Insulin sensitivity in calves decreases substantially during the first 3 months of life and is unaffected by weaning or fructo-oligosaccharide supplementation.

Veal calves at the age of 4 to 6 mo often experience problems with glucose homeostasis, as indicated by postprandial hyperglycemia, hyperinsulinemia, and insulin resistance. It is not clear to what extent the ontogenetic development of calves or the feeding strategy [e.g., prolonged milk replacer (MR) feeding] contribute to this pathology. The objective of this study was therefore to analyze effects of MR feeding, weaning, and supplementation of short-chain fructo-oligosaccharides (FOS) on the development of glucose homeostasis and insulin sensitivity in calves during the first 3 mo of life. Thirty male Holstein-Friesian calves (18±0.7 d of age) were assigned to 1 of 3 dietary treatments: the control (CON) group received MR only, the FOS group received MR with the addition of short-chain FOS, and the solid feed (SF) group was progressively weaned to SF. The CON and FOS calves received an amount of MR, which gradually increased (from 400 to 1,400 g/d) during the 71-d trial period. For the SF calves, the amount of MR increased from 400 to 850 g/d at d 30, and then gradually decreased, until completely weaned to only SF at d 63. The change in whole body insulin sensitivity was assessed by intravenous glucose tolerance tests. Milk tolerance tests were performed twice to assess changes in postprandial blood glucose, insulin, and nonesterified fatty acid responses. Whole-body insulin sensitivity was high at the start (16.7±1.6×10(-4) [µU/mL](-1)), but decreased with age to 4.2±0.6×10(-4) [µU/mL](-1) at the end of the trial. The decrease in insulin sensitivity was most pronounced (~70%) between d 8 and 29 of the trial. Dietary treatments did not affect the decrease in insulin sensitivity. For CON and FOS calves, the postprandial insulin response was 3-fold higher at the end of the trial than at the start, whereas the glucose response remained similar. The SF calves, however, showed pronounced hyperglycemia and hyperinsulinemia at the end of the trial, although weaning did not affect insulin sensitivity. We conclude that whole body insulin sensitivity decreases by 75% in calves during the first 3 mo of life. Weaning or supplementation of short-chain FOS does not affect this age-related decline in insulin sensitivity. Glucose homeostasis is not affected by supplementation of short-chain FOS in young calves, whereas postprandial responses of glucose and insulin to a MR meal strongly increase after weaning.

Lactose in milk replacer can partly be replaced by glucose, fructose, or glycerol without affecting insulin sensitivity in veal calves.

Calf milk replacer (MR) contains 40 to 50% lactose. Lactose strongly fluctuates in price and alternatives are desired. Also, problems with glucose homeostasis and insulin sensitivity (i.e., high incidence of hyperglycemia and hyperinsulinemia) have been described for heavy veal calves (body weight >100 kg). Replacement of lactose by other dietary substrates can be economically attractive, and may also positively (or negatively) affect the risk of developing problems with glucose metabolism. An experiment was designed to study the effects of replacing one third of the dietary lactose by glucose, fructose, or glycerol on glucose homeostasis and insulin sensitivity in veal calves. Forty male Holstein-Friesian (body weight=114 ± 2.4 kg; age=97 ± 1.4 d) calves were fed an MR containing 462 g of lactose/kg (CON), or an MR in which 150 g of lactose/kg of MR was replaced by glucose (GLU), fructose (FRU), or glycerol (GLY). During the first 10d of the trial, all calves received CON. The CON group remained on this diet and the other groups received their experimental diets for a period of 8 wk. Measurements were conducted during the first (baseline) and last week of the trial. A frequently sampled intravenous glucose tolerance test was performed to assess insulin sensitivity and 24 h of urine was collected to measure glucose excretion. During the last week of the trial, a bolus of 1.5 g of [U-(13)C] substrates was added to their respective meals and plasma glucose, insulin, and (13)C-glucose responses were measured. Insulin sensitivity was low at the start of the trial and remained low [1.2 ± 0.1 and 1.0 ± 0.1 (mU/L)(-1) × min(-1)], and no treatment effect was noted. Glucose excretion was low at the start of the trial (3.4 ± 1.0 g/d), but increased in CON and GLU calves (26.9 ± 3.9 and 43.0 ± 10.6g/d) but not in FRU and GLY calves. Postprandial glucose was higher in GLU, lower in FRU, and similar in GLY compared with CON calves. Postprandial insulin was lower in FRU and GLY and similar in GLU compared with CON calves. Postprandial (13)C-glucose increased substantially in FRU and GLY calves, indicating that calves are able to partially convert these substrates to glucose. We concluded that replacing one third of lactose in MR by glucose, fructose, or glycerol in MR differentially influences postprandial glucose homeostasis but does not affect insulin sensitivity in veal calves.

