<p><strong>BACKGROUND: </strong>Due to high rates of comorbidities and rapid progression, youth with type 2 diabetes may benefit from early and aggressive treatment. However, until 2019, the only approved medications for this population were metformin and insulin.</p>

<p><strong>OBJECTIVE: </strong>To investigate patterns and predictors of treatment escalation within 5 years of metformin monotherapy initiation for youth with type 2 diabetes in clinical practice.</p>

<p><strong>SUBJECTS: </strong>Commercially-insured patients with incident youth-onset (10-18 years) type 2 diabetes initially treated with metformin only. METHODS: Retrospective cohort study using a patient-level medical claims database with data from 2000 - 2020. Frequency and order of treatment escalation to insulin and non-insulin antihyperglycemics were determined and categorized by age at diagnosis. Cox proportional hazards regression was used to evaluate potential predictors of treatment escalation, including age, sex, race/ethnicity, comorbidities, complications, and metformin adherence (medication possession ratio ≥0.8).</p>

<p><strong>RESULTS: </strong>The cohort included 829 (66% female; median age at diagnosis 15 years; 19% Hispanic, 17% Black) patients, with median 2.9-year follow-up after metformin initiation. One-quarter underwent treatment escalation (n=207; 88 to insulin, 164 to non-insulin antihyperglycemic). Younger patients were more likely to have insulin prescribed prior to other antihyperglycemics. Age at diagnosis (HR 1.14, 95% CI 1.07-1.21), medication adherence (HR 4.10, 95% CI 2.96-5.67), Hispanic ethnicity (HR 1.83, 95% CI 1.28-2.61), and diabetes-related complications (HR 1.78, 95% CI 1.15-2.74) were positively associated with treatment escalation.</p>

<p><strong>CONCLUSIONS: </strong>In clinical practice, treatment escalation for pediatric type 2 diabetes differs with age. Off-label use of non-insulin antihyperglycemics occurs, most commonly among older adolescents. This article is protected by copyright. All rights reserved.</p>

<p><strong>BACKGROUND: </strong>Risk-based screening for type 2 diabetes (T2D) in youth with overweight/obesity is recommended, but rates remain low in practice. Identification of factors impacting provider ordering and patient completion of testing may guide strategies to improve screening.</p>

<p><strong>OBJECTIVE: </strong>To evaluate predictors of hemoglobin A1c (A1c)-based T2D screening in pediatric primary care.</p>

<p><strong>METHODS: </strong>This retrospective cohort study included 10 to 18 year-old patients with overweight/obesity (body mass index [BMI] Z-score ≥1.04) followed in a large academic-affiliated pediatric primary care network, 2009 to 2018. Percentages of patients with ordered and completed A1c were determined, and multivariable Cox proportional hazards regression was used to evaluate independent predictors of screening.</p>

<p><strong>RESULTS: </strong>34 927 (48.0% female; 52.5% with BMI Z-score ≥1.64) youth followed for a median of 3.0 years were included. 21% (7457) of patients had screening ordered and 14% (4966) completed screening during follow-up. In multivariable regression, after controlling for race/ethnicity, BMI, family history of diabetes and age, males were significantly less likely to have ordered screening, but were equally or more likely to complete screening if ordered.</p>

<p><strong>CONCLUSIONS: </strong>Male adolescents were less likely to undergo A1c-based T2D screening due to differential ordering practices. The source of this differential practice should be pursued to avoid under-recognition of cardiometabolic risk in at-risk male youth.</p>

<p><strong>BACKGROUND: </strong>Prediabetes awareness in adults has been associated with improved weight management. Whether youth with prediabetes diagnosis experience similar improvements is unknown.</p>

<p><strong>OBJECTIVE: </strong>To investigate the association between prediabetes identification and body mass index trajectory in overweight and obese adolescents.</p>

<p><strong>SUBJECTS: </strong>Youth who were followed longitudinally in a large academic-affiliated primary care network and who were overweight/obese while 10-18 years old.</p>

<p><strong>METHODS: </strong>Retrospective cohort study. Subjects were categorized as "screened" if at least 1 hemoglobin A1c (HbA1c) result was available. Time series analysis was used to determine the difference in difference (DID) in body mass index Z-score (BMI-Z) slope before and after HbA1c between: 1) screened youth found to have prediabetes-range HbA1c (5.7-6.4%, 39-46 mmol/mol) versus normal HbA1c, and 2) screened versus age-matched unscreened obese youth.</p>

<p><strong>RESULTS: </strong>4,184 (55.6% female) screened subjects (median follow-up 9.7 years) were included. 637 (15.2%) had prediabetes-range HbA1c. Prediabetes was associated with a greater decrease in BMI-Z slope than normal HbA1c (DID: -0.023/year [95% CI: -0.042 to -0.004]). When compared to age-matched unscreened subjects (n=2,087), screened subjects (n=2,815) experienced a greater decrease in BMI-Z slope after HbA1c than unscreened subjects at a matched age (DID: -0.031/y [95% CI -0.042 to -0.021]).</p>

<p><strong>CONCLUSIONS: </strong>BMI-Z trajectory improved more among youth with prediabetes-range HbA1c but also stabilized in screened youth overall. Prospective studies are needed to identify provider- and patient-level drivers of this observation. This article is protected by copyright. All rights reserved.</p>

<p><strong>PURPOSE OF REVIEW: </strong>Because the incidence of type 2 diabetes and prediabetes in children is rising, routine screening of those at risk is recommended. In 2010, the ADA made the recommendation to include hemoglobin A1c (HbA1c) as a diagnostic test for diabetes, in addition to the oral glucose tolerance test or fasting plasma glucose. Our objective was to assess the pediatric literature with regard to HbA1c test performance and discuss advantages and disadvantages of use of the test for diagnostic purposes.</p>

<p><strong>RECENT FINDINGS: </strong>HbA1c has a number of advantages, including elimination of the need for fasting, lower variability, assay standardization, and long-term association with future development of diabetes. It also has many drawbacks. It can be affected by a number of non-glycemic factors, including red blood cell turnover, hemoglobinopathies, medications, race, and age. In particular, it performs differently in children compared with adults, generally with lower sensitivity for prediabetes (as low as 0-5% in children vs 23-27% in adults) and lower area under the receiver operating characteristic curve (AUC) (0.53 vs 0.73 for prediabetes), and it has lower efficacy at a higher cost, compared with other tests of glycemia. Finally, HbA1c may perform very differently across diverse populations according to race/ethnicity; in Chinese populations, the proportion of individuals classified with prediabetes based on HbA1c predominates compared with IFG (77% for HbA1c vs 27.7% for IFG), whereas in US populations, it is the opposite (24.8% for HbA1c vs 80.1% for FPG). HbA1c is controversial because although it is convenient, it is not a true measure of glycemia. The interpretation of HbA1c results requires a nuanced understanding that many primary care physicians who are ordering the test in greater numbers do not possess. Alternative markers of glycemia may hold promise for the future but are not yet endorsed for use in practice. Further studies are needed to determine appropriate thresholds for screening tests and the long-term impact of screening and identification.</p>