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Initial hunger prevents energy accumulation
Sustained self-regulation of energy intake. Initial hunger is associated with low pre-meal blood glucose and prevents energy accumulation.
Mario Ciampolini,1§ Riccardo Bianchi,2 Boudewijn de Pont,3 David Lovell-Smith,4 Massimiliano Sifone5, Martine van Weeren3, Willem de Hahn3, Lorenzo Borselli1, Angelo Pietrobelli6
1Unit of Preventive Gastroenterology, Department of Paediatrics, Università di Firenze, 50132 Florence, Italy
2Department of Physiology and Pharmacology, and Robert F. Furchgott Center for Neural and Behavioral Sciences. State University of New York Downstate Medical Center, Brooklyn, New York, USA 3AMC, 1100 DD Amsterdam, The Netherlands
4Department of General Practice and Primary Health Care,
University of Auckland, Auckland, New Zealand
5Department of Statistics, Università di Firenze, Florence, Italy
6Paediatric Unit, Università di Verona, Verona, Italy
§ Corresponding author:
E-mails of co-authors:
Riccardo Bianchi
Boudewijn de Pont
David Lovell-Smith
Massimiliano Sifone
Martine van Weeren
Willem de Hahn
Lorenzo Borselli No address
Angelo Pietrobelli
Supported by the Italian Ministry of University, Research, Science and Technology grants for the years 1998-2002 and ONLUS Nutrizione e Prevenzione, Firenze for years 2003-2008.
Abstract
Background: Excessive energy intake has been implicated in obesity, diabetes, hypertension and coronary artery disease. Dietary restraint has been unsuccessful as a method for the self-regulation of eating. Self-recognition of initial hunger is less arduous than dietary restraint and may eliminate energy accumulation.
Objectives: 1) To identify whether the experience of initial hunger is correlated with mean blood glucose (BG) in a population after end of tutorial contacts. 2) To investigate whether a meal pattern in which initial hunger is present pre-meal (initial hunger meal pattern, IHMP) is associated with reduced energy accumulation over a 5 month period.
Methods: Subjects were trained to identify sensations of initial hunger then adjust food intake so that initial hunger was present pre-meal at each mealtime. The purpose of training was to provide meal-by-meal feedback for self-regulation of food intake. We first compared reports of initial hunger with pre-prandial BG reports to before training. In a randomised trial we then measured metabolic biomarkers of energy accumulation in 89 trained adults and 31 controls, before training in the IHMP and 5 months after training.
Results: At baseline, 5040 3738 BG diary reports identified a baseline group with a high prevalence of initial hunger and mean BG of < 81.8 mg/dL (LBG; n = 34) and a group with a low prevalence of initial hunger and BG > 81.8 mg/dL (HBG; n = 55). The baseline LBG 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, the LBG group maintained constant values, whereas the HBG subjects significantly decreased pre-prandial 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).
Conclusion: Initial hunger arises mainly at a BG of 81.8 mg/dL or below. Above this concentration, meals are associated with biomarkers of energy accumulation.
Introduction
Finding ways to enhance self-regulatory dietary skills may alleviate some of the most prevalent diseases in industrialised societies, including obesity, diabetes, hypertension and coronary artery disease. Dietary regimes that attempt to restrain eating have been unsuccessful [1, 2] leading to the feasibility of self-regulation of energy intake being questioned [3]. A key reason for this lack of success may be that most dietary methods rely on weekly or monthly measurements of weight or skin-fold thickness or (in the case of diabetics) glycated haemoglobin. These measurements provide no immediate feedback to dieters, who ingest food at least three times daily. We therefore sought a method that would allow mealbymeal feedback. We hypothesised that subjects would accept this method more readily than blunt restraint and demonstrate increased regulation of energy intake.
Blood glucose (BG) concentration is a reliable index of energy availability to body cells [4 – 6]. BG slowly declines in the absence of food intake during the day until a physiological system of signalling emerges prompts eating [7 - 9]. However, in Italy, as in most countries, people generally eat at fixed mealtimes. This suggests that they are not necessarily responding to physiological eating signals. Some untrained subjects have reported pre-meal “hunger” but such self-reports were variably associated with high or low BG in the previous validation of initial hunger [9] suggesting that perceived hunger in untrained subjects might be a poor indicator of their underlying metabolic state [9, 10].
