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PubMed2001

Obesity in childhood and adolescence: clinical diagnosis and management.

The industrialized countries around the world are experiencing an epidemic of childhood obesity. The level of fatness of a child at which morbidity increases acutely and/or later in life is determined on an individual basis. Overall, however, childhood obesity substantially increases the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge of the role of neuropeptides such as pro-opiomelanocortin, neuropeptide Y and the melanocyte-concentrating hormone receptors. Environmental and exogenous factors are the main contributors to the development of a high degree of body fatness early in life. Studies involving twins suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders, including a number of endocrine disorders, such as Cushing's syndrome and hypothyroidism, and genetic syndromes, such as Prader-Labhard-Willi syndrome and Bardet-Biedl syndrome, that can present with obesity. A simple diagnostic algorithm allows for differentiation between primary and secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia, back pain and psychosocial problems. It is somewhat ironic that the definition of obesity in childhood is not an easy one. Direct measurements of body fat content, such as hydrodensitometry, bioimpedance, or dual-energy X-ray absorptiometry, are useful tools in scientific studies. Body mass index (BMI) is, however, now generally accepted to be a good clinical measure for the definition of obesity in children and adolescents. In preadolescent boys, BMI also relates to muscle mass and should be used for the definition of fat mass with great caution. An increased risk of death from cardiovascular disease in adults has been found in patients whose BMI had been greater than the 75th percentile as adolescents. Therapeutic strategies include psychological and family therapy, modification of lifestyle and behavior, and nutritional education. The role of regular exercise and exercise programs is emphasized, while surgical procedures and drugs used in adult obesity are still not generally recommended for obese children. Obesity is the most common chronic disorder in industrialized countries, and its impact on individual lives as well as on health economics must be recognized by physicians and the public alike. This review aims to increase awareness of the health burden and economic dimension of the epidemic of childhood obesity that is occurring around the globe.

Adolescent↗
PubMed2002

[Sporadic registration of obesity as secondary diagnosis].

INTRODUCTION: The aim was to examine the extent to which obese patients, who are followed up for an obesity-related disease in an outpatient clinic, are correctly registered with the secondary diagnosis of obesity. MATERIAL AND METHODS: We investigated the number of patients at the Endocrine Outpatient Clinic, Rigshospitalet, Copenhagen, who were registered in the patient administrative system with the primary diagnosis of type 2 diabetes, and how many of these were registered with the secondary diagnosis of obesity. RESULTS: Of 233 patients with type 2 diabetes, 79 had a BMI between 25.0 and 29.9 kg/m2 (overweight) and 108 a BMI > 30 kg/m2 (obesity). Thus, 80% of these patients were overweight or obese. Of the 108 patients with a BMI > 30 kg/m2. only 13 (12%) were registered with the secondary diagnosis of obesity, and of 17 severely obese patients with a BMI > 40 kg/m2 only four (24%) were registered with the secondary diagnosis of obesity. DISCUSSION: Obese patients with type 2 diabetes are seldom correctly registered with the secondary diagnosis of obesity. The actual practice of registration probably causes a large underestimation of the impact, and thereby of the magnitude of the economic cost of and the contribution of obesity to total health care costs. Improved registration of obesity as secondary diagnosis in obesity-related diseases is needed.

Body Mass Index↗
PubMed2001

Gastric restrictive procedures to treat obesity: reasons for failure and long-term evaluation of the results of operative revision.

