Recognizing Hunger. Self-Regulation of Food Intake and Energy Balance
Abstract and Figures
The 500 bacterial species that inhabit the alimentary canal have been a source of interest for me since employment in the Gastroenterology Unit . It is now increasingly recognized that between 5 and 15 percent of these bacteria stimulate pathogenic immune responses, abetted by high insulin resistance. Early on in my career I realized that both insulin resistance and the gut microbiota are susceptible to changes in food intake habits. In particular both improve with the phase III contractions that are associated with hunger.
I am very happy to have travelled this long and twisting road of investigation. Each bend has brought insights and renewed enthusiasm. The moment of discovery is the most fulfilling in the career of any scientist. Yet reporting our methods and findings, as we are here, brings a fresh wave of insights of increasing fascination.
... According to many studies (Ciampolini et al., 1990(Ciampolini et al., , 2006(Ciampolini et al., , 2014Fisher & Birch., 2002), nutrients disappearing from circulation may settle either on the liver or on the adipose tissue or being burned out. The storage is however reversible because it is strictly related to a high blood glucose concentration (BG). ...
... We have chosen to consider the phases of both energy expenditure and energy supply (at meals) in adults as well as in children. The IH (Ciampolini et al., 1990(Ciampolini et al., , 2006(Ciampolini et al., , 2014Fisher & Birch, 2002) appeared after suspension of meals as a sensation, i.e. as a subjective (psychic) event in adults and as a physical manifestation (individual, according to the mothers' evaluation) in children. In the single individual this event coincided constantly with the same BG. ...
... The overall sterile inflammation or pro-inflammatory state represents one of the most important notions acquired by medical physiopathology in the last century (Brandtzaeg et al., 1989;Hecht et al., 2007;Festa et al., 2000;Reaven 2006;Smith 2007;Bigorgne et al., 2008;Cani et al., 2007;Stratton et al., 2000;Bruun et al., 2003;Davidson et al., 1984;Van der Waaij et al., 2008;Sartor, 2008). Such a state is associated both to increased vascular, autoimmune and tumor risks but also to degenerative and functional disorders (Ciampolini et al., 1990(Ciampolini et al., , 2006(Ciampolini et al., , 2014Fisher & Birch., 2002). In addition it facilitates the onset of autoimmune and allergic diseases like arthritis and eczema. ...
Background: Obesity, diabetes, asthma, autism, birth defects, dyslexia, attention deficit-hyperactivity disorder, and schizophrenia have increased in children in the last half century. The will (decision) to eat develops often when previous energy intake has been incompletely exhausted. Objective: The will to eat develops after stimuli (often external) that do not correlate with energy availability in blood. Training a relation between hunger sensations (Initial Hunger, IH) and Blood Glucose (BG) as an index of energy availability allows an IH Meal Pattern that is associated with low mean BG and insulin sensitivity. Lack of any relation between the will to eat and the energy availability is a widespread error that may be responsible of health deterioration in children as well as in adults. Methods: After meal suspension and with synchronous blood glucose (BG) measurements, we taught patients to distinguish hunger sensations that are conditioned from those that arise after meal suspension (Initial Hunger, IH). This hunger (after meal suspension) signals a complete exhaustion of previous intake and is appropriate for meal onset to obtain meal-by-meal fasting nutrient levels and low BG prior to the next meal and establish an even balance. This pattern has been termed the Initial Hunger Meal Pattern (IHMP). Results: In contrast with untrained control subjects, trained subjects accurately recognized IH by synchronous BG measurements. We report here the identification of Initial Hunger (the subjective limit), the daily adjustments to three arousals for weeks and months, the diffusion of the error in untrained child and adult population, the validations of the IH and BG assessments and the improvements of 18 parameters by IHMP. Conclusion: The will to eat develops as a conditioned event and this conditioned will causes positive energy imbalance and insulin resistance/fattening. The imbalancing will to eat may be corrected by becoming aware of differences between the conditioned sensations of hunger and the sensations that develop after meal suspension.
... According to many studies (Ciampolini et al., 1990(Ciampolini et al., , 2006(Ciampolini et al., , 2014Fisher & Birch., 2002), nutrients disappearing from circulation may settle either on the liver or on the adipose tissue or being burned out. The storage is however reversible because it is strictly related to a high blood glucose concentration (BG). ...
... We have chosen to consider the phases of both energy expenditure and energy supply (at meals) in adults as well as in children. The IH (Ciampolini et al., 1990(Ciampolini et al., , 2006(Ciampolini et al., , 2014Fisher & Birch, 2002) appeared after suspension of meals as a sensation, i.e. as a subjective (psychic) event in adults and as a physical manifestation (individual, according to the mothers' evaluation) in children. In the single individual this event coincided constantly with the same BG. ...
... The overall sterile inflammation or pro-inflammatory state represents one of the most important notions acquired by medical physiopathology in the last century (Brandtzaeg et al., 1989;Hecht et al., 2007;Festa et al., 2000;Reaven 2006;Smith 2007;Bigorgne et al., 2008;Cani et al., 2007;Stratton et al., 2000;Bruun et al., 2003;Davidson et al., 1984;Van der Waaij et al., 2008;Sartor, 2008). Such a state is associated both to increased vascular, autoimmune and tumor risks but also to degenerative and functional disorders (Ciampolini et al., 1990(Ciampolini et al., , 2006(Ciampolini et al., , 2014Fisher & Birch., 2002). In addition it facilitates the onset of autoimmune and allergic diseases like arthritis and eczema. ...
Background: We have worked out an alimentary behaviour based on a meal- after -meal individual limit of energy intake (IHMP). We have then studied the energy intake, the pre-prandial blood glucose concentration (blood glucose, BG) and the body weight of a group of children with chronic not specific diarrhea. Finally we have added BG tolerance tests to clinically healthy adults in order to ascertain a possible association between IHMP and insulin sensitivity, should functional disorders or overweight problems arise.Objective: With the present study we want to verify if mothers are capable of maintaining the IHMP and low pre-prandial BG levels in the eight years following the initial training, also in absence of diarrhea relapses. In adults the IHMP is associated to a good insulin sensitivity and this fact should be taken into consideration in order to reduce the increase of non - trasmissible deseases in the Western World.Methods: We recruited children with not specific chronic diarrhea (bowel functional disorders) and selected randomly 53 mother-child pairs as the control group and 100 to be trained. Mothers were taught both how to recognise the correspondence between the individual manifestations of hunger and the BG concentration (Initial Hunger Meal Pattern, IHMP). The aim was to get low BG levels before each meal, and, thanks to the skill acquired, to stop the insulin resistance. The energy intake and the pre-prandial BG levels were reported in weekly diaries while the symptoms were recorded through structured interviews after 3 and 6 months and after 2,4,6,8 years.Results: Energy intake reductions were significantly larger in trained than in control subjects at all 6 surveys after recruitment (P < 0.04 to < 0.0001) although growth was similar, Diarrhea and vomiting significantly dropped both in the trained group and in the control one compared to the beginning of the research. Larger reductions from base values in days with diarrhea in trained children (compared with controls) were found for the three initial months and in drug administration at the surveys after 2 years and after 8 yearsConclusion: Chronic non-specific diarrhea of the second year of life is associated with high energy intake and high pre-prandial BG for incomplete exhaustion of previous energy intake. In adults, this habit is associated with fattening/insulin resistance.
... This review aimed at giving a rapid and compressive outlook on our published demonstrations that are all convergent. Conditioned intake is not limited to overweight people and gastroenterology patients but appears to be as a global, durable, although correctable, health impairment that either activates or worsens inflammation in this or other organ till its devastation [21] [31]. Some authors have already reproduced our training [32] [33]. ...
... Vegetables and fruit were suggested in an amount between 500 and 1000 grams per day over 8 years of age. This amount prevented BG depressions in hyperinsulinemic subjects who wanted to decrease body weight [31]. ...
Presenting author details
Full name: Mario Ciampolini
Contact number: 039055215744 mlciampolini@fastwebnet.it
Session name Pathogenesis of Alimentary Diabetes and solution by loss of 20% body weight, and by attainment of Initial Hunger as well as of low BG before meals.
Category: (Oral presentation/
1st Abstract: Learning the recognition of Initial Hunger (IH)
Background: The will to eat is a decision associated with conditioned responses and with unconditioned body sensations that reflect changes in metabolic biomarkers. The body feelings described as hunger have often components that are conditioned by time, social behavior and sight of food. Blood glucose is a biomarker of current energy availability and of hunger. Extensive rat and human studies showed that blood glucose declines coincided with spontaneous feelings of hunger, with metabolic insufficiency and meal initiation.
Objectives: Investigating whether the decision to eat can be delayed until blood glucose is allowed to fall to low levels, when feeding behavior is (mostly) unconditioned.
Methods: 7-week pilot study. 158 adults suffering from diarrhea, abdominal pain, and dyspepsia were recruited and randomized to experimental (trained; n = 80) and control (untrained; n = 78) groups. Subjects of experimental group were trained to ignore meal times and to pay attention to their earliest sensations of hunger or discomfort, so to measure glucose concentrations (blood glucose,BG) with glucometer. They were instructed to associate their sensations of hunger with BG value. The control group followed their normal routine. In the final investigative session (after compilation of a 7 days dairy) all patients were asked to estimate their preprandial BG and a blood sample was taken to measure BG through a glucose autoanalyzer.
Results: At the end of the 7-week training period, estimated and measured glycemic values were found to be linearly correlated in the trained group (r = 0.82; p = 0.0001) but not in the control (untrained) group (r = 0.10; p = 0.40). Fewer subjects in the trained group were hungry than those in the control group (p = 0.001). The 18 hungry subjects of the trained group had significantly lower glucose levels (80.1 ± 6.3 mg/dL) than the 42 hungry control subjects (89.2 ± 10.2 mg/dL; p = 0.01). Moreover, the trained hungry subjects estimated their BG (78.1 ± 6.7 mg/dL; estimation error: 3.2 ± 2.4% of the measured BG) more accurately than the control group (75.9 ± 9.8 mg/dL; estimation error: 16.7 ± 11.0%; p = 0.0001). In addiction the estimation error of the entire trained group (4.7 ± 3.6%) was significantly lower than that of the control subjects (17.1 ± 11.5%; p = 0.0001).
Conclusion: Patients could be trained to accurately estimate their blood glucose and to recognize their sensations of initial hunger at low glucose concentrations. These results suggest that it is possible to learn a behavioral distinction between unconditioned and conditioned hunger, and to modulate intake to achieve three IH arousals per day.
... This review aimed at giving a rapid and compressive outlook on our published demonstrations that are all convergent. Conditioned intake is not limited to overweight people and gastroenterology patients but appears to be as a global, durable, although correctable, health impairment that either activates or worsens inflammation in this or other organ till its devastation [21] [31]. Some authors have already reproduced our training [32] [33]. ...
... Vegetables and fruit were suggested in an amount between 500 and 1000 grams per day over 8 years of age. This amount prevented BG depressions in hyperinsulinemic subjects who wanted to decrease body weight [31]. ...
Background: Obesity, diabetes, asthma, autism, birth defects, dyslexia, attention deficit-hyperactivity disorder and schizophrenia have increased in children in the last half century. These increases may depend on the widespread, well known error in energy balance: the unremitting addition of fat at any will (decision) to eat. In most (60%) but not all people, the decision arises as conditioned before energy exhaustion of the energy available from previous meals. After meal suspension for few hours (up to 48 hours), healthy subjects identified the arousal of sensations of hunger that we named Initial Hunger (IH). After this identification, subjects distinguished IH from conditioned sensations before subsequent meals by mental comparison of the current arousal with the remembered IH. BG decreased to 76.6 ± 3.7 mg/dL and hunger sensations (Initial hunger, IH) arose spontaneously and corresponded to the complete exhaustion of the previous meals. Objective: Not Insulin Dependent (NID) diabetic people differ from fattening people in this: after meal suspension, they do not develop any hunger sensation nor the associated low blood glucose (BG). Methods: Meal suspension lets IH arise and after no arousal, reduction of energy intake. The two subjects consumed meals that provided at least 20 grams of animal protein and up to one kg of not-starchy vegetable (NSV) for 6 to 12 months. At reappearance of IH, we implemented an Initial Hunger Meal Pattern (IHMP). Results: We tried to implement IHMP training in two obese (BMI of 39 and 33) adults out of two consecutive recruitments of subjects who showed high fasting BG. We found an absence of BG decline to 76.6 ± 3.7 mg/dL and an absence of any hunger sensation after eating suspension. Both subjects lost 13% - 20% of their body weight and recovered 76.6 ± 3.7 mg/dL of BG and hunger sensations, i.e., went off diabetes. IHMP maintained the decreased body weight in the subsequent months. Conclusion: Diabetes develops for inveterate conditioned intake (when previous energy intake has not been fully exhausted before meals), excessive fattening (with presumed excessive post-absorption emission of fatty acids from fatty tissues), permanent loss of BG decline to 76.6 ± 3.7 mg/dL and permanent loss of physiological signals of hunger. A healthy, non-diabetic life may be recovered by painless loss of weight up to 20%. The body weight remained stable by implementing IHMP at reappearance of hunger sensations. This costs accurate energy intake planning instead of hunger endurance.
... This review aimed at giving a rapid and compressive outlook on our published demonstrations that are all convergent. Conditioned intake is not limited to overweight people and gastroenterology patients but appears to be as a global, durable, although correctable, health impairment that either activates or worsens inflammation in this or other organ till its devastation [21] [31]. Some authors have already reproduced our training [32] [33]. ...
... Vegetables and fruit were suggested in an amount between 500 and 1000 grams per day over 8 years of age. This amount prevented BG depressions in hyperinsulinemic subjects who wanted to decrease body weight [31]. ...
... Vegetables and fruit were suggested in an amount between 500 and 1000 grams per day over 8 years of age. This amount prevented BG depressions in hyperinsulinemic subjects who wanted to decrease body weight [31]. ...
... We assumed BG as an index of energy availability in blood and in all tissues [1 -20] and conceived the preprandial BG measurements as a check to protect the subject from poorly manifested hypoglycemia and to assess energy balance between meals [9]. At IH arousal, the same background (BG) suggested that IH recognition was accurate. ...
... We assumed BG as an index of energy availability in blood and in all tissues [1 -20] and conceived the preprandial BG measurements as a check to protect the subject from poorly manifested hypoglycemia and to assess energy balance between meals [9]. At IH arousal, the same background (BG) suggested that IH recognition was accurate. ...
... We assumed BG as an index of energy availability in blood and in all tissues [1 -20] and conceived the preprandial BG measurements as a check to protect the subject from poorly manifested hypoglycemia and to assess energy balance between meals [9]. At IH arousal, the same background (BG) suggested that IH recognition was accurate. ...
Abstract
Background: Obesity, diabetes, asthma, autism, birth defects, dyslexia, attention deficit-hyperactivity disorder, schizophrenia have increased in children in the last half century. These increases may depend on the widespread, well known error in energy balance: the unremitting addition of fat at any will (decision) to eat. In most (60%) but not all people, the decision arises as conditioned before energy exhaustion of the energy available from previous meals. After meal suspension for few hours (up to 48 hours), healthy subjects distinguished initial hunger (IH) from conditioned sensations by mental comparison with the hunger that they initially experienced after meal suspension for hours, less than 48 hours. BG decreased to 76.6 ± 3.7 mg/dL and hunger sensations (Initial hunger, IH) arose spontaneously and corresponded to the complete exhaustion of the previous meals.
Objective: Diabetic people differ from fattening people in this: after meal suspension, they do not develop any hunger sensation nor the associated low blood glucose (BG).
Methods: Meal suspension to let arise IH and after no arousal, limitation of energy intake. The two subjects consumed meals that provided 100 to 200 grams of animal protein and up to one kg of not-starchy vegetable (NSV) for 6 to 12 months. At remergence of IH, we implemented an Initial Hunger Meal Pattern (IHMP).
Results: We tried to implement IHMP training in two obese (BMI of 39 and 33), diabetic adults out of two consecutive recruitments. We found an absence of BG decline to 76.6 ± 3.7 mg/dL and an absence of any hunger sensation after eating suspension. Both subjects lost 13 - 20% of their body weight and recovered 76.6 ± 3.7 mg/dL of BG and hunger sensations before at least one meal a day, i.e., went off diabetes. IHMP maintained the decreased body weight in the subsequent months.
Conclusion: Diabetes develops for inveterate conditioned intake (when previous energy intake has not been fully exhausted before meals), excessive fattening, (with presumed excessive post-absorption emission of fatty acids from fatty tissues), permanent loss of BG decline to 76.6 ± 3.7 mg/dL and permanent loss of physiological signals of hunger. A healthy, non-diabetic life may be recovered by painless loss of weight up to 20%. The body weight remained stable by implementing IHMP at reappearance of hunger sensations. This costs accurate energy intake planning for any meal instead of hunger endurance.
