The search for an optimized treatment of hypoglycemia. Carbohydrates in tablets, solutin, or gel for the correction of insulin reactions.

Recommendations for the treatment of insulin reactions are based more on habit than data. We investigated the efficacy in correcting blood glucose levels and alleviating clinical symptoms of hypoglycemia of seven orally administered carbohydrates--glucose in solution, tablets, and gel; sucrose in solution and tablets; a hydrolized polysaccharide solution; and orange juice--each of which provided 15 g of carbohydrate. Forty-one type I diabetic patients recently treated with insulin agreed to submit to artificially induced hypoglycemia by an intravenous injection of insulin. Corrective therapy was given when patients experienced symptoms and asked for treatment. Mean blood glucose levels 10 minutes after ingestion were found to be similar whether correction was dispensed with the tablets and the solutions of glucose, those of sucrose, or the polysaccharide preparation. However, almost no increment was obtained at this time point with the gel or the fruit juice. Fifteen and 20 minutes after carbohydrate intake, blood glucose levels were higher with the tablet forms than with the solutions, although differences only became signifiant for sucrose. Glycemic responses were again consistently lower with the sucrose gel and the orange juice. Clinical symptoms were alleviated in 14.0 +/- 0.8 minutes (mean +/- SEM) with sucrose and glucose in solution or tablets. We conclude that in moderately severe hypoglycemia, ingestion of 15 g of carbohydrate in the form of glucose or sucrose tablets or as a solution provides an effective therapy; both sugars seem equivalent. Even if sucrose lumps are better recommended in terms of cost and availability, they may not be recommendable in terms of palatability. Glucose gel or orange juice cannot be recommended, at least in light of our experimental procedure and at the dosage used therein.

Undigestible sugars in food products.

In the field of sucrose replacement, low-energy bulk ingredients must be used to lower the energy density of food. Ideally, low-energy bulk ingredients as a substitute for sucrose should have significantly less energy, possess physical and chemical properties that precisely match those of sucrose in all food applications, provide secondary health benefits (such as being noncariogenic, being useful for diabetics, and having fiber-like effects), confer no negative side effects, and be completely safe at any amount of consumption. The food industry has developed a range of low-energy bulk ingredients. Most of these are legally permitted in food applications and are undigestible sugars (eg, polyols and fructo-oligosaccharides). Their main nutritional properties (energy value, digestive tolerance, and cariogenicity) are related to their fate in the digestive tract, especially their capacity to be used and fermented by bacteria.

Insulin and glycemic responses in healthy humans to native starches processed in different ways: correlation with in vitro alpha-amylase hydrolysis.

The aim of the study was to elucidate how extracted starches submitted to food processing (or not) can influence plasma insulin and glucose responses in healthy subjects. Native starches from wheat, manihot, smooth peas, or mung beans were tested either raw, as starch gels (boiled and cooled), or cooked and cooled after a preliminary industrial processing: extrusion cooking for wheat, tapioca for manihot, and noodles for mung beans. Eighteen healthy subjects randomly assigned received three different starches under one form of conditioning. All products were submitted to in vitro alpha-amylolysis. Raw manihot starch produced the lowest (p less than 0.05) metabolic responses. Cooking significantly (p less than 0.01) increased plasma responses. However, cooked mung bean noodles gave metabolic responses similar to those of raw products. Close correlations were found between percentages of in vitro starch hydrolysis at 30 min and mean areas under the glycemic curves and the insulinemic curves (r = 0.95, p less than 0.001).

Insulinemic and glycemic indexes of six starch-rich foods taken alone and in a mixed meal by type 2 diabetics.

The glycemic index concept neglects the insulin secretion factor and has not been systematically studied during mixed meals. Six starch-rich foods were tested alone and in an isoglucido-lipido-protidic meal in 18 NIDDs and compared with a glucose challenge. These test meals were randomly assigned using a three factor experiment design. All three tests contained 50 g carbohydrate; mixed meals were adjusted to bring the same amount of fat (20 g), protein (24 g), water (300 mL), and calories (475 kcal) but not the same amount of fiber. Whatever the tested meals, foods elicited a growing glycemic index hierarchy from beans to lentils, rice, spaghetti, potato, and bread (mean range: 0.21 +/- 0.12-92 +/- 0.12, p less than 0.001). Mixing the meals significantly increased the insulinemic indexes (p less than 0.05) and introduced a positive correlation between glycemic and insulinemic indexes (n = 6, r = 0.903; p less than 0.05). The glycemic index concept remains discriminating, even in the context of an iso-glucido-lipido-protidic meal. Insulinemic indexes do not improve discrimination between foods taken alone in type 2 diabetics: they only discriminate between foods during mixed meals, similarly to glycemic indexes.

