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Fasting is increasingly popular to manage metabolic and inflammatory diseases. Despite the role that the human gut microbiota plays in health and diseases, little is known about its composition and functional capacity during prolonged fasting when the external nutrient supply is reduced or suppressed. We analysed the effects of a 10-d periodic fasting on the faecal microbiota of fifteen healthy men. Participants fasted according to the peer-reviewed Buchinger fasting guidelines, which involve a daily energy intake of about 1046 kJ (250 kcal) and an enema every 2 d. Serum biochemistry confirmed the metabolic switch from carbohydrates to fatty acids and ketones. Emotional and physical well-being were enhanced. Faecal 16S rRNA gene amplicon sequencing showed that fasting caused a decrease in the abundance of bacteria known to degrade dietary polysaccharides such as Lachnospiraceae and Ruminococcaceae. There was a concomitant increase in Bacteroidetes and Proteobacteria ( Escherichia coli and Bilophila wadsworthia ), known to use host-derived energy substrates. Changes in taxa abundance were associated with serum glucose and faecal branched-chain amino acids (BCAA), suggesting that fasting-induced changes in the gut microbiota are associated with host energy metabolism. These effects were reversed after 3 months. SCFA levels were unchanged at the end of the fasting. We also monitored intestinal permeability and inflammatory status. IL-6, IL-10, interferon γ and TNFα levels increased when food was reintroduced, suggesting a reactivation of the postprandial immune response. We suggest that changes in the gut microbiota are part of the physiological adaptations to a 10-d periodic fasting, potentially influencing its beneficial health effects., (© The Author(s) 2019.)

Dietary modification has been the cornerstone of cardiovascular disease (CVD) prevention since the middle of the last century when the American Heart Association (AHA) first issued recommendations. For the vast majority of that time the focus has been on saturated fat, with or without concomitant guidance for total or unsaturated fat. Over the past few years there has been a renewed debate about the relation between dietary saturated fat and CVD risk, prompted by a series of systematic reviews that have come to what appears to be different conclusions. This triggered a robust discourse about this controversy in the media that in turn has led to confusion in the general public. The genesis of the different conclusions among the systematic reviews has been identified in several studies on the basis of isocaloric substitution analyses. When the data were analyzed on the basis of polyunsaturated fat replacing saturated fat, there was a positive relation between dietary saturated fat and CVD. When the data were analyzed on the basis of carbohydrate replacing saturated fat, there was a null relation between dietary saturated fat and CVD. When the substitution macronutrient was not taken into consideration, the differential effects of the macronutrient substitution went unrecognized and the relations judged as null. The lack of distinction among substituted macronutrients accounted for much of what appeared to be discrepancies. Dietary guidance consistent with replacing foods high in saturated fat with foods high in unsaturated fat, first recommended more than 50 y ago, remains appropriate to this day., (Copyright © The Author(s) 2019.)

A new purified polysaccharide (PNP40c-1) with a molecular weight of 2.06 × 10 5 Da was obtained from pine nuts (Pinus koraiensis Sieb. et Zucc.). Structural analysis indicated that PNP40c-1 is a homogeneous heteropolysaccharide composed of arabinose, rhamnose and glucose in a molar ratio of 2.98:1.00:0.52. The major backbone consisted of →3,4)-α-l-Arap(1→, →4)-α-l-Arap3Me(1→, →3)-α-l-Rhap(1→ and →6)-β-d-Glcp(1→, and the side chain is β-d-Glcp-(1→ linked at C4-position of →3,4)-α-l-Arap(1→. In addition, the hepatoprotective effect of PNP40c-1 was investigated by human hepatocyte cell line L02 treated with carbon tetrachloride (CCl 4 ). Results suggested that PNP40c-1 could protect L02 cells from CCl 4 -induced damage by enhancing the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), increasing the level of non-enzymatic antioxidant glutathione (GSH), suppressing lipid perioxidation and further reducing the leakage of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hence, PNP40c-1 could be a promising functional food to serve as hepatoprotective agent., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To determine the acute effects of carbohydrate (CHO) ingestion following a bout of maximal eccentric resistance exercise on key anabolic kinases of mammalian target of rapamycin and extracellular signal-regulated kinase (ERK) pathways. The authors' hypothesis was that the activation of anabolic signaling pathways known to be upregulated by resistance exercise would be further stimulated by the physiological hyperinsulinemia resulting from CHO supplementation., Methods: Ten resistance-trained men were randomized in a crossover, double-blind, placebo (PLA)-controlled manner to ingest either a noncaloric PLA or 3 g/kg of CHO beverage throughout recovery from resistance exercise. Muscle biopsies were collected at rest, immediately after a single bout of intense lower body resistance exercise, and after 3 hr of recovery., Results: CHO ingestion elevated plasma glucose and insulin concentrations throughout recovery compared with PLA ingestion. The ERK pathway (phosphorylation of ERK1/2 [Thr202/Tyr204], RSK [Ser380], and p70S6K [Thr421/Ser424]) was markedly activated immediately after resistance exercise, without any effect of CHO supplementation. The phosphorylation state of AKT (Thr308) was unchanged postexercise in the PLA trial and increased at 3 hr of recovery above resting with ingestion of CHO compared with PLA. Despite stimulating-marked phosphorylation of AKT, CHO ingestion did not enhance resistance exercise-induced phosphorylation of p70S6K (Thr389) and rpS6 (Ser235/236 and Ser240/244)., Conclusion: CHO supplementation after resistance exercise and hyperinsulinemia does not influence the ERK pathway nor the mTORC1 target p70S6K and its downstream proteins, despite the increased AKT phosphorylation.

Scope: Dietary protein restriction elicits hyperphagia and increases energy expenditure; however, less is known of whether these responses are a consequence of increasing carbohydrate content. The effects of protein-diluted diets with fixed carbohydrate content on energy balance, hormones, and key markers of protein sensing and thermogenesis in tissues are determined., Methods and Results: Obesity-prone rats (n = 13-16 per group) are randomized to diets containing fixed carbohydrate (52% calories) and varying protein concentrations: 15% (control), 10% (mild protein restriction), 5% (moderate protein restriction) or 1% (severe protein restriction) protein calories, or protein-matched to 5% protein, for 21 days. Propranolol and ondansetron are administered to interrogate the roles of sympathetic and serotonergic systems, respectively, in diet-induced changes in energy expenditure. It is found that mild-to-moderate protein restriction promotes transient hyperphagia, whereas severe protein restriction induces hypophagia, with alterations in meal patterns. Protein restriction enhances energy expenditure that is partly attenuated by propranolol, but not ondansetron. Moderate to severe protein restriction decreases gains in body weight, lean and fat mass, decreased postprandial glucose and leptin, but increased fibroblast growth factor-21 concentrations. Protein-matching retains lean mass suggesting that intake of dietary protein, but not calories, is important for preserving lean mass. Notably, protein restriction increases the protein and/or transcript abundance of key amino acid sensing molecules in liver and intestine (PERK, eIF2α, ATF2, CHOP, 4EBP1, FGF21), and upregulated thermogenic markers (β2AR, Klotho, HADH, UCP-1) in brown adipose tissue., Conclusion: Low-protein diets promote hyperphagia and sympathetically mediated increase in energy expenditure, prevent gains in tissue reserves, and concurrently upregulate hepatic and intestinal amino acid sensing intermediaries and thermogenic markers in brown adipose tissue., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Stearoyl CoA desaturase 1 (SCD1) is a key enzyme in lipogenesis as it catalyzes the synthesis of monounsaturated fatty acids (MUFAs), mainly oleate (18:1n9) and palmitoleate (16:1n7) from saturated fatty acids (SFA), stearate (18:0) and palmitate (16:0), respectively. Studies on SCD1 deficiency in mouse models demonstrated beneficial metabolic phenotypes such as reduced adiposity and improved glucose tolerance. Even though, SCD1 represents a potential target to resolve obesity related metabolic diseases; SCD1 deficiency causes endoplasmic reticulum (ER) stress and activates unfolded protein response (UPR). The induction of ER stress in response to SCD1 deficiency is governed by the cofactor, PGC-1α. However, the mechanism by which SCD1 deficiency increases PGC-1α and subsequently induces ER stress still remains elusive. The present study demonstrates that despite reduced lipogenesis, liver specific SCD1 deficiency activates the mechanistic target of rapamycin complex 1 (mTORC1) along with induction of PGC-1α and ER stress. Further, mTORC1 inhibition attenuates SCD1 deficiency-mediated induction of both PGC-1α and ER stress. Similar observations were seen by restoring endogenously synthesized oleate, but not palmitoleate, suggesting a clear mTORC1-mediated regulation of ER stress during SCD1 deficiency. Overall, our results suggest a model whereby maintaining adequate levels of hepatic oleate is required to suppress mTORC1-mediated ER stress. In addition, the activation of mTORC1 by SCD1 deficiency reveals an important function of fatty acids in regulating different cellular processes through mTORC1 signaling.

