Metabolic changes in serum metabolome in response to a meal

Purpose

The change in serum metabolic response from fasting state to postprandial state provides novel insights into the impact of a single meal on human metabolism. Therefore, this study explored changes in serum metabolite profile after a single meal.

Methods

Nineteen healthy postmenopausal women with normal glucose tolerance participated in the study. They received a meal consisting of refined wheat bread (50 g carbohydrates, 9 g protein, 4.2 g fat and 2.7 g dietary fibre), 40 g cucumber and 300 mL noncaloric orange drink. Blood samples were collected at fasting and five postprandial time points. Metabolic profile was measured by nuclear magnetic resonance and targeted liquid chromatography–mass spectrometry. Changes over time were assessed with multivariate models and ANOVA, with baseline as control.

Results

The metabolomic analyses demonstrated alterations in phospholipids, amino acids and their breakdown products, glycolytic products, acylcarnitines and ketone bodies after a single meal. More specifically, phosphatidylcholines, lysophosphatidylcholines and citrate displayed an overall declining pattern, while leucine, isoleucine, methionine and succinate increased initially but declined thereafter. A sharp decline in acylcarnitines and ketone bodies and increase in glycolytic products postprandially suggest a switch in the body’s energy source from β-oxidation to glycolysis. Moreover, individuals with relatively high postprandial insulin responses generated a higher postprandial leucine responses compared to participants with lower insulin responses.

Conclusions

The study demonstrated complex changes from catabolic to anabolic metabolism after a meal and indicated that the extent of postprandial responses is different between individuals with high and low insulin response.

     

The onset of diabetes and poor metabolic control increases gingival bleeding in children and adolescents with insulin-dependent diabetes mellitus

Abstract Gingival health (bleeding on probing) and oral hygiene (plaque percent) were assessed in 2 groups of children and adolescents with insulin-dependent diabetes mellitus (IDDM). 1st study group included 12 newly diagnosed diabetic children and adolescents (age range 6.3-14.0 years, 5 boys and 7 girls). They were examined on the 3rd day after initial hospital admission and at 2 weeks and 6 weeks after initiation of insulin treatment. Gingival bleeding decreased after 2 weeks of insulin treatment (37.8% versus 19.0%. p < 0.001. paired t-test). and remained at the same level when examined 1 month later while glucose balance was excellent. Another group (n=80) of insulin-dependent diabetic children and adolescents (age range 11.7 - 18.4 years, 44 boys and 36 girls) with a mean duration of diabetes 6.0 years (range 0.3-15.0 years) were examined 2× at 3-month intervals. Subjects with poor blood glucose control (glycosylated haemoglobin, HbA₁, values over 13%) had more gingival bleeding (46.3% on examination 1, 41.7% on examination 2) than subjects with HbA₁ values less than 10% (mean gingival bleeding 35.2% and 26.9%, respectively) or subjects with HbA₁ values between 10 to 13% (mean gingival bleeding 35.6% and 33.4%, respectively). Differences were significant on both examinations (p < 0.05, Anova). and remained significant after controlling the groups for differences in age, age at the onset of diabetes, duration of diabetes and pubertal stage (Ancova). Results were not related to differences or changes in dental plaque status, supporting the concept that imbalance of glucose metabolism associated with diabetes predisposes to gingival inflammation. An increase in gingival bleeding in association with hyperglycaemia suggests that hyperglycaemia-associated biological alterations, which lower host resistance toward plaque, have apparently taken place. Consequently, although not all gingivitis proceeds into a destructive periodontal disease, prevention of plaque-induced gingival inflammation should be emphasised, particularly in children and adolescents with poorly controlled diabetes.     