Influence of the type of indigestible carbohydrate on plasma and urine short-chain fatty acid profiles in healthy human volunteers.

BACKGROUND/OBJECTIVES: Health effects of whole grain foods are becoming more evident. In this study, we analysed the short-chain fatty acid profiles in urine and serum derived from the colonic fermentation process of (13)C-barley meals, prepared from barley grown under (13)CO(2) atmosphere. SUBJECTS/METHODS: In a crossover study, five volunteers ingested intact barley kernels (high content of non-starch polysaccharides (NSP) and resistant starch (RS)) and barley porridge (high content of NSP only). Using a newly developed stable isotope technology, we monitored 14 and 24 h postprandially (13)C-acetate, (13)C-propionate and (13)C-butyrate in plasma and urine, respectively. The oro-cecal transit time (OCTT) of the meals was measured with the hydrogen breath test. RESULTS: The OCTT was 6 h and did not differ between the two test meals. An increase of (13)C-acetate was observed already early after ingestion of the meals (<6 h) and was attributed to early fermentation of the test meal. A rise in plasma (13)C-propionate in the fermentation phase could only be detected after the porridge and not after the kernel meal. An increase in (13)C-butyrate was only found in the fermentation phase and was higher after the barley kernels. Urine (13)C-short-chain fatty acids data were consistent with these observations. CONCLUSIONS: The difference in the profiles of (13)C-acetate, (13)C-propionate and (13)C-butyrate indicates that NSP combined with RS results in an altered fermentation profile than dietary fibre alone.

The interaction of short-chain fatty acids with adipose tissue: relevance for prevention of type 2 diabetes.

Short chain fatty acids (SCFA) are the main bacterial metabolites of colonic fermentation processes. The physiological relevance of the SCFA for the host outside the gastrointestinal tract is getting increased attention. In this review we will focus on the effect of SCFA on inflammation processes in the host in relation to insulin resistance. Obesity has been associated with a pro-inflammatory state of the adipose tissue that is associated with whole body insulin resistance leading to type 2 diabetes. Recently, two G protein-coupled receptors (GPCR) for SCFA, GPCR 41 and GPCR43, were described that are mainly expressed by immune cells but also by adipose tissue. Propionate can induce the satiety hormone leptin and reduce expression of inflammatory cytokines and chemokines indicating that SCFA have anti-inflammatory effects in human adipose tissue. In addition, in human nutritional experiments we observed that whole grain products could counteract a glucose-induced tumour necrosis factor α and interleukin-6 increase which was associated with increased plasma butyrate concentrations. This suggests that dietary fibre can produce a SCFA profile that could have anti-inflammatory effects in the body. The physiological relevance of these observations especially in relation to obesity-associated inflammation and insulin resistance is discussed.

A curve fitting approach to estimate the extent of fermentation of indigestible carbohydrates.

