28 research outputs found
The epidemiology of chronic liver disease in older people with type 2 diabetes mellitus: the Edinburgh Type 2 Diabetes Study
No full textIncreasingly 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.
era.ed.ac.uk/handle/1842/21101
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
Diabetes and life-long cognitive ability
No full textThere is a widespread consensus that diabetes impairs cognitive functioning. However, some recent findings have shown that many health conditions generally thought to be detrimental to cognitive functioning are in fact linked to pre-morbid cognitive ability, suggesting reverse causation. To better understand the causality in diabetes-cognition relationship, this study investigates the association of older-age diabetes with concurrent and childhood cognitive functioning
Outdoor Mosquito Control Using Odour-Baited Devices: Development and Evaluation of a Potential New Strategy to Complement Indoor Malaria Prevention Methods
No full textA considerable effort is currently underway to develop a malaria vaccine based on live Plasmodium falciparum sporozoites. The first requisite of a sporozoite vaccine is the guarantee of parasite arrest prior to the onset of the pathogenic blood stage. Immunisation with genetically attenuated parasites (GAP) that arrest in the liver forms a promising approach. Work in this thesis describes the development and characterisation of a P. berghei Δb9Δslarp GAP that fully arrests in the liver. Immunisation of multiple mouse strains with low numbers of Δb9Δslarp GAP resulted in sterile protection. The Δb9Δslarp GAP is there- fore the leading GAP vaccine candidate. Work in this the- sis further describes the effect of varying the parameters of sporozoite inoculation on parasite liver load. These findings provide a rationale for the design of clinical trials aimed at the administration of live attenuated P. falciparum sporozoites
Body piercing: a dangerous practice in type 1 diabetes?
No full textBody piercing is becoming increasingly common, but is not without complications. We present the cases of two patients with type 1 diabetes who required hospital admission following tongue piercing. These cases led us to survey the current practice of piercing establishments in the Lothian area. This revealed inconsistencies and a lack of information regarding the management of diabetes following piercing. As a result of this, an information leaflet was produced which is now available to all patients with diabetes who have a piercing performed. Copyright © 2006 John Wiley & Sons, Ltd
Adrenal insufficiency in patients on long-term opioid analgesia
No full text\ua9 2016 John Wiley & Sons Ltd Objective: Opioid analgesia has been implicated as a cause of secondary adrenal insufficiency, but little is known of the prevalence of this potentially serious adverse effect in patients with chronic pain. Design: Cross-sectional study of chronic pain patients on long-term opioid analgesia. Patients: Patients attending tertiary chronic pain clinics at the Western General Hospital, Edinburgh, treated with long-term opioid analgesia (n = 48) with no recent exposure to exogenous glucocorticoids. Results: Four patients (8\ub73%) had basal morning plasma cortisol concentrations below 100 nmol/l, of whom three failed to achieve a satisfactory cortisol response to exogenous ACTH1-24 stimulation (peak cortisol >430 nmol/l). Basal cortisol was positively associated with age (R = 0\ub7398, P = 0\ub7005) and negatively associated with BMI (R = −0\ub7435, P = 0\ub7002). Conclusions: Suppression of the hypothalamic−pituitary−adrenal axis is present in a clinically significant proportion of chronic pain patients treated with opioid analgesia. Studies of larger populations should be conducted to better define the prevalence and potential clinical consequences of adrenal insufficiency in this context
Are blood ketones a better predictor than urine ketones of acid base balance in diabetic ketoacidosis?
No full textCardiovascular disease, type 2 diabetes and carotid ultrasound
No full textCardiovascular disease contributes significantly to global morbidity and mortality
and is particularly prevalent among individuals with Type 2 diabetes, which is
thought to in part be due to the association between diabetes and the metabolic
syndrome. Traditional cardiovascular risk prediction scores perform well in the
general population but their use in people with Type 2 diabetes is limited as they are
thought to underperform in high risk groups. Indeed, the use of any risk prediction in
people with Type 2 diabetes is a point of discussion among clinicians as people with
diabetes are thought by some to be at immediate high risk of CVD, whereas others
view them as having a degree of modifiable risk which can be addressed using risk
prediction. In the general population, novel markers such as cIMT and carotid
plaque, as well as other potential biomarkers of cardiovascular risk, have been
explored as possible adjuncts to risk scores in the prediction of cardiovascular
disease. The evidence for their use in general populations has been established,
although there have been no firm conclusions with regard to recommendations for
their use, which is partly due to the high degree of variability in cIMT measurement.
