Sex hormone-binding globulin (SHBG) has emerged as one of the multiple genetic and environmental factors that potentially contribute to the pathophysiology of Type 2 diabetes mellitus (T2DM). In addition to epidemiologic studies demonstrating a consistent relationship between decreased levels of serum SHBG and incident T2DM, recent genetic studies also reveal that transmission of specific polymorphisms in the SHBG gene influence risk of T2DM. On the molecular level, elucidation of the multiple interactions between SHBG and its receptors in various target tissues, suggest physiologic roles for SHBG that are more complex than the simple transport of sex hormones in serum. Taken together, these data provide support for an expanded role of SHBG in the pathophysiology of insulin resistance and T2DM.

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Bone disease is a frequent complication in adolescents and adults with cystic fibrosis (CF). Early detection and monitoring of bone mineral density and multidisciplinary preventive care are necessary from childhood through adolescence to minimize CF-related bone disease (CFBD) in adult CF patients. Approaches to optimizing bone health include ensuring adequate nutrition, particularly intake of calcium and vitamins D and K, addressing other secondary causes of low bone density such as hypogonadism, encouraging weight bearing exercise, and avoiding bone toxic medications. Of the currently available anti-resorptive or anabolic osteoporosis medications, only bisphosphonates have been studied in individuals with CF. Future studies are needed to better understand the optimal approach for managing CFBD.

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Aims: Human placental lactogen (hPL) acts via the prolactin receptor (PRLR) on maternal b-cells to mediate increases in b-cell mass and function during normal pregnancy. This interaction between hPL and PRLR is essential to maintain normal glucose homeostasis and to address the increased metabolic demands of pregnancy. Given the importance of the PRLR-hPL axis in pancreatic islet cell adaptation to pregnancy, we hypothesized that genetic variation in the PRLR gene could influence risk of development of gestational diabetes mellitus (GDM). DNA samples from 96 mothers affected by GDM and 96 unaffected cases were genotyped for 8 selected single nucleotide polymorphisms (SNPs) in PRLR. Results: Significant associations were identified in two SNPs analyzed. The minor alleles of PRLR SNPs rs10068521 and rs9292578 were more frequently observed in GDM cases than controls and were associated with a 2.36-fold increased risk for GDM in those carrying the minor allele. Conclusion: SNPs of the PRLR gene 5¢ UTR and promoter region are associated with increased risk for GDM in a population of Chilean subjects.

The 2q37 deletion syndrome, also described in the literature as brachydactyly-mental retardation syndrome (MIM 600430), is caused by deletion or haploinsufficiency of the HDAC4 gene, which encodes the histone deacetylase 4 protein. Although the most commonly described hallmark features of the 2q37 deletion syndrome include brachydactyly type E, developmental delay, obesity, autistic features, and craniofacial or skeletal dysmorphism, a literature review of 101 published cases plus two newly reported individuals indicates that there is a high degree of variability in the presence of some of the features that are considered the most characteristic of the syndrome: overweight and obesity (34%), cognitive-behavioral issues (79%), dysmorphic craniofacial features (86%), and type E brachydactyly (48%). These features overlap with other neurodevelopmental conditions, including Smith-Magenis syndrome (SMS), and may be incompletely penetrant or demonstrate variable expressivity, depending on the specific chromosomal anomaly. With the advent of fluorescence in situ hybridization (FISH), array-based comparative genomic hybridization, and next-generation DNA sequencing, more detailed molecular diagnoses are possible than in years past, enabling refined characterization of the genotype-phenotype correlation for subjects with 2q37 deletions. In addition, investigations into molecular and gene expression networks are expanding in neurodevelopmental conditions, and we surveyed HDAC4 downstream gene expression by quantitative real-time polymerase chain reaction, further implicating HDAC4 in its role in the regulation of RAI1. Correlation of clinical data defining the impact on downstream gene expression and the potential clinical associations across neurodevelopment will improve our understanding of these complex conditions and potentially lead to common therapeutic approaches. K E Y W O R D Sautism spectrum disorder, behavioral disturbances, brachydactyly type E, developmental delay, HDAC4, obesity

Poor growth has long been a characteristic feature of cystic fibrosis (CF) and is significantly linked to lung function and overall health status. Improvements in pulmonary and nutrition care for patients with cystic fibrosis (CF) have resulted in better growth outcomes; however, height gains have not paralleled the improvements in weight in children with CF, and patients with more severe CF mutations remain significantly more affected. Many factors affect the growth hormone-IGF-1 axis and the growth plate of the long bones, including the chronic inflammatory state associated with CF. There are also increasing data on the direct effects of CFTR on bone and implications for CFTR modulators in attaining optimal growth. Treatments aimed at improving growth in CF are also reviewed here.

Eating disorders and disturbed body image have been reported in individuals with cystic fibrosis (CF) and may contribute to poor weight gain, reduced lung function and increased mortality. CF individuals often look and feel different from their peers and bear the additional burden of body-altering side effects of treatment. As a result, the impact of disorders such as binge eating, anorexia nervosa, and bulimia nervosa may adversely affect the social, emotional, and physical development of those with CF. Multiple risk factors may contribute to the development of an eating disorder in CF. Growth failure is affected by the physical impairments of CF, including pancreatic insufficiency, high energy demands, respiratory infections, and delayed and stunted growth and puberty. Psychological factors, such as CF associated depression and anxiety, intense focus on BMI, lack of control in a chronic disease, and preoccupation with morbidity and mortality, likely further contribute. Exercise inefficiency, secondary to poor lung function, low BMI and pulmonary exacerbations, and the potential for medication manipulation are also additional risk factors. The intense scrutiny around BMI may lead to a poor relationship with food, including disordered eating habits, abnormal mealtime behaviors, and stressful caregiver-patient interactions regarding meals. This further contributes to a discrepancy between ideal CF nutritional standards and the reality of the challenges of appropriate daily energy intake for an individual with CF. It is imperative that CF providers are equipped to identify potential eating disorders and disturbed body image in their CF patients. Improved screening and monitoring practices should be developed and implemented, with multidisciplinary support from all CF care team members, including dietitians, mental health professionals, and social workers, to best support holistic care and optimize outcomes. Increased attention to these concerns may help reduce CF related morbidity and mortality.