On 5th December 2017, we woke up to the headlines: “A cure for diabetes: Crash diet can REVERSE Type 2 in three months…” and “I beat type 2 diabetes with 200-calorie drinks”.
The headlines came from a study published in The Lancet entitled “Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial.” (Ref 1)
The study made a bold claim: “Our DiRECT study provides the first evidence from a randomised trial of a dietary and lifestyle intervention with remission of type 2 diabetes as a primary outcome.”
The researchers said that they had searched articles published between 1st January 1980 and 30th October 2017 for non-surgical clinical trials with a primary outcome of remission of type 2 diabetes. “Our search terms were ‘diabetes and remission’ and ‘clinical trial’… No trials were identified.”
I don’t think that the researchers looked hard enough. Within minutes of seeing The Lancet study, Sam Feltham emailed me to say “what about the Dr Eric Westman paper?” (Ref 2) This classic study is in my EndNotes, it was referenced in two recent comprehensive reviews of low carbohydrate diets (Refs 3, 4) and it has been cited 226 times at the time of writing this post. It is fair to say that it is well known, therefore.
Westman et al undertook a randomised controlled dietary trial (first tick) in 84 people with type 2 diabetes (second tick). The primary outcome was the same measure of diabetes remission as The Lancet study – HbA1c and medication reduction/elimination (third tick). The 2008 paper used the word “reversing”, rather than remission. The conclusion of this study was “Dietary modification led to improvements in glycemic control and medication reduction/elimination in motivated volunteers with type 2 diabetes. The diet lower in carbohydrate led to greater improvements in glycemic control, and more frequent medication reduction/elimination than the low glycemic index diet. Lifestyle modification using low carbohydrate interventions is effective for improving and reversing type 2 diabetes” (my emphasis).
Other evidence before this study
There have also been other studies proving different components of the claim made in The Lancet paper:
* Remission in a randomised trial in PRE-diabetes.
In 2016, an article was published by Stentz et al entitled “Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial.” (Ref 5) This study involved 24 people with pre-diabetes randomised to either a high protein (30% protein, 30% fat, 40% carbohydrate) intervention, or the typical high carbohydrate government advice (15% protein, 30% fat, 55% carbohydrate). All meals were provided to all participants for six months. After 6 months, 100% of the people on the high protein diet had remission of their pre-diabetes (defined as normal glucose tolerance), whereas only 33% of the high carbohydrate group had remission of their pre-diabetes.
* Remission in a non-randomised trial in type 2 diabetes.
In 2017, the seminal publication from the Virta Health team reported on a non-randomised intervention with 262 adults with type 2 diabetes. (Ref 6) This study involved the reduction/ elimination of medication, alongside a ketogenic diet (typical carbohydrate intake below 30g a day and protein intake targeted to a level of 1.5g per kg of body weight). The primary outcome was HbA1c. Weight and medication use were secondary outcomes. At 10 weeks, 15% of participants had achieved an HbA1c level of <6.5%, while taking no medication. The researchers concluded “biomarkers of type 2 diabetes can be reversed…”
* Remission in a randomised trial of diabetes and pre-diabetes, without mentioning remission or reversal.
The Saslow et al study from 2014 was a randomised controlled trial in adults with diabetes or pre-diabetes. (Ref 7) The intervention was a very low carb high fat ketogenic diet. The control was the standard advice from the American Diabetes Association. The primary end point was reduction in HbA1c. A secondary endpoint was discontinuation of diabetes medications. Both were significantly greater in the ketogenic diet group. While this small study did not claim remission or reversal of type 2 diabetes, it achieved these in a number of cases.
There is also a systematic review and meta-analysis of 20 randomised controlled trials (tick) for dietary interventions in type 2 diabetes (tick). I would be surprised if at least one of these had not achieved remission/reversal, defined by HbA1c and medication use. (Ref 8)
None of these studies was referenced by The Lancet paper.
The Lancet Study
The Lancet study involved 306 people recruited between July 2014 and August 2017 from 49 primary care practices in Scotland and the Tyneside region of England. The trial was described as a cluster-randomised trial. This meant that the 49 practices were randomly assigned to provide either the intervention or best-practice care guidelines (the control). The individuals recruited in each practice would then follow the protocol randomly set for that practice.
The participants were aged between 20-65 years and they had been diagnosed with type 2 diabetes within the previous 6 years. They had BMIs in the range 27-45 kg/m2 and were not taking insulin. There were a number of interesting exclusions for participants. People were not allowed to take part in the trial if they had any of the following: weight loss of more than 5kg within the past 6 months; current HbA1c of 12% or more (≥ 108mmol/mol); current treatment with anti-obesity drugs; and/or presence of an eating disorder. There were other exclusions, but these piqued my interest, as they gave the study a higher chance of success.
The intervention involved i) removal of diabetes and blood pressure medications on day 1; ii) total diet replacement with a 825-853 kcal/day liquid formula for 3-5 months; iii) “stepped food reintroduction” for 2-8 weeks; and iv) “structured support for long-term weight loss maintenance”. There was next to no information in the article about steps iii and iv – I’ve written to the corresponding author to ask what the food and calorie intake was in these two key phases, after the liquid diet.
