Search

Introduction: Defects in fat processing, in particular non-esterified fatty acids (NEFA), may hold the link between obesity, hyperlipidaemia, insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The secretion of insulin, more effective at inhibiting lipolysis than glucose production, is inhibited by high NEFA levels. I hypothesised that postprandial hormone alterations following Roux-en-Y gastric bypass (RYGB) improve adipocyte insulin sensitivity through the peripheral effects of incretins. Methods: Participants with T2DM (n=9) and without T2DM [NDM] (n=10) underwent RYGB for morbid obesity. Fasting and postprandial blood was analysed for glycaemic, lipidaemic and gut hormones changes around surgery. Intra-operatively, adipose tissue biopsies were taken and lipolysis assessed during a 2hr incubation with pre- and post-RYGB plasma and relevant hormonal concentrations. Results: By post-operative day 4, there were improvements in IR (p<0.0001) and reduced fasting insulin levels (p=0.0017) despite no reduction in postprandial insulin (p=0.6714). Fasting NEFA levels were reduced in NDM (p<0.05) but not in the T2DM group (p=0.0816), whilst postprandial NEFA (∆AUC [360min]) reduced in the T2DM group (p<0.0001) but not in the NDM group (p=0.4111), ANOVA p<0.05. Significant changes in gut hormone levels around RYGB were noted, in fasting: reduced GIP (p=0.0079), PYY (p=0.0066) and ghrelin levels (p=0.0005); post-prandial: increased GLP-1 (p=0.0018) and PYY levels (p<0.0001); reduced GIP (p=0.0318) and ghrelin levels (p=0.0004). Incubation of adipocytes in both fasting and postprandial plasma post-RYGB resulted in increased lipolysis versus pre-RYGB plasma (peripheral p=0.0235 and p=0.0205, respectively [n=8]). Insulin and PYY inhibited lipolysis but no effect of GLP-1, GIP and ghrelin on lipolysis was detected. Conclusions: Although likely that postprandial hormonal alterations improve adipocyte lipolysis through their peripheral effects, it is most likely the global reduction in insulin levels, thereby reducing the anti-lipolytic effect, combined with overall improvements in IR, responsible for these findings and not the peripheral effects of incretins.

Background: Papillary Thyroid Cancer (PTC) is a common endocrine cancer which metastases to the cervical lymph nodes (LN). The frequency of metastasis is poorly defined. The imaging modalities commonly employed to detect these metastases have limitations. The aim of this study was to define the extent of cervical LN metastases, the role of imaging in their detection and to determine long term outcomes. Design and Methods: The study was designed in two parts. A. Systematic reviews of incidence of cervical LN metastases in PTC and the use of imaging modalities in detection of these LN. B. Retrospective Cohort Study of PTC patients: Data from three centres in London over the last 9 years was collected and analysed. Results: I. Systematic reviews: A. Central LN Dissection (LND): 21 studies provided data for 4188 patients. Among patients who underwent prophylactic central LND (pCLND), 772 had positive central LN (44.8 %). B. Lateral LND: 19 studies provided data for 5587 patients. Out of 2048 patients who underwent pLLND, 1177 were found to have positive lateral LNs (57.5%). C. Imaging of metastatic cervical LN Ultrasound: The sensitivity to detect central and lateral cervical LN was 38.4% and 27.2% respectively. Computerised Tomography: The sensitivity to detect central LN was 67%. For lateral LN none of the studies calculated the sensitivity accurately. II. Results from the Cohort Study 44 patients were included in the analyses. 53.8% had positive LN when pLLND dissection was performed. Recurrence free survival between the two cohorts was not statistically significant. Overall survival was 100% for both groups. Conclusions: Prophylactic LND yielded metastatic central and lateral LN in about half of all patients with PTC. Imaging modalities currently utilised for detection of metastatic central and lateral cervical LN have low sensitivities. In our cohort of patients, prophylactic lateral lymph node dissection did not show any significant difference in terms of long term outcomes.