BACKGROUND AND OBJECTIVE: Bariatric surgery has included a large number of operative procedures, some of which have become extinct and others, such as gastric restrictive procedures, which continue to be performed. While these operative procedures play an important role in the management of obesity, they are associated with significant failure rates. This study was performed to evaluate the results of operations performed on patients to revise failed gastric restrictive procedures. METHODS: During the past 15 years operative revision of gastric restrictive procedures was performed on 65 patients. The demographic, operative, and postoperative information has been prospectively collected. The patients were divided into 20 non-obese patients who weighed less than 250 pounds (range 90-247 pounds) and 45 obese patients weighing more than 250 pounds (range 256-527 pounds). The primary indications for operation on the non-obese patients were intragastric foreign body, gastric fistula, gastroesophageal reflux, and non emptying gastric pouch. The obese patients underwent revision for gastroesophageal reflux and failure to maintain weight loss. The obese patients frequently had obesity associated health problems including sleep apnea (N = 5), hypertension (N = 6), diabetes (N = 5) and ventral hernia (N = 30). The operative procedures in the non-obese patients consisted of revision of a gastroplasty in two patients, conversion of a gastroplasty to a gastric bypass in 12 patients and revision of a gastric bypass in eight patients. In the obese patient group, eight patients underwent revision of a gastroplasty, 19 patients had a gastroplasty converted to a gastric bypass and 14 patients underwent revision of a gastric bypass. The mean +/- SEM length of follow-up was 57 +/- 8 months. RESULTS: There were two postoperative deaths, one from a pulmonary embolus and one from unknown cause. There was no significant difference regarding the results of the various operations to revise gastric restrictive procedures on the weight of the non-obese patients at long-term follow-up. When obese patients underwent revision of a gastric bypass procedure, they lost 69 +/- 9 pounds which was significantly less than the 82 +/- 12 pounds lost by the patients who underwent revision of a gastroplasty. Conversion of gastroplasty operations to gastric bypass operations in obese patients resulted in the loss of 110 +/- 7 pounds at long-term follow-up. CONCLUSIONS: Revision of gastric restrictive procedures can be performed with durable control of obesity; however, revision of gastric bypass restrictive procedures in obese patients produced the least benefit.

Adult↗
PubMed2003

[Relationships between infant lifestyle and adolescent obesity. The Enzan maternal-and-child health longitudinal study].

OBJECTIVE: A longitudinal study was analyzed to clarify relationships between infant lifestyle, obesity, features of family life and adolescent obesity. SUBJECTS AND METHODS: Subjects in the present study were born between April 1987 and March 1991, in Enzan City, Yamanashi prefecture. Infant height and weight were measured and questionnaires were collected at medical check-ups at 1.5- and 3-year-of age. Adolescent height and weight were measured in April 2000. Obese adolescents were defined as those with on obesity index > or = 20%. RESULTS: At 1.5-years-of age, 883 responses to the questionnaire were obtained, and 737 subjects were followed to adolescence (83.5%). Mean follow-up period was 10 years 11 months. A high Kaup index at 1.5-years-of age (odds ratio (OR) 2.61; 95% confidence interval (CI) 1.11-6.12) and when 3-years-of age (OR 5.34; CI 2.54-11.23), as well as maternal obesity (OR 5.32; CI 2.67-10.60) represented risk factors for adolescent obesity. Of the lifestyle items, "playing alone inside" at 1.5-years-of age (adjusted OR 3.01; CI 1.01-8.99) and "taking snacks without time constraints" at 3-years-of age (adjusted OR 2.12; CI 1.25-3.61) were additional risk factors. In food items, only low intake of cow's milk displayed a significant relationship with adolescent obesity, the link being negative with an adjusted OR of 0.63 (CI 0.41-0.95). Covariance structural analysis was performed and a causal model was constructed. Maternal obesity, obesity at 3-years-of age, playing alone inside, taking snacks without time constraints, and low intake of cow's milk were all associated with obesity in infancy. Maternal obesity affected methods of answering child demands, in turn affecting snacking habits. CONCLUSIONS: Adolescent obesity displays relationships with maternal obesity, a high Kaup index in infancy, play activity, snacking habits, and intake of cow's milk. Although genetic factors exert a strong influence, these components of infant lifestyle all play a role in the development of adolescent obesity.

Adolescent↗
PubMedDate not supplied

[Influence of visceral obesity on blood pressure values in patients with essential hypertension].

