Sodium-glucose co-transporter 2 inhibitors are a type of medication that helps kidneys remove excess sugar from the body through urine in people who have trouble regulating the amount of sugar in their blood (type 2 diabetes mellitus ). These medications also lower the chance of heart attack, heart failure or sudden interruption of blood flow to the brain (stroke) in those people who had already had one of those in the past. No definite explanation for this action has been established as yet and this has not been confirmed in people with no such history. These medications may also slow the chance of worsening of kidney function. These actions might be explained by changes in the space red blood cells take up in the total volume of the blood (haematocrit), after treatment. We wish to explore whether those people with greater changes in changes in the space red blood cells take up have better outcomes related to the heart and blood vessels and kidney. This would mean that such changes could be used to guide treatment to those who would benefit the most.
Aims:
To investigate whether the change in haematocrit (absolute or percentage change) after SGLT2i institution in patients with T2DM is associated with the risk of subsequent development of cardiorenal outcomes and death from any cause.
Methods/design:
We will perform a series of open cohort studies including all patients with type 2 diabetes mellitus who have been initiated treatment with SGLT2i to investigate the association of change in haematocrit with the risk of developing cardiorenal outcomes and all-cause mortality.
Outcomes:
The primary outcome is the composite end-point, including all-cause mortality, myocardial infarction, ischaemic heart disease, and stroke. Secondary outcomes are all-cause mortality, myocardial infarction, ischaemic heart disease, stroke, transient ischemic attack, peripheral arterial disease, heart failure, atrial fibrillation, and chronic kidney diseases. Back pain will be used as a negative control outcome in this study.
Exposures:
The change in haematocrit
Participants:
Individuals with a diagnosis of type 2 diabetes aged 40 years and over will be eligible for this study. All participants must have been registered with the general practice for at least one year before the index date (start of follow-up).
Covariates:
Sociodemographic characteristics (e.g. Index of Multiple Deprivation), diabetes-related characteristics, comorbidities, biomarkers, and drug prescriptions will be adjusted to account for residual confounding.
Methods:
Except for the outcome of all-cause mortality, competing risk Cox proportional hazard regression models will be used to calculate crude and adjusted hazard ratios, together with their corresponding 95% CIs.
Intended public health benefit
If the magnitude of change in haematocrit is associated with the subsequent cardiorenal outcomes, it could be used as a marker of the future expected response. The public health benefit from such knowledge would be important since a more tailored approach to pharmacotherapy in type 2 diabetes might be facilitated.
Primary outcome:
composite end-point including
1. all-cause mortality,
2. myocardial infarction
3. ischaemic heart disease
4. stroke
Secondary outcomes:
1. all-cause mortality.
2. myocardial infarction
3. ischaemic heart disease
3. stroke
4. transient ischemic attack
5. peripheral arterial disease
6. heart failure,
7. atrial fibrillation
8. chronic kidney disease stage 3 to 5
Chronic back pain will be used as negative control outcome in this study.
Konstantinos Toulis - Chief Investigator - University of Birmingham
Jingya Wang - Corresponding Applicant - University of Birmingham
Krishnarajah Nirantharakumar - Collaborator - University of Birmingham
Luyuan Tan - Collaborator - University of Birmingham
Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation