2013APP技术报告-儿童和青少年2型糖尿病的管理

DOI: 10.1542/peds.2012-3496 ; originally published online January 28, 2013;Pediatrics Stephen J. Spann and Susan K. Flinn Prazar, Terry Raymer, Richard N. Shiffman, Vidhu V. Thaker, Meaghan Anderson, Shelley C. Springer, Janet Silverstein, Kenneth Copeland, Kelly R. Moore, Greg E. Management of Type 2 Diabetes Mellitus in Children and Adolescents http://pediatrics.aappublications.org/content/early/2013/01/23/peds.2012-3496 located on the World Wide Web at: The online version of this article, along with updated information and services, is of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point publication, it has been published continuously since 1948. PEDIATRICS is owned, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly by guest on January 30, 2013pediatrics.aappublications.orgDownloaded from www.medlive.cn TECHNICAL REPORT Management of Type 2 Diabetes Mellitus in Children and Adolescents abstract OBJECTIVE: Over the last 3 decades, the prevalence of childhood obe- sity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. This technical report describes, in detail, the procedures undertaken to develop the recommendations given in the accompanying clinical practice guide- line, “Management of Type 2 Diabetes Mellitus in Children and Ado- lescents,” and provides in-depth information about the rationale for the recommendations and the studies used to make the clinical practice guideline’s recommendations. METHODS: A primary literature search was conducted relating to the treatment of T2DM in children and adolescents, and a secondary lit- erature search was conducted relating to the screening and treatment of T2DM’s comorbidities in children and adolescents. Inclusion criteria were prospectively and unanimously agreed on by members of the committee. An article was eligible for inclusion if it addressed treat- ment (primary search) or 1 of 4 comorbidities (secondary search) of T2DM, was published in 1990 or later, was written in English, and included an abstract. Only primary research inquiries were consid- ered; review articles were considered if they included primary data or opinion. The research population had to constitute children and/or adolescents with an existing diagnosis of T2DM; studies of adult patients were considered if at least 10% of the study population was younger than 35 years. All retrieved titles, abstracts, and articles were reviewed by the consulting epidemiologist. RESULTS: Thousands of articles were retrieved and considered in both searches on the basis of the aforementioned criteria. From those, in the primary search, 199 abstracts were identified for possible inclu- sion, 58 of which were retained for systematic review. Five of these studies were classified as grade A studies, 1 as grade B, 20 as grade C, and 32 as grade D. Articles regarding treatment of T2DM selected for inclusion were divided into 4 major subcategories on the basis of type of treatment being discussed: (1) medical treatments (32 stud- ies); (2) nonmedical treatments (9 studies); (3) provider behaviors (8 studies); and (4) social issues (9 studies). From the secondary search, an additional 336 abstracts relating to comorbidities were identified for possible inclusion, of which 26 were retained for systematic re- view. These articles included the following: 1 systematic review of literature regarding comorbidities of T2DM in adolescents; 5 expert Shelley C. Springer, MD, MBA, MSc, JD, Janet Silverstein, MD, Kenneth Copeland, MD, Kelly R. Moore, MD, Greg E. Prazar, MD, Terry Raymer, MD, CDE, Richard N. Shiffman, MD, Vidhu V. Thaker, MD, Meaghan Anderson, MS, RD, LD, CDE, Stephen J. Spann, MD, MBA, and Susan K. Flinn, MA KEY WORDS childhood, clinical practice guidelines, comanagement, diabetes, management, treatment, type 2 diabetes mellitus, youth ABBREVIATIONS AAP—American Academy of Pediatrics ACE—angiotensin-converting enzyme ADA—American Diabetes Association AHA—American Heart Association BG—blood glucose CAM—complementary and alternative medicine CES-D—Center for Epidemiologic Studies Depression Scale CVD—cardiovascular disease HbA1c—hemoglobin A1c LDL-C—low-density lipoprotein cholesterol PCP—primary care provider QDS—Quality Data Set RCT—randomized controlled trial T1DM—type 1 diabetes mellitus T2DM—type 2 diabetes mellitus This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication. The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. All technical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time. www.pediatrics.org/cgi/doi/10.1542/peds.2012-3496 doi:10.1542/peds.2012-3496 PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2013 by the American Academy of Pediatrics e648 FROM THE AMERICAN