Gallbladder and Gastric Motility in Obese Children and Adults
Gallbladder and Gastric Motility in Obese Children and Adults
Consecutive lean and obese subjects were enrolled from three different age groups: 50 newborns aged 1–12 months (male : female = 32:18), 18 pre-adolescents aged 7–8 years, (male : female = 15:3), and 99 adults aged 22–80 years (male : female = 43:56).
Subjects were recruited at the Maternity and Pediatric Ward at the Hospital of Bisceglie (newborns and pre-adolescents) and in the Department of Internal Medicine at the University Medical School of Bari (adults), during routine outpatient visits.
Among the newborns, 44 were lean and six were obese (mean age 5 ± 1 months, range 1–12); among the pre-adolescents, 11 were lean and seven were obese (mean age 7 ± 0.1 years, range 6–8). Among the adults, 32 patients were obese (mean age 48 ± 3 years, range 22–74, 13 males) and 67 were lean (mean age 43 ± 2 years, range 22–80, 34 males). In each subgroup, lean and obese subjects were homogeneous for gender and age distribution.
Subjects were neither under medications nor were they affected by conditions that were able to influence gastrointestinal motility and secretory functions. Obese subjects were not under weight-reducing diets. The presence of diabetes was excluded by accurate medical history and clinical assessment in pre-adolescents and adults and by blood glucose analysis in all enrolled newborns. Gallstone disease was an exclusion criterion, since this clinical condition can potentially affect gallbladder and gastric motility.
For calculation of obesity, different algorythms were used. In newborns and pre-adolescents, standard measurements included height, weight, BMI and calculation of Z-score and percentile conversion from standard Normal Table. The MedCalc 3000 routine was used according to age (i.e. younger or older than 2 years) and gender. The final result served to distinguish between lean and obese subjects. In adults, obesity was defined as a BMI equal to or greater than 30 kg/m.
This was an independent, investigator-driven, open-label trial devoid of any industrial support. The study was approved by the Institutional Review Board in the Department of Internal Medicine at the Hospital of Bisceglie. All adult subjects and parents of each child gave their written informed consent and permission to use their medical records.
Functional ultrasonography was used as part of the routine work-up during abdominal examination. Gallbladder and gastric emptying were simultaneously studied with Toshiba Capasee scanner and Esaote AU450 equipped with a 3.5 MHz convex probe. Subjects were in a sitting position during the ingestion of milk (10 mL/Kg in newborns, 200 mL in pre-adolescents, containing 7.5 g lipids) or a standard liquid test meal in adults (Nutridrink, Nutricia, Milano, Italy) consisting of a 200 mL solution with 12 g (20%) protein, 11.6 g (19%) fat, and 36.8 g (61%) carbohydrates for a total of 300 kcal (1260 kJ, 455 mOsm/L). Tests started in the morning, with subjects in the fasting state (at least 12 h) and were invariably performed by experienced examiners (A.D.C and P.P.).
Fasting and postprandial gallbladder volumes were measured by sagittal and transverse scans of the gallbladder at its largest dimension at 5–15 min intervals during a 20-min examination for newborns and a 120-min examination for pre-adolescents and adults. In newborns, the observation time was shorter than that in adults, since in all subjects the maximal gallbladder emptying and the start of gallbladder refilling were invariably observed within 20 min from meal ingestion. Gallbladder volume was measured from frozen sonograms assuming an ellipsoid shape of the organ, a reliable method when gallbladder shape is not highly irregular, which was the case in this study. Indices of gallbladder motility were as follows: fasting volume (mean of three measurements at −15, −5 and 0 min before test meal, expressed in mL); residual volume (minimum volume measured postprandially, in mL and percent of fasting volume); ejection volume (maximum fraction of bile evacuated from the gallbladder, calculated by subtraction of residual volume from fasting volume and expressed in mL and percent of fasting volume).
The study of gastric kinetics was performed by monitoring time-dependent changes of antral areas, a well standardized technique in adults and in children. The gastric antrum was identified by longitudinal scans at the epigastrium at the level of antral-body connection in a single transversal section. The superior mesenteric vein and the aorta were landmark points. The antral area was measured in the fasting state at its maximal size between two contractions, and subsequently monitored at regular time intervals postprandially. The following indices served to assess gastric emptying: antral (basal) area in cm (mean of two measurements starting 5 min before the meal), maximal postprandial antral area, measured 2 min after meal ingestion, postprandial antral areas taken at 5 min intervals from meal ingestion, minimal postprandial antral area observed throughout the 2 h emptying curve, and half-emptying time. Antral emptying curves were obtained by plotting antral areas versus time. In order to obviate inter-individual variability of antrum size, postprandial areas were normalized to maximal areas after subtracting basal areas according to the following standard formula: 100 × (At − a)/(A2 − a), where At = postprandial area at any given time; a = basal area; A2 = maximal antral area (measured at 2 min postprandially). Half-emptying time was the time at which 50% decrease of antral area occurred (T1/2, min), and was calculated by linear regression analysis from the linear part of antral emptying curve. This index closely correlates with the scintigraphic half-emptying time. In newborns the observation time was shorter than in adults, since in all subjects antral areas had returned to initial basal values within 20 min from meal ingestion.
Data are expressed as the mean ± standard error (SE). Continuous variables were analyzed using analysis of variance (anova), followed by Fisher's least significant difference (LSD) test. Correlations were assessed by calculating Spearman's rs. Differences between two subgroups were evaluated by Student's t test. A two-tailed probability (P) value of less than 0.05 was considered statistically significant. All calculations were performed with the NCSS 2007 statistical software (NCSS, PASS, and GESS. NCSS. Kaysville, Utah, USA).
Methods
Patients
Consecutive lean and obese subjects were enrolled from three different age groups: 50 newborns aged 1–12 months (male : female = 32:18), 18 pre-adolescents aged 7–8 years, (male : female = 15:3), and 99 adults aged 22–80 years (male : female = 43:56).
Subjects were recruited at the Maternity and Pediatric Ward at the Hospital of Bisceglie (newborns and pre-adolescents) and in the Department of Internal Medicine at the University Medical School of Bari (adults), during routine outpatient visits.
Among the newborns, 44 were lean and six were obese (mean age 5 ± 1 months, range 1–12); among the pre-adolescents, 11 were lean and seven were obese (mean age 7 ± 0.1 years, range 6–8). Among the adults, 32 patients were obese (mean age 48 ± 3 years, range 22–74, 13 males) and 67 were lean (mean age 43 ± 2 years, range 22–80, 34 males). In each subgroup, lean and obese subjects were homogeneous for gender and age distribution.
Subjects were neither under medications nor were they affected by conditions that were able to influence gastrointestinal motility and secretory functions. Obese subjects were not under weight-reducing diets. The presence of diabetes was excluded by accurate medical history and clinical assessment in pre-adolescents and adults and by blood glucose analysis in all enrolled newborns. Gallstone disease was an exclusion criterion, since this clinical condition can potentially affect gallbladder and gastric motility.
Calculation of Obesity
For calculation of obesity, different algorythms were used. In newborns and pre-adolescents, standard measurements included height, weight, BMI and calculation of Z-score and percentile conversion from standard Normal Table. The MedCalc 3000 routine was used according to age (i.e. younger or older than 2 years) and gender. The final result served to distinguish between lean and obese subjects. In adults, obesity was defined as a BMI equal to or greater than 30 kg/m.
This was an independent, investigator-driven, open-label trial devoid of any industrial support. The study was approved by the Institutional Review Board in the Department of Internal Medicine at the Hospital of Bisceglie. All adult subjects and parents of each child gave their written informed consent and permission to use their medical records.
Ultrasonographic Studies
Functional ultrasonography was used as part of the routine work-up during abdominal examination. Gallbladder and gastric emptying were simultaneously studied with Toshiba Capasee scanner and Esaote AU450 equipped with a 3.5 MHz convex probe. Subjects were in a sitting position during the ingestion of milk (10 mL/Kg in newborns, 200 mL in pre-adolescents, containing 7.5 g lipids) or a standard liquid test meal in adults (Nutridrink, Nutricia, Milano, Italy) consisting of a 200 mL solution with 12 g (20%) protein, 11.6 g (19%) fat, and 36.8 g (61%) carbohydrates for a total of 300 kcal (1260 kJ, 455 mOsm/L). Tests started in the morning, with subjects in the fasting state (at least 12 h) and were invariably performed by experienced examiners (A.D.C and P.P.).
Gallbladder Studies
Fasting and postprandial gallbladder volumes were measured by sagittal and transverse scans of the gallbladder at its largest dimension at 5–15 min intervals during a 20-min examination for newborns and a 120-min examination for pre-adolescents and adults. In newborns, the observation time was shorter than that in adults, since in all subjects the maximal gallbladder emptying and the start of gallbladder refilling were invariably observed within 20 min from meal ingestion. Gallbladder volume was measured from frozen sonograms assuming an ellipsoid shape of the organ, a reliable method when gallbladder shape is not highly irregular, which was the case in this study. Indices of gallbladder motility were as follows: fasting volume (mean of three measurements at −15, −5 and 0 min before test meal, expressed in mL); residual volume (minimum volume measured postprandially, in mL and percent of fasting volume); ejection volume (maximum fraction of bile evacuated from the gallbladder, calculated by subtraction of residual volume from fasting volume and expressed in mL and percent of fasting volume).
Gastric Studies
The study of gastric kinetics was performed by monitoring time-dependent changes of antral areas, a well standardized technique in adults and in children. The gastric antrum was identified by longitudinal scans at the epigastrium at the level of antral-body connection in a single transversal section. The superior mesenteric vein and the aorta were landmark points. The antral area was measured in the fasting state at its maximal size between two contractions, and subsequently monitored at regular time intervals postprandially. The following indices served to assess gastric emptying: antral (basal) area in cm (mean of two measurements starting 5 min before the meal), maximal postprandial antral area, measured 2 min after meal ingestion, postprandial antral areas taken at 5 min intervals from meal ingestion, minimal postprandial antral area observed throughout the 2 h emptying curve, and half-emptying time. Antral emptying curves were obtained by plotting antral areas versus time. In order to obviate inter-individual variability of antrum size, postprandial areas were normalized to maximal areas after subtracting basal areas according to the following standard formula: 100 × (At − a)/(A2 − a), where At = postprandial area at any given time; a = basal area; A2 = maximal antral area (measured at 2 min postprandially). Half-emptying time was the time at which 50% decrease of antral area occurred (T1/2, min), and was calculated by linear regression analysis from the linear part of antral emptying curve. This index closely correlates with the scintigraphic half-emptying time. In newborns the observation time was shorter than in adults, since in all subjects antral areas had returned to initial basal values within 20 min from meal ingestion.
Statistical Analysis
Data are expressed as the mean ± standard error (SE). Continuous variables were analyzed using analysis of variance (anova), followed by Fisher's least significant difference (LSD) test. Correlations were assessed by calculating Spearman's rs. Differences between two subgroups were evaluated by Student's t test. A two-tailed probability (P) value of less than 0.05 was considered statistically significant. All calculations were performed with the NCSS 2007 statistical software (NCSS, PASS, and GESS. NCSS. Kaysville, Utah, USA).