Abstract
We provide an in-depth review of the role of androgens in male maturation and development, from the fetal stage through adolescence into emerging adulthood, and discuss the treatment of ...disorders of androgen production throughout these time periods. Testosterone, the primary androgen produced by males, has both anabolic and androgenic effects. Androgen exposure induces virilization and anabolic body composition changes during fetal development, influences growth and virilization during infancy, and stimulates development of secondary sexual characteristics, growth acceleration, bone mass accrual, and alterations of body composition during puberty.
Disorders of androgen production may be subdivided into hypo- or hypergonadotropic hypogonadism. Hypogonadotropic hypogonadism may be either congenital or acquired (resulting from cranial radiation, trauma, or less common causes). Hypergonadotropic hypogonadism occurs in males with Klinefelter syndrome and may occur in response to pelvic radiation, certain chemotherapeutic agents, and less common causes. These disorders all require testosterone replacement therapy during pubertal maturation and many require lifelong replacement.
Androgen (or gonadotropin) therapy is clearly beneficial in those with persistent hypogonadism and self-limited delayed puberty and is now widely used in transgender male adolescents. With more widespread use and newer formulations approved for adults, data from long-term randomized placebo-controlled trials are needed to enable pediatricians to identify the optimal age of initiation, route of administration, and dosing frequency to address the unique needs of their patients.
Graphical Abstract
Graphical Abstract
A closed-loop system (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes. In this 16-week trial, the glucose level was in the target range for a ...greater percentage of time with a closed-loop system than with a sensor-augmented insulin pump.
Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk for long-term complications and creating an immense management burden for caregivers. We ...conducted the first evaluation of the Omnipod 5 Automated Insulin Delivery System in this population.
A total of 80 children aged 2.0-5.9 years used the investigational system in a single-arm study for 13 weeks following 14 days of baseline data collection with their usual therapy.
There were no episodes of severe hypoglycemia or diabetic ketoacidosis. By study end, HbA1c decreased by 0.55% (6.0 mmol/mol) (P < 0.0001). Time with sensor glucose levels in target range 70-180 mg/dL increased by 10.9%, or 2.6 h/day (P < 0.0001), while time with levels <70 mg/dL declined by median 0.27% (P = 0.0204).
Use of the automated insulin delivery system was safe, and participants experienced improved glycemic measures and reduced hypoglycemia during the study phase compared with baseline.
Hybrid closed-loop systems increase time-in-range (TIR) and reduce glycemic variability. Person-reported outcomes (PROs) are essential to assess the utility of new devices and their impact on quality ...of life. This article focuses on the PROs for pediatric participants (ages 6-13 years) with type 1 diabetes (T1D) and their parents during a trial using the Tandem Control-IQ system, which was shown to increase TIR and improve other glycemic metrics.
One hundred and one children 6 to 13 years old with T1D were randomly assigned to closed-loop control (CLC) or sensor-augmented pump (SAP) in a 16-week randomized clinical trial with extension to 28 weeks during which the SAP group crossed over to CLC. Health-related quality of life and treatment satisfaction measures were obtained from children and their parents at baseline, 16 weeks, and 28 weeks.
Neither the children in the CLC group nor their parents had statistically significant changes in PRO outcomes compared with the SAP group at the end of the 16-week randomized controlled trial and the 28-week extension. Parents in the CLC group reported nonsignificant improvements in some PRO scores when compared with the SAP group at 16 weeks, which were sustained at 28 weeks. Sleep scores for parents improved from "poor sleep quality" to "adequate sleep quality" between baseline and 16 weeks, however, the change in scores was not statistically different between groups.
Children with T1D who used the Control-IQ system did not experience increased burden compared with those using SAP based on person-reported outcomes from the children and their parents. Clinical Trials Registration: NCT03844789.
We assessed predictors of rising hemoglobin A1c (HbA1c) during long-term use of closed-loop control (CLC) in children aged 6-13 years with type 1 diabetes. Participants used a CLC system during a ...16-week randomization phase followed by a 12-week extension phase. We compared an "Increased-HbA1c" group (
= 17, ≥0.5% rise in HbA1c between randomization and extension phases) to a "Maintained-Improvement" group (
= 18, had stable or improved HbA1c). The Increased-HbA1c group had higher pre-CLC HbA1c (8.42% ± 0.80 vs. 7.45% ± 0.93,
= 0.002). Contrary to a-priori hypotheses, there were no differences in Δ-height-for-age
-score, a surrogate for a pubertal growth spurt (+0.16 vs. -0.15,
= 0.113), or number of carbohydrate boluses per day, a surrogate for missed boluses (4.4 ± 2.2 vs. 5.2 ± 2.1,
= 0.263). Both groups maintained high rates in closed-loop. Thus, some children exhibit meaningful rise in HbA1c after initial CLC use, likely from multiple contributing factors, and may benefit from added encouragement during ongoing use.
Glycemic control is particularly challenging for toddlers and preschoolers with type 1 diabetes (T1D), and data on the use of closed-loop systems in this age range are limited.
We studied use of a ...modified investigational version of the Tandem t:slim X2 Control-IQ system in children aged 2 to 5 years during 48 h in an outpatient supervised hotel (SH) setting followed by 3 days of home use to examine the safety of this system in young children. Meals and snacks were not restricted and boluses were estimated per parents' usual routine. At least 30 min of daily exercise was required during the SH phase. All participants were remotely monitored by study staff while on closed-loop in addition to monitoring by at least one parent throughout the study.
Twelve participants diagnosed with T1D for at least 3 months with mean age 4.7 ± 1.0 years (range 2.0-5.8 years) and hemoglobin A1c of 7.3% ± 0.8% were enrolled at three sites. With use of Control-IQ, the percentage of participants meeting our prespecified goals of less than 6% time below 70 mg/dL and less than 40% time above 180 mg/dL increased from 33% to 83%. Control-IQ use significantly improved percent time in range (70-180 mg/dL) compared to baseline (71.3 ± 12.5 vs. 63.7 ± 15.1,
= 0.016). All participants completed the study with no adverse events.
In this brief pilot study, use of the modified Control-IQ system was safe in 2-5-year-old children with T1D and improved glycemic control.
Background
Data on the use of Control‐IQ, the latest FDA‐approved automated insulin delivery (AID) system for people with T1D 6 years of age or older is still scarce, particularly regarding ...nonglycemic outcomes. Children with T1D and their parents are at higher risk for sleep disturbances. This study assesses sleep, psycho‐behavioral and glycemic outcomes of AID compared to sensor‐augmented pump therapy (SAP) therapy in young children with T1D and their parents.
Methods
Thirteen parents and their young children (ages 7–10) on insulin pump therapy were enrolled. Children completed an initial 4‐week study with SAP using their own pump and a study CGM followed by a 4‐week phase of AID. Sleep outcomes for parents and children were evaluated through actigraphy watches. Several questionnaires were administered at baseline and at the end of each study phase. CGM data were used to assess glycemic outcomes.
Results
Actigraphy data did not show any significant change from SAP to AID, except a reduction of number of parental awakenings during the night (p = 0.036). Parents reported statistically significant improvements in Pittsburgh Sleep Quality Index total score (p = 0.009), Hypoglycemia Fear Survey total score (p = 0.011), diabetes‐related distress (p = 0.032), and depression (p = 0.023). While on AID, time in range (70–180 mg/dL) significantly increased compared to SAP (p < 0.001), accompanied by a reduction in hyperglycemia (p = 0.001).
Conclusions
These results suggest that use of AID has a positive impact on glycemic outcomes in young children as well as sleep and diabetes‐specific quality of life outcomes in their parents.
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