Type 2 Diabetes remission
For those interested in dietary treatments for type 2 diabetes (T2D), the last few months have sure been really exciting. Firstly, in December 2017, Lean et al. (2017) published in The Lancet the results from their last trial conducted in the UK, the Diabetes Remission Clinical Trial (DiRECT). Secondly, this past month (February 2018), Hallberg et al. (2018) have published in Diabetes Therapy their results from the Virta Treatment, conducted in the USA and being the follow-up of their previously published study in 2017.
Although probably other important studies on dietary management of T2D have been published lately, these two studies are especially important as they did not just achieve diabetes improvement, but even diabetes remission. This post is not intended to be an exhaustive analysis of these papers but rather a comparison and some considerations of their main characteristics and findings.
In few words, both studies comprised 2 groups of T2D participants:
In DiRECT, the control group was assigned to “diabetes care under current guidelines and standards from the National Institute of Health and Care Excellence in England and the Scottish Intercollegiate Guidelines Network in Scotland”. The intervention group was asked to follow the Counterweight-Plus weight management programme.
In Virta’s study, the control group was established with “patients … who were recently referred to the local diabetes education program by their primary care physician or endocrinologist where they were counselled by registered dietitians on diabetes self-management, nutrition, and lifestyle”. The intervention group was provided with a continuous care intervention (Virta´s treatment) based on a very low carbohydrate ketogenic diet (KD) and continuous monitoring.
DiRECT control group
As described by the authors and according to the dietary guidelines back in 2014 (when the recruitment took place), was most likely encouraged to follow the official UK dietary recommendations, based on “The eatwell plate/guide”.
After 1 year, on average, participants gain 1 kg of weight, their HbA1c increased 0.1%, their serum triglyceride increased by 0.09 mmol/L and their blood pressure did not decrease (and so, there was no changes in antihypertensive drugs prescription for hypertensive participants at baseline). But, that’s not all, because mean antidiabetic drug prescribed increased, and these drugs were commenced in 8 participants (5%). On the “bright side”, 6 participants (4%) achieved diabetes remission (while losing 4.5 kg on average), and antidiabetic medications were stopped in 1 participant, who did not lose weight and had a HbA1c value of 7.9% (still in the diabetes range).
Virta control group
In this case participants were recruited in 2015 and 2016 and treated according to the Standards of Medical Care in Diabetes.
From then to now (2018) the dietary advise has not changed much and fat intake recommendations are those applied for the general population. This translates into a low-fat high-carb diet with carbohydrate intake from low glycaemic vegetables, fruits, whole grains, legumes and dairy products. After a year, no changes were noted for any of the variables measured.
DiRECT intervention group
Participants in the intervention group were asked to follow the Counterweight-Plus weight management programme (Table). After 1 year, on average, participants lost 10 kg and their HbA1c fell by -0.9%, their serum triglyceride decreased by -0.31 mmol/L, 109 participants (74%) were taking no antidiabetics medication (with mean HbA1c = 6.4%), the mean number of antidiabetic medications prescribed decreased and antihypertensive drugs were withdrawn in 38 (48%) of 80 participants were taking them at baseline. At 1 year, 36 participants (24%) lost 15 kg or more and 68 participants (46%) went into remission (authors defined it as HbA1c < 6.5% after 2 months taking no antidiabetes medication).
Interestingly, during the 1st phase, participants lost 14.5 kg, but gained weight during the food reintroduction phase (+1 kg) and the weight loss management phase (+2 kg).
Virta intervention group
Participants in the intervention group were assigned to a continuous care intervention (Table 1). After 1 year, on average, participants reduced their HbA1c, fasting glucose, fasting insulin, weight, systolic blood pressure, diastolic blood pressure, triglycerides and hs-CRP (a marker of inflammation). On the other hand, LDL and HDL cholesterol increased.
The authors do not define T2D remission and neither do they specify the number of patients achieving remission (if any). However, 52 participants achieved HbA1c < 6.5% while taking no antidiabetic medication, so we could boldly say that 25% of patients in this group achieved remission.
What does this all mean?
We would like to argue that these studies reveal some remarkable things.
The standard treatment, either in the USA or in the UK, does not seem to work as after 1 year of treatment participants, in general, did not improve their T2D markers, in some cases they worsened and in very few cases they improved. So, is this the best we can do? If any patient diagnosed with T2D is expected to get these outcomes after following the official recommendations, then it is quite reasonable that T2D is considered a chronic, progressive, irreversible disease.
Losing a considerable amount of weight when obese was linked in these studies to T2D remission. This weight loss was achieved after 3 months when restricting calories (to approx. 800 kcal/day) or after 12 months when restricting carbohydrates (to ≤30 g/day).
The results of these studies show that T2D is, at least in some cases, not chronic, progressive and irreversible. Dietary modifications can put T2D into remission, presumably at no cost for patients and reducing expenses for the corresponding health services.
Although weight loss is important, there are other factors to consider when evaluating dietary interventions such as markers of inflammation, the lipid profile, blood pressure, body composition… Hallberg et al. conducted a thorough analysis of a long list of measures, demonstrating that a low-carb high-fat ketogenic diet was not only effective in reducing HbA1c and body weight, but also in improving many other aspects, including general inflammation. Unfortunately, Lean et al. did not analyse such an extensive list of variables so there is no way to compare the whole effect of their intervention.
In further posts, we will get deeper into these studies’ design to point out some of the most interesting aspects and some potential improvements that should be addressed in future trials.
Hallberg, S. J., McKenzie, A. L., Williams, P. T., Bhanpuri, N. H., Peters, A. L., Campbell, W. W., . . . Volek, J. S. (2018). Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study. Diabetes Ther. doi:10.1007/s13300-018-0373-9
Lean, M. E., Leslie, W. S., Barnes, A. C., Brosnahan, N., Thom, G., McCombie, L., . . . Taylor, R. (2017). Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. doi:10.1016/S0140-6736(17)33102-1