Comment: This solution of diabetes aims to enlarge the population minority that at recruitment presents a preprandial Mean BG of 76.6 ± 3.7 mg/dL. In the frustrated Western Countries would be a cultural change that only tiny parts of societies would be able to sustain. We expected help and support by the American Society for Nutrition, National Institute for Health and other National Authorities. Our findings by a portable device have a 6% to 7% difference from authoanalyzer in 85 hospital comparisons on the same blood sample and are confirmed by a world of coherent results on doubly labelled water, on Glucose ToleranceTests, on body weight change, etc. etc.
Key words; energy balance, energy intake, even energy balance, blood glucose, even blood glucose, homeostasis, fattening, insulin resistance, diabetes
Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly , a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat–fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet–induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.
A set of spontaneous hunger sensations, Initial Hunger (IH), has been associated with low blood glucose concentration (BG). These sensations may arise pre-meal or can be elicited by delaying a meal. With self-measurement of BG, subjects can be trained to formally identify and remember these sensations (Hunger Recognition). Subjects can then be trained to ensure that IH is present pre-meal for most meals and that their pre-meal BG is therefore low consistently (IH Meal Pattern). IH includes the epigastric Empty Hollow Sensation (the most frequent and recognizable) as well as less specific sensations such as fatigue or light-headedness which is termed inanition. This report reviews the method for identifying IH and the effect of the IH Meal Pattern on energy balance. In adults, the IH Meal Pattern has been shown to significantly decrease energy intake by one-third, decrease preprandial BG, reduce glycosylated hemoglobin, and reduce insulin resistance and weight in those who are insulin resistant or overweight. Young children as well as adults can be trained in Hunger Recognition, giving them an elegant method for achieving energy balance without the stress of restraint-type dieting. The implications of improving insulin sensitivity through improved energy balance are as wide as improving immune activity.
Childhood obesity due to the consumption of excess calories is a severe problem in developed countries. In a previous investigation on toddlers, hospital laboratory measurements showed an association of food-demand behavior with constant lower blood glucose before meals than for scheduled meals. We hypothesize that maternal scheduling of meals for toddlers results in excess energy intake compared to feeding only on demand (previously "on request").
We tested the cross-sectional null hypothesis of no difference in energy intake between scheduled (automatic) and demanded meals (administered after evaluation) in 24 mother-toddler (21 months old at entry) pairs with chronic, nonspecific diarrhea presenting at a clinic. We tested the same hypothesis in a subset of 14 toddlers by measuring the resting (sleeping) metabolic rate 4 hours after lunch, as well as the total daily energy expenditure (TEE) in 10 toddlers.
We trained mothers to recognize meal demands (as in the previous investigation) and to provide food in response, but required no blood glucose measurements before meals. Energy intake was assessed by a 10-day food diary, resting metabolic rate (RMR) by respiratory analyses (indirect calorimetry) in 14 toddlers, and TEE by doubly labeled water in 10 toddlers. Their blood parameters, anthropometry, and number of days with diarrhea were assessed before training and 50 days after training.
RMR decreased from 58.6 ± 7.8 to 49.0 ± 9.1 kcal/kg/d (P < 0.001) and TEE decreased from 80.1 ± 6.9 to 67.8 ± 10.0 kcal/kg/d (P < 0.001). Energy intake decreased from 85.7 ± 15.3 to 70.3 ± 15.8 kcal/kg/d (P < 0.001). The height Z-score increased significantly, while weight growth was normal. Toddlers entering the study over the median RMR decreased their RMR significantly more than those below the median RMR (P < 0.01).
Scheduled meal suspension induces meal demand frequency to increase. Demanded meals are associated with significantly lower energy intake, RMR, and TEE than scheduled meals. Feeding on demand may be an effective skill in a strategy for reducing excess energy intake in the long term and in regulating body weight in toddlers and children.
Background:
There are strong logical reasons why energy expended in metabolism should influence the energy acquired in food-intake behavior. However, the relation has never been established, and it is not known why certain people experience hunger in the presence of large amounts of body energy.
Objective:
We investigated the effect of the resting metabolic rate (RMR) on objective measures of whole-day food intake and hunger.
Design:
We carried out a 12-wk intervention that involved 41 overweight and obese men and women [mean ± SD age: 43.1 ± 7.5 y; BMI (in kg/m(2)): 30.7 ± 3.9] who were tested under conditions of physical activity (sedentary or active) and dietary energy density (17 or 10 kJ/g). RMR, daily energy intake, meal size, and hunger were assessed within the same day and across each condition.
Results:
We obtained evidence that RMR is correlated with meal size and daily energy intake in overweight and obese individuals. Participants with high RMRs showed increased levels of hunger across the day (P < 0.0001) and greater food intake (P < 0.00001) than did individuals with lower RMRs. These effects were independent of sex and food energy density. The change in RMR was also related to energy intake (P < 0.0001).
Conclusions:
We propose that RMR (largely determined by fat-free mass) may be a marker of energy intake and could represent a physiologic signal for hunger. These results may have implications for additional research possibilities in appetite, energy homeostasis, and obesity. This trial was registered under international standard identification for controlled trials as ISRCTN47291569.
A store's placement of foods in prominent locations increases their rate of purchase, and consumption of foods high in sugar, fat, and salt increases risks of chronic diseases. Such placement should thus be treated as a risk factor, and steps should be taken to mitigate that risk.
In some studies, tight glycemic control with insulin improved outcomes in adults undergoing cardiac surgery, but these benefits are unproven in critically ill children at risk for hyperinsulinemic hypoglycemia. We tested the hypothesis that tight glycemic control reduces morbidity after pediatric cardiac surgery.
In this two-center, prospective, randomized trial, we enrolled 980 children, 0 to 36 months of age, undergoing surgery with cardiopulmonary bypass. Patients were randomly assigned to either tight glycemic control (with the use of an insulin-dosing algorithm targeting a blood glucose level of 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) or standard care in the cardiac intensive care unit (ICU). Continuous glucose monitoring was used to guide the frequency of blood glucose measurement and to detect impending hypoglycemia. The primary outcome was the rate of health care-associated infections in the cardiac ICU. Secondary outcomes included mortality, length of stay, organ failure, and hypoglycemia.
A total of 444 of the 490 children assigned to tight glycemic control (91%) received insulin versus 9 of 490 children assigned to standard care (2%). Although normoglycemia was achieved earlier with tight glycemic control than with standard care (6 hours vs. 16 hours, P<0.001) and was maintained for a greater proportion of the critical illness period (50% vs. 33%, P<0.001), tight glycemic control was not associated with a significantly decreased rate of health care-associated infections (8.6 vs. 9.9 per 1000 patient-days, P=0.67). Secondary outcomes did not differ significantly between groups, and tight glycemic control did not benefit high-risk subgroups. Only 3% of the patients assigned to tight glycemic control had severe hypoglycemia (blood glucose <40 mg per deciliter [2.2 mmol per liter]).
Tight glycemic control can be achieved with a low hypoglycemia rate after cardiac surgery in children, but it does not significantly change the infection rate, mortality, length of stay, or measures of organ failure, as compared with standard care. (Funded by the National Heart, Lung, and Blood Institute and others; SPECS ClinicalTrials.gov number, NCT00443599.).
Scheduled meals are considered to be equivalent to those requested by the infant (null hypothesis). In adults, we have found high blood glucose before scheduled meals and low blood glucose after recognition of validated initial hunger. Low preprandial blood glucose is associated with a decrease in energy intake and body weight both in adults who are overtly overweight and in those who are of normal weight with insulin resistance (hidden overweight). In this study, we investigated the validity of the null hypothesis between scheduled and requested meals in 2-year-old infants with chronic nonspecific diarrhea.
We trained a "recognizing request" meal pattern in 70 mother-infant pairs. The trained meal pattern consisted of administering food after a first request that we validated by blood glucose measurement in the hospital laboratory. Using a 7-day food diary, mothers reported preprandial blood glucose measurements for their infants three times a day. We assessed mean preprandial blood glucose, daily energy intake, days with diarrhea, blood parameters, and anthropometry before training and 4 months after training, and compared the results with measurements in 73 randomly selected untrained controls.
In the trained group, there was a decrease in mean blood glucose from 86.9 ± 9.4 mg/dL to 76.4 ± 6.7 mg/dL (P < 0.0001), as well as a decrease in energy intake and days with diarrhea in comparison with control infants who maintained scheduled meals. Only two of 21 infants who had a mean blood glucose lower than 81.2 mg/dL at recruitment showed a statistically significant decrease in mean blood glucose, whereas 36 of 49 infants above this cutoff level showed a statistically significant decrease after training (Chi-square test, P < 0.0001).
Requested meals are associated with low preprandial blood glucose, significantly lower energy intake, and recovery from diarrhea, whereas scheduled meals are associated with high blood glucose, higher energy intake, and persistence of diarrhea. The disparities in blood glucose levels and energy intake disprove the null hypothesis, suggesting the need for a change from scheduled to requested meals early on in food administration, ie, during the neonatal period.
Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known.
We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]).
At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy, P=0.005). The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care.
Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.
Obesity in childhood is associated with increased cardiovascular risk. It is uncertain whether this risk is attenuated in persons who are overweight or obese as children but not obese as adults.
We analyzed data from four prospective cohort studies that measured childhood and adult body-mass index (BMI, the weight in kilograms divided by the square of the height in meters). The mean length of follow-up was 23 years. To define high adiposity status, international age-specific and sex-specific BMI cutoff points for overweight and obesity were used for children, and a BMI cutoff point of 30 was used for adults.
Data were available for 6328 subjects. Subjects with consistently high adiposity status from childhood to adulthood, as compared with persons who had a normal BMI as children and were nonobese as adults, had an increased risk of type 2 diabetes (relative risk, 5.4; 95% confidence interval [CI], 3.4 to 8.5), hypertension (relative risk, 2.7; 95% CI, 2.2 to 3.3), elevated low-density lipoprotein cholesterol levels (relative risk, 1.8; 95% CI, 1.4 to 2.3), reduced high-density lipoprotein cholesterol levels (relative risk, 2.1; 95% CI, 1.8 to 2.5), elevated triglyceride levels (relative risk, 3.0; 95% CI, 2.4 to 3.8), and carotid-artery atherosclerosis (increased intima-media thickness of the carotid artery) (relative risk, 1.7; 95% CI, 1.4 to 2.2) (P ≤ 0.002 for all comparisons). Persons who were overweight or obese during childhood but were nonobese as adults had risks of the outcomes that were similar to those of persons who had a normal BMI consistently from childhood to adulthood (P>0.20 for all comparisons).
Overweight or obese children who were obese as adults had increased risks of type 2 diabetes, hypertension, dyslipidemia, and carotid-artery atherosclerosis. The risks of these outcomes among overweight or obese children who became nonobese by adulthood were similar to those among persons who were never obese. (Funded by the Academy of Finland and others.).
During hunger, a series of high-amplitude contractions of the stomach and small intestine (phase III), which form part of a cycle of quiescence and contractions (known as the migrating motor complex, MMC), play a “housekeeping” role prior to the next meal, and may contribute toward the development of hunger. Several gastrointestinal (GI) hormones are associated with phase III MMC activity, but currently the most prominent is motilin, thought to at least partly mediate phase III contractions of the gastric MMC. Additional GI endocrine and neuronal systems play even more powerful roles in the development of hunger. In particular, the ghrelin-precursor gene is proving to have a complex physiology, giving rise to three different products: ghrelin itself, which is formed from a post-translational modification of des-acyl-ghrelin, and obestatin. The receptors acted on by des-acyl-ghrelin and by obestatin are currently unknown but both these peptides seem able to exert actions which oppose that of ghrelin, either indirectly or directly. An increased understanding of the actions of these peptides is helping to unravel a number of different eating disorders and providing opportunities for the discovery of new drugs to regulate dysfunctional gastric behaviors and appetite. To date, ghrelin and motilin receptor agonists and antagonists have been described. The most advanced are compounds which activate the ghrelin and motilin receptors which are being progressed for disorders associated with gastric hypomotility.
Meals begin and end subjectively. We trained healthy subjects to recognize initial hunger as a preprandial target for meal consumption, and to create a "recognizing hunger" or initial hunger meal pattern.
Training subjects to "recognize hunger" lowers blood glucose (BG) and improves energy balance, and lowers metabolic risks and bodyweight. A minority may have low BG and low metabolic risks at recruitment, but the others may recover this favorable condition by training.
In a 7-day food diary, subjects reported their preprandial BG measurements; BG and energy availability by blood were assessed at the lowest BG during the day, and diary-mean BG thus characterized the individual meal pattern (daily energy intake). We analyzed the same diaries of a recent paper on a global, randomized comparison of subjects trained in "recognizing hunger" with control subjects. This time, we checked whether subjects who had maintained low BG (LBG subgroup) at recruitment were able to decrease mean BG and metabolic risk factors during "hunger recognition" like those who presented high BG (HBG subgroup).
At recruitment, the BG means of 120 investigated subjects were within mean confidence limits of ± 3.84 mg/dL, and we could stratify subjects in ten small strata of which each significantly differed by mean BG. Mean BG was stable in each control subject over five months; the mean absolute change being 6.0 ± 4.6 mg/dL. Only three out of 34 trained subjects who had lower mean BG than 81.8 mg/dL significantly decreased mean BG, whereas 41 out of 55 subjects whose mean BG was greater than 81.8 mg/dL significantly decreased mean BG after training (P < 0.0001). At recruitment, the LBG subgroup showed significantly lower insulin, lower BG area under curve (AUC) in the oral glucose tolerance test (GTT), and lower HbA1c than the HBG group. After training, only HBG subjects, compared with HBG controls, significantly decreased preprandial BG from 91.6 ± 7.7 mg/dL to 81.0 ± 7.7 mg/dL, in association with a decrease of HbA1c from 4.81% ± 0.44% to 4.56% ± 0.47%, of GTT insulin AUC from 244 ± 138 mU/L to 164 ± 92 mU/L, and of energy intake from 1872 ± 655 kcal to 1251 ± 470 kcal (P < 0.001), with an increase of indices of insulin sensitivity from 5.9 ± 3.3 to 9.8 ± 5.6 and of beta cell function from 1.0 ± 0.7 to 1.4 ± 1.1 (P < 0.05). LBG subjects only decreased weekly-diary BG standard deviation in comparison with controls.
At recruitment, the 120 subjects maintained mean BG at one personal level of ten possibilities, and 34 subjects were below 81.8 mg/dL (LBG) and 55 were over (HBG). The 55 HBG subjects showed higher mean insulin resistance, HbA1c, other cardiovascular risk factors, and increased bodyweight compared with the 34 LBG subjects. A total of 41 out of the 55 HBG subjects regressed to LBG with training.
It is well established that central corticotropin releasing factor (CRF) signaling mediates the gastrointestinal responses to stress. However, as shown in the brain, both CRF receptors and ligands are also widely expressed in the colon and the ileum of humans and rodents, and stress modulates their expression. Several functional studies documented that peripheral injection of CRF or urocortin stimulates colonic transit, motility, Fos expression in myenteric neurons, and defecation through activation of CRF(1) receptors, whereas it decreases ileal contractility via CRF(2) receptors. Additionally, intraperitoneal administration of CRF induces colonic mast cells degranulation via both CRF(1) and CRF(2) receptors and increases ion secretion and mucosal permeability to macromolecules, which can in turn promote intestinal inflammation and alter visceral sensitivity. Most peripheral CRF-induced alterations of colonic and ileal functions mimic effects which are observed after stress exposure, and CRF receptor antagonists given peripherally prevent stress-induced GI dysfunction. Furthermore, CRF peptides can reproduce secretomotor and mucosal alterations in vitro. Therefore, accumulated clinical and preclinical evidence supports in addition to the brain, a role for peripheral CRF signaling in mediating stress-induced effects on gastrointestinal sensorimotor, mucosal and immune functions, that may be components of underlying mechanisms involved in stress-related impact on inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS).
Studies in mice indicate that the gut microbiome influences both sides of the energy-balance equation by contributing to nutrient absorption and regulating host genes that affect adiposity. However, it remains uncertain as to what extent gut microbiota are an important regulator of nutrient absorption in humans.
With the use of a carefully monitored inpatient study cohort, we tested how gut bacterial community structure is affected by altering the nutrient load in lean and obese individuals and whether their microbiota are correlated with the efficiency of dietary energy harvest.
We investigated dynamic changes of gut microbiota during diets that varied in caloric content (2400 compared with 3400 kcal/d) by pyrosequencing bacterial 16S ribosomal RNA (rRNA) genes present in the feces of 12 lean and 9 obese individuals and by measuring ingested and stool calories with the use of bomb calorimetry.
The alteration of the nutrient load induced rapid changes in the gut microbiota. These changes were directly correlated with stool energy loss in lean individuals such that a 20% increase in Firmicutes and a corresponding decrease in Bacteroidetes were associated with an increased energy harvest of ≈150 kcal. A high degree of overfeeding in lean individuals was accompanied by a greater fractional decrease in stool energy loss.
These results show that the nutrient load is a key variable that can influence the gut (fecal) bacterial community structure over short time scales. Furthermore, the observed associations between gut microbes and nutrient absorption indicate a possible role of the human gut microbiota in the regulation of the nutrient harvest. This trial was registered at clinicaltrials.gov as NCT00414063.
Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestinal microbiota, mucosal barrier function, and the immune system have been shown to play a role in the disorder's pathogenesis.
Studies examining the microecology of the gastrointestinal (GI) tract have identified specific microorganisms whose presence appears related to disease; in CFS, a role for altered intestinal microbiota in the pathogenesis of the disease has recently been suggested. Mucosal barrier dysfunction promoting bacterial translocation has also been observed. Finally, an altered mucosal immune system has been associated with the disease. In this article, we discuss the interplay between these factors in CFS and how they could play a significant role in GI dysfunction by modulating the activity of the enteric nervous system, the intrinsic innervation of the gut.
If an altered intestinal microbiota, mucosal barrier dysfunction, and aberrant intestinal immunity contribute to the pathogenesis of CFS, therapeutic efforts to modify gut microbiota could be a means to modulate the development and/or progression of this disorder. For example, the administration of probiotics could alter the gut microbiota, improve mucosal barrier function, decrease pro-inflammatory cytokines, and have the potential to positively influence mood in patients where both emotional symptoms and inflammatory immune signals are elevated. Probiotics also have the potential to improve gut motility, which is dysfunctional in many CFS patients.
Inflammatory bowel disease (IBD) is hypothesized to result from stimulation of immune responses against resident intestinal bacteria within a genetically susceptible host. Mast cells may play a critical role in IBD pathogenesis, since they are typically located just beneath the intestinal mucosal barrier and can be activated by bacterial antigens.
This study investigated effects of mast cells on inflammation and associated neoplasia in IBD-susceptible interleukin (IL)-10-deficient mice with and without mast cells. IL-10-deficient mast cells produced more pro-inflammatory cytokines in vitro both constitutively and when triggered, compared with wild type mast cells. However despite this enhanced in vitro response, mast cell-sufficient Il10(-/-) mice actually had decreased cecal expression of tumor necrosis factor (TNF) and interferon (IFN)-gamma mRNA, suggesting that mast cells regulate inflammation in vivo. Mast cell deficiency predisposed Il10(-/-) mice to the development of spontaneous colitis and resulted in increased intestinal permeability in vivo that preceded the development of colon inflammation. However, mast cell deficiency did not affect the severity of IBD triggered by non-steroidal anti-inflammatory agents (NSAID) exposure or helicobacter infection that also affect intestinal permeability.
Mast cells thus appear to have a primarily protective role within the colonic microenvironment by enhancing the efficacy of the mucosal barrier. In addition, although mast cells were previously implicated in progression of sporadic colon cancers, mast cells did not affect the incidence or severity of colonic neoplasia in this inflammation-associated model.
Background. Excessive energy intake has been implicated in diabetes, hypertension, coronary artery disease, and obesity. Dietary restraint has been unsuccessful as a method for the self-regulation of eating. Recognition of initial hunger (IH) is easily learned, can be validated by associated blood glucose (BG) concentration, and may improve insulin sensitivity. Objective. To investigate whether the initial hunger meal pattern (IHMP) is associated with improved insulin sensitivity over a 5-month period. Methods. Subjects were trained to recognize and validate sensations of IH, then adjust food intake so that initial hunger was present pre-meal at each meal time (IHMP). The purpose was to provide meal-by-meal subjective feedback for self-regulation of food intake. In a randomised trial, we measured blood glucose and calculated insulin sensitivity in 89 trained adults and 31 not-trained controls, before training in the IHMP and 5 months after training.
Results. In trained subjects, significant decreases were found in insulin sensitivity index, insulin and BG peaks, glycated haemoglobin, mean pre-meal BG, standard deviation of diary BG (BG as recorded by subjects' 7-day diary), energy intake, BMI, and body weight when compared to control subjects. Conclusion. The IHMP improved insulin sensitivity and other cardiovascular risk factors over a 5-month period.
Dietary restraint is largely unsuccessful for controlling obesity. As an alternative, subjects can easily be trained to reliably recognize sensations of initial hunger (IH) a set of physiological sensations which emerge spontaneously, not necessarily at planned mealtimes, and may be the afferent arm of a homeostatic system of food intake regulation. Previously we have reported that IH is associated with blood glucose concentration (BG) below 81.8 mg/dL (4.55 mmol/l), (low blood glucose, LBG), and that a pattern of meals in which IH is present pre-meal (IHMP) improved insulin sensitivity, HbA1c and other cardiovascular risk factors. Here we report the effect upon weight in overweight and normal weight subjects.
To investigate whether the IHMP is associated with sustained loss of weight in overweight subjects over a 5 month period.
Seventy four overweight subjects (OW: BMI > 25) and 107 normal weight (NW) subjects were randomly allocated to either trained (OW: N = 51; NW N = 79) or control (OW: N = 23; NW: N = 28) groups. All subjects were allocated post-randomization into either low or high mean pre-meal BG groups (LBG and HBG groups) using a demarcation point of 81.8 mg/dL.
A significant longitudinal decrease was found in body weight (trained NW: -2.5 ± 4.6 kg; OW -6.7 ± 4.5 kg; controls: NW +3.5 ± 4.0 kg and OW -3.4 ± 4.0 kg; P = 0.006 and 0.029) and in energy intake, mean BG, standard deviation of diary BG (BG as recorded by subjects' 7-day diary), BMI, and arm and leg skin-fold thickness in (OW and NW) HBG subjects. OW LBG subjects significantly decreased body weight (trained: -4.0 ± 2.4 kg; controls: -0.4 ± 3.7 kg; P = 0.037). 26 NW LBG subjects showed no longitudinal difference after training as did 9 control subjects.
Over a 5 month period the IHMP resulted in significant loss of weight in OW subjects compared to controls practicing dietary restraint. NW subjects maintained weight overall, however NW HBG subjects also lost weight compared to controls.
Change in body composition, specifically loss of fat-free mass and gain in fat mass, in older adults is a major pathway leading to the onset of functional decline and physical disability.
The objective was to determine the association of activity-related energy expenditure with change in body mass and composition among older men and women.
Total energy expenditure (TEE) was assessed over 2 wk by using the doubly labeled water method in 302 community-dwelling older adults aged 70-82 y. Resting metabolic rate (RMR) was measured by using indirect calorimetry, and the thermic effect of meals was estimated at 10% of TEE. Activity energy expenditure (AEE) was calculated as [TEE(0.9) - RMR]. Total body mass, fat-free mass (FFM), and fat mass (FM) were assessed by dual-energy X-ray absorptiometry annually over a mean (+/-SD) of 4.9 +/- 1.3 y.
In multivariate models adjusted for baseline age, smoking status, and race, men and women had a decline (in kg/y) in body mass (men: -0.34, 95% CI: -0.71, 0.02; women: -0.45, 95% CI: -0.71, -0.19) and FFM (men: -0.48, 95% CI: -0.67, -0.29; women: -0.14, 95% CI: -0.026, -0.03). No changes (in kg/y) were observed in FM (men: 0.14, 95% CI: -0.10, 0.38; women: -0.28, 95% CI: -0.49, -0.07). In men and women, higher AEE at baseline was associated with greater FFM. The average change in these outcomes (ie, slope), however, was similar across tertiles of AEE.
These data suggest that accumulated energy expenditure from all physical activities is associated with greater FFM, but the effect does not alter the trajectory of FFM change in late life.
Evaporative cooling of ambient air (EC) is a main path for heat stress relief in cattle kept in the shade of semi-confining structures. Evaporative cooling is particularly efficient in hot dry climates. We examined the potential of EC for heat stress relief in cattle in moderately warm and humid climates. The feasibility was examined by the reduction in ambient temperature (T(ac)) produced by EC as a function of ambient temperature (T(a)) and humidity (RH(a)). A data set (n = 139) of temperature and relative humidity (RH) produced by EC over a range of air temperature (25 to 50 degrees C) and humidity (10 to 70% RH) was analyzed by polynomial second order regressions. The analyses produced equations for the relations between ambient air temperature and ambient humidity and between respective conditions in air cooled by EC (T(c), RH(c)). Linear regressions were computed for a narrower temperature range (30 to 40 degrees C). In all equations, R(2) were >0.94 and regression terms were statistically significant. The T(ac) obtained by EC diminished by 0.3 degrees C per degrees C rise in T(a), indicating a reduced efficiency of EC with rising T(a). The T(ac) obtained by EC also was markedly reduced by rising ambient humidity and increased by RH(c). An attempt to sustain T(ac) at greater RH(a) by allowing a rise in RH(c) would only restore 2/3 of the reduction in T(ac) because the coefficient for the RH(a) effect on T(ac) is 1.5 larger than that of RH(c). The T(ac) attained by EC partially depends on the humidity in the cooled environment. Elevated RH(c) may impede animal skin and respiratory evaporative heat loss and lead to moisture accumulation in bedding. If the upper desired limit for RH(c) is 70%, at RH(a) smaller than 45% (typical for hot-dry environments) the T(ac) is larger than 7.5 degrees C, at RH(a) greater than 55% T(ac) is reduced to less than 5 degrees C, and at RH(a) of 57.5 to 60% T(ac) is about 2.5 degrees C. Coupling EC with forced air movement when T(ac) is small may partially assist in alleviation of heat stress by enhancing the smaller convective heat loss at ambient temperatures above 30 degrees C. These indicate a limited role for EC in relief of heat stress in moderately warm and humid conditions when RH(a) is greater than 50 to 55%. Forced evaporation of water from the surface of the animal by sequential hair coat wetting coupled with forced air movement is an alternative little affected by ambient humidity.