Please note the immediate, profound, implications of (i) – participants were taken off diabetes and blood pressure medications on day 1. The paper noted that blood glucose and blood pressure were regularly monitored to see if drugs needed to be reintroduced. This means that it is now known (if it were not before) that people with type 2 diabetes can be taken off medication and that type 2 diabetes can be managed with diet. The low carb community has been saying this for years.
The study set out to measure two primary outcomes: weight loss of 15 kg or more, and remission of diabetes, which was defined as HbA1c of less than 6.5% (<48 mmol/mol) after at least 2 months off all anti-diabetic medications, between baseline and 12 months.
The results were reviewed at 12 months. Weight loss of 15 kg or more was recorded in 36 people (24%) in the intervention group and in no one in the control group. Diabetes remission was achieved in 68 (46%) people in the intervention group and in 6 (4%) people in the control group. Remission was closely connected to weight loss. 76 people gained weight during the study! None of these 76 people achieved remission. Remission was achieved in: 6 of 89 people who maintained a 0-5kg weight loss; 19 of 56 people with a 5-10kg weight loss; 16 of 28 people with a 10-15kg weight loss and 31 of 36 people who lost 15kg or more.
The average (mean) weight reduction was 10 kg in the intervention group and 1kg in the control group. These are impressive results.
The first phase of the intervention was three months long and this could be extended to five months if wished by the participant. This phase involved a meal replacement diet with four sachets a day, each sachet providing approximately 200 calories. The macronutrient composition of the liquid phase of the diet was 59% carbohydrate, 13% fat, and 26% protein. As noted above, there were no details in the paper about the food reintroduction phase (of 2-8 weeks) or the “ongoing structured programme for long-term weight loss maintenance” thereafter. The structured food reintroduction phase was reported to contain “about 50% carbohydrate, 35% total fat, and 15% protein.” That was the only information provided.
One of the newspaper articles covering the study contained more detail. Two of the participants in The Lancet trial, Isobel and Tony, were interviewed by the Daily Mail. Isobel, 65, was diagnosed with type 2 diabetes in 2011. She was put on medication, but her blood sugars actually increased and she gained weight and was put on even more medication. In 2013 she “jumped” at the opportunity of taking part in the trial. Isobel started in October 2014 at 15 stone and stayed on the milkshakes for 17 weeks, after which time she was down to 12 stone 4lb. Her blood sugars were reduced and her diabetes was in remission. Isobel described the next two years as “calorie restriction of 1,000-1,200 a day”. She now says she eats normally, but she monitors her weight and eats less as soon as she gains. Isobel will need to sustain perpetual calorie reduction to maintain her weight loss and diabetes status. As Stunkard and McLaren Hume showed back in 1959, barely 2% of people achieve significant sustained weight loss with calorie deficit beyond 2 years. (Ref 9)
Tony, 52, had huge motivation to adhere to the trial, as his father had died from complications of type 2 diabetes. He was 14 stone 7lb at the start of the study in October 2013 (at 5’8″). After 12 weeks Tony’s weight was 11 stone and his diabetes was in remission. He is now 11 stone 9lb and describes his current diet as “porridge for breakfast, cheese salad for lunch and chicken salad for dinner.”
Low calorie vs. low carbohydrate
A very low calorie diet is also a low carbohydrate diet. The Lancet study diet, providing 825-853 kcal/day, of which 59% was carbohydrate, thus provided 122-126g of carbohydrate a day. Professor Tim Noakes and Dr Johann Windt defined <130 g carbohydrate/day as an LCHF diet. (Ref 3) 850 kcal/day is also quite high for a very low calorie diet. In 2011, Professor Roy Taylor (the corresponding author in The Lancet study) was the senior author on an article about a trial involving 11 people, which concluded that type 2 diabetes could be reversed with extreme calorie restriction (600 kcal/day in this trial). (Ref 10) 600 kcal/day would be well below 100g of carbohydrate per day.
I will update this post when I hear back from the corresponding author on the food and calorie intake beyond the liquid diet phase. We don’t know the carbohydrate intake for Isobel, but Tony’s typical diet, as described above, could be under 100g of carbohydrate per day.
This brings us to…
You wouldn’t think so with the fanfare from this study, but it has been known for some time that a number of interventions can reverse type 2 diabetes. There are currently three options:
1) Bariatric surgery. As the Virta study reported: “The most comprehensive study of surgical intervention to prevent or reverse type 2 diabetes is the Swedish Obese Subjects Trial demonstrating an 8-fold reduction in the incidence of the disease at 2 years.” (Ref 11)
Barbaric surgery (as the “Word” spell-checker corrects it to!) comes with many other complications, lifelong supplementation and long term nutritional deficiency and so should be the absolute last resort. (Bariatric surgeons often describe a bypass as a last resort, when calorie deficit diets have been tried and failed. However, I have not seen low carb tried as a ‘last resort’ before barbaric surgery).