ACADEMY OF PEDIATRICS by guest on January 30, 2013pediatrics.aappublications.orgDownloaded from www.medlive.cn opinions presenting global recommendations not based on evidence; 5 cohort studies reporting natural history of disease and comorbidities; 3 with specific attention to comorbidity patterns in specific ethnic groups (case-control, cohort, and clinical report using adult literature); 3 reporting an association between microalbuminuria and retinopathy (2 case-control, 1 cohort); 3 reporting the prevalence of nephropathy (cohort); 1 reporting peripheral vascular disease (case series); 2 discussing retinopathy (1 case-control, 1 position statement); and 3 addressing hyperlipidemia (American Heart Association position statement on cardiovascular risks; American Diabetes Association consensus statement; case series). A breakdown of grade of recommendation shows no grade A studies, 10 grade B studies, 6 grade C studies, and 10 grade D studies. With regard to screening and treatment recommendations for comorbidities, data in children are scarce, and the available literature is conflicting. Therapeutic recommendations for hypertension, dyslipidemia, retinopathy, microalbuminuria, and depression were summarized from expert guideline documents and are presented in detail in the guideline. The references are provided, but the committee did not independently assess the supporting evidence. Screening tools are provided in the Supplemental Information. Pediatrics 2013;131:e648–e664 INTRODUCTION This technical report details the pro- cedures undertaken to develop the recommendations given in the accom- panying clinical practice guideline, “Management of Type 2 Diabetes Melli- tus in Children and Adolescents.” What follows is a description of the process, including the committee’s objectives; methods of evidence identification, re- trieval, review, and analysis; and sum- maries of the committee’s conclusions. Statement of the Issue Over the last 3 decades, type 2 diabetes mellitus (T2DM), a disease previously confined to adult patients, has mark- edly increased in prevalence among children and adolescents. Currently, in the United States, approximately 1 in 3 new cases of diabetes mellitus diag- nosed in patients younger than 18 years is T2DM,1,2 with a disproportionate re- presentation in ethnic minorities,3,4 especially among adolescents.5 This trend is not limited to the United States but is occurring internationally as well.6 The rapid emergence of childhood T2DM poses challenges to the physician who is unequipped to treat adult diseases en- countered in children. Most diabetes training and educational materials designed for pediatric patients address type 1 diabetes mellitus (T1DM) and em- phasize insulin treatment and glucose monitoring, which may or may not be appropriate for children with T2DM.7,8 Most medications used for T2DM have been tested for safety and efficacy only in individuals older than 18 years, and there is scant scientific evidence for optimal management of children with T2DM.9,10 Extrapolation of data from adult studies to pediatric populations may not be valid because the hormonal milieu of the prepubescent and pubes- cent patient with T2DM can affect treatment goals and modalities in ways heretofore unencountered in adult patients.11 The United States has a severe shortage of pediatric endocrinologists, making access to these specialists difficult or, in some cases, impossible.12 Vast geo- graphic areas lack a pediatric endo- crinologist: in 2011, 3 states had no pediatric endocrinologists, and 22 had fewer than 10, and the situation is un- likely to improve in the near future.13 In 2004, the National Association of Child- ren’s Hospitals and Related Institutions performed a workforce survey and found that patients had to wait almost 9 weeks for an appointment to see an endocrinologist.14 Because the number of patients with T1DM and T2DM has increased since then, this situation is presumably worse today. Regardless of their age, most patients in the United States who have T2DM are cared for by primary care providers (PCPs).15 Furthermore, given the expected in- creases in the national and global inci- dence of T2DM and the near impossibility that the pediatric endocrine workforce will increase proportionately, PCPs must be prepared for and capable of managing children and adolescents who have un- complicated T2DM. Numerous experts have argued that the ideal care of a child with T2DM is provided through a team approach, with care shared among a pediatric endocrinologist, diabetes nurse edu- cator, nutritionist, and behavioral spe- cialist.16–18 In areas of limited access to pediatric endocrinologists, however, contact with the pediatric