However, the evidence for their use in people with Type 2 diabetes is sparse, despite
the use of such markers as surrogate CV endpoints in clinical trials.
This thesis aimed to describe the frequency, distribution and change of cIMT and
carotid plaque, as well as to explore the relationship of cIMT and carotid plaque with
cardiovascular risk factors, prevalent cardiovascular disease and future
cardiovascular events in older people with Type 2 diabetes. The association between
cIMT, carotid plaque and other novel risk markers was also explored.
The analysis was performed using data from the Edinburgh Type 2 Diabetes Study
(ET2DS). This study is a large, prospective cohort study of 1066 men and women
with Type 2 diabetes, aged 60-75 years at recruitment, living in Edinburgh and the
Lothians. cIMT and carotid plaque were measured at year 1 follow up of the study.
Variables concerning cardiovascular risk factors used in this thesis were obtained
from the data collection performed at baseline and year 1. A mean of 3.5 years of
follow up was available for analysis and is complete for the baseline cohort as data
linkage was performed.
Mean values of cIMT in the ET2DS were comparable with other studies of cIMT in
people with Type 2 diabetes and may indeed be higher than cIMT in the general
population. Measurement of cIMT by the sonographer was comparable with
computer aided measurements. Increasing cIMT was independently associated
(although only modestly) with increasing age, male sex and raised systolic blood
pressure. Mean cIMT was associated with prevalent vascular disease and was
predictive of incident global cardiovascular events and coronary artery events (but
not stroke) over and above UKPDS risk factors, although the clinical impact of this
on the reclassification of vascular risk (as demonstrated by net reclassification index
(NRI)) was limited.
There was a high prevalence of carotid plaque, and in particular “high risk” plaque,
in the ET2DS. Different measures of carotid plaque were independently associated
with several cardiovascular risk factors. Carotid plaque thickness was independently
associated, albeit modestly, with increasing age, male sex, duration of diabetes and
hypertension, plaque score with increasing age, hypertension, smoking and low BMI,
and high risk plaque with hypertension and low BMI. All measures of carotid plaque
were associated with prevalent vascular disease. However, despite these
associations, carotid plaque did not have any additional predictive value for incident
cardiovascular events over and above UKPDS risk factors.
Finally, measures of cIMT and carotid plaque in the ET2DS were associated with the
biomarkers ankle brachial index (ABI) and NTproBNP. In addition these markers
were significantly higher in those individuals with prevalent vascular disease,
suggesting a more extensive exploration of the association of these markers in
relation to cardiovascular disease in the ET2DS may be warranted. cIMT and carotid plaque are modestly associated with traditional cardiovascular risk
factors and prevalent cardiovascular disease in older adults with Type 2 diabetes.
