dc.contributor.advisor | Price, Jackie | en |
dc.contributor.advisor | Fallowfield, Jonathan | en |
dc.contributor.advisor | Strachan, Mark | en |
dc.contributor.author | Morling, Joanne Rebecca | en |
dc.date.accessioned | 2017-04-12T14:22:35Z | |
dc.date.available | 2017-04-12T14:22:35Z | |
dc.date.issued | 2015-07-04 | |
dc.identifier.uri | http://hdl.handle.net/1842/21101 | |
dc.description.abstract | Increasingly chronic liver disease is being acknowledged as a complication of type 2
diabetes, in particular non-alcoholic fatty liver and non-alcoholic fatty liver disease.
Rates of non-alcoholic fatty liver are higher in people with type 2 diabetes than in the
general population, with prevalence rates believed to be between 40-70%. Given the
aging Scottish population and the obesity driven diabetes epidemic, the problem of
chronic liver disease is likely to increase.
Despite this there has been little investigation into the natural history of nonalcoholic
fatty liver disease and the risks of clinically significant chronic liver
disease in community based cohorts because diagnosis has been heavily reliant on
liver biopsy. The use of liver biopsy is limited in both research and clinical practice
due to its associated high mortality (1/1000) and morbidity and also due to practical
limitations (sampling variability, semi-quantitative scoring systems). As a result the
use of non-invasive markers of liver injury (non-specific liver injury, steatosis,
steatohepatitis, liver fibrosis and surrogates of advanced portal hypertension) are
rising, in the diagnosis of chronic liver disease, however, their utility in both
community cohorts and patients with type 2 diabetes has not been widely studied.
The aims of the studies presented in the thesis, using the Edinburgh Type 2 Diabetes
Study, were: (i) to describe the distributions of a range of non-invasive markers of
steatohepatitis and liver fibrosis in older people with type 2 diabetes, their
relationship with metabolic and liver disease risk factors, and to compare the
agreement of different non-invasive markers of hepatic fibrosis; (ii) to determine the
frequency (prevalence and incidence) of and risk factors for clinically significant
chronic liver disease in people with type 2 diabetes; and (iii) to determine the
importance of chronic liver disease as a risk factor (or risk marker) for cardiovascular
mortality or morbidity in type 2 diabetes.
Prior to undertaking this work I undertook a detailed systematic review of the
literature relating to the use of non-invasive markers of hepatic fibrosis to inform the
choice of markers used in the study.
Examination of a wide range of potential markers of steatohepatitis and liver fibrosis
found varied relationships with diabetes history. Most commonly, elevated markers
of steatohepatitis and liver fibrosis were associated with older age and higher body
fat measures. However, most of these relationships between liver markers and body
fat measures lost statistical significance when limiting the population to only those
with hepatic steatosis and/or non-alcoholic fatty liver disease.
There were marked differences in the associations between different liver fibrosis
markers and potential diabetes and metabolic risk factors, suggesting that these
markers are not actually measuring the same underlying “fibrosis” condition. There
was poor correlation between the five markers of liver fibrosis studied. Using the top
vigintile (5%) of each marker resulted in excellent agreement on the absence of
advanced liver disease but poor agreement on the presence of advanced liver disease.
The prevalence of clinically significant CLD (defined as cirrhosis, HCC or gastrooesophageal
varices) was 2.2% - 0.9% diagnosed prior to enrolment with an
additional 1.4% identified by study investigations. Over nearly 6 years of follow-up,
only 1.4% of the cohort developed incident clinically significant CLD.
Higher levels of systemic inflammation, steatohepatitis and hepatic fibrosis markers
were associated with both unknown prevalent and incident clinically significant
chronic liver disease. Less than half of participants developing incident significant
disease were identified as high risk by the study investigations. Abnormal liver
enzymes were statistically significantly associated with incident cases, however the
presence of hepatic steatosis was not.
There were 372/1033 (36.0%) patients with prevalent CVD and 319 (30.9%) with
prevalent CAD at baseline. After mean follow-up of 4.4 years there were 44/663
incident CVD events, including 27 CAD events. There were 30/82 CVD related
deaths.
However, risk of dying from or developing CVD was no higher in subjects with
steatosis than in those without. There was also no statistically significant
relationship between CVD and steatohepatitis or liver fibrosis. The only statistically
significant relationship between CVD and any liver markers was with GGT
(prevalent CVD, OR 1.28, p=0.007; incident CAD, OR 2.35, p=0.042), suggesting
that in our study population, CLD may have little effect on the development of, or
mortality from, CVD.
