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Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes.

Metformin often promotes weight loss in patients with obesity with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism may be attributed to decreased food intake. This study has tested the effect of metformin on satiety and its efficacy in inducing weight loss. Twelve diet-treated NIDDM women with obesity were randomly given two dose levels (850 mg or 1700 mg) of metformin or placebo at 0800 for three consecutive days followed by a meal test on the third day on three occasions using a 3x3 Latin square design. The number of sandwich canapes eaten in three consecutive 10-minute periods beginning at 1400 hours was used to quantitate food intake, and the level of subjective hunger was rated just before the sandwich meal with a linear analogue hunger rating scale at 1400 after a 6-hour fast. The prior administration of metformin produced a reduction in calorie intake after each of the two doses of metformin treatment. The 1700-mg metformin dose had the most marked appetite suppressant action. Similarly, hunger ratings were significantly lowered after metformin, and the effect was most pronounced after the administration of 1700 mg of metformin. To assess the efficacy of metformin in reducing bodyweight, 48 diet-treated NIDDM women with obesity who had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA (American Diabetes Association) diet before being randomized to receive either metformin (850 mg) or placebo twice daily in a double-blind fashion for 24 weeks. A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind placebo period followed the 24-week double-blind treatment period. Subjects treated with metformin continued to lose weight throughout 24 weeks of treatment; their mean maximum weight loss was 8 kg greater than that of the placebo group, with corresponding lower HbA1C and fasting blood glucose levels at the end of the active treatment period. These results indicate that metformin decreases calorie intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM patients with obesity.

Adult↗

Human pharmacokinetics and tolerability of L-365,260, a novel cholecystokinin-B antagonist.

A study was conducted to examine the tolerability and pharmacokinetics of single and multiple oral doses of L-365,260, a novel antagonist for type B cholecystokinin (CCK) receptors and to quantify effects of selective blockade of type B CCK receptors through treatment with L-365,260 on measures of anxiety, hunger, and cognitive performance. Healthy volunteers were given single oral doses of up to 50 mg of L-365,260 and multiple oral doses of up to 25 mg every 6 hours for 10 days. Plasma concentrations of L-365,260 were quantified by means of high-performance liquid chromatography. Anxiety and hunger were assessed by visual analog scale and the Spielberger State Anxiety Index. Cognitive testing was used to evaluate attention level and short-term memory. L-365,260 was rapidly absorbed and a biphasic pattern of elimination was demonstrated with a terminal half-life (t1/2) of 8 to 12 hours. The mean (n = 6) values for peak plasma concentration (C(max)) and time to peak concentration (t(max)) of L-365,260 were 503 ng/mL and 1.25 hours, respectively, after a single 50-mg oral dose. Accumulation of L-365,260 plasma concentrations was seen after the prescribed multiple-dose regimens. Steady state was achieved after 3 days of oral administration. L-365,260 had an acceptable tolerability profile after oral administration. No changes in measures of anxiety, hunger, or short-term memory were observed at doses of L-365,260 shown to have antagonist activity at the CCK-B receptor.

Administration, Oral↗

Micro- and macroanalyses of patterns within a meal in anorexia and bulimia nervosa.

Hospitalized women with anorexia nervosa and/or bulimia nervosa and dietarily restrained and unrestrained, clinically normal women were provided with a multi-item breakfast meal. Eating patterns and hunger and satiety ratings were assessed. Subjects were offered three foods which varied in fat and carbohydrate contents. Anorectic-restrictors differed most from the control subjects: they had a longer meal duration, a slower overall rate of eating, more frequent pauses during the meal, and more short bouts of eating. They also displayed abnormal ratings of hunger and satiety: they were generally less hungry, had less urge to eat, and were more full than controls of bulimics. Both anorectic and bulimic patients showed more variability in total energy intake than did the controls. Patients usually displayed one of two patterns - either severe restriction or overeating. Abnormal hunger and satiety patterns indicating confusion typified the responses of bulimics; additionally, they showed more urge to eat in the post-meal period than did the controls. A higher proportion of fat in the initial part of the breakfast was related to a larger meal size for the bulimics. It is suggested that these techniques may be useful in evaluating the outcome of treatment for eating disorder patients.