Pasta cooking time: influence on starch digestion and plasma glucose and insulin responses in healthy subjects.

The influence of pasta cooking time on starch digestion and plasma glucose and insulin responses was studied in 12 healthy subjects. During 3 consecutive days, one of three pasta test meals (50 g starch) cooked for 11, 16.5, and 22 min was served to each volunteer in a random order. Hydrogen and methane breath excretion was measured after pasta ingestion; plasma responses were compared with those of an equivalent oral glucose-tolerance test. No significant differences were found between cooking times and plasma indices, orocecal transit time, or incremental hydrogen excretion (delta peak hydrogen). With one exception, pasta meals that were completely absorbed were ingested by methane producers. Postprandial delta peak hydrogen was significantly lower in methane than in nonmethane producers (p less than 0.02). These results point to a lack of influence of cooking time on nutritional characteristics of pasta and suggest that starch malabsorption determined by breath-hydrogen-test criteria may be underestimated in methane producers.

Chronic consumption of short-chain fructooligosaccharides by healthy subjects decreased basal hepatic glucose production but had no effect on insulin-stimulated glucose metabolism.

We aimed to study the effects of chronic ingestion of short-chain fructooligosaccharides (FOS), an indigestible carbohydrate, on hepatic glucose production, insulin-mediated glucose metabolism, erythrocyte insulin binding, and blood lipids in healthy subjects. Twelve healthy volunteers received either 20 g FOS/d or sucrose for 4 wk in a double-blind crossover design. FOS did not modify fasting plasma glucose and insulin concentrations. Mean (+/- SEM) basal hepatic glucose production was lower after FOS than after sucrose consumption (2.18 +/- 0.10 compared with 2.32 +/- 0.09 mg.kg-1, min-1, respectively; P < 0.02, paired Student's t test). However, neither insulin suppression of hepatic glucose production nor insulin stimulation of glucose uptake measured by hyperinsulinemic clamp was significantly different between the two dietary periods. Erythrocyte insulin binding was also comparable. Serum triacylglycerols, total and high-density- lipoprotein cholesterol, apolipoproteins A-I and B, and lipoprotein(a) were not modified by FOS. To try to understand why FOS did not increase serum lipids, the in vitro production of short-chain fatty acids from FOS was evaluated by using human fecal inoculum and compared with that from lactulose, which was found to increase serum lipids. FOS produced an acetate-propionate ratio two times lower than that of lactulose. We conclude that 4 wk of 20 g FOS/d decreased basal hepatic glucose production but had no detectable effect on insulin-stimulated glucose metabolism in healthy subjects. The colonic fermentation pattern of undigestible carbohydrates may be relevant to predicting their metabolic effects.

Satiating effect of proteins in healthy subjects: a comparison of egg albumin, casein, gelatin, soy protein, pea protein, and wheat gluten.

The influence of six dietary protein types (egg albumin, casein, gelatin, soy protein, pea protein, and wheat gluten) on satiety and food intake was investigated. Twelve healthy subjects ingested six protein-manipulated lunches (approximately 5.2 MJ, 22% of energy as protein) according to a within-subjects design. Test meals were controlled for energy, macronutrients, fiber, and palatability. Nearly 65% of total protein varied between sessions. After lunch, satiety was assessed for 8 h and energy and macronutrients intakes were measured for 24 h. Blood was collected for determination of postprandial plasma glucose and insulin responses. Results showed no effect of the type of protein on satiety, on 24-h energy or macronutrient intakes, or on postprandial plasma glucose and insulin concentrations. These findings differ in part from those obtained previously in humans, which suggested that proteins may be differentiated in terms of their satiating capacities. We conclude that varying the protein source in a mixed meal does not affect food behavior in healthy humans, probably because coingestion of carbohydrate and fat with protein buffers the kinetics of the physiologic mechanisms implicated in postprandial satiety after a protein load.

