The aim of this thesis was to assess the relationships between glycaemic exposure and β-cell function with prevalence, incidence and progression of diabetic retinopathy (DR) over 5 years in newly-diagnosed treatment-naïve subjects with type2 diabetes mellitus (T2DM). At diagnosis, we studied 544 subjects and demonstrated DR was independently associated with fasting and postprandial hyperglycaemia and reduced fasting β-cell function during standardized meal and intravenous glucose challenge. The insulin-independent component of glucose tolerance (SG) was also impaired and independently associated with presence of DR at diagnosis. We followed up 233 subjects over 5 years and established independent association between chronic glycaemic exposure (HbA1c,/fasting/ postprandial hyperglycaemia) at diagnosis and incident DR during this period. We also demonstrated that fasting and postprandial β-cell responsiveness to nutrient challenge along with SG at baseline was independently associated with development of DR over 5 years. There was no difference in glycaemic status between those with or without DR at 5 years highlighting the relevance of early history of glycaemic exposure in our subjects to future incidence of DR. Finally, in 45 T2DM subjects with DR at diagnosis, fasting, postprandial glucose and HbA1c along with fasting, postprandial β-cell responsiveness at diagnosis were all independently associated with DR progression. Thus, this study has indicated that hyperglycaemia resulting from pancreatic β-cell deficiency contributes to the risk of development and progression of DR. The data emphasises the need for earlier diagnosis of T2DM and cautious normalization of glycaemia to eliminate glucotoxicity on the already impaired β-cell function. The evidence indicates the potential value of supporting β-cell function aiming to achieve near-normal glycaemia and thus preventing the onset and progression of DR in subjects with T2DM.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:716019 |
| Date | January 2016 |
| Creators | Roy Chowdhury, Sharmistha |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/101021/ |
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