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Refeeding hypertension in obese spontaneously hypertensive rats.

Very-low-calorie diets lower blood pressure acutely in obese humans and rats. However, refeeding after dietary restriction produces mild hypertension in rats. Refeeding hypertension was characterized in genetically obese spontaneously hypertensive rats (obese SHR, Koletsky rat), a model of genetic obesity and hypertension. Obese SHR were fed a restricted diet (Optifast) for 12 days, refed ad libitum for 28 days, dieted again for 12 days, and then refed 4 days and killed. Control obese SHR and lean SHR littermates were fed ad libitum continuously. Dietary restriction led to rapid weight loss followed by prompt regain to baseline weight after return to unrestricted food intake. Heart rate fell with institution of the low-calorie diet and returned to baseline on refeeding. Blood pressure became elevated during refeeding in dieted obese SHR relative to ad libitum fed obese SHR controls. The fall in blood pressure after ganglionic blockade with chlorisondamine was exaggerated in refed obese SHR, and cardiac beta-adrenergic receptors were downregulated. Both of these findings imply increased sympathetic tone. The left ventricular wall was thicker in the refed obese SHR than in the ad libitum fed obese SHR. Shorter cycles of weight loss and regain in lean SHR led to transient increases in blood pressure and heart rate. Cycles of dietary restriction and refeeding in obese SHR elicit sustained blood pressure elevation via sympathetic activation and exacerbate cardiac hypertrophy. Drastic fluctuations in nutrient intake may not be advantageous in hypertension.

Animals↗

Obesity among Kuwait University students: an explorative study.

University students' dietary habits have been criticised for their nutritional inadequacy and faddism. Kuwait University students may face the risk of obesity because of affluence and modernization and the dynamic changes in their level of physical activity and caloric intake. This promoted a study of a random sample of 842 Kuwait University students for dietary and socioeconomic factors associated with obesity. Weight and height were measured to calculate the body mass index (BMI), which is the weight in kilograms divided by the height in meters squared (kg/m2). Obesity was classified into grade 1 and 2 (BMI > 25 and > 30 kg/m2). The associated factors studied and obtained through questionnaires included gender, age, marital status, parental obesity, education and occupation, dieting, last dental and health check-up, year of study, number of siblings (total, brothers and sisters), eating in between meals, high school and college GPA and major, exercising, number of regular meals eaten, obese relatives, those living at home, and servants, highest desired degree, birth order, having a chronic disease, countries prefer visiting, family income, governorate, and socioeconomic status (SES). Grade 1 and 2 obesity were found to be 32.0 and 8.9%, respectively. Factors that were found to be significantly associated with obesity included gender, age, marital status, obesity among parents, dieting, last physical check-up, year of study, number of brothers, sisters and regular meals eaten and high school GPA. Logistic regression analysis revealed that the same factors significantly contributed to the development of obesity except the last four. The level of obesity among Kuwait University students is high. Obesity is a risk factor for a variety of chronic diseases. There is a need to address the challenge of instituting measures that would reduce the future ill-effects of obesity on young adults. It is widely believed that during the young adult years many important health habits are formed and set. It is at this stage (or earlier) that wellness and self-care programming for college students is essential and worthy of being explored and its efficacy assessed.

Adolescent↗

Effect of obesity and erect/supine posture on lateral cephalometry: relationship to sleep-disordered breathing.

Craniofacial and upper airway anatomy, obesity and posture may all play a role in compromising upper airway patency in patients with the sleep apnoea/hypopnoea syndrome. The aim of this study was to investigate the relationship between obesity, facial structure and severity of sleep-disordered breathing using lateral cephalometric measurements and to assess the effect of body posture on cephalometric measurements of upper airway calibre variables in obese and non-obese subjects. Lateral cephalometry was carried out in erect and supine postures in 73 awake male subjects randomly selected from patients referred for polysomnography who had a wide range of apnoea/hypopnoea frequencies (1-131 events x h sleep(-1)). Subjects were divided into non-obese (body mass index (BMI) < 30 kg x m(-2); n=42) and obese (BMI > or = 30 kg x m(-2); n=31) groups. Significant but weak correlations were found between apnoea/hypopnoea index (AHI) and measurements reflecting upper airway dimensions: uvular protrusion-posterior pharyngeal wall (r=-0.26, p<0.05) and hyoid-posterior pharyngeal wall (r=0.26, p<0.05). Multiple regression using both upper airway dimensions improved the correlation to AHI (r=0.34, p=0.01). Obese subjects had greater hyoid-posterior pharyngeal wall distances than non-obese subjects, both erect (42+/-5 versus 39+/-4 mm, respectively (mean+/-SD) p<0.01) and supine (43+/-5 versus 40+/-4 mm, p<0.05). Skeletal craniofacial structure was similar in obese and non-obese subjects. In conclusion, measurements reflecting upper airway size were correlated with the severity of sleep-disordered breathing. Differences in upper airway size measurements between obese and non-obese subjects were independent of bony craniofacial structure.

Adult↗

Obese patients with abdominal pain presenting to the emergency department do not require more time or resources for evaluation than nonobese patients.

OBJECTIVES: The authors describe the evaluation of obese and nonobese adult patients with abdominal pain presenting to an emergency department (ED). The hypothesis was that more ED and hospital resources are used to evaluate and treat obese patients. METHODS: A prospective observational study of obese (n = 98; body mass index > or = 30 kg/m2) and nonobese (n = 176; body mass index < 30 kg/m2) adults presenting to the ED with abdominal pain was performed. ED length of stay (LOS) was the primary outcome. Secondary outcomes included use of laboratory tests, computed tomography, and ultrasonography, and rates of consultations, operations, and admissions. ED diagnoses were compared between the two groups. RESULTS: Obese patients were older (41.9 vs. 38.3 years; p = 0.027) and more often female (69% vs. 51%; p = 0.003) than nonobese patients. There were no significant differences between obese and nonobese patients in either the primary or the secondary outcome measures. Obese patients were similar to nonobese patients in regard to LOS (457 vs. 486 minutes), laboratory studies (3.2 vs. 2.9 tests), abdominopelvic computed tomographic scans (30% vs. 31%), and abdominal ultrasounds (16% vs. 13%). Obese and nonobese patients were also similar in their rates of consultations (27% vs. 31%), operations (14% vs. 12%), and admissions (18% vs. 24%). No difference was found for LOS between obese and nonobese patients as evaluated by the Wilcoxon rank-sum test (p = 0.81). Logistic regression analysis controlling for baseline characteristics revealed no significant differences between obese and nonobese patients for secondary outcome variables. ED diagnoses for obese and nonobese patients were similar except that genitourinary diagnoses were less common in obese patients (8% vs. 21%; p = 0.01). CONCLUSIONS: In contradiction to the hypothesis, the results suggest that LOS and ED resource use in obese patients with abdominal pain are not increased when compared with nonobese patients.

Abdominal Pain↗

A longitudinal hormonal profile of the genetically obese mouse.

Obese mice (C57BL/6J ob/ob) and their lean littermates were studied at various ages from immediately post weaning until 62 weeks of age, at which mortality increased markedly. Several age-related changes were noted. 1) Plasma glucose levels were elevated in obese mice 5-20 weeks and 62 weeks of age, but were similar to those in the lean mice at 20-60 weeks of age. Plasma insulin levels were elevated in obese mice, and there were no age-related differences. 2) Brain serotonin was elevated in obese mice at all ages and increased with age in both obese and lean animals. 3) Pituitary contents of ACTH and beta-endorphin were elevated in young obese mice and increased further as these mice approached their life expectancy. 4) The ratios of ACTH to beta-endorphin immunoreactivities were similar in obese and lean mice, except in obese mice over 50 weeks of age where this ratio was increased. We conclude that: 1) the obese mouse is characterized by hyperinsulinemia and hyperadrenocorticism throughout its life; 2) the insulin resistance of the obese mouse improves at 20 weeks of age, yet deteriorates as its life expectancy is approached; 3) the obese mouse has an elevated brain serotonin content similar to previously described elevations of the putative neurotransmitters dopamine and norepinephrine in these mice; and 4) as the obese mouse approaches its life expectancy, abnormalities may occur in the synthesis, processing, or secretion of ACTH and/or beta-endorphine.

Adrenocorticotropic Hormone↗

Eotaxin and obesity.

CONTEXT: Asthma and obesity incidence is increasing worldwide, and asthma is often more severe in the obese. Eotaxin, a CC chemokine, is important in extrinsic asthma, an inflammatory disorder. OBJECTIVE: Our objective was to examine the relation between eotaxin and obesity. DESIGN: We conducted a comparison study of eotaxin in mice fed high-fat vs. standard chow diet for 26 wk, in obese vs. lean humans, in obese humans before and after 4-6 wk of weight loss, and in sc vs. visceral adipose tissue from patients undergoing bariatric surgery. SETTING: Our clinical study occurred in an outpatient weight loss program. PATIENTS: Patients were obese adults with metabolic syndrome (n = 40) and nine morbidly obese bariatric surgery patients. INTERVENTION: Intervention was a very-low-calorie diet. MAIN OUTCOME MEASURES: We assessed circulating eotaxin and eotaxin mRNA levels in adipose tissue. RESULTS: Serum eotaxin levels were significantly higher in obese mice, and adipose mRNA levels correlated positively with serum eotaxin levels. Adipose tissue explants from obese mice showed increased secretion of eotaxin compared with explants from lean mice. In obese patients, plasma eotaxin levels were significantly higher than in lean controls and significantly reduced after weight loss, and eotaxin mRNA levels were 4.7-fold higher in visceral than sc adipose tissue. CONCLUSIONS: Circulating eotaxin and eotaxin mRNA levels in visceral adipose tissue were increased in obesity in mice and humans. Adipose tissue explants secrete eotaxin, and the stromal/vascular component of adipose tissue seems to be the predominant source of eotaxin. Diet-induced weight loss in humans led to reduction in plasma eotaxin levels, demonstrating that clinical interventions that target obesity can modulate systemic eotaxin levels.

3T3 Cells↗

Association between neuromedin U gene variants and overweight and obesity.

BACKGROUND: Neuromedin U (NMU) is an anorexic neuropeptide expressed in the hypothalamus. Mice lacking the NmU gene are hyperphagic and obese, whereas mice overexpressing Nmu are hypophagic and lean. OBJECTIVE: Our objective was to investigate whether variants in NMU are associated with human obesity. DESIGN: The coding region of NMU was analyzed for variants in obese Czech children and obese Danish adults. Identified missense variants were investigated for cosegregation with obesity in families or association with obesity in the general population. SETTING: The study was performed at Steno Diabetes Center, Denmark, and Department of Pediatrics, Charles University, Czech Republic. SUBJECTS AND METHODS: A total of 289 Czech children and adolescents with early-onset obesity and 84 Danish obese adults were analyzed for variants in NMU. A NMU Ala19Glu polymorphism was genotyped in 5851 Danish subjects of the Inter99 cohort, and a rare NMU Arg165Trp mutation was sequenced in the proband family and in 53 lean and unrelated Czech subjects. RESULTS: The rare NMU Arg165Trp variant cosegregated with childhood obesity in a Czech family. Homozygous carriers of the Glu allele of the NMU Ala19Glu polymorphism were more common in the overweight and obese subjects; the Glu/Glu frequency was 0.4 (95% confidence interval, 0.2-0.6) among 2586 lean subjects (BMI < 25 kg/m2) and 0.9 (95% confidence interval, 0.7-1.1) among 3265 overweight and obese subjects (body mass index >or= 25 kg/m2) [odds ratio, 2.5 (1.2-5.3); P = 0.01]. CONCLUSION: Amino acid variants in NMU associate with overweight and obesity, suggesting that NMU is involved in energy regulation in humans.

Adolescent↗

What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean +/- SD, 58.0 +/- 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 +/- 2.6 mg/min.kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 +/- 1.1 mg/min.kg lean body mass). Despite comparable total body fatness between groups (45.2 +/- 5.3% vs. 44.8 +/- 6.6%; P: = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 +/- 53 vs. 211 +/- 85 cm(2); P: < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 +/- 126 vs. 442 +/- 144 cm(2); P: = NS), total fat mass (38.1 +/- 10.6 vs. 40.0 +/- 11.8 kg), muscle attenuation (42.2 +/- 2.6 vs. 43.6 +/- 4.8 Houndsfield units), and physical activity energy expenditure (1060 +/- 323 vs. 1045 +/- 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P: values ranging between 0.01-0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P: < 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity (<20 yr old) compared with 29% of the MAO subjects (P: = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r(2) = 0.35; P: < 0.05 in both cases). Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.

Adipose Tissue↗

Effects of cardiac rehabilitation and exercise training in obese patients with coronary artery disease.

STUDY OBJECTIVE: To determine the effects of cardiac rehabilitation and exercise training in obese coronary patients. DESIGN: We compared data before and after cardiac rehabilitation between obese and nonobese patients. SETTING: Two large teaching institutions. PATIENTS: 116 obese (body mass index [BMI] > or = 27.8 kg/m2 for men and > or = 27.3 kg/m2 for women; mean, 31.2 +/- 3.2 kg/m2] and 198 (mean BMI, 24.6 +/- 2.1 kg/m2) nonobese patients with recent cardiac events. INTERVENTIONS: A 3-month (36-session) formal, outpatient phase 2 cardiac rehabilitation and supervised exercise training program. MEASUREMENTS AND RESULTS: At baseline, obese patients had higher levels of total cholesterol (p < 0.01), low-density lipoprotein-cholesterol (LDL-C [p < 0.01]), LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio (p < 0.01), percentage body fat (p < 0.02), and a higher prevalence of hypertension (p < 0.05) than the nonobese patients, but the prevalence of diabetes mellitus and of other coronary risk factors was similar. After cardiac rehabilitation, there were modest reductions in the prevalence of obesity (116 patients [37%] vs 104 patients [33%]) and severe obesity (BMI > or = 35 kg/m2 [3.5 vs 2.5%]), although these improvements were not statistically significant. The obese patients had improvements in exercise capacity (+24%; p < 0.001), BMI (-3%; p < 0.0001), LDL-C (-4%; p = 0.07), HDL-C (+6%; p < 0.001), and LDL-C/HDL-C ratio (-10%; p < 0.01). Although reduction in BMI was greater in the obese patients (-3 vs 0%; p < 0.0001), improvement in exercise capacity was greater in the nonobese (+36 vs +24%; p < 0.01); improvements in lipid fractions and percentage body fat were statistically similar between the groups. CONCLUSION: Modest reductions in BMI, obesity, and severe obesity occur after cardiac rehabilitation. In addition, obese patients demonstrate significant improvements in most coronary risk factors after rehabilitation, although improvements in exercise capacity are greater in nonobese patients. Potentially, more significant improvements in exercise capacity and lipid values may occur by specifically targeting obese patients for further weight reduction and exercise training after major cardiac events.

Adipose Tissue↗

Comparison between insulin tolerance test, growth hormone (GH)-releasing hormone (GHRH), GHRH plus acipimox and GHRH plus GH-releasing peptide-6 for the diagnosis of adult GH deficiency in normal subjects, obese and hypopituitary patients.

OBJECTIVE: It has been gradually realized that GH may have important physiological functions in adult humans. The biochemical diagnosis of adult GHD is established by provocative testing of GH secretion. The insulin-tolerance test (ITT) is the best validated. The ITT has been challenged because of its low degree of reproducibility and lack of normal range, and is contra-indicated in common clinical situations. Furthermore, in severely obese subjects the response to the ITT frequently overlaps with those found in non-obese adult patients with GHD. DESIGN: The aim of the present study was to evaluate the diagnostic capability of four different stimuli of GH secretion: ITT, GHRH, GHRH plus acipimox (GHRH+Ac), and GHRH plus GHRP-6 (GHRH+GHRP-6), in two pathophysiological situations: hypopituitarism and obesity, and normal subjects. METHODS: Eight adults with hypopituitarism (four female, four male) aged 41-62 Years (48.8+/-1.4 Years), ten obese normal patients (five female, five male) aged 38-62 Years (48.1+/-2.5 Years), with a body mass index of 34.2+/-1.2 kg/m(2), and ten normal subjects (five female, five male) aged 33-62 Years (48.1+/-2.8 Years) were studied. Four tests were performed on each patient or normal subject: An ITT (0.1 U/kg, 0.15 U/kg for obese, i.v., 0 min), GHRH (100 microg, i.v., 0 min), GHRH (100 microg, i.v., 0 min) preceded by acipimox (250 mg, orally, at -270 min and -60 min) (GHRH+Ac); and GHRH (100 microg, i.v., 0 min) plus GHRP-6 (100 microg, i.v., 0 min) (GHRH+GHRP-6). Serum GH was measured by radioimmunoassay. Statistical analyses were performed by Wilcoxon rank sum and by Mann-Whitney tests. RESULTS: After the ITT the mean peak GH secretion was 1.5+/-0.3 microg/l for hypopituitary, 10.1+/-1.7 microg/l (P<0.05 vs hypopituitary) for obese and 17.8+/-2.0 microg/l (P<0.05 vs hypopituitary) for normal. GHRH-induced GH secretion was 2+/-0.7 microg/l for hypopituitary, 3.9+/-1.2 microg/l (P=NS vs hypopituitary) for obese and 22.2+/-3.8 microg/l (P<0.05 vs hypopituitary) for normal. After GHRH+Ac, mean peak GH secretion was 3.3+/-1.4 microg/l for hypopituitary, 14.2+/-2.7 microg/l (P<0.05 vs hypopituitary) for obese and 35.1+/-5.2 microg/l (P<0.05 vs hypopituitary) for normal. GHRH+GHRP-6 induced mean peak GH secretion of 4.1+/-0.9 microg/l for hypopituitary, 38.5+/-6.5 microg/l (P<0.05 vs hypopituitary) for obese and 68.1+/-5.5 microg/l (P<0.05 vs hypopituitary) for normal subjects. Individually considered, after ITT, GHRH or GHRH+Ac, the maximal response in hypopituitary patients was lower than the minimal response in normal but higher than the minimal response in obese subjects. In contrast, after GHRH+GHRP-6 the maximal response in hypopituitary patients was lower than the minimal response in normal and obese subjects. CONCLUSIONS: This study suggests that, in this group of patients, although both acipimox and GHRP-6 partially reverse the functional hyposomamotropism of obesity after GHRH, but are unable to reverse the organic hyposomatotropism of hypopituitarism, the combined test GHRH+GHRP-6 most accurately distinguishes both situations, without the side effects of ITT.

Adult↗

Prepregnant overweight and obesity diminish the prolactin response to suckling in the first week postpartum.

OBJECTIVE: The population subgroups with the highest proportion of overweight and obese women often are characterized by the lowest rates of initiation and shortest durations of breastfeeding. We previously documented that these 2 population-level trends may be related. In a population of white women who lived in a rural area, we observed that prepregnant overweight and obesity were associated with failure to initiate and also to sustain lactation. The means by which being overweight or obese negatively affect lactational performance is unknown and likely to be multifactorial in origin, including the simple mechanical difficulties of latching on and proper positioning of the infant. In addition, we have shown that prepregnant body mass index (BMI) is negatively associated with the timing of lactogenesis II, the onset of copious milk secretion. Although the effects of obesity on the prolactin response to infant suckling have never been studied, we postulated that maternal obesity could compromise this important response. We proposed that this might occur because obesity alters the 24-hour spontaneous release of prolactin and also because prolactin secretion is blunted in response to various stimuli among obese subjects. The fall in progesterone concentration that occurs immediately postpartum is the trigger for the onset of copious milk secretion, but maintenance of prolactin and cortisol concentrations is necessary for this trigger to be effective. Adipose tissue concentrates progesterone. We proposed that this additional source of progesterone would lead to consistently higher progesterone concentrations among obese compared with normal-weight women. This, in turn, would lead to a delay in reaching the appropriate concentration to trigger the onset of lactogenesis II. We tested the hypotheses that a reduced prolactin response to suckling and higher-than-normal progesterone concentration in the first week after delivery might be among the means by which maternal overweight could compromise early lactation. METHODS: We enrolled 40 mothers of term infants from the same population that we studied previously. We measured serum prolactin and progesterone concentrations by radioimmunoassay before and 30 minutes after the beginning of a suckling episode at 48 hours and 7 days after delivery. We used path analysis to develop a parsimonious multivariate prediction of the prolactin response to suckling at 48 hours and 7 days postpartum. RESULTS: As expected, prolactin values decreased from 48 hours to 7 days postpartum. Women who were overweight or obese (using the Institute of Medicine's cutoff for women of a BMI >26 kg/m2) before conception had a lower prolactin response to suckling than normal-weight women at 48 hours but not at day 7. In multivariate analyses, overweight/obesity, primiparity, and birth weight were negatively associated with the prolactin response to suckling at 48 hours. After adjustment for confounding by time since delivery and the duration of the nursing episode, only overweight/obesity remained a significant negative predictor of prolactin response to suckling at day 7. Concentrations of progesterone decreased dramatically from 48 hours to 7 days postpartum but did not differ between normal-weight and overweight/obese women at either time. In addition, the decreases in progesterone concentrations from 48 hours to 7 days postpartum did not differ between the prepregnant BMI groups. CONCLUSION: The unique and important finding from this study is that overweight/obese women had a lower prolactin response to suckling. This would be expected to compromise the ability of overweight/obese women to produce milk and, over time, could lead to premature cessation of lactation. These findings are important because, during our observation period (just before and after lactogenesis II, the time of onset of copious milk secretion), the prolactin response to suckling is more important for milk production than it is later in lactation. We have previously shown that a high proportion of the overweight and obese women in women in this population who give up on breastfeeding do so at this time. This finding thus provides evidence of a biological basis for this association, and additional study of it is likely to be informative. We postulated that there would be consistently higher progesterone concentrations in the early postpartum period among obese compared with normal-weight women because adipose tissue is an extraplacental source of this hormone. This hypothesis was not supported in this study because there were no significant differences between normal-weight and overweight/obese women in progesterone concentrations at either 48 hours or 7 days postpartum. The values that we observed at these times were similar to those reported by others in the early postpartum period. The findings from this study add plausibility to our observation that initiation, not just duration of breastfeeding, is negatively affected by maternal overweight/obesity. Although women should begin pregnancy at a healthy weight and gain reasonably during gestation, not all will. Pediatricians can help overweight/obese women to succeed at breastfeeding by targeting them for contact with a lactation consultant before discharge from the hospital to be sure that they have received optimal advice on breastfeeding techniques. In addition, early contact with the mother after discharge--by calling her at home to offer her support and counseling for breastfeeding, by scheduling the first pediatric visit earlier than for other patients, or by enlisting the assistance of public health nurses for a home visit if this is possible--would help overweight/obese women to continue to breastfeed. Being overweight or obese is negatively associated with the prolactin response to suckling in the first week postpartum and, thus, may contribute to early lactation failure.

Adult↗

Screening and counseling associated with obesity diagnosis in a national survey of ambulatory pediatric visits.

OBJECTIVE: To examine clinician-reported diagnosis of obesity and frequency of blood pressure assessment and diet and exercise counseling during ambulatory visits made by children and adolescents. METHODS: The National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey 1997 to 2000 were combined for visits to clinicians of 2- to 18-year-olds. Well-child visits (WCVs) were examined for frequencies of obesity diagnosis, blood pressure screening, and diet and exercise counseling in relation to patient and clinician characteristics. Multivariate models examined the relationship of patient and visit characteristics with diet and exercise counseling. RESULTS: Of the 32 930 ambulatory visits made by 2- to 18-year-olds in 1997-2000, obesity was diagnosed at 0.78% of all visits and 0.93% of WCVs. Blood pressure assessment was reported in 61.1% of WCVs with obesity diagnosis compared with 43.9% of WCVs without obesity diagnosis. WCVs with obesity diagnosis had higher diet counseling rates (88.4% vs 35.7%) and higher exercise counseling rates (69.2% vs 18.6%). Diet counseling was reported for 88.4% and exercise counseling was reported for 69.2% of visits with an obesity diagnosis compared with 35.7% and 18.6% during WCVs without a diagnosis of obesity. In multivariate analyses, factors associated with diet counseling at WCVs were diagnosis of obesity (odds ratio [OR]: 12.9; 95% confidence interval [CI]: 3.0-55.3), being seen by pediatricians (OR: 2.5; 95% CI: 1.6-3.9), 2- to 5-year-olds compared with 12- to 18-year-olds (OR: 0.7; 95% CI: 0.5-1.0), and self-pay compared with private insurance visits (OR: 0.6; 95% CI: 0.4-0.9). Associations with exercise counseling were similar to those for diet counseling, but exercise counseling occurred less frequently in visits by black youths compared with white youths (OR: 0.5; 95% CI: 0.3-0.8). CONCLUSIONS: Clinicians may overlook obesity during WCVs. Programs to increase obesity diagnosis could improve diet and exercise counseling rates, but even with diagnosis of obesity, significant opportunities for screening and intervention are missed.

Adolescent↗

Obesity and risk of low self-esteem: a statewide survey of Australian children.

OBJECTIVE: There is variation in the psychological distress associated with child obesity. Low self-esteem, when observed, provides very little information about the nature of the distress and no indication of the proportion of obese children affected. This study used a domain approach to self-competence to evaluate self-esteem in a representative sample of Australian children. PARTICIPANTS AND METHODS: A total of 2813 children (mean age: 11.3 years) took part in the study. They were recruited from 55 schools and were all in the last 2 years of primary school. Participants completed the Self-perception Profile for Children, a measure of body shape perception, and their height and weight were measured. RESULTS: Obese children had significantly lower perceived athletic competence, physical appearance, and global self-worth than their normal weight peers. Obese girls scored lower in these domains than obese boys and also had reduced perceived social acceptance. Obese children were 2-4 times more likely than their normal weight peers to have low domain competence. In terms of prevalence, 1 of 3 obese boys and 2 of 3 obese girls had low appearance competence, and 10% and 20%, respectively, had low global self-worth. Body dissatisfaction mediated most of the association between BMI and low competence in boys but not in girls. CONCLUSIONS: Obesity impacts the self-perception of children entering adolescence, especially in girls, but in selected areas of competence. Obese children are at particular risk of low perceived competence in sports, physical appearance, and peer engagement. Not all obese children are affected, although the reasons for their resilience are unclear. Quantifying risk of psychological distress alongside biomedical risk should help in arguing for more resources in child obesity treatment.

