Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS: In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS: Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS: Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS: In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS: Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS: Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Meal ingestion provokes entry of lipoproteins containing fat from the previous meal: possible metabolic implications

Background: Prolonged and exaggerated postprandial plasma triacylglycerol (TAG) concentrations are considered as an independent risk factor for coronary artery disease. Western populations eat many meals at regular intervals, and can be in a postprandial state for at least 17h of a 24h period. After consuming 2 meals an early plasma TAG peak has been observed after the second meal, the origin of which is unclear. Aim of the study: To test the hypothesis that the early TAG peak observed following sequential meals was of intestinal origin and represented fat derived from the previous meal. Methods: Postprandial plasma lipaemic responses of 17 healthy postmenopausal women were studied by giving a test breakfast followed by a lunch. Watermiscible retinyl palmitate (RP) was added to the breakfast, but not the lunch test meal. Plasma TAG, retinyl esters (RE) and apo B-48 were determined for a 10h period following breakfast. Results: In response to the test meals, RE, apo B-48 and TAG showed multiple peaks. Despite omission of RP from the lunch, RE showed an early peak response after ingestion of lunch in 15 of 17 subjects. The peak response after lunch of all three markers appeared significantly earlier compared with their respective peak responses after the breakfast (P < 0.0001). The area of RE response after lunch was significantly correlated with the RE lipaemic response to the breakfast (r = 0.67; P < 0.004) and to the fasting TAG concentration (r = 0.48; P < 0.05). Conclusions: Since the lunch did not contain RP, the distinctive second influx of RE after lunch was believed to have originated from the breakfast. This, together with the fact that all three markers showed an earlier response to the lunch than the breakfast, supports the view that ingestion of a second meal provokes entry of fat from the previous meal, from an as yet unidentified site (gut, enterocytes, lymph). The results indicate that the degree of TAG "storage" from previous meals might be a function of TAG tolerance and provide a possible site of regulation of the entry of fat into the systemic circulation.

Impact of lipoprotein lipase gene polymorphism, S447X, on postprandial triacylglycerol and glucose response to sequential meal ingestion

Lipoprotein lipase (LPL) is a key rate-limiting enzyme for the hydrolysis of triacylglycerol (TAG) in chylomicrons and very low-density lipoprotein. Given that postprandial assessment of lipoprotein metabolism may provide a more physiological perspective of disturbances in lipoprotein homeostasis compared to assessment in the fasting state, we have investigated the influence of two commonly studied LPL polymorphisms (rs320, HindIII; rs328, S447X) on postprandial lipaemia, in 261 participants using a standard sequential meal challenge. S447 homozygotes had lower fasting HDL-C (p = 0.015) and a trend for higher fasting TAG (p = 0.057) concentrations relative to the 447X allele carriers. In the postprandial state, there was an association of the S447X polymorphism with postprandial TAG and glucose, where S447 homozygotes had 12% higher TAG area under the curve (AUC) (p = 0.037), 8.4% higher glucose-AUC (p = 0.006) and 22% higher glucose-incremental area under the curve (IAUC) (p = 0.042). A significant gene–gender interaction was observed for fasting TAG (p = 0.004), TAG-AUC (Pinteraction = 0.004) and TAG-IAUC (Pinteraction = 0.016), where associations were only evident in men. In conclusion, our study provides novel findings of an effect of LPL S447X polymorphism on the postprandial glucose and gender-specific impact of the polymorphism on fasting and postprandial TAG concentrations in response to sequential meal challenge in healthy participants

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Pre-meal tomato (Lycopersicon esculentum) intake can have anti-obesity effects in young women?

The effect of pre-meal tomato intake in the anthropometric indices and blood levels of triglycerides, cholesterol, glucose, and uric acid of a young women population (n=35, 19.6 ± 1.3 years) was evaluated. During 4 weeks, daily, participants ingested a raw ripe tomato (~90 g) before lunch. Their anthropometric and biochemical parameters were measured repeatedly during the follow-up time. At the end of the 4 weeks, significant reductions were observed on body weight (-1.09 ± 0.12 kg on average), % fat (-1.54 ± 0.52%), fasting blood glucose (-5.29 ± 0.80 mg/dl), triglycerides (-8.31 ± 1.34 mg/dl), cholesterol (-10.17 ± 1.21 mg/ dl), and uric acid (-0.16 ± 0.04 mg/dl) of the participants. The tomato pre-meal ingestion seemed to interfere positively in body weight, fat percentage, and blood levels of glucose, triglycerides, cholesterol, and uric acid of the young adult women that participated in this study.