The authors expect that a physiological signalling system will prompt unconditioned eating and avoid conditioned eating. By conditioned eating we mean eating in response to external stimuli such as mealtime, sight or smell of food, talk about food or any other learned association. In the explorative search for a subject’s own signalling system we prescribedencouraged subjects to avoid taking meals until an actual sensation of hunger appeared [9]. We then asked them to note its subjective character then, measure BG using a portable glycometer. Linking the subjective sensation with BG measurement helped subjects to characterize hunger, differentiate it from other sensations and to recall it. It also allowed us to categorise subjects’ experiences and make inter-individual objective comparisons. Subjects typically noted the spontaneous appearance of gastric pangs, feelings of emptiness, hollowness and mental or physical weakness and that these were associated with low BG measurements. We term these bodily symptoms “initial hunger” [9], and use “initial” to differentiate this degree of hunger from the acutely uncomfortable sensations that can develop when a meal is delayed. After a few days of trial and error subjects were able to adjust of their food intake (either content, portion size, or timing) so that initial hunger appeared at the usual three mealtimes per day. In the event, for example, that a subject overate in a particular meal then he or she could compensate by delaying or skipping the subsequent meal to ensure the return of initial hunger. This pattern of eating in which initial hunger is present pre-meal at each meal is what we term the IHMP or initial hunger meal pattern.
In a hospital laboratory check after two weeks of BG measurements, the sensitivity in distinguishing by subjective sensation a BG ≤ 81 mg/dL from ≥ 85 mg/dL was 93.3% [9]. Only one subject reported initial hunger at a BG of 87 mg/dL (4.8 mmol/l). We therefore wondered whether a pre-meal mean BG could be identified within a population that would reliably distinguish between a mainly conditioned meal pattern and a mainly unconditioned one (induced by initial hunger). We reasoned that such an objective demarcation point might be useful in training future subjects in the subjective recognition of initial hunger. A BG demarcation point could also be useful in lending greater validity to the association between initial hunger and BG estimation [9], in verifying subject compliance in hunger studies and in assessing healthy or non-healthy eating behaviour of a population. To identify this demarcation point, we investigated mean BG longitudinally, namely as reported before 21 meals by 7-d diary in 89 subjects before and after training.
Since BG concentration is under tight metabolic control [4 - 6], a habitual elevation of a few mg/dL of BG before the onset of meals could make a difference in weight and metabolic biomarkers over months or years. To assess prevention of energy accumulation, we investigated body weight, body mass index (BMI), glucose tolerance, insulin sensitivity and glycated hemoglobin (HbA1c) before and after training in initial hunger, in a randomized comparison with 31 control subjects.
Methods
Recruitment of subjects
The Paediatric Gastroenterology Unit of Florence University recruited 153 subjects to this study. This unit diagnoses and treats celiac disease in children and adults. Aged 18 to 60 years, subjects suffered from symptoms of functional bowel disorders such as dyspepsia, abdominal pain, and diarrhoea (Figure 1). They showed no morphological, physical or biochemical signs of organic disease [9, 11, 12]. Subjects with impaired glucose tolerance (fasting plasma-glucose 115 mg/dL (6.4 mmol/l)), and non-insulin dependent diabetes mellitus (NIDDM), celiac, liver, heart, brain and kidney diseases, were excluded from this study (Fig 1). Twenty-four subjects withdrew (Fig 1). Informed consent was obtained from all subjects. The local Hospital Ethics Committee approved the study in compliance with the Helsinki Declaration.
Sample size
The value of diary BG SD [17] was the interesting difference in diary BG means between control and trained subjects in four possible subgroups. The sample size had to avoid the error alpha at 0.025 and the error beta at 0.05 level of single significance. Thus, the required number for comparison between the smallest subgroups was 13 subjects for each subgroup. This number had to be increased by a factor of 1.5 for the difference in size recruitment between trained and control subgroups [13]. The sum of the two smallest subgroups had thus to amount to about 40 subjects.
Study intervention
Subjects were assigned to a list by a dietician. The list included randomised in covered blocks (2:1) randomised by random numbers [13]) into trained and control groups (Figure 1). The purpose of the training was to help subjects to self- regulate their food intake. Subjects were trained in the IHMP, first by identifying initial hunger using BG as a reference, then by cultivating its presence pre-meal as outlined above (introduction). Consumption of up to 1 kg of fruit/vegetables per day and physical exercise for half an hour a day were recommended [9, 14 - 16] as aids to ensure initial hunger appeared pre-meal.
The control group The subjects of the control group followed their normal routines except for the prescription of physical exercise for half an hour (free-living; Figure 1) and increasing meal size by up 1 kg of fruit/vegetables a day.
