Limitations of the DiaRem Score in Predicting Remission of Diabetes Following Roux-En-Y Gastric Bypass (RYGB) in an ethnically Diverse Population from a Single Institution in the UK

Purpose This study aimed to determine the predictive power of the DiaRem score following Roux-en-Y gastric bypass to identify patients who would have diabetes remission at 1 year in an ethnically diverse population. Methods We performed a retrospective review of 262 patients with type 2 diabetes mellitus who underwent RYGB at the Imperial Weight Centre, UK, from 2007 to 2014. Data was collected on the parameters required to calculate the DiaRem score as well as pre- and post-surgical weight and the ethnicity of the subjects. Results The studied cohort was ethnically diverse (61.3 % Caucasian, 10.3 % Asian, 5.3 % black, 2.6 % mixed and 20.6 % other). At 1-year post-surgery, there were significant reductions in mean weight (133.4 to 94.3 kg) and BMI (46.7 to 33.3 kg/m2). The mean HbA1c decreased from 8.2 to 6.1 %, and 32.5 % of the cohort underwent either partial or complete remission. 67.8 % of the patients that were classified in group 1 of the DiaRem score (most likely to have remission) had complete remission. However, 22.9 % of the patients predicted to have the least chance of remission had either partial or complete remission. Conclusions In this ethnically diverse cohort, the DiaRem score remains a useful tool to predict diabetes remission in those that have a low DiaRem score (high chance for remission) but was more limited in its predictive power in those with a high DiaRem score (least likely to have remission). Caution must be used in the application of this model in populations other than the US white Caucasian population used to derive the score

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

The role of the aryl hydrocarbon receptor-interacting protein gene in familial

CONTEXT: Mutations have been identified in the aryl hydrocarbon receptor-interacting protein (AIP) gene in familial isolated pituitary adenomas (FIPA). It is not clear, however, how this molecular chaperone is involved in tumorigenesis. OBJECTIVE: AIP sequence changes and expression were studied in FIPA and sporadic adenomas. The function of normal and mutated AIP molecules was studied on cell proliferation and protein-protein interaction. Cellular and ultrastructural AIP localization was determined in pituitary cells. PATIENTS: Twenty-six FIPA kindreds and 85 sporadic pituitary adenoma patients were included in the study. RESULTS: Nine families harbored AIP mutations. Overexpression of wild-type AIP in TIG3 and HEK293 human fibroblast and GH3 pituitary cell lines dramatically reduced cell proliferation, whereas mutant AIP lost this ability. All the mutations led to a disruption of the protein-protein interaction between AIP and phosphodiesterase-4A5. In normal pituitary, AIP colocalizes exclusively with GH and prolactin, and it is found in association with the secretory vesicle, as shown by double-immunofluorescence and electron microscopy staining. In sporadic pituitary adenomas, however, AIP is expressed in all tumor types. In addition, whereas AIP is expressed in the secretory vesicle in GH-secreting tumors, similar to normal GH-secreting cells, in lactotroph, corticotroph, and nonfunctioning adenomas, it is localized to the cytoplasm and not in the secretory vesicles. CONCLUSIONS: Our functional evaluation of AIP mutations is consistent with a tumor-suppressor role for AIP and its involvement in familial acromegaly. The abnormal expression and subcellular localization of AIP in sporadic pituitary adenomas indicate deranged regulation of this protein during tumorigenesis

Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers.

Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease.This article is freely available via PubMed Central. Click on the 'Additional Link' above to access the full text