Anorexia Nervosa↗

The effect of soup on satiation.

We compared the influence of three solid/liquid preloads to a no-preload condition given at lunchtime on hunger ratings and energy intake of the lunch and subsequent dinner in 12 lean and 10 overweight young men. The preloads (vegetables and water, strained vegetable soup, chunky soup) were of the same composition and volume but differed in distribution of nutrients between the liquid and the solid phases, and in the size of solid particles. Hunger ratings were reduced by the preloads; there was a significantly greater suppression of hunger after the chunky soup than after the vegetables and water. In both groups, the soups reduced energy intake at lunch, although the chunky soup had the most effect. In the overweight subjects, a reduced lunch intake was also followed by a reduced dinner intake. The benefit to weight control of large particles in soup should be evaluated.

Adult↗

Dietary restraint anxiety and its relationship to human eating behavior.

Ninety-five female university students completed Stunkard and Messick's (Journal of Research Psychosomatic Research, 29, 71-83, 1985) Three-Factor Eating Questionnaire, measuring three dimensions of human eating behavior: cognitive restraint, disinhibition, and hunger susceptibility. They were led through the visualization of a neutral or pleasant scene and a food scene, but were instructed that they would not be able to eat the food. Only hunger susceptibility was found to be significantly correlated with ratings of subjective anxiety (SUDS) and urge to eat in the not eating situation after any variability associated with the neutral scene was removed. That is, internal (hunger) and external (incentive) cues when linked to not eating are sources of anxiety. Treatment programmes for obesity might well include desensitization of these cues.

Adolescent↗

Satiety does not affect gustatory activity in the nucleus of the solitary tract of the alert monkey.

Feeding to satiety decreases the acceptability of the taste of food. In order to determine whether the responsiveness of gustatory neurons in the nucleus tractus solitarius (NTS) is influenced by hunger, neural activity in the NTS was analyzed while monkeys were fed to satiety. Gustatory neural activity to glucose, fruit juice, NaCl, HCl and quinine HCl was measured before, while and after the monkey was fed to satiety with glucose, fruit juice or sucrose. While behavior turned from avid acceptance to active rejection upon repletion, the responsiveness of NTS neurons to the stimulus array, including the satiating solution, was unmodified. It is concluded that at the first central synapse of the taste system of the primate, neural responsiveness is not influenced by the normal transition from hunger to satiety. This is in contrast to the responses of a population of neurons recorded in the hypothalamus, which only occur to the taste of food when the monkey is hungry. Thus, NTS gustatory activity appears to occur independently of normal hunger and satiety, whereas hypothalamic neuronal activity is more closely related to the influence of motivational state on behavioral responsiveness to gustatory stimuli.

Animals↗

The effect of posture on gastric emptying and intragastric distribution of oil and aqueous meal components and appetite.

BACKGROUND: It is uncertain whether gastric emptying of fat is determined mainly by its physical characteristics or chemical composition. In particular, the intragastric distribution of extracellular fat and the importance of that distribution to gastric emptying of fat is controversial. The effects of posture on gastric emptying, intragastric distribution, and appetite after ingestion of a meal containing oil and aqueous phases was evaluated. METHODS: Eleven volunteers consumed 60 mL 99mTc-(V)-thiocyanate-labeled olive oil and 290 mL 113mIn-labeled soup while sitting and while lying in the left lateral decubitus position. Hunger before and after the meal was recorded. RESULTS: In the sitting position, oil emptied from the stomach more slowly (P < 0.01) whereas in the decubitus position oil emptied faster (P < 0.01) than the aqueous phase. Oil was preferentially retained in the proximal stomach when sitting (P < 0.01), and more oil was retained in the distal stomach in the decubitus position (P < 0.05). The amount of oil that emptied in the first 180 minutes was not different between the two postures. The aqueous phase emptied much more slowly (P < 0.01) in the decubitus position. At 120 minutes and 180 minutes, subjects were less hungry (P < 0.05) in the decubitus position. In the decubitus position, hunger at 120 minutes and 180 minutes was related to the retention of oil (r > or = 0.79; P < 0.01) in the stomach. CONCLUSIONS: These results indicate that (1) gravity has a major effect on the intragastric distribution and relatively little effect on total stomach emptying of oil, and (2) postprandial hunger is affected by posture and, in the decubitus position, is inversely related to the amount of oil that has entered the small intestine.

