International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity最新文献

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Epidemiology of childhood obesity--methodological aspects and guidelines: what is new? 儿童肥胖流行病学——方法学方面和指南:有什么新发现?
Y Wang
{"title":"Epidemiology of childhood obesity--methodological aspects and guidelines: what is new?","authors":"Y Wang","doi":"10.1038/sj.ijo.0802801","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802801","url":null,"abstract":"<p><strong>Introduction: </strong>It is still a matter of debate as to how to define obesity in young people, although a growing consensus is to use body mass index (BMI) cutoffs to classify obesity in children and adolescents.</p><p><strong>Objective: </strong>This article provides a brief overview of issues related to the assessment of obesity in children and adolescents.</p><p><strong>Results: </strong>At present, BMI is probably the best choice among available measures. BMI can be easily assessed at low cost, and has a strong association with body fatness and health risks. However, as an indirect measure of adipose tissue, BMI has a number of limitations. Cole et al published a set of sex- and age-specific BMI cutoffs, which had been developed based on data collected in six countries, and the reference has been recommended for international use. Recently, several researchers have raised concerns regarding this international reference. It has been argued that population-specific standards should be used due to biological differences between populations.</p><p><strong>Conclusion: </strong>BMI is a valid and feasible indirect measure of body fatness, but it suffers from a number of limitations. More efforts are needed to develop valid classifications of childhood obesity.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":"28 Suppl 3 ","pages":"S21-8"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24813691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 134
Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents. PPAR γ 2和ADR β 3之间的基因-基因相互作用增加了儿童和青少年肥胖的风险。
M C Ochoa, A Marti, C Azcona, M Chueca, M Oyarzábal, R Pelach, A Patiño, M J Moreno-Aliaga, M A Martínez-González, J A Martínez
{"title":"Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents.","authors":"M C Ochoa,&nbsp;A Marti,&nbsp;C Azcona,&nbsp;M Chueca,&nbsp;M Oyarzábal,&nbsp;R Pelach,&nbsp;A Patiño,&nbsp;M J Moreno-Aliaga,&nbsp;M A Martínez-González,&nbsp;J A Martínez","doi":"10.1038/sj.ijo.0802803","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802803","url":null,"abstract":"<p><strong>Aims: </strong>Multiple genes are likely to be involved in obesity and these genes may interact with environmental factors to influence obesity risk. Our aim was to explore the synergistic contribution of the two polymorphisms: Pro12Ala of the PPAR gamma 2 gene and Trp64Arg of the ADR beta 3 gene to obesity risk in a Spanish children and adolescent population.</p><p><strong>Methods: </strong>We designed a sex- and age-matched case-control study. Participants were 185 obese and 185 control children (aged 5-18 y) from the Navarra region, recruited through Departments of Pediatrics (Hospital Virgen del Camino, Navarra University Clinic and several Primary Health Centers). The obesity criterion (case definition) was BMI above the 97th percentile according to Spanish BMI reference data for age and gender. Anthropometric parameters were measured by standard protocols. The genotype was assessed by PCR-RFLP after digestion with BstUI for PPAR gamma 2 mutation and BstNI for ADR beta 3 variants. Face-to-face interviews were conducted to assess the physical activity. Using a validated physical activity questionnaire, we computed an activity metabolic equivalent index (METs h/week), which represents the physical exercise during the week for each participant. Statistical analysis was performed by conditional logistic regression, taking into account the matching between cases and controls.</p><p><strong>Results: </strong>Carriers of the polymorphism Pro12Ala of the PPAR gamma 2 gene had a significantly higher obesity risk than noncarriers (odds ratio (OR)=2.18, 95% CI=1.09-4.36) when we adjusted for sex, age and physical activity. Moreover, the risk of obesity was higher (OR=2.59, 95% CI=1.17-5.34) when family history of obesity was also taken into account in the model. The OR for obesity linked to both polymorphisms (PPAR gamma 2 and ADR beta 3) was 5.30 (95% CI=1.08-25.97) when we adjusted for sex, age and physical activity. After adjustment for family history of obesity, the OR for carriers of both polymorphisms was 19.5 (95% CI=2.43-146.8).</p><p><strong>Conclusions: </strong>A synergistic effect between polymorphism Pro12Ala of the PPAR gamma 2 gene and Trp64Arg of the ADR beta 3 gene for obesity risk was found in a case-control study including children and adolescents.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":"28 Suppl 3 ","pages":"S37-41"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802803","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24813693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 50