Galectin-3 and galectin-3 binding proteins (G3BP) are implicated as key players in metastasis. In the current study, we evaluated the effect of pectic polysaccharides on galectin-3 and G3BP mediated metastasis in vitro (cells) and in vivo (tissues). In vitro study (double immunostaining) confirms the presence of galectin-3 on the cell surface and G3BP in the interlinking region of the cells confirming the role of G3BP in bridging galectin-3 molecules. Dietary carrot (Daucus carota) pectic polysaccharide (CRPP) blocked the expression of galectin-3 and G3BP more effectively (80%), whereas the expressions were reduced to 60% upon treatment with swallow root (Decalepis hamiltonii) pectic polysaccharide (SRPP), β‑carotene and deferoxamine (antiproliferative drug). Ginger (Gingiber officinale) pectic polysaccharide (GRPP) showed only 20% reduction. CRPP reduced 80% of tumor incidence followed by cyclophosphamide - a chemotherapeutic drug (77%), SRPP (67%) and GRPP (45%). Further 3-5 folds reduction in galectin-3/G3BP expression followed by infiltration of macrophages into the deeper layer of the skin by CRPP and SRPP suggested the anticancer property via immunomodulation. Surface Plasmon Resonance (SPR) studies confirm galectin-3 and G3BP interaction, which are disrupted during the treatment with dietary pectic polysaccharides (DPP) (Supplementary Scheme-1). Overall data demonstrate the role of DPPs as potential anticancer alternatives., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: This study aimed to examine the effect of CHO-E consumption after high-intensity exercise on insulin, cortisol hormones and blood glucose responses, which is important for performance and recovery in athletes. Methods: Sixteen volunteers, male athletes, participated into this study. Athletes were divided into two groups as experiment (CHO-E) and placebo (PLA). Blood was taken from the athletes three times as basal, post-exercise (PE) and 2 h after ingestion of supplement (PS). Results: When inter-group comparisons, insulin was significantly higher in the CHO-E group than the PLA group at the PS phase ( p  < .05). Cortisol significantly decreased in the CHO-E group at the PS compared to the PE ( p  < .05). Conclusions: Carbohydrate-electrolyte consumption after high-intensity exercise, accelerates the recovery process by providing optimal recovery, and enable the metabolism to remain in the anabolic state by preventing it from entering in the catabolic process as well as provides hormonal balance in metabolism.

This study aims to investigate the effects of Rhodiola rosea polysaccharide (RRP) on the growth performance and nonspecific immunity of red swamp crayfish Procambarus clarkia. RRP was prepared by hot water extraction and partly characterised by high-performance liquid chromatography and sugar composition analyses. Three diets supplemented with three different levels of RRP (0.2, 0.6 and 1 g kg diet -1 ) were formulated and tested for growth performance and nonspecific immunity of red swamp crayfish Procambarus clarkii, while a diet without any RRP supplementation served as control. After 8 weeks of feeding, body weight gain, feed efficiency, survival rate, phenoloxidase activity, superoxide dismutase activity, glutathione peroxidase level, total haemocyte count and number of hyaline cells, semigranular cells and granular cells and resistance to Aeromonas hydrophila were higher than those of the control. Moreover, based on the efficiency of RRP on the growth performance and nonspecific immunity of crayfish, the optimum dose of RRP was found to be 0.6 g kg diet -1 . Hence, intake of diets containing RRP could enhance the growth performance, immune responses and improve resistance of crayfish to infection by A. hydrophila., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

New Findings: What is the central question of this study? What are the effects of isomaltulose, an ingredient in carbohydrate-electrolyte beverages to maintain glycaemia and attenuate the risk of dehydration during exercise heat stress, on postexercise rehydration and physiological heat loss responses? What is the main finding and its importance? Consumption of a 6.5% isomaltulose-electrolyte beverage following exercise heat stress restored hydration following a 2 h recovery as compared to a 2% solution or water only. While the 6.5% isomaltulose-electrolytes increased plasma volume and plasma osmolality, which are known to modulate postexercise heat loss, sweating and cutaneous vascular responses did not differ between conditions. Consequently, ingestion beverages containing 6.5% isomaltulose-electrolytes enhanced postexercise rehydration without affecting heat loss responses., Abstract: Isomaltulose is a disaccharide carbohydrate widely used during exercise to maintain glycaemia and hydration. We investigated the effects of ingesting a beverage containing isomaltulose and electrolytes on postexercise hydration state and physiological heat loss responses. In a randomized, single-blind cross-over design, 10 young healthy men were hypohydrated by performing up to three 30 min successive moderate-intensity (50% heart rate reserve) bouts of cycling, each separated by 10 min, while wearing a water-perfusion suit heated to 45°C. The protocol continued until a 2% reduction in body mass was achieved. Thereafter, participants performed a final 15 min moderate-intensity exercise bout followed by a 2 h recovery. Following cessation of exercise, participants ingested a beverage consisting of (i) water only (Water), (ii) 2% isomaltulose (CHO-2%), or (iii) 6.5% isomaltulose (CHO-6.5%) equal to the volume of 2% body mass loss within the first 30 min of the recovery. Changes in plasma volume (ΔPV) after fluid ingestion were greater for CHO-6.5% compared with CHO-2% (120 min postexercise) and Water (90 and 120 min) (all P ≤ 0.040). Plasma osmolality remained elevated with CHO-6.5% compared with consumption of the other beverages at 30 and 90 min postexercise (all P ≤ 0.050). Urine output tended to be reduced with CHO-6.5% compared to other fluid conditions (main effect, P = 0.069). Rectal and mean skin temperatures, chest sweat rate and cutaneous perfusion did not differ between conditions (all P > 0.05). In conclusion, compared with CHO-2% and Water, consuming a beverage consisting of CHO-6.5% and electrolytes during recovery under heat stress enhances PV recovery without modulating physiological heat loss responses., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

Increasing the provision of non-fibrous carbohydrates (NFC) during the prepartum period is a feeding strategy that has been recommended to facilitate the transition to the onset of lactation and improve dairy cow performance, but results are contradictory, probably because most studies have confounded the effects of level and source of energy. The objective of this experiment was to evaluate the effect of the source of carbohydrate offered in the prepartum diet on postpartum cow performance. Holstein dairy cows (n=24) were assigned to receive diets with either low (LNFC), or high (HNFC) levels of NFC during the last 3 weeks before expected calving date according to a randomized complete block design. Soybean hulls and corn grain were the main energy ingredients in the LNFC and HNFC total mixed rations (TMR), respectively, and diets were designed to be isocaloric and isoproteic. After calving, all cows were managed as a single group until day 56 postpartum and grazed on improved pastures and were supplemented with a TMR. Body condition score evaluation and blood sampling were performed weekly throughout the experimental period to monitor the metabolic status of the animals. Prepartum glucose concentrations tended to be greater in HNFC than LNFC, but there was no effect on prepartum or postpartum insulin concentrations. Although nutrient intake was greater in the immediate week after calving in HNFC than LNFC, treatment did not affect milk yield and composition. In conclusion, increasing the NFC intake during the prepartum period, at a similar level of energy and protein intake, had a marginal residual effect on postpartum intake, and did not affect metabolic status or milk production.

This study investigated protective effects of mannan oligosaccharide (MOS) inclusion on growth performance, intestinal oxidative status, and barrier integrity of cyclic heat-stressed broilers. A total of 240 one-day-old chicks were allocated into 3 treatments of 10 replicates each. Control broilers reared at a thermoneutral temperature were fed a basal diet, whereas broilers in heat stress and MOS groups raised at a cyclic high temperature (32 to 33°C for 8 h/d) were given the basal diet supplemented with 0 or 250 mg/kg MOS, respectively. Compared with control group, heat stress decreased (P < 0.05) average daily gain and feed conversion ratio during grower, finisher, and entire periods, average daily feed intake during finisher and entire periods, and ileal superoxide dismutase activity at 42 D, whereas increased (P < 0.05) rectal temperature at 21 and 42 D and jejunal malondialdehyde content at 42 D. Dietary MOS increased (P < 0.05) average daily gain, average daily feed intake, and feed conversion ratio during finisher and entire periods, but decreased (P < 0.05) jejunal malondialdehyde concentration of heat-stressed broilers at 42 D. Heat stress decreased (P < 0.05) jejunal villus height (VH) and claudin-3 gene expression at 21 D, and VH and VH: crypt depth (CD) ratio in jejunum and ileum as well as mRNA abundances of jejunal mucin 2 and occludin, and ileal mucin 2, zonula occludens-1, and occludin, and claudin-3 at 42 D, whereas increased (P < 0.05) serum D-lactate acid content at 21 and 42 D, and serum diamine oxidase activity and jejunal CD at 42 D. The MOS supplementation increased (P < 0.05) jejunal VH at 21 D, VH and VH: CD of jejunum and ileum at 42 D, mRNA abundances of jejunal occludin and ileal mucin 2, zonula occludens-1, and occludin at 42 D, whereas reduced (P < 0.05) ileal CD at 42 D. These results suggested that MOS improved growth performance, and oxidative status and barrier integrity in the intestine of broilers under cyclic heat stress., (© 2019 Poultry Science Association Inc.)

Objective: Type I diabetes is a disease characterised by an extreme reduction in serum insulin levels. Diet and exercise have gained considerable attention in the treatment of diabetes. Therefore, this study was carried out to investigate the effect of diet with carbohydrate but without daily energy restriction on various metabolites (glucose, triglycerides, cholesterol, lactate), some electrolytes (Ca, Mg, Na, K, P, Cl) and essential metals (Mn, Co, Cu, Se, Zn, Fe) in the blood of rats with streptozotocin-induced diabetes. Materials and methods: Thirty-three male rats were divided into four groups of standard rat diet (SR)-fed control, SR-diet fed diabetics, low carbohydrate-standard protein-high fat (LCSPHF) diet-fed diabetics, and very low carbohydrate-high protein-high fat (VLCHPHF) diet-fed diabetics. Diabetes was induced by an i.p. injection of 50 mg/kg streptozotocin. The rats were fed with the specially prepared diets for 28 days. Results: The decreased-serum Cl and the increased-serum glucose levels were only the difference between the controls and SR diet-fed diabetic rats regarding to measured parameters. Lowering carbohydrate and increasing fat ratio in diet caused an increase in serum cholesterol and triglyceride levels leading to an increased-serum Fe and Ca, and decreased-serum Na and Cu levels in diabetic rats. Conclusion: The serum mineral changes should be taken into consideration together with the changes in serum glucose, cholesterol, and triglyceride levels for the secondary complications of diabetes mellitus.

Introduction: Clinical guidelines recommend that patients with type 1 diabetes (T1D) learn carbohydrate counting or similar methods to improve glycaemic control. Although systematic educating in carbohydrate counting is still not offered as standard-of-care for all patients on multiple daily injections (MDI) insulin therapy in outpatient diabetes clinics in Denmark. This may be due to the lack of evidence as to which educational methods are the most effective for training patients in carbohydrate counting. The objective of this study is to compare the effect of two different educational programmes in carbohydrate counting with the usual dietary care on glycaemic control in patients with T1D., Methods and Analysis: The study is designed as a randomised controlled trial with a parallel-group design. The total study duration is 12 months with data collection at baseline, 6 and 12 months. We plan to include 231 Danish adult patients with T1D. Participants will be randomised to one of three dietician-led interventions: (1) a programme in basic carbohydrate counting, (2) a programme in advanced carbohydrate counting including an automated bolus calculator or (3) usual dietary care. The primary outcome is changes in glycated haemoglobin A1c or mean amplitude of glycaemic excursions from baseline to end of the intervention period (week 24) between and within each of the three study groups. Other outcome measures include changes in other parameters of plasma glucose variability (eg, time in range), body weight and composition, lipid profile, blood pressure, mathematical literacy skills, carbohydrate estimation accuracy, dietary intake, diet-related quality of life, perceived competencies in dietary management of diabetes and perceptions of an autonomy supportive dietician-led climate, physical activity and urinary biomarkers., Ethics and Dissemination: The protocol has been approved by the Ethics Committee of the Capital Region, Copenhagen, Denmark. Study findings will be disseminated widely through peer-reviewed publications and conference presentations., Trial Registration Number: ClinicalTrials.gov Registry (NCT03623113)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Extensive skeletal muscle accumulation (ESMA) of F-FDG adversely affects the visual interpretation of F-FDG PET/computed tomography (CT) images. We mainly investigated factors related to ESMA that are based on food compositions., Methods: From January 2018 to June 2018, a total of 5554 patients underwent F-FDG PET/CT imaging with at least a 4-hour fast. Among them, 49 patients who exhibiting ESMA and 50 sex-matched and age-matched patients without ESMA were included in the study. The following factors were analysed: BMI, plasma glucose, gastric residue, the total energy of food the patient had before F-FDG injection and the percentages of the food ingredients. Multivariate analysis was performed to evaluate related risk factors between two groups., Results: In brief, 49 cases and 50 controls were identified. The BMI, gross energy, gross energy of protein, gross energy of carbohydrate and proportion of protein of case group were not significantly different from that of the controls (P ≥ 0.05). The plasma glucose was significantly higher in the case group than in the control group (P = 0.002). The positivity of gastric food residue would more easily demonstrate ESMA than those without gastric food residue (P < 0.0001). The fasting time before scan, gross energy of fat, proportion of fat and proportion of carbohydrate in case group were significantly different with control group. After multivariate analysis, fasting time, gastric food residue and proportion of carbohydrate were investigated as independent risk factors., Conclusion: To avoid ESMA, patients should take a lower proportion of carbohydrate before receiving an F-FDG administration.

Purpose: Manipulation of meal macronutrient may be a useful way to modulate meal-induced thermogenesis (MIT) to induce increases in energy expenditure. The objective of this study was to examine in adolescents with obesity and of healthy weight and the effect of a high protein and high carbohydrate meal on MIT., Methods: An acute cross-over study with adolescents aged 11-19 years was undertaken. Participants consumed in random order, a high 79% carbohydrate (HCHO), and a high 55% protein (HP) meal (adjusted to 25% of energy requirements). MIT and subjective appetite were assessed for 4 h postprandial and an ad libitum lunch served. Data calculated as total AUC and expressed as mean ± SEM., Results: Thirteen adolescents with obesity (mean BMI z score 2.3 ± 0.1) and 13 healthy weight (BMI z score 0.0 ± 0.2) participated. Mean MIT (% of energy intake) was greater after the HP (8.19 ± 0.709%) compared with the HCHO meal (4.36 ± 0.480%) (p < 0.001). The HP compared with the HCHO meal promoted greater fullness (12,994 ± 1208 vs 11,186 ± 1220 mm/4 h) (p = 0.016) and decreased hunger (8868 ± 1315 vs 10984 mm ± 1438 mm/4 h) (p = 0.007). These effects observed were independent of body weight., Conclusions: High protein meals can increase MIT and fullness and reduce hunger compared with high carbohydrate meals in adolescents with obesity. Future research is warranted to determine if MIT can be targeted through manipulation of dietary choices to support weight management strategies., Trial Registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Trial ID: ACTRN12612001066875.

Scope: Obesity causes DNA damage, which is causally related to several disorders including cancer, infertility, and cognitive dysfunctions. The aim of this study is to investigate whether weight loss improves the integrity of the genetic material., Methods and Results: Overweight mice are fed ad libitum either with a Western diet (WD), with a 40% caloric restricted WD, or with a high carbohydrate low protein (HCLP) diet. Caloric restriction and also the HCLP diet lead to ca. 30% weight loss, which is paralleled by decreased DNA damage ("comet" formation) and oxidative damage of purines in inner organs, additionally the activity of nucleotide excision repair increased. The effects are more pronounced in animals that have received the HCLP chow. Results of biochemical analyses indicate that the reduction of DNA damage is associated with a decrease of pro-inflammatory cytokines and lower insulin levels., Conclusion: The study indicates that weight loss may prevent obesity-associated adverse health effects due to reduction of overall DNA damage., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We investigated the effect of oral curcumin, on bone health of rats fed a high-fructose diet. Suckling pups (males = 65, females = 63) were gavage with 0.5% DMSO, curcumin (500 mg/kg), fructose (20%, w/v) or a combination of curcumin and fructose daily from postnatal days 6 to 21. Then the rats were weaned onto normal rat feed for six weeks and each group was sub-divided into two subgroups: one had plain tap water and the other had fructose (20%, w/v) to drink. Blood was assayed for plasma total osteocalcin. Morphometry and radiographic bone density assessments were made on the femora and tibiae. The lengths, masses and Seedor indices of the bones were similar (p > 0.05, ANOVA) across the groups. Males that received curcumin with or without fructose during suckling and weaned onto a high-fructose diet had lower (p ≤ 0.05, ANOVA) osteocalcin concentration versus the other males. Similarly, in females rats, curcumin alone or administered with fructose resulted in lower (p ≤ 0.05, ANOVA) osteocalcin concentration versus female rats administered the vehicle control. Neonatal curcumin-induced decrease in plasma total osteocalcin concentration may predispose to adverse consequences on glucose metabolism and bone health.