Adolescent↗

Decreased resistance to extinction in ob/ob mice following operant training.

Inconsistent results have emerged from past studies in which operant conditioning paradigms were used to assess the hunger motivation of genetically obese mice relative to that of normal mice. Methodological considerations indicated the need to examine operant performance to a criterion, rather than performance during time-based sessions, and then to focus upon response differences in resistance to extinction. Therefore, genetically obese (ob/ob) mice and normal littermates were trained successfully to bar-press for 100 food rewards on either a CRF or a FR-10 schedule of reinforcement. Extinction behavior was then examined over 9 daily 1-hr sessions. While obese and normal mice evidenced similar patterns of learning, or response discrimination for food rewards, they evidenced different levels of hunger motivation during extinction conditions. Obese mice displayed a greater reduction in responding across extinction sessions, or less resistance to extinction, than normal mice following training on both schedules of reinforcement. These findings suggest that ob/ob mice exhibit lower levels of hunger motivation than normal littermates.

Animals↗

Effect of food change on consumption, hedonics, and salivation.

This study assessed the influence of introducing a new food after repeated presentations of one food on food consumption, hedonics, and salivation. Male subjects were provided repeated 150-calorie courses of pizza or cheeseburger until satiety. Hedonics and salivation were measured before each course. Subject were then provided an additional 450 calorie course of the same or the new food. During the development of satiety, subjects showed reliable increases in fullness and decreases in hunger and hedonics. Salivation briefly increased to maximal salivation, followed by reliable decreases. No differences in pattern of change for fullness, hunger, hedonics or salivation were noted across foods. Presentation of the new food resulted in significantly greater caloric consumption than another serving of the same food (130 vs. 44.5 kcal), an increase in hedonics and salivation relative to presentation of the same food, with no influence on hunger or fullness. These results suggest that after satiety develops, response recovery for subjective, physiological, and behavioral components of eating can be observed when new, palatable foods are presented.

Adolescent↗

A direct measure of satiety disturbance in patients with bulimia nervosa.

To determine whether patients with bulimia nervosa (BN) experience the development of satiety during a meal differently than control subjects, a novel laboratory meal procedure was employed. Eleven women with BN and 11 women without eating disorders consumed a yogurt shake meal after being instructed to binge. After each 75-g increment consumed, the subjects were signaled by a tone to fill out a questionnaire on which they were asked to rate various sensations on visual analog scales. The sensations included "Fullness", "Hunger", "Desire" for a favorite food, "Pleasantness" of consuming the shake, "Sickness", and having "Enough" to consume. Although patients, before purging, consumed significantly more food than the controls, who did not purge (1597 +/- 626.5 g vs. 1004 +/- 362.5 g, mean +/- SD), their final questionnaire ratings were not significantly different from the controls' ratings. Patients ate significantly more than the controls before reaching 50% of their range of "Hunger" rating and 75% of their "Full", "Desire", "Sick", and "Enough" rating ranges. The patients also ate significantly more than the controls between 75% and 100% of their "Hunger" rating range. These data suggest that one possible mechanism for overeating in patients with BN may be their failure to perceive or respond as normal subjects do to the range of sensations associated with satiety. Collecting ratings as a function of intake may provide a method for assessing and studying eating disturbances in clinical populations.

Adult↗

Failure of naltrexone to affect the pleasantness or intake of food.

