Pakistan Prevention Programme for Gestational Diabetes Mellitus (PPP-GDM): a feasibility study

Type 2 diabetes (T2DM) and gestational diabetes mellitus (GDM) are escalating problems worldwide. Depending on the population studied, 1-14% of all pregnancies are complicated by GDM. In Pakistan, we estimate prevalence of GDM is 8% and this has huge financial costs to health care. Further, pregnancies complicated by GDM have increased incidence of fetal, maternal, and childhood long term complications. Therefore, there is an urgent need to implement a coordinated approach to prevent T2DM. It is established that lifestyle modification with weight loss/moderate exercise can reduce T2DM by up to 58% in high risk people. Our research question for the future full randomized trial is 'in women with gestational diabetes mellitus, is a lifestyle intervention programme focusing on physical activity and weight maintenance feasible in a developing country to decrease the risk of diabetes?
To inform the design of a larger full trial, we will first undertake a feasibility study to test whether the components of the main study can all work together. Specifically, it is focused on the processes of the main study to ensure the integrity of the study protocol including:
- recruitment to study
- willingness of participants to be randomised
- randomisation process
- consent for blood tests
- refinement and delivery of the intervention
- acceptability and adherence to the intervention
- follow-up assessments

Achievement of these components will be analysed to inform decisions about progression and the experience accumulated will assist in the refinement of the design of the full trial. In addition, we will estimate
the mean and standard deviation of the primary outcome to confirm the trial sample size calculations.
Many benefits will arise from this development grant proposal:
1. Academic beneficiaries through publication in peer reviewed journals and presentations at national and international conferences.
2. As there is little research on this topic in low- and middle-income countries (LMICs), we will develop and pilot a novel intervention that will subsequently be tested in a larger trial. This then has potential to be scaled-up in other LMICs.
3. Reducing and/or slowing the rise in diabetes in LMICs is a challenge for all and our developmental proposal will be of interest and use to clinicians and researchers in Pakistan as well as globally.
4. The close collaboration between researchers based at the University of Birmingham, UK and Agha Khan University in Pakistan will further enhanced this international collaboration.
5. This will then lead to increasing research capacity both in the UK and Pakistan.
6. We will also generate data in this in this feasibility and subsequent full trial which will be available for other researchers - though the data collected from the follow-on trial is more likely to be a richer database of qualitative and quantitative material.
7. Prevention of diabetes in women with GDM once the intervention is scale up and fully implemented in Pakistan.
8. Policy makers in Pakistan will have a robust, evidence-based intervention as part of their health plan.

Diabetes Mellitus (DM) is major,global challenge and has implications for patients, family and wider society. The majority of people with DM live in low- and middle-income countries and poses an enormous financial costs. Gestational diabetes mellitus(GDM) is defined as any degree of glucose intolerance during pregnancy. Risk factors for GDM include family history of diabetes, age >30 years, being overweight/obese at time of conception, and being of South Asian origin. In antenatal women at Aga Khan University Hospital, Pakistan, prevalence of GDM was 8%. Pregnancies complicated by GDM have increased incidence of foetal, maternal and childhood obesity with associated long term risks. Therefore, there is an urgent need to implement a coordinated approach to prevent DM and it' is established that lifestyle modification can reduce T2DM by up to 58% in high risk people.
Our research question for the future full randomized trial is 'in women with GDM, is a lifestyle intervention programme focusing on physical activity and weight maintenance feasible in a developing country to decrease the risk of diabetes?
To inform the design of a larger full trial, we will first undertake a feasibility study to test whether the components of the main study can all work together. Specifically, it is focused on the processes of the main study to ensure the integrity of the study protocol including:
- recruitment to study
- willingness of participants to be randomised
- randomisation process
- consent for blood tests
- refinement and delivery of the intervention
- acceptability and adherence to the intervention
- follow-up assessments
Achievement of these components will be analysed as a proportion to inform decisions about progression and the experience accumulated will assist in the future trial design. In addition, we will estimate the mean and standard deviation of the primary outcome to confirm the trial sample size calculations.

Summary
Reducing risk of diabetes in women with gestational diabetes mellitus is intrinsically of high impact. However, we have also prioritised methods to maximise impact from an early stage in study design. The qualitative aspects for example, will establish what are the precise barriers that may hinder implementation of any interventions, the follow-on trial and sustainability and scaling up of the proven interventions. The impact of the program will be enhanced by its novelty due to scarcity of literature on preventing diabetes in high risk women (i.e. those with gestational diabetes mellitus); using community health workers to deliver the intervention as well as voice/text messaging in a LMIC such as Pakistan.
There is a very high chance that we can improve care with a complex and yet low cost intervention utilising the findings of this development grant. Demographic, shift to chronic diseases, growth in middle-income and educated articulating demands for better care, are some of the pressures currently imposed upon the health services in countries like Pakistan - these will further increase the need for and receptivity to our findings. The ultimate aim of this development grant is to:
1. informed by research into current practice and analysis of what is feasible and potentially good value for money during this development proposal.
2. design and implement a full RCT in major public and private hospitals in Pakistan. Application of our findings from the barriers and facilitators to optimal management has the potential to impact at the following levels:
1. The patient and public
2. The health system
3. The region and country (Pakistan) where the work is undertaken
4. The other LMIC's
5. The global academic level where the experience gained in this venture will inform the design of further international collaborative initiatives.

The impact will be both direct and indirect at many of these levels as well as immediate and long term. These will be a lasting legacy of the project.

Effective health systems policies, strengthening governance and improving care
The probability that emerging policies will be effective is maximised in two ways:
1. The UK and Pakistan partners have considerable experience of working with service partners that will benefit the development of policies to be recommended.
2. For the main intervention implementation trial, we propose established methods that highlight stake-holder involvement as a guiding principle for. A crucial stake-holder constituency in our study are the service users who not only contribute by giving their opinions and sharing experience, but also by suggesting improvements and adaptations - the powerful method of 'end-user innovation'. Involving service managers and policy makers will create a pathway through which sound practices can become embedded in governance structures.


Capacity for health service research
Research beneficiaries in the short and long term will benefit, both in the UK and Pakistan locally and nationally through training and knowledge sharing, and collaboration opening opportunities for future projects.

Patients and public
Most LMIC's are experiencing an expanding number of middle income families who are more articulate and demanding of the health services so that many years of richer country experience are likely to be concertinaed into a short period of time.Service planners are looking for methods to improve the quality of services and our findings will assist in this task.These will be maximised through our publications and public dissemination.

Economic impact: Once fully implemented, the intervention will reduce diabetes and out of pocket spending by patients, their families and cost saving more widely. This will improve their productivity through better health that in itself will increase economic ability of their family unit.