Type 2 diabetes has traditionally been perceived as a non-reversible, progressive condition that eventually requires insulin therapy. Recent evidence, however, has been mounting in showing that type 2 diabetes, if diagnosed early, can be fully reversed with intense lifestyle modifications in a subset of patients.
In the current study published in Diabetic Medicine in September 2019, investigators followed prospectively about 900 adult diabetes patients age 40-70 over five years. Individuals who lost more than 10% of body weight within the first few years of the study, had the best chance of eliminating diabetes, as documented by A1c <6.5%.
At the study conclusion, 30% of adults achieved diabetes remission. Important to note that remission or reversal was accomplished independently of any specific lifestyle modifications, except the >10% weight loss.
More clinical trials are needed to confirm the above results. Nonetheless, intensive weight loss at the onset of diabetes diagnosis could be reasonable general advice for people who are overweight or obese.
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Diabetic Medicine
ADDITION
September 2019
Aim
To quantify the association between behaviour change and weight loss after diagnosis of Type 2 diabetes, and the likelihood of remission of diabetes at 5-year follow up.
Method
We conducted a prospective cohort study in 867 people with newly diagnosed diabetes aged 40–69 years from the ADDITION‐Cambridge trial. Participants were identified via stepwise screening between 2002-2006, and underwent assessment of weight change, physical activity (EPAQ2 questionnaire), diet (plasma vitamin C and self‐report), and alcohol consumption (self‐report) at baseline and 1 year after diagnosis.
ADDITION was examined at 5 years after diabetes diagnosis via HbA1c level. We constructed log binomial regression models to quantify the association between change in behaviour and weight over both the first year after diagnosis and the subsequent 1–5 years, as well as remission at 5‐year follow‐up.
Results
Diabetes remission was achieved in 257 participants (30%) at 5‐year follow‐up.
Compared with people who maintained the same weight, those who achieved ≥10% weight loss in the first year after diagnosis had a significantly higher likelihood of remission [RR 1.77, p<0.01].
In the subsequent 1–5 years, achieving ≥10% weight loss was also associated with remission [RR 2.43, p<0.01].
Conclusion
In a population‐based sample of adults with screen‐detected Type 2 diabetes, weight loss of ≥10% early in the disease trajectory was associated with a doubling of the likelihood of remission at 5 years.
This was achieved without intensive lifestyle interventions or extreme calorie restrictions. Greater attention should be paid to enabling people to achieve weight loss following diagnosis of Type 2 diabetes.
What’s new?
- Biochemical remission of Type 2 diabetes in the absence of pharmacological or surgical intervention has been shown to be achievable.
- This has been previously demonstrated in short‐term studies and only in selected populations through intensive weight loss programmes.
- We found that weight loss of ≥10% in the first few years after diagnosis was strongly associated with remission of Type 2 diabetes at 5 years.
- This was achieved without intensive lifestyle interventions or extreme calorie restrictions.
- Our findings should inform discussions with people who have newly diagnosed Type 2 diabetes as a motivation towards remission of the disease without restrictive and sometimes unachievable calorie restrictions.
More from the publication
Type 2 diabetes affects 400 million people globally and has been characterized as a lifelong progressive disease; however, biochemical remission or ‘cure’, defined as a level of glycaemia below the diagnostic threshold (HbA1c <6.5%) in the absence of pharmacological or surgical interventions, is achievable through significant calorie restriction and weight loss.
Although there are varying definitions of remission in the literature, we have adhered to that based on HbA1c levels in line with UK and US national guidance. Intensive low‐calorie diet (total energy intake of 624–700 kcal/day) for 8 weeks was associated with remission in 87% of people with recently diagnosed diabetes (<4 years) and in 50% of people with longstanding disease (>8 years).
Similarly, the Action for Health in Diabetes (Look AHEAD) study included an intensive 4‐year programme, designed to increase physical activity and reduce initial weight by ≥7%. Participants had a median diabetes duration of 5 years and, in the first year after the intervention, 11.5% achieved partial or complete remission compared to only 2.0% in the usual care group.
In the DIRECT trial, participants who had been diagnosed with diabetes in the previous 6 years underwent an intensive intervention, including withdrawal of diabetes and blood pressure medication, diet replacement of 825–853 kcal/day through a formula diet for 3–5 months, stepped food reintroduction (2–8 weeks), and structured support for long‐term weight loss maintenance. Remission was achieved in 46% of the intervention group. Collectively, these studies support the hypothesis that healthy behaviour change and weight loss can result in remission of diabetes.
