The role of nutrition in the development of normal cognition.

The goal of this section of the meeting was to review the relation between nutrition and cognition. The topics selected for discussion included generalized malnutrition, iodine deficiency, iron metabolism, and the relation of fatty acids to the development of the nervous system. Each subject is immense and demands a detailed exposition, but can be treated here only in brief form. However, these short essays should give some insight into the status of our current knowledge.

Relationships between glucose metabolism and thermogenesis with and without prior exercise in obese women with non-insulin-dependent diabetes mellitus.

The rate of insulin-stimulated glucose disposal is reduced in individuals with insulin resistance, and is associated with a blunted or absent increase in energy expenditure in response to a glucose load. The magnitude of the effect of glucose on energy expenditure (EGEE) may be a function of opposing changes in the rate of glucose disposal (Rd) and hepatic glucose production (HGP). In this study, six women with non-insulin-dependent diabetes mellitus (NIDDM) were studied on a metabolic ward in each of three conditions. On days 1 and 2, they did no exercise (NX) or else performed low-intensity exercise ([LO] 3,118 kJ [745 kcal]) at 50% maximal oxygen consumption [V0(2)max]) or high-intensity exercise ([HI] 3,114 kJ [744 kcal] at 75% V0(2)max). On day 3, infusion of 6,6(2)H-glucose in the basal state was immediately followed by infusion of glucose, 6,6(2)H-glucose, and insulin at fixed rates. Indirect calorimetry was performed during the last 30 minutes of each infusion. EGEE was not different among the three conditions (mean +/- SEM: NX -0.18 +/- 0.11, LO -0.08 +/- 0.05, and HI -0.08 +/- 0.07 kJ/min) and was inversely related to steady-state plasma glucose concentration, a direct measure of insulin resistance (r = -.89, P < .05). EGEE was positively correlated with glucose Rd (r = .94, P < .001) and negatively correlated with HGP (r = -.91, P < .05). The data indicate that the glucose effect on energy expenditure was slightly positive in the more insulin-sensitive individuals, but negative in the more insulin-resistant subjects. The EGEE appears to be determined by the relative balance between energy required to store glucose and energy saved by suppression of glucose production.

Risk factors for diabetes and cardiovascular disease in young Australian aborigines. A 5-year follow-up study.

OBJECTIVE: To test the hypothesis that hyperinsulinemia and glucose intolerance are present at an early age in australian aborigines and can be used to predict the eventual development of NIDDM. RESEARCH DESIGN AND METHODS: Baseline anthropometric, pubertal stage, and blood pressure data were collected for 100 Australian aboriginal children and adolescents in 1989. Plasma concentrations of glucose, insulin, C-peptide, triglycerides, and LDL, HDL, and total cholesterol were measured before and during an oral glucose tolerance test. All measurements were repeated in 74 individuals from the original study population in 1994. Results were compared among hyperinsulinemic and normoinsulinemic subjects, and subjects with normal or abnormal glucose tolerance. RESULTS: The percentage of subjects who were overweight increased from 2.7% at baseline to 17.6% 5 years later. At a mean age of 18.5 years, 8.1% of the population had impaired glucose tolerance (IGT), 2.7% had diabetes, and 21.6% had elevated cholesterol concentrations in plasma. Dyslipidemia was particularly prevalent among male subjects in the population: 34.4% had elevated plasma cholesterol and 21.9% had elevated LDL cholesterol values. Of the eight subjects who had diabetes or IGT in 1994, four were classified as hyperinsulinemic in 1989 and four were not. CONCLUSIONS: The major finding of this study is the high prevalence of risk factors for NIDDM and cardiovascular disease in this population of aboriginal children and adolescents. Abnormalities of carbohydrate and lipid metabolism were well established by late in the second decade of life. Although many subjects had high insulin levels and there was evidence of insulin resistance in the population, hyperinsulinemia did not predict the development of abnormal glucose tolerance 5 years later.

Carbohydrate malabsorption.

