Janet H. Silverstein

Type 2 diabetes in children and adolescents

Arlen L. Rosenblooma, Janet H. Silversteinb, Shin Amemiyac, Phil Zeitlerd and Georgeanna J Klingensmithe abDivision of Endocrinology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; cDivision of Endocrinology, Department of Pediatrics, Saitama Medical University, Saitama, Japan; dDivision of Endocrinology, Department of Pediatrics, The Children’s Hospital, University of Colorado Denver, Aurora, CO, USA; eDepartment of Pediatrics, The Children’s Hospital and Barbara Davis Center, University of Colorado Denver, Aurora, CO, USA. Corresponding author: Professor Emeritus Arlen L Rosenbloom Division of Endocrinology Department of Pediatrics, University of Florida College of Medicine, 1701 SW 16th Avenue Gainesville, FL 32608 USA. e-mail: rosenal@peds.ufl.edu

Prevention and Treatment of Pediatric Obesity: An Endocrine Society Clinical Practice Guideline Based on Expert Opinion

Objective: Our objective was to formulate practice guidelines for the treatment and prevention of pediatric obesity. Conclusions: We recommend defining overweight as body mass index (BMI) in at least the 85th percentile but < the 95th percentile and obesity as BMI in at least the 95th percentile against routine endocrine studies unless the height velocity is attenuated or inappropriate for the family background or stage of puberty; referring patients to a geneticist if there is evidence of a genetic syndrome; evaluating for obesity-associated comorbidities in children with BMI in at least the 85th percentile; and prescribing and supporting intensive lifestyle (dietary, physical activity, and behavioral) modification as the prerequisite for any treatment. We suggest that pharmacotherapy (in combination with lifestyle modification) be considered in: 1) obese children only after failure of a formal program of intensive lifestyle modification; and 2) overweight children only if severe comorbidities persist despite intensive lifestyle modification, particularly in children with a strong family history of type 2 diabetes or premature cardiovascular disease. Pharmacotherapy should be provided only by clinicians who are experienced in the use of antiobesity agents and aware of the potential for adverse reactions. We suggest bariatric surgery for adolescents with BMI above 50 kg/m2, or BMI above 40 kg/m2 with severe comorbidities in whom lifestyle modifications and/or pharmacotherapy have failed. Candidates for surgery and their families must be psychologically stable and capable of adhering to lifestyle modifications. Access to experienced surgeons and sophisticated multidisciplinary teams who assess the benefits and risks of surgery is obligatory. We emphasize the prevention of obesity by recommending breast-feeding of infants for at least 6 months and advocating that schools provide for 60 min of moderate to vigorous daily exercise in all grades. We suggest that clinicians educate children and parents through anticipatory guidance about healthy dietary and activity habits, and we advocate for restricting the availability of unhealthy food choices in schools, policies to ban advertising unhealthy food choices to children, and community redesign to maximize opportunities for safe walking and bike riding to school, athletic activities, and neighborhood shopping.

Limited Joint Mobility in Childhood Diabetes Mellitus Indicates Increased Risk for Microvascular Disease

We detected limited mobility of small and large joints in 92 (30 per cent) of 309 patients with diabetes who were one to 28 years old. Among patients who had had diabetes for more than 4.5 years (the shortest duration at which microvascular complications were noted), 82 of 169 had joint limitation. Forty-one of these 82 also had microvascular complications, but only 10 of the 87 patients without joint limitation had complications. Life-table analysis indicated an 83 per cent risk for microvascular complications after 16 years of diabetes if joint limitation was present, but only a 25 per cent risk if joint limitation was absent. Consequently, limited joint mobility identifies a population exceptionally at risk for the early development of microvascular complications, and intervention to forestall or prevent these complications can now be focused.

A Prospective Study of the Development of Diabetes in Relatives of Patients with Insulin-Dependent Diabetes

BACKGROUND The presence of cytoplasmic islet-cell autoantibodies has been recognized as a risk factor for the development of diabetes mellitus in relatives of patients with insulin-dependent diabetes mellitus (IDDM), but the magnitude of the risk is unknown, as is the influence of other factors, such as age, sex, and race. METHODS From 1979 through 1989, we studied 4015 initially nondiabetic relatives of 1590 probands with IDDM to determine the risk of IDDM according to the presence and titer of autoantibodies, as well as other factors. RESULTS Of the 4015 nondiabetic relatives, 125 (3.1 percent) had islet-cell antibodies in their initial serum samples, and 40 contracted IDDM. Islet-cell antibodies were most frequent (4.3 percent) in relatives who were under 20 years of age (P = 0.001) and in those (4.8 percent) from families with more than one affected member (a multiplex pedigree) (P = 0.003). Independent risk factors for the development of diabetes in the relatives included age of less than 10 years at the time of the initial study (P = 0.001), membership in a multiplex pedigree (P = 0.02), and a positive test for islet-cell antibodies in the initial serum sample (P = 0.0001). Twenty-seven of the relatives in whom diabetes developed (67.5 percent) had positive tests for islet-cell antibodies before the diagnosis of IDDM, giving a relative risk of IDDM of 68 (95 percent confidence interval, 34 to 134) for antibody-positive relatives. Islet-cell-antibody titers of 20 Juvenile Diabetes Foundation units or higher were associated with an increasing risk of diabetes. CONCLUSIONS Nondiabetic relatives of probands with IDDM who are in the first two decades of life, are members of multiplex pedigrees, and have increased titers of islet-cell antibodies are the most likely to contract IDDM themselves.

Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus.

We randomly assigned 46 patients (mean age, 11.7 years; range, 4.5 to 32.8) with newly diagnosed insulin-dependent diabetes mellitus within two weeks of beginning insulin to receive either corticosteroids for 10 weeks plus daily azathioprine for one year or no immunosuppressive therapy. Half the 20 immunosuppressed patients completing the one-year trial had satisfactory metabolic outcomes (hemoglobin A1c less than 6.8 percent; stimulated peak C peptide greater than 0.5 nmol per liter; insulin dose less than 0.4 U per kilogram of body weight per day) as compared with only 15 percent of the controls. Three of 20 immunosuppressed patients, but no controls, were insulin independent at one year. Two of these continue to receive azathioprine without insulin after more than 27 months of follow-up. The response to immunosuppression correlated with older age, better initial metabolic status, and lymphopenia (less than 1800 lymphocytes per cubic millimeter) resulting from immunosuppression. The side effects of azathioprine included vomiting in one patient and mild hair loss in several others. Prednisone use resulted in a transient cushingoid appearance, weight gain, and hyperglycemia. The growth rate remained normal in all patients. We conclude that early immunosuppression with short-term use of corticosteroids plus daily azathioprine can improve metabolic control in some patients with insulin-dependent diabetes mellitus, but results from this unblinded study are preliminary and require further confirmation and long-term follow-up.

Controlled Clinical Trial of Dichloroacetate for Treatment of Congenital Lactic Acidosis in Children

OBJECTIVE. Open-label studies indicate that oral dichloroacetate (DCA) may be effective in treating patients with congenital lactic acidosis. We tested this hypothesis by conducting the first double-blind, randomized, control trial of DCA in this disease. METHODS. Forty-three patients who ranged in age from 0.9 to 19 years were enrolled. All patients had persistent or intermittent hyperlactatemia, and most had severe psychomotor delay. Eleven patients had pyruvate dehydrogenase deficiency, 25 patients had 1 or more defects in enzymes of the respiratory chain, and 7 patients had a mutation in mitochondrial DNA. Patients were preconditioned on placebo for 6 months and then were randomly assigned to receive an additional 6 months of placebo or DCA, at a dose of 12.5 mg/kg every 12 hours. The primary outcome results were (1) a Global Assessment of Treatment Efficacy, which incorporated tests of neuromuscular and behavioral function and quality of life; (2) linear growth; (3) blood lactate concentration in the fasted state and after a carbohydrate meal; (4) frequency and severity of intercurrent illnesses and hospitalizations; and (5) safety, including tests of liver and peripheral nerve function. OUTCOME. There were no significant differences in Global Assessment of Treatment Efficacy scores, linear growth, or the frequency or severity of intercurrent illnesses. DCA significantly decreased the rise in blood lactate caused by carbohydrate feeding. Chronic DCA administration was associated with a fall in plasma clearance of the drug and with a rise in the urinary excretion of the tyrosine catabolite maleylacetone and the heme precursor δ-aminolevulinate. CONCLUSIONS. In this highly heterogeneous population of children with congenital lactic acidosis, oral DCA for 6 months was well tolerated and blunted the postprandial increase in circulating lactate. However, it did not improve neurologic or other measures of clinical outcome.

Sports Drinks and Energy Drinks for Children and Adolescents: Are They Appropriate?

Sports and energy drinks are being marketed to children and adolescents for a wide variety of inappropriate uses. Sports drinks and energy drinks are significantly different products, and the terms should not be used interchangeably. The primary objectives of this clinical report are to define the ingredients of sports and energy drinks, categorize the similarities and differences between the products, and discuss misuses and abuses. Secondary objectives are to encourage screening during annual physical examinations for sports and energy drink use, to understand the reasons why youth consumption is widespread, and to improve education aimed at decreasing or eliminating the inappropriate use of these beverages by children and adolescents. Rigorous review and analysis of the literature reveal that caffeine and other stimulant substances contained in energy drinks have no place in the diet of children and adolescents. Furthermore, frequent or excessive intake of caloric sports drinks can substantially increase the risk for overweight or obesity in children and adolescents. Discussion regarding the appropriate use of sports drinks in the youth athlete who participates regularly in endurance or high-intensity sports and vigorous physical activity is beyond the scope of this report.

