14 research outputs found
The role of gut hormones in mediating the beneficial effects of RYGB on glycaemia and energy balance
No full textObesity and type 2 diabetes are both on the rise. Bariatric surgery is currently the most efficient treatment for obesity. Early weight-loss-independent improvement in glycaemia and longer-term ‘remission’ of type 2 diabetes are typically observed post-RYGB. The Gut hormones, GLP-1, OXM and PYY (GOP), are augmented post-prandially after RYGB. They are anorectic and have the potential to enhance beta cell function and increase energy expenditure.
We hypothesized that the elevation in GOP levels, mediate the beneficial metabolic effects of RYGB.
GOP infused subcutaneously at combined doses of 4/4/0.4 pmol/kg/min, successfully, replicated the peak post-prandial circulating levels of the individual hormone post-RYGB.
Subsequently, GOP at 4/4/0.4 pmol/kg/min was infused chronically for 28 days in obese volunteers with type 2 diabetes, in a randomised single-blinded placebo-controlled study. Effects of GOP on Energy Intake (EI), Appetite ratings, Energy Expenditure, Anthropometrics and Glycaemia were assessed and compared to the effects of RYGB on similar parameters.
Both an acute and chronic GOP infusion led to a significant reduction in EI, comparable to the effect of RYGB. A similar enhancement in satiety and decrease in ‘prospective food intake’ were observed following GOP and RYGB. However, only RYGB volunteers displayed a significant increase in Diet-induced-Thermogenesis. Weight loss was superior following RYGB compared to GOP at a similar time-frame. Nonetheless, a comparable and significant improvement in Fructosamine, HbA1c, Fasting and Post-prandial Glucose, was generated following both interventions at 4 weeks. Enhancement in beta cell function and insulin sensitivity appeared to be important.
In summary, the gut hormones - GOP, are the likely candidates mediating 1) the reduction in EI post-RYGB by promoting satiety and contributing to weight loss 2) the improvement in glycaemia, early after surgery, irrespective of weight loss.
Other mechanisms appear to be responsible for the increase in EE and the majority of weight loss, post-RYGB.Open Acces
Bone perspectives in functional hypothalamic amenorrhoea: an update and future avenues
No full textOne of the most important and potentially long-lasting detrimental consequences of Functional Hypothalamic Amenorrhoea (FHA) is
on skeletal homeostasis. Beyond oestrogen deficiency, FHA is associated with a cascade of additional neuro-endocrine and metabolic
alterations, some adaptive, but which combine to disrupt skeletal homeostasis. Ultimately, this leads to a two-fold increased risk
of fractures in women with FHA compared to healthy eumenorrhoeic women. Although the cornerstone of management of
FHA-related bone loss remains recovery of menses via restoration of metabolic/psychological balance, there is rapidly developing
evidence for hormonal manipulations (with a particular emphasis on route of administration) and other pharmacological
treatments that can protect or improve skeletal homeostasis in FHA. In this mini-review, we provide an update on the
pathophysiology, clinical management and future avenues in the field from a bone perspective
Public involvement Insight Report - Proposed clinical trial to understand how Tirzepatide affects bone health in people living with obesity
No full textPublic involvement insights about a proposed trial for GLP1 medicatio
Which test should the bariatric physician use to test for postprandial hypoglycaemia - prolonged oral glucose tolerance test versus mixed meal test?
No full textClinical practice patterns in bone health assessment and management in endogenous Cushing's Syndrome
No full textObjective
Skeletal fragility is a common complication of endogenous Cushing's Syndrome (CS), although specific guidelines for managing bone health are lacking. This study aimed to assess clinicians' current engagement with bone health assessment and management in patients with endogenous CS.
Design
Retrospective-cohort design.
Patients
Seventy-nine patients with confirmed endogenous CS, treated at a tertiary endocrine centre.
Measurements
The frequency of bone health assessment, evidenced by vitamin D measurement, and bone health management, evidenced by a composite outcome of calcium and/or vitamin D optimisation and/or initiation of bone-protective agents, was recorded. Changes in bone mineral density (BMD), measured by Dual-energy X-ray absorptiometry (DEXA) and fracture prevalence were assessed pre- and post-CS treatment.
Results
Vitamin D was measured in only 43% (34/79), and bone health was managed in only 39.2% (31/79). BMD was assessed in 44.3% (35/79) during active CS; of these, 22.9% had osteoporosis. Improved BMD was observed within a year of CS remission. Fractures occurred in 17.7% (14/79) within 2 years of CS diagnosis, and 12 additional fractures occurred during follow-up despite CS remission. Treatment with bone-protective agents expedited recovery with a significant increase in lumbar spine BMD, compared to those not treated.
