Dr Callum Livingstone
Dr Livingstone was appointed as Consultant Chemical Pathologist/Senior Lecturer in 2001. He is deputy director of Guildford Peptide Hormones Supraregional Assay Service (SAS) located in the Clinical Laboratory, Royal Surrey County Hospital. Clinical interests include lipidology and clinical nutrition.
Specialist Registrar in Chemical PathologyNewcastle-upon-Tyne University Hospitals NHS Trust.April 1996-April 2001.
MRC post-doctoral researcherGlucose Transport Group, Biochemistry Department, Glasgow University.April 1993-April 1996.
PhD studentMolecular Pharmacology Group, Biochemistry Department, Glasgow University.October 1989-April 1993.Thesis title: 'Interactions between insulin and adenlyl cylase signalling.'
SHO in PathologyRoyal Gwent Hospital, Newport.February 1989-August 1989.(Duties in Clinical Haematology, Clinical Biochemistry and Histopathology)
SHO in MedicineRoyal Gwent Hospital, Newport.August 1988-February 1989.(3 months General Medicine/Cardiology and 3 months Geriatric Medicine)
JHO in General MedicineCrosshouse Hospital, Kilmarnock.February 1988-August 1988.
JHO in General SurgeryCrosshouse Hospital, Kilmarnock.August 1987-February 1988.
Insulin resistance, insulin-like growth factors and clinical nutrition.
Module organiser, HCSMOO8, MSc Health and Clinical SciencesModule organiser, BMSM010, MSc Nutritional MedicineChairman of Board of Studies, MSc Health and Clinical Sciences
Livingstone C. Insulin-like growth factor-I and clinical nutrition. Clin Sci 2013; 125: 265-280.
Livingstone C. IGF2 and cancer. Endo Rel Canc 2013; 20: R321-R339
Livingstone C, Borai A. IGF-II: its role in physiology and metabolic disease. Clin Endocrinol 2014; 80: 773-781.
Walsh J, Karanjia ND, Taylor A, Livingstone C. Selenium status in patients receiving short term parenteral nutrition: frequency of deficiency and response to a standard supplementation regimen. ISRN Pathology 2013 http://dx.doi.org/10.1155/2013/604954
Borai A, Livingstone C, Heald AH, Ferns G. Delta insulin-like growth factor binding protein-1 (IGFBP-1): A measure of hepatic insulin resistance? Ann Clin Biochem 2013; 51: 269-276.
Borai A, Bahijri S, Livingstone C, Nawajka, Bawazeer A, Baarmah Z, Shanaa A, Kadam I, Abdelaal M, Assessment of the use of Becton Dickinson plain and serum separator tubes in measurement of 25-hydroxyvitamin D3 (25OHD3) by HPLC and immunoassay methods. J Clin Lab Anal 2014
Conference papersHamilton J, Wark G, Livingstone C. An investigation into the clinical utility of serum IGF-I and IGFBP-3 measurement in adult patients receiving parenteral nutrition.EuroLabFocus, Liverpool, Oct 2014.
A number of protein-energy markers are currently available whose measurement is a useful adjunct to clinical nutritional assessment. These include transferrin (Tf), prealbumin and retinol binding protein (RBP). Other nutritional markers of recognised value but not currently in widespread use are insulin-like growth factor-I (IGF-I) and leptin. Currently no single marker can assess overall nutritional status but their levels may be of value of in providing information on metabolic status ie catabolism or anabolism, determining prognosis, and in monitoring of nutrition support. All have limitations in that their serum levels can be altered by factors other than the patient's nutritional status, most importantly the acute phase response. Clinicians requesting measurement of these proteins need to be mindful of any confounding factors when interpreting results. Levels should be interpreted along with clinical findings and the results of other investigations including an inflammatory marker such as C-reactive protein (CRP). © 2007 Rila Publications Ltd.