endocri- nology team might involve contact at diagnosis for initial diabetes educa- tion and intermittently thereafter; annually, with interval care by a PCP and interval communication with the pediatric endocrinology team; or at every visit, for those patients who are either doing poorly or are taking insulin. In areas where access to subspecialists is hampered by geographic distances and/or professional shortages, care provided by local generalists who are skilled in treating children and youth with T2DM is likely to improve access to medical care. Although there are no pediatric studies evaluating this issue, the committee believes that this im- proved access to care might result in: PEDIATRICS Volume 131, Number 2, February 2013 e649 FROM THE AMERICAN ACADEMY OF PEDIATRICS by guest on January 30, 2013pediatrics.aappublications.orgDownloaded from www.medlive.cn � Reduced wait times and increased timeliness of care. � Reduced economic burden to the patient, including reduced need to travel and reduced time lost from work and/or school. � Potentially improved patient reten- tion. Kawahara et al19 reported that 56.9% of patients with T2DM stopped coming to their hospital diabetes clinic appointments, most commonly because they were “too busy” to keep their appointments. Recent advances in medical technol- ogy have the potential to ameliorate limited access to specialists. Reporting on the provision of clinical specialty diabetes care to remote locations using telemedicine, Malasanos et al20 found that weekly telemedicine clinics were able to effectively replace quarterly face-to-face clinics after an initial face- to-face clinic visit. This more frequent contact provided by the telemedicine clinics resulted in improved hemoglo- bin A1c (HbA1c) concentrations, better patient satisfaction, fewer days missed from work or school, more time spent with the patient during clinic visits, and fewer subsequent hospitalizations and emergency department visits. Tele- medicine is costly, however, and requires equipment to be in place at both the subspecialist’s office and the remote clinic; it is, therefore, not ap- propriate for every practice. It is pos- sible that a similar model of service could be provided by a generalist working locally and in close commu- nication with a specialist. For family physicians and others who care for adult patients, managing T2DM in children poses potential challenges. The first is that what works for adults may not work for children. Experiences and results observed in adults do not necessarily apply to children. Children (and even adolescents) are not small adults; they have a changing hormonal environment, have differences in phy- siology, and their growth can have effects on medication doses, toxicity, and responses.11 As a result, general- ists who are confident in caring for adults with diabetes may attempt to apply adult practice experiences to children, in whom these may not nec- essarily be appropriate. Kaufman cited data on various drugs’ effects in chil- dren and argued that harm may occur if children with T2DM are treated like adults with T2DM.11 The author called for treatment trials for children with T2DM, to “better define the risk-benefit ratio in children and youth, since this may differ substantially from that in the adult type 2 diabetic population.” In contrast, others have noted that most adolescents with T2DM are similar to adults in terms of size and reproduc- tive maturity and argued that, in the absence of studies specifically targeted to adolescents, treatment regimens can be extrapolated from studies of adults with T2DM; they do agree, how- ever, that more randomized controlled trials (RCTs) are needed in the pedi- atric population.1 A second challenge is presented by the conflicting evidence regarding out- comes in patients with diabetes who are managed by generalists versus subspecialists. Some studies in adult patients indicate that generalists are capable of achieving outcomes similar to those of subspecialists. Greenfield et al21 observed that physiologic and functional status (ie, physical, psy- chological, social functioning) were similar at both 2 and 4 years and mortality was similar at 7 years in adult hypertensive patients with di- abetes treated in multispecialty groups versus health maintenance organiza- tion general practices. Other studies indicate that generalists may achieve outcomes similar to those of diabetes specialists, as long as they have input from subspecialists. Indeed, unlike diseases in several other specialties, care for children with di- abetes that is conducted by generalists without input from specialists may be inferior to that provided by specialists. Ziemer et