In a recent study published in the journal Dr the natureResearchers examined the core framework of the National Health Service (NHS) Diabetes Prevention Program (DPP) implemented in the United Kingdom (UK).
This program is considered the most comprehensive behavior change program for pre-diabetes worldwide.
They tested the program to determine whether it was effective in improving the health of people with prediabetes, particularly their glycated hemoglobin (HbA1c), excess body weight and serum lipid levels, as well as cardiovascular health risk factors.
Background
The NHS DPP targets people with non-diabetic hyperglycaemia (or prediabetes) and provides face-to-face quality assured intensive lifestyle and behavior change support to prevent or delay the onset of type 2 diabetes (T2DM).
Specifically, it offered weight loss, diet and physical activity goals to its target population over 13 group sessions implemented over nine months. It has been rolled out on a large scale offering 100,000 referrals in 2021.
As T2D and diabetes-related deaths continue to increase worldwide, there is a need to implement population-level measures to prevent or delay the onset of T2D, improve its diagnosis, and address its cardiovascular risk factors.
Clinical trials, such as the United States (US) Diabetes Prevention Study, provide proof of principle that lifestyle and behavior changes are effective when delivered in one-on-one sessions with incentives. A recent meta-analysis also showed that lifestyle changes can reverse prediabetes in adults.
However, it remains unclear whether behavior change programs work in real-world settings. The most common reason for this is the suspicion among clinicians that lifestyle counseling does not work for the majority of people representing the general population because they have low health literacy and unwillingness to engage.
Accordingly, at present, a significant proportion of adults in England with prediabetes do not participate in intensive lifestyle counseling due to system-level (unavailability of NHS DPP) or clinician- and patient-level.
About the study
In the current study, researchers used de-identified electronic health records (EHRs) of more than two million patients across a fifth of UK general practices.
These records were obtained from the Clinical Practice Research Datalink (CPRD) Aurum and the NHS England Hospital Episode Statistics Admitted Patient Care (HES APC) database. This data broadly represents the national population in terms of geographical coverage, socio-economic deprivation, gender and age.
These individuals aged 18 to 80 years had their HbA1c assessed between 1 January 2017 and 31 December 2018, indicating that their HbA1c levels were between 42-47 mmol mol.−1 Last year.
The researchers applied regression analysis, a reliable quasi-experimental technique, to estimate the causal effect of referral to intensive lifestyle counseling on all study outcomes.
They used a fuzzy regression discontinuity (FRD) design that prospectively assigned treatment to estimate the effect of patients present just above the eligibility threshold, resulting in the compounder’s average causal effect (CACE). CACE is analogous to the intention-to-treat (ITT) effect in a target trial.
Primary outcome was change in HbA1c level from baseline to final follow-up. Then, there were secondary outcomes, such as changes in body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), serum cholesterol and triglyceride levels.
Exploratory analyzes investigated the effect of program referrals on newly prescribed diabetes medications, blood pressure- or lipid-lowering medications, any T2D-related complications (eg, ocular, neurological, renal), mortality, and hospitalization for a major adverse event. Cardiovascular events (MACE).
The follow-up study began six months after the baseline HbA1c assessment and ended with an outcome or censoring, for example, due to death.
Note that the NHS DPP began a phased roll-out in 2016, with waves 1, 2, and 3 from 1 June 2016, 1 April 2017 and 1 April 2018. Difference-in-differences analysis comparing GP patients at waves 1 and 2 with patients from wave 3 (control) practices.
Finally, the researchers present an analysis using regional variation in NHS DPP coverage as an instrumental variable (IV) for the actual receipt of program referrals.
discussion
The researchers noted that 26,970 patients were referred to a behavior change program or intensive lifestyle counseling at any time in the 12 months following baseline HbA1c assessment, of which 77.7% received an NHS DPP referral.
In the robustness analysis, where they restricted the referral window to three months after the baseline HbA1c assessment and only considered NHS DPP referrals, only 620 patients received a referral. Referral effects were similar, albeit with slightly larger reductions in HbA1c than in the primary analysis.
There is mixed evidence of improvement in glycemic control in people with prediabetes in controlled trials; In contrast, this study corroborates indications from previous correlational studies suggesting beneficial effects of NHS DPP participation on HbA1c levels and weight control.
They found that the beneficial effect of referral to intensive lifestyle counseling on HbA1c at follow-up was significant (−0.10 mmol mol−1 to −0.85 mmol mol−1) although the clinical significance of a 0.85 mmol mol−1 While reductions in HbA1c are difficult to measure at an individual level, they are meaningful at a population level.
Among patients eligible for the NHS DPP in the initial cohort, 28.1% of patients started the intervention. Scaling the impact of program referrals to selected bandwidths reduced HbA1c concentrations in patients by ~3 mmol mol−1They strictly adhere to the referral intervention.
Having an HbA1c concentration above the eligibility threshold for NHS DPP was associated with a small increase in the odds of being prescribed diabetes medication immediately after treatment assignment, which increased at follow-up. There were no breaks between newly prescribed lipid- and blood pressure-lowering drugs.
In secondary analyses, referral to intensive lifestyle counseling significantly reduced BMI by −1.35 kg m−2 and body weight by −2.99 kg. However, referral to intensive lifestyle counseling did not significantly reduce diabetes complications, emergency hospitalization for MACE, and mortality in exploratory analyses.
Furthermore, while both men and women significantly improved their BMI, the effect estimates suggested greater improvement in men than in women.
In a difference-in-difference analysis, the group-time average treatment effect estimated favorable implementation of the NHS DPP to improve glycemic control.
Analysis using regional variation in NHS DPP coverage also showed a significant beneficial effect of program referral on follow-up HbA1c assessment.
Conclusion
This research supports further investment in structured, population-level behavioral interventions and targeted prevention strategies for individuals at risk of T2D, particularly those not within the scope of conventional care pathways.
Importantly, these programs can also extend benefits to other non-communicable diseases such as cancer or infectious diseases (eg, influenza, coronavirus disease 2019 [COVID-19]), which can have more serious effects in people with diabetes.
Overall, the research highlights a promising path to improve population-wide health more broadly.