Sulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis.

Circulating insulin-like growth factor 1 (IGF-1) has been shown to act as a negative feedback regulator of growth hormone (GH) gene expression; however, the mechanism of this negative feedback is poorly understood. Activation and regulation of GH gene expression require the binding of the transcription factor POU1F1 to the GH promoter along with cyclic AMP (cAMP) response element binding protein (CREB) binding protein (CBP). We investigate the role of CBP as a target of IGF-1 somatotroph regulation using the MtT/S somatotroph cell line. IGF-1 significantly inhibits basal GH mRNA levels but not POU1F1 levels. Chromatin immunoprecipitation assays demonstrate inhibition of CBP binding to the GH promoter after IGF-1 treatment. We hypothesized that IGF-1 receptor (IGF-1R) signaling disrupts the POU1F1/CBP complex to inhibit gene expression. In support, the use of a mutant CBP (S436A) construct, which lacks a critical phosphorylation site, leads to the loss of IGF-1 inhibition. The studies of CBP (S436A) knock-in mice show elevated serum GH levels, a greater response to GH releasing hormone (GHRH) stimulation along with lower weight gain, and decreased body fat. Our data confirm the inhibitory effects of IGF-1 on GH expression at the level of the promoter and provide evidence of CBP's role as a target of IGF-1R signaling.T he regulation of growth hormone (GH) is primarily influenced by the antagonistic actions of the hypothalamic hormones growth hormone releasing hormone (GHRH) and somatostatin (SRIF); however, it also well documented that the release of GH may be influenced by other factors and proteins produced both centrally and peripherally (2,5,8,14,45,47). Insulin-like growth factor 1 (IGF-1), which is produced primarily in the liver under the direct influence of GH, has an important role in not only somatic growth and metabolism but also negative feedback of GH release by targeting both the hypothalamus and pituitary (7,22,39,43). Several in vitro studies have demonstrated the ability of IGF-1 to decrease GH gene expression and hormone release (33,40,(52)(53)(54). Furthermore, transgenic animals with perturbations in the GH axis also demonstrate IGF-1's direct and indirect roles in regulation of the somatotroph (27,30,35,49,51). IGF-1R is a heterotetrameric glycoprotein comprised of two extracellular alpha subunits, which bind IGF-1, and two transmembrane beta subunits, which contain tyrosine kinase activity (13,22). Upon ligand binding to the receptor, two major pathways, the Ras/Raf/ mitogen-activated protein (MAP) kinase and the phosphatidylinositol 3-kinase (PI3 kinase) pathway, have been shown to play a role in mediating IGF-1 responses (16,17,24,26).Although in vitro and in vivo studies of IGF-1 negative feedback have proposed specific targets that ultimately affect GH expression and release, a mechanism of regulation at the cellular level remains unclear. We chose to first study IGF-1 regulation using an in vitro approach with the MtT/S cell line, which is an established rat tumor somatotroph cell line t...

Objective Both youth self-regulation and quality of parental involvement have been associated with blood glucose levels (HbA1c) of youth with type 1 diabetes mellitus (T1DM). However, it is unclear whether and how youth and parental factors interact in their relation to youth HbA1c. The differential susceptibility hypothesis proposes that youth with high negative affectivity (NA) and low effortful control (EC) may be more susceptible to the deleterious impact of lower quality parenting behaviors but also reap greater benefit from higher quality parenting behaviors. This study investigated whether youth temperament would moderate the link between diabetes-specific parental assistance (e.g., checking blood sugar) or support (e.g., encouraging, praising) and HbA1c among youth with T1DM. Methods Primary caregivers of youth with T1DM (N = 101; M age = 12.02, SD = 2.43) completed surveys on diabetes-specific parental involvement and youth temperament. Medical information (i.e., HbA1c) was obtained from chart review. Results Multiple regression analyses indicated that youth NA and EC significantly interacted with parental assistance, but not support. Specifically, higher parental assistance was associated with higher HbA1c among youth with high NA or high EC. High assistance was only linked to lower HbA1c for youth with low NA. Conclusions Results suggest that optimal levels of parental involvement related to better T1DM outcomes depend on youth’s NA or EC. Consistent with the goodness-of-fit framework, when parenting approaches match youth’s temperament, youth with T1DM may be better able to maintain lower HbA1c. Family interventions for pediatric T1DM management may take into consideration youth temperament.

Objective: Positive parenting (e.g., parental warmth, mindful parenting) has been posited to promote effective pediatric type 1 diabetes mellitus (T1DM) management. This promotive effect may partly be conferred by fostering child self-regulatory development, such as executive function (EF). However, no research has examined whether better child EF serves as a mechanism underlying associations between positive parenting and child blood glucose levels (HbA1c). Moreover, it is unclear whether mindful parenting offers a unique benefit beyond that of parental warmth-a key pillar of effective parental involvement in T1DM management. Methods: Primary caregivers of children with T1DM (N 5 101; Mage 5 12.02) reported on parenting behaviors and child EF. Children's medical information was obtained through chart review. Path analysis was used to examine direct and indirect relations in the cross-sectional data. Results: The path analysis indicated that only parental warmth, not mindful parenting, was significantly associated with lower HbA1c. Both parental warmth and mindful parenting were significantly related to better child EF, but child EF did not mediate the associations between parenting and HbA1c. Conclusion: Parental warmth may constitute a key parenting behavior promoting effective pediatric T1DM management. Enhancing parental warmth may be an important target of interventions aiming to improve HbA1c. Although child EF was unrelated to HbA1c in this sample, given positive associations between parental warmth and mindfulness and child EF, longitudinal research is warranted to examine whether these positive parenting behaviors may confer long-term benefits for T1DM self-management through improved EF.