Professor Roy Taylor also presided over a very valuable clinical trial, which demonstrated that the improvement in glucose control observed for type 2 diabetics, following gastric bypass, was due to the calorie restriction (and thus a bypass wasn’t necessary to achieve benefit). (Ref 12) Taylor had first reported this fact – “The effect of the surgery is explicable solely in terms of energy restriction” – in an article in 2008. (Ref 13)
2) A very low calorie diet. As this Lancet study confirmed, a very low calorie diet can put type 2 diabetes into remission, but this has been known for some time. The Virta article (McKenzie et al) contained an excellent synopsis of evidence available to date. In their introduction, McKenzie et al listed a number of studies – from 1976 to 2017 – that used very low calorie diets to control blood glucose levels, while stopping or reducing diabetes medications. Just because the word “remission” is new, the achievement is not. The Bauman et al study, from 1988, was described by McKenzie et al as “After 19 months, 10 patients remained in remission”. (Ref 14)
3) A low carbohydrate diet. A very low calorie diet is also a low carbohydrate diet, but a low carbohydrate diet per se can put type 2 diabetes into remission. (Refs 2,6,7,15,16)
The importance of this study
This study is potentially the most important public health publication of 2017. IF this study can place “remission of type 2 diabetes” at the forefront of primary care objectives in the UK (and then hopefully worldwide), it will be a game changer for the epidemics of obesity and type 2 diabetes.
For approximately 10 years, the low carbohydrate community has been screaming for a dietary solution to be used for obesity and type 2 diabetes. This community is tiny compared to the low calorie world. IF this low calorie option opens the door for dietary solutions, then primary care providers should be obliged to offer patients any proven dietary options:
Would you like very low calorie (which is also low carb), which comes with hunger, nutritional deficiency, inability to socialise (during the liquid phase at least) and a lifelong demand on your willpower? Or would you like low carbohydrate, which avoids hunger, is nutritionally rich, is catered for in any restaurant from McDonalds (no bun) to The Ivy and which is being sustained without monk-like discipline?
The low carb community needs to emphasise the flexibility of approach more. The hard core of 5% carbohydrate, 15% protein and 80% is not necessary to achieve weight loss and remission of type 2 diabetes. Many people can do very well in the LCHF range of carbohydrate intake, rather than at the ketogenic level, as defined by Noakes and Windt. (Ref 3) Dr David Unwin has achieved remission in diabetes with a very pragmatic and practical diet sheet. (Refs 15, 16) Dr David Cavan, with work not yet published, has been reversing type 2 diabetes in Bermuda with carbohydrate intake nearer 100g/day than 25g/day. (Ref 17) Such intake is likely to be far more acceptable to patients and is aligned with the carbohydrate intake in this low calorie study.
The most critical contribution of this Lancet study is that the control was “best-practice care by guidelines.” No one receiving “best-practice care by guidelines” lost 15kg or more and just 4% of people in this group achieved diabetes remission vs. 46% of people in the intervention group. This study has proven that current ‘best practice’ guidelines are achieving next to nothing. They are a pathway to more medications over time and ultimately the eyesight and limb loss, which is the most horrific end game for diabetics (both types).
This study has not only shown that “remission” should be firmly at the forefront of primary care objectives; it has surely shown that current guidelines are medical malpractice.
Ref 1: Lean MEJ, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The Lancet 2017.
Ref 2: Westman EC, Yancy WS, Mavropoulos JC, Marquart M, McDuffie JR. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutrition & metabolism 2008.
Ref 3: Noakes TD, Windt J. Evidence that supports the prescription of low-carbohydrate high-fat diets: a narrative review. Br. J. Sports Med. 2017.
Ref 4: Feinman RD, Pogozelski WK, Astrup A, et al. Dietary Carbohydrate restriction as the first approach in diabetes management. Critical review and evidence base. Nutrition (Burbank, Los Angeles County, Calif.) 2014
Ref 5: Stentz FB, Brewer A, Wan J, et al. Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial. BMJ Open Diabetes Research & Care 2016.
Ref 6: McKenzie LA, Hallberg JS, Creighton CB, et al. A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes. JMIR Diabetes 2017.
Ref 7: Saslow LR, Kim S, Daubenmier JJ, et al. A Randomized Pilot Trial of a Moderate Carbohydrate Diet Compared to a Very Low Carbohydrate Diet in Overweight or Obese Individuals with Type 2 Diabetes Mellitus or Prediabetes. PLoS One 2014.
Ref 8: Ajala O, English P, Pinkney J. Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes. The American journal of clinical nutrition 2013.
Ref 9: Stunkard A M-HM. The results of treatment for obesity: A review of the literature and report of a series. A.M.A. Archives of Internal Medicine 1959.
Ref 10: Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011.
Ref 11: Sjöström L, Lindroos A-K, Peltonen M, et al. Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 Years after Bariatric Surgery. New England Journal of Medicine 2004.
Ref 12: Steven et al. “Calorie restriction and not glucagon-like peptide-1 explains the acute improvement in glucose control after gastric bypass in Type 2 diabetes.” Diabetes Med. (2016).
Ref 13: Taylor R (2008