Scope: The epithelial glycocalyx development is of great importance for microbial colonization. Human milk oligosaccharides (hMOs) and non-digestible carbohydrates (NDCs) may modulate glycocalyx development., Methods and Results: The effects of hMOs and NDCs on human gut epithelial cells (Caco2) are investigated by quantifying thickness and area coverage of adsorbed albumin, heparan sulfate (HS), and hyaluronic acid (HA) in the glycocalyx. Effects of hMOs (2'-FL and 3-FL) and NDCs [inulins with degrees of polymerization (DP) (DP3-DP10, DP10-DP60, DP30-DP60) and pectins with degrees of methylation (DM) (DM7, DM55, DM69)] are tested using immunofluorescence staining at 1 and 5 days stimulation. HMOs show a significant enhancing effect on glycocalyx development but effects are structure-dependent. 3-FL induces a stronger albumin adsorption and increases HS and HA stronger than 2'-FL. The DP3-DP10, DP30-60 inulins also increase glycocalyx development in a structure-dependent manner as DP3-DP10 selectively increases HS, while DP30-DP60 specifically increases HA. Pectins have less effects, and only increase albumin adsorption., Conclusion: Here, it is shown that 2'-FL and 3-FL and inulins stimulate glycocalyx development in a structure-dependent fashion. This may contribute to formulation of effective hMO and NDC formulations in infant formulas to support microbial colonization and gut barrier function., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Historically, low-carbohydrate (CHO) and very-low-CHO diets have been used for weight loss. Recently, these diets have been promoted for type 2 diabetes (T2D) management. This scientific statement provides a comprehensive review of the current evidence base available from recent systematic reviews and meta-analyses on the effects of low-CHO and very-low-CHO diets on body weight, lipoprotein lipids, glycemic control, and other cardiometabolic risk factors. In addition, evidence on emerging risk factors and potential safety concerns of low-CHO and very-low-CHO diets, especially for high-risk individuals, such as those with genetic lipid disorders, was reviewed. Based on the evidence reviewed, low-CHO and very-low-CHO diets are not superior to other dietary approaches for weight loss. These diets may have advantages related to appetite control, triglyceride reduction, and reduction in the use of medication in T2D management. The evidence reviewed showed mixed effects on low-density lipoprotein cholesterol levels with some studies showing an increase. There was no clear evidence for advantages regarding effects on other cardiometabolic risk markers. Minimal data are available regarding long-term (>2 years) efficacy and safety. Clinicians are encouraged to consider the evidence discussed in this scientific statement when counseling patients on the use of low-CHO and very-low-CHO diets., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Dietary carbohydrates have been shown to influence cognitive performance and satiety in children. However, it remains unclear whether the carbohydrate source is a primary determinant of cognitive performance and satiety. The objective was to compare the effects of white potatoes and other carbohydrate-containing foods on cognitive performance, glycemic response, and satiety in children. On 6 separate mornings, in random order, children ( n = 22) consumed 50 g of available carbohydrates from microwaved mashed potatoes (prepared from fresh potatoes then frozen), deep-fried potato strips (French fries), hash browns, white rice, white beans, or skipped a meal. Cognitive performance, glycemic response, and satiety were measured over 180 min. Cognitive performance was measured using a battery of tests assessing verbal declarative memory, spatial memory, short-term memory, working memory, and information processing speed. Although cognitive performance after the treatment meals did not differ from meal skipping, children recalled more words after French fries (9.1 ± 0.4 words) compared with mashed potatoes (8.2 ± 0.3 words; p = 0.001) and white rice (8.4 ± 0.3 words; p = 0.04) on the verbal declarative memory test. Blood glucose concentrations were higher after white rice compared with white beans, mashed potatoes, and hash browns ( p < 0.05). Change from baseline subjective average appetite (mm/kcal) was lower after mashed potatoes compared with all other treatment meals ( p < 0.05). In conclusion, verbal declarative memory was higher after French fries and subjective average appetite was lower after mashed potatoes. Future longitudinal studies are needed to confirm these short-term findings and to elucidate the mechanism of action.

Published evidence exploring the effects of dietary resistant starch (RS) on human cardiometabolic health is inconsistent. This review aimed to investigate the effect of dietary RS type 2 (RS2) supplementation on body weight, satiety ratings, fasting plasma glucose, glycated hemoglobin (HbA1c), insulin resistance and lipid levels in healthy individuals and those with overweight/obesity, the metabolic syndrome (MetS), prediabetes or type 2 diabetes mellitus (T2DM). Five electronic databases were searched for randomized controlled trials (RCTs) published in English between 1982 and 2018, with trials eligible for inclusion if they reported RCTs involving humans where at least one group consumed ≥ 8 g of RS2 per day and measured body weight, satiety, glucose and/or lipid metabolic outcomes. Twenty-two RCTs involving 670 participants were included. Meta-analyses indicated that RS2 supplementation significantly reduced serum triacylglycerol concentrations (mean difference (MD) = -0.10 mmol/L; 95% CI -0.19, -0.01, P = 0.03) in healthy individuals ( n = 269) and reduced body weight (MD = -1.29 kg; 95% CI -2.40, -0.17, P = 0.02) in people with T2DM ( n = 90). However, these outcomes were heavily influenced by positive results from a small number of individual studies which contradicted the conclusions of the majority of trials. RS2 had no effects on any other metabolic outcomes. All studies ranged from 1-12 weeks in duration and contained small sample sizes (10-60 participants), and most had an unclear risk of bias. Short-term RS2 supplementation in humans is of limited cardiometabolic benefit.

Objective: In our randomized controlled trial, we investigated the impact of healthy eating (HE) aiming for restricted gestational weight gain (GWG) and physical activity (PA) interventions on maternal and neonatal lipid metabolism., Research Design and Methods: Obese pregnant women ( n = 436) were included before 20 weeks' gestation and underwent glucose testing (oral glucose tolerance test) and lipid profiling at baseline and 24-28 and 35-37 gestational weeks after an at least 10-h overnight fast. This secondary analysis had a factorial design with comparison of HE ( n = 221) versus no HE ( n = 215) and PA ( n = 218) versus no PA ( n = 218). Maternal changes in triglycerides (TG), LDL cholesterol, HDL cholesterol, free fatty acids (FFAs), and leptin from baseline to end of pregnancy and neonatal outcomes were analyzed using general linear models with adjustment for relevant parameters., Results: At 24-28 weeks' gestation, FFAs (mean ± SD, 0.60 ± 0.19 vs. 0.55 ± 0.17 mmol/L, P < 0.01) were increased after adjustment for FFA at baseline, maternal age, BMI at time of examination, gestational week, insulin resistance, self-reported food intake, self-reported physical activity, and maternal smoking, and GWG was lower (3.3 ± 2.6 vs. 4.3 ± 2.8 kg, P < 0.001, adjusted mean differences -1.0 [95% CI -1.5; -0.5]) in HE versus no HE. Fasting glucose levels (4.7 ± 0.4 vs. 4.6 ± 0.4 mmol/L, P < 0.05) and 3-β-hydroxybutyrate (3BHB) (0.082 ± 0.065 vs. 0.068 ± 0.067 mmol/L, P < 0.05) were higher in HE. Significant negative associations between carbohydrate intake and FFA, 3BHB, and fasting glucose at 24-28 weeks' gestation were observed. No differences between groups were found in oral glucose tolerance test or leptin or TG levels at any time. Furthermore, in PA versus no PA, no similar changes were found. In cord blood, elevated FFA levels were found in HE after full adjustment (0.34 ± 0.22 vs. 0.29 ± 0.16 mmol/L, P = 0.01)., Conclusions: HE intervention was associated with reduced GWG, higher FFAs, higher 3BHB, and higher fasting glucose at 24-28 weeks of gestation, suggesting induction of lipolysis. Increased FFA was negatively associated with carbohydrate intake and was also observed in cord blood. These findings support the hypothesis that maternal antenatal dietary restriction including carbohydrates is associated with increased FFA mobilization., (© 2019 by the American Diabetes Association.)

This study aimed to determine the relative efficacy of the macronutrients, protein, fat and carbohydrate to induce satiation and satiety in rats in relation to macronutrient activation of neurons in the nucleus of the solitary tract (NTS). Male Sprague Dawley rats were schedule-fed twice a day for 2 h, receiving 100% of daily ad-libitum energy intake. On test day 1, 30 min before the first scheduled meal of the day, rats were gavaged with an 8 kcal isocaloric, isovolumetric solution of a glucose, lipid or peptone macronutrient solution or a non-caloric saline solution. To assess satiation, thirty minutes later rats were given access to food for 2 h and food intake determined. A second 2 h food access period 3 h later was used for assessment of satiety. On the second test day, rats were gavaged as before and killed 90 min after food presentation. Blood was collected for measurement of circulating metabolic markers. Brains were removed for analysis of c-Fos expression by in situ hybridization in the NTS. Rats which received saline consumed a similar amount of food compared to pre-gavage intakes. However, rats gavaged with a caloric macronutrient solution all reduced food intake by 18-20 kcal. Interestingly, the reduction in caloric intake was greater than the caloric value of the macronutrient solution gavaged and was sustained following the second scheduled meal. Quantification by in situ hybridization of c-Fos mRNA expression in the NTS 90 min post-gavage, showed a significant increase with each macronutrient, but was 24-29% higher with a lipid or peptone gavage compared to a glucose gavage. In conclusion, when delivered directly to the stomach, all macronutrients can be equally effective in inducing satiation with significant neuronal activation in the NTS of the hindbrain., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background & Aims: Carbohydrates (CHO) and leucine (LEU) both have insulinotropic properties, and could therefore enhance the protein anabolic capacity of dietary proteins, which are important nutrients in preventing muscle loss in patients with Chronic Obstructive Pulmonary Disease (COPD). LEU is also known to activate protein anabolic signaling pathways independent of insulin. Based on our previous findings in COPD, we hypothesized that whole body protein anabolism is enhanced to a comparable extent by the separate and combined co-ingestion of CHO and LEU with protein., Methods: To disentangle the protein anabolic effects of CHO and/or free LEU when co-ingested with a high-quality protein, we studied 10 patients with moderate to very severe COPD and dyspnea (GOLD: II-IV, mMRC dyspnea scale ≥ 2), at risk for muscle loss, and 10 healthy age- and gender-matched controls. On four occasions, in a single-blind randomized crossover design, each subject ingested a drink containing 0.6 g/kg fat-free mass (ffm) hydrolyzed casein protein with, a) no add-ons (protein), b) 0.3 g/kg ffm CHO (protein + CHO), c) 0.095 g/kg ffm leucine (protein + LEU), d) both add-ons (protein + CHO + LEU). Whole body protein breakdown (PB), protein synthesis (PS), and net protein balance (= PS - PB) were measured by IV primed and continuous infusion of L-[ring- 2 H 5 ]-phenylalanine and L-[ 13 C 9 , 15 N]-tyrosine. L-[ 15 N]-phenylalanine was added to the protein drinks to measure splanchnic extraction., Results: In both groups, whole body PS, PB and net protein balance responses were comparable between the four protein drinks, despite higher postprandial plasma LEU concentrations for the LEU supplemented drinks (P < 0.05), and higher insulin concentrations for the CHO supplemented drinks as compared to the protein only drink (P < 0.05)., Conclusions: Adding CHO and/or LEU to a serving of high-quality protein does not further augment whole body protein anabolism in dyspneic COPD patients at risk for muscle loss or healthy older adults., Trial Registry: ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The liver enzyme cytochrome P450 1A2 (CYP1A2) is responsible for 90% of caffeine metabolism, while caffeine exerts many of its effects via antagonist binding to adenosine A2a receptors (ADORA2A). This study aimed to examine whether functional single nucleotide polymorphisms (SNPs) in 1976T > C (ADORA2A; rs5751876) and -163C > A (CYP1A2; rs762551) influence the effect of caffeine on the postprandial glucose (GLU) response to a carbohydrate meal. We report that individuals with the 1976T > C CC, but not CT/TT genotypes display elevated GLU levels after consuming caffeine and carbohydrate (CHO + CAFF) versus carbohydrate only (CHO). The GLU area under the curve (AUC) was also greater during the CHO + CAFF condition compared to the CHO condition in CC, but not the CT/TT genotypes. The -163C > A AC/CC, but not AA, genotypes displayed greater GLU concentrations 60-min post meal during CHO + CAFF versus CHO. Our data suggest that caffeine-induced impairments in postprandial glycaemia are related to 1976T > C and -163C > A SNPs.