Carbohydrate malabsorption is a very important clinical entity, particularly in pediatrics, where, if untreated, it can lead to malnutrition and failure to thrive. Malabsorption that can be treated readily with elimination of the offending carbohydrate. Knowledge by the physician of the specific mechanisms involved in the physiology of carbohydrate absorption and digestion will help in the handling of the clinical situation of malabsorption.

Absorption of fructose by isolated small intestine of rats is via a specific saturable carrier in the absence of glucose and by the disaccharidase-related transport system in the presence of glucose.

Previous studies have shown that the absorption of fructose is aided by simultaneous ingestion of glucose. The aim of the present study was to reproduce this finding in vitro to better understand the mechanism of the effect of glucose on absorption of fructose. The phenomena could not be reproduced with everted sleeves of rat intestine or brush border vesicles. In a perfused segment of isolated intestine, it was possible to demonstrate that the transport of fructose was accelerated when glucose was present in the perfusion medium. The enhanced transport was inhibited by sucrose and also by acarbazone, an inhibitor of intestinal alpha-disaccharidases. Phlorizin had no effect on the transport of fructose. The results of these studies indicate that there is a specific carrier for fructose saturated with a low concentration of the sugar, and that in the presence of glucose there is joint absorption of the two sugars by the disaccharidase-related transport system.

Maternal obesity and body composition of the neonate.

Obese women generally deliver heavier infants, but the body composition of these infants is unknown. The principal objective of this study was to determine if neonates of obese women have more adipose tissue. At 35-36 weeks of gestation, a fasting blood sample was collected from 37 pregnant women. Shortly after birth, the body fat of the neonates was measured with an infant total-body electrical conductivity (TOBEC) instrument using a prediction equation derived from 10 miniature pigs. At 6 weeks post partum, the infant body fat was measured a second time, and the body fat of each mother was measured using an adult TOBEC instrument. We found no differences between the obese (n = 16) and lean subjects (n = 21) in the concentrations of glycerol, beta-hydroxybutyrate, triglyceride, total cholesterol, high-density lipoprotein cholesterol, or glucose in the blood. However, the insulin concentration was elevated in the obese women (199 +/- 57 pmol/l) as compared with the lean women (128 +/- 68 pmol/l, p < 0.01). At birth, maternal adiposity (% body fat) was significantly associated with infant adiposity (r = 0.37, p < 0.05). However, by 6 weeks post partum the association no longer existed. Multiple regression analysis showed that maternal adiposity, fasting glucose level, and gestational age are independently associated at birth with infant adiposity.

Effects of exercise intensity on insulin sensitivity in women with non-insulin-dependent diabetes mellitus.

Exercise enhances insulin sensitivity in people with non-insulin-dependent diabetes mellitus (NIDDM), but the intensity of exercise necessary to optimize the effect is unknown. Eight women with NIDDM were studied on a metabolic ward in each of three conditions: 1) low-intensity exercise (LO) that consisted of treadmill walking at 50% of maximal O2 consumption on days 1 and 2, 2) high-intensity exercise (HI) that consisted of walking at 75% of maximal O2 consumption, and 3) no exercise (NX). The duration of exercise was adjusted so that energy expenditure was equal in both exercise conditions. On day 3, glucose, [6,6-2H]glucose, and insulin were infused at fixed rates for 3 h. Insulin sensitivity was determined both by steady-state plasma glucose concentration and rate of glucose disposal per unit plasma insulin. Steady-state plasma glucose concentration and rate of glucose disposal per unit plasma insulin were almost identical after LO or HI; values were significantly greater than after NX. Plasma glucose response to a test meal was the same among the three conditions, but plasma insulin response was lower for HI and LO compared with NX. We conclude that under these conditions LO is as effective as HI in enhancing insulin sensitivity in people with NIDDM.

Unusual high-density lipoprotein subclass distribution during late pregnancy.