In all these studies, however, selected participants were recruited to intensive weight loss interventions. Evidence is therefore required from representative population‐based samples undergoing less intensive interventions that are more feasible and potentially scalable to the wider population. Furthermore, most studies have either examined remission in the short term or amongst people who have lived with diabetes for a few years, or both. It is unclear if behaviour change and weight loss early in the disease trajectory could lead to long‐term remission. This is important as there could be a window of opportunity following diagnosis when people might be more receptive to interventions concerning weight loss. Using data from the ADDITION‐Cambridge population‐based study of screening for Type 2 diabetes, we quantified the association between behaviour change and weight loss in the year after diagnosis and the subsequent 4 years, in relation to the likelihood of remission of diabetes at 5‐year follow‐up.
- In this prospective cohort study, we investigated the association between weight loss and remission of Type 2 diabetes at 5 years. We found that modest weight loss of ≥10% in the first year or first 5 years after diagnosis was strongly associated with remission of Type 2 diabetes.
The present findings support and add to previous research that has demonstrated associations between weight loss and remission of Type 2 diabetes. For example, The DIRECT trial, also set in UK primary care, reported varying rates of remission of diabetes, depending on weight loss. The trial had aimed for a 15‐kg weight loss through an intensive intervention that included withdrawal of antidiabetic and antihypertensive drugs, total diet replacement (825–853 kcal/day formula diet for 3–5 months), stepped food reintroduction (2–8 weeks), and structured support for long‐term weight loss maintenance.
On average, 10 kg (15%) of weight was lost in the intervention group and half of the participants achieved remission. Other studies with similar intensive interventions in highly selected populations include the Counterbalance trial and the Look AHEAD trial. The Look AHEAD trial did not report remission as a primary outcome, but did include intensive support through dietary and physical activity programmes which resulted in remission. Whilst our observational findings are consistent with these trials, the specific amount of weight loss required to achieve remission varies.
Most previous studies advocate significant weight loss (>15%), with the DIRECT, Counterbalance and Look AHEAD trials reporting between 5‐ and 20‐kg weight loss in order to achieve diabetes remission. However, while baseline HbA1c values were lower in our screen‐detected cohort, our results suggest that more modest weight loss of >10% is associated with a higher likelihood of remission if this occurs early in the disease trajectory. This may provide some rationale for motivating people with newly diagnosed Type 2 diabetes to lose weight rather than focusing on specific and potentially unachievable weight targets. Previous studies have shown that, when attempting to lose weight, people often set unrealistically high weight loss goals that could be detrimental to success, and evidence on whether weight loss counselling with specific targets is always successful is inconsistent.
Indeed, the DIRECT trial did not manage to achieve the weight loss targets intended for most participants, with only 24% managing the 15‐kg target weight loss despite the intensive support. Furthermore, these interventions are unlikely to be scalable to the wider population because of their intensity and cost and the limited availability of facilitators. Our data suggest that, in addition to extending availability of intensive weight loss interventions, policymakers should consider a range of accessible approaches targeting weight loss amongst people with newly diagnosed diabetes.
Finally, while we observed associations between weight change and remission, we did not observe consistent associations between behaviour change and remission. This might be attributable to the differential precision of the exposure measurements, most of which were self‐reported and therefore subject to error and bias. For example, we found that self‐reported alcohol intake was associated with remission. Although there is some mixed evidence in the literature suggesting that moderate alcohol intake could be associated with positive cardiovascular outcomes, our findings were not consistent between adjusted and unadjusted models. It is therefore unlikely to be a true association. It could be due to chance or residual confounding.
The present study included people with Type 2 diabetes from a large population‐based sample across an extensive geographical area in the East of England in routine clinical follow‐up. We used measures of remission that are available in clinical practice to allow translation of our findings to practice. There was heterogeneity in this cohort with regard to socio‐economic groups, disease severity and health behaviours. There were also no specific dietary or physical activity restrictions for participants. This means that the study is generalizable to wider diabetes populations outside clinical trial cohorts; however, the sample was not ethnically diverse, comprising predominantly white European participants, which reflects the local population.
Other strengths include the duration of follow‐up which was 5 years; most previous remission studies were of < 12 months’ duration. Also, participant retention in the present cohort was high, being 95% at 1‐year follow‐up and 83% at the 5‐year follow‐up. Behaviours were measured using previously validated questionnaires and repeated measures with the same instruments, reducing our concerns about measurement error. We did, however, conduct a number of hypothesis tests, so chance remains a plausible explanation for our findings.
- In conclusion, remission of Type 2 diabetes is achievable in the longer term with modest weight loss of >10% early in the disease trajectory. This can be achieved without intensive interventions in free‐living populations. Our findings should inform discussions with people who have newly diagnosed Type 2 diabetes as motivation towards remission of the disease without restrictive and sometimes unachievable calorie restrictions. Further work is needed to replicate these findings in more ethnically and socially diverse populations. Further examination will need to include an assessment of the relationship between remission and longer‐term clinical outcomes, such as mortality.