Obesity significantly increases the risk for the occurrence of cardiovascular disease in patients with essential hypertension. The aim of the study was to assess the frequency of obesity, measured by different methods, in patients with essential hypertension, its effect on arterial pressure, and to determine the best correlation between indicators of obesity and arterial pressure. The study included 88 patients with essential hypertension, 32 males, mean age 59.4 (+/- 10.4) years, and 56 females, mean age 62.9 (+/- 8.8) years. Body weight (BW) and height (BH), waist circumference (WC), and body mass index (BMI) were measured for each subject. Arterial pressure was determined using mercury sphygmomanometer. Overweight patients were defined as those with BMI 25-29.9 kg/m2, while obese as those with > or = 30 kg/m2. Abdominal obesity was assessed by WC. WC values exceeding 102 cm for men and 88 cm for women indicated obesity. Body measures of male patients were higher than those for women (BW 92.5 (+/- 14.5) vs 76.7 (+/- 11.5) p < 0.001; BH 175.4 (+/- 7.4) vs 163.4 (+/- 5.8) p < 0.001), significantly higher waist circumference values (102.4 (+/- 12.2) vs 94.1 (+/- 13.9) p = 0.006), with no differences in age, BMI, and arterial pressure values (p > 0.05). Also, no differences were observed in the number of uncontrolled hypertensive patients or number of overweight or obese patients (p > 0.05). The number of obese patients did not differ significantly with regard to the various measurement methods employed (BMI: M 50%, F 37%; waist measurement: M 51%, F 54%). A significant difference was noted in arterial pressure values only in the male patient group on comparing patients with normal BW and obese patients (systolic blood pressure (SBP) 156 (+/- 22.5) vs 142 (+/- 6.4) p = 0.04; diastolic blood pressure (DBP) 94 (+/- 11.6) vs 82.5 (+/- 6.4) p = 0.05). The correlation between obesity indicators and arterial pressure was significant for WC only in the male group (SBP r = 0.33, DBP r = 0.35, p < 0.05). The frequency of obesity does not differ with regard to the determined obesity indicators. Obese men have higher risk for increased arterial pressure values. WC values correlate better with arterial pressure values as it is a more accurate indicator of abdominal obesity.

Abdominal Fat↗
PubMed1989

[Android and gynecoid types of obesity as factors in the onset of certain related diseases].

The prevalence of some diseases was studied in 238 android and 720 gynoid obese women and 180 android obese men with the aim to establish the relationship between the type of obesity and relevant diseases. In the selected group of obese patients (25 android and 90 gynoid obese women and 26 android obese men) fed on a reducing diet (1000 kcal--4.2 M.J.) 67 women were engaged in intensified physical activity during the 90 days of dieting. The relationship between the weight loss and the type of obesity as well as the relationship between the weight loss in women engaged in intensified physical activity and those abstaining from it was investigated. The investigation has shown that the prevalence of hypertension, coronary heart disease and diabetes was much higher in men and women affected by the android type of obesity than in women affected by the gynoid type of obesity. The prevalence of gallbladder's as well as venous system diseases and spondylosis in women affected by both types of obesity was much higher than in android obese men, but the prevalence of constipation was higher in gynoid obese women. From data relating to response to reducing diet it is concluded that the weight loss was equal among the women affected by the android and gynoid types of obesity, but the weight loss in android and gynoid obese women engaged in intensified physical activity was significantly higher than in those abstaining from it.2+herefore, for the prevention and

Adult↗
PubMed1986

Pharmacokinetics and dynamics of (+/-)-verapamil in lean and obese Zucker rats.

To evaluate the mechanism of obesity-induced changes in pharmacokinetics and pharmacodynamics of verapamil observed in humans, single-dose and steady-state kinetic/dynamic studies in obese Zucker rats were done. Seven lean and five obese Zucker rats received a single dose of verapamil (2 mg/kg) and plasma samples were obtained for verapamil concentrations over the following 7 hr. Terminal elimination half-life was significantly prolonged in obese animals compared to lean (mean +/- S.D., 2.68 +/- 0.87 hr obese vs. 1.39 +/- 0.35 hr lean; P less than .01) due to the significantly increased total volume of distribution observed in the obese animals (1.62 +/- 0.28 liters obese vs. 0.83 +/- 0.14 liters lean; P less than .001). There was no significant difference in the total clearance (0.45 +/- 0.16 liters/hr obese vs. 0.43 +/- 0.10 liters/hr lean; NS) between lean and obese animals. A physiological explanation for the increased volume of distribution was evaluated by determining actual distribution of verapamil into tissue during steady-state infusion. Six lean and six obese animals received a loading infusion of verapamil (25 micrograms/min) for 1.2 hr in lean and 1.6 hr in obese rats followed by a constant infusion of 5 micrograms/min for the next 2.5 to 3 hr. Steady-state clearance was similar between groups (0.349 +/- 0.095 liters/hr obese vs. 0.244 +/- 0.066 liters/hr lean; NS). Plasma verapamil concentration at the termination of steady-state infusion was similar between lean and obese rats (0.91 +/- 0.24 microgram/ml obese vs. 1.26 +/- 0.33 microgram/ml lean).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

The cholesterol saturation of bile and its reduction by chenodeoxycholic acid in massively obese patients.