Plasma lipoprotein distribution during late pregnancy is unusual since high-density lipoprotein (HDL) levels are increased in the presence of hypertriglyceridemia; the latter is usually associated with decreases in HDL levels. To determine whether there is a relationship between late-pregnancy lipid levels and specific HDL subclasses, HDL size distribution was determined by nondenaturing gradient gel electrophoresis (GGE) in a group of 36 women at 35 to 36 weeks of gestation and again at 6 weeks' postpartum, and in a group of 10 nonpregnant women. At 35 to 36 weeks of gestation, plasma triglyceride (TG) and cholesterol concentrations were significantly increased over postpartum levels (218 +/- 62 v 112 +/- 69 mg/dL and 234 +/- 48 v 197 +/- 36 mg/dL, respectively). During late pregnancy, apolipoprotein A-I (apo A-I) and HDL cholesterol concentrations were also increased relative to postpartum levels (211 +/- 42 v 168 +/- 20 mg/dL and 63 +/- 13 v 53 +/- 11 mg/dL, respectively). GGE analysis indicated that at 35 to 36 weeks of gestation, 86% of the subjects had a substantial increase of the most buoyant and largest of the HDL species, HDL2b; postpartum and nonpregnant HDL subclass distribution was characterized by the predominance of HDL3a, which are smaller, more dense HDL. The shift in the HDL subclass distribution during late pregnancy was associated with significant positive correlations between HDL2b and apo A-I (r = .50, P < .05) and HDL cholesterol (r = .60, P < .001). There were significant elevations in the concentrations of cholesteryl ester transfer protein (CETP) and estrogen during late pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Fructose absorption.

Fructose found in modern diets as a constituent of the disaccharide sucrose is absorbed by a well-characterized absorptive system integrating enzymatic hydrolysis of the disaccharide and transfer of the resulting two monosaccharides through the apical membrane of the epithelial cell. The increasing use of high-fructose syrups and crystalline fructose prompted new studies aimed at the determination of the absorptive capacity for free fructose in the human gut. Results indicate that the capacity for fructose absorption is small compared with that for sucrose and glucose and is much less than previously estimated. The unexpected finding that the simultaneous ingestion of glucose can prevent fructose malabsorption suggests that the pair of monosaccharides might be absorbed by the disaccharidase-related transport system as if they were the product of the enzymatic hydrolysis of sucrose. This absorptive mechanism might not be able to transport fructose when ingested without glucose.

The effect of exercise on fructose absorption.

The effect of exercise on intestinal absorption of fructose was evaluated in 10 subjects after they consumed four beverages, each containing a total of 50 g carbohydrate: 100% fructose (100F), 95% fructose and 5% glucose (95F), 70% fructose and 30% glucose (70F), and 100% glucose (100G), as well as a water placebo. With 100F and 95F, breath hydrogen, which is an index of incomplete absorption, increased significantly in all subjects. In contrast, hydrogen excretion did not increase in any subject after consumption of 100G or water, or in five of seven subjects who consumed 70F. The rapid increase in hydrogen excretion observed when consumption of 100F was followed by exercise was not noted during a comparable nonexercise trial. These data suggest that intestinal capacity for absorption of fructose is readily saturated after ingestion of amounts as small as 50 g and that exercise, which reduces intestinal transit time, can cause incomplete absorption of fructose.

Intestinal absorption of fructose in the rat.

The objective of this study was to investigate the mechanisms involved in intestinal absorption of fructose. The results indicate that adult rats readily absorbed 0.4 g of fructose, an amount equivalent to 1.4-1.6 g fructose/kg body wt. Acute malabsorption of fructose occurred with doses greater than 0.6 g (2.1-2.4 g/kg body wt). Continued exposure to dietary fructose resulted in a decrease in the evidence of colonic fermentation. Glucose or galactose administered with fructose enhanced the absorption of fructose. The greatest absorption was observed when equal amounts of fructose and glucose were given simultaneously. If glucose was ingested as a polymer (starch or dextrin), the stimulatory effect was dependent on the digestibility of the polymer. Sucrose given with the fructose and glucose diminished the absorption of fructose. Acarbazone, a specific inhibitor of alpha-glucosidases, including sucrase, also inhibited the facilitating effect of glucose and galactose in absorption of fructose. These results give evidence for joint absorption of the two monosaccharides, fructose and glucose.

