Development of a local protocol and method to measure Beta-Cell Function in individuals with Pre-diabetes and Type 2 Diabetes
|dc.identifier.citation||Kanaan, R. (2018). Development of a local protocol and method to measure Beta-Cell Function in individuals with Pre-diabetes and Type 2 Diabetes (Thesis, Bachelor of Biomedical Sciences with Honours). University of Otago. Retrieved from http://hdl.handle.net/10523/8603||en|
|dc.description.abstract||Type 2 diabetes mellitus (T2DM) is long-term metabolic disorder characterised by high blood glucose (BG), insulin resistance and poor insulin secretion. T2DM is preceded by pre-diabetes characterised by altered glucose metabolism where BG levels are higher than normal, but do not fall within the T2DM range. High rates of T2DM are present in Māori, Pacific and South Asian New Zealanders compared to European New Zealanders. These disparities in the New Zealand (NZ) population are not improving with current approaches. However, targeting the progression from pre-diabetes to T2DM could be an opportunity to improve the health status of New Zealanders. The PROGRESS NZ study, being conducted by the University of Otago, Wellington, is currently investigating differences between people with pre-diabetes and T2DM in the NZ population. This Honours project is a subset of this study. T2DM results from a combination of insulin resistance and pancreatic β-cell failure. However, the relative contributions of each pathway vary between individuals. It is necessary to quantify β-cell function (βCF) for the assessment of insulin sensitivity. This thesis will focus on the development of a local method to measure βCF, the development of the C-peptide enzyme-linked immunosorbent assay (ELISA) and the deconvolution of the data. The tolerability of the techniques will be assessed. This study aimed to recruit 20 participants for the PROGRESS NZ feasibility study. The hyperinsulinaemic-isoglycaemic clamp technique was employed to measure insulin sensitivity and the stepped insulin secretion test with arginine (SISTA) was used to measure βCF. The tolerability of both techniques was examined in the study population. Because of recruitment delays, practical issues with running the SISTA and adverse events incurred with some of the earlier participants, this Honours study was only able to include data from five-participants who completed the SISTA study. Baseline SISTA results were used to measure βCF in five-participants. Insulin secretion was measured during two consecutive 30-minute hyperglycemic steps (2.8 and 5.6mmol/L above baseline BG), followed by an intravenous arginine bolus (8.3mL of 60% arginine). Insulin secretion was quantified using blood C-peptide concentrations. Local protocols were setup for the analysis of C-peptide concentrations using an ELISA. The data underwent deconvolution to model pre-hepatic insulin secretion rate. The acute insulin response (AIR), derived from the highest insulin secretion value, minus baseline insulin at basal glucose, was used to analyse βCF. The AIR to arginine (AIRarg) was tenfold greater than that elicited by the first hyperglycemic step in participant 1 (2978.83 vs. 298.15pmol/min). Participant 2 showed only a slight difference (1442.79 vs. 1115.37pmol/min). Participant 3 showed fourfold difference (2918.75 vs. 797.5pmol/min). Participant 4 showed a fivefold difference (7489.36 vs. 1566.4pmol/min). Lastly, Participant 5 showed an elevenfold difference (4696.03 vs. 409.13pmol/min). The mean insulin secretion elicited by the arginine bolus was approximately fivefold greater than the 1st hyperglycemic step (3905.15 ±2311.19 vs. 837.31 ±520.70pmol/min). This project has focused on developing a local method and protocol. We have overcome some of the challenges in conducting the SISTA such as thrombophlebitis and extravasation injury, including setting up the C-peptide ELISA and applied the deconvolution method to local data. The results of the five-participants illustrate the outcome of that work, in addition they highlight the large variability in the participants and the pathogenesis of diabetes.|
|dc.publisher||University of Otago|
|dc.rights||All items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.|
|dc.title||Development of a local protocol and method to measure Beta-Cell Function in individuals with Pre-diabetes and Type 2 Diabetes|
|thesis.degree.name||Bachelor of Biomedical Sciences with Honours|
|thesis.degree.grantor||University of Otago|
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