Acute effects of meal fatty acid composition on insulin sensitivity in healthy post-menopausal women

Postprandial plasma insulin concentrations after a single high-fat meal may be modified by the presence of specific fatty acids although the effects of sequential meal ingestion are unknown. The aim of the present study was to examine the effects of altering the fatty acid composition in a single mixed fat-carbohydrate meal on glucose metabolism and insulin sensitivity of a second meal eaten 5 h later. Insulin sensitivity was assessed using a minimal model approach. Ten healthy post-menopausal women underwent four two-meal studies in random order. A high-fat breakfast (40 g fat) where the fatty acid composition was predominantly saturated fatty acids (SFA), n-6 polyunsaturated fatty acids (PUFA), long-chain n-3 PUFA or monounsaturated fatty acids (MUFA) was followed 5 h later by a low-fat, high-carbohydrate lunch (5.7 g fat), which was identical in all four studies. The plasma insulin response was significantly higher following the SFA meal than the other meals after both breakfast and lunch (P<0.006) although there was no effect of breakfast fatty acid composition on plasma glucose concentrations. Postprandial insulin sensitivity (SI(Oral)) was assessed for 180 min after each meal. SI(Oral) was significantly lower after lunch than after breakfast for all four test meals (P=0.019) following the same rank order (SFA < n-6 PUFA < n-3 PUFA < MUFA) for each meal. The present study demonstrates that a single meal rich in SFA reduces postprandial insulin sensitivity with 'carry-over' effects for the next meal.

EFFECT OF FLUID AND FOOD INTAKE ON THE BODY COMPOSITION EVALUATION OF ELDERLY PERSONS

Background: Several studies have shown that liquid and food intake interfere with the evaluation of body composition in adults. However, since there are no reports about this interference in the elderly population, the need to fast for this evaluation may be dispensable. Objectives: The objective of the present study was to assess the influence of liquid and solid food on the measurement of body composition by bioelectrical impedance analysis (BIA) and by dual energy X-ray absorptiometry (DXA). Design: Forty-one male volunteers aged 62 to 87 years participated in the study. The subjects were submitted to evaluation of body composition by DXA and BIA under fasting conditions and 1 hour after the ingestion of breakfast (500 ml of orange juice and one 50 g bread roll with butter). Results: There was no significant difference in the variables fat-free mass (FFM) or fat mass (FM) between the fasting condition and the evaluation performed 1 hour after the meal as measured by BIA or DXA. There was also no significant difference when the same variables were compared between methods. Conclusion: In the present study, the ingestion of 500 ml orange juice and of one bread roll with butter by elderly subjects did not affect the results of the parameters of body composition determined by BIA or DXA. Thus, these exams could be performed without the rigor of fasting, often poorly tolerated by the elderly.

Whole body protein metabolism and resting energy expenditure in pregnant Gambian women.

Whole body protein metabolism and resting energy expenditure (REE) were measured at 11, 23, and 33 wk of pregnancy in nine pregnant (not malnourished) Gambian women and in eight matched nonpregnant nonlactating (NPNL) matched controls. Rates of whole body nitrogen flux, protein synthesis, and protein breakdown were determined in the fed state from the level of isotope enrichment of urinary urea and ammonia during a period of 9 h after a single oral dose of [15N]glycine. At regular intervals, REE was measured by indirect calorimetry (hood system). Based on the arithmetic end-product average of values obtained with urea and ammonia, a significant increase in whole body protein synthesis was observed during the second trimester (5.8 +/- 0.4 g.kg-1.day-1) relative to values obtained both for the NPNL controls (4.5 +/- 0.3 g.kg-1.day-1) and those during the first trimester (4.7 +/- 0.3 g.kg-1.day-1). There was a significant rise in REE during the third trimester both in the preprandial and postprandial states. No correlation was found between REE after meal ingestion and the rate of whole body protein synthesis.

Energy metabolism during the postexercise recovery in man.

In order to explore the magnitude and duration of the long-term residual effect of physical exercise, a mixed meal (55% CHO, 27% fat and 18% protein) was given to 10 young male volunteers on two occasions: after a 4-h resting period, and on the next day, 30 min after completion of a 3-h exercise at 50% VO2max. Energy expenditure and substrate utilization were determined by indirect calorimetry for 17 h after meal ingestion. The fuel mix oxidized after the meal was characterized by a greater contribution of lipid oxidation to total energy expenditure when the meal was ingested during the post-exercise period as compared with the meal ingested without previous exercise. During the night following the exercise, the stimulation of energy expenditure observed during the early recovery period gradually faded out. However, resting energy expenditure measured the next morning was significantly higher (+4.7%) than that measured without previous exercise. It is concluded that intense exercise stimulates both energy expenditure and lipid oxidation for a prolonged period.

Long-term effects of Roux-en-Y gastric bypass on postprandial plasma lipid and bile acids kinetics in female non diabetic subjects: A cross-sectional pilot study.