As an apparent adaptation to predictably long episodes of fasting, the sit-and-wait foraging Burmese python experiences unprecedented regulation of gastrointestinal and cardiovascular performance with feeding and fasting. The ingestion of a meal signals the quiescent gut tissues to start secreting digestive acid and enzymes, to upregulate intestinal brush-border enzymes and nutrient transporters, and to grow. An integrated phenomenon, digestion is also characterized by increases in the mass, and presumably the function, of the heart, pancreas, liver and kidneys. Once digestion is complete, the python's stomach and small intestine rapidly downregulate performance. Much of the modulation of intestinal function can be explained by the 5-fold increase in microvillus length and apical surface area with feeding, and the subsequent shortening of the microvilli after digestion has finished. Digestion for the Burmese python is a relatively expensive endeavor, evident by the as much as a 44-fold increase in metabolic rate and equivalent in cost to as much as 37% of the meal's energy. Their large metabolic response is supported by substantial increases in ventilation and cardiac output and the apparent catabolism of glucose and lipids. Unmatched in the magnitude of its numerous physiological responses to feeding, the Burmese python is a very attractive model for examining the capacities and regulatory mechanisms of physiological performance.
Background: Ad libitum, low-carbohydrate diets decrease caloric intake and cause weight loss. It is unclear whether these effects are due to the reduced carbohydrate content of such diets or to their associated increase in protein intake.
Objective: We tested the hypothesis that increasing the protein content while maintaining the carbohydrate content of the diet lowers body weight by decreasing appetite and spontaneous caloric intake.
Design: Appetite, caloric intake, body weight, and fat mass were measured in 19 subjects placed sequentially on the following diets: a weight-maintaining diet (15% protein, 35% fat, and 50% carbohydrate) for 2 wk, an isocaloric diet (30% protein, 20% fat, and 50% carbohydrate) for 2 wk, and an ad libitum diet (30% protein, 20% fat, and 50% carbohydrate) for 12 wk. Blood was sampled frequently at the end of each diet phase to measure the area under the plasma concentration versus time curve (AUC) for insulin, leptin, and ghrelin.
Results: Satiety was markedly increased with the isocaloric high-protein diet despite an unchanged leptin AUC. Mean (±SE) spontaneous energy intake decreased by 441 ± 63 kcal/d, body weight decreased by 4.9 ± 0.5 kg, and fat mass decreased by 3.7 ± 0.4 kg with the ad libitum, high-protein diet, despite a significantly decreased leptin AUC and increased ghrelin AUC.
Conclusions: An increase in dietary protein from 15% to 30% of energy at a constant carbohydrate intake produces a sustained decrease in ad libitum caloric intake that may be mediated by increased central nervous system leptin sensitivity and results in significant weight loss. This anorexic effect of protein may contribute to the weight loss produced by low-carbohydrate diets.
The insulin-resistant (IR) syndrome may be an impetus for the development of hypertension (HTN). Unfortunately, the mechanism by which this could occur is unclear. Our laboratory and others have described impaired endothelium-mediated relaxation in IR, mildly hypertensive rats. The purpose of the current study is to determine if HTN is most likely a cause or result of impaired endothelial function. Sprague-Dawley rats were randomized to receive a fructose-rich diet for 3, 7, 10, 14, 18, or 28 days or were placed in a control group. The control group received rat chow. After diet treatment, animals were instrumented with arterial cannulas, and while awake and unrestrained, their blood pressure (BP) was measured. Subsequently, endothelium-mediated relaxation to acetylcholine was determined tin vitro) by measuring intraluminal diameter of phenylephrine-preconstricted mesenteric arteries (similar to 250 mu M). Serum insulin levels were significantly elevated in all groups receiving fructose feeding compared with control, whereas there were no differences in serum glucose levels between groups. Impairment of endothelium-mediated relaxation starts by clay 14 [mean percent maximal relaxation (E-max): 69 +/- 10% of baseline] and becomes significant by day 18 (E-max: 52 +/- 11% of baseline; P < 0.01). However, the mean BP (mmHg) does not become significantly elevated until day 28 [BP: 132 +/- 1 (day 28) vs. 116 +/- 3 (control); P < 0.05]. These findings demonstrate that both IR and endothelial dysfunction occur before HTN in this model and suggest that endothelial dysfunction may be a mechanism linking insulin resistance and essential HTN.
Background: The results of epidemiologic studies indicate that higher intakes or blood concentrations of folate are associated with a lower risk of colorectal neoplasia; however, only one study assessed the role of homocysteine.
Objective: We assessed the relation between biochemical and dietary markers of folate status and colorectal adenoma recurrence.
Design: Analyses were conducted in 1014 men and women aged 40–80 y who had undergone removal of all colorectal polyps. Diet and supplement use were ascertained through a food-frequency questionnaire administered at study entry. Blood collected at baseline was used to measure plasma folate and homocysteine concentrations. Unconditional logistic regression was used to assess the odds of recurrence associated with the intakes of folate, methionine, and vitamins B-6 and B-12 and with plasma folate and homocysteine.
Results: Relative to subjects in the highest quartile of plasma homocysteine, those in the lowest quartile had an odds ratio (OR) of adenoma recurrence of 0.69 (95% CI: 0.47, 1.02; P for trend = 0.02) after adjustment for confounding factors. Lower odds of recurrence were shown for higher plasma folate (OR: 0.66; 95% CI: 0.46, 0.97) and higher total intakes (dietary plus supplemental) of folate (OR: 0.61; 0.42, 0.89) and vitamin B-6 (OR: 0.65; 0.45, 0.94). Slightly weaker and nonsignificant associations were shown for dietary folate, methionine, and total vitamin B-12.
Conclusions: A lower recurrence of colorectal adenomas was shown in subjects with higher intakes and plasma concentrations of folate. Additional markers involved in folate metabolism, including lower homocysteine and higher vitamin B-6 intake, were also associated with lower odds of recurrence.
While there are no liver diseases specific to advanced age, the presentation, clinical course and management of liver diseases in the elderly may differ in important respects from younger individuals. The management of older patients with specific liver diseases should be informed by these differences. Alcoholic liver disease presents at a more advanced stage, drug induced liver disease and viral hepatitis may also be more severe. It is increasingly recognised that primary hepatocellular cancer arises in elderly cirrhotics regardless of the etiology of the cirrhosis, the risk highest in hemochromatosis and cirrhosis arising from hepatitis B and C.
Bringing up children to scheduled meals promotes current extent of overweight and insulin resistance. The spontaneous arousal of hunger sensations at low blood glucose concentration is different from scheduled arousal. Memorization of spontaneous arousals and reports of their identity in later occasions may be confirmed by biochemical, physiological and physical measurements stating the identity of metabolic conditions. This review reports this distinction and the identification by training of initial hunger (IH). Validated IH includes epigastric sensations (the most frequent and recognizable) and mental and physical sensations. A meal pattern solicited by validated IH may be maintained for months and years up to old age. This pattern reduces energy intake by a third, and decreases mean weekly preprandial BG, glycated Hb, insulin resistance and body weight in those who are insulin resistant or overweight.
The commonly-held view that stress can elicit eating, and that this eating is an attempt by the organism to reduce anxiety, is critically examined. It is shown that a variety of factors, other than food-deprivation and palatability, can elicit eating in animals and man. Many of these elicitors do not have obvious aversive correlates. It is argued, by analogy with avoidance learning, that the eating cannot produce a reduction in the aversiveness of the eliciting stimulus, since the eating behaviour would not be strengthened and maintained. It is suggested that the eliciting stimuli simply activate the organism, making it more responsive to external, food-related stimuli, which direct behaviour towards eating. These stimuli elicit metabolic responses associated with eating, which serve to increase activation, and strengthen the eating response further.