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Instrumental procedures and validations
All 120 subjects who completed the study compiled validated seven-day-home-diaries in which they reported BG measurements (by glucometer) before the three main meal times [9, 14 - 16]. Diaries were completed at baseline (before training), after the first seven weeks of training and at five months after baseline. The diaries provided the weekly ‘mean BG’ and other assessments (food intake, time spent in bed, and time spent in gym and outdoors). Our previous laboratory studies include more details on validation of BG measurements compared to estimations [9]; comparison of energy intake and total energy expenditure as assessed by doubly labelled water in infants [17]; and methods for anthropometric measurements, structured interviews, and clinical blood tests [9, 14 - 16].
Oral glucose-tolerance test (GTT)
After a 12-hour overnight fast, all subjects were given a 75 g-oral glucose load. Venous blood samples were taken immediately before the glucose was administered, and 30, 60, 90, 120, and 180 minutes thereafter to determine plasma glucose and serum insulin. Serum insulin was measured with the IMx insulin assay (Abbott Lab. Diagn. Div. USA) [18]. Areas under the curve (AUCs) provided the main GTT parameters.
Setting
The trained group lived under tutorial assistance for seven weeks, and maintained the new strategies of food consumption and energy expenditure that they learned during the initial training for a further three months without tutorial contacts (Figure 1). Otherwise subjects continued their regular work or recreational activities.
Objectives
We wished to 1) identify whether the experience of initial hunger is correlated with mean blood glucose (BG) in a population and 2) investigate whether the IHMP is associated with reduced energy accumulation over a 5 month period.
Outcomes
Five months after the start of the training period the following parameters were assessed:
1. Indexes of the main metabolic risk factors included BG and HbA1c values [19], and BG and insulin AUCs, as well as the GTT measurements of BG and insulin concentrations (see above). The primary outcome was insulin AUC that was expected to be in correlation with the others.
2. Well-being was assessed by seven parameters. Structured interviews ascertained the number of the preceding 90 days in which each of five functional symptoms (diarrhoea, vomiting, headache, epigastric or abdominal pain) had occurred. The hours of daily physical activity and time spent in sleep reported in the seven-day diary were also assessed since an increase in the first and a decrease in the second suggests well-being improvement.
3. Nutrition was assessed by monitoring the following blood indices: hemoglobin (Hb), mean cellular volume (MCV), transferrin saturation, plasma ferritin, zinc, folates, and vitamin B12 [14].
4. Cardiovascular parameters assessed were systolic and diastolic blood pressures, plasma LDL cholesterol/HDL cholesterol ratio, triglycerides, and HDL cholesterol.
5. Body weight and BMI were measured.
6. Energy balance was assessed through measurement of arm and leg skinfold thickness changes during the five-month investigation interval [20], and by assessment of reported energy and vegetable intake.
7. A training effect and correlations between the two body size parameters (weight and BMI), the two energy-balance parameters (arm and skinfold thickness), the four metabolic indexes (mean BG and HbA1c values, and BG and insulin AUCs), and the three (energy, fruit and vegetable) intake factors were longitudinally investigated (i.e. on post minus pre differences) by simple, linear correlation and regression analyses in all of the 120 subjects completing the study (Figure 1).
Compliance was indicated by BG means of 21 values annotated in the diaries, by their SD and by HbA1c measures.
Sample size
Statistics
Values are expressed as means ± SD. Chi-square analyses on the subject number who significantly decreased mean diary BG served to find the BG cut-off value that separated low initial BG from high initial BG-trained subjects with the highest statistical significance (see below). A logistic regression analysis investigated the association of the training and BG mean, Hb1c, insulin and BG AUCs, intakes and anthropometric measures (trained vs. untrained control groups) for significance of multiple results [21]. The significance of difference and correlation was set at P < 0.05 in these analyses. Yates test and two-tailed Student’s t-test on paired or unpaired samples according to data requirements were used to analyse the significance of difference and two-tailed Student’s t-test or Pearson test for correlation. The significance was set at P < 0.05 for single measurements and at P < 0.025 for the GTT insulin and BG AUCs [13]. The trials on well being, nutrition, and cardiovascular risks comprised 5 to 7 tests each [13,21]. The Chi-square for trend assessed the global significance of improvements in these trials. The significance was set at P < 0.01 for the outcome of a single measurement in these trials. The Bonferroni correction was applied when required in the evaluation of multiple comparisons results [13, 21]. In multiple analyses, the “<” symbol indicates the least significant P. Custom-made software was used to tabulate data for statistical analyses. Microsoft Excel (Microsoft Corp., USA) and SAS 8 (SAS Institute Inc., Cary, NC, USA) were used for data presentation and for statistical analyses.