Manganese (Mn) is an essential dietary micronutrient. It is an integral component of various enzymes required for the synthesis of glycosaminoglycans and glycoproteins, which are the key components of connective tissue. Mn also activates prolidase, making proline available for the synthesis of collagen. Together these processes are required for tissue maintenance and wound healing. Mn is also required for energy metabolism, in particular for ATP synthesis. It is a cofactor for various mitochondrial enzymes, including superoxide dismutase, which metabolises superoxide generated during oxygen consumption. These roles of Mn are essential for normal functioning of various organ systems and of the immune system. Whilst Mn deficiency is very rare in patients receiving parenteral nutrition (PN), Mn toxicity is a relatively common complication
Glutathione (GSH) is the most abundant intracellular antioxidant, the dysregulation of which is widely implicated in disease states. There is in vitro and clinical evidence that abnormal glutathione status is involved in β-cell dysfunction and in the pathogenesis of long-term complications of diabetes. Interest has developed in the potential for therapeutic modification of glutathione status in the treatment of diabetes. There is evidence which supports the use of glutathione pro-drugs, lipoic acid and vitamin supplementation but further studies are required before these enter widespread use. Studies into the role of oxidative stress in diabetes rely heavily on the ability to measure glutathione, which has been a problematic analyte to measure in the laboratory. New electrochemical methods being developed should speed up the rate at which data can be accumulated and will help define clinical utility for its measurement.
IGF-I (insulin-like growth factor-I) is a peptide hormone, produced predominantly by the liver in response to pituitary GH (growth hormone), which is involved in a wide variety of physiological processes. It acts in an endocrine, paracrine and autocrine manner to promote growth. The production of IGF-I signals the availability of nutrients needed for its anabolic actions. Recently, there has been growing interest in its role in health and disease. IGF-I has long been known to be regulated by nutrition and dysregulated in states of under- and over-nutrition, its serum concentrations falling in malnutrition and responding promptly to refeeding. This has led to interest in its utility as a nutritional biomarker. A considerable evidence base supports utility for measurement of IGF-I in nutritional contexts. Its concentration may be valuable in providing information on nutritional status, prognosis and in monitoring nutritional support. However, it is insufficiently specific for use as a screening test for under nutrition as its serum concentration is influenced by many factors other than nutritional status, notably the APR (acute-phase response) and endocrine conditions. Concentrations should be interpreted along with clinical findings and the results of other investigations such as CRP (C-reactive protein). More recently, there has been interest in free IGF-I which holds promise as a nutritional marker. The present review covers nutritional regulation of IGF-I and its dysregulation in disease, then goes on to review recent studies supporting its utility as a nutritional marker in clinical contexts. Although not currently recommended by clinical guidelines, it is likely that, in time, measurement of IGF-I will become a routine part of nutritional assessment in a number of these contexts.
Aim: Saudi and Caucasian subjects, matched for adiposity, and of differing glycaemic status were compared using several insulin sensitivity indices and to also to assess insulin, glucose and insulin-like growth factor binding protein-1 (IGFBP-1) responses to intravenous glucose. Methods: Subjects with normal glucose tolerance (NGT; n = 24), impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 12), and type 2 diabetes (DM; n = 13) were recruited from Saudi (n = 33) and Caucasian (n = 28) populations. All had specimens taken in the context of a standard oral glucose tolerance test at their first visit and had the insulin sensitivity parameter (Si) determined by frequently-sampled intravenous glucose tolerance test (FSIVGTT) at a second visit. Results: Saudis in the NGT and pooled glucose intolerance categories had significantly higher diastolic blood pressure (p < 0.001, p < 0.05 respectively) and HbA1c (p < 0.01, p < 0.05 respectively) compared to Caucasians. Caucasians in the NGT category had significantly higher Si, fasting and 2 h IGFBP-1 (p < 0.01, p < 0.05 and p < 0.01 respectively) compared to Saudis. Two hours following oral or intravenous glucose serum IGFBP-1 decreased to 44% (p < 0.001) and 50% (p < 0.05) of baseline levels respectively. Conclusions: Our data suggest that adult Saudis with normal glucose tolerance appear to be more insulin resistant than Caucasians matched for adiposity. In normal individuals at 2 h the IGFBP-1 level will be about half the baseline level regardless of the route of glucose administration. © 2009 Diabetes India.