Euglycemic hyperinsulinemic clamp to assess posthepatic glucose appearance after carbohydrate loading. 1. Validation in pigs.

BACKGROUND: Precise knowledge of the rate of glucose absorption after meal feeding requires invasive methods in humans. OBJECTIVE: This study aimed to validate in an animal model a technique combining the euglycemic hyperinsulinemic clamp and oral carbohydrate loading (OC-Clamp) as a noninvasive procedure to quantify the posthepatic appearance of glucose after oral carbohydrate loading. DESIGN: Twenty-one pigs were fitted with arterial, jugular, portal, and duodenal catheters and a portal blood flow probe. At glucose clamp steady state, duodenal glucose (0.9 g/kg; DG-Clamp) and oral carbohydrate (140 g corn or mung bean starch as part of a mixed meal; OC-Clamp) were administered while the glucose infusion was progressively reduced to compensate for the incremental posthepatic appearance of glucose. [3-3H]glucose was used to assess the glucose turnover rate. RESULTS: Hepatic glucose production was totally suppressed by insulin infusion, and the whole-body glucose turnover rate remained stable during glucose absorption. The incremental portal appearance of glucose after the DG load was not altered by hyperinsulinemia, and the cumulative posthepatic appearance of glucose was 63 +/- 3% (x +/- SEM) of the DG load. The net hepatic portal appearance of glucose remained constant during absorption (34 +/- 3% of the load). After the OC load, the respective portal appearance rates of glucose were significantly different between carbohydrate sources; however, the rates paralleled those of the posthepatic appearance of glucose. Again, net hepatic glucose uptake expressed as portal appearance was similar for both carbohydrates. CONCLUSIONS: The results validate the OC-Clamp method to monitor the posthepatic appearance of glucose after carbohydrate ingestion and to discriminate between different carbohydrate sources. The results suggest that the technique be used in humans.

Euglycemic hyperinsulinemic clamp to assess posthepatic glucose appearance after carbohydrate loading. 2. Evaluation of corn and mung bean starches in healthy men.

BACKGROUND: The rate of absorption of glucose from carbohydrates is important in several aspects of health. We recently validated a noninvasive technique in pigs, euglycemic hyperinsulinemic clamp plus oral carbohydrate loading (OC-Clamp), to quantify the rate of net posthepatic appearance of glucose after ingestion of carbohydrates. OBJECTIVE: The OC-Clamp procedure was performed in 8 healthy men to compare the net posthepatic appearance of glucose after ingestion of 1 of 3 carbohydrates. DESIGN: Human volunteers underwent the OC-Clamp procedure at an insulin infusion rate of 1.5 mU x kg(-1) x min(-1) (n = 5). The oral carbohydrate load (1 g/kg) consisted of glucose, cornstarch, or mung bean starch. During the OC-Clamp procedure, the glucose infusion rate decreased during absorption to maintain plasma glucose steady state and the decrease reflected the net posthepatic appearance of glucose. In addition, carbohydrates were loaded without insulin infusion (n = 6) and glycemic indexes were calculated (with glucose as the reference). RESULTS: The mean (+/-SEM) glycemic index of cornstarch was higher (95 +/- 18) than that of mung bean starch (51 +/- 13). In the OC-Clamp experiments, the posthepatic appearance of glucose and cornstarch did not differ significantly and represented 79.4 +/- 5.0% and 72.6 +/- 4.0%, respectively, of the load after complete absorption (within 3 h). In contrast, the net posthepatic appearance of glucose from mung bean starch was significantly lower (35.6 +/- 4.6% of the load, P < 0.001) than that from glucose and cornstarch, even 4.5 h postprandially. CONCLUSIONS: The OC-Clamp technique allows a continuous assessment of net posthepatic appearance of glucose after ingestion of carbohydrates and significant discrimination between corn and mung bean starches.

Reducing ice cream energy density does not condition decreased acceptance or engender compensation following repeated exposure.

