New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

GH safety workshop position paper: A critical appraisal of recombinant human GH therapy in children and adults

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-Term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-Term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

Objective The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations: Table 1

The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH)

Multiple forms of child maltreatment and abuse -specific characteristics: Relationships to psychological adjustment

This investigation examined the co-occurrence of various forms of maltreatment and maltreatment severity, as well as the interaction between these two variables, as possible contributors to adult adjustment difficulties. Participants included 1396 college students (1013 females and 383 males), who were recruited from undergraduate psychology classes. Respondents completed self-report, Web-based questionnaires [Computer Assisted Maltreatment Interview (CAMI); Trauma Symptom Checklist-40 (TSC-40)]. Participants were categorized based on the number of childhood maltreatment types and the severity of maltreatment experienced. The possible contributions of co-occurring maltreatment and abuse severity were examined with respect to trauma symptomatology among participants. Results indicate that 14% of the total sample experienced more than one type of child maltreatment and as expected, these participants generally reported experiencing greater levels of trauma symptomatology as the number of abuse types increased. Respondents who reported co-occurring maltreatment also generally experienced more severe individual types of abuse. Among participants reporting isolated abuse types, sexual abuse victims reported greater trauma symptomatology than did those who reported only physical abuse. Interestingly, participants reporting psychological abuse as their only maltreatment type reported higher levels of trauma symptoms than did respondents who experienced either physical abuse or neglect in isolation from all others. Results provided mixed support for the association between maltreatment severity and trauma symptomatology, as there was an interaction effect between severity and the number of abuse types with respect to adult adjustment. The implications of these findings are discussed with respect to research and clinical work with maltreatment populations

Unique and Combined Contributions of Multiple Child Abuse Types and Abuse Severity to Adult Trauma Symptomatology

Studies have documented the co-occurrence and cumulative impact of multiple types of child maltreatment on later psychosocial difficulties. Other research suggests that child abuse characteristics indicative of severity may also increase risk of later adjustment problems. However, little effort has been made to examine the co-occurrence of both multiple types of maltreatment and abuse severity within a single study. The present investigation examines self-reported child maltreatment and adult functioning in a geographically diverse sample of 1,396 undergraduate students. Results indicate that experiencing multiple types of maltreatment is positively associated with more severe abuse. Although increased maltreatment types and more severe abuse are each associated with greater trauma symptomatology, abuse severity is the stronger of the two predictors. Finally, number of maltreatment types and severity of maltreatment interact to predict greater levels of trauma symptomatology. These results highlight the importance of considering both co-occurring abuse types and severity in research and clinical work with adult victims

Fecal Transplantation for —“All Stool May Not Be Created Equal”

Clostridium difficile is a gram-positive bacterium that is recognized as a causative organism of pseudomembranous enterocolitis. This infection has become a major public health challenge and is a source of considerable morbidity and mortality in those infected. We present a 62-year-old African American female with a long history of HIV infection, who presented with abdominal pain and continuous diarrhea due to pseudomembranous colitis. After failing multiple episodes of conventional therapy, it was decided to treat her with fecal microbiota transplantation. Fecal microbiota transplantation was given on 3 separate occasions from a biological-related donor without success. It was only after a fourth transplant was done with a nonrelated donor that the patient resolved her diarrhea within 48 hours. We suggest that fecal samples from different donors have different abilities to cure Clostridium difficile colitis in at least this immunosuppressed patient