Ahmad Moolla

L‐arginine promotes gut hormone release and reduces food intake in rodents

To investigate the anorectic effect of L‐arginine (L‐Arg) in rodents.

Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy?

Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care.

Leadership development for early career doctors

CMO Clinical Advisor Alumni c/o Faculty of Medical Leadership and Management, London, UK (C E M Coltart MRCP, R Cheung BMBCh, A Ardolino MSc, B Bray MBChB, B Rocos MRCS, A Bailey MBChB, R Bethune MA, J Butler MRCOG, M Docherty MRCP, K Drysdale MBChB, A Fayaz FRCA, F Greaves BMBCh, J Haff erty BMBCh, A N J Malik MRCOphth, A Moolla MBBS, L Morganstein MBChB, F Pathiraja MPH, A Shah MBChB, G Sleat MRCS, V Tang MBBS, I Yardley FRCS); and Institute of Global Health and Innovation, Imperial College, St Mary’s Hospital, London, UK (Prof Liam Donaldson MD)

l -phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents

Objective:High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have a role in appetite regulation and satiety. We investigated the effects of l-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents.Methods:We investigated the effects of the aromatic amino-acid and calcium-sensing receptor (CaSR) agonist l-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal (GI) hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo. We also examined the effect of oral l-Phe administration on glucose tolerance in rats.Results:Oral administration of l-Phe acutely reduced food intake in rats and mice, and chronically reduced food intake and body weight in diet-induced obese mice. Ileal l-Phe also reduced food intake in rats. l-Phe stimulated GLP-1 and PYY release, and reduced plasma ghrelin, and also stimulated insulin release and improved glucose tolerance in rats. Pharmacological blockade of the CaSR attenuated the anorectic effect of intra-ileal l-Phe in rats, and l-Phe-induced GLP-1 release from STC-1 and primary L cells was attenuated by CaSR blockade.Conclusions:l-Phe reduced food intake, stimulated GLP-1 and PYY release, and reduced plasma ghrelin in rodents. Our data provide evidence that the anorectic effects of l-Phe are mediated via the CaSR, and suggest that l-Phe and the CaSR system in the GI tract may have therapeutic utility in the treatment of obesity and diabetes. Further work is required to determine the physiological role of the CaSR in protein sensing in the gut, and the role of this system in humans.

Prevalence and severity of non-alcoholic fatty liver disease are underestimated in clinical practice: impact of a dedicated screening approach at a large university teaching hospital

To define the attitudes and current clinical practice of diabetes specialists with regard to non‐alcoholic fatty liver disease and, based on the results, implement an evidenced‐based pathway for non‐alcoholic fatty liver disease assessment.

Complications of diabetes: progress, but significant challenges ahead

The prevalence of type-2 diabetes (T2D) is growing rapidly worldwide and societal costs associated with T2D are immense (1). In many countries, diabetes is now a major cause of cardiovascular disease, renal failure, blindness and lower limb amputation, and a significant proportion of healthcare expenditure is undertaken in the management of diabetes and its attendant complications. It is estimated that at the time of diagnosis, around half of people with T2D may have a complication related to diabetes (2). Cardiovascular disease accounts for much of the premature mortality seen in people with T2D. With growing prevalence and increasing costs of treatments, diabetes is set to add further pressure on healthcare systems worldwide, particularly amongst countries at the forefront of economic development.

Liver Biochemical Abnormalities in Turner Syndrome: a Comprehensive Characterisation of an Adult Population.

Abnormal liver function tests (LFTs) are frequent in Turner syndrome (TS). The causes and clinical significance are unclear.