The essential trace element zinc (Zn) has a large number of physiologic roles, in particular being required for growth and functioning of the immune system. Adaptive mechanisms enable the body to maintain normal total body Zn status over a wide range of intakes, but deficiency can occur because of reduced absorption or increased gastrointestinal losses. Deficiency impairs physiologic processes, leading to clinical consequences that include failure to thrive, skin rash, and impaired wound healing. Mild deficiency that is not clinically overt may still cause nonspecific consequences, such as susceptibility to infection and poor growth. The plasma Zn concentration has poor sensitivity and specificity as a test of deficiency. Consequently, diagnosis of deficiency requires a combination of clinical assessment and biochemical tests. Patients receiving parenteral nutrition (PN) are susceptible to Zn deficiency and its consequences. Nutrition support teams should have a strategy for assessing Zn status and optimizing this by appropriate supplementation. Nutrition guidelines recommend generous Zn provision from the start of PN. This review covers the physiology of Zn, the consequences of its deficiency, and the assessment of its status, before discussing its role in PN.
Insulin-like growth factors (IGFs) are peptide hormones that have significant structural homology with insulin. IGF binding proteins (IGFBPs), in particular IGFBP-1, are important determinants of IGF activity such as enhancing peripheral glucose uptake, decreasing hepatic glucose output and modifying lipid metabolism. Herein factors which alter IGFBP-1 and the utility of measuring IGFBP-1 are considered as the role of IGFBP-1 is explored within the context of insulin resistance and the development of cardiovascular disease. © SAGE Publications 2012.
The essential trace element copper (Cu) is required for a range of physiologic processes, including wound healing and functioning of the immune system. The correct amount of Cu must be provided in parenteral nutrition (PN) if deficiency and toxicity are to be avoided. While provision in line with the standard recommendations should suffice for most patients, Cu requirements may be higher in patients with increased gastrointestinal losses and severe burns and lower in those with cholestasis. The tests of Cu status that are currently available for clinical use are unreliable. Serum Cu concentration is the most commonly ordered test but is insensitive to Cu deficiency and toxicity and is misleadingly increased during the acute phase response. These limitations make it difficult for prescribers to assess Cu status and to decide how much Cu to provide. There is a need for better tests of Cu status to be developed to decrease uncertainty and improve individualization of Cu dosing. More information is needed on Cu requirements in disease and Cu contamination of PN components and other intravenous fluids. New multi–trace element products should be developed that provide Cu doses in line with the 2012 American Society for Parenteral and Enteral Nutrition recommendations. This article discusses the evaluation and treatment of Cu deficiency and toxicity in patients treated with PN.
