The benefits of good glycaemic control in both type I and type II diabetes mellitus are undoubtedly proven. Most national bodies have recommended glycaemic targets, with an HbA(1c) to achieve between 6.5 and 7.5%. However, it is well known that even in clinical trials, and routinely in clinical practice, the majority of patients fail to achieve optimal glycaemic control. The reasons for this failure are complex and multifactorial. Healthcare providers often delay the initiation and intensification of insulin unnecessarily. This stems from a fear of causing hypoglycaemia or weight gain in patients, from doubts about patients' self-care abilities and/or from inadequate resources to provide the necessary structured education to support patient self-management. Patients may be poorly adherent to treatment advice-particularly behavioural aspects such as self-monitoring, diet and exercise-although this may itself derive from inadequate access to effective diabetes education. There is, however, a limit to what can be achieved with existing exogenous insulin therapies due to their imperfect pharmacokinetic and pharmacodynamic profiles. Prominent among these imperfections is the problem of variability of effect from injection to injection with basal insulin formulations. Improvements in this area should benefit control and tolerability.
AIM: To review the available data in Spain about the socio-demographic and home environmental determinants in children and adolescents. METHOD: Review of the main studies conducted in Spain that have analysed the relationship between overweight and socio-economic and environmental determinants in children and adolescents. RESULTS: In children aged 6–7 y from Aragón (Spain), the socio-demographic determinants of childhood overweight were size of municipality, year of examination, gender, and province; in adolescents aged 13–14 y, the socio-demographic determinants were year of examination, type of school, size of municipality, gender, and province; overweight showed a significant positive main effect with public schools and low municipality size. In a nationally representative sample of Spanish adolescents from 13 to 18.5 y (AVENA Study), there was a significant relationship between overweight and socio-economic status in males but not in females; in males, the lowest overweight prevalences were observed in both extreme socio-economic groups; moreover, overweight prevalences increased when socio-economic status decreased, from the high to the medium–low socio-economic group. The studied variables related with family environment did not show any significant effect in overweight prevalence. CONCLUSION: Better knowledge of the relationship between social class and childhood obesity would lead to clearer hypotheses for the relationship in adults and might improve the preventive measures by identifying children at risk.
OBJECTIVES: To estimate the prevalence of insulin resistance syndrome (IRS) in a representative sample of youth. To test for the independent contribution of insulin resistance (IR) and adiposity to clustering of metabolic risk factors. To identify the underlying components of IRS. To examine the relationship between adiposity and fasting plasma levels of free fatty acids (FFA). METHODS: In 1999, we conducted a school-based survey of a representative sample of youth aged 9, 13 and 16 y in Quebec, Canada. Age-specific questionnaire data, standardized clinical measurements and a fasting blood sample were available for 2244 subjects. Fasting insulin and HOMA were used as surrogate measures of IR. RESULTS: In all age–sex groups, adiposity indices, blood pressure (BP), plasma glucose and triglycerides (TG) increased significantly with increasing insulin quartiles while HDL cholesterol (HDL-C) decreased. The overall prevalence of IRS defined as hyperinsulinaemia combined with two or more risk factors including overweight, high systolic BP, impaired fasting glucose, high TG and low HDL-C, was 11.5% (95% CI: 10.2–12.9). There were no significant differences in the prevalence of IRS across ages or between sexes. The independent contribution of adiposity to clustering of risk factors was stronger than that of fasting insulin (or HOMA-IR). Factor analysis revealed three factors (BMI/insulin/lipids, BMI/insulin/glucose and diastolic/systolic BP) consistent across ages suggesting that more than one pathophysiologic process underlies IRS. Although elevation of FFA might be in the causal pathway linking obesity to IR, we did not detect any consistent association between measures of fatness and fasting plasma FFA. CONCLUSION: IRS is highly prevalent in youth, even among children as young as age 9 y. Factor analysis identifies three physiologic domains within IRS with a unifying role for markers of IR and adiposity.
