edible pine seeds and that exhibits an unusual polymethylene-interrupted structure. Earlier studies suggested that Scia inhibited the in vitro expression and activity of the Stearoyl-CoA Desaturase 1 (SCD1), the hepatic Δ9-desaturase involved in the formation of mono-unsaturated fatty acids. To confirm this hypothesis, rats were given 10% Scia in diets balanced out with n-6 and n-3 fatty acids. In those animals receiving the Scia supplement, monoene synthesis in the liver was reduced, which was partly attributed to the inhibition of SCD1 expression. As a consequence, the presence of Scia induced a 50% decrease in triglycerides in blood plasma due to a reduced level of VLDL-secreted triglycerides from the liver. In non-fasting conditions, results showed that Scia-induced inhibition of SCD1 led to a decrease in the proportions of 16:1n-7 and 18:1n-7 in the liver without impacting on the level of 18:1n-9, suggesting that only triglycerides with neosynthesized monoenes are marked out for release. In conclusion, this in vivo study confirms that Scia highly inhibits SCD1 expression and activity. The work was performed on normo-triglyceride rats over six weeks, suggesting promising effects on hyper-triglyceridemic models.

Effects of D-Chiro-Inositol on Glucose Metabolism in db/db Mice and the Associated Underlying Mechanisms.

In this study, we observed the effect of D-chiro-inositol (DCI) on glucose consumption in type 2 diabetic db/db mice, and investigated the relevant mechanism. We discovered that the stability of 24-h blood glucose under the nonfasting condition and decreased glucose tolerance were both alleviated after treatment with DCI. Moreover, the content of glycosylated protein and advanced glycation end products in the serum was reduced, the damage in the liver tissue was alleviated, and the synthesis of liver glycogen was significantly promoted. In addition, DCI increased the expression of insulin receptor substrate 2 (IRS2), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), glucose transporters 4 (GLUT4), and phospho-AKT (S473) protein. In contrast, DCI decreased the expression level of glycogen synthase kinase 3β (GSK3β) protein in liver tissue to various degrees, as shown by immunohistochemistry and western blotting. Furthermore, DCI increased the mRNA expression of IRS2, PI3K, AKT, and GLUT4, and reduced that of GSK3β in liver tissue, as demonstrated by polymerase chain reaction. Finally, DCI promoted glucose consumption in high glucose-stimulating HepG2 cells and increased the expression of IRS2 protein in HepG2 cells, as revealed by fluorescence staining and flow cytometry. Our results indicate that DCI can significantly improve glucose metabolism in diabetic mice and HepG2 cells. This effect may be associated with the upregulation of IRS2, PI3K, AKT, and GLUT4 and downregulation of GSK3β.

Glycated hemoglobin and glycated albumin in patients with diabetes undergoing hemodiafiltration

BackgroundOnline hemodiafiltration (OHDF), which results in high albumin leakage, is now widely used in Japan for dialysis, since the national insurance system began reimbursing its costs in 2012. Glycated albumin (GA) levels are affected by albumin leakage into effluent dialysate fluid. Therefore, GA levels in patients requiring diabetes-related dialysis undergoing OHDF require monitoring. However, there have been no previous reports on glycemic control indicators of patients with diabetes undergoing OHDF. We aimed to develop a glycemic control index for patients requiring diabetes-related dialysis undergoing OHDF.MethodsThis study comprised 133 diabetic patients undergoing OHDF. We examined the correlation between GA and glycated hemoglobin (HbA1c) levels. We analyzed effluent dialysate fluid samples from 41 patients classified into 3 groups, namely, group A, non-protein-leaking OHDF (n = 20); group B, protein-leaking OHDF (n = 14); and group C, highly efficient protein-leaking OHDF (n = 7). We examined the association between GA and HbA1c levels in each group and among patients.ResultsA significant positive correlation was observed between GA and HbA1c levels (r = 0.562, p < 0.0001). There was no significant correlation between pre-dialysis blood glucose levels and HbA1c or GA levels as observed on regular blood tests performed under non-fasting conditions. Patients were classified into 2 groups based on their mean albumin levels (3.4 g/dL cutoff). The correlation between HbA1c and GA levels was found to be weaker in the 51 patients with mean albumin levels < 3.4 g/dL (r = 0.399, p = 0.0037) than in the 82 patients with mean albumin levels ≥ 3.4 g/dL (r = 0.674, p < 0.0001). When the hemodiafilter performance was assessed, no correlation was observed between HbA1c and GA levels in group C patients.ConclusionsGA levels may be underestimated in patients undergoing OHDF because of the effect of albumin leakage into the effluent dialysate fluid. If a stable hemoglobin value can be maintained during OHDF therapy, then GA and HbA1c levels should be used as a glycemic control index for patients requiring diabetes-related dialysis, considering the dialysis treatment method and protein permeability of the dialyzers and hemodiafilters.

P6193Dalcetrapib reduces incident diabetes in patients with recent acute coronary syndrome

Abstract Background Among patients with acute coronary syndrome (ACS) who do not have diabetes, incident diabetes is common and associated with an adverse prognosis. Some data suggest that high density lipoprotein (HDL) has favourable effects on beta cell function and that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes in conjunction with increased HDL cholesterol (HDL-C) concentration. Dalcetrapib is a CETP inhibitor under ongoing evaluation as a potential cardiovascular therapy. Purpose We compared the effect of treatment with dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome (ACS). Methods In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg or placebo daily, beginning 4–12 weeks after ACS. Absence of diabetes at baseline was based upon medical history, no use of diabetes medication, haemoglobin A1c &lt;6.5%, and plasma glucose level &lt;7 mmol/L (if measured under fasting conditions) or &lt;11.1 mmol/L (if measured under non-fasting conditions). Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, use of a diabetes medication, HbA1c ≥6.5%, or two measurements of plasma glucose ≥7 mmol/L (fasting) or ≥11.1 mmol/L (non-fasting). The association of incident diabetes with baseline and on-treatment HDL-C was determined. Results At baseline, 10621 patients (67% of the trial cohort) did not have diabetes and formed the analysis cohort. Over median follow-up of 31 months, incident diabetes was identified in 392 of 5314 patients (7.4%) assigned to dalcetrapib and 505 of 5307 (9.5%) assigned to placebo (odds ratio [OR] 0.76; 95% confidence interval [CI] 0.66–0.87; P&lt;0.001). This corresponds to an absolute reduction in incident diabetes of 2.1%, and a need to treat 47 patients (for 31 months) to prevent 1 case of diabetes. Kaplan-Meier estimates of the cumulative incidence of diabetes are shown in the Figure. Across both treatment groups, incident diabetes was inversely associated with baseline HDL-C (OR 0.98 for 1 mg/dL increase in baseline HDL-C; 95% CI 0.97–0.98, P&lt;0.001). In the dalcetrapib group, there was a further inverse association of incident diabetes with the change in HDL-C on assigned treatment (OR 0.98 for 1 mg/dL increase in HDL-C from baseline; 95% CI 0.97–0.99, P=0.002). Dalcetrapib was safe and generally well-tolerated in the trial. Conclusions In patients with recent ACS who do not have diabetes at baseline, incident diabetes is common. Dalcetrapib treatment reduced the relative risk of incident diabetes by 24% and the absolute risk by 2.1% over a median of 31 months. The reduction in incident diabetes with dalcetrapib was associated with increased HDL-C on treatment. Acknowledgement/Funding The dal-OUTCOMES trial was funded by F. Hoffmann LaRoche