Inflammatory mediators in overweight and obese Spanish adolescents. The AVENA Study. 超重和肥胖西班牙青少年的炎症介质。AVENA研究。
J Wärnberg, L A Moreno, M I Mesana, A Marcos
{"title":"Inflammatory mediators in overweight and obese Spanish adolescents. The AVENA Study.","authors":"J Wärnberg,&nbsp;L A Moreno,&nbsp;M I Mesana,&nbsp;A Marcos","doi":"10.1038/sj.ijo.0802809","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802809","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to clarify if there is an association between overweight and a state of chronic, low-grade inflammation in adolescents.</p><p><strong>Design: </strong>The study is a part of the cross-sectional multicenter study AVENA, designed to evaluate the nutritional status of a representative sample of Spanish adolescents. The adolescents were divided into two groups: (1) nonoverweight and (2) overweight/obesity using the International Obesity Task Force (IOTF) standards.</p><p><strong>Subjects: </strong>A geographically representative subsample of the AVENA study including 493 Spanish adolescents, aged 13-18 y (236 females/257 males), participated in this study.</p><p><strong>Measurements: </strong>Serum C-reactive protein (CRP) and in vitro production of interleukin 6 and tumor necrosis factor alpha were measured, together with a detailed anthropometry.</p><p><strong>Results: </strong>The inflammatory markers showed generally higher values in subjects with overweight/obesity than in those with nonoverweight, with only CRP showing significant differences (the means were 0.83 and 1.27 mg/l in the nonoverweight and overweight/obesity groups, respectively).</p><p><strong>Conclusion: </strong>Although we have not studied if adolescent overweight and obesity play an initiating role in the development of future diseases, we suggest it may induce a chronic low-grade inflammatory state, which points out the importance of maintaining an appropriate body weight, to avoid obesity-related diseases in adulthood.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":"28 Suppl 3 ","pages":"S59-63"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802809","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24813697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 71
The prevalence of the metabolic syndrome and type 2 diabetes mellitus in children and adolescents. 儿童和青少年代谢综合征和2型糖尿病的患病率。
D Molnár
{"title":"The prevalence of the metabolic syndrome and type 2 diabetes mellitus in children and adolescents.","authors":"D Molnár","doi":"10.1038/sj.ijo.0802811","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802811","url":null,"abstract":"<p><strong>Objective: </strong>To review the prevalence of the metabolic syndrome and type 2 diabetes in children and adolescents.</p><p><strong>Method: </strong>Literature review.</p><p><strong>Results: </strong>It is well demonstrated that cardiovascular risk factors are frequent in childhood obesity and they tend to cluster. However, the frequency of the metabolic syndrome in childhood and adolescence has been investigated only by few studies. In spite of the diverse criteria used for defining the metabolic syndrome, it is evident that the syndrome is already highly prevalent among obese children and adolescents. Population-based data suggest that the epidemic of pediatric obesity is being followed by an increase of type 2 diabetes mellitus, especially in the United States and in minorities. For the European countries, there are no population-based incidence and prevalence data concerning type 2 diabetes mellitus in children and adolescents. From the available data, the magnitude of the problem in the European Caucasian population seems to be much less than in North America.</p><p><strong>Conclusion: </strong>There is an urgent need to establish internationally acceptable criteria for the metabolic syndrome in children and adolescents and to commence screening for this syndrome. Although type 2 diabetes mellitus is still rare among European children, screening is recommended for type 2 diabetes mellitus or impaired glucose tolerance in children and especially in adolescents with substantial risk for the development of this disease.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":"28 Suppl 3 ","pages":"S70-4"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24813595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 120
Hormones regulating lipid metabolism and plasma lipids in childhood obesity. 儿童肥胖中调节脂质代谢和血浆脂质的激素。
M Gil-Campos, R Cañete, A Gil