al22 used an RCT design to examine the effect of providing 5 minutes of direct feedback from an endocrinologist to a PCP every 2 weeks. Performance in the feedback group was sustained after 3 years, and performance decayed in a comparison group that received computer-generated decision support reminders, including a flow-sheet section showing previous clinical data and a recommendations section. Specialist feedback contrib- uted independently to intensification of diabetes management. In addition, “clinical inertia” (defined as failure by providers to intensify pharmacologic therapy for hyperglycemia) was more likely in a primary care versus a di- abetes clinic setting (91% vs 52%) and resulted in higher HbA1c concentra- tions among patients.23 How these observations might be ap- plied to the child who has T2DM is not entirely clear, but they suggest that regular, direct contact between the generalist and a specialist can have a positive outcome on these patients. De Berardis et al24 reported that, com- pared with adult patients with diabetes mellitus who were seen in general practice offices, patients cared for in diabetes clinics were more likely to conform with process-of-care mea- sures, including HbA1c concentrations, blood pressure, total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, microalbuminuria test- ing, and foot and eye examinations and were more likely to have adequate concentrations of total cholesterol. No differences were found in glycemic, blood pressure, or LDL-C control, how- ever. In that same study, all process-of- care measures improved when the patient was seen by a single physician e650 FROM THE AMERICAN ACADEMY OF PEDIATRICS by guest on January 30, 2013pediatrics.aappublications.orgDownloaded from www.medlive.cn as opposed to being seen by several different physicians. No similar studies have been performed in children, and it is therefore unknown whether simi- lar outcomes can be achieved in the pediatric population. A third challenge is presented by the fact that children with T2DM are overrepresented among racial and ethnic minority populations and are more likely to be living in poverty; therefore, they may face significant challenges in accessing specialists, even under the best situations.25 Recognizing these barriers to care and patients’ real-world needs, it is the committee’s consensus that it is impractical to ex- pect every patient with T2DM to be able to access a pediatric endocrinologist on a regular basis. It is also unreasonable to assume that these visits will be fre- quent enough to provide the level of care needed to maintain the best pos- sible metabolic control. For this reason alone, PCPs must have a thorough knowledge of the management of T2DM, including its unique aspects related to childhood and adolescence. The committee also believes it is the PCP’s responsibility to obtain the re- quisite skills for such care and to com- municate and work closely with a diabetes team of subspecialists when- ever possible. For this reason, when treatment goals are not met, the com- mittee encourages clinicians to consult with an expert trained in the care of children and adolescents with T2DM. When first-line therapy fails (eg, metfor- min), recommendations for intensifying therapy should be generally the same for pediatric and adult populations. The picture is constantly changing, however, as new drugs are being introduced, and some drugs that initially seemed to be safe exhibit adverse effects with wider use. Clinicians should, therefore, remain alert to new developments in this area. Seeking the advice of an expert can help ensure that the treatment goals are appropriately set and that clinicians benefit from cutting-edge treatment in- formation in this rapidly changing area. Stated Objective of the American Academy of Pediatrics Because the PCP caring for children will likely encounter T2DM, the Amer- ican Academy of Pediatrics (AAP), the Pediatric Endocrine Society, the American Academy of Family Physi- cians, the American Diabetes Associ- ation (ADA), and the American Dietetic Association undertook a cooperative effort to develop clinical guidelines for the treatment of T2DM in children and adolescents, for the benefit of subspe- cialists and generalists alike. Represen- tatives from these groups collaborated on developing an evidence profile that served as a major source of information for the accompanying clinical practice guideline recommendations. This re- port, based on a review of the current medical literature covering a period from January 1, 1990, to July 1, 2009, provides a set of evidence-based guide- lines for the management and treatment of T2DM in children and adolescents. It should b