Massively obese patients are at high risk for developing cholesterol gallstones. The objectives of this study were to determine the influence of massive obesity on the cholesterol saturation of bile, and to examine the effect of massive obesity on the ability of chenodeoxycholic acid to decrease biliary cholesterol saturation. Gallbladder bile collected at surgery from massively obese patients was significantly more saturated with cholesterol than bile from non-obese patients who were matched for age, sex and gallstone status (P less than 0.01). Median biliary cholesterol saturation index values for groups of subjects were: no gallstones-not obese (0.83); no gallstones-obese (1.14); gallstones-not obese (1.08); gallstones-obese (1.37). Furthermore, a 5-week course of chenodeoxycholic acid (6 mg/kg/day) was less effective in reducing biliary cholesterol saturation in massively obese patients. The bile of 4 of 10 obese patients remained supersaturated, compared to only one of 10 non-obese patients. These results indicate that biliary cholesterol saturation is raised in massive obesity and that in this condition, the biliary lipid response to chenodeoxycholic acid is diminished. This may explain why obese patients have a relatively poor response to gallstone dissolution therapy with this bile acid.

Adult↗
PubMed1996

Prevalence of obesity in Greek hypertensives.

An association of obesity and hypertension is well recognised and there is a direct positive relationship between body weight or body mass index (BMI) and blood pressure (BP), although the mechanisms responsible for weight-related increases of BP are still unknown. Obesity does appear to be an independent risk factor for premature mortality, especially when it is associated with other risk factors such as hyperinsulinemia and glucose intolerance (or diabetes), hyperlipidemia, and hypertension. However, there are differences among racial and ethnic subgroups. The aim of our study was the investigation of the prevalence of obesity and its severity among Greek hypertensive patients in comparison to normotensive controls. We have studied a large enough sample of Greek hypertensives consisting of 1101 patients (504 male/597 female, 23-85 years of age) and 242 normotensive controls (136 male/106 female, 23-75 years of age). In all patients and normotensive controls BMI (ie weight/height in 2mm) was measured, as well as the waist-to-hip (W/H) ratio. A BMI of less than 27 was accepted as normal, a BMI of 27-32 as indicating mild to moderate obesity, a BMI of 32-37 as an index of severe obesity, and a BMI > 37 as a measure of very severe obesity. Obesity in hypertensive patients was more frequent than in normotensive controls (62.5% vs 54.2%, P = 0.024), and hypertensive women were more commonly obese than hypertensive men (67.16% vs 56.8%, P = 0.002). Severe and very severe obesity was more common in hypertensive women than in men (20.7% vs 9.68%, P < 0.001, and 8.1% vs 0.52%, P < 0.0001, respectively), although obesity of severe and very severe degree was equally found in hypertensives and normotensives of both sexes. BMI of all hypertensives was significantly greater in comparison to that of normotensives (30.13 +/- 0.44 vs 26.74 +/- 0.76, mean +/- s.e., P < 0.0001); W/H ratio of hypertensives was significantly greater than that of normotensives, indicating more frequent central obesity in hypertensives. We conclude that obesity in Greek hypertensive patients is more frequent than in normotensive controls, while hypertensive women have more severe obesity than hypertensive men, and are more frequently obese than men.

Adult↗
PubMed1996

Economic consequences of sick-leave and early retirement in obese Swedish women.

