NIHR Signal Being overweight or obese is linked with heart disease even without other metabolic risk factors

People with certain metabolic risk factors who are obese are two and a half times as likely to develop heart disease as healthy people of normal weight. But those who are obese without these other risk factors still have a 28% increased risk of heart disease compared with healthy people of normal weight.

This suggests excess weight should be seen as an independent risk factor, challenging the idea that people can be “fat but fit”.

From the NIHR Dissemination Centre

Setmelanotide for pro-opiomelanocortin deficiency obesity

Body fat and food intake are regulated by signals from the brain to the gut. One of the important hormones that is responsible for this is pro-opiomelanocortin (POMC). In a very small group of people there is a lack of this hormone (due to a genetic mutation), referred to as POMC deficiency. This causes severe overeating which leads to obesity and high blood sugar in children. Very few adults have been observed with this condition, which may be due to high death rates in adolescence. Pale skin that does not tan and red hair are common signs of POMC deficiency obesity.
Currently there are no licensed treatment options for POMC deficiency obesity, however weight loss medicines orlistat and methylcellulose are the only treatment options offered. Setmelanotide is being developed to treat pro-opiomelanocortin (POMC) deficiency obesity. If marketed setmelanotide could be the first effective treatment option aimed specifically at this patient group as it replaces one of the key hormones that is lacking in POMC deficiency patients (melanocytestimulating hormone). It has been shown to reduce hunger and has resulted in substantial weight loss in previous patients.


From NIHR Innovation Observatory

Calcium and phosphorus supplementation of human milk for preterm infants

Review to determine whether addition of calcium and phosphorus supplements to human milk leads to improved growth and bone metabolism of preterm infants without significant adverse effects

Cochrane Database of Systematic Reviews

Key European guidelines for the diagnosis and management of patients with phenylketonuria

European guidelines designed to optimise phenylketonuria (PKU) care.

Hyperammonaemia : urea cycle disorders NAGS deficiency (N-Acetyl glutamate synthase deficiency)

New protocol from the British Inherited Metabolic Disease Group (BIMDG) on NAGS deficiency in hyperammonaemia.

Association of Vitamin B12 with Pro-Inflammatory Cytokines and Biochemical Markers Related to Cardiometabolic Risk in Saudi Subjects

Nutrients. 2016 Sep 6;8(9). pii: E460.

This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population.

UHCW Research: McTernan PG and Tripathi G

Modulation of Metabolic Rate in Response to a Simple Cognitive Task

Archives of Medicne 2016 8:4.9. DOI: 10.21767/1989-5216.1000153

The effect of cognitive activity on human metabolic rate is incompletely understood. To investigate changes in human metabolism during periods of cognitive demand, we measured the effect of simple cognitive activity on energy expenditure during a cognitive task.

UHCW Research: Ahmed Al-Naher, Thomas M Barber and Sudhesh Kumar

Mechanisms of triglyceride metabolism in patients with bile acid diarrhea

World Journal of Gastroenterology. 22 (30) (pp 6757-6763), 2016. Date of Publication: 14 Aug 2016.

Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor a. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-?, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia.


UHCW Research: Arasaradnam R.P., McFarlane M.; Nwokolo C.;

Circulating betatrophin in healthy control and type 2 diabetic subjects and its association with metabolic parameters

J. Diabetes Complicat. 30:7 pp.1321-1325

Betatrophin, a newly identified liver and adipose tissue-derived hormone, has been suggested as an inducer of β-cell proliferation in mice. However, the physiological role of betatrophin remains poorly understood in humans. Hence, the aim of this study was to investigate circulating betatrophin concentrations in normal and type 2 diabetes mellitus (T2DM) Saudi subjects and its association with various metabolic parameters. In this cross-sectional study, 200 Saudi adults (81 healthy non-T2DM controls, age: 41.43±8.35 [mean±SD]; BMI: 31.58±5.49 and 119 T2DM subjects, age: 48.78±11.76years; BMI: 30.25±4.83kg/m(2)) were studied. Anthropometric and fasting serum biochemical data were collected. Circulating betatrophin was measured using an enzyme-linked immunosorbent assay (ELISA) based kit. We observed significantly higher levels of betatrophin in T2DM subjects compared to healthy controls (882.19±329.06 vs 657.14±261.04pg/ml, p<0.001). Furthermore, in T2DM subjects, betatrophin level was positively associated with blood pressure and serum fasting glucose (p<0.05). Our results suggest that circulating betatrophin is significantly elevated in subjects with T2DM compared to healthy controls. Increase in the level of betatrophin in T2DM subjects might be a compensatory mechanism for enhanced insulin demand in T2DM condition.

UHCW Research: Kumar, Sudhesh

Cascade Screening for Familiar Hypercholesterolemia: PCR Methods with Melting-Curve Genotyping for the Targeted Molecular Detection of Apolipoprotein B and LDL Receptor Gene Mutations to Identify Affected Relatives

Journal of Applied Laboratory Medicine, DOI: 10.1373/jalm.2016.020610 Published August 2016
 A key objective of the UK National Institute for Health and Care Excellence (NICE) pathway for diagnosis of familial hypercholesterolemia (FH) is the identification of affected relatives of index cases through cascade screening. At present, there is no systematic appraisal of available methodological options to identify the appropriate diagnostic testing protocol that would allow cost-effective cascade genetic screening. The majority of FH-causing mutations identified in the LDL receptor (LDLR) or apolipoprotein B (APOB) genes are single-nucleotide changes. This pattern of mutations suggests that PCR methods using melting curve–based genotyping might offer a convenient methodological approach for screening relatives.

The study generates proof-of-concept evidence of methods suitable for detecting single nucleotide substitutions and insertions that can deliver reliable, easy, low-cost, and rapid family screening of FH patients and can be adopted by nonspecialist molecular diagnostic laboratories.

UHCW Research: Sarojini Pandey,Mike Khan and Dimitris K. Grammatopoulos

What factors need to be considered when prescribing for lactose intolerant adults?

This Medicines Q&A discusses the types of lactose intolerance people may suffer from, how to determine the lactose content of medicines, and what factors healthcare professionals should consider when prescribing for lactose intolerant patients.

- Specialist Pharmacy Service

The interplay between heart failure, metabolism and body composition

The interplay between heart failure, metabolism and body composition

Br J Hosp Med (Lond). 2016 Jun;77(6):362-4. doi: 10.12968/hmed.2016.77.6.362.

A complex interplay exists between heart failure, metabolic status and body composition. The idiosyncrasies of these relationships are poorly understood, but they offer prognostic value and potential clinical utility. Current understanding of this relationship and known clinical value are discussed in this article.

UHCW Research - McAloon CJ, O'Hare P, Osman F, Randeva HS