Liraglutide 3.0 mg in the treatment of adults with obesity and prediabetes using real-world UK data: A clinical evaluation of a multi-ethnic population.

UK guidelines recommend liraglutide 3.0 mg in adults treated within specialist weight management services with BMI ≥35 kg/m2, prediabetes and high cardiovascular disease risk. We aimed to clinically evaluate liraglutide 3.0 mg in specialist weight management services. We evaluated liraglutide 3.0 mg in weight management services at Guys and St Thomas' NHS Foundation Trust. Objective body weight (BW) was measured at baseline and 4 months, allowing classification as 'responders' (≥5% BW reduction) and 'non-responders' (<5% BW reduction). One hundred and twenty-one patients were evaluated. At 4 months, 76.0% attended follow-up (82.6% responders, 17.4% non-responders); BW (-8.6 kg, 95%CI:-9.8, -7.4 kg), BMI (-3.2 kg/m2, 95%CI: -3.6, -2.8) and %-BW (-6.6%, IQR: -8.8%, -5.2%) significantly reduced. In responders, HbA1c reduced by -5.0 mmol/mol (IQR: -7.0. -4.0 mmol/mol). In responders BW continued to reduce up to 12 months (4 m: -10.2 kg, p < .0001; 6 m: -15.6 kg, p < .0001; 9 m: -16.5 kg, p < .0001; 12 m: -16.7 kg, p < .01). Those of Black African and Caribbean ethnicity experienced less BW loss than those of white ethnicity (4.12 kg, p = .017) and had a greater attrition rate. In adults with obesity and prediabetes who are treated within specialist weight management services, liraglutide 3.0 mg reduces BW and HbA1c. Those of Black African and Caribbean ethnicity experienced less BW reduction and greater attrition at 4 months. Further evaluation of the ethnic differences in response to obesity pharmacotherapy is required.

Ockham's Razor for a Retinal Lesion and Acromegaly and Breaking the Vicious Circle.

Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is rare. Treatment consists of surgical removal of the primary tumor, cytostatic therapy, "cold" or radioactive somatostatin analogue treatment, and medical therapy for acromegaly, if needed. A 53 year-old female had an ocular lesion noted on a routine optician visit, originally considered to be an ocular melanoma. She had a bronchial carcinoid successfully removed 22 years previously. She had acromegalic features with an enlarged pituitary gland on magnetic resonance imaging and, additionally, metastatic lesions in her bones, liver, and thyroid gland. Elevated GHRH levels (>250× upper limit of normal) suggested a metastatic lung neuroendocrine tumor secreting GHRH. Cold and radioactive somatostatin analogue therapy reduced both GHRH and insulin-like growth factor 1 (IGF-1) levels, but normalization of the biochemical markers of acromegaly was only achieved after pegvisomant was introduced. Complete control of IGF-1 was achieved, and this may have hindered the growth of the metastatic lesions as well, as the patient remains well 13 years after the diagnosis of metastatic disease and 35 years after the original lung operation. A gradual rise in prolactin levels over last 4 years was noted, which is likely due to the prolonged effect of GHRH on prolactin-secreting cells. The diagnosis of this case applied the law of parsimony from the Ockham's razor principle. We consider that breaking the vicious circle of IGF-1 feeding the metastatic tumor was key for the long-term outcome of this case.

Are serotonin metabolite levels related to bone mineral density in patients with neuroendocrine tumours?

BACKGROUND: Bone mineral density (BMD) is influenced by multiple factors. Recent studies have highlighted a possible relationship between serotonin and BMD. Patients with neuroendocrine tumours (NETs) frequently have elevated urinary 5-hydroxy-indoleacetic acid (5-HIAA) levels, a serotonin metabolite. Evaluation of the relationship between 5-HIAA and BMD in patients with NETs may provide insights into the relationship between serotonin and BMD. METHODS: One-year audit of consecutive patients with NETs within two institutions. Relationships between urinary 5-HIAA and dual X-ray absorptiometry (DEXA)-scan-measured BMD were investigated by group comparisons, correlation and regression. RESULTS: Of 65 patients with NETs, 19 did not participate or were excluded. Of 46 subjects evaluated (48·9% males, 63·8 ± 10·5 years, BMI 26·6 ± 4·4 kg/m(2) ) with 32 gastrointestinal, 9 pancreatic, 3 pulmonary and 2 ovarian NETs, 72·3% had the carcinoid syndrome. Median interval from diagnosis was 4·0 years (IQR 2·0-6·0); 41·3% had osteoporosis and 32·6% osteopaenia (WHO definition). The group with a higher urinary 5-HIAA had a lower hip BMD (total T-score and Z-score), confirmed on individual analysis (Spearman's rank correlation -0·41, P = 0·004; -0·44, P = 0·002, respectively); urinary 5-HIAA was not found to be an independent predictor for BMD on multiple linear regression analysis. CONCLUSION: These data of patients with NETs with higher serotonin metabolites having a lower BMD at the hip in group and individual comparisons, warrants further evaluation. Urinary 5-HIAA measurement alone cannot be used to predict future BMD. A larger cohort with prospective design including fractures as a clinical outcome will aid these data in determining whether patients with NETs should be subject to targeted osteoporosis prevention.

Can faulty antennae increase adiposity? The link between cilia proteins and obesity.

Primary cilia are sensory organelles that protrude from the surface of most mammalian cell types. In humans and mice, mutations in proteins required for normal cilia function have been identified as causing a class of disorders with overlapping phenotypes known as ciliopathies. Recent evidence has linked obesity in ciliopathies to both the regulation of energy homeostasis in the hypothalamus and to adipogenesis. This article considers the role of cilia in these processes and whether cilia dysfunction may be relevant to more common forms of obesity.