Transketolase-like protein 1 expression predicts poor prognosis in colorectal cancer

Background: Transketolase-like protein 1 (TKTL1) is an isoform of tranketolase, a key protein in a cancer cell's glucose metabolism that causes rapid cell growth and controls the non-oxidative part of the pentose phosphate pathway (PPP). Its overexpression occurs in several human cancer types. Our purpose was to study whether TKTL1 expression in colorectal cancer tissue associates with these patients’ prognosis. Methods: We collected retrospectively patient data and tissue samples from 840 colorectal cancer patients treated at Helsinki University Hospital, then stained tumor tissue microarrays for TKTL1 by immunohistochemistry, and compared immunohistochemical tissue expression with clinico-pathological parameters and survival. Results: High expression of TKTL1 associated with high Dukes stage, non-mucinous adenocarcinoma, and left-sided disease. Patients with high TKTL1 expression had poorer prognosis than those with low expression, with a 5-year disease-specific survival of 55.7% vs. 62.7%. Conclusion: We show that high TKTL1 in tumor tissue can lead to poor survival in colorectal cancer. TKTL1 thus can serve as a candidate marker for identifying patients at risk of recurrent disease.     

Imaging of tumor hypoxia to predict treatment sensitivity

Non-invasive detection of tumor hypoxia using radiolabeled 2-nitroimidazoles has been a major effort during the last two decades. Recent years have witnessed the introduction of several new compounds which are chemically related to [(18)F]fluoromisonidazole (FMISO) but show slight but distinct differences in biodistribution and metabolic clearance. Although [(18)F]FMISO has shown clinical potential it suffers from suboptimal oxygen dependent tissue contrast and newer agents seek to improve this essential feature. The limited data on other interesting tracers keeps the investigators busy at demonstrating the potential advantages over [(18)F]FMISO while efforts should start to concentrate on proving the clinical significance of such techniques in the form of outcome data from image-guided therapy modification. We review here our experiences with two hypoxia-avid agents [(18)F]fluoroerythronitromidazole (FETNIM) and [(18)F] 2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) and focus on the similarities and differences of these two tracers in comparison to other radiolabeled 2-nitroimidazoles. It is recognized that only [(18)F]FMISO has thus far shown clinical utility and newer tracers need to be tested against this circumstance.     

Effect of Polydextrose on Subjective Feelings of Appetite during the Satiation and Satiety Periods: A Systematic Review and Meta-Analysis

Introduction: Subjective feelings of appetite are measured using visual analogue scales (VAS) in controlled trials. However, the methods used to analyze VAS during the Satiation (pre- to post-meal) and Satiety (post-meal to subsequent meal) periods vary broadly, making it difficult to compare results amongst independent studies testing the same product. This review proposes a methodology to analyze VAS during both the Satiation and Satiety periods, allowing us to compare results in a meta-analysis. Methods: A methodology to express VAS results as incremental areas under the curve (iAUC) for both the Satiation and Satiety periods is proposed using polydextrose as a case study. Further, a systematic review and meta-analysis on subjective feelings of appetite was conducted following the PRISMA methodology. Meta-analyses were expressed as Standardized Mean Difference (SMD). Results: Seven studies were included in the meta-analysis. There were important differences in the methods used to analyze appetite ratings amongst these studies. The separate subjective feelings of appetite reported were Hunger, Satisfaction, Fullness, Prospective Food Consumption, and the Desire to Eat. The method proposed here allowed the results of the different studies to be homogenized. The meta-analysis showed that Desire to Eat during the Satiation period favors polydextrose for the reduction of this subjective feeling of appetite (SMD = 0.24, I² < 0.01, p = 0.018); this effect was also significant in the sub-analysis by sex for the male population (SMD = 0.35, I² < 0.01, p = 0.015). There were no other significant results. Conclusion: It is possible to compare VAS results from separate studies. The assessment of iAUC for both the Satiation and Satiety periods generates results of homogeneous magnitudes. This case study demonstrates, for the first time, that polydextrose reduces the Desire to Eat during the Satiation period. This may explain, at least in part, the observed effects of polydextrose on the reduction of levels of energy intake at subsequent meals.     

Human Monocytic U937 Cells Kill Salmonella In Vitro by NO-Independent Mechanisms

Nitric oxide (NO) has a central role in host defense against intracellular microbes. HLA-B27 has been shown to directly modulate host-microbe interaction in vitro, leading to the impaired elimination of Salmonella in human monocytic U937 cells. Here, we studied whether impaired elimination of Salmonella would result from differences in NO production between HLA-B27- and HLA-A2-transfected U937 cells. Both human monocytic transfectants produced NO equally well and killed Salmonella via NO-independent mechanisms.