Objectives Previous studies have investigated the impact of venesection upon different metabolic indices in patients with various conditions (e.g., type 2 diabetes and iron overload). We aimed to investigate the changes on different metabolic indices including glycemic, iron, lipids and inflammatory markers at different time points after blood donation in male subjects with normal glucose tolerance.Design and methods 42 male subjects were recruited to the study. Glucose tolerance was assessed by oral glucose tolerance test before (visit A) and after the blood donation (1 day, visit B; 1 week, visit C; 3 weeks, visit D; and 3 months, visit E). Fasting glucose, HbA1c, insulin, lipids, uric acid, C-reactive protein, iron stores and insulin resistance (HOMA-IR, ISI-gly) indices were measured. A repeated measures ANOVA was used for comparisons of quantitative variables between different visits. Results All subjects had normal glucose tolerance according to WHO criteria. Fasting glucose, insulin and HOMA-IR were significantly higher (~ 2%, p < 0.05; ~ 21%, p < 0.01; and ~ 11%, p < 0.05 respectively) at visit B following donation. At visit D, the mean ± SE for HbA1c (5.28 ± 0.06%) was significantly lower with a difference in percentage of ~− 3% and p < 0.05 compared to visit A (5.44 ± 0.06%). Ferritin decreased significantly at visits B, C, D and E (~− 8%, p < 0.01, ~− 24%, p < 0.001, ~− 39%, p < 0.001 and ~− 29%, p < 0.01 respectively), when compared to visit A. Conclusions At different time points after blood donation, glycemic status and iron stores are affected significantly in male blood donors with normal glucose tolerance. The changes were particularly evident three weeks after donation. Hence, the interpretation of these parameters in male blood donors needs to take this into account, and the mechanisms resulting in these effects need to be clarified.
Whole blood donation has immunomodulatory effects, and most of these have been observed at short intervals following blood donation. This study aimed to investigate the impact of whole blood donation on lymphocyte subsets over a typical inter-donation interval. Healthy male subjects were recruited to study changes in complete blood count (CBC) (n = 42) and lymphocyte subsets (n = 16) before and at four intervals up to 106 days following blood donation. Repeated measures ANOVA were used to compare quantitative variables between different visits. Following blood donation, changes in CBC and erythropoietin were as expected. The neutrophil count increased by 11.3% at 8 days (p
Insulin resistance is one of the major aggravating factors for metabolic syndrome. There are many methods available for estimation of insulin resistance which range from complex techniques down to simple indices. For all methods of assessing insulin resistance it is essential that their validity and reliability is established before using them as investigations. The reference techniques of hyperinsulinaemic euglycaemic clamp and its alternative the frequently sampled intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance. However, many simple methods, from which indices can be derived, have been assessed and validated e.g. homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI). Given the increasing number of simple indices of IR it may be difficult for clinicians and researchers to select the most appropriate index for their studies. This review therefore provides guidelines and advices which must be considered before proceeding with a study.
Selenium (Se) is an essential micronutrient with antioxidant, anti-inflammatory and immunological properties. It is an important component of parenteral nutrition (PN). In 2012, ASPEN increased its standard recommendation on Se provision in PN for adults and recommended that commercially available multi-trace element (MTE) products should be modified accordingly. Some patients’ Se requirements are higher than the standard recommendation. Nutrition support teams (NSTs) should be able to identify these patients and provide additional Se. Recently, there has been interest in supplemention of Se at high doses for critically ill patients to improve clinical outcomes. This is called pharmaconutrition. This article provides guidance on providing Se in PN and on its use as a pharmaconutrient.
OBJECTIVE - To determine the effect of parenteral nutrition on plasma phosphate levels and to evaluate the incidence of refeeding hypophosphataemia. SUBJECTS AND SETTING - 250 adult patients started consecutively on parenteral nutrition (PN) were monitored at The Royal Surrey County Hospital, a 530-bed, non-teaching, secondary care trust incorporating medical and surgical care, paediatrics, intensive care, maternity services and a regional cancer centre. DESIGN - Data on plasma levels of magnesium and phosphate, relevant interventions performed and nutrition outcomes was collated by the Trust Nutrition Support Team. RESULTS - 36 patients (15 per cent) were found to be hypophosphataemic before commencing PN. 86 patients (34.4 per cent) developed refeeding hypophosphataemia within seven days after commencing PN. It was considered severe (less than 0.5mmol/L phosphate) in 10.8 per cent. Refeeding hypophosphataemia reached a nadir at three days and recovered in over 75 per cent of patients within 10 days without intervention. Cancer patients appear to be at greater risk than non-cancer patients for developing refeeding hypophosphataemia. Plasma magnesium levels did not mimic phosphate levels. CONCLUSION - Recognition of hypophosphataemia and the development of guidelines for its management in the care of PN patients are important.
