NDPS Data Show Minor Weight Loss Can Almost Halve T2D Risk

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For individuals currently in high-risk glycemic categories, losing 2 to 3 kg (4.5-6.5 lb) in combination with increased physical activity over 2 years nearly halved the risk of developing type 2 diabetes (T2D).

For individuals in high-risk glycemic categories, losing 2 to 3 kg (4.5-6.5 lb) in combination with increased physical activity over 2 years nearly halved the risk of developing type 2 diabetes (T2D). Findings of the Norfolk Diabetes Prevention Study (NDPS), which paired some participants with diabetes prevention mentors (DPMs), were published in JAMA Internal Medicine.

Between 1980 and 2014, the global diabetes population quadrupled to 422 million individuals. This increase was matched “by what has been described as a worldwide epidemic of the intermediate glycemic categories that carry a high risk of T2D.”

Early prevention trials, which are used for current prevention programs, were mostly carried out in populations defined as high risk based on impaired glucose intolerance using an oral glucose tolerance test, as opposed to elevated fasting plasma glucose (FPG) or impaired fasting glucose (IFG).

Because no prevention trial of more than 2 years’ duration has used glycated hemoglobin (HbA1C) as the diabetes diagnostic primary end point, the prevention evidence base does not align with current diagnostic approaches. “We cannot assume that the outcomes of earlier trials (in different high-risk glycemic populations with IGT) are translatable to populations with current high-risk intermediate glycemic categories, who differ in pathophysiology, progression rates, and vascular risk,” the authors explained.


They conducted the randomized clinical trial in England to test the efficacy of a group-based lifestyle intervention supported by trained volunteers with T2D (DPMs) in reducing T2D incidence among those within current prediabetes glycemic categories. NDPS is the largest diabetes prevention research study in the world in the past 30 years.

The 7-year research program randomized eligible participants into 3-arms with up to 46 months of follow-up. Interventions were delivered by trained health care professionals alone, by diabetes prevention facilitators (DPFs), or delivered jointly by DPFs and DPMs. They aimed to support maintenance of changes in physical activity and diet. Specifically, patient-centered counseling techniques were used to encourage decision-making about behavior changes and increase motivation to change.

Development of T2D, based on paired HbA1C level of 6.5% or greater, or paired with FPG of 126 mg/dL or greater, was the study’s primary outcome. Between October 2011 and June 2017, 424 eligible participants were randomized into the standard theory-based lifestyle intervention arm (INT), 426 into the combined INT-DPM arm, and 178 into the control arm receiving usual care (CON).

The mean (SD) participant age was 65.3 (10) years while mean follow-up was 24.7 (13.4) months. The researchers found:

  • A total of 156 participants progressed to T2D, which comprised 39 of 171 receiving CON (22.8%), 55 of 403 receiving INT (13.7%), and 62 of 414 receiving INT-DPM (15.0%)
  • There was no significant difference between the intervention arms in the primary outcome (odds ratio [OR], 1.14; 95% CI, 0.77-1.7; P = .51)
  • Each intervention arm had significantly lower odds of T2D (INT: OR, 0.54; 95% CI, 0.34-0.85; P = .01; INT-DPM: OR, 0.61; 95% CI, 0.39-0.96; P = .033; combined: OR, 0.57; 95% CI, 0.38-0.87; P = .01)
  • The effect size was similar in all glycemic, age, and social deprivation groups
  • Intervention costs per participant were $153
  • Individuals with a current high-risk intermediate glycemic category of IFG and/or NDH were 40% to 47% less likely to develop T2D in the intervention groups compared with controls over an average 24 months
  • The INT-DPM group at 12 months had a significantly lower mean (SD) weight (−1.76 kg [−3.88 lb]), waist circumference (−2.48 cm [−.98 in]), and BMI

Although the enhanced intervention with trained DPMs did not further reduce the risk of T2D development, roughly 1 person was prevented from developing T2D for every 11 who received intervention.

“These findings are relevant to normal clinical practice, as nearly half of the older adult population now has a high-risk glycemic category or diabetes, as do one-third of young adults with obesity, with IFG constituting the largest element,” the researchers wrote. In addition, lifestyle changes were sustained for at least 2 years while weight loss was not put back on.

Because participants come from largely White populations, these results may not be generalizable to more ethnically diverse populations, marking a limitation to the study.

“We have now shown a significant effect in T2D prevention, and we can be very optimistic that even a modest weight loss, and an increase in physical activity, in real world programs like this have a big effect on the risk of getting T2D,” said Michael Sampson, MD, a chief investigator of NDPS.


Sampson M, Clark A, Bachmann M, et al. Lifestyle intervention with or without lay volunteers to prevent type 2 diabetes in people with impaired fasting glucose and/or nondiabetic hyperglycemia: a randomized clinical trial. JAMA Intern Med. Published online November 2, 2020. doi:10.1001/jamainternmed.2020.5938