DIABETES REMISSION: FACT OR FANTASY?

If you have had a diagnosis of type 2 diabetes, can it be reversed or ‘cured’ if you do all the right things?

This was a question that scientists at the University of Glasgow asked themselves in 2015 when they began the Diabetes Remission Clinical Trial (DiRECT (1)). They recruited people aged 20-65 years who had been diagnosed with type 2 diabetes less than 6 years earlier and had a body mass index (BMI) in the range 27 to 45 kg/m2 (indicative of excess body fat). Substantial weight loss using ‘shakes’ (known formally as total meal replacement products) was the aim for the first 3-5 months of the trial, followed by support to help maintain the weight loss for up to 2 years. They defined diabetes remission as reaching a glycated hemoglobin level of <6.5% (or <48 mmol/mol) and no need for diabetes (blood glucose lowering) medications. A control group received best practice care from their General Medical Practitioner (GP).

In total, they recruited 306 people who were randomly assigned to the intervention group or the control group. At the 12-month timepoint the investigators published their first findings in the prestigious medical journal The Lancet (1). They reported that nearly 1 in 4 people in the intervention group had lost 15 kg or more, compared with zero people in the control group. Diabetes remission was achieved in nearly half of those in the intervention group and just 6 people in the control group.

Further analyses showed that the greater the weight loss, the greater the chances of remission. For example, roughly 1 in 3 of those who had lost 5-10 kg were in remission, compared with 86% of those who lost 15 kg or more. Serious adverse events were rare, affecting only 7 people in the intervention group and 2 in the control group. The researchers made waves when they concluded that remission of type 2 diabetes is possible under the guidance of GP’s.

One year later, the group published their 24-month findings: 36% of the people in the intervention group were still in remission, compared with less than handful in the control group (2). On average, most participants regained about 2 kg. Even though many had resumed their diabetes medication (40% in those in the intervention group), the result was still stunning – sustained remission was indeed possible and linked to a longer period of weight loss maintenance.

The DiRECT study has had its fair share of controversy, firstly because the term ‘remission’ could be interpreted in different ways. Secondly, the study was great advertising for the food manufacturers who were selling total meal replacements. These had long been disparaged by members of the health professions because they were not ‘real food’. However, like the PREVIEW study that used a brief 8-week weight loss period on these formula diets, the rate of weight loss was fast and furious (3). This delighted the participants but not everyone was on board. Was it perfectly safe to lose weight in this manner? In fact, up ‘til then, most cases of diabetes remission had only been obtained using expensive, hard-to-access bariatric surgery. However, we now know that substantial weight loss (10%, or about 10 kg (22 Pounds) if you weigh 100 kg (220 Pounds)) reduces the amount of fat in the liver and pancreas, and reboots the pancreatic beta-cells responsible for making insulin. They (beta-cells) appear to have a ‘second wind’.

The greatest challenge for diabetes remission is to maintain the weight loss. That’s not easy – most of us have lost weight only to find it is all-too-easy to regain it. Indeed, in the past, as many as 19 in 20 people found they were back to their starting weight (or even more) within 6-12 months. Researchers are therefore turning their minds to how best to achieve weight loss maintenance.

One of the largest studies of this kind is the PREVIEW Study (3). People were eligible if they had risk factors for developing type 2 diabetes (e.g., they had pre-diabetes), as well as a body mass index of 25 kg/m2 or more. Over 2300 people used total meal replacements supplied by Cambridge® to lose at least 8% of their body weight in just 8 weeks. In fact, nearly 8 in 10 were successful, losing an average of 11% of their starting weight. The people were then randomly allocated to one of two different lifestyle interventions for the next 3 years. Using group instruction and other behavioural techniques, the researchers reported that nearly 1 in 4 people was able to maintain a weight loss of 8% or more, and 1 in 2 succeeded in maintaining 5% weight loss. In other words, long term weight loss maintenance is more achievable now than in the past.

Contrary to their hypothesis, the PREVIEW researchers found that a higher protein-lower GI diet was not superior to a conventional healthy diet with less protein and higher GI. But the story does not end there. A secondary analysis revealed that people consuming more protein and lower GI carbs were indeed more successful in maintaining weight loss (4), recording less hunger and food craving (5). In addition, these individuals achieved lower levels of glycated hemoglobin, indicating a reduced risk of developing type 2 diabetes in the future.

In PREVIEW and other studies of this kind, people were not permitted to continue to use total meal replacements to maintain their weight loss, even though many expressed the desire to do so. Would it be helpful to use them on a regular basis to lose a kilo or two whenever necessary? And how should we employ them? Would using them for 1-2 weeks be long enough? Would using them 5 days, once a month be best? Studies to answer these questions are currently in progress.

In the meantime, yes, you can send type 2 diabetes into remission, and fast weight loss using meal replacements is both a safe and effective way to kick-start the process.

1. Lean and colleagues. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open- label, cluster-randomised trial. Lancet. 2018.
2. Lean and colleagues. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2019
3. Raben and colleagues. The PREVIEW intervention study: Results from a 3-year randomized 2 x 2 factorial multinational trial investigating the role of protein, glycaemic index and physical activity for prevention of type 2 diabetes. Diabetes Obes Metab. 2021
4. Zhu and colleagues. Dose-Dependent Associations of Dietary Glycemic Index, Glycemic Load, and Fiber With 3-Year Weight Loss Maintenance and Glycemic Status in a High-Risk Population: A Secondary Analysis of the Diabetes Prevention Study PREVIEW. Diabetes Care, 2021
5. Zhu and colleagues. A High-Protein, Low Glycemic Index Diet Suppresses Hunger but Not Weight Regain After Weight Loss: Results From a Large, 3-Years Randomized Trial (PREVIEW). Frontiers in Nutrition, 2021

Professor Jennie Brand-Miller holds a Personal Chair in Human Nutrition in the Charles Perkins Centre and the School of Life and Environmental Sciences, at the University of Sydney. She is recognised around the world for her work on carbohydrates and the glycemic index (or GI) of foods, with over 300 scientific publications. Her books about the glycemic index have been bestsellers and made the GI a household word.