OBJECTIVES: The preferences for high-fat foods are believed to be based on their sensory attributes and energy density; however less is known about how such preferences might be weakened, other than in response to deterioration in flavor or textural quality. The aim of the present study was to see whether acceptability of reduced fat/energy foods would wane as the original post-ingestive nutritional benefits are reduced when palatability remains essentially constant. DESIGN: Repeated measures, within-subjects design conducted in two counterbalanced three week trials. SETTING/SUBJECTS: Sixteen normal-weight males (mean age 25.8 +/- 1.2 y) came to our laboratory at the Hôpital Hotel Dieu in Paris to eat an afternoon snack on 13 consecutive days (excluding weekends). INTERVENTION/OUTCOME MEASURES: Intake was recorded following repeated exposure to two flavors of standard (10% fat as a percentage of total solids weight), and low (3%) fat ice cream. One group received standard vanilla or low-fat strawberry ice cream on alternate days for two consecutive weeks; these flavor associations were reversed for a second group. The two flavors were rated as equipalatable at the beginning of the experiment at all energy levels. RESULTS: Subjects consumed the same quantity of ice cream throughout the experimental period, independent of energy density or flavor. Consequently, aggregate (summed) energy intake for subjects consuming low-fat ice cream was significantly lower (by 581 kJ (139 kcal), 15.4 g fat). Food intake records for the 24 h period immediately following the test sessions revealed no compensation for fat or energy. Despite the 28% reduction in energy density for the low-fat version, acceptance for the flavors associated with the reduced-energy versions had not declined by the end of the experimental period. CONCLUSIONS: The findings suggest that acceptance of reduced-fat foods may not be critically dependent on the post-ingestive metabolic effects when the reductions in energy density are small. Further tests with more severe reductions, and perhaps over more prolonged time periods, will be necessary to determine at what level of substitution acceptance might begin to deteriorate.

Varying the protein source in mixed meal modifies glucose, insulin and glucagon kinetics in healthy men, has weak effects on subjective satiety and fails to affect food intake.

OBJECTIVE: To evaluate the influence of three dietary protein types (casein, gelatin, soy protein) on satiety and food intake, at two levels of loading (total energy of test meals: 3.6 or 1.8 MJ). DESIGN: The study employed a repeated measures design. Test meals were controlled for energy, macronutrients, fiber and palatability, and contained about 23% energy as protein (of which about 65% was experimentally manipulated). Postprandial subjective satiety and hunger, plasma glucose, insulin and glucagon were assessed for 8 h, and energy and macronutrient intakes were monitored for 24 h. SUBJECTS: Nine healthy normal-weight men. RESULTS: No effect of the type of protein on 24 h energy and macronutrient intakes was observed despite a significant effect of protein source on the kinetics of peripheral metabolic responses (but only after 3.6 MJ lunches), and inconsistent effects on subjective hunger and satiety responses A casein-enriched lunch delayed glucose and insulin responses for 1.5 h, compared with soy protein, probably due to a lag in gastric emptying. CONCLUSION: Varying the protein source in a mixed meal modifies glucose, insulin and glucagon kinetics in healthy men, but these variations in satiety-implicated factors have inconsistent effects on subjective satiety and fail to affect food intake. SPONSORSHIP: Eridania Béghin-Say, Vilvoorde, Belgium and Association Nationale de la Recherche Technique, France (Convention CIFRE no 537/94).

Nutritional aspects of short-chain fructooligosaccharides: natural occurrence, chemistry, physiology and health implications.

Short-chain fructooligosaccharides occur in a number of edible plants, such as chicory, onions, asparagus, wheat... They are a group of linear fructose oligomers with a degree of polymerisation ranging from n = 1 up to 5 (oligosaccharides). Short-chain fructooligosaccharides, to a large extent, escape digestion in the human upper intestine and reach the colon where they are totally fermented mostly to lactate, short chain fatty acids (acetate, propionate and butyrate), and gas, like dietary fibres. As a consequence of their fermentation, their caloric value is approximately 2 Kcal/g. A faecal bulking effect of fructooligosaccharides has been observed in humans. An important property of short-chain fructooligosaccharides is the stimulation of bifidobacterial growth specifically while suppressing the growth of potentially harmful species such as, for example, Clostridium perfringens in the colon. It is associated with a decrease in faecal pH, an increase in faecal or colonic organic acids, a decrease in the production of nitrogenous end products in urine and stools, a decrease in faecal bacterial enzymatic activities and a modification in faecal neutral sterols. The short-chain fructooligosaccharides enhance magnesium absorption in humans and have been shown, in animal models, to reduce colon tumour development by enhancing both colon butyrate concentrations and local immune system effectors.