{"title":"Hormones regulating lipid metabolism and plasma lipids in childhood obesity.","authors":"M Gil-Campos,&nbsp;R Cañete,&nbsp;A Gil","doi":"10.1038/sj.ijo.0802806","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802806","url":null,"abstract":"<p><strong>Objective: </strong>To review the mechanisms by which leptin, insulin and adiponectin influence lipid metabolism and plasma lipids in obesity, as well as to describe the associations between these hormones in prepubertal children.</p><p><strong>Method: </strong>Revision of relevant papers published in the last 5 y related to the interactions of leptin, insulin and adiponectin, with special emphasis on those reporting potential mechanisms by which these hormones regulate lipid metabolism and plasma lipids. We also provide original results concerning the relationships found between plasma lipids and leptin, and insulin and adiponectin in prepubertal obese children.</p><p><strong>Results: </strong>Recent data in the literature shed new light to explain the effects of both leptin and adiponectin in the regulation of lipid metabolism in peripheral tissues. Activation of the AMP-dependent kinase pathway and subsequent increased fatty acid oxidation seems to be the main mechanism of action of these hormones in the regulation of lipid metabolism. In addition, we have found that insulin plasma levels are positively associated to leptin but negatively correlated with adiponectin in obese children. Adiponectin is negatively associated to plasma lipid markers of metabolic syndrome but positively related to HDL-cholesterol, whereas insulin and leptin show opposite patterns. These results support the effect of adiponectin in increasing insulin sensitivity and decreasing plasma triglycerides.</p><p><strong>Conclusion: </strong>Leptin, insulin and adiponectin are associated hormones that regulate lipid metabolism in childhood. Adiponectin appears to be the missing link to explain the alterations in lipid metabolism and plasma lipids seen in obesity.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":"28 Suppl 3 ","pages":"S75-80"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802806","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24813596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 61
Body composition in adolescents: measurements and metabolic aspects. 青少年的身体组成:测量和代谢方面。
G Rodríguez, L A Moreno, M G Blay, V A Blay, J M Garagorri, A Sarría, M Bueno
{"title":"Body composition in adolescents: measurements and metabolic aspects.","authors":"G Rodríguez,&nbsp;L A Moreno,&nbsp;M G Blay,&nbsp;V A Blay,&nbsp;J M Garagorri,&nbsp;A Sarría,&nbsp;M Bueno","doi":"10.1038/sj.ijo.0802805","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802805","url":null,"abstract":"<p><strong>Introduction: </strong>Adolescence is a decisive period in human life in which important body composition changes occur. Increase of total body mass and its relative distribution are mainly related to gender and pubertal development.</p><p><strong>Objective: </strong>This review explores the specific measurements that may be used in this age group to assess excess body fat and to define obesity and overweight.</p><p><strong>Results: </strong>Identification of subjects at risk for adiposity requires simple anthropometric cutoffs for the screening of overweight and obesity. In this context, BMI criterion is the most frequently used but, in spite of its high sensitivity and specificity, an important number of adolescents classified as overweight or obese do not have really high adiposity (32.1% of females and 42% of males). Excess total body fat and intra-abdominal visceral fat are related to metabolic abnormalities that increase the risk of cardiovascular diseases. Waist circumference seems to be the best simple anthropometric predictor for the screening of the metabolic syndrome in children and adolescents.</p><p><strong>Conclusions: </strong>Early identification of adolescents at risk for adiposity and its related metabolic complications requires reliable, simple and specific measures of excess body fat for this age group.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":"28 Suppl 3 ","pages":"S54-8"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24813696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 179
Overweight and obesity epidemic among children. Answer from European countries. 超重和肥胖在儿童中流行。来自欧洲国家的回答。
I Lissau
{"title":"Overweight and obesity epidemic among children. Answer from European countries.","authors":"I Lissau","doi":"10.1038/sj.ijo.0802822","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802822","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the methods and results used and conclusions found in available published papers on childhood overweight and obesity in Europe.</p><p><strong>Surveys: </strong>This paper compares the two available published papers on the prevalence of child and adolescent overweight and obesity in Europe. The first paper was published in November 2003 and was based on 20 previously conducted surveys performed from 1992 to 2001. The other paper was published in January 2004 and was based on data from the WHO collaborative survey 'Health Behaviour in School Children', which collected the data in 1997-1998 within a period of 9 months. Height and weight were included as optional questions and 13 European countries, Israel and United States participated.</p><p><strong>Methods: </strong>In both papers, body mass index (BMI) was used. In the first paper, measured BMI was used and prevalence of overweight was calculated using IOTF cutoff points. In the other paper, overweight and obesity prevalences were calculated from self-reported height and weight using an internal study reference standard.