Obesity is associated with high blood cholesterol and high risk for developing diabetes and cardiovascular disease. Therefore, management of body weight and obesity are increasingly considered as an important approach to maintaining healthy cholesterol profiles and reducing cardiovascular risk. The present review addresses the effects of conjugated linoleic acid (CLA) on fat deposition, body weight and composition, safety, as well as mechanisms involved in animals and humans. Animal studies have shown promising effects of CLA on body weight and fat deposition. The majority of the animal studies have been conducted using CLA mixtures that contained approximately equal amounts of trans-10, cis-12 (t10c12) and cis-9, trans-11 (c9t11) isomers. Results of a few studies in mice fed CLA mixtures with different ratios of c9t11 and t10c12 isomers have indicated that the t10c12 isomer CLA may be the active form of CLA affecting weight gain and fat deposition. Inductions of leptin reduction and insulin resistance are the adverse effects of CLA observed in only mice. In pigs, the effects of CLA on weight gain and fat deposition are inconsistent, and no adverse effects of CLA have been reported. A number of human studies suggest that CLA supplementation has no effect on body weight and insulin sensitivity. Although it is suggested that the t10c12 CLA is the antiadipogenic isomer of CLA in humans, the effects of CLA on fat deposition are marginal and more equivocal as compared to results observed in animal studies. Mechanisms through which CLA reduces body weight and fat deposition remain to be fully understood. Proposed antiobesity mechanisms of CLA include decreased energy/food intake and increased energy expenditure, decreased preadipocyte differentiation and proliferation, decreased lipogenesis, and increased lipolysis and fat oxidation. In summary, CLA reduces weight gain and fat deposition in rodents, while produces less significant and inconsistent effects on body weight and composition in pigs and humans. New studies are required to examine isomer-specific effects and mechanisms of CLA in animals and humans using purified individual CLA isomers.
OBJECTIVE: To investigate the effects of variable amounts of tobacco smoking on body mass index and waist-to-hip ratio among current smokers. DESIGN: Population-based cohort study. SUBJECTS: A total of 22 059 apparently healthy men and women, who enrolled in the Greek EPIC cohort, aged 25–84 years, who had never smoked (14 751) or were current cigarette smokers (7308). MEASUREMENTS: Body mass index and waist-to-hip ratio (by anthropomentry), amount of tobacco smoking and energy expenditure (by an interviewer-administered, lifestyle questionnaire), energy intake and ethanol intake (by an interviewer-administered, validated, semiquantitative, food frequency questionnaire), at enrollment. RESULTS: In comparison to nonsmokers, smokers of the average number of cigarettes have lower body mass index. Among smokers, however, increased amount of smoking tends to be positively associated with body mass index, particularly among men. Waist-to-hip ratio is positively associated with amount of cigarettes smoked per day, among both men and women. CONCLUSION: Among smokers, tobacco smoking is positively associated with body mass index and waist-to-hip ratio. Our data suggest that the lower body mass index of smokers compared to nonsmokers reflects personality characteristics of those who choose to smoke and that the tendency to gain weight after smoking cessation may have behavioral rather than tobacco-related pharmacological roots.
OBJECTIVE: This paper explores the major changes in diet and physical activity patterns around the world and focuses on shifts in obesity. DESIGN: Review of results focusing on large-scale surveys and nationally representative studies of diet, activity, and obesity among adults and children. SUBJECTS: Youth and adults from a range of countries around the world. MEASUREMENTS: The International Obesity Task Force guidelines for defining overweight and obesity are used for youth and the body mass index ≥25 kg/m2 and 30 cutoffs are used, respectively, for adults. RESULTS: The nutrition transition patterns are examined from the time period termed the receding famine pattern to one dominated by nutrition-related noncommunicable diseases (NR-NCDs). The speed of dietary and activity pattern shifts is great, particularly in the developing world, resulting in major shifts in obesity on a worldwide basis. Data limitations force us to examine data on obesity trends in adults to provide a broader sense of changes in obesity over time, and then to examine the relatively fewer studies on youth. Specifically, this work provides a sense of change both in the United States, Europe, and the lower- and middle-income countries of Asia, Africa, the Middle East, and Latin America. CONCLUSION: The paper shows that changes are occurring at great speed and at earlier stages of the economic and social development of each country. The burden of obesity is shifting towards the poor.