cIMT has been shown to be predictive of incident events while carotid plaque was
not, in people with Type 2 diabetes, over and above traditional cardiovascular risk
factors, although its impact on risk reclassification may only be small. Further
evidence is required from the longer follow up of the ET2DS before firm conclusions
can be drawn on the usefulness of cIMT and carotid plaque as risk markers in people
with Type 2 diabetes. In addition, large collaborative studies could be used to further
explore the relationship of carotid plaque, and change in cIMT with incident
cardiovascular events, as well as exploring the additive effect of cIMT and plaque on
risk prediction
Effects of prior experience on shelter-seeking behavior of juvenile American lobsters
No full textAuthor Posting. © University of Chicago, 2017. This article is posted here by permission of University of Chicago for personal use, not for redistribution. The definitive version was published in Biological Bulletin 232 (2017): 101-109, doi:10.1086/692697.Shelter-seeking behaviors are vital for survival for a range of juvenile benthic organisms. These behaviors may be innate or they may be affected by prior experience. After hatching, American lobsters Homarus americanus likely first come into contact with shelter during the late postlarval (decapodid) stage, known as stage IV. After the subsequent molt to the first juvenile stage (stage V), they are entirely benthic and are thought to be highly cryptic. We hypothesized that postlarval (stage IV) experience with shelter would carry over into the first juvenile stage (stage V) and reduce the time needed for juveniles to locate and enter shelters (sheltering). We found some evidence of a carryover effect, but not the one we predicted: stage V juveniles with postlarval shelter experience took significantly longer to initiate sheltering. We also hypothesized that stage V juveniles would demonstrate learning by relocating shelters more quickly with immediate prior experience. Our findings were mixed. In a maze, juveniles with immediate prior experience were faster to regain visual contact with shelter, suggesting that they had learned the location of the shelter. In contrast, there was no significant effect of immediate prior experience on time to initiate sheltering in an open arena, or in the maze after juveniles had regained visual contact. We conclude that very young (stage V) juvenile lobsters modify their shelter-seeking behavior based on prior experiences across several timescales. Ecologically relevant variation in habitat exposure among postlarval and early juvenile lobsters may influence successful recruitment in this culturally and commercially important fishery species.This work was supported by a Woods Hole Oceanographic
Institution Postdoctoral Scholar Award (MWJ), a National
Science Foundation Graduate Research Fellowship (SRB),
NOAA Saltonstall-Kennedy Grant (MWJ), and National Science
Foundation Grant IOS-0843440 (JA).2018-04-0
Evaluation of serum markers of neuronal damage following severe hypoglycaemia in adults with insulin-treated diabetes mellitus
No full textBackground Neurone-specific enolase (NSE) and protein S-100 (S-100) may be used as markers of acute neuronal damage in humans with neurological disorders. Method To evaluate their use following a single episode of severe hypoglycaemia (defined as an episode requiring external assistance to aid recovery), serum concentrations of NSE and S-100 were measured following hypoglycaemia which had not caused persistent neurological impairment in 16 patients with insulin-treated diabetes (the \u27hypo\u27 subjects), and in three diabetic patients who died following severe hypoglycaemia. The serum proteins were also measured in 10 subjects with insulin-treated diabetes who had not experienced an episode of severe hypoglycaemia within the preceding year (the \u27control\u27 subjects). Results No differences in serum concentrations of NSE and S-100 were observed between the \u27control\u27 and the \u27hypo\u27 subjects at either 36 hours or seven days after the episode of severe hypoglycaemia (p>0.05). However, in two of the three subjects who died following hypoglycaemia, serum concentrations of the markers were markedly elevated. Conclusions. Any neuronal injury occurring during severe hypoglycaemia that is not associated with persistent neurological deficit is insufficient to provoke elevation of these serum markers. However, the measurement of serum concentrations of NSE and S-100 may have a prognostic role in evaluating clinical outcome following severe hypoglycaemia which is associated with neurological damage. Copyright (C) 1999 John Wiley & Sons, Ltd
Fatal Haemorrhage following Fine Needle Aspiration of the Thyroid
No full text Fine needle aspiration is routinely performed as part of the assessment of thyroid nodules. It is generally regarded as a very safe procedure, though rarely significant bleeding can occur in its aftermath. A 79-year-old female was referred for assessment of an incidental thyroid nodule which had been identified on computed tomography of the chest and extended into the retrosternal space. The patient was referred for fine needle aspiration under ultrasound guidance. Three passes were made with a 25 gauge needle into the nodule; a haemorrhagic aspirate was obtained and sent for cytological examination. Several hours later, the patient developed a cough and progressive breathlessness and died at home before she could be taken to hospital. The key finding from the post-mortem was extensive haemorrhage within the capsule of thyroid. In the absence of another identifiable aetiology, the cause of death was considered to be acute haemorrhage into the thyroid gland. Thyroid fine needle aspiration is generally a safe procedure, but it is important to recognise that, rarely, major complications can occur. </jats:p
