An investigation of the determinants of plasma glucose and micronutrient concentrations in patients with critical illness

Ghashut, Rawia (2015) An investigation of the determinants of plasma glucose and micronutrient concentrations in patients with critical illness. PhD thesis, University of Glasgow.

Abstract

This thesis describes a series of observational studies that examine the relationship between the systemic inflammatory response, glucose, micronutrients concentrations and outcomes in patients with critical illness with reference to a large nutrition screen cohort. Data and stored samples were available from cohorts which had been defined previously. The critical illness cohort comprised of medical or surgical patients ≥ 18 years admitted to the Intensive Care Unit (ICU) of the Glasgow Royal Infirmary (GRI) between September 2006 and December 2008. The nutrition screen cohort comprised samples and associated information which had been processed by the Pathological Biochemistry Department of the GRI. The samples had been received for vitamin and / or trace element assessment of patients from both GRI and other Scottish hospitals between January 2006 and March 2013. Samples had been referred to the lab for analysis of a number of variables related to nutrition, including glucose, albumin, C-reactive protein (CRP), lutein, lycopene, vitamins A, B1, B2, B6, C, D and E, and zinc, selenium, copper, and manganese. Data was not available for all variables for all samples, hence studies varied in the number of observations. plasma glucose was measured in sodium floride blood sample whole-blood samples underwent for routine analysis of concentrations of lutein, lycopene, α-carotene and β-carotene, 25-hydroxyvitamin D (25 (OH) D), ascorbic acid (vitamin C), α-tocopherol (vitamin E) in plasma, zinc, selenium, copper, B1, B2, B6 in plasma and red cells.
In Chapter 2 the relationship between glucose and markers of the systemic inflammatory response was examined in detail in patients from the critical illness cohort (n=100). The results of this study showed that plasma glucose concentration - even within the context of tight insulin protocol - was influenced by many factors. Surgical and medical patients differed in their requirements for insulin; medical patients have higher plasma glucose and insulin administration accordingly compared with surgical patients. However, catecholamine and steroid administration were also associated with higher insulin requirements.
In Chapter 3 the relationship between plasma asymmetric dimethylarginine (ADMA) and related arginine metabolism (homoarginine, arginine, symmetric dimethylarginine (SDMA)) and outcome was examined in patients from critical illness cohort (n=104). Patients with critical illness experience metabolic disorders including catabolism and hyperglycaemia and these were associated with poor outcome. Plasma ADMA and SDMA concentrations were higher in patients with critical illness and were also associated with disease severity and mortality. In contrast, plasma homoarginine concentrations were lower in patients with critical illness and were also associated with disease severity and mortality. These results suggest that ADMA metabolism is perturbed with likely knock on effects on nitric oxide synthase (NOS) and endothelial function. There is a need for further work on in vivo dimethylaminohydrolase (DDAH) activity in critical illness and the effect of critical illness on the cationic amino acid transporters (CAT)-mediated exchange of ADMA between intra and extra-cellular compartments. It was proposed that ADMA and SDMA may not only be indicators of the severity of illness and may even contribute to adverse events in patients with critical illness.
In Chapter 4 the relationship between markers of the systemic inflammatory response, as evidenced by CRP and albumin, and mortality, in patients from critical illness cohort (n=261) was examined. In this cohort, the combination of CRP and albumin predicted ICU and hospital mortality as effectively as APACHE II.
In Chapter 5 the relationship between markers of the systemic inflammatory response and plasma glucose was examined in a nutrition screen cohort (n=5248). The results of this study showed that plasma concentrations of glucose were independently positive and negative associated with both CRP and albumin respectively, and were consistent with the systemic inflammatory response as having an impact on glucose concentrations. However, such relationships were not apparent in patients with critical illness (n=116). It was concluded that plasma concentrations of glucose were independently associated with both CRP and albumin, and were consistent with the systemic inflammatory response as a determinant of its concentrations.
In Chapter 6 the relationship between markers of the systemic inflammatory response and plasma concentrations of carotenoids was examined in a nutrition screen cohort (n=1074). The results of this study showed that the clinical interpretation of plasma carotenoids requires knowledge of the magnitude of the systemic inflammatory response, even after adjustment for cholesterol. It was concluded that a reliable clinical interpretation can be made only for plasma lutein, lycopene and β-carotene if the CRP is less than 20 mg/L.
In Chapter 7 the relationship between markers of the systemic inflammatory response and plasma 25-hydroxyvitamin D (25(OH) D) was examined in a nutrition screen cohort (n=5327, and in patients from critical illness cohort n=117). The results of this study showed that plasma concentrations of 25(OH) D were independently associated with both CRP and albumin. It was concluded that the systemic inflammatory response was a major confounding factor in determining vitamin D status.
In Chapter 8 the relationship between markers of the systemic inflammatory response and plasma vitamin E (α-tocopherol) and vitamin C (ascorbic acid) was examined in a nutrition screen cohort (n=359, n=494 respectively and in patients from critical illness cohort n= 82). The results of this study showed that α-tocopherol/ cholesterol ratio and ascorbic acid were independently associated with both CRP and albumin. It was concluded that the systemic inflammatory response was a major confounding factor in determining vitamin E and C status.
In Chapter 9 the relationship between markers of the systemic inflammatory response and plasma zinc, selenium was examined in a nutrition screen cohort (n=743, n=833, respectively and in patients from the critical illness cohort n= 114). The results of this study showed that plasma concentrations of zinc were associated with both CRP and albumin. However, the impact of the systemic inflammatory response (as evidenced by elevation of CRP concentrations) on plasma zinc concentrations could be largely adjusted by albumin concentrations. Plasma concentrations of selenium were associated with both CRP and albumin. However, the impact of the systemic inflammatory response on plasma selenium concentrations could not be reasonably adjusted by albumin concentrations. It was concluded that plasma zinc and selenium concentrations were independently associations with CRP and albumin as markers of systemic inflammatory response.
In Chapter 10 the relationship between markers of the systemic inflammatory response and red cell zinc, selenium and copper was examined in patients from critical illness cohort (n= 125). The results of this study showed that altered red cell concentrations of zinc, selenium and copper were likely to be more reliable measures of status in the presence of a systemic inflammatory response.
In Chapter 11 the relationship between markers of the systemic inflammatory response and red cell vitamins B1, B2 and B6 was examined in nutrition screen cohort (n= 553, n=251, n= 313, respectively and in patients from critical illness cohort n=94). The results of this study showed that in contrast to plasma concentrations of B1, B2 and B6, red cell concentrations do not fall as a part of the systemic inflammatory response. It was concluded that red cell concentrations of B1, B2 and B6 were likely to be more reliable measures of status in the presence of a systemic inflammatory response.
In summary, studies in the present thesis showed that, during the systemic inflammatory response, plasma concentration of glucose had multiple determinants other than insulin. Furthermore, in the presence of systemic inflammatory response, plasma lutein, lycopene, α-carotene and β-carotene, 25 (OH) D, C, E, zinc, selenium, and copper were unreliable, and that intracellular micronutrients concentrations such as red cell zinc, selenium, copper, B1, B2 and B6, were more reliable as indicators of vitamin and trace element status in patients subject to nutrition screen and in patients with critical illness. These results have implications for the assessment of glucose and micronutrient status in the general population and for treatment in patients with critical illness.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: R Medicine > R Medicine (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
• Supervisor's Name: Kinsella, Professor John and Donald . C, Professor McMillan
• Date of Award: 2015
• Depositing User: Dr Rawia Ghashut
• Unique ID: glathesis:2015-6616
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 18 Aug 2015 09:11
• Last Modified: 20 Aug 2015 07:53
• URI: https://theses.gla.ac.uk/id/eprint/6616