BACKGROUND: Information about the extent of carbohydrate digestion and fermentation is critical to our ability to explore the metabolic effects of carbohydrate fermentation in vivo. We used cooked (13)C-labelled barley kernels, which are rich in indigestible carbohydrates, to develop a method which makes it possible to distinguish between and to assess carbohydrate digestion and fermentation. MATERIALS AND METHODS: Seventeen volunteers ingested 86 g (dry weight) of cooked naturally (13)C enriched barley kernels after an overnight fast. (13)CO(2) and H(2) in breath samples were measured every half hour for 12 h. The data of (13)CO(2) in breath before the start of the fermentation were used to fit the curve representing the digestion phase. The difference between the area under curve (AUC) of the fitted digestion curve and the AUC of the observed curve was regarded to represent the fermentation part. Different approaches were applied to determine the proportion of the (13)C-dose available for digestion and fermentation. RESULTS: Four hours after intake of barley, H(2)-excretion in breath started to rise. Within 12 h, 24-48% of the (13)C-dose was recovered as (13)CO(2), of which 18-19% was derived from colonic fermentation and the rest from digestion. By extrapolating the curve to baseline, it was estimated that eventually 24-25% of the total available (13)C in barley would be derived from colon fermentation. CONCLUSION: Curve fitting, using (13)CO(2)- and H(2)-breath data, is a feasible and non-invasive method to assess carbohydrate digestion and fermentation after consumption of (13)C enriched starchy food.

The role of colonic metabolism in lactose intolerance.

Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance.

Whole grain foods for the prevention of type 2 diabetes mellitus.

BACKGROUND: Diet as one aspect of lifestyle is thought to be one of the modifiable risk factors for the development of type 2 diabetes mellitus (T2DM). Information is needed as to which components of the diet could be protective for this disease. OBJECTIVES: To asses the effects of whole-grain foods for the prevention of T2DM. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, CINAHL and AMED. SELECTION CRITERIA: We selected cohort studies with a minimum duration of five years that assessed the association between intake of whole-grain foods or cereal fibre and incidence of T2DM. Randomised controlled trials lasting at least six weeks were selected that assessed the effect of a diet rich in whole-grain foods compared to a diet rich in refined grain foods on T2DM and its major risk factors. DATA COLLECTION AND ANALYSIS: Two authors independently selected the studies, assessed study quality and extracted data. Data of studies were not pooled because of methodological diversity. MAIN RESULTS: One randomised controlled trial and eleven prospective cohort studies were identified. The randomised controlled trial, which was of low methodological quality, reported the change in insulin sensitivity in 12 obese hyperinsulinemic participants after six-week long interventions. Intake of whole grain foods resulted in a slight improvement of insulin sensitivity and no adverse effects. Patient satisfaction, health related quality of life, total mortality and morbidity was not reported. Four of the eleven cohort studies measured cereal fibre intake, three studies whole grain intake and two studies both. Two studies measured the change in whole grain food intake and one of them also change in cereal fibre intake. The incidence of T2DM was assessed in nine studies and changes in weight gain in two studies. The prospective studies consistently showed a reduced risk for high intake of whole grain foods (27% to 30%) or cereal fibre (28% to 37%) on the development of T2DM. AUTHORS' CONCLUSIONS: The evidence from only prospective cohort trials is considered to be too weak to be able to draw a definite conclusion about the preventive effect of whole grain foods on the development of T2DM. Properly designed long-term randomised controlled trials are needed. To facilitate this, further mechanistic research should focus on finding a set of relevant intermediate endpoints for T2DM and on identifying genetic subgroups of the population at risk that are most susceptible to dietary intervention.

Effects of yogurt and bifidobacteria supplementation on the colonic microbiota in lactose-intolerant subjects.