Two separate studies were conducted to investigate the effects of oral naltrexone on the pleasantness ratings of foods and food intake. In both studies, normal-weight, nondieting males rated hunger, fullness, mood and the pleasantness of the taste of a variety of foods before and after double-blind administration of 50 mg of naltrexone or placebo. All subjects received a test meal, in a counterbalanced, repeated measures design. In the first study, 12 subjects were given a self-selection test meal after overnight deprivation. In the second study 14 subjects were given an ice cream test meal with no deprivation. In both experiments the pleasantness of the taste of the foods, sensory-specific satiety, hunger ratings and overall energy intake were not differentially influenced by naltrexone administration. In Experiment 2, intake of the ice cream was greater after active drug administration because subjects who received active drug on the first session ate less ice cream in the placebo session. In conclusion, in the short term, naltrexone had no impact on hunger, sensory-specific satiety or food intake.

Adolescent↗

Human eating: diagnosis and prognosis.

Despite substantial recent progress, we remain without a comprehensive theory of human eating. The constraining influence of the single-factor, hunger-satiety model of feeding in animals is addressed. Three aspects of human eating--counter-regulation in dieters, the effects of social models, and the influence of distress on eating--are reviewed briefly, in an attempt to demonstrate that a simple hunger-satiety model cannot handle the data. It is imperative that we consider social, cognitive, and other influences on eating as important casual agents in their own right; these influences are not necessarily mediated by their effect on hunger-satiety. A comprehensive theory of human eating is not likely to appear soon, but there are grounds for optimism in the process (rather than the final result) of research.

Animals↗

Effects of deprivation on salivary flow in the apparent absence of food stimuli.

Salivation performance in the absence of food-related stimuli was measured with an absorbent technique in 19 subject under no (0-1 h) and moderate (4-6 h) levels of food deprivation. Overall, salivation was reliably (p less than 0.05) greater the higher the hours of deprivation. Results also revealed a reliable positive correlation between hours of deprivation and subjective ratings of hunger. For subjects whose hunger ratings coincided with hours of deprivation, analysis of the salivation data yielded highly reliable (p less than 0.01) differences due to deprivation/hunger. For subjects who reported the same level of hunger at different hours of deprivation, there were no reliable differences in salivation due to deprivation.

Adult↗

Aspartame: effect on lunch-time food intake, appetite and hedonic response in children.

Two experiments were conducted, each with 20 healthy 9-10-year-old children. After an overnight fast, subjects were given a standardized breakfast at 0830 hrs, the treatments at 1030 hrs, and a lunch containing an excess of foods at 1200 hrs. Visual analog scales of hunger, fullness, and desire to eat were administered 5 min before and 20 and 85 min after treatment. Lunch-time food intake was measured. In experiment 1, either aspartame (34 mg/kg), or the equivalent sweetness of sodium cyclamate, was given in an ice slurry (300 ml) of unsweetened strawberry Kool-Aid with carbohydrate (1.75 g/kg polycose). In experiment 2, drinks (300 ml) contained either sucrose (1.75 g/kg) or aspartame (9.7 mg/kg). In both experiments, significant meal- and time-dependent effects were observed for subjective feelings of hunger, fullness and desire to eat. Treatments, however, did not affect either subjective feelings of appetite or lunch-time food intake. Thus, aspartame consumed without or with carbohydrate, did not affect either hunger or food intake of children when compared with the sweeteners sodium cyclamate and sucrose, respectively.

Appetite↗

Ineffectiveness of ceruletide to reduce food intake and body weight in obese women hospitalized for weight reduction and treated with a restricted diet. A double-blind study.

Ceruletide is a synthetic decapeptide closely resembling the 8-carboxy-terminal peptide of cholecystokinin (CCK-8) with which it shares several biological properties. In a double-blind study versus placebo, we evaluated the effects of ceruletide on self-rated hunger and food intake at lunch time, as well as on body weight in 14 obese women hospitalized for weight reduction and on a restricted diet. During two 6-day courses of treatment with ceruletide or placebo, ceruletide 0.3 microgram/kg b.wt. or an equivalent volume of its diluent were injected IM at 11.30 a.m., i.e., 30 min before lunch. Feelings of hunger were quantitated, using a visual analogue self-rating scale, prior to the injection of ceruletide or placebo and 30 min thereafter, i.e., just prior to the start of meal ingestion, as well as 2 hr after the start of the meal. Duration and caloric content of food ingested at lunch, as well as morning body weight, were recorded daily. Ceruletide, compared to placebo, did not significantly influence any of the above variables. However, in the first three experimental days, the increase in self-rated hunger from values before the injection to 30 min thereafter was less marked, though not significantly so (0.05 less than p less than 0.1), with ceruletide than with placebo. Thus, it appears that ceruletide, under the experimental conditions of the present study, was not effective in enhancing the patients' motivation to lose weight and to further restrict their food intake at lunch time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Non food-related environmental stimuli induce increased meal intake in healthy women: comparison of television viewing versus listening to a recorded story in laboratory settings.

The objective of the present study, performed under laboratory conditions, was to assess the impact of two non food-related environmental stimuli (television and auditory stimulus) on meal intake. Normal weight women (N = 48) ate lunch in the laboratory once a week for four weeks. All lunches were identical and included popular traditional foods, of which participants could eat ad libitum. The first and last lunches were eaten in the absence of the environmental stimuli (control conditions); in the other two tests, presented in random order, subjects ate while either watching television or listening to a recorded story. Energy intakes were determined for each meal, as were ratings of hunger, satiety and meal palatability. Subjects filled out the Three Factor Eating Questionnaire at the end of the meal series. Meal size was significantly larger in the presence of both environmental stimuli than in both control conditions (+11.6%, 280 kJ, p < 0.01). Television viewing induced a significant stimulation of intake, equal to, but not greater than the effect of the auditory stimulus. Ratings of hunger, satiety, and palatability were not significantly different between conditions, despite the differences in intake. These results suggest that environmental, non food-related stimuli could stimulate intake regardless of hunger-satiety or palatability conditions. Environmental stimulation of eating should be tested in other populations, eg subjects with weight control problems, and other conditions, e.g. free-living.

Adolescent↗

Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy.

Leptin deficiency has been associated with extreme obesity and hyperphagia in rodents and humans. A rare genetic disorder in humans yields the absence of the hormone leptin, extreme obesity, and a ravenous appetite. Reports on these rare cases have indicated that therapy using leptin injections can yield significant weight loss and changes in appetite. The aim of this report on acute leptin therapy in three leptin deficient adults was to provide a microanalysis of changes in eating behavior and ratings of hunger and satiety. In addition to substantial weight loss, 15 weeks of leptin therapy was associated with approximately 50% reduction in food intake and substantial changes in ratings of hunger and satiety before most meals. After short-term leptin therapy, the three participants ate until ratings indicated they were satiated, which was comparable to the ratings before leptin therapy. These findings suggest that one of the primary effects of acute leptin therapy may be to reduce the ravenous hunger associated with leptin deficiency, resulting in reduced food intake and significant weight loss. These results are discussed in the context of the scientific literature pertaining to leptin and its effects on appetite and obesity.

Adult↗

Motivational state modulates the hedonic value of food images differently in men and women.

We investigated visual alimentary alliesthesia in non-fasted (N = 369) and fasted participants (N = 257) viewing photographs of food. Fasted participants were asked to not eat for 12 h before the session. Each participant was shown food and non-food images and rated each image on valence (i.e., pleasantness). The strongest evidence of alliesthesia was found in women. Fasting enhanced the pleasantness of food images for each of the food categories in women, although this alliesthesia effect was smaller in response to dessert foods compared to the less-pleasantly-rated food categories. In addition, non-fasting women exhibited significant positive correlations between hunger ratings and valence ratings of three of the five food categories. There was no significant difference in valence ratings of food between fasting vs. non-fasting men, but non-fasting men showed correlations between hunger and valence that were similar to those observed among the women. No evidence was found of hunger- or fasting-induced enhancement of hedonic ratings of non-foods in women or men, indicating the specificity of the alliesthesia effect for the food images only.

Adolescent↗