Objective: This study examines the long-term effects of ingesting hydrolyzed beef protein versus carbohydrate on indirect markers of immunity during 10 weeks of endurance training in master-aged triathletes ( n  = 16, age 35-60 years). Methods: Participants were randomly assigned to either a hydrolyzed beef protein (PRO, n  = 8) or nonprotein isoenergetic carbohydrate (CHO, n  = 8) condition, which consisted of ingesting 20 g of each supplement, mixed with water, once a day immediately post workout, or before breakfast on nontraining days. Salivary human neutrophil peptides (HNP1-3) were measured before and after performing an incremental endurance test to volitional exhaustion at both pre and post intervention. Additionally, baseline levels of platelets, neutrophils, eosinophil basophils, monocytes, and lymphocytes were determined at pre and post intervention. Results: No significant changes in baseline concentration and secretion rate of salivary HNP1-3 were observed for either treatment. The CHO group showed a nonsignificant decrease in resting HNP1-3 concentrations following the intervention ( p  = 0.052, effect size d  = 0.53). Protein supplementation demonstrated a significant reduction in lymphocyte counts pre to post intervention (mean [SD]: 2.30 [0.57] vs. 1.93 [0.45] 10 3 /mm 3 , p  = 0.046, d  = 0.77), along with a moderate but not statistically significant increase ( d  = 0.75, p  = 0.051) of the neutrophil-to-lymphocyte ratio. Conclusions: In master-aged triathletes, postworkout ingestion of only protein, with no carbohydrate, may not be as effective as carbohydrate alone to attenuate negative long-term changes of some salivary and cellular immunological markers. Future studies should consider the co-ingestion of both macronutrients.

Our objective was to evaluate the effects of diet starch concentration and fermentability on energy intake and energy balance during the early postpartum (PP) period. Fifty-two multiparous Holstein cows were used in a randomized block design experiment with a 2 × 2 factorial arrangement of treatments. Treatment rations were formulated to 22% or 28% starch concentration (LS and HS, respectively) with dry ground corn (DGC) or high moisture corn (HMC) as the primary starch source. Rations were formulated for 22% forage neutral detergent fiber (NDF) and 17% crude protein and fed from 1 to 23 d PP. Starch concentration was adjusted by altering concentrations of corn grain and soyhulls. Dry matter intake and milk yield were measured daily, and milk components, milk composition, body condition score (BCS), body weight (BW), and back fat thickness (BFT) were measured weekly. Feeds and refusals as well as fecal samples were collected, and digestibility was determined weekly. High moisture corn (HMC) decreased dry matter and net energy (NE L ) intakes compared with DGC more when included in an HS diet (3.9 kg/d and 3.2 Mcal/d) than in an LS diet (0.9 kg/d and 0.6 Mcal/d). The HMC treatment decreased NDF digestibility 3.7 percentage units compared with DGC when included in the HS diet but had little effect when included in an LS diet. Compared with DGC, HMC increased weekly BW and BFT loss when included in an HS diet (-34.7 vs. -8.4 kg/wk and -0.12 vs. -0.10 cm/wk) and decreased weekly BW loss but increased weekly BFT loss when included in an LS diet (-18.9 vs. -21.4 kg/wk and -0.11 vs. -0.02 cm/wk). Weekly BCS loss increased for HMC compared with DGC (-0.33 vs. -0.23 unit/wk). High moisture corn also decreased milk NE L output compared with DGC (28.2 vs. 31 Mcal/d), but had little effect on energy balance, which was improved by HS compared with LS (-14.7 vs. -16.8 Mcal/d). Over time, concentrations of milk de novo fatty acids (<16 carbons) increased and concentration of milk preformed fatty acids (>16 carbons) decreased for all treatments, but yields of both sources as well as yield of mixed fatty acids (C16:0 plus C16:1 cis-9 and iso-C16:0) decreased over time with increased SF. Feeding HMC decreased energy intake and milk energy output, but it had little effect on energy balance during the early PP period., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

In addition to oxidative stress due to the increase of free radicals, estrogen deficiency is associated with changes in enzymatic activity, glutathione redox ratio (GSH/GSSG), and the content of oxidative markers such as malondialdehyde. Tibolone, a synthetic steroid, has been used as an elective treatment for the relief of menopausal symptoms. However, the acute effects of hormonal therapy with tibolone on metabolic parameters and oxidative stress markers associated with the first stages of estrogen deficiency are still unknown. The study aimed to evaluate if the acute administration of tibolone reduces oxidative stress in ovariectomized rats fed high-fat-and-fructose diet. Rats were fed a standard diet or a diet consisting of 10% lard-supplemented chow and 20% high-fructose syrup in the drinking water plus tibolone or vehicle for seven days. Weight, cholesterol, triglycerides, and glucose levels, as well as antioxidant enzymes and oxidative stress markers were quantified in the serum of each experimental group. It was observed that seven days of diet and tibolone treatment in the ovariectomized group reduced weight, triglycerides, cholesterol, glucose levels and advanced glycation end products but did not change GSH/GSSG ratio nor the enzymatic activity of superoxide dismutase. Also, both glutathione peroxidase and glutathione reductase activity decreased, as well as malondialdehyde levels. These results suggest that the acute treatment with tibolone prevented the changes in the metabolic parameters analyzed as well as the increase in the levels of malondialdehyde and AGEs induced by ovariectomy and high-fat diet., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

A 10-week feeding trial was conducted to investigate the response of glucosensing system to glucose in Japanese flounder Paralichthys olivaceus (initial body weight: 7.14 ± 0.10 g) fed diets with different carbohydrate content. Two experimental diets were designed as carbohydrate free (CF) and suitable carbohydrate (SC) supplementation, respectively. The dietary carbohydrate contents were 0.93% and 15.6%, respectively. After a 10-week feeding trial, a glucose tolerance test (GTT) was performed. Results showed that after the last meal in the feeding trial, the blood glucose of fish fed with diet CF peaked at 3 h (4.64 ± 0.29 mM), the duration of hyperglycemia was about 5 h (1-6 h). The blood glucose in SC group peaked at 9 h (3.28 ± 0.66 mM), and the duration of hyperglycemia was approximately 6 h (6-12 h). After GTT, blood glucose reached the first peak at 6 h both in the two groups, and the duration of hyperglycemia was obvious 24 h. During the 3-12 h after injection, blood glucose level in SC group was significantly higher than that in CF group. However, blood glucose level in group SC was significantly lower than that in group CF at 24 h. The blood glucose level decreased to half of the peak at 10.97 h after injection of glucose in SC group and at 27.26 h in CF group. The 6-24 h clearance ability in SC group (6.57 ± 1.68%/h) was significantly higher than that in CF group (2.81 ± 1.11%/h). Compared with CF diet, SC diet significantly increase the expression of glucosensing-related genes including glucose facilitative transporter type 2, glucokinase, inward rectifier K + channel pore type 6.2, sulfonylurea receptor, carnitine palmitoyltransferase 1b, hydroxyacyl-CoA dehydrogenase, cytochrome c oxidase subunit 4, mitochondrial uncoupling protein 2a, liver X receptor, sodium/glucose co-transporter 1, a heterodimer of type 1 receptor subunits depending on T1R2 + T1R3 in liver and intestine. Meanwhile, activities of glucokinase, pyruvate kinase and glycogen synthase in liver, and hepatic glycogen content were also increased. In conclusion, glucosensing systems in Japanese flounder are responsive to dietary carbohydrate levels, especially the suitable dietary carbohydrate level, at which the glucose tolerance capacity of Japanese flounder was improved., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Strong evidence during the last few decades has highlighted the importance of nutrition for sport performance, the role of carbohydrates (CHO) being of special interest. Glycogen is currently not only considered an energy substrate but also a regulator of the signaling pathways that regulate exercise-induced adaptations. Thus, low or high CHO availabilities can result in both beneficial or negative results depending on the purpose. On the one hand, the depletion of glycogen levels is a limiting factor of performance during sessions in which high exercise intensities are required; therefore ensuring a high CHO availability before and during exercise is of major importance. A high CHO availability has also been positively related to the exercise-induced adaptations to resistance training. By contrast, a low CHO availability seems to promote endurance-exercise-induced adaptations such as mitochondrial biogenesis and enhanced lipolysis. In the present narrative review, we aim to provide a holistic overview of how CHO availability impacts physical performance as well as to provide practical recommendations on how training and nutrition might be combined to maximize performance. Attending to the existing evidence, no universal recommendations regarding CHO intake can be given to athletes as nutrition should be periodized according to training loads and objectives.