The importance of strict glycaemic control in reducing diabetes-related outcomes is well recognised. Yet, despite the range of available treatment options, clinical experience suggests that individuals with diabetes frequently fail to achieve good glucose control. Instead, patients often have poorly controlled, unpredictable blood glucose levels. In insulin-treated patients, one of the reasons for this may be the inherently variable action of exogenously injected insulin. For example, the currently available longer-lasting insulin preparations that aim to provide a continuous basal level of circulating insulin are associated with markedly variable action both between and within subjects. Unpredictable insulin action contributes to variable blood glucose control, which in addition to increasing the risk of hypoglycaemia has also been shown to be an independent risk factor for mortality. It is hoped that advances in longer-lasting insulin preparations will provide significant benefits to patients, improving control and reducing variability. A new, long-lasting analogue, insulin detemir, has been shown to be significantly less variable than other basal insulin preparations in pharmacological and clinical studies. The improved predictability in insulin response offered by insulin detemir may be associated with a number of clinical benefits including a reduction in hypoglycaemia and weight gain.
Obesity is the central promoter of the metabolic syndrome which also includes disturbed fibrinolysis in addition to hypertension, dyslipidaemia and impaired glucose tolerance/type 2 diabetes mellitus. Plasminogen activator inhibitor-1 (PAI-1) is the most important endogenous inhibitor of tissue plasminogen activator and uro-plasminogen activator, and is a main determinant of fibrinolytic activity. There is now compelling evidence that obesity and, in particular, an abdominal type of body fat distribution are associated with elevated PAI-1 antigen and activity levels. Recent studies established that PAI-1 is expressed in adipose tissue. The greater the fat cell size and the adipose tissue mass, the greater is the contribution of adipose production to circulating PAI-1. Experimental data show that visceral adipose tissue has a higher capacity to produce PAI-1 than subcutaneous adipose tissue. Studies in human adipocytes indicate that PAI-1 synthesis is upregulated by insulin, glucocorticoids, angiotensin II, some fatty acids and, most potently, by cytokines such as tumour necrosis factor- α and transforming growth factor- β , whereas catecholamines reduce PAI-1 production. Interestingly, pharmacological agents such as thiazolidinediones, metformin and AT 1 -receptor antagonists were found to reduce adipose expression of PAI-1. In addition, weight loss by dietary restriction or comprehensive lifestyle modification is effective in lowering PAI-1 plasma levels. In conclusion, impaired fibrinolysis in obesity is probably also due to an increased expression of PAI-1 in adipose tissue. An altered function of the endocrine system and an impaired auto-/paracrine function at the fat cell levels may mediate this disturbance of the fibrinolytic system and thereby increase the risk for cardiovascular disease.
OBJECTIVE: To assess the relationship between weight cycling and some cardiovascular risk factors in a wide sample of obese subjects. DESIGN: Cross-sectional study with retrospective evaluation of weight and dieting history. SUBJECTS: In all, 459 obese subjects, 340 women and 119 men (age: 19–65 y; BMI: 30–69 kg/m 2 ). MEASUREMENTS: Body composition and fat distribution (by bioelectrical impedance analysis and anthropometry), systolic and diastolic blood pressure, plasma glucose, total and HDL cholesterol, triglycerides, insulin and insulin resistance by HOMAir, various weight cycling indices. RESULTS: A positive correlation between weight cycling indices, BMI and percent body fat was found in both genders. Also, the maximum absolute amount of weight regained following a single diet episode was significantly associated to insulin and HOMAir in both genders. However, these correlations disappeared when the data were controlled for age and BMI. CONCLUSION: In obese subjects of both genders weight cycling, and in particular weight regain, does not appear to be associated with adverse effects on body composition, fat distribution or cardiovascular risk factors in an independent manner, but rather in relation to fat accumulation over years.
