Type 2 diabetes (T2D) is a major health problem in the UK. It is due to abnormally high blood sugar levels and directly linked to increased body fat (e.g. obesity). When people living with obesity develop T2D it is known as ‘diabesity’, and the numbers are expected to significantly rise in the coming years. This is concerning given that both obesity and T2D can cause long-term damage to bodily organs such as the brain, heart, liver, and kidneys. The treatment of diabesity involves making changes to a person’s lifestyle to induce weight loss, which can then be combined with medication or even surgery. Despite this advice, weight loss is hard to achieve and maintain for many people. Our concern is that most people with diabesity are unable to obtain a healthy weight and get good control of their diabetes leading to chronic health problems and high healthcare costs and utilisation. If this is true, then we need to reconsider how we treat the condition, especially early on. In our study, we will look at what happens to people over ten years after they are first diagnosed with diabesity. We will do this by looking at changes in their weight, blood tests, and health conditions using data routinely recorded by general practitioners. We will then assess what treatments people had to see which are more effective at improving weight loss, controlling T2D, and preventing organ damage. This will help us develop better treatment pathways to prevent long-term problems and healthcare costs.
Type 2 diabetes (T2D) is a major public health burden directly linked to high body mass index (BMI). The combination of T2D and obesity is termed ‘diabesity’, which is a major risk factor for many conditions including cardiovascular disease. Despite anti-diabetic medications, many patients remain overweight with poor diabetic control and the estimated annual rates of weight normalisation among obese individuals is <1%. Bariatric surgery is the most effective treatment for obesity with profound anti-diabetic effects. However, <1% of suitable patients undergo surgery, and it is not scalable. Consequently, novel endoscopic treatments and medications have been developed that could be introduced earlier, and in combination. However, we first need to define the long-term problems to warrant future research.
A UK cohort study will be conducted looking at long-term health outcomes among patients living with obesity at the point they are diagnosed with T2D between 2005-2023. CPRD data, including deprivation and ethnicity, will be analysed over 10-years from the point of T2D diagnosis. We hypothesise most patients will not regain normal BMI, have ongoing poor diabetic control, and have adverse health outcomes including major cardiovascular events. Primary outcomes will be major cardiovascular events and mortality. Secondary outcomes will look at changes in HbA1c, number and use of anti-diabetic medications, biometric data, and adverse health outcomes. Regression models will be used to determine relationships between outcomes and covariates. Results will provide the foundation for future research into early, intensive treatment for diabesity as ‘top-down’ strategies to reverse diabetes and achieve weight loss. To emulate this future prospective research, we will conduct a target trial emulation to assess the impact of treatment allocation to bariatric surgery, intensive medical therapy, or standard medical therapy within the first 18 months of diabesity diagnosis. Primary outcomes will be major cardiovascular events, cardiovascular death, and all-cause mortality.
Primary outcome(s)
The following primary outcomes will be used for both the cohort study and target trial emulation:
• Number of major adverse cardiovascular events (defined as a non-fatal myocardial infarction, coronary artery disease, coronary artery stenting, coronary artery bypass grafting, non-fatal stroke, or cardiovascular death) at 5- and 10-years. • All-cause mortality
These represent hard outcomes that are more easily coded and analysed than surrogate markers of diabetic control and weight loss.
The following secondary outcomes will be used for the cohort study:
• Average level of HbA1c (mmol/mol) at 5- and 10-years after the diagnosis of T2D.
• Average difference in HbA1c (mmol/mol) between baseline (at diagnosis) and 5- and 10-years.
• Average number and dose of oral anti-diabetic medications being used at 5- and 10-years after the diagnosis of T2D.
• Average difference in the number and dose of oral anti-diabetic medications being used between baseline (diagnosis) and 5- and 10-years.
• Proportion of patients taking insulin at 5- and 10-years after the diagnosis of T2D.
• Average BMI at 5- and 10-years after the diagnosis of T2D.
• Average difference in BMI between baseline (diagnosis) and 5- and 10-years.
• Proportion of patients with a BMI above the following thresholds at 5- and 10-years:
o BMI ≥30 kg/m2.
o BMI ≥35 kg/m2.
o BMI ≥40 kg/m2.
• Number of patients with at least stage 4 chronic kidney disease (defined by an eGFR <30 ml/min/1.73 m2 or need for dialysis) at 5- and 10-years after the diagnosis of T2D.
• Number of hospital hospital admission, bed days, and critical care use (HES APC linked data)
• Number of patients undergoing at least one lower limb amputation at 5- and 10-years after the diagnosis of T2D.
• Number of patients diagnosed with anxiety and/or depression at 5- and 10-years after the diagnosis of T2D.
• Number of patients undergoing bariatric surgery (defined as sleeve gastrectomy, gastric bypass, or gastric band) at 5- and 10-years after the diagnosis of T2D.
The following secondary outcomes will be used for the target trial emulation:
• Proportion of patients achieving a BMI ≤ 25 kg/m2 after 5-years and 10 years
• Proportion of patients achieving a BMI < 30 kg/m2 after 5-years and 10 years
• Proportion of patients achieving a BMI ≤ 35 kg/m2 after 5-years and 10 years
• Average time (days) to achieve a BMI ≤ 25 kg/m2
• Average time (days) to achieve a BMI < 30 kg/m2
• Proportion of patients achieving a HbA1c ≤ 48 mmol/mol after 5-years and 10 years
• Proportion of patients achieving a HbA1c < 53 mmol/mol after 5-years and 10 years
• Proportion of patients in the standard or intensive medical therapy groups who subsequently undergo bariatric surgery
Michail Katsoulis - Chief Investigator - University College London ( UCL )
Benjamin Norton - Corresponding Applicant - University College London ( UCL )
James Bailey - Collaborator - University College London ( UCL )
Kenneth Man - Collaborator - University College London ( UCL )
Victoria Yorke-Edwards - Collaborator - University College London ( UCL )
James Bailey - Collaborator - University College London ( UCL )
Kenneth Man - Collaborator - University College London ( UCL )
Michail Katsoulis - Collaborator - University College London ( UCL )
Victoria Yorke-Edwards - Collaborator - University College London ( UCL )
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;CPRD Aurum Ethnicity Record;CPRD GOLD Ethnicity Record