OBJECTIVES: To describe the pattern of sick-leave and disability pension in an obese sample and to estimate the Incremental, indirect cost due to sick-leave and early retirement for the obese fraction of the Swedish female population. DESIGN: A retrospective study of sick-leave and disability pension in health examined obese subjects was performed. The indirect cost of obesity in Sweden was estimated from reported and recorded sick-leave and disability pension in the sample and from the estimated prevalence of obesity in the country. SUBJECTS: 1298 obese persons aged 30-59 y. The mean age was 46 years. The mean body mass Index was 39 kg/m2 (range 28-68). SETTING: The obese subjects were recruited from eight counties in Sweden. RESULTS: As compared to the general Swedish population the obese subjects had 1.5-1.9 times higher sick-leave during one year. Twelve percent of the obese women had disability pension while the corresponding figure in the general population was 5%. The incremental cost of sick-leave and disability pensions attributable to obesity was 3.6 billion SEK during one year, which is equivalent to about 300 million USD per million female adult population. The total cost for sick-leave and disability pension due to absence from work for the obese fraction of the Swedish female population was 10.5 billion SEK during one year. CONCLUSION: Obesity represents a major health problem with significant economic implications for the society. Approximately 10 percent of the total cost of loss of productivity due to sick-leave and disability pensions in women may be related to obesity and obesity-related diseases.

Adult↗
PubMed1996

Obesity as a protective factor for postmenopausal osteoporosis.

BACKGROUND: Obesity is considered a protective factor for osteoporosis improving bone mass and maintaining higher levels of estrogen during menopause. OBJECTIVE: To determine the association of obesity with bone mineral density (BMD), and its relationship with sex hormone levels. DESIGN: A case-control study in Caucasian obese and non obese postmenopausal women. SUBJECTS: 113 obese and 50 non-obese postmenopausal women. MEASUREMENTS: BMD (dual-photon X-ray absorptiometry) at cervical femur. Ward's triangle, proximal radius and lumbar spine. Plasma levels of glucose, insulin, total estrogen, follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHA-S) and testosterone. RESULTS: Mean BMD at femoral sites were significantly higher in obese women (femoral neck: 0.849 +/- 0.124 g/cm2 vs 0.753 +/- 0.095 g/cm2, P < 0.001; Ward's triangle: 0.634 +/- 0.134 g/cm2 vs. 0.553 +/- 0.100 g/cm2, P < 0.001). Mean BMD at lumbar spine was 0.906 +/- 0.138 g/cm2 in obese women and 0.849 +/- 0.137 g/cm2 in non obese, P < 0.017. A decreased risk of osteopenia in femoral neck (Age adjusted OR = 0.36, 95%CI 0.17-0.75) and in lumbar spine (Age adjusted OR = 0.43, 95%CI 0.20-0.91) in obese women was observed. Although total estrogen were similar in both groups, in obese women, SHBG was lower (68.6 +/- 26.84 nmol/l vs. 85.1 +/- 31.18 nmol/l, P < 0.001), and postglucose load insulin levels were higher, than in non obese (77.2 +/- 50.4 Ul/ml vs. 49.4 +/- 24.1 Ul/ml, P < 0.0005). CONCLUSION: The findings confirm a higher BMD in obese women and suggest that obesity exerts protection due to a decreased SHBG thus increasing free sex steroids. Besides, hyperinsulinemia may produce a decline in the production of IGFBG-1, leading to an increase of IGF-1, that may stimulate the proliferation of osteoblasts.

Bone Density↗
PubMed1998

GP documentation of obesity: what does it achieve?

BACKGROUND: Obesity is a major and increasing health problem in the United Kingdom, and, until recently, the government health promotion package for general practice reimbursed general practitioners for documenting obesity. Despite poor evidence for effectiveness of interventions in primary care, documentation of obesity could possibly improve patient awareness and knowledge, or provide public health information. AIM: To assess patient perception of obesity and its health risk, and the accuracy of estimating obesity using patient information. METHOD: Subjects were consecutive attenders to a general practitioner (GP) at a single urban practice in the South and West Region. Outcome measures were 'measured' body mass index (BMI) calculated from measured weight and height, 'estimated' BMI using patient information, and patient perception of obesity and the health risks of obesity. RESULTS: There is good correlation between 'estimated' and 'measured' BMI (intraclass correlation 0.91). Estimated BMI is lower than measured BMI (mean 0.77 lower), and the difference increases with age and level of BMI: for BMIs of < 20, 20-24.99, 25-29.99, and > or = 30 the mean differences (estimated-measured) were -0.06, -0.46, -0.98 and -1.72 respectively. Estimated obesity (BMI > 30) is reasonably sensitive (70%), specific (99%), and predictive (93% positive predictive value) of measured obesity (kappa 0.78). All obese subjects are aware that they are overweight, and most of them (78%, 95% confidence interval 66-88%) are aware that their weight is a health risk. CONCLUSION: Obese patients attending GPs' surgeries are likely to know if they are overweight, or could easily estimate from their knowledge of height and weight that they were overweight with reasonable accuracy. Obese subjects also know that their weight carries health risks. Thus, measurement of obesity in the general population is not likely to improve risk assessment or patient knowledge significantly. Without evidence for effective intervention or improved decision-making in primary care, reimbursement guidelines linked to the documentation of obesity in the population are probably an inefficient use of resources.