Adolescent↗

[Maternal overweight and obesity in Mexican school-age children. National Nutrition Survey, 1999].

OBJECTIVE: To assess the effects of maternal overweight and obesity as risk factors for overweight and obesity in Mexican school-age children (5 to 11 years old) who participated in the National Nutrition Survey 1999 (NNS-99). MATERIAL AND METHODS: Information obtained by the NNS-99 was used to evaluate the relationship between maternal overweight and obesity and overweight or obesity in school-age children. Multivariate logistic regression analysis was used. RESULTS: A total of 9 259 children were studied. The prevalence of overweight or obesity was 19%, according to the criteria suggested by Cole.Thirty-nine percent of mothers were overweight and 26.4% were obese. After controlling for age, gender, and other sociodemographic characteristics, children of overweight mothers had a 1.9 times higher risk of being obese (95%CI 1.62-2.18), and children of obese mothers had a 3.4 times higher risk of being obese (95%CI 2.96-4.00), compared to children of mothers with normal BMI. CONCLUSION: Maternal overweight and obesity are risk factors for overweight or obesity in Mexican school-age children. Interventions to prevent obesity in children should be aimed towards promoting family lifestyle changes and modifying obesigenic environments.

Adolescent↗

Clinical pharmacokinetics of drugs in obesity. An update.

Obesity is common enough to constitute a serious medical and public health problem. Drug prescription for obese patients is difficult since dosages based on pharmacokinetic data obtained in normal-weight individuals could induce errors. In obese patients, physiopathological modifications are likely to affect drug tissue distribution and elimination. Body constitution is characterised by a higher percentage of fat and a lower percentage of lean tissue and water. Although the cardiac output and total blood volume are increased, the blood flow per gram of fat is less than in nonobese individuals. Histological hepatic alterations are commonly reported in morbidly obese individuals. A higher glomerular filtration rate is also observed. Most of the pharmacokinetic information concerning obesity deals with distribution. Published data concerning molecules with moderate and weak lipophilicity are homogeneous. In obese compared with normal weight individuals, the total volume of distribution (Vd) is moderately increased (aminoglycosides, caffeine) or similar (H2-blockers, neuromuscular blockers), but the Vd corrected by kilogram of actual bodyweight is significantly smaller. These drugs distribute to a limited extent in excess bodyweight. For highly lipophilic drugs, despite this common characteristic, discrepancies in distribution in obesity exist between drugs belonging to different pharmacological classes. Some drugs show a clear augmentation of Vd and elimination half-life (benzodiazepines, carbamazepine, trazodone, verapamil, sufentanil), indicating a marked distribution into adipose tissue. For others, Vd and Vd/kg are decreased (cyclosporin, propranolol), suggesting that factors other than lipid solubility intervene in tissue distribution. As a general trend, the total clearance (CL) of drugs metabolised by oxidation, conjugation or reduction, and also of drugs with flow-dependent hepatic clearance, is not diminished in obesity. Usually CL is identical in obese and nonobese individuals, sometimes it is increased in obesity (enflurane, halothane, prednisolone, some benzodiazepines). With some drugs a significant reduction in CL is observed in obese individuals (methylprednisolone, propranolol). Renal clearance of aminoglycosides and cimetidine increases in obese individuals. Practical guidelines for dosage adjustment are proposed. For drugs with distribution restricted to lean tissues, the loading dose should be based on the ideal bodyweight of patients. For drugs markedly distributed into fat tissue the loading dose is based on total bodyweight. Adjustment of the maintenance dose depends on possible changes in CL. In some cases (atracurium, prednisolone) dosage adjustment does not follow these recommendations, owing to pharmacodynamic data.

Humans↗

Effects of obesity on pharmacokinetics implications for drug therapy.