BACKGROUND: Low-income patients are disproportionately affected by obesity. Routine care is available to this population at the Venice Family Clinic (VFC) in Los Angeles. The current study examined the effectiveness of nutrition clinic utilizing meal replacements (Slim-Fast, Slim-Fast Foods Co., FL, USA) in low-income patients over a 6-month period compared with the routine care by their primary care physician (PMD) prior to enrolling in the nutrition clinic at similar time intervals METHODS: In total, 63 patients (51 F; 49±0.8 yo) who had been followed at the VFC by their PMD for at least 6 months were enrolled in this study. Patients had a body mass index (BMI) of 40±1.1 kg/m 2 , were 72% Hispanic, 25% Caucasian, and 3% African American. They had the following co-morbidities: hypertension (HTN) 45%, diabetes mellitus II (DM II) 50%, gastroesophageal reflux disease (GERD) 34%, osteoarthritis 51%, and hypercholesterolemia 48%. All patients were provided with meal replacements to be taken twice a day and were instructed to consume one complete low calorie meal per day. Weights at the first visit to the nutrition clinic, 1, 3, and 6 months after enrollment in nutrition clinic were compared to their weights at the same time intervals during routine visits to their PMD prior to enrollment in the nutrition clinic. RESULTS: There was no significant weight change during the 6 months prior to enrollment in the nutrition program despite receiving care by a PMD. At 6 months after participating in the nutrition program, there was a mean decrease of 7% body weight with a reduction in BMI from 40–37 kg/m 2 ( P ≤0.05). CONCLUSION: Implementation of nutrition clinic utilizing meal replacements in this low-income patient population was effective in achieving a significant reduction in weight over 6 months of treatment.
BACKGROUND: Obese patients are often affected by hypertension, dyslipidaemia, impaired glucose metabolism, and suffer from cardiovascular disease (CVD), related to the characteristic metabolic alterations. AIM OF THE STUDY: To evaluate reduction of risk factors for CVDs in morbid-obese patients (body mass index (BMI)>40kg/m 2 ) after weight loss upon bariatric surgery intervention of biliary-intestinal bypass. SUBJECTS: 45 (17 men, 28 women) morbid-obese patients (age: 19–49 y, BMI>40 kg/m 2 ). All patients were selected on the basis of medical history, physical and biochemical evaluation and of psychiatric tests, which were performed on all individuals admitted to our Day Hospital to verify the safety of surgical intervention. MEASUREMENTS: Body weight, body composition (by dual X-ray absorptiometry, DXA), blood pressure, lipid profile, fibrinogen and glucose metabolism were monitored at baseline and 1, 3, 6, 9, 12, 24 and 36 months after surgery. RESULTS: A significant and persistent weight loss was present in all patients at the end of the 3 y follow-up period ( P <0.001), with a progressive reduction of total and trunk fat mass as evaluated by means of DXA. Additionally, a parallel significant reduction in systolic ( P <0.001) and diastolic ( P <0.001) blood pressure was observed. Total and LDL cholesterol were significantly reduced ( P <0.001), while HDL showed no modifications; triglycerides declined progressively during the 3 y follow-up ( P <0.001). Fibrinogen decreased from 364.5±82.4 to 266.4±45.7 mg/dl at the end of the period ( P <0.001). Fasting glucose levels and glucose levels 120 min after an oral glucose tolerance test were reduced from 95.1±20.3 to 78.6±9.1 mg/dl ( P <0.001) and from 116.9±34.7 to 77.6±15.5 mg/dl ( P <0.001), respectively, at baseline and at the end of the study. Moreover, fasting insulin decreased from 30.0±20.4 to 8.6±2.9 μUI/ml ( P <0.001) after 3 y, while insulin levels after (120 min) oral glucose load decreased from 105.5±61.5 to 12.0±6.0 μUI/ml ( P <0.001). CONCLUSION: Our results show that biliary-intestinal bypass may represent a valid and alternative therapeutic approach in patients with morbid obesity since it induces a significant and stable reduction of body weight and obesity-related risk factors for CVD.