Glycaemic index concept and metabolic diseases.

Glycaemic response is not just a function of a compound belonging to the class of simple sugars or to the class of starches, or in other words, the size of the molecule. Glycaemic response to carbohydrates depends on several factors, particularly the chemical nature of the glucids, their origin, their mode of preparation, the physical form under which food is consumed, the presence of other nutrients (lipids, proteins) and fiber. Glycaemic and insulinemic indexes can be used to semi-quantitatively classify types of food as a function of their power to raise glucose and insulin levels. A recent mera-analysis of a dozen clinical trials has shown the utility of replacing high glycaemic index carbohydrates with low glycaemic index carbohydrates to improve different metabolic parameters in patient subgroups at risk (DDM, NIDDM, high triglyceride levels, etc.). In addition, this knowledge can eliminate the need to systematically forbid all sugars and sweet foods, and thus in an apparent paradox, to respect both food behavior and enjoyment alongside compliance with dietary advice.

The cumulative effect of small dietary changes may significantly improve nutritional intakes in free-living children and adults.

BACKGROUND/OBJECTIVES: The ELPAS (Etude Longitudinale Prospective Alimentation et Santé) study was an 8-month randomized controlled dietary modification trial designed to test the hypothesis that family dietary coaching would improve nutritional intakes and weight control in 2026 free-living children and parents. It resulted in significant nutritional changes, with beneficial effects on body mass index in adults. In these ancillary analyses, we investigated dietary changes throughout the intervention. SUBJECTS/METHODS: Before the study, modeling analyses were carried out on the French Association Sucre Produits Sucrés Consommation et Communication (ASPCC) food-consumption database to identify the most efficient dietary intervention strategy. During the study, all participants performed monthly three nonconsecutive 24-h dietary recalls: this allowed for measuring changes in the number of servings per day and serving size for each targeted food category throughout the intervention. RESULTS: Modeling analyses showed that targeting only the 10 main foods contributing to fat and carbohydrate intakes did not allow for reaching the ELPAS nutritional goals. As a result, it was decided to target more foods and to propose several types of dietary advice (such as change in serving size, change in cooking method, food substitution). This strategy led to many appropriate dietary changes during the intervention, but only a few of them reached significance. The mean number of servings per day was indeed significantly modified for only 7% of the targeted food categories in children and 17% in parents. The mean serving size was modified for only 12% of targeted food categories in children and 9% in parents. CONCLUSIONS: The cumulative effect of small dietary changes may induce significant nutritional improvements, with limited burden for populations.

Plasma and urine kinetics of erythritol after oral ingestion by healthy humans.

The plasma and urine kinetics of erythritol and the effect of erythritol on plasma glucose and insulin levels were studied in human volunteers administered a single oral dose of 1 g erythritol/kg body wt. The plasma level of erythritol increased during the first 30 to 40 min, reaching a maximum value of approximately 2.2 mg/ml after 90 min. Plasma levels of erythritol then declined gradually to approximately 1.5 to 1.7 mg/ml at the end of the 3-hr sampling period. An average of 30% of the ingested amount of erythritol was excreted unchanged in the urine during the first 3 hr. Total urinary excretion increased to 78% after 24 hr. Renal clearance of erythritol was approximately half that of creatinine, indicating tubular reabsorption of erythritol by the kidney. Mean plasma glucose and insulin levels, measured for up to 3 hr after ingestion, were unaffected by erythritol. The results of this study indicate that erythritol was readily absorbed following oral administration and was excreted unchanged in the urine. Less than 20% of erythritol remained unabsorbed and was available for colonic fermentation and potential production of short-chain fatty acids. Its caloric value was estimated to be < or = 0.4 kcal/g.

Gastrointestinal response and plasma and urine determinations in human subjects given erythritol.