Insulin-like growth factor 2 (IGF2) is a 7.5 kDa mitogenic peptide hormone expressed by liver and many other tissues. It is three times more abundant in serum than IGF1, but our understanding of its physiological and pathological roles has lagged behind that of IGF1. Expression of the IGF2 gene is strictly regulated. Over-expression occurs in many cancers and is associated with a poor prognosis. Elevated serum IGF2 is also associated with increased risk of developing various cancers including colorectal, breast, prostate and lung. There is established clinical utility for IGF2 measurement in the diagnosis of non-islet cell tumour hypoglycaemia, a condition characterised by a molar IGF2:IGF1 ratio >10. Recent advances in understanding of the pathophysiology of IGF2 in cancer have suggested much novel clinical utility for its measurement. Measurement of IGF2 in blood and genetic and epigenetic tests of the IGF2 gene may help assess cancer risk and prognosis. Further studies will determine whether these tests enter clinical practice. New therapeutic approaches are being developed to target IGF2 action. This review provides a clinical perspective on IGF2 and an update on recent research findings.
Insulin-like growth factor-II (IGF-II) is a widely expressed 7·5 kDa mitogenic peptide hormone. Although it is abundant in serum, understanding of its physiological role is limited compared with that of IGF-I. IGF-II regulates foetal development and differentiation, but its role in adults is less well understood. Evidence suggests roles in a number of tissues including skeletal muscle, adipose tissue, bone and ovary. Altered IGF-II expression has been observed in metabolic conditions, notably obesity, diabetes and the polycystic ovary syndrome. This article summarizes what is known about the actions of IGF-II and its dysregulation in metabolic and endocrine diseases. The possible causes and consequences of dysregulation are discussed along with the implications for diagnostic tests and future research.
Homocysteine has gathered considerable interest in recent years after being implicated in the pathogenesis of various clinical conditions. It has been an elusive target with many conflicting studies casting some confusion over its significance, and much more needs to be done to ascertain its pathophysiological role--especially with respect to regimes aimed at lowering its plasma concentration. Central to this is the development of robust analytical strategies for its determination. This review summarizes the clinical relevance of homocysteine as a diagnostic marker of disease and explores and critically assesses the detection methods that have been developed.
It is important for the dietitian to be able to interpret lipid profiles because the results usually have implications for the nutritional management of patients. The situations in which lipid measurements are requested can be divided into those occurring in non-acute settings − such as primary care and lipid out-patient clinics − and those occurring in acute settings. In non-acute settings, a lipid profile is usually requested when assessing cardiovascular (CV) risk, whereas in acute settings triglyceride alone is often measured for monitoring patients treated with nutrition support. This article discusses the interpretation of lipid results in these two settings.
The ability to interpret biochemical results is an important skill for the dietitian, one which will become increasingly important as new tests relevant to nutrition are developed. Also, it is often the dietitian who has to act on results as well, either by adjusting nutrient provision or by advising medical colleagues to do so. Although plenty of information has been published on how to interpret biochemical results, the subject is not covered comprehensively in any one publication intended for dietitians. By consolidating some of the available information, this series aims to provide readers with practical guidance which they can apply in the workplace. In the space available, it will focus on the tests most relevant to dietetic practice, including those which can be difficult to interpret and on which dietitians often seek advice from laboratory staff. This first article provides general guidance both on requesting of tests and on interpreting the results.
