Hemoglobin A1c and Type 2 Diabetes Incidence Among Adolescents With Overweight and Obesity.

Importance: With the increase in prediabetes among adolescents with overweight and obesity, identifying those at highest risk for type 2 diabetes (T2D) can support prevention strategies. Objective: To assess T2D risk by hemoglobin A1c (HbA1c) levels among adolescents with overweight and obesity. Design, Setting, and Participants: This retrospective cohort study was conducted using data for January 1, 2010, to December 31, 2019, from a large California health care system. The study population comprised adolescents aged 10 to 17 years who had a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) at or above the 85th percentile, had HbA1c measured during 2010 to 2018, and did not have preexisting diabetes. Data abstraction and analyses were conducted from January 1, 2020, to November 16, 2023. Exposures: Baseline HbA1c, with covariates including BMI category (overweight: 85th to <95th percentile; moderate obesity: 100% to <120% of 95th percentile; or severe obesity: ≥120% of 95th percentile), age, sex, race and ethnicity, and Neighborhood Deprivation Index score. Main Outcomes and Measures: The main outcome was incident T2D during follow-up through 2019, including cumulative incidence and multivariable hazard ratios (HRs) with 95% CIs using Cox proportional hazard regression analyses. Results: This study included 74 552 adolescents with a mean (SD) age of 13.4 (2.3) years. More than half (50.6%) were female; 26.9% of individuals had overweight, 42.3% had moderate obesity, and 30.8% had severe obesity. Individuals identified as Asian or Pacific Islander (17.6%), Black (11.1%), Hispanic (43.6%), White (21.6%), and other or unknown race or ethnicity (6.1%). During follow-up, 698 adolescents (0.9%) developed diabetes, and 626 (89.7%) had T2D; 72 individuals (10.3%) who had type 1, secondary, or other diabetes were censored. The overall T2D incidence was 2.1 (95% CI, 1.9-2.3) per 1000 person-years, with a 5-year cumulative incidence of 1.0% (95% CI, 0.9%-1.1%). Higher baseline HbA1c (from <5.5% to 5.5%-5.6%, 5.7%-5.8%, 5.9%-6.0%, 6.1%-6.2%, and 6.3-6.4%) was associated with higher 5-year cumulative T2D incidence (from 0.3% [95% CI, 0.2%-0.4%] to 0.5% [0.4%-0.7%], 1.1% [0.8%-1.3%], 3.8% [3.2%-4.7%], 11.0% [8.9%-13.7%], and 28.5% [21.9%-36.5%], respectively). In addition, higher baseline HbA1c was associated with greater T2D risk (reference [HbA1c <5.5%]: HR, 1.7 [95% CI, 1.3-2.2], 2.8 [2.1-3.6], 9.3 [7.2-12.1], 23.3 [17.4-31.3], and 71.9 [51.1-101.1], respectively). Higher BMI category, older age, female sex, and Asian or Pacific Islander race (HR, 1.7 [95% CI, 1.3-2.2]), but not Black race or Hispanic ethnicity (compared with White race), were also independent indicators of T2D. In stratified analyses, incremental risk associated with higher HbA1c was greater for Asian or Pacific Islander and White adolescents than for Black and Hispanic adolescents. Conclusions and Relevance: In this cohort study of adolescents with overweight and obesity, T2D risk increased substantially with baseline HbA1c above 6.0%. Risk varied by BMI, age, sex, and race and ethnicity. These findings suggest that diabetes surveillance in adolescents should be tailored to optimize identification among high-risk subgroups.

Hypoglycemia in infants and children.

Our understanding of the many different causes of hypoglycemia has vastly expanded in recent years. Most hypoglycemic disorders in infants and children are due to defects in the metabolic systems involved in fasting adaptation or the hormone control of these systems. As a result of these defects, infants and children have an abnormal adaptation to fasting, which results in hypoglycemia. The "critical sample" allows one to assess the integrity of the fasting systems when hypoglycemic. An understanding of the pathophysiology of these disorders establishes a foundation for a rational approach in evaluating the etiology of the hypoglycemia and developing the most appropriate management plan.

Use of the recombinant human TSH stimulated thyroglobulin level and diagnostic whole body scan in children with differentiated thyroid carcinoma.

The recombinant human thyrotropin (TSH) (rhTSH) stimulated thyroglobulin (Tg) level is a useful tumor marker for disease surveillance in adults with differentiated thyroid carcinoma (DTC). We report our institution's experience using rhTSH in children. Seven children with DTC on thyroid hormone suppressive therapy after total thyroidectomy and radioablation received rhTSH (0.9 mg i.m.) on day 1 and 2. TSH rose to 224 +/- 93 mIU/l on day 2 and 13 +/- 5 mIU/l on day 5. Serum Tg level and diagnostic whole body radioiodine scan (DxWBS) were assessed on day 5. Five children were disease free: all had negative DxWBS; two had Tg < or = 2.1 ng/ml; two had anti-Tg antibodies; and one had no Tg measured. Two children had recurrent disease: one had a negative DxWBS and Tg of 15 ng/ml; and one had a positive DxWBS and no Tg measured. There were no adverse effects from rhTSH. These results suggest that rhTSH can be safely used for disease surveillance in children with DTC.

Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism.

OBJECTIVES: To characterize the clinical features and insulin regulation in infants with hypoglycemia due to prolonged neonatal hyperinsulinism. STUDY DESIGN: Data were collected on 26 infants with hypoglycemia due to neonatal hyperinsulinism that later resolved. Acute insulin response (AIR) tests to calcium, leucine, glucose, and tolbutamide were performed in 11 neonates. Results were compared to children with genetic hyperinsulinism due to mutations of the adenosine triphosphate-dependent potassium (K(ATP)) channel and glutamate dehydrogenase (GDH). RESULTS: Among the 26 neonates, there were significantly more males, small-for-gestational-age infants, and cesarean deliveries. Only 5 of the 26 had no identifiable risk factor. Hyperinsulinism was diagnosed at a median age of 13 days (range, 2 to 180 days) and resolved by a median age of 181 days (range, 18 to 403 days). Diazoxide was effective in 19 of the 21 neonates treated. In the 11 neonates tested, the AIRs to calcium, leucine, glucose, and tolbutamide resembled those in normal controls and differed from genetic hyperinsulinism due to K(ATP) channel and GDH mutations. CONCLUSIONS: We define a syndrome of prolonged neonatal hyperinsulinism that is responsive to diazoxide, persists for several months, and resolves spontaneously. AIR tests suggest that both the K(ATP) channel and GDH have normal function.