OBJECTIVE:Obesity in children impacts on their health in both the short and long term. Having an accurate and precise body composition assessment, it may be possible to control growth process and predict adult status in order to reduce the risk factors for various diseases.METHOD:To review methods for body composition assessment that may provide new insights into the clinical practicality of paediatric obesity prevention/treatment. To present which specific outcome measurements in paediatric obesity prevention trials could be used to detect subjects at risk as early as possible.RESULTS:We discussed body composition measurements that could be used in daily clinical practice and as outcome measurements in prevention trials.CONCLUSION:These measurement procedures could be associated with methods for preventing obesity onset or retarding the weight gain associated with ageing.
OBJECTIVE: To determine whether abnormal obese-like neural responses to a meal persist in postobese individuals, who achieved and maintained a normal body weight despite a past history of severe obesity. DESIGN AND SUBJECTS: Cross-sectional study of the brain's response to tasting and consuming a satiating meal in 11 postobese (age: 40±6 y, body mass index (BMI): 23.6±1.9 kg/m 2 ), 23 obese (age: 29±6 y, BMI: 39.6±3.8 kg/m 2 ) and 21 lean (age: 33±9 y, BMI: 22.8±2.1 kg/m 2 ) subjects. MEASUREMENTS: Regional cerebral blood flow (rCBF, a marker of neural activity) at baseline (after a 36-h fast), after tasting and after consuming a satiating liquid meal was assessed using positron emission tomography and state-dependent changes (taste-baseline; satiation-baseline), and compared across groups. Subjective ratings of hunger and fullness were measured by a visual analogue scale and body fatness by dual-energy X-ray absorptiometry. RESULTS: In response to tasting the liquid meal, changes in rCBF were different in the obese as compared to the lean individuals ( P <0.05, corrected for multiple comparisons) in the middle insula (peak voxel, x =−41, y =1, z =8; Montreal Neurological Institute coordinates) and posterior cingulate cortex (peak voxel, x =17, y =−47, z =40). The middle insular cortex exhibited a similar increase of neural activity in the obese and postobese subjects, whereas in the lean subjects the regional activity did not change. In the posterior cingulate cortex, the changes in rCBF in the postobese subjects were not different from those in the other groups. In response to a satiating amount of the same liquid meal, changes in rCBF were different in the obese as compared to the lean individuals ( P <0.05, corrected for multiple comparisons) in the posterior hippocampus (peak voxel, x =21, y =−45, x =4), posterior cingulate cortex (peak voxel, x =17, y =−47, z =40), and amygdala (peak voxel, x =27, y =1, z =−24). The posterior hippocampus exhibited a similar decrease of neural activity in the obese and postobese subjects, whereas in the lean subjects the regional activity increased. In the posterior cingulate cortex and amygdala, the changes in rCBF were not different between the postobese and lean individuals. None of the changes in neural activity were correlated with the age of the individuals, the subjective ratings of hunger and fullness, or the meal induced-changes in plasma glucose, insulin, or serum free fatty acids. CONCLUSION: Persistence of abnormal neural responses to a meal in the postobese individuals, a group at high risk for relapse, indicates that a predisposition to obesity may involve areas of the brain that control complex aspects of eating behavior including anticipation and reward, chemosensory perception, and autonomic control of digestion (insular cortex), as well as enteroception and learning/memory (hippocampus).