In conclusion, the potential for using non-invasive biomarkers to diagnose clinically
significant chronic liver disease in type 2 diabetes remains limited, however chronic
liver disease is a significant problem in older people with type 2 diabetes and is
frequently undiagnosed. | en |
dc.contributor.sponsor | other | en |
dc.language.iso | en | |
dc.publisher | The University of Edinburgh | en |
dc.relation.hasversion | Morling JR, Fallowfield JA, Guha IN, Nee LD, Glancy S, Williamson RM, Robertson RM, Strachan MWJ, Price JF. Using non-invasive markers to identify liver fibrosis in people with type 2 diabetes mellitus: the Edinburgh Type 2 Diabetes Study. Journal of Hepatology 2014;60(2):384-391. | en |
dc.relation.hasversion | Morling JR, Fallowfield JA, Williamson RM, Nee LD, Jackson AP, Glancy S, Reynolds RM, Hayes PC, Guha IN, Strachan MWJ, Price JF. Non-invasive hepatic markers (ELF and CK18) in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Liver International 2014;34(8):1267-77. | en |
dc.relation.hasversion | Morling JR, Fallowfield JA, Guha IN, Williamson RM, Ali M, Nee LD, Glancy S, Guha IN, Strachan MWJ, and Price JF. Clinically significant chronic liver disease in older people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetic Medicine 2015;32(s1):17 | en |
dc.relation.hasversion | Morling JR, Fallowfield JA, Williamson RM, Robertson CM, Nee LD, Glancy S, Guha IN, Strachan MWJ, and Price JF. Cardiovascular disease and markers of liver injury in Type 2 diabetes: the Edinburgh Type 2 Diabetes Study (ET2DS). Diabetic Medicine 2014;31(s1):74 | en |
dc.relation.hasversion | Morling JR, Fallowfield JA, Williamson RM, Robertson CM, Nee LD, Glancy S, Guha IN, Strachan MWJ, and Price JF. Biochemical and radiological factors associated with the development of advanced liver disease: the Edinburgh Type 2 Diabetes Study (ET2DS). Diabetic Medicine 2014;31(s1):138 | en |
dc.relation.hasversion | Morling JR, Williamson RM, Guha IN, Fallowfield JA, Price JF and Strachan MWJ. Markers of hepatic inflammation and fibrosis in older people with Type 2 diabetes: the Edinburgh Type 2 Diabetes Study (ET2DS). Diabetic Medicine 2013; 30(s1):157 | en |
dc.relation.hasversion | Morling JR, Williamson RM, Robertson CM, Fallowfield JA, Guha IN, Strachan MWJ and Price JF. Hepatic inflammation and fibrosis markers are associated with cardiovascular risk factors but not cardiovascular disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study (ET2DS). Diabetic Medicine 2013; 30(s1):157 | en |
dc.relation.hasversion | Morling JR, Williamson RM, Robertson CM, Guha IN, Fallowfield JA, Strachan MWJ and Price JF. Hepatic inflammation and fibrosis markers are associated with cardiovascular risk factors but not cardiovascular disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. The Lancet 2013;381:S79 | en |
dc.relation.hasversion | Morling JR, Strachan MWJ, Williamson RM, Price JF, Fallowfield JA and Guha IN. Liver fibrosis in people with type 2 diabetes mellitus: The Edinburgh Type 2 Diabetes Study. Gut 2012;61(s2):A28 | en |
dc.relation.hasversion | Morling JR, Fallowfield JA, Guha IN, Williamson RM, Ali M, Nee LD, Glancy S, Strachan M and Price J. The prevalence and incidence of chronic liver disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Association of British Clinical Diabetologists SpR Meeting 2014 | en |
dc.relation.hasversion | Morling JR, Fallowfield JA, Guha IN, Williamson RM, Ali M, Nee LD, Glancy S, Strachan M and Price J. The burden of chronic liver disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Association of British Clinical Diabetologists Autumn Meeting 2014 | en |
dc.subject | epidemiology | en |
dc.subject | chronic liver disease | en |
dc.subject | type 2 diabetes | en |
dc.title | Epidemiology of chronic liver disease in older people with type 2 diabetes mellitus: the Edinburgh Type 2 Diabetes Study | en |
dc.type | Thesis or Dissertation | en |
dc.type.qualificationlevel | Doctoral | en |
dc.type.qualificationname | PhD Doctor of Philosophy | en |