This study was undertaken to examine the influence of erythritol on certain plasma and urinary parameters and to assess the gastrointestinal response of humans given erythritol at single oral doses of 0.4 or 0.8 g/kg body wt/day. Three groups of six healthy volunteers each received a midmorning snack containing the equivalent of 0.4 or 0.8 g erythritol/kg body wt or 0.8 g sucrose/kg body wt. A fourth group received no snack and served as a negative control group. Consumption of erythritol did not affect plasma osmolarity, water consumption, or diuresis, and no significant variations in plasma or urine electrolyte balance were observed. Plasma glucose and insulin concentrations also were not affected by erythritol. Gastrointestinal responses to erythritol were comparable to those of sucrose. Plasma and urine erythritol concentrations increased within 2 hr of ingestion in proportion to the amount ingested. Approximately 60% of the erythritol dose was eliminated in the urine within 22 hr. The results of this study demonstrate that ingestion of erythritol at doses of up to 0.8 g/kg body wt does not alter plasma or urine osmolarity or electrolyte balance and is well tolerated by the digestive tract.

Alpha-amylase (EC 3.2.1.1) susceptibility rather than viscosity or gastric emptying rate controls plasma responses to starch in healthy humans.

The relationship between starch alpha-amylase (EC 3.2.1.1) susceptibility, plasma responses and gastric emptying rates has been investigated in humans. Nine randomly chosen healthy subjects were given three carbohydrate test meals (25 g starch or equivalent glucose units): two maize starch pastes with (a) 240 (S24) or (b) 500 (S50) g amylose/kg, and a glucose solution (GS). At 30 min, in vitro starch alpha-amylolysis was 48 (SD 4)% for S24 and 35 (SD 4)% for S50. Test meals differed in viscosity (mPa x s: S24, 54,000; S50, 190; GS, 4). Carbohydrates were labelled with 99mTechnetium and isotope gastric emptying was measured by external gamma counting. Carbohydrate isotopic gastric emptying patterns were exponential. Half gastric emptying time (min) was significantly (P less than 0.05) shorter for S50 (19(SD 2] than for GS (26(SD 2] or S24 (29(SD 2]. No correlation was found between half gastric emptying time and plasma response values. Values for peak insulin (pmol/l) above fasting were significantly (P less than 0.05) different: GS, 306 (SD 11); S24, 227 (SD 11); S50, 187 (SD 11). It is concluded that alpha-amylase susceptibility of the test carbohydrates is a determining factor in the insulin response of healthy subjects, while viscosity of the test meals and gastric emptying rate have no effect.

The use of low glycaemic index foods improves metabolic control of diabetic patients over five weeks.

The aim of the present study was to determine whether any benefit might occur from lowering the glycaemic index of diet in the medium term in diabetic patients. Eighteen well-controlled diabetic patients (12 Type 1 and 6 Type 2 non-insulin-treated), were assigned to either a high mean glycaemic index or low mean glycaemic index diet for 5 weeks each in a random order using a cross-over design. The two diets were equivalent in terms of nutrient content and total and soluble fibre content. The glycaemic indices were 64 +/- 2 (mean +/- SD) % and 38 +/- 5% for the two diets. The high glycaemic index diet was enriched in bread and potato and the low glycaemic index diet in pasta, rice, and legumes. At the end of the study periods, the following variables were improved on the low compared to the high glycaemic index diet: fructosamine (3.9 +/- 0.9 vs 3.4 +/- 0.4 mmol l-1, p less than 0.05); fasting blood glucose (10.8 +/- 2.8 vs 9.6 +/- 2.7 mmol l-1, p less than 0.02); 2-h postprandial blood glucose (11.6 +/- 2.9 vs 10.3 +/- 2.5 mmol l-1, p less than 0.02); mean daily blood glucose (12.0 +/- 2.5 vs 10.4 +/- 2.7 mmol l-1, p less than 0.02); serum triglycerides (1.5 +/- 0.9 vs 1.2 +/- 0.6 mmol l-1, p less than 0.05). No significant differences were found in body weight, HbA1C, insulin binding to erythrocytes, insulin and drug requirements, and other circulating lipids (cholesterol, HDL-cholesterol, phospholipids, Apolipoprotein A1, Apolipoprotein B). Thus the inclusion of low glycaemic index foods in the diet of diabetic patients may be an additional measure which slightly but favourably influences carbohydrate and lipid metabolism, requires only small changes in nutritional habits and has no known deleterious effects.