Ectopic fat stores: housekeepers that can overspill into weapons of lean body mass destruction
AIM: These studies were performed to test the hypothesis that endogenous neuropeptide Y (NPY) acting on the NPY Y5 receptor subtype contributes to the control of food intake. The hypothesis was tested using S 25585—a newly synthesized NPY Y5 receptor antagonist. METHODS AND RESULTS: S 25585 was shown to be a high-affinity antagonist of the NPY Y5 receptor subtype (IC50 5 nM) with no significant affinity toward other NPY receptor subtypes and over 40 other receptors, channels or uptake systems. S 25585 (7.5 mg/kg, i.p.) did not induce a conditioned taste aversion, significantly alter need-induced sodium appetite or induce pica, suggesting that at this dose the compound did not induce illness or malaise. In satiated rats, S 25585 (5.0 and 7.5 mg/kg, i.p.) significantly decreased the overfeeding induced by i.c.v. injection of NPY (1 μg) and the highly selective NPY Y5 receptor agonist [hPP1−17, Ala31, Aib32]NPY (0.7 μg). In rats fasted for 4 h immediately before the dark phase, analysis of the microstructure of feeding behavior revealed that S 25585 significantly increased latency to eat and significantly decreased the duration and size of the meals without altering the meal number or eating rate. Analysis of the behavioral satiety sequence at this time revealed that the animals passed through the normal pattern of feeding, grooming and resting. Although S 25585 appeared to be influencing a physiological system controlling appetite, this does not involve the NPY Y5 receptor since the antagonist also markedly reduced food intake in the NPY Y5 knockout mouse. CONCLUSIONS: The results presented do not support a role for the NPY Y5 receptor in the control of food intake. The results further illustrate that it is imperative that the activity of any new NPY Y5 antagonist be assessed in the NPY Y5 knockout mouse before assuming that its effect on food intake is due to blockade of this receptor.
In the treatment of diabetes, the positive correlation between weight gain and glycaemic control is well known. Inappropriate weight gain has been demonstrated in landmark diabetes studies, with insulin or oral antidiabetic drugs. Weight increase is associated with accelerated deterioration in beta-cell function in type II diabetes, and increases in hypertension and lipid levels in both type I and type II diabetes. Concerns about increasing weight may be a barrier to initiation or to intensification of insulin therapy. Insulin introduction may be delayed in type II diabetes, and patients may under-dose their insulin to avoid gaining weight. Insulin detemir is a new long-acting soluble insulin analogue where protraction is achieved by reversible binding to albumin. As a result, it has consistent absorption and low variability from injection to injection. Studies of insulin detemir in basal-bolus regimens in type I and type II diabetes have shown significantly less weight gain compared with NPH. There is speculation about potential mechanisms for these outcomes and results from ongoing investigations are awaited. The insulin detemir data suggest that weight gain with insulin therapy is not inevitable. The potential therefore exists for improving glycaemic control while maintaining weight stability, resulting in immediate and long-term benefits for patients.
OBJECTIVE: To investigate whether current smoking and lifetime snuff use are associated with a lifetime history of major (≥5 kg) intentional weight loss in young adults, and to examine the dependence of this association on familial factors. DESIGN: Cross-sectional population-based questionnaire survey of young adult Finnish twins participating in the fourth wave of the longitudinal FinnTwin-16-study in 2000–2002. SUBJECTS: A total of 4521 young adult Finnish twins aged 23–27 y. MEASUREMENTS: Questionnaire data on the number of intentional weight-loss episodes and on body mass index (BMI), cigarette smoking and snuff use, educational level, and number of subjects' own children. RESULTS: Current daily smoking was strongly associated with a history of two or more intentional major weight-loss episodes (lost ≥5 kg twice or more lifetime) both in women odds ratio (OR 1.87; 95%; confidence interval (CI) 1.39–2.50) and in men (OR 2.00; 95% CI 1.37–2.90). Frequent lifetime snuff use was statistically significantly associated with recurrent intentional weight loss episodes in men (OR 1.51; 95% CI 1.08–2.13). Among the twin pairs discordant for daily smoking, the smoking twin was more likely than the nonsmoking co-twin to have recurrent intentional weight-loss episodes (OR 1.57; 95% CI 1.03–2.41). These episodes were also strongly associated with high BMI. Education was inversely related to recurrent intentional weight-loss episodes in men. CONCLUSION: Tobacco use is strongly associated with a lifetime history of recurrent intentional major weight-loss episodes in early adulthood. This represents a major challenge to existing attitudes on smoking prevention and the promotion of healthful weight control.