BACKGROUND AND AIMS: Formerly obese patients having undergone Roux-en-Y gastric bypass (RYGB) display both an accelerated digestion and absorption of carbohydrate and an increased plasma glucose clearance rate after meal ingestion. How RYGB effects postprandial kinetics of dietary lipids has yet not been investigated. METHODS: Plasma triglyceride (TG), apoB48, total apoB, bile acids (BA), fibroblast growth factor 19 (FGF19), and cholecystokinin (CCK) were measured in post-absorptive conditions and over 4-h following the ingestion of a mixed test meal in a cross-sectional, pilot study involving 11 formerly obese female patients 33.8 ± 16.4 months after RYGB surgery and in 11 weight- and age-matched female control participants. RESULTS: Compared to controls, RYGB patients had faster (254 ± 14 vs. 327 ± 7 min, p < 0.05) and lower (0.14 ± 0.04 vs. 0.35 ± 0.07 mM, p < 0.05) peak TG responses, but their peak apoB48 responses tended to be higher (2692 ± 336 vs. 1841 ± 228 ng/ml, p = 0.09). Their postprandial total BA concentrations were significantly increased and peaked earlier after meal ingestion than in controls. Their FGF19 and CCK concentrations also peaked earlier and to a higher value. CONCLUSIONS: The early postprandial apoB48 and BA responses indicate that RYGB accelerated the rate of dietary lipid absorption. The lower postprandial peak TG strongly suggests that the RYGB simultaneously increased the clearance of TG-rich lipoproteins. CLINICAL TRIAL REGISTRATION: NCT01891591.

Metabolic response to feeding in Tupinambis merianae: Circadian rhythm and a possible respiratory constraint

The diurnal tegu lizard Tupinambis merianae exhibits a marked circadian variation in metabolism that is characterized by the significant increase in metabolism during part of the day. These increases in metabolic rate, found in the fasting animal, are absent during the first 2 d after meal ingestion but reappear subsequently, and the daily increase in metabolic rate is added to the increase in metabolic rate caused by digestion. During the first 2 d after feeding, priority is given to digestion, while on the third and following days, the metabolic demands are clearly added to each other. This response seems to be a regulated response of the animal, which becomes less active after food ingestion, rather than an inability of the respiratory system to support simultaneous demands at the beginning of digestion. The body cavity of Tupinambis is divided into two compartments by a posthepatic septum (PHS). Animals that had their PHS surgically removed showed no significant alteration in the postprandial metabolic response compared to tegus with intact PHS. The maximal metabolic increment during digestion, the relative cost of meal digestion, and the duration of the process were virtually unaffected by the removal of the PHS.

Blood oxygen affinity increases during digestion in the South American rattlesnake, Crotalus durissus terrificus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Glucose intolerance caused by a defect in the entero-insular axis: A study in gastric inhibitory polypeptide receptor knockout mice

Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic β cells. GIPR−/− mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR−/− mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.

Consistent reduction of postprandial glucagon and insulin by lixisenatide in the GetGoal clinical trial programme

Background and aims: Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in subjects with type 2 diabetes mellitus. We evaluated 2-hour glucose, glucagon and insulin changes following a standardized mixed-meal tolerance test before and after 24 weeks of treatment with the once-daily prandial GLP-1 receptor agonist lixisenatide (approved for a therapeutic dose of 20 μg once daily) in six randomized, placebo-controlled studies within the lixisenatide Phase III GetGoal programme. In the studies, the mixed-meal test was conducted before and after: (1) lixisenatide treatment in patients insufficiently controlled despite diet and exercise (GetGoal-Mono), (2) lixisenatide treatment in combination with oral antidiabetic drugs (OADs) (GetGoal-M and GetGoal-S), or (3) lixisenatide treatment in combination with basal insulin ± OAD (GetGoal-Duo 1, GetGoal-L and GetGoal-L-Asia).Materials and methods: A meta-analysis was performed (lixisenatide n=1124 vs placebo n=707) combining ANCOVA least squares (LS) mean values using an inverse variance weighted analysis. Results: Lixisenatide significantly reduced 2-hour postprandial glucose from baseline (LS mean difference vs placebo: -4.9 mmol/L, p<0.0001, Figure) and glucose excursions (LS mean difference vs placebo: -4.5 mmol/L, p<0.0001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs placebo: -19.0 ng/L, p<0.0001) and insulin (LS mean difference vs placebo: -64.8 pmol/L, p<0.0001), although the glucagon/insulin ratio was increased (LS mean difference vs placebo: 0.15, p=0.02) compared with placebo. Conclusion: The results show that lixisenatide potently reduces the glucose excursion after meal ingestion in subjects with type 2 diabetes, in association with marked reductions in glucagon and insulin levels. It is suggested that diminished glucagon secretion and slower gastric emptying contribute to reduced hepatic glucose production and delayed glucose absorption, enabling postprandial glycaemia to be controlled with less demand on beta-cell insulin secretion. Clinical Trial Registration Number: NCT00688701; NCT00712673; NCT00713830; NCT00975286; NCT00715624; NCT00866658 Supported by: Sanofi