The advanced lesions of atherosclerosis represent the culmination of a specialized form of chronic inflammation followed by a fibroproliferative process that takes place within the intima of the affected artery. Proliferation of smooth muscle cells and generation of connective tissue occur. Proliferation results from interactions between arterial smooth muscle, monocyte-derived macrophages, T lymphocytes, and endothelium. The initial lesion of atherosclerosis, the fatty streak, begins as an accumulation of monocytederived macrophages and T lymphocytes, which adhere and migrate into the intima of the affected artery. Smooth muscle cells, which are present in the intima or which migrate into the intima from the media, then replicate. Monocyte-derived macrophages and T cells also replicate during lesion formation and progression due to the production of cytokines and growth-regulatory molecules. These molecules determine whether there is proliferation and lesion progression or inhibition of proliferation and lesion regression. Several growthregulatory molecules may play critical roles in this process, including platelet-derived growth factor (PGDF), transforming growth factor beta, fibroblast growth factor, heparinbinding epidermal growth factor-like growth factor, and others. PDGF may be one of the principal components in this process because protein containing the PDGF B-chain has been demonstrated within activated lesion macrophages during every phase of atherogenesis. The presence of this growth factor and its receptors on lesion smooth muscle cells creates opportunities for smooth muscle chemotaxis and replication. Smooth muscle proliferation depends upon a series of complex signals based upon cellular interactions in the local microenvironment of the artery. The intracellular signalling pathways for mitogenesis versus chemotaxis are being investigated for smooth muscle. The roles of the cytokines and growth-regulatory peptides involved in these cellular interactions represent critical points of departure for intervention and the development of new diagnostic methods. In addition, magnetic resonance imaging has been developed to demonstrate the fine structure of lesions of atherosclerosis in peripheral arteries not subject to cardiac motion. This noninvasive methodology holds great promise for the future of these approaches.
Bringing up children to scheduled meals promotes current extent of overweight and insulin resistance. The
spontaneous arousal of hunger sensations at low blood glucose concentration is different from scheduled arousal.
Memorization of spontaneous arousals and reports of their identity in later occasions may be confirmed by biochemical,
physiological and physical measurements stating the identity of metabolic conditions. This review reports this distinction
and the identification by training of initial hunger (IH). Validated IH includes epigastric sensations (the most frequent
and recognizable) and mental and physical sensations. A meal pattern solicited by validated IH may be maintained
for months and years up to old age. This pattern reduces energy intake by a third, and decreases mean weekly
preprandial BG, glycated Hb, insulin resistance and body weight in those who are insulin resistant or overweight.
Previous studies showed that breast-feeding correlates with lower cholesterol levels later in life but have not used a randomized design. This prospective study sought to test the proposal that breast milk feeding makes for a better lipoprotein profile in adolescents born preterm. Preterm infants were randomly assigned in 2 parallel trials to receive (in trial 1) either donated banked breast milk or preterm formula; or (in trial 2) either standard term formula or preterm formula. In both trials, the assigned preparation constituted the entire diet or supplemented mother's milk. During follow up of 216 adolescents 13 to 16 years of age, measurements were made of the ratio of low-density to high-density lipoprotein cholesterol (LDL to HDL); the ratio of apolipoprotein B to apolipoprotein A-1 (apoB to apoA-1); and the concentration of C-reactive protein (CRP), a marker of the inflammatory process in atherosclerosis.
The mean LDL to HDL ratio was 14% lower in adolescents who had received banked breast milk compared with those given preterm formula, a significant difference. CRP levels also were significantly lower in the former group. No differences were noted between the banked breast milk and preterm formula groups in HDL cholesterol, apoA-1, triglyceride, or the apoB to apoA-1 ratio. Differences in LDL cholesterol and apoB were of borderline significance. The LDL to HDL ratio remained significantly lower in the banked breast milk group after adjusting for age, gender, body mass index, social class, birth weight, and gestation. There were no significant differences in the lipoprotein profile or CRP levels between infants randomized to receive term formula and those given preterm formula, even after adjusting for possible confounding factors. Consuming a larger proportion of human milk was associated with lower LDL to HDL and apoB to apoA-1 ratios, independently of gestation and potential confounding factors. Concentrations of CRP correlated positively with both lipoprotein ratios.
The type of infant nutrition permanently influences the lipoprotein profile in adolescence. Breast milk feeding would appear to lower the risk of atherosclerosis and cardiovascular disease later in life.
Just over a decade ago, a single-center Belgian study showed that normalization of blood glucose in critically ill patients lowered hospital mortality by more than 30%.(1) Although subsequent studies were unable to reproduce these findings, the appeal of such a straightforward intervention was too great to resist: guidelines from professional organizations(2),(3) were published, and editorial commentary(4) highlighted initiatives by the Institute for Healthcare Improvement, the Joint Commission on Accreditation of Healthcare Organizations, and the Volunteer Hospital Association that incorporated tight glucose control as a standard. Indeed, the prestigious Codman Award of the Joint Commission was presented in 2004 for . . .
Most postprandial studies have investigated the response of a single meal, yet the ingestion of sequential meals is more typical in a Western society. The aim of this review is to explain how natural and stable isotope tracers of fatty acids have been used to investigate the metabolism of dietary fat after single and multiple meals, with a focus on in vivo measurements of adipose tissue metabolism. When stable isotope tracers are combined with arteriovenous difference measurements, very specific measurements of metabolic flux across tissues can be made. We have found that adipose tissue is a net importer of dietary fat for 5 h following a single test meal and for most of the day during a typical three-meal eating pattern. When dietary fat is cleared from plasma, some fatty acids 'spillover' into the plasma and contribute up to 50% of postprandial plasma NEFA concentrations. Therefore, plasma NEFA concentrations after a meal reflect the balance between intracellular and extracellular lipolysis in adipose tissue. This balance is altered after the acute ingestion of fructose. The enzyme lipoprotein lipase is a key modulator of fatty acid flux in adipose tissue and its rate of action is severely diminished in obese men. In conclusion, in vivo studies of human metabolism can quantify the way that adipose tissue fatty acid trafficking modulates plasma lipid concentrations. This has implications for the flux of fatty acids to tissues that are susceptible to ectopic fat deposition such as the liver and muscle.
Specific dietary and other lifestyle behaviors may affect the success of the straightforward-sounding strategy "eat less and exercise more" for preventing long-term weight gain.
We performed prospective investigations involving three separate cohorts that included 120,877 U.S. women and men who were free of chronic diseases and not obese at baseline, with follow-up periods from 1986 to 2006, 1991 to 2003, and 1986 to 2006. The relationships between changes in lifestyle factors and weight change were evaluated at 4-year intervals, with multivariable adjustments made for age, baseline body-mass index for each period, and all lifestyle factors simultaneously. Cohort-specific and sex-specific results were similar and were pooled with the use of an inverse-variance-weighted meta-analysis.
Within each 4-year period, participants gained an average of 3.35 lb (5th to 95th percentile, -4.1 to 12.4). On the basis of increased daily servings of individual dietary components, 4-year weight change was most strongly associated with the intake of potato chips (1.69 lb), potatoes (1.28 lb), sugar-sweetened beverages (1.00 lb), unprocessed red meats (0.95 lb), and processed meats (0.93 lb) and was inversely associated with the intake of vegetables (-0.22 lb), whole grains (-0.37 lb), fruits (-0.49 lb), nuts (-0.57 lb), and yogurt (-0.82 lb) (P≤0.005 for each comparison). Aggregate dietary changes were associated with substantial differences in weight change (3.93 lb across quintiles of dietary change). Other lifestyle factors were also independently associated with weight change (P<0.001), including physical activity (-1.76 lb across quintiles); alcohol use (0.41 lb per drink per day), smoking (new quitters, 5.17 lb; former smokers, 0.14 lb), sleep (more weight gain with <6 or >8 hours of sleep), and television watching (0.31 lb per hour per day).
Specific dietary and lifestyle factors are independently associated with long-term weight gain, with a substantial aggregate effect and implications for strategies to prevent obesity. (Funded by the National Institutes of Health and others.).
A slow rate of intrauterine growth is a major risk factor for several common noncommunicable diseases, which include the following: coronary heart disease (CHD), hypertension, and type 2 diabetes. Likewise, growth patterns in infancy and childhood have been identified as important factors linked to the pathogenesis of these disorders. In this overview, patterns of growth associated with CHD, type 2 diabetes, and related metabolic traits in adult life are presented on the basis of findings from the Helsinki Birth Cohort Study (HBCS) 1934-1944. Later risk of CHD was associated with small body size at birth and during infancy, followed by an increase in body size later in childhood. This pattern of growth has been associated with dyslipidemia in later life, which offers an explanation for the observed findings. Type 2 diabetes and CHD share several risk factors. The early growth of persons who later develop type 2 diabetes includes a small body size at birth as well as a small body size during infancy. An early age at adiposity rebound was associated with a markedly increased risk of type 2 diabetes in adulthood. The patterns of growth associated with type 2 diabetes are also associated with alterations in body composition, which predisposes to insulin resistance and the metabolic syndrome. The presented findings suggest that to be able to understand the pathogenesis of several noncommunicable diseases, the diseases need to be studied from a life-course perspective, and prenatal and childhood growth as well as adult characteristics need to be taken into account.