AIMS: Colonic metabolism of lactose may play a role in lactose intolerance. We investigated whether a 2-week supplementation of Bifidobacterium longum (in capsules) and a yogurt enriched with Bifidobacterium animalis could modify the composition and metabolic activities of the colonic microbiota in 11 Chinese lactose-intolerant subjects. METHODS AND RESULTS: The numbers of total cells, total bacteria and the Eubacterium rectale/Clostridium coccoides group in faeces as measured with fluorescent in situ hybridization and the faecal beta-galactosidase activity increased significantly during supplementation. The number of Bifidobacterium showed a tendency to increase during and after supplementation. With PCR-denaturing gradient gel electrophoresis, in subjects in which B. animalis and B. longum were not detected before supplementation, both strains were present in faeces during supplementation, but disappeared after supplementation. The degree of lactose digestion in the small intestine and the oro-caecal transit time were not different before and after supplementation, whereas symptom scores after lactose challenge decreased after supplementation. CONCLUSIONS: The results suggest that supplementation modifies the amount and metabolic activities of the colonic microbiota and alleviates symptoms in lactose-intolerant subjects. The changes in the colonic microbiota might be among the factors modified by the supplementation which lead to the alleviation of lactose intolerance. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides evidence for the possibility of managing lactose intolerance with dietary lactose (yogurt) and probiotics via modulating the colonic microbiota.

Low-dose acarbose does not delay digestion of starch but reduces its bioavailability.

AIMS: Slowly digestible starch is associated with beneficial health effects. The glucose-lowering drug acarbose has the potential to retard starch digestion since it inhibits alpha-amylase and alpha-glucosidases. We tested the hypothesis that a low dose of acarbose delays the rate of digestion of rapidly digestible starch without reducing its bioavailability and thereby increasing resistant starch flux into the colon. METHODS: In a crossover study, seven healthy males ingested corn pasta (50.3 g dry weight), naturally enriched with (13)C, with and without 12.5 mg acarbose. Plasma glucose and insulin concentrations, and (13)CO(2) and hydrogen excretion in breath were monitored for 6 h after ingestion of the test meals. Using a primed continuous infusion of D-[6,6-(2)H(2)] glucose, the rate of appearance of starch-derived glucose was estimated, reflecting intestinal glucose absorption. RESULTS: Areas under the 2-h postprandial curves of plasma glucose and insulin concentrations were significantly decreased by acarbose (-58.1 +/- 8.2% and -72.7 +/- 7.4%, respectively). Acarbose reduced the overall 6-h appearance of exogenous glucose (bioavailability) by 22 +/- 7% (mean +/-se) and the 6-h cumulative (13)CO(2) excretion by 30 +/- 6%. CONCLUSIONS: These data show that in healthy volunteers a low dose of 12.5 mg acarbose decreases the appearance of starch-derived glucose substantially. Reduced bioavailability seems to contribute to this decrease to a greater extent than delay of digestion. This implies that the treatment effect of acarbose could in part be ascribed to the metabolic effects of colonic starch fermentation.

Effect of lactose on oro-cecal transit in lactose digesters and maldigesters.

BACKGROUND: The transit time of the small intestine, in addition to lactase activity, may influence lactose digestion and thus play a role in the occurrence of lactose intolerance. The objectives of this study were to investigate the effect of lactose on the oro-cecal transit time (OCTT) in lactose digesters and maldigesters as well as the possible mechanisms underlying these effects. MATERIALS AND METHODS: Twenty-eight Chinese subjects and 16 Dutch subjects underwent one glucose and one lactose challenge in two single-blinded tests. Twenty of the Chinese subjects without complaints after the challenge then underwent another lactose challenge. A 6-h symptom score (SSC) was recorded, breath-hydrogen concentration was measured and OCTT after consumption of glucose and lactose was determined with the lactose-[13C] ureide breath test. The lactose digestion index (LDI) was determined in both the Dutch and 20 Chinese subjects with the 13C/2H-glucose test. RESULTS: Lactose digesters (n = 13) and maldigesters (n = 20) were classified based on the results of the LDI and the breath-hydrogen test. The OCTT after the lactose and glucose challenges did not differ in the digesters, whereas in the maldigesters the OCTT, after the lactose challenge, was shorter than that after glucose. There was no difference in OCTT after the glucose challenge between the maldigesters and the digesters. However, the OCTT after the lactose challenge in the maldigesters was shorter than that in the digesters. The LDI of the digesters was significantly higher than that of the maldigesters. The OCTT after the lactose challenge was not correlated to the LDI in the maldigesters nor in the digesters. Based on the SSC after the one glucose and two lactose challenges, a tolerant (n = 7) and an intolerant (n = 5) group were classified in the Chinese subjects. The two groups did not differ in their LDI or OCTT after the lactose challenge. The OCTT after the lactose challenge was not correlated to the SSC or the LDI. CONCLUSIONS: Lactose triggers a faster oro-cecal transit in lactose maldigesters, but not in digesters. However, this could not be explained by intestinal distension resulting from the osmotic load posed by maldigested lactose, and thus suggests a direct effect of lactose on intrinsic factors regulating intestinal motility.

