DIADEM-I: Early T2D Reversible with Intensive Lifestyle Interventions

In the DIADEM-I study, intensive lifestyle interventions in younger patients with early type 2 diabetes not only effected significant weight loss at 12 months but led to diabetes remission on more than 60% and normoglycemia in over 30% of participants as well. Results from this study — conducted in the Middle East and North Africa — were published in The Lancet Diabetes & Endocrinology.

“Current recommendations for diabetes management focus strongly on the use of medications to control blood glucose, blood lipids, and blood pressure. However, this approach results in a substantial patient burden and health-care costs. Insufficient focus has been placed on addressing the underlying reversible causes of diabetes,” wrote Shahrad Taheri, MBBS, of Weill Cornell Medicine Qatar, Qatar Foundation, Doha, Qatar, and colleagues.

“We did the Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I) trial, which is the first randomized controlled trial in young patients with early diabetes (duration of 3 years or less) in primary care and who are from the Middle East and north Africa region, to examine the effect of a 12-month intensive lifestyle intervention, incorporating a total diet replacement phase (with formula low-energy diet meal replacement products), on weight loss and glycemic control,” they added.

The DIADEM-I study is an open-label, parallel-group, randomized controlled trial conducted by Taheri and fellow researchers in primary care and community settings in Qatar. It builds on results from the DiRECT trial, in which UK researchers found that weight loss achieved via 3 months of a very-low calorie, total meal-replacement diet brought about remission of type 2 diabetes. The DiRECT study, however, was done primarily in white participants.

Therefore, Taheri et al set out to study the effects of intensive lifestyle interventions in participants from the Middle East and North Africa. They compared the effects of intensive lifestyle interventions with usual medical care on weight loss and glycemic outcomes in 147 participants (mean age: 42.1 years; mean BMI: 34.9 kg/m²

Participants were randomized to either intensive lifestyle intervention—comprised of a total diet replacement phase followed by gradual reintroduction of food combined with physical activity support, and a weight-loss maintenance phase, which included structured lifestyle support—or usual medical care based on clinical guidelines.

During the 12-month study, those in the intervention group lost significantly more of their mean bodyweight compared with those in the control group (11.98 kg [95% CI: 9.72-14.23] vs 3.98 kg [95% CI: 2.78-5.18]) for an adjusted mean difference of −6.08 kg (95% CI: −8.37 to −3.79; P ˂ 0.0001). Further, more of those in the intervention group achieved a >15% weight loss during the 12 months than those in the control group (21% vs 1%, respectively; P ˂ 0.0001).

Greatest weight losses in the intervention group were seen during the total diet replacement phase between study initiation and 3 months. During months 3-6, weight loss continued but more slowly, after which it was maintained until 12 months.

Taheri and colleagues defined diabetes remission as an HbA1c of less than 6.5% with no pharmacologic treatment for at least 3 months. In the intervention group, a full 61% of participants experienced remission of diabetes, compared with only 12% of those in the control group (OR: 12.03; 95% CI: 5.17-28.03; P ˂ 0.001), and normoglycemia—defined as HbA1c of less than 5.7% with no pharmacologic treatment for at least 3 months — occurred in 33% vs 4%, respectively (OR: 12.07; 95% CI: 3.43-42.45; P ˂ 0.0001).

Those in the intervention group also demonstrated greater reductions in mean HbA1c compared with controls (adjusted difference: −0.62; 95% CI: −0.92 to −0.33; P=0.020). After 12 months, fewer participants in the intervention group were taking diabetes medications as well (6% of 68 versus 81% of 72 participants, respectively).

Also notable was that significantly fewer patients in the intervention group were still taking antihypertensive therapy (16% versus 35% participants; P ˂ 0.001) or lipid lowering medications (26% versus 76%; OR: 0.11; 95% CI: 0.05-0.24; P ˂ 0.001) at 12 months.

The same pattern was seen in the total number of medications for any condition. By 12 months, the mean number of medications taken was significantly lower in the intervention group compared with the control group (P ˂ 0.001). Those in the intervention group were taking a mean of 3.5 medications at baseline. At 12 months, this was reduced to a mean of 2.0 medications. This compares with participants in the control group, who took a mean of 3.6 medications at baseline, which increased rather than decreased to a mean of 4.9 medications at 12 months.

Participants in the intervention group also reduced the length of time they spent sitting each day by 40.8 minutes, while those in the control group increased this time by 68.8 minutes (adjusted difference: −88.1 min; 95% CI: −162.2 to −14.0; P=0.020). However, there was no significant between-group difference in the time spent doing moderate and vigorous activity.

Finally, researchers found that patient-reported quality-of-life scores were increased in the intervention group and reduced in the control group (adjusted difference: 4.03; 95% CI: 1.12-9.19; P=0.124). Mental health outcomes, however, did not differ between the groups.

In the control group, five serious adverse events occurred in four participants, including four hospitalizations due to supraventricular tachycardia, abdominal pain, pneumonia, and epididymo-orchitis, and one for hyperglycemia.

Limitations of the study include the limited geographical area included, use of only one multidisciplinary team to deliver the intervention, and limiting outcomes assessment to 12 months. Follow-up of this cohort, however, is ongoing.

“Our findings show that type 2 diabetes is reversible in a significant proportion of patients, provided that the condition is managed early, and they challenge the commonly held view that type 2 diabetes is a lifelong condition that requires continuous pharmacotherapy to control the associated symptoms and prevent complications,” concluded Taheri and fellow researchers.

Ron Taylor, BSc, MB ChB, MD, FRCP, FRCPE, of Newcastle University, Newcastle upon Tyne, UK, commented on the importance of the racial differences in the study cohorts used in the DIADEM-I and the DiRECT studies in an accompanying editorial.

“The degree of fat deposition in the liver and pancreas is known to be typically lower in people of black African ethnicity, and whether type 2 diabetes in other ethnic groups shares the same pathogenesis and would respond to weight loss in the same way has been questioned. Additionally, attitudes to weight loss and food are affected by cultural factors, and willingness to achieve weight loss cannot be assumed,” he wrote.

Results from Taheri and colleagues are, therefore, of great importance, Taylor added.

“These data are striking for two major reasons. First, it is clear that remission of type 2 diabetes follows adequate weight loss in people from the Middle East and north Africa. The degree of weight loss in individuals who received the intensive lifestyle intervention in this study was similar to that observed in the UK DiRECT study,” he wrote. “Second, no cultural barriers to achieving weight loss through diet were encountered, and participants in the intervention group maintained weight loss of 10–15 kg for up to 1 year,” he concluded.

1. In younger patients with early type 2 diabetes in the Middle East and North Africa, intensive lifestyle interventions brought about significant weight loss as well as increased remission of diabetes and normoglycemia.

2. Results from the DIADEM-I study confirm the benefits of intensive lifestyle interventions in those of Middle Eastern and North African descent.

E.C. Meszaros, Contributing Writer, BreakingMED™

Cat ID: 13

Topic ID: 76,13,730,13,669,918