Type 2 diabetes is increasingly diagnosed in obese children and adolescents. Evidence suggests that this disease commonly progresses more rapidly in youth compared to 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 three treatment approaches in new onset type 2 diabetes in obese youth (n=699; ages 10–17): monotherapy with metformin, metformin with roziglitazone, 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 were unable to maintain glycemic control using metformin alone. Combination therapy of metformin with rosiglitazone resulted in better durability of glycemic control, and the metformin plus intensive lifestyle 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 BMI. After 3.9 years, 33.8% of participants had hypertension and 16.6% had microalbuminuria. Only 55.9% of participants had an LDL-cholesterol <100 mg/dl after 3 years and 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.

Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM.

OBJECTIVE : To examine associations of sleep duration and regularity with dietary intake and eating-related cognitions among adolescents who are overweight/obese.  METHODS : Participants were 315 adolescents being evaluated through Healthy Kids, Healthy Weight. Outcomes were reported sleep duration and regularity (bedtime shift, wake-time shift, sleep duration shift). Major predictors were dietary intake (e.g., consumption of calories and sugar-sweetened beverages) and eating-related cognitions (food preoccupation, eating self-efficacy).  RESULTS : Findings were that staying up (i.e., bedtime shift) and sleeping in later (i.e., wake-time shift) on weekends compared with weekdays significantly relates to drinking more sugar-sweetened beverages, the latter for males. Sleeping in on weekends was related to greater food preoccupation.  CONCLUSIONS : Sleep regularity was the most important variable in its relationships with dietary intake. Evaluating sleep patterns and improving them with behavioral interventions should be considered as an additional weight loss strategy to promote dietary adherence.

OBJECTIVEData 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 METHODSObese 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.RESULTSGastrointestinal (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.CONCLUSIONSThe 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.

Objective To understand the factors associated with glycemic control after starting insulin in youth with type 2 diabetes following glycemic failure (persistent HbA1c ≥8%) with metformin alone, metformin + rosiglitazone or metformin + lifestyle in the TODAY study. Methods Change in HbA1c after add‐on insulin therapy and the factors predictive of glycemic response were evaluated. At 1‐year postinsulin initiation, 253 youth had a mean of 3.9 ± 1.0 visits since the time of insulin initiation. Participants were divided into three groups according to glycemic control: consistent decrease in HbA1c by ≥0.5%, change <0.5%, or consistent increase in HbA1c ≥0.5%, at 75% or more of the visits. Results Within 1‐year postinsulin initiation, 33.2% of participants had a consistent HbA1c decrease of ≥0.5%, 46.2% changed HbA1c <0.5%, and 20.6% had an increase ≥0.5%. At randomization into TODAY and at time of insulin initiation, the three glycemia groups were similar in age, sex, race‐ethnicity, pubertal stage, BMI z‐score, diabetes duration, and insulin secretion indices. Consistent HbA1c improvement was associated with higher insulin sensitivity (1/fasting insulin) at randomization and at time of failure, higher adiponectin at randomization, and was not associated with indices of β‐cell function. Conclusions Response to add‐on insulin was highly variable among youth in TODAY. Greater insulin sensitivity and higher adiponectin concentrations at randomization were associated with improved glycemic control after initiation of insulin. Due to limited information on adherence to insulin injections, the roles of adherence to the prescribed insulin regimen or psychosocial factors are unknown.