Adolescent↗
PubMed1994

The Influence of Obesity on the Self-Reported Health Status of Chamorros and other Residents of Guam.

PURPOSE OF THE PAPER. We report on an analysis of the relationship of obesity to self-assessments of physical health for a probability sample of Guam's indigenous (Chamorro) and resident populations. Further, we examine whether Guam's populations fit a Western model, in terms of viewing obesity as an unhealthy condition. As background for our analysis, we review the literature on (1) the relationship between obesity and chronic noninfectious diseases; (2) social and behavioral associations of obesity; and (3) the reliability of self-assessed physical health and measures of obesity. METHODS. The data analyzed were taken from a Behavioral Risk Factor Survery (BRFS) conducted on Guam in 1991. We employed various standard univariate (chi-square analysis, ANOVA) and multivariate (OLS regression and logisitic regression analusis) statistical procedures in exploring our data and testing hypotheses on the correlates and associations of self-reported health and obesity. PRINCIPAL FINDINGS. Controlling for ethnicity, age, gender, marital and socioeconomic status, we found that obesity and being Chamorro was associated significantly with low assessments of physical health and that income was a signifcant predictor of higher self-assessments. A small sample of Micronesians, with a slightly greater level of obesity than the Chamorros, did not show the same tendency towards lower self-evaluation of their health. This probably reflects their lesser degree of internalizaition of Western ideas about obesity, appearance and health. When controlling for self-assessments of physical health, obesity was also shown to be related significantly with dieting by Chamorro women but was not a significant predictor of their increased participation in physical exercise. Young males were significantly more likely to report participation in physical exercise regardless of their weight or ethnicity. CONCLUSIONS. We hypothesize that historical (acculturative) changes to the diet and life ways of Chamorros, together with a likely genetic predisposition to store fat, has led to the relatively high levels of obesity seen on Guam today. Because of internalization of Western ideals about obesity and appearance, and increased community awareness of the health perils of obesity, Chamorros are at a public health crossroads. Effective health interventions must reckon with powerful genetic and cultural cross-currents. RELEVANCE TO ASIAN PACIFIC ISLANDER AMERICAN POPULATIONS. Colleagues are encouraged to examine the effects of ethnicity and acculturation on the health attitudes, behaviors, and status of other Pacific Islander and Asian populations. The creation of such a comparative data base will service APIA health interventions. KEY WORDS. Guam, Chamorros, Asian Pacific Islander Americans, survey, obesity, self-evaluated health status, socioeconomic status, cross-cultural comparisons.

Journal Article↗
PubMed1981

The relationship between the hyperplastic pancreatic islet and insulin insensitivity in obesity.

In summary, the present review provides evidence in support of the proposition that pancreatic islet cell hyperplasia precedes the development of insulin insensitivity in the obese mouse and, it is likely, that similar events occur in obese humans. Moreover, the hyperplastic pancreatic islet appears to be responsible for the development of insulin insensitivity, since suppression of the hyperplastic islet, by either alloxan or streptozotocin administration to the obese mouse, results in amelioration of insulin insensitivity in vivo. Since no change occurred in the degree of obesity or in adipocyte cell size or number, it is evident that insulin sensitivity is independent of obesity per se. Hence, although obesity and insulin insensitivity frequently co-exist, insulin insensitivity is independent of obesity and is due rather to the presence of pancreatic islet cell hyperplasia. Light and electron microscopy of the hyperplastic pancreatic islets of the obese mouse reveal increased numbers of A- B- and D-cells. Islet suppression with alloxan or streptozotocin results in the selective reduction of B-cells with preservation of A- and D-cells. Therefore, restoration of insulin sensitivity in the obese mouse following pancreatic islet cell suppression appears to be directly related to suppression of B-cell hypersecretion. Biochemical studies of muscle and adipose tissues from the obese mouse reveal profound insulin unresponsiveness without clear cut improvement in vitro following pancreatic islet cell suppression and restoration of insulin sensitivity in vivo. These data are consistent with a relatively modest reduction in the number of available insulin receptors upon these tissues in relation to the marked insulin resistance and imply an impairment of insulin action beyond the insulin receptor interaction [either transport or intracellular action(s)] as the major site(s) of insulin resistance in the muscle and adipose tissues of obese mice. Conversely a reduction of insulin receptors upon hepatocytes of obese mice and their improvement following a reduction of B-cell hypersecretion support the proposition that the number of available insulin receptors may be the major site for the regulation of insulin action upon that tissue. Finally, evidence is presented which suggests that an inability of insulin to limit hepatic gluconeogenesis may be the predominant cause of insulin insensitivity in the obese mouse.