BACKGROUND: Ghrelin, a 28 amino-acid peptide secreted primarily from the stomach has been identified as the endogenous ligand for the growth hormone secretagogue receptor. Ghrelin is suppressed in the postprandial state and has been linked to both type II diabetes and obesity. AIMS: To investigate the effects of a period of overfeeding with high-fat dietary supplements on plasma ghrelin levels in nonobese men. METHODS: Six healthy males (21–34 y; BMI 21–24 kg/m 2 ) underwent the dietary intervention after completing diet and exercise diaries for 7 days. For 3 further weeks subjects followed their own diet diary supplemented with 125 ml single cream and 50 g roasted peanuts (88 g fat, 15 g Protein, 8 g carbohydrate) every day. Oral fat tolerance tests (OFTT) were undertaken at baseline, 7, 14 and 21 days of fat supplementation. The diet was increased in energy by 3.9 MJ/day and from a mean of 29–45% energy intake from fat with a small weight gain noted each week ( P =0.009). RESULTS: Ghrelin concentrations were significantly reduced during the baseline OFTT. The postprandial ghrelin response (AUC) was significantly reduced following 2 weeks of dietary supplementation ( P =0.005) increasing the suppression of plasma ghrelin by 18% despite only a 3% increase in body weight. Plasma triacylglycerol ( P =0.009) and leptin ( P =0.035) concentrations were also elevated and postprandial pancreatic polypeptide levels decreased ( P =0.038) following dietary-supplementation. CONCLUSIONS: These results suggest that the metabolic profile associated with obesity, including a reduction in plasma ghrelin levels, may be related to recent dietary energy intake and precedes the development of significant adiposity.
OBJECTIVE:An unexplained phenotype of mice overexpressing human UCP3 is their improved glucose homeostasis. Since overexpression of UCP3 might affect the energy charge of the cell, we investigated whether these mice have an increased AMP-activated protein kinase (AMPK) activity. METHODS:Mitochondrial localisation of UCP3 was determined by immunoelectronmicroscopy and AMPK activity was measured in medial gastrocnemius of control mice and mice overexpressing human UCP3. RESULTS:Mice overexpressing human UCP3 had 5.8 fold higher levels of UCP3 protein, for which mitochondrial localisation was confirmed by immunoelectronmicroscopy. The ATP/AMP ratio was significantly lower in mice over-expressing UCP3 compared to the wild-type (10.9+/-1.6 vs 20.4+/-1.9 AU, P=0.03). Over-expression of UCP3 resulted in increased AMPK alpha1 activity (1.23+/-0.05 vs 1.00+/-0.06 normalized values, P=0.004) and a tendency towards increased AMPK alpha2 activity (1.18+/-0.08 vs 1.00+/-0.10 normalized values, P=0.08). CONCLUSION:Increased AMPK activity provides a plausible explanation for the improved glucose tolerance characteristic for these mice.
OBJECTIVE: Three critical periods have been suggested for the development of obesity during childhood: fetal, ages 4–6 y, and adolescence. The prevalence of obesity in elementary school children is increasing in Japan, and the present study examines whether this rising prevalence occurs during the elementary school period (age 6–11 y) or is occurring prior to entry into elementary school. DESIGN: Repeated cross-sectional sampling of cohorts of children for the prevalence of obesity. SETTING AND PARTICIPANTS: The data from 81 264 first grade and 87 849 seventh grade children (94 and 87% of the total populations, respectively) between 1989 and 2002 in Kagoshima City were analyzed. Data were also obtained from nationwide surveys published by the Ministry of Japan between 1989 and 2001. MEASUREMENTS: Obesity was defined by the body mass index for an age- and sex-specific 95th percentile cutoff point in Japanese children. Trends in obesity and odds ratios of the prevalence of obesity were also determined. RESULTS: The period 1989–2001/2 showed significant increases in the prevalence of obesity for both genders, in both first and seventh grades, and in both Kagoshima City and nationwide. The odds ratios for the prevalence of obesity of 12-y-old children calculated against the prevalence of obesity within the same cohort at 6 y old revealed that a significant risk for development of obesity during the elementary school years applied only to boys from around 1993 onward in Kagoshima City and applied throughout the study period in nationwide Japan. CONCLUSION: Obesity prevalence increases for boys during elementary school years but does not significantly increase for girls. A rising trend for becoming obese before starting elementary school was present for both boys and girls over the period 1989–2001. Educational programs to improve nutrition and physical activity, especially for boys, are becoming increasingly necessary.