Management of Newly Diagnosed Type 2 Diabetes Mellitus (T2DM) in Children and Adolescents

Over the past 3 decades, the prevalence of childhood obesity 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. The rapid emergence of childhood T2DM poses challenges to many physicians who find themselves generally ill-equipped to treat adult diseases encountered in children. This clinical practice guideline was developed to provide evidence-based recommendations on managing 10- to 18-year-old patients in whom T2DM has been diagnosed. The American Academy of Pediatrics (AAP) convened a Subcommittee on Management of T2DM in Children and Adolescents with the support of the American Diabetes Association, the Pediatric Endocrine Society, the American Academy of Family Physicians, and the Academy of Nutrition and Dietetics (formerly the American Dietetic Association). These groups collaborated to develop an evidence report that served as a major source of information for these practice guideline recommendations. The guideline emphasizes the use of management modalities that have been shown to affect clinical outcomes in this pediatric population. Recommendations are made for situations in which either insulin or metformin is the preferred first-line treatment of children and adolescents with T2DM. The recommendations suggest integrating lifestyle modifications (ie, diet and exercise) in concert with medication rather than as an isolated initial treatment approach. Guidelines for frequency of monitoring hemoglobin A1c (HbA1c) and finger-stick blood glucose (BG) concentrations are presented. Decisions were made on the basis of a systematic grading of the quality of evidence and strength of recommendation. The clinical practice guideline underwent peer review before it was approved by the AAP. This clinical practice guideline is not intended to replace clinical judgment or establish a protocol for the care of all children with T2DM, and its recommendations may not provide the only appropriate approach to the management of children with T2DM. Providers should consult experts trained in the care of children and adolescents with T2DM when treatment goals are not met or when therapy with insulin is initiated. The AAP acknowledges that some primary care clinicians may not be confident of their ability to successfully treat T2DM in a child because of the child’s age, coexisting conditions, and/or other concerns. At any point at which a clinician feels he or she is not adequately trained or is uncertain about treatment, a referral to a pediatric medical subspecialist should be made. If a diagnosis of T2DM is made by a pediatric medical subspecialist, the primary care clinician should develop a comanagement strategy with the subspecialist to ensure that the child continues to receive appropriate care consistent with a medical home model in which the pediatrician partners with parents to ensure that all health needs are met.

Comparison of Parent-Only vs Family-Based Interventions for Overweight Children in Underserved Rural Settings: Outcomes From Project STORY

OBJECTIVE To assess the effectiveness of parent-only vs family-based interventions for pediatric weight management in underserved rural settings. DESIGN A 3-arm randomized controlled clinical trial. SETTING All sessions were conducted at Cooperative Extension Service offices in underserved rural counties. PARTICIPANTS Ninety-three overweight or obese children (8-14 years old) and their parent(s). INTERVENTION Families were randomized to (1) a behavioral family-based intervention, (2) a behavioral parent-only intervention, or (3) a wait-list control group. OUTCOME MEASURE The primary outcome measure was change in childrens standardized body mass index (BMI). RESULTS Seventy-one children completed posttreatment (month 4) and follow-up (month 10) assessments. At the month 4 assessment, children in the parent-only intervention demonstrated a greater decrease in BMI z score (mean difference [MD], 0.127; 95% confidence interval [CI], 0.027 to 0.226) than children in the control condition. No significant difference was found between the family-based intervention and the control condition (MD, 0.065; 95% CI, -0.027 to 0.158). At month 10 follow-up, children in the parent-only and family-based intervention groups demonstrated greater decreases in BMI z score from before treatment compared with those in the control group (MD, 0.115; 95% CI, 0.003 to 0.220; and MD, 0.136; 95% CI, 0.018 to 0.254, respectively). No difference was found in weight status change between the parent-only and family-based interventions at either assessment. CONCLUSIONS A parent-only intervention may be a viable and effective alternative to family-based treatment of childhood overweight. Cooperative Extension Service offices have the potential to serve as effective venues for the dissemination of obesity-related health promotion programs.

Impact of Psychosocial Factors on Quality of Life in Overweight Youth

Objective: The psychosocial functioning of overweight youth is a growing concern. Research has shown that overweight children report lower quality of life (QOL) than their non‐overweight peers. This study sought to extend the literature by examining the association between peer victimization, child depressive symptoms, parent distress, and health‐related QOL in overweight youth. Mediator models are used to assess the effect of child depressive symptoms on the relationship between psychosocial variables and QOL.