Type 2 diabetes and rheumatoid arthritis (RA) are 2 common conditions that affect people’s health related quality of life and add to the burden of health care costs.
Type 2 diabetes and RA may share some of the same underlying risk factors such as chronic inflammation. RA may increase the risk of diabetic complications eg. Foot ulcer, eye disease and kidney problems among patients with type 2 diabetes. For management of RA, patients are usually prescribed conventional disease modifying anti-rheumatic drugs which are also known as cDMARDs. Some of the cDMARDs such as methotrexate may protect against diabetic kidney disease, while some others eg hydroxychloroquine may increase the risk of diabetic eye problems. There is little evidence directly supporting how the drugs affect the development of these complications.
In order to provide useful guidance for the patients of type 2 diabetes who also have a diagnosis of RA, it is important to find out the effects of these different cDMARDs on the risk of developing diabetic complications including those of the eyes, feet and kidney problems. To do this we will use detailed information on diagnoses and prescriptions from primary care records to see if the risk of diabetic complications differs in patients with both type 2 diabetes and RA who are prescribed different cDMARDS.
Chronic inflammation contributes to the aetiology of RA and type 2 diabetes and may influence the progression of microvascular complications. RA may increase the level of inflammation among patients with type 2 diabetes, leading to a greater risk of developing microvascular complications. The cDMARDs suppress overactive immune and inflammatory response, which reduces the level of inflammation. These drugs contribute to controlling insulin resistance, and may reduce the risk of microvascular complications among patients with type 2 diabetes and RA.
Literatures have evaluated the effect of cDMARDs on type 2 diabetes. There is paucity of data evaluating the effect of these drugs on the risk of microvascular complications. There may reversely be deleterious effect of cDMARDs, such as hydroxychloroquine inducing retinopathy, which may exacerbate conditions. The potential hazardous effect of glucocorticoids on hyperglycaemia and insulin may further the progression of microvascular complications.
The population will be a cohort of patients with diagnosis of type 2 diabetes and RA. We will use time-variant data to evaluate the effect of cDMARDs on sight threatening retinopathy, neuropathy and nephropathy. Five mutually exclusive groups will be identified:
1) methotrexate with or without any cDMARDs other than hydroxychloroquine (not be taking hydroxychloroquine);
2) hydroxychloroquine with or without any other cDMARDs other than methotrexate (not be taking methotrexate);
3) methotrexate and hydroxychloroquine with or without other cDMARDs;
4) other cDMARDs (sulfasalazine, leflunomide) without methotrexate or/and hydroxychloroquine;
5) no drug use (after initiation when considering as a time-dependent exposure).
HR and 95% CIs will be calculated for the occurrence of outcomes using a time-dependent Cox regression model. We will treat cDNARDs as time-varying covariates with a fixed follow-up interval of 3 months. Other cDMARDs groups will be used as reference group. We will also compare glucocorticoid users to non-users by extended Cox hazard regression model in time-variant analysis.
Primary outcomes:
• incident diabetic retinopathy
• incident diabetic foot disease
• incident diabetic nephropathy
Krishnarajah Nirantharakumar - Chief Investigator - University of Birmingham
Zhaonan Wang - Corresponding Applicant - University of Birmingham
Anuradhaa Subramanian - Collaborator - University of Birmingham
Dawit Zemedikun - Collaborator - University of Birmingham
Francesca Crowe - Collaborator - University of Birmingham
Jonathan Hazlehurst - Collaborator - University of Birmingham
Krishnarajah Nirantharakumar - Collaborator - University of Birmingham
Patient Level Index of Multiple Deprivation