The bidirectional relationship between tuberculosis and diabetes mellitus has long been recognised,
and is of mounting importance as diabetes increases in prevalence globally, including in areas with a
high tuberculosis incidence. Evidence based strategies for management of this important cohort are
still lacking. This thesis explores three key areas of interest within this broad field.
Chapter Five presents a retrospective cohort from the United Kingdom with active tuberculosis, and
compares characteristics and tuberculosis treatment outcomes between groups with and without
diabetes. With diabetes largely well controlled, and increased age and comorbidities adjusted for,
diabetes was not independently associated with an adverse tuberculosis treatment outcome,
highlighting the importance of good quality glycaemic control in the tuberculosis-diabetes group.
Chapter Six uses a case control study to explore the hypothesis that anti-tuberculosis drug exposure is
lower in individuals with diabetes. Two hour post dose concentrations and 0-24 hour area under the
curve derived from population pharmacokinetic modelling were not found to be significantly lower in
the diabetes group. This conclusion is largely supported by the literature presented in a review of
similar studies in Chapter Two, and suggests that therapeutic drug monitoring may not be a key
intervention for this group.
Chapter Seven presents a sub-study of the pharmacokinetic cohort, comparing HbA1c results at
tuberculosis diagnosis and at 16 weeks into treatment. Results showed evidence of transient
hyperglycaemia defined by change in HbA1c with tuberculosis treatment alone, which was associated
with markers of more severe tuberculosis disease. This supports evidence presented in the systematic
review in Chapter Three, suggesting that a diagnosis of diabetes should not be made based on a single
result at time of tuberculosis diagnosis and that a larger study of this phenomenon is warranted.