Adipose Tissue↗
PubMed2006

Is extreme obesity a risk factor for cardiac surgery? An analysis of patients with a BMI > or = 40.

BACKGROUND: The increasing prevalence of obesity is a public health concern and perceived as a potential risk factor in open heart surgery. We critically appraised the literature available regarding postoperative complications in obese patients. METHODS: A single-center retrospective evaluation of complication rates (1999-2004) in cardiac surgical patients categorized by body mass index (BMI) was conducted. The overall incidence of complications (CX), renal failure (RF), hemodialysis (HD), atrial fibrillation (AF), cardiac arrest (CA), infections (INF), stroke (CVA and TIA), prolonged ventilation (VENT), and pulmonary embolism (PE) were observed. Patients with normal BMI (20-30) served for comparison, obesity and extreme obesity (ExtOb) were defined as BMI 30-40 and > or =40, respectively. RESULTS: In our institutional review of 1920 patients, 1780 met the inclusion criteria with BMI<20 (n=53), 20-30 (n=1056), 30-40 (n=592), and > or =40 (n=79) based on National Health and Nutrition Examination Survey (NHANES) criteria. Significant increase in complications (STS database guideline definitions) were observed with a BMI> or =40, 58% versus 47% (p=0.04). Extremely obese patients (ExtOb) had increased length of stay (LOS) (11.4 days vs 9.6 days; p< or =0.01), rate of renal failure (14.3% vs 5%; p< or =0.01) and prolonged ventilation (39%; p=0.01) compared to non-obese patients. Extremely obese had no significant increase in hemodialysis (7.3% vs 3.2%; p=0.11) or stroke (5.2% vs 2.9%; p=0.29). Obese patients (Ob) had increased LOS (10 days vs 9.6 days; p=0.04) and prolonged ventilation (28.3% vs 23.5%; p=0.03). CONCLUSIONS: Cardiac surgery can be performed without significant increase in perioperative and 30-day mortality in obese and extremely obese patients. Overall complication rates and LOS in patients with BMI> or =40 is increased and demands attention. We provide evidence that rates of few specific complications increase with extreme obesity. For risk stratification in the setting of an obesity epidemic, we advocate an interdisciplinary approach in obese patients undergoing elective cardiac surgery.

Acute Kidney Injury↗
PubMed2006

Ciliary neurotrophic factor restores gallbladder contractility in leptin-resistant obese diabetic mice.