From a classical point of view, gastric motility acts to clear the stomach between meals, whereas postprandial motility acts to provide a reservoir for food, mixing and grinding the food and to assure a controlled flow of food to the intestines.
To summarise findings that support the role of gastric motility as a central mediator of hunger, satiation and satiety.
A literature review using the search terms 'satiety', 'satiation' and 'food intake' was combined with specific terms corresponding to the sequence of events during and after food intake.
During food intake, when gastric emptying of especially solids is limited, gastric distension and gastric accommodation play an important function in the regulation of satiation. After food intake, when the stomach gradually empties, the role of gastric distension in the determination of appetite decreases and the focus will shift to gastric emptying and intestinal exposure of the nutrients. Finally, we have discussed the role of the empty stomach and the migrating motor complex in the regulation of hunger signals.
Our findings indicate that gastric motility is a key mediator of hunger, satiation and satiety. More specifically, gastric accommodation and gastric emptying play important roles in the regulation of gastric (dis)tension and intestinal exposure of nutrients and hence control satiation and satiety. Correlations between gastric accommodation, gastric emptying and body weight indicate that gastric motility can also play a role in the long-term regulation of body weight.
Type 2 diabetes mellitus (DM) is associated with an increased risk of colorectal cancer (CRC); it is not clear if this association varies by sex or other factors. Insulin use might also be associated with CRC risk. We investigated associations of type 2 DM and insulin use with CRC risk.
The Cancer Prevention Study II Nutrition Cohort is a prospective study of cancer incidence. In 1992 or 1993, adult participants (n = 184,194) completed a detailed, self-administered questionnaire. Follow-up questionnaires were sent in 1997 and every 2 years thereafter. Cox proportional hazards regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (CI), adjusting for covariates.
After exclusions, 73,312 men and 81,663 women remained in the final analytic cohort; 1567 men (227 with type 2 DM) and 1242 women (108 with type 2 DM) were diagnosed with colon or rectal cancer by 2007. Among men, type 2 DM was associated with increased risk of incident CRC compared to not having type 2 DM (RR: 1.24; 95% CI: 1.08-1.44); risk was higher for participants with type 2 DM using insulin (RR: 1.36; 95% CI: 1.05-1.78), and participants with type 2 DM not using insulin (RR: 1.22, 95% CI: 1.04-1.45). Among women, type 2 DM and insulin use were not associated with risk of incident CRC (RR: 1.01; 95% CI: 0.82-1.23 and RR: 0.95; 95% CI: 0.64-1.41, respectively).
There is a modest association between type 2 DM and CRC among men, but not women. Insulin use is not associated with a substantially increased risk of CRC.
The connection between inflammation and tumorigenesis is well-established and in the last decade has received a great deal of supporting evidence from genetic, pharmacological, and epidemiological data. Inflammatory bowel disease is an important risk factor for the development of colon cancer. Inflammation is also likely to be involved with other forms of sporadic as well as heritable colon cancer. The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and could differ between colitis-associated and other forms of colorectal cancer. Recent work has elucidated the role of distinct immune cells, cytokines, and other immune mediators in virtually all steps of colon tumorigenesis, including initiation, promotion, progression, and metastasis. These mechanisms, as well as new approaches to prevention and therapy, are discussed in this review.
Functional dyspepsia is a common gastrointestinal disorder. The pathogenesis of functional dyspepsia remains unclear. Functional dyspepsia may begin after a bout of gastroenteritis (post-infectious functional dyspepsia) or de novo (nonspecific functional dyspepsia). The aim of this study was to investigate the prevalence and probable mechanisms of post-infectious functional dyspepsia.
Functional dyspepsia patients with a history of unsanitary food intake and acute gastroenteritis 6-12 months ago were enrolled. (13)C-UBT confirmed absence of H. pylori infection. Controls consisted of healthy nondyspeptic volunteers and patients with nonspecific functional dyspepsia. Gastric biopsies were used for routine histology, immunohistochemistry, electron microscopy, ELISA, HPLC assays and Western blot examination.
Eighty-five subjects were entered including 35 with post-infectious functional dyspepsia, 30 with nonspecific functional dyspepsia, and 20 healthy controls. The number of mast cells in post-infectious functional dyspepsia and nonspecific functional dyspepsia were significantly greater than that in healthy controls. The number of enterochromaffin cells (ECs) in post-infectious functional dyspepsia was significantly higher than those in nonspecific functional dyspepsia or in healthy controls. The number of mast cells and ECs increased with the density of chronic inflammatory cells. The release of histamine and 5-hydroxytryptamine from gastric mucosa of post-infectious functional dyspepsia patients was significantly greater than those from nonspecific functional dyspepsia or healthy controls. Tryptase protein expression was higher in post-infectious functional dyspepsia and nonspecific functional dyspepsia than in healthy controls. The histological score of chronic gastric inflammation was greater in post-infectious functional dyspepsia versus patients with nonspecific functional dyspepsia or healthy controls. Electron microscopy showed secreting granules in the cytoplasm of both mast cells and ECs. The number of activated mast cells and Ecs at a distance of < 5 microm of nerve fibers were significantly greater in post-infectious functional dyspepsia versus nonspecific functional dyspepsia or controls.
Dyspepsia may occur after an acute onset of gastroenteritis in a part of patients. Potent chemicals derived from mast cells and ECs, including histamine, tryptase and 5-hydroxytryptamine may be involved in the pathogenesis of post-infectious functional dyspepsia.
Corticotropin-releasing hormone (CRH) is an important neuro-endocrine mediator of the stress response. Local effects of CRH in the intestinal mucosa have become evident in recent years. We showed that CRH activates CRH receptor subtypes R1 and R2 on subepithelial mast cells, thereby inducing increased transcellular uptake of protein antigens in human colonic biopsies in Ussing chambers. Ongoing studies also implicate local cholinergic signaling in regulation of macromolecular permeability in the human colon. Since increased uptake of antigenic molecules is associated with mucosal inflammation, our findings may have implications for understanding stress-related intestinal disorders.
Approximately 1 in ten patients with irritable bowel syndrome (IBS) believe their IBS began with an infectious illness. Prospective studies have shown that 3% to 36% of enteric infections lead to persistent new IBS symptoms; the precise incidence depends on the infecting organism. Whereas viral gastroenteritis seems to have only short-term effects, bacterial enteritis and protozoan and helminth infections are followed by prolonged postinfective IBS (PI-IBS). Risk factors for developing PI-IBS include, in order of importance, prolonged duration of initial illness, toxicity of infecting bacterial strain, smoking, mucosal markers of inflammation, female gender, depression, hypochondriasis, and adverse life events in the preceding 3 months. Age older than 60 years might protect against PI-IBS, whereas treatment with antibiotics has been associated with increased risk. The mechanisms that cause PI-IBS are unknown but could include residual inflammation or persistent changes in mucosal immunocytes, enterochromaffin and mast cells, enteric nerves, and the gastrointestinal microbiota. Adverse psychological factors contribute to persistent low-grade inflammation. The prognosis for patients with PI-IBS is somewhat better than for those with unselected IBS, but PI-IBS can still take years to resolve. There are no specific treatments for PI-IBS; these should be tailored to the predominant bowel disturbance, which is most frequently diarrhea.
The role of anorexia of infection as a mechanism of host defense was studied by force-feeding infected mice to a normal energy intake. Their mortality and survival times were then compared with those of infected mice feeding ad libitum. Mortality was increased and survival time shortened in force fed animals. Our observations suggest that anorexia, by reducing energy intake, has a significant role in the early defense of the host.
The A. have studied 28 pairs of rats; 17 pairs received 1,1 g of soya oil; 7 pairs were starved. The partners were kept; one at the environmental temperature of 6 degrees C, the other at 30 degrees C. After a night, all rats were tested for xylose absorption. Xylose intestinal absorption in the rats kept at the environmental temperature of 30 degrees C after soya oil decreased of 42,88 +/- 8,14 of the value found at 6 degrees C; it decreased of 15,59 +/- 3,20% after a night of fast. Both decreases were significant (P less 0.01).
