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To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly.

We introduce a new approach for automated guideline-based-care quality assessment, the bidirectional knowledge-based assessment of compliance (BiKBAC) method, and the DiscovErr system, which implements it. Our methodology compares the guideline's Asbru-based formal representation, including its intentions, with the longitudinal medical record, using a top-down and bottom-up approach. Partial matches are resolved using fuzzy temporal logic. The system was evaluated in the type 2 Diabetes management domain, comparing it to three expert clinicians, including two diabetes experts. The system and the experts commented on the management of 10 patients, randomly selected from 2,000 diabetes patients. On average, each record spanned 5.23 years; the data included 1,584 medical transactions. The system provided 279 comments. The experts made 181 different unique comments. The completeness (recall) of the system was 91% when the gold standard was comments made by at least two of the three experts, and 98%, compared to comments made by all three experts. The experts also assessed all of the 114 medication-therapy-related comments, and a random 35% of the 165 tests-and-monitoring-related comments. The system's correctness (precision) was 81%, compared to comments judged as correct by both diabetes experts, and 91%, compared to comments judged as correct by one diabetes expert and at least as partially correct by the other. 89% of the comments were judged as important by both diabetes experts, 8% were judged as important by one expert, and 3% were judged as less important by both experts. Adding the validated system comments to the experts' comments, the completeness scores of the experts were 75%, 60%, and 55%; the expert correctness scores were respectively 99%, 91%, and 88%. Thus, the system could be ranked first in completeness and second in correctness. We conclude that systems such as DiscovErr can effectively assess the quality of continuous guideline-based care. [ABSTRACT FROM AUTHOR]