BACKGROUND: Obesity and diabetes are major risk factors for cholesterol gallstones, and the majority of obese people are leptin-resistant. Our previous work has shown that both leptin-deficient (Lepob) and leptin-resistant (Lepdb) obese diabetic mice have decreased in vitro gallbladder motility. Leptin administration to leptin-deficient (Lepob) animals restores gallbladder motility and reverses obesity and hyperinsulinemia. However, additional leptin in leptin-resistant obesity would not be expected to improve obesity-related parameters. Recent studies demonstrate that ciliary neurotrophic factor (CNTF) reduces weight and hyperinsulinemia in leptin-resistant obesity. Our hypothesis is that CNFT would cause weight loss, lower blood sugars, and restore gallbladder contractility in leptin-resistant (Lepdb) mice. MATERIALS AND METHODS: 20 C57b/6J and 20 Lepdb 8-week-old female mice were injected daily with either intraperitoneal saline or 0.3 microg/g CNTFAx15 for 17 days. Gallbladders were mounted in muscle baths and stimulated with acetylcholine, neuropeptide Y, and cholecystokinin. Gallbladder volume, serum glucose, insulin, liver weight, liver fat, and gallbladder responses were measured. Data were analyzed by ANOVA. RESULTS: Saline treated obese mice had greater body weight and obesity parameters, but decreased gallbladder contractility to neurotransmitters compared to saline treated lean mice. CNTF administration to obese mice decreased body weight and obesity parameters, and restored gallbladder contractility. CNTF treated lean animals had weight loss and decreased gallbladder contraction to acetylcholine and cholecystokinin compared to saline treated lean animals. CONCLUSIONS: Ciliary neurotrophic factor (CNTF) causes 1) weight loss, 2) improvement of diabetes, and 3) alterations in gallbladder motility that is improved in obese mice but decreased in lean mice. We conclude that CNTF may improve gallbladder contractility in leptin-resistant obesity with diabetes.

Animals↗
PubMed2003

Gallbladder motility in agouti-yellow and leptin-resistant obese mice.

BACKGROUND: Obesity is a polygenic disorder that is associated with gallstone disease. We have previously shown that leptin deficiency in obese mice correlates with decreased gallbladder motility, suggesting that leptin plays a role in the link between gallstone disease and obesity. However, most obese humans are leptin-resistant, and relatively few are leptin-deficient. To confirm that leptin dysfunction is responsible for impaired gallbladder motility in obese mice, we hypothesized that leptin-resistant obese mice (Lep(db)) would have abnormal gallbladder motility while obese mice with intact leptin function (Agouti Yellow, A(y)) would have normal gallbladder motility. MATERIALS AND METHODS: Eighteen lean control (C57BL/6J), 10 A(y) and 12 Lep(db) female mice were fasted overnight, weighed, and livers and gallbladders were harvested. Liver weights and gallbladder volumes were measured. Gallbladder contractile responses (N/cm(2)) to acetylcholine (10(-5)M), neuropeptide Y (10(-8,-7,-6) M) and cholecystokinin (10(-10,-9,-8,-7)M) were determined in muscle bath chambers. Results were analyzed by analysis of various (ANOVA) and with the Mann-Whitney Rank Sum Test. RESULTS: Both Agouti yellow (A(y)) and leptin-resistant (Lep(db)) obese mice had body weights, liver weights and gallbladder volumes that were significantly greater (P < 0.01) than lean control mice. Leptin-resistant obese mice had gallbladder responses to acetylcholine, neuropeptide Y and cholecystokinin that were significantly less (P < 0.01) than both lean control and Agouti yellow obese mice. CONCLUSIONS: These data suggest that (1). leptin-resistant obese mice (Lep(db)) have abnormal gallbladder motility and (2). obese mice with normal leptin metabolism (A(y)) have normal gallbladder response to neurotransmitters. We conclude that leptin represents a link between obesity, gallbladder motility and gallstone formation.

Acetylcholine↗
PubMed1975

Renal transport of organic acids and bases in genetically obese mice.

Accumulation of p-aminohippurate (PAH) and N-methylnicotinamide (NMN) by renal cortical slices was used to estimate transport capacity for organic anions and cations, respectively. In a previous study, renal organic anion transport appeared to be selectively depressed in animals rendered obese by high fat feeding. However, the effects of obesity could not be discretely separated from the effects of the 30% fat diet used to produce the obesity. Genetically obese hyperglycemic mice provided a model to determine the effect of obesity on renal transport systems without the complication due to diet. Accumulation of both PAH and NMN was depressed in renal cortical slices from genetically obese mice. Addition of plasma from thin or obese animals increased PAH accumulation by slices from thin animals. Accumulation by slices from obese animals was unaffected by addition of plasma. Oxygen consumption with acetate in the medium was less in kidneys from obese mice than kidneys from thin mice. Thus, in addition to inhibition of transport capacity, renal cortex of genetically obese mice has a biochemical defect that prevents response to stimulators. It is concluded that several renal functions are depressed in the genetically obese hyperglycemic mouse. Whether the depressed function results from the obesity or is concomitant with the gene for obesity is as yet undertermined.

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