Influence of a subsequent meal on the oro-cecal transit time of a solid test meal.

BACKGROUND: Oro-cecal transit time (OCTT) is determined for clinical diagnostics of intestinal complaints and research purposes. Ingestion of a subsequent meal during the test period shortens the OCTT of a liquid test meal (glucose solution), as previously reported. This study was conducted to determine whether the same phenomenon occurs after ingestion of a solid test meal. MATERIALS AND METHODS: The OCTT of a pancake was measured with the lactose-[(13)C]-ureide breath test on two occasions in 28 volunteers. All the volunteers took the same subsequent meal once at 4 h and at 6 h after ingestion of the pancake. RESULTS: In 16 of the 56 tests no increase in breath-(13)CO(2) was observed. No statistically significant difference was found between the OCTTs of the test meal after ingestion of the subsequent meal at 4 h or 6 h (367; 311-405 min and 290; 370-405 min, median quartiles, respectively) (P = 0.14, n = 18). Only a subgroup (n = 4) with a short OCTT in the test with the 4-h subsequent meal (278; 259-296 min) tended to have a longer OCTT in the test with the 6-h subsequent meal (390; 379-401 min; P = 0.059). CONCLUSION: The effect of the ingestion of a subsequent meal on the transit time of a test meal is shown to be dependent on the physical form and/or caloric content of the test meal.

[Nutrition and health--carbohydrates, the risks to health from the postprandial glycaemic response and the possibilities for its manipulation]. / Voeding en gezondheid--koolhydraten, het gezondheidsrisico van de postprandiale glykemische respons en de mogelijkheden voor beïnvloeding.

Carbohydrates are the most important source of food-derived energy. The metabolic effects of different types of carbohydrate can vary considerably, partially due to differences in glucose and insulin response. Several studies indicate that postprandial hyperglycaemia is associated with an increased risk of cardiovascular disease in patients with diabetes mellitus. For these patients, and possibly also for individuals with impaired glucose tolerance as well as for the healthy population at large, it may be of benefit to prevent postprandial hyperglycaemia. In order to manipulate the postprandial glycaemic response, an understanding of the underlying mechanisms of this response is crucial. The postprandial blood glucose level is influenced by a number of factors, such as the amount and type of ingested carbohydrates, gastric emptying rate and digestion and secretion of gastrointestinal and other hormones. Different approaches can be chosen to prevent postprandial hyperglycaemia, including changes in the diet and the use of drugs that delay gastric emptying or digestion of carbohydrates. The administration of gastrointestinal hormones or manipulation of the secretion of these hormones, are also possibilities. Investigating the regulation of the postprandial blood-glucose concentration and its possible manipulation could result in new approaches to preventing postprandial hyperglycaemia.

Oro-cecal transit time: influence of a subsequent meal.

