Sumana Narasimhan

Youth-Onset Type 2 Diabetes Mellitus: Lessons Learned From the TODAY Study

Type 2 diabetes mellitus is increasingly diagnosed in obese children and adolescents. Evidence suggests that this disease commonly progresses more rapidly in youth compared with adults and is associated with high rates of early microalbuminuria, hypertension, and dyslipidemia. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study was the first multiethnic, multicenter randomized trial in the United States to compare 3 treatment approaches in obese youth with new-onset type 2 diabetes (n=699; ages 10-17 years): monotherapy with metformin, metformin with rosiglitazone, and metformin with an intensive lifestyle intervention. The primary outcome was glycemic control. Diabetes-related complications and cardiovascular risk factors were also examined. Approximately half of the participants could not maintain glycemic control by using metformin alone. Combination therapy with metformin and rosiglitazone resulted in better durability of glycemic control, and metformin plus intensive lifestyle intervention was intermediate but not superior to metformin alone. Deterioration in glycemic control was associated with rapid loss of beta cell function, not worsened insulin sensitivity, and could not be explained by differences in adherence or body mass index. After 3.9 years, 236 (33.8%) of participants had hypertension and 116 participants (16.6%) had microalbuminuria. Only 55.9% of participants had a low-density lipoprotein cholesterol level less than 100 mg/dL (to convert to mmol/L, multiply by 0.0259) after 3 years, and 71 of 517 participants (13.7%) had retinopathy. The significance of the findings from this important trial for the management of youth and young adults with youth-onset type 2 diabetes and its complications is discussed. An aggressive multifaceted approach is needed to prevent or forestall premature microvascular and macrovascular complications in youth-onset type 2 diabetes.

Safety and tolerability of the treatment of youth-onset type 2 diabetes: The TODAY experience

OBJECTIVE Data related to the safety and tolerability of treatments for pediatric type 2 diabetes are limited. The TODAY clinical trial assessed severe adverse events (SAEs) and targeted nonsevere adverse events (AEs) before and after treatment failure, which was the primary outcome (PO). RESEARCH DESIGN AND METHODS Obese 10- to 17-year-olds (N = 699) with type 2 diabetes for <2 years and hemoglobin A1c (A1C) ≤8% on metformin monotherapy were randomized to one of three treatments: metformin, metformin plus rosiglitazone (M + R), or metformin plus lifestyle program (M + L). Participants were followed for 2–6.5 years. RESULTS Gastrointestinal (GI) disturbance was the most common AE (41%) and was lower in the M + R group (P = 0.018). Other common AEs included anemia (20% before PO, 14% after PO), abnormal liver transaminases (16, 15%), excessive weight gain (7, 9%), and psychological events (10, 18%); the AEs were similar across treatments. Permanent medication reductions/discontinuations occurred most often because of abnormal liver transaminases and were lowest in the M + R group (P = 0.005). Treatment-emergent SAEs were uncommon and similar across treatments. Most (98%) were unrelated or unlikely related to the study intervention. There were no deaths and only 18 targeted SAEs (diabetic ketoacidosis, n = 12; severe hypoglycemia, n = 5; lactic acidosis, n = 1). There were 62 pregnancies occurring in 45 participants, and 6 infants had congenital anomalies. CONCLUSIONS The TODAY study represents extensive experience managing type 2 diabetes in youth and found that the three treatment approaches were generally safe and well tolerated. Adding rosiglitazone to metformin may reduce GI side effects and hepatotoxicity.

Idiopathic Short Stature: Decision Making in Growth Hormone Use

Short stature is a common concern in pediatrics. Several ambiguities and controversies persist, especially with regard to criteria, cost, medical necessity and outcomes of growth hormone (GH) therapy for idiopathic short stature (ISS). Due to these ambiguities and controversies, a series of decisions by primary care physicians (whether to refer the short child to a pediatric endocrinologist), pediatric endocrinologist (whether to recommend GH treatment), families (whether to raise concern about short stature and whether to agree to undertake treatment), and third party payers (whether to cover the costs of GH therapy) influence which individual short children will receive GH in the US. Together, these decisions determine overall GH use. Apart from child’s growth characteristics, several non-physiological factors drive the critical decisions of these stakeholders. This article focuses on current ambiguities and controversies regarding GH therapy in ISS, discusses the decision-makers involved in GH therapy, and explores the factors influencing their decisions.

Physical Activity Self-Efficacy and Fitness: Family Environment Relationship Correlates and Self-Esteem as a Mediator among Adolescents Who Are Overweight or Obese

BACKGROUND Little is known regarding how dimensions of the family social environment relate to fitness levels and physical activity self-efficacy (PASE) among adolescents who are overweight or obese and whether these relationships are mediated by self-esteem. METHODS Potential associations were evaluated between relationship subdomains (cohesion, conflict, expressivity) of the Family Environment Scale (FES), self-esteem (Rosenberg Self-Esteem Scale, RSES), and PASE and fitness, using recovery heart rate [RHR, beats per minute (bpm)] from a 3-minute submaximal step test at baseline. Participants were 108 adolescents who were overweight or obese and were seeking weight-loss treatment as part of the Healthy Kids, Healthy Weight 12-week multidisciplinary pediatric weight management program. Structural equation modeling (SEM) was used to simultaneously evaluate paths between these variables and test for mediation. RESULTS In multivariable models, higher FES cohesion (β = -2.18, s.e. = 0.98; p = 0.02), expressivity (β = -1.97, s.e. = 0.99; p < 0.05), and PASE (β = -0.64, s.e. = 0.33; p < 0.05) scores were associated with lower RHR, which represents higher fitness. Furthermore, higher FES conflict scores were associated with lower RSES scores (β = -0.83, s.e. = 0.29; p < 0.01), and FES conflict (β = -0.63, s.e. = 0.22; p < 0.01) and RSES (β = 0.33, s.e. = 0.07; p < 0.01) were associated with PASE scores. In a good-fitting multivariate SEM [Comparative Fit Index (CFI) = 1.00; Standardized Root Mean Square Residual (SRMR) = 0.02; Tucker-Lewis index (TLI) = 1.22; Root Mean Squared Error of Approximation (RMSEA) <0.01], RSES mediated the relationship between FES conflict and PASE (sum of indirect paths: β = -0.30, s.e. = 0.11; p < 0.01) scores. CONCLUSIONS Our results highlight the importance of the relationship domain of the family environment on self-esteem, PASE, and physical fitness in adolescents who are overweight or obese.