Conclusions
Our data demonstrate that skeletal impairment and fragility fractures are highly prevalent in endogenous CS, and fracture risk may persist despite remission. However, currently, bone health is inadequately assessed and managed. These findings identify an urgent need for improved awareness, assessment, and management of bone-health in this high-risk population and call for specific evidence-based practice guidelines
Weight loss by low calorie diet versus gastric bypass surgery in people with diabetes results in divergent brain activation patterns: an functional MRI study
No full textOBJECTIVE: Weight loss achieved with very-low-calorie diets (VLCDs) can produce remission of type 2 diabetes (T2D), but weight regain very often occurs with reintroduction of higher calorie intakes. In contrast, bariatric surgery produces clinically significant and durable weight loss, with diabetes remission that translates into reductions in mortality. We hypothesized that in patients living with obesity and prediabetes/T2D, longitudinal changes in brain activity in response to food cues as measured using functional MRI would explain this difference.
RESEARCH DESIGN AND METHODS: Sixteen participants underwent gastric bypass surgery, and 19 matched participants undertook a VLCD (meal replacement) for 4 weeks. Brain responses to food cues and resting-state functional connectivity were assessed with functional MRI pre- and postintervention and compared across groups.
RESULTS: We show that Roux-en-Y gastric bypass surgery (RYGB) results in three divergent brain responses compared with VLCD-induced weight loss: 1) VLCD resulted in increased brain reward center food cue responsiveness, whereas in RYGB, this was reduced; 2) VLCD resulted in higher neural activation of cognitive control regions in response to food cues associated with exercising increased cognitive restraint over eating, whereas RYGB did not; and 3) a homeostatic appetitive system (centered on the hypothalamus) is better engaged following RYGB-induced weight loss than VLCD.
CONCLUSIONS: Taken together, these findings point to divergent brain responses to different methods of weight loss in patients with diabetes, which may explain weight regain after a short-term VLCD in contrast to enduring weight loss after RYGB
The metabolomic effects of tripeptide gut hormone infusion compared to Roux-en-Y gastric bypass and caloric restriction
No full textContext: The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are regulators of energy intake and glucose homeostasis, and are thought to contribute to the glucose-lowering effects of bariatric surgery. Objective: To establish the metabolomic effects of a combined infusion of GLP-1, OXM and PYY (tripeptide “GOP”) in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD). Design and setting: Sub-analysis of a single-blind, randomised, placebo-controlled study of GOP infusion (ClinicalTrials.gov NCT01945840), including VLCD and RYGB comparator groups. Patients and interventions: 25 obese patients with type 2 diabetes or prediabetes were randomly allocated to receive a 4-week subcutaneous infusion of GOP (n=14) or 0.9% saline control (SAL; n=11). An additional 22 patients followed a VLCD, and 21 underwent RYGB surgery. Main outcome measures: Plasma and urine samples collected at baseline and 4 weeks into each intervention were subjected to cross-platform metabolomic analysis, followed by unsupervised and supervised modelling approaches to identify similarities and differences between the effects of each intervention. Results: Aside from glucose, very few metabolites were affected by GOP, contrasting with major metabolomic changes seen with VLCD and RYGB. Conclusions: Treatment with GOP provides a powerful glucose-lowering effect but does not replicate the broader metabolomic changes seen with VLCD and RYGB. The contribution of these metabolomic changes to the clinical benefits of RYGB remains to be elucidated
The early improvement of glycaemia following RYGB can be mimicked by a Very Low Calorie Diet in obese volunteers with diabetes
No full textRoles of increased glycemic variability, GLP-1 and glucagon in hypoglycaemia after Roux-en-Y gastric bypass
No full textObjective Roux-en-Y Gastric Bypass (RYGB) surgery is currently the most effective treatment for diabetes and obesity. An increasingly recognized complication of RYGB surgery is postprandial hypoglycemia (PPH). The pathophysiology of PPH remains unclear with multiple mechanisms suggested including nesidioblastosis, altered insulin clearance and increased glucagon-like-1 peptide (GLP-1) secretion. Whilst many PPH patients respond to dietary modification, some have severely disabling symptoms. Multiple treatments have been trialled ranging from acarbose, to both GLP-1 agonists and antagonists, even to reversal of RYGB. A greater understanding of the pathophysiology of PPH could guide the development of new therapeutic strategies. Methods We studied a cohort of PPH patients at the Imperial Weight Center. We performed continuous glucose monitoring to characterize their altered glycemic variability. We also performed a mixed meal test (MMT) and measured gut hormone concentrations. Results We found increased glycemic variability in our cohort of PPH patients, specifically a higher Mean Amplitude Glucose Excursion (MAGE) score of 4.9. We also demonstrated significantly greater and earlier increases in insulin and GLP-1 concentration in patients who had hypoglycemia in response to an MMT (MMT Hypo) relative to those that did not (MMT Non-Hypo). There was a significantly increased glucagon secretion in the MMT Hypo group versus the Non-hypo group. No significant differences in oxyntomodulin, GIP or peptide YY secretion were seen between these two groups. Conclusion An early peak in GLP-1 and glucagon, due to post-operative L-cell hypertrophy and aberrant processing of proglucagon, may trigger an exaggerated insulinotropic response to eating in patients with PPH.</p