Obesity is a worldwide problem, with major health, social and economic implications. The adaptation of drug dosages to obese patients is a subject of concern, particularly for drugs with a narrow therapeutic index. The main factors that affect the tissue distribution of drugs are body composition, regional blood flow and the affinity of the drug for plasma proteins and/or tissue components. Obese people have larger absolute lean body masses as well as fat masses than non-obese individuals of the same age, gender and height. However, the percentage of fat per kg of total bodyweight (TBW) is markedly increased, whereas that chrome P450 isoforms are altered, but no clear overview of drug hepatic metabolism in obesity is currently available. Pharmacokinetic studies provide differing data on renal function in obese patients. This review analyses recent publications on several classes of drugs: antibacterials, anticancer drugs, psychotropic drugs, anticonvulsants, general anaesthetics, opioid analgesics, neuromuscular blockers, beta-blockers and drugs commonly used in the management of obesity. Pharmacokinetic studies in obesity show that the behaviour of molecules with weak or moderate lipophilicity (e.g. lithium and vecuronium) is generally rather predictable, as these drugs are distributed mainly in lean tissues. The dosage of these drugs should be based on the ideal bodyweight (IBW). However, some of these drugs (e.g. antibacterials and some anticancer drugs) are partly distributed in adipose tissues, and their dosage is based on IBW plus a percentage of the patient's excess bodyweight. There is no systematic relationship between the degree of lipophilicity of markedly lipophilic drugs (e.g. remifentanil and some beta-blockers) and their distribution in obese individuals. The distribution of a drug between fat and lean tissues may influence its pharmacokinetics in obese patients. Thus, the loading dose should be adjusted to the TBW or IBW, according to data from studies carried out in obese individuals. Adjustment of the maintenance dosage depends on the observed modifications in clearance. Our present knowledge of the influence of obesity on drug pharmacokinetics is limited. Drugs with a small therapeutic index should be used prudently and the dosage adjusted with the help of drug plasma concentrations.

Adrenergic beta-Antagonists↗

Blood glucose, insulin, and free fatty acid levels during oral glucose tolerance tests in 158 obese children.

In 158 obese children, aged from three months to 15 years, blood glucose, immunoreactive insulin, and free fatty acid levels were measured during a standard oral glucose tolerance test carried out prior to treatment. The results were analyzed for the total sample as well as for three age groups: 0-5 years, 6-10 years, and 11-15 years and compared with those of 70 normal-weight children matched for age and sex. Glucose tolerance is normal in the obese children. It is different from the controls only two hours after glucose loading, when a slight but significant elevation is found. The glucose levels at one and two hours are significantly higher in the obese children of group III than in the younger ones. Fasting F.F.A. levels are similar in normal and obese children, but the F.F.A. decrease following glucose absorption is significantly diminished in the obese. The F.F.A. levels of the youngest obese are significantly higher than those of the older ones. A constant and important hyperinsulinism, fasting and postabsorptive, is demonstrated in obese children of all ages, even before five years and at the beginning of obesity. Age- and sex-related differences in insulin secretion are much more marked in the obese than in normal children. The degree of hyperinsulinemia is related to the degree of obesity, but not to its duration. The results suggest that hyperinsulinism is associated with obesity from its onset rather than being a long-term consequence of overweight. However, the origin of hyperinsulinism in obesity and the mechanism of insulin resistance still remain obscure.

Adolescent↗

Hypersection of pancreatic somatostatin in the obese Zucker rat: effects of food restriction and age.

Islets of 5-mo-old obese Zucker rats secreted 50% more somatostatin (SRIF) in response to 8.3 mM or 16.7 mM glucose than did islets from lean controls; the islet SRIF contents of obese and lean rats were similar. As expected, islets of obese rats demonstrated a greater basal and a fivefold greater glucose-induced insulin release and also a twofold greater insulin content than did islets from lean rats. Obese rats were pair fed with lean animals from the age of 9 wk until killed, when 5 mo old. While this curtailed the weight gain of obese rats to that of lean controls, it caused no reduction in the percent body weight found in the form of lipid. The responses of the pancreatic delta and beta cells to pair feeding were markedly different. Pair feeding caused no alteration in either SRIF content or glucose-induced SRIF release, while the expected reductions in both islet insulin content and glucose-induced insulin secretion were observed. Islets from older obese Zucker rats (15--18 mo old) had four to five times greater contents of both SRIF and insulin than did islets from age-matched lean controls. The obese rats of this age had a moderate glucose intolerance. SRIF secretion from the islets of such rats was distinctly greater than from those of lean controls at all glucose concentrations tested (range, 1.0--16.7 mM). The delta cells of the older obese rats had lost their sensitivity to glucose, while those of lean controls remained sensitive. Beta cells of islets from both obese and lean 15-mo-old rats remained glucose sensitive. Under all conditions tested, secretion of SRIF and insulin was greater from islets of obese than lean rats. The results demonstrate a marked difference in pancreatic delta and beta cell responses to pair feeding in the obese Zucker rat. At present, the role played by hypersecretion of pancreatic SRIF in the obesity syndrome of the Zucker rat remains obscure.

Aging↗