Influence of maternal body habitus and glucose tolerance on birth weight.

Many physicians believe that macrosomia is a hallmark of a pregnancy complicated by glucose intolerance. Because the prevalence of obesity is increased among women with gestational diabetes, fetal overgrowth may be attributable at least in part to maternal obesity. We studied 2069 black, Latina, Chinese, and white mother-infant pairs to determine the interaction between maternal body habitus, maternal glucose homeostasis, and certain indices of fetal growth. Chinese women had a significantly higher serum glucose 1 hour after administration of 50 g glucose (136.6 +/- 32.7 mg/dL) than any of the other three ethnic groups. Black women had a significantly lower value for glucose (114.8 +/- 28.2 mg/dL) than either Chinese or Latina women (124.9 +/- 31.4 mg/dL). Results for Latina and white women (121.5 +/- 26.2 mg/dL) were not significantly different. Body mass index (BMI) was used to classify the subjects. The regression coefficient for the entire sample indicated a modest association of glucose with increased birth weight when maternal BMI was controlled. The BMI of the Chinese infants had a significant association with higher concentrations of glucose after administration of 50 g glucose. Maternal body habitus should be considered a major confounder in studies of the relationship of maternal glucose tolerance and infant birth weight.

Development of ornithine metabolism in the mouse intestine.

Circulating arginine available for synthesis of protein is produced in the kidney of the adult mammal by the action of the last two enzymes of the urea cycle, argininosuccinate synthase and argininosuccinate lyase. In a previous publication, we reported the presence of a complete biosynthetic pathway for arginine in the intestine of the neonatal mouse at a time when no other endogenous sources of arginine were available. Our present study was aimed at the determination of the source of ornithine used by the intestine of the neonatal mouse for the synthesis of arginine. We established the developmental profile of the two intestinal mitochondrial enzymes, pyrroline 5-carboxylate synthase and ornithine aminotransferase, responsible for the conversion of glutamate to ornithine. Both enzymatic activities were found to be significantly elevated throughout the suckling period with a peak of activity during the 2nd wk of life. Glutamate dehydrogenase activity in the intestine did not appear to be developmentally regulated during the suckling and weaning periods; therefore, this enzyme was used as a convenient marker to quantify mitochondrial preparations. Ornithine decarboxylase activity was undetectable in the intestine of the mouse during the suckling period and was detected briefly at weaning, indicating that ornithine synthesized in the intestinal mitochondria is probably not diverted actively into the polyamine pathway and is available for synthesis of arginine by the enzymes of the urea cycle.

Glucose tolerance in pregnancy: ethnic variation and influence of body habitus.

Little is known about ethnic differences in glucose tolerance during pregnancy. In this study we examined 3366 Hispanic, Chinese, black, and non-Hispanic white women in a universal screening program for gestational diabetes mellitus. After maternal age and body mass index were controlled, Chinese women had a significantly higher serum glucose level 1 hour after 50 gm of oral glucose (134.8 +/- 1.2, mean +/- SE) than any of the remaining three groups. Black women had a significantly lower value (113.3 +/- 1.3, mean +/- SE) than either Chinese or Hispanic women (124.4 +/- 0.9, mean +/- SE). Results for Hispanic women and non-Hispanic white women (121.4 +/- 1.6, mean +/- SE) were not different. The screening glucose levels of Chinese women were substantially higher than other ethnic groups even when women with gestational diabetes were removed from the analysis, indicating that the observed differences were not solely due to a higher frequency of gestational diabetes among the Chinese. The incidence of gestational diabetes was significantly greater for Chinese (7.3%) and Hispanic (4.2%) women than for black (1.7%) and non-Hispanic white (1.6%) women. Among women who had a 3-hour glucose tolerance test, the area under the glucose curve was significantly associated with maternal age and body mass index. The demonstrated heterogeneity of glucose tolerance between ethnic groups may be of importance in determining the threshold for diabetic fetopathy, and it is possible that ethnicity-specific standards will need to be developed.