The prevalence of type 2 diabetes is increasing in the UK. Many people with type 2 diabetes require glucose-lowering therapy including insulin when lifestyle interventions fail to provide adequate glucose control. Some epidemiological studies report an association between insulin use in type 2 diabetes and an increased risk of serious adverse events when compared with other glucose-lowering therapies. However, these findings should be interpreted with caution due to the risk of confounding by indication. The aim of this thesis was to characterise the epidemiology of type 2 diabetes and to investigate the risk of serious adverse events associated with increasing insulin dose in people with type 2 diabetes prescribed insulin therapy. A series of retrospective, observational studies were conducted using data from the Clinical Practice Research Datalink. People with type 2 diabetes were identified and prevalence and incidence rates calculated. The risk of all-cause mortality, major cardiovascular events and cancer in people with type 2 diabetes who progressed to insulin with or without metformin were evaluated using multivariate models. Between 1991 and 2010, the estimated incidence and prevalence of clinically diagnosed and recorded type 2 diabetes increased three-fold. During the same period, the estimated number of people with diagnosed and recorded type 2 diabetes treated with insulin increased seven-fold. Estimated insulin dose was associated with an increased risk of all-cause mortality in people with type 2 diabetes receiving insulin monotherapy (aHR 1.54, 95% CI 1.32–1.78, for 1 unit/kg/day increase in insulin dose) and in those treated with insulin with or without metformin (1.48, 1.31–1.70). However, the use of metformin in combination with insulin was associated with a reduction in risk compared with insulin alone (0.60, 0.52–0.68). Due to the limitations associated with observational studies, further research is required in order to improve our understanding of the risks and benefits of exogenous insulin in type 2 diabetes.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:667908 |
| Date | January 2015 |
| Creators | Holden, Sarah E. |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/77715/ |
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