</p><p><strong>Results: </strong>The first paper found a north-south trend in overweight in Europe, whereas the second found a more equal distribution of overweight in European children. Thus, overweight was significantly increased among 13 y olds of both sexes in Finland, Ireland, and Greece, and in Portuguese girls. Among 15 y olds, the prevalence of overweight was significantly increased in Greek boys, and in Danish and Portuguese girls. On the contrary, in Lithuania, there was a significantly low prevalence of overweight among both ages and both sexes.</p><p><strong>Conclusion: </strong>Critical reviews of the results of the two published papers show that the year of data collection, methods and use of appropriate statistics are of critical importance for the conclusion drawn from comparative epidemiological surveys on the prevalence of overweight.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":"28 Suppl 3 ","pages":"S10-5"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24812625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 83
Micro-environmental and socio-demographic determinants of childhood obesity. 儿童肥胖的微观环境和社会人口决定因素。
L A Moreno, C Tomás, M González-Gross, G Bueno, J M Pérez-González, M Bueno
{"title":"Micro-environmental and socio-demographic determinants of childhood obesity.","authors":"L A Moreno,&nbsp;C Tomás,&nbsp;M González-Gross,&nbsp;G Bueno,&nbsp;J M Pérez-González,&nbsp;M Bueno","doi":"10.1038/sj.ijo.0802798","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802798","url":null,"abstract":"<p><strong>Aim: </strong>To review the available data in Spain about the socio-demographic and home environmental determinants in children and adolescents.</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>In children aged 6-7 y from Aragon (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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":"28 Suppl 3 ","pages":"S16-20"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802798","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24812627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 79
The reality of glycaemic control in insulin treated diabetes: defining the clinical challenges. 胰岛素治疗糖尿病血糖控制的现实:定义临床挑战。
M Davies
{"title":"The reality of glycaemic control in insulin treated diabetes: defining the clinical challenges.","authors":"M Davies","doi":"10.1038/sj.ijo.0802745","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802745","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":"28 Suppl 2 ","pages":"S14-22"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802745","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24633491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 92
Engineering predictability and protraction in a basal insulin analogue: the pharmacology of insulin detemir. 基础胰岛素类似物的工程可预测性和延长性:地特米胰岛素的药理学。
P Kurtzhals
{"title":"Engineering predictability and protraction in a basal insulin analogue: the pharmacology of insulin detemir.","authors":"P Kurtzhals","doi":"10.1038/sj.ijo.0802746","DOIUrl":"https://doi.org/10.1038/sj.ijo.0802746","url":null,"abstract":"<p><p>The suboptimal nature of the absorption profiles of human insulin formulations following subcutaneous administration has prompted the development of insulin analogues better suited for therapeutic use in diabetes mellitus. A particular challenge has been to engineer long-acting agents that do not produce unduly variable responses from one injection to another. One recent approach that has met with success has been to acylate, the insulin molecule with a fatty acid, thereby enabling reversible albumin binding. The first clinically available agent of this type is insulin detemir. Pharmacological studies have established that this principle is effective in prolonging action, primarily by retarding absorption. The solubility of insulin detemir in the vial and after injection and an important buffering mechanism effected by plasma albumin binding explain a significant decrease in within-subject variability of pharmacodynamic response observed in repeat isoglycaemic clamp studies where insulin detemir was compared to other basal insulin products. Owing to the extremely high ratio of albumin-binding sites to insulin detemir molecules at therapeutic concentrations, no safety considerations have been identified pertaining to albumin binding. The insulin detemir molecule retains the molecular pharmacological properties of native human insulin, including a physiological balance between metabolic and mitogenic potencies. Thus, insulin detemir offers the promise of an improved tolerability:efficacy ratio in the clinical setting.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":"28 Suppl 2 ","pages":"S23-8"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802746","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24633492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 123
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