Manganese (Mn) is an essential micronutrient required for the activity of metalloenzymes. It is an essential component of parenteral nutrition (PN), but requirements are low. Mn status is difficult to assess, with the commonest method being measurement of its concentration in whole blood. This method has limitations, including artifactually high concentrations resulting from contamination of specimen tubes. Mn toxicity is a well-recognized complication of PN, the risk of which increases if there is cholestasis or if the patient has received high doses. It usually presents with parkinsonian-like symptoms but may be detected presymptomatically as hypermanganesemia or as increased signal intensity of the basal ganglia upon T1-weighted magnetic resonance imaging. Caution is necessary when providing Mn for patients on long-term PN (>1 month). It is advisable to withhold supplementation if hypermanganesemia or cholestasis develops. Deficiency of Mn is rare in patients treated with PN. PN regimens are contaminated with Mn in amounts likely to meet requirements. Consequently, it is debated whether PN should be routinely supplemented with Mn. The currently recommended dose of Mn in adults treated with PN is 55 μg/d, but the doses provided by most currently available multi–trace element products exceed this. In response to calls for new products to be developed, 2 new multi–trace element products are currently available in Europe that provide Mn doses of 55 μg/d. Once these products are in general use, it is likely that the incidence of Mn toxicity will decrease.
Iron (Fe) is the most abundant trace element (TE) in the body. Although it is an essential nutrient there is no worldwide consensus on whether it should be routinely provided in parenteral nutrition (PN). Indeed, there is a transatlantic difference in practice, Fe being routinely provided in PN in Europe but not in the United States (US). This is reflected in the formulation of the multi-TE (MTE) products used in the two continents. This article discusses the provision of Fe for patients treated with PN, including the arguments for and against providing it in PN itself. It also discusses the assessment of Fe status in patients treated with PN.
We present the case of a 62-year-old man on the intensive care unit with pancreatitis. Since early in his admission, and for the remainder of his prolonged stay in intensive care, he has received parenteral nutrition for intestinal failure. The whole blood manganese concentration was significantly increased after 2½ months of parenteral nutrition (PN). Three months into his stay, he developed a resting tremor and extra-pyramidal dyskinesia. In the absence of other neurological symptoms, and with no history of essential tremor, Parkinsonism or cerebral signs, hypermanganesaemia was presumed to be the cause. We review manganese metabolism and toxicity in patients who are fed with parenteral nutrition and review the current recommendations and guidelines.
Serum TE levels have limitations which make the results difficult to interpret, especially in the acute setting. Because of these limitations, practitioners need to consider factors other than TE levels when assessing TE status. This article discusses five TEs encountered in dietetic practice namely zinc (Zn), copper (Cu), selenium (Se), manganese (Mn) and iron (Fe) suggesting a practical approach to assessing the status of each. For the purposes of description they are considered individually, but in practice they should be considered together. There is a need for new tests of TE status to be developed which are reliable in the acute setting. Until such tests are available, the assessment of TE status will entail some uncertainty and practitioners should be mindful of this when deciding on TE provision.
Over recent years there has been considerable interest in the role of the insulin-like growth factor (IGF) system in health and disease. It has long been known to be dysregulated in states of under- and overnutrition, serum IGF-I levels falling in malnourished patients and responding promptly to nutritional support. More recently, other proteins in this system have been observed to be dysregulated in both malnutrition and obesity. Currently no biochemical marker is sufficiently specific for use in screening for malnutrition, but levels may be valuable in providing information on nutritional status and in monitoring of nutritional support. All have limitations as nutritional markers in that their serum levels are influenced by factors other than nutritional status, most importantly the acute phase response (APR). Levels should be interpreted along with clinical findings and the results of other investigations such as C-reactive protein (CRP). This paper reviews data supporting the use of proteins of the IGF system as nutritional markers.
Copper (Cu) is an essential trace element which is an important component of parenteral nutrition (PN). The Cu status of patients is difficult to assess, mainly because of the limitations of currently available laboratory tests. This can make it difficult to decide on the amount of Cu to provide in PN for individual patients. However, it is important to provide the correct amount if Cu deficiency and toxicity are to be avoided. This article provides guidance for nutrition support teams (NSTs) on assessing Cu status and estimating individual requirements in patients treated with PN.