BACKGROUND: Small intestinal and oro-cecal transit time (OCTT) is determined for clinical diagnostics and research purposes. Experimental protocols used vary with respect to the inclusion of a subsequent meal during the test period. This study was conducted to elucidate whether the ingestion of a subsequent meal during the test period influences the OCTT of the test meal. MATERIALS AND METHODS: The OCTT of a liquid test meal, measured with the lactose-[(13)C]ureide breath test, was compared between four groups of healthy volunteers (n = 36) who consumed the subsequent meal at different time points. Also, the OCTT was determined twice in eight subjects; a subsequent meal was ingested after 180 min (test A) and after 360 min (test B). RESULTS: An apparently meal-related increase in median OCTT was observed. The OCTT of the eight volunteers measured in test A (210; 210-349 median; quartiles) was significantly shorter than that found in test B (345; 300-375 min, P = 0.016). As result of the ingestion of the subsequent meal at 180 min the OCTT was shortened by 90; 64-116 min in 7/8 subjects. CONCLUSION: These data indicate that the ingestion of a subsequent meal affects the OCTT of a liquid test meal. This phenomenon could be explained by the increased intestinal motility in response to a meal, and should be taken into account when designing protocols for measurements of the OCTT and in the interpretation of small intestinal absorption studies.

Lactose intolerance: analysis of underlying factors.

BACKGROUND: We studied the degree of lactose digestion and orocecal transit time (OCTT) as possible causes for the variability of symptoms of lactose intolerance (LI) in a sample of a population with genetically determined low lactase activity. METHODS: Lactose digestion index (LDI) was measured by the recently developed 13C-lactose/2H-glucose test. The OCTT was determined using the breath hydrogen test. Based on a 6-h symptom score (SSC) after a challenge dose of 25 g of lactose the subjects were divided into a tolerant group (T: n= 15; SSC = 0) and an intolerant group (IT: n= 28; SSC 1-40). The intolerant group was subdivided according to the severity of symptoms: group ITa (n = 17; mild symptoms without diarrhoea) and group ITb (n = 11; with diarrhoea). RESULTS: The LDI was lower in the intolerant group (0.34 +/- 0.14) (mean +/- SD) than in the tolerant group (0.47 +/- 0.14) (P = 0.008). The OCTT of group IT (60, 30-90 min) (median, quartiles) was significantly shorter than that of group T (105, 60-120 min) (P = 0.003) and was positively correlated with the LDI (P = 0.050). In groups ITa and ITb the OCTT (60, 30-90 min; 60, 26-83 min) and LDI (0.30 +/- 0.14; 0.39 +/- 0.14) were similar. CONCLUSIONS: Lactose digestion capacity, which is determined by small intestinal lactase activity as well as by OCTT, affects the occurrence of lactose intolerance. However, the major difference in intolerance symptoms is caused by differences in the colonic processing of maldigested lactose.

The 13C/2H-glucose test for determination of small intestinal lactase activity.

To diagnose hypolactasia, determination of lactase enzyme activity in small intestinal biopsy material is considered to be the golden standard. Because of its strongly invasive character and the sampling problems, alternative methods have been looked for. We analysed the 13C-glucose response in serum after consumption of 25 g of naturally enriched 13C-lactose. As an internal standard, 0.5 g of 2H-glucose was added and the 2H-glucose response in serum was measured simultaneously. The studies were performed in healthy volunteers with a background of genetically determined lactase nonpersistence (n = 12; low lactase activity) and lactase persistence (n = 27; high lactase activity). The results were compared with those of the lactose hydrogen breath test, the lactose 13CO2 breath test and the previously described 13C-lactose digestion test. After consumption of 13C-lactose and 2H-glucose, the mean ratio 13C-glucose/2H-glucose concentration in serum at 45-75 min was 0.26 +/- 0.09 in the low lactase activity group and 0.93 +/- 0.17 in the high lactase activity group (P < 0.01). Threshold of the ratio between digesters and maldigesters was calculated as 0.46. Accuracy of the new test was superior to all other tests. We conclude that the 13C/2H-glucose test has the potential of determining the small intestinal lactase activity in vivo and of estimating the amount of lactose which is digested in the small intestine.