A study of the association between diabetes and fibrotic multimorbidity

Study type
Protocol
Date of Approval
Study reference ID
24_003977
Lay Summary

Diabetes is a condition where a person cannot control their blood sugar levels. There are two main types of diabetes. Type 1 diabetes is when a person cannot produce insulin which is needed to control blood sugar it can develop at any age but is often diagnosed when people are young. People with type 1 diabetes must inject themselves with insulin to control their blood sugar levels. In contrast, Type 2 diabetics are insulin resistant, when insulin does not work as well. People with type 2 diabetes can be managed with a combination of lifestyle (by the foods they eat), non-insulin medications and insulin. In both types of diabetes, if blood sugar levels are not controlled, people with diabetes may get damage to their eyes, kidneys, and nerves.

Some diseases such as diabetes can cause organ scarring, damaging the affected organ, and decreasing its ability to function, eventually leading to organ failure. These diseases can be referred to as being fibrotic. We will investigate if more people with diabetes and damaged eyes/ kidneys/ nerves have other fibrotic conditions, compared with people with diabetes without damaged eyes/ kidneys/ nerves. We will also look to see if less people with diabetes who are on certain medication get fibrotic conditions compared with people on other medication for diabetes and those who are prescribed insulin, as a marker for more advanced diabetes. This will benefit public health as it will inform us if there are other conditions associated with diabetes that are also fibrotic.

Technical Summary

Fibrosis can affect any organ; fibrotic conditions are characterised by excessive, uncontrolled deposition of extracellular matrix in the effected site, this in turn alters the tissue’s extracellular environment, leading to organ failure. Despite fibrosis leading to eventual organ death, there is still a large gap in the understanding of fibrotic diseases’ aetiologies and pathways. Fibrotic multi-morbidity is defined as the simultaneous occurrence of more than one fibrotic condition in a patient. Previous work using a Delphi methodology determined conditions which were always/ sometimes fibrotic using clinical consensus. As a result of this work diabetes mellitus was defined as being sometimes fibrotic.
In the UK, Diabetes mellitus (DM) affects a substantial proportion of the population, with over 4.3 million people affected. Around 90% of DM cases in the UK are of type 2 diabetes, we will explore both type 1 and type 2 diabetes.
We will explore complications associated with poor diabetes management/ control (diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy and in the case of type 2 diabetics alone we will also apply NICE treatment guidelines to classify the medication stage). We will then look to see based upon the people with and without ‘poor diabetes management/control’ the proportion of people with fibrotic conditions differs, as well as the average number of fibrotic conditions.
We will use linked CPRD Aurum with HES APC, ONS data as well as IMD data. CPRD Aurum data will be used to define the complications and prescription data will also be analysed. CPRD Aurum, HES APC and ONS data will be used to define fibrotic conditions. Our primary outcome is diagnosis of a fibrotic condition. We will use Logistic regression models.
This work will look to provide further insight into whether diabetes management is associated with fibrotic conditions.

Health Outcomes to be Measured

Percentage of people with fibrotic conditions and fibrotic multimorbidity, subgrouped by diabetes management and related disease complications (e.g. retinopathy)
Association between diabetes management and diagnosis of fibrotic conditions (subgrouped).

Collaborators

Jennifer Quint - Chief Investigator - Imperial College London
Georgie Massen - Corresponding Applicant - Imperial College London
Gisli Jenkins - Collaborator - Imperial College London
Iain Stewart - Collaborator - Imperial College London
Louise Wain - Collaborator - University of Leicester
Sarah Cook - Collaborator - Imperial College London

Linkages

HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation