Abstract
Worldwide, the escalating Type 2 diabetes mellitus (T2DM) pandemic adversely impacts individuals, families/whānau, health systems, and society. While genetic and other factors contribute, T2DM is a potentially preventable lifestyle associated disease. However, little progress has been made in reducing its prevalence. Individuals with abnormally high blood glucose concentrations which do not reach diagnostic thresholds for T2DM are classified as having pre-diabetes and may be at risk of developing T2DM. As pre-diabetes is a heterogeneous condition, the related health risks for this group are variable and incompletely understood. For an individual, the detection of pre-diabetes provides an important opportunity to intervene to prevent or delay the onset of T2DM. Currently, weight loss achieved through dietary modification and increased physical activity is the most effective diabetes prevention strategy. Nevertheless, lifestyle modifications are difficult to implement and sustain and can be ineffective. Additionally, research examining how pre-diabetes care is undertaken in Aotearoa/New Zealand (NZ) is lacking.
This situation calls for new, proven, widely acceptable, and easily implemented individual-level interventions to add to the suite of diabetes prevention tools. Additionally, we need to understand how pre-diabetes care is currently delivered and what supports or inhibits its success. Finally, to reduce T2DM and ensure health service provision is optimised and sustainable, we need to identify which individuals with pre-diabetes are at greatest risk of developing adverse health outcomes. This thesis presents an extensive literature review and three studies addressing specific aspects of these research gaps.
The first study tests the efficacy of novel interventions for pre-diabetes. Using a 2 x 2 factorial design placebo-controlled double-blinded randomised controlled trial (RCT) conducted in adults with pre-diabetes, this study examines the effect of six months of supplementation with probiotic and prebiotic interventions on the primary outcome of glycated haemoglobin (HbA1c) at six months. The interventions included the probiotic Lactobacillus rhamnosus HN001(HN001) 6 x 109 colony-forming units per day (cfu/day) administered by capsule and cereal containing 4 g/day oat-derived beta-glucan (OBG). Outcomes were measured at three, six and nine months. Multiple secondary outcomes relevant to T2DM were also examined. These included fasting plasma glucose (FPG), fasting insulin, homeostatic model of insulin resistance (HOMA-IR), fasting lipids, blood pressure, body weight, waist circumference (WC), body mass index (BMI), and mental wellbeing.
This study found no evidence of clinical benefit from the supplementation with either HN001 and/or OBG cereal on HbA1c or any secondary outcomes and does not support the clinical use of these interventions in populations with pre-diabetes.
During the development and conduct of the first study, it became apparent that clinicians have variable perspectives about pre-diabetes and uncertainties regarding its significance. This observation led to the second study, a multiple case study examining how diabetes prevention work is conducted in general practices in NZ. Two qualitative case studies were undertaken in separate general practices serving ethnically and socioeconomically contrasting populations. Data including focus groups and clinical note reviews were collected and analysed sequentially. Focus group data were analysed using deductive and inductive thematic analysis. Clinical data were coded and extracted into single clinical case summaries, then compared. Both case studies were analysed separately before completing a cross-case comparison.
Four themes illustrating the adverse impacts of multiple factors on pre-diabetes care were developed. Contractual arrangements and the predominantly disease-centred focus of care reduced the priority and importance of pre-diabetes management within general practices. Clinicians expressed uncertainties about the importance of pre-diabetes and who was most likely to develop T2DM, noting it was difficult to identify those who had the greatest health risks. Inconsistency in screening and pre-diabetes care and support were also identified. When care was provided, the social determinants of health influenced patients’ ability to engage with and respond to pre-diabetes care.
The third study was developed in response to clinical questions revealed in the case study, regarding which people with HbA1c-defined pre-diabetes in NZ have the greatest health risks. This was an exploratory secondary analysis of baseline data from all participants in study one which examined the cardio-metabolic health profile of this study population. In contrast to a singular focus on hyperglycaemia, this study utilised the construct of metabolic syndrome (MetS), incorporating a matrix of fasting plasma glucose, waist circumference, high-density lipoprotein cholesterol, and triglycerides to describe this group’s cardio-metabolic health. MetS severity scores, measured as Z-scores, have been associated with the future development of T2DM and cardiovascular disease. Therefore, MetS Z-scores based on BMI were used to calculate the severity of MetS as a continuous measure. The study considered the clinical utility of characterising the study sample in this way.
Seventy-four percent of the study population had MetS, and the severity of MetS was highly variable, with scores ranging from -1.0 to 2.8. The prevalence and severity of MetS differed according to ethnicity and HbA1c level; however, all groups included individuals with widely differing severity of MetS. This study demonstrated a more nuanced understanding of cardio-metabolic risks associated with pre-diabetes was achieved when assessed using MetS-Z-BMI rather than HbA1c or MetS alone. The development of contemporary tools, similar to MetS severity scores, but using biomarkers commonly assessed in clinical practice may be useful to stratify risk, inform treatment decision-making and monitor changing cardio-metabolic health in those with pre-diabetes.
Findings from this thesis contribute to the body of knowledge regarding pre-diabetes and individual-level diabetes prevention. Multiple implications related to policy, clinical practice and future research are discussed.