Background: We investigated the effects of preoperative oral carbohydrate loading on intraoperative catabolism, nutritional parameters, and adipocytokine levels during anesthesia., Methods: Study participants were randomized to two groups who were allowed to consume either no more than 250 mL of 18% oral carbohydrate solution (Arginaid Water: AW group) or no more than 500 mL of plain water (PW group) within the 2 hours before surgery, with no intraoperative glucose administration. Percentage changes from preoperative values of resting metabolic rate (RMR) and total body water (TBW), determined by bioelectrical impedance analysis (BIA), were compared. Blood levels of serum ketone bodies, free fatty acids (FFAs), insulin, 3-methyl histidine, blood glucose, retinol binding protein, adiponectin, and leptin were measured. BIA measurement and blood sampling were performed on entry to the operating room (M1) and 2 hours after the induction of anesthesia (M2). Chi squared test, Mann-Whitney U test, and Wilcoxon's test were used for comparisons of parameters. P values less than 0.05 constituted a significant difference., Results: Seventeen patients per group (34 patients total) were enrolled. RMR and TBW values did not differ between M1 and M2 measurements. Participants in the AW group had lower blood ketone body and FFA levels and higher insulin levels at M1. However, their ketone body and FFA levels rose and insulin levels fell after 2 hours, although ketone body and FFA levels in the AW group were still lower than those in the PW group. Although retinol binding protein, adiponectin, and leptin levels were not different in terms of preoperative oral carbohydrate loading, the levels of these substances in both groups were lower after 2 hours compared with levels on operating room entry., Conclusions: Preoperative oral carbohydrate loading without intraoperative glucose administration appears to suppress catabolism for 2 hours after the start of surgery., Competing Interests: The authors have declared that no competing interests exist.

G 0 /G 1 switch gene 2 (G0S2) is a specific inhibitor of adipose triglyceride lipase (ATGL), the rate-limiting enzyme for intracellular lipolysis. Recent studies show that G0S2 plays a critical role in promoting triacylglycerol (TG) accumulation in the liver, and its encoding gene is a direct target of a major lipogenic transcription factor liver X receptor (LXR)α. Here we sought to investigate a lipolysis-independent role of G0S2 in hepatic triglyceride synthesis. Knockdown of G0S2 decreased hepatic TG content in mice with ATGL ablation. Conversely, overexpression of G0S2 promoted fatty acid incorporation into TGs and diacylglycerols in both wild-type and ATGL-deficient hepatocytes. Biochemical characterization showed that G0S2 mediates phosphatidic acid synthesis from lysophosphatidic acid (LPA) and acyl-coenzyme A. In response to a high-sucrose lipogenic diet, G0S2 is up-regulated via LXRα and required for the increased TG accumulation in liver. Furthermore, deletion of a distinct 4-aa motif necessary for the LPA-specific acyltransferase (LPAAT) activity impaired G0S2's ability to mediate TG synthesis both in vitro and in vivo . These studies identify G0S2 as a dual-function regulator of lipid metabolism as well as a novel mechanism whereby hepatic TG storage is promoted in response to lipogenic stimulation. In addition to its role as a lipolytic inhibitor, G0S2 is capable of directly promoting TG synthesis by acting as a lipid-synthesizing enzyme.-Zhang, X., Xie, X., Heckmann, B. L., Saarinen, A. M., Gu, H., Zechner, R., Liu, J. Identification of an intrinsic lysophosphatidic acid acyltransferase activity in the lipolytic inhibitor G 0 /G 1 switch gene 2 (G0S2).

Clarke, JS, Highton, J, Close, GL, and Twist, C. Carbohydrate and caffeine improves high-intensity running of elite rugby league interchange players during simulated match play. J Strength Cond Res 33(5): 1320-1327, 2019-The study examined the effects of carbohydrate and caffeine ingestion on simulated rugby league interchange performance. Eight male elite rugby league forwards completed 2 trials of a rugby league simulation protocol for interchange players 7 days apart in a randomized crossover design, ingesting either carbohydrate (CHO; 40 g·h) or carbohydrate and caffeine (CHO-C) (40 g·h + 3 mg·kg) drink. Movement characteristics, heart rate, ratings of perceived exertion (RPE), and countermovement jump (CMJ) height were measured during the protocol. CHO-C resulted in likely to very likely higher mean running speeds (effect size [ES] 0.43-0.75), distance in high-intensity running (ES 0.41-0.64), and mean sprint speeds (ES 0.39-1.04) compared with CHO. Heart rate was possibly to very likely higher (ES 0.32-0.74), and RPE was likely to very likely lower (ES -0.53 to 0.86) with CHO-C. There was a likely trivial to possibly higher CMJ in CHO-C compared with CHO (ES 0.07-0.25). The coingestion of carbohydrate with caffeine has an ergogenic effect to reduce the sense of effort and increase high-intensity running capability that might be used to enhance interchange running performance in elite rugby league players.

High red meat intake is associated with the risk of colorectal cancer (CRC), whereas dietary fibers, such as resistant starch (RS) seemed to protect against CRC. The aim of this study was to determine whether high-amylose potato starch (HAPS), high-amylose maize starch (HAMS), and butyrylated high-amylose maize starch (HAMSB)-produced by an organocatalytic route-could oppose the negative effects of a high-protein meat diet (HPM), in terms of fermentation pattern, cecal microbial composition, and colonic biomarkers of CRC. Rats were fed a HPM diet or an HPM diet where 10% of the maize starch was substituted with either HAPS, HAMS, or HAMSB, for 4 weeks. Feces, cecum digesta, and colonic tissue were obtained for biochemical, microbial, gene expression (oncogenic microRNA), and immuno-histochemical (O 6 -methyl-2-deoxyguanosine (O 6 MeG) adduct) analysis. The HAMS and HAMSB diets shifted the fecal fermentation pattern from protein towards carbohydrate metabolism. The HAMSB diet also substantially increased fecal butyrate concentration and the pool, compared with the other diets. All three RS treatments altered the cecal microbial composition in a diet specific manner. HAPS and HAMSB showed CRC preventive effects, based on the reduced colonic oncogenic miR17-92 cluster miRNA expression, but there was no significant diet-induced differences in the colonic O 6 MeG adduct levels. Overall, HAMSB consumption showed the most potential for limiting the negative effects of a high-meat diet.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in humans, and ranges from steatosis to non-alcoholic steatohepatitis (NASH), the latter with risk of progression to cirrhosis. The Göttingen Minipig has been used in studies of obesity and diabetes, but liver changes have not been described. The aim of this study was to characterize hepatic changes in Göttingen Minipigs with or without diabetes, fed a diet high in fat, fructose, and cholesterol to see if liver alterations resemble features of human NAFLD/NASH., Methods: Fifty-four male castrated minipigs (age 6 to 7 months) were distributed into four groups and diet-fed for 13 months. Groups were: lean controls fed standard diet (SD, n = 8), a group fed high fat/fructose/cholesterol diet (FFC, n = 16), a group fed high fat/fructose/cholesterol diet but changed to standard diet after 7 months (diet normalization, FFC/SD, n = 16), and a streptozotocin-induced diabetic group fed high fat/fructose/cholesterol diet (FFC DIA , n = 14). At termination, blood samples for analyses of circulating biomarkers and liver tissue for histopathological assessment and analyses of lipids and glycogen content were collected., Results: In comparison with SD and FFC/SD, FFC and FFC DIA pigs developed hepatomegaly with increased content of cholesterol, whereas no difference in triglyceride content was found. FFC and FFC DIA groups had increased values of circulating total cholesterol and triglycerides and the hepatic circulating markers alkaline phosphatase and glutamate dehydrogenase. In the histopathological evaluation, fibrosis (mainly located periportally) and inflammation along with cytoplasmic alterations (characterized by hepatocytes with pale, granulated cytoplasm) were found in FFC and FFC DIA groups compared to SD and FFC/SD. Interestingly, FFC/SD also had fibrosis, a feature not seen in SD. Only two FFC and three FFC DIA pigs had > 5% steatosis, and no hepatocellular ballooning or Mallory-Denk bodies were found in any of the pigs., Conclusions: Fibrosis, inflammation and cytoplasmic alterations were characteristic features in the livers of FCC and FFC DIA pigs. Overall, diabetes did not exacerbate the hepatic changes compared to FFC. The limited presence of the key human-relevant pathological hepatic findings of steatosis and hepatocellular ballooning and the variation in the model, limits its use in preclinical research without further optimisation.

For an increased incorporation of plant ingredients in aquafeeds at the expense of fish meal (FM) and fish oil (FO), more knowledge is needed on the effects at the intestine level of dietary vegetable oils (VO) and carbohydrates (CH), and of possible interactions. For that purpose, in this study, the activities of digestive pancreatic enzymes (amylase, lipase, total alkaline proteases), gut microbiota, and histomorphology were assessed in gilthead sea bream (IBW 71.0 ± 1.5 g) fed four diets differing in lipid source (FO or a blend of VO) and carbohydrate content (0% or 20% gelatinized starch) for 81 days. No major changes in digestive enzyme activities were noticed in fish fed the experimental diets. Dietary VO, but not CH content, modified intestinal microbial profile, by increasing the similarity of bacterial communities. Especially when combined with CH, dietary VO promoted abnormal enterocyte architecture. Liver histology was also accessed, and an increased cytoplasmic vacuolization of hepatocytes was related with dietary CH inclusion, being only significantly different in fish fed FO-based diets. Overall, nutritional interactions between dietary lipid source and carbohydrate content were not observed on digestive enzyme activities and microbial profile. However, the intestine histological modifications observed in fish fed the VOCH+ diet suggest a negative interaction between dietary VO and CH. This requires a more in depth assessment in future studies as it can have negative consequences at a functional level.

This study aims to investigate the effects of dietary Porphyra yezoensis polysaccharides (PPs) on growth performance and nonspecific immunity of juvenile grass carp (Ctenopharyngodon idella). Four hundreds of juvenile grass carps were randomly divided into four groups, i.e. one control group received basal diet and three treatment groups received diets supplemented with three different levels of PPs (1, 3, and 5 g kg -1 ) and tested for growth performance, survival percent, intestine digestive-enzyme activities, superoxide dismutase (SOD) activity, catalase (CAT) activity, glutathione peroxidase (GPx) activity, serum total protein, lysozyme, alkaline phosphatase, complement C3 and complement C4 and resistance to Aeromonas hydrophila of juvenile grass carp. After 60 days of feeding, the diet supplemented with an appropriate dose of PPs significantly increased growth performance, survival percent, intestine digestive-enzyme activities, SOD activity, CAT activity, GPx activity, serum lysozyme, alkaline phosphatase, complement C3, and complement C4 and resistance to Aeromonas hydrophila of juvenile grass carp compared with the control group and the optimum dose of PPs was found to be 3 g kg -1 . Results showed that dietary PPs can improve growth performance and nonspecific immunity of juvenile grass carps and can thus be used as a diet supplement for them., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: To quantify the insulin requirement for a high-protein meal compared with a low-protein meal, controlling for carbohydrate and fat content., Methods: In this crossover study, young people with Type 1 diabetes were randomized to consume a high- (60 g) or low-protein meal (5 g), each containing 30 g carbohydrate and 8 g fat. A variation of the insulin clamp technique was used to determine the insulin requirements to maintain euglycaemia for the following 5 h., Results: A total of 11 participants (mean ± sd age 16.5 ± 2.7 years, HbA 1c 52 ± 8.7 mmol/mol [6.9 ± 0.8%], diabetes duration 6.9±5.1 years) completed the study. The mean insulin requirements for the high-protein meal were higher than for the low-protein meal [10.3 (CI 8.2, 12.57) vs 6.7 units (CI 4.7, 8.8); P=0.001], with inter-individual requirements ranging from 0.9 to six times the low-protein meal requirement. Approximately half the additional insulin [1.1 units/h (CI 0.5, 1.8; P=0.001)] was given in the first 2 h, compared with an additional 0.5 units/h (CI -0.2, 1.2; P=0.148) in the second 2 h and 0.1 units (CI -0.6, 0.8; P=0.769) in the final hour., Conclusions: A high-protein meal requires ~50% more insulin to maintain euglycaemia than a low-protein meal that contains the same quantity of carbohydrate. The majority is required within the first 2 h. Inter-individual differences exist in insulin requirements for dietary protein., (© 2018 Diabetes UK.)

Purpose: High protein weight loss diets are effective in aiding body weight management. However, high protein and low carbohydrate intakes can alter colonic fermentation profiles in humans and may impact on colonic health. This study aims to identify the most important dietary contributors to colonic fermentation during diet-controlled weight loss., Methods: Overweight or obese male volunteers (n = 18) consumed a body weight maintenance diet (fed at 1.5× basic metabolic rate, BMR) followed by three weight loss diets (fed at 1× BMR) for 10 days each in a cross-over design. Weight loss diets were designed as normal protein (NPWL, 15% of energy from protein, 55% from carbohydrate), normal protein enriched with free amino acids and moderate amounts of carbohydrate (NPAAWL, 15% of energy from protein, 15% from free AA, 40% from carbohydrate) or high protein containing moderate amounts of carbohydrate (HPWL, 30% of energy from protein, 40% from carbohydrate). Faecal samples collected at the end of each diet period were profiled for dietary metabolites using LC-MS/MS., Results: This study shows that the NPWL diet only induced very minor changes in the faecal metabolome, whereas NPAAWL and HPWL diets decreased carbohydrate-related metabolites (butyrate, ferulic acid) and increased protein-related metabolites. Most faecal metabolites were correlated with dietary carbohydrate and not protein intake., Conclusion: This study demonstrates that dietary carbohydrate is the main driver of colonic fermentation in humans and that a balance between dietary carbohydrate and protein should be maintained when designing safe, effective and healthy weight loss diets.

Plant origin, processing, and domestic preparation may affect the postprandial glycemic response (PGR) of starchy foods. The objective of this study was to examine the possibility of integrating domestically cooked non-cereal starchy foods commonly consumed in Northeast Asia into glycemic management diet, and compare their glycemic characteristics with those of waxy and non-waxy whole grains and starchy beans. In a randomized crossover trial, ten healthy subjects consumed dried lily bulb (LB), lotus seed (LS), adlay (AD), waxy black rice (BR), millet (MI), and adzuki bean (AB), pre-soaked and each cooked for two time durations. Acute PGR tests and in vitro carbohydrate digestion were carried out for each test food. Both the LS and AB meals achieved low glycemic index (GI 21⁻51), while the other starchy foods failed to show significant difference with rice (GI 83⁻109). The hydrolysis indexes of LS and AB were 37.7%⁻61.1%, significantly lower than other test foods. The in vitro tests indicated that pre-soaking resulted in high rapidly digestible starch (RDS) and low resistant starch (RS). Careful choice of whole grain materials, minimized pre-soaking, and moderate cooking may be critical factors for successful postprandial glycemic management for diabetic and pre-diabetic.

Aims: To assess the role played by carbohydrates, fat and proteins in the management of Type 2 diabetes., Background: Diabetes research tends to reflect the interests of academics or the pharmaceutical industry, rather than those of people living with Type 2 diabetes. The James Lind Alliance and Diabetes UK addressed this issue by defining the research priorities of people living with Type 2 diabetes. Three of the top 10 research priority questions focused on lifestyle., Methods: A narrative review was undertaken with a structured search strategy using three databases. Search terms included the three macronutrients and Type 2 diabetes. No restrictions were placed on macronutrient quantity or length of study follow-up. Outcomes included changes in HbA 1c , body weight, insulin sensitivity and cardiovascular risk., Results: There is no strong evidence that there is an optimal ratio of macronutrients for improving glycaemic control or reducing cardiovascular risk. Challenges included defining the independent effect of macronutrient manipulation and identifying the effects of macronutrients, independent of foods and dietary patterns. Extreme intakes of macronutrients may be associated with health risks., Conclusions: It is challenging to formulate food-based guidelines from studies based on macronutrient manipulation. Structured education should be offered to support individuals in discovering their optimal, individual dietary approach. Recommendations for dietary guidelines should be expressed in terms of foods and not macronutrients., (© 2018 Diabetes UK.)

Dietary management has been a mainstay of care in Type 1 diabetes since before the discovery of insulin when severe carbohydrate restriction was advocated. The use of insulin facilitated re-introduction of carbohydrate into the diet. Current management guidelines focus on a healthy and varied diet with consideration of glycaemic load, protein and fat. As a result of frustration with glycaemic outcomes, low-carbohydrate diets have seen a resurgence in popularity. To date, low-carbohydrate diets have not been well studied in the management of Type 1 diabetes. Studies looking at glycaemic outcomes from low-carbohydrate diets have largely been cross-sectional, without validated dietary data and with a lack of control groups. The participants have been highly motivated self-selected individuals who follow intensive insulin management practices, including frequent blood glucose monitoring and additional insulin corrections with tight glycaemic targets. These confounders limit the ability to determine the extent of the impact of dietary carbohydrate restriction on glycaemic outcomes. Carbohydrate-containing foods including grains, fruit and milk are important sources of nutrients. Hence, low-carbohydrate diets require attention to vitamin and energy intake to avoid micronutrient deficiencies and growth issues. Adherence to restricted diets is challenging and can have an impact on social normalcy. In individuals with Type 1 diabetes, adverse health risks such as diabetic ketoacidosis, hypoglycaemia, dyslipidaemia and glycogen depletion remain clinical concerns. In the present paper, we review studies published to date and provide clinical recommendations for ongoing monitoring and support for individuals who choose to adopt a low-carbohydrate diet. Strategies to optimize postprandial glycaemia without carbohydrate restriction are presented., (© 2018 Diabetes UK.)

Aim: To conduct a systematic review and meta-analysis to evaluate the effect of carbohydrate restriction on glycaemic control in Type 2 diabetes., Methods: We searched Medline, EMBASE and CINAHL for the period between 1976 and April 2018. We included randomized controlled trials comparing carbohydrate restriction with a control diet which aimed to maintain or increase carbohydrate intake, and that reported HbA 1c as an outcome and reported the amount of carbohydrate consumed during or at the end of the study, with outcomes reported at ≥3 months., Results: We identified 1402 randomized controlled trials, 25 of which met the inclusion criteria, incorporating 2132 participants for the main outcome. Definitions of low carbohydrate varied among the studies. The pooled effect estimate from meta-analysis was a weighted mean difference of -0.09% [95% CI -0.27, 0.08 (P = 0.30); I 2 72% (P <0.001)], suggesting no effect on HbA 1c of restricting the quantity of carbohydrate. A subgroup analysis of diets containing 50-130 g carbohydrate resulted in a pooled effect estimate of -0.49% [95% CI -0.75, -0.23 (P <0.001); I 2 0% (P = 0.56)], suggesting a clinically and statistically significant effect on HbA 1c in favour of low-carbohydrate diets in studies of ≤6 months' duration., Conclusions: There was no overall pooled effect on HbA 1c in favour of restricting carbohydrate; however, restriction of carbohydrate to 50-130 g per day had beneficial effects on HbA 1c in trials up to 6 months. Future randomized controlled trials should be of >12 months' duration, assess pre-study carbohydrate intake, use recognized definitions of low-carbohydrate diets and examine reasons for non-adherence to prescribed diets in greater detail., (© 2018 Diabetes UK.)

Purpose: The responsiveness of older individuals' skeletal muscle to anabolic strategies may be impaired. However, direct comparisons within the same experimental setting are sparse. The aim of this study was to assess the resting and post-resistance exercise muscle protein synthesis rates in response to two types of milk protein and carbohydrate using a unilateral exercise leg model., Methods: Twenty-seven older (69 ± 1 year, mean ± SE) men were randomly assigned one of three groups: Whey hydrolysate (WH), caseinate (CAS), or carbohydrate (CHO). By applying stable isotope tracer techniques (L-[ 15 N]phenylalanine), the fasted-rested (basal) myofibrillar fractional synthesis rate (FSR) was measured. Hereafter, FSR was measured in the postprandial phase (0.45 g nutrient/kg LBM) in both legs, one rested (fed-rest) and one exercised (10 × 8 reps at 70% 1RM; fed-exercise). In addition, the activity of p70S6K and venous plasma insulin, phenylalanine, and leucine concentrations were measured., Results: Insulin, phenylalanine, and leucine concentrations differed markedly after intake of the different study drinks. The basal FSR in WH, CAS, and CHO were 0.027 ± 0.003, 0.030 ± 0.003, and 0.030 ± 0.004%/h, the fed-rested FSR were 0.043 ± 0.004, 0.045 ± 0.003, and 0.035 ± 0.004%/h, and the fed-exercised FSR were 0.041 ± 0.004, 0.043 ± 0.004, and 0.034 ± 0.004%/h, respectively. No significant differences were observed at any state between the groups. Fed-rested- and fed-exercised FSR were higher than basal (P < 0.001). 3 h after exercise and feeding, no significant group differences were detected in the activity of p70S6K., Conclusions: Milk protein and carbohydrate supplementation stimulate myofibrillar protein synthesis in older men, with no further effect of heavy resistance exercise within 0-3 h post exercise.

Purpose: Type 2 diabetes mellitus (T2DM) is characterized by both impaired pancreatic β-cell function (BCF) and insulin resistance. In the etiology of T2DM, BCF basically determines whether a person with a certain degree of insulin resistance develops T2DM, as β-cells are able to compensatorily increase insulin secretion. The effects of dietary intake on BCF are largely unknown. Our study aim was to investigate whether dietary macronutrient intake predicts BCF., Methods: Prospective data (median follow-up 7 years) of 303 individuals recruited from the CODAM study population (aged 40-70 years, 39% women) were analyzed. BCF was measured by C-peptide deconvolution and physiological modeling of data from a 5-point, 75-g, 2-h oral glucose tolerance test. Macronutrient intake was estimated by a 178-item Food Frequency Questionnaire., Results: Associations adjusted for relevant covariates of baseline macronutrient intake with model-derived parameters describing BCF (glucose sensitivity, rate sensitivity or potentiation) or C-peptidogenic index were detected for trans fat [standardized regression coefficient (95%-CI) glucose sensitivity - 0.14 (- 0.26, - 0.01)] per g, cholesterol [potentiation 0.20 (0.02, 0.37)] per 100 mg, dietary fiber [glucose sensitivity 0.21 (0.08, 0.33)] per 10 g, MUFA glucose sensitivity 0.16 (0.02, 0.31) per 10 g, and polysaccharide [potentiation - 0.24 (- 0.43, - 0.05), C-peptidogenic index - 0.16 (- 0.29 - 0.03); odds ratio lowest versus highest tertile (95%-CI) rate sensitivity 1.51 (1.06, 2.15)) per 50 g., Conclusions: In this population at high risk for developing T2DM, polysaccharide and trans fat intake were associated with worse BCF, whereas increased intake of MUFA, dietary cholesterol, and fiber were associated with better BCF.

Gut appetite hormone responses may be influenced by meal macronutrients and obesity. The primary aim of this study was to examine in adolescents with obesity and of healthy weight the effect of a high-protein and a high-carbohydrate meal on postprandial gut appetite hormones. A postprandial cross-over study with adolescents 11⁻19 years old was undertaken. Participants consumed, in random order, a high 79% carbohydrate (HCHO) and a high 55% protein (HP) meal. Ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and self-reported appetite were assessed for four hours postprandial. Total energy intake from an ad libitum lunch and remaining 24 h was assessed. Eight adolescents with obesity (OB) and 12 with healthy weight (HW) participated. Compared with HW, OB adolescents displayed a smaller ghrelin iAUC (-25,896.5 ± 7943 pg/mL/4 h vs. -60,863.5 ± 13104 pg/mL/4 h) ( p = 0.008) with no effect of meal ( p > 0.05). The suppression of ghrelin relative to baseline was similar between OB and HW. Ghrelin suppression was greater following the HP vs. HCHO meal (effect of meal, p = 0.018). Glucose and insulin response were greater following HCHO vs. HP, with responses more marked in OB (time × weight × meal interaction, p = 0.003 and p = 0.018, respectively). There were no effects of weight or macronutrient on GLP-1 or PYY, appetite or subsequent energy intake. The present study demonstrates that dietary protein can modulate postprandial ghrelin responses; however, this did not translate to subsequent changes in subjective appetite or energy intake.

Various functions of dietary sphingolipids have been reported; however, little is known about marine sphingolipids. Ceramide 2-aminoethylphosphonate (CAEP), an abundant sphingolipid in marine mollusks, frequently has a unique triene type of sphingoid base [2-amino-9-methyl-4,8,10-octadecatriene-1,3-diol (d19:3)]. We previously reported that dietary CAEP prepared from the skin of squid was digested in the intestinal mucosa of mice via ceramides to yield free sphingoid bases. How dietary CAEP is then used in the body remains unclear. Here, we investigated the absorption of dietary CAEP using a lipid absorption assay on the lymph collected from rats with thoracic duct cannulation. Our results reveal that sphingoid bases derived from CAEP, including d16:1, d18:1, and d19:3, were detected in the lymph after administration of CAEP. Lymphatic recovery of d19:3 was lower than that of other sphingoid bases. A large fraction of the absorbed sphingoid bases was present as complex sphingolipids, whereas a smaller portion was present in the free form. Fatty acids in ceramide moieties found in the lymph were partially different from dietary CAEP, which indicates that sphingoid bases derived from CAEP could be, at least in part, resynthesized into complex sphingolipids. Future studies should elucidate the metabolism of sphingoid bases derived from CAEP., (Copyright © 2019 Tomonaga et al.)

Pre-diabetes is a long-lasting condition that precedes type 2 diabetes (T2D). T2D has been shown to suppress the immune response. However, it remains unclear if immune activation occurs before the onset of T2D during the progression of the pre-diabetic state. This study sought to characterize the changes in general immunity occurring during the progression from pre-diabetes to T2D. Male rats were fed a high-fat high-carbohydrate diet for 20 weeks (pre-diabetes induction period) and kept on the same diet being monitored for a further 12 weeks (experimental period). Blood was collected for haemocytometer analysis on week 0, 4, 8, and 12 of the experimental period after which the animals were sacrificed. Plasma was collected from centrifuged blood for ELISA (TNF-α, CRP, P-selectin, CD40 L, fibrinogen, and IL-6). Blood neutrophils percentage significantly decreased at week 12 possibly due to recruited neutrophils migrating to an inflamed area such as visceral adipose tissue as further observed. Due to hyperglycaemia, there was significant increase in blood lymphocytes percentage at week 12. Blood monocytes percentage significantly increased at week 12. Monocytes recruited and circulated in blood due to hyperglycaemia for glucose uptake to decrease it from circulation. Blood eosinophils percentage significantly decreased at week 12. Eosinophils migrated to inflamed areas such as visceral adipose tissue as further observed. Blood basophils percentage significantly increased due to their recruitment and activation. TNF-α, CRP, and IL-6 increased significantly after 12 weeks. There was also upregulation of fibrinogen, P-selectin, and CD40L. The results of this study show that there are changes in immune cells concentration and that immune cells such as neutrophils and eosinophils migrate to inflamed areas such as adipose tissue. There is also upregulation of various inflammatory cytokines. Based on these findings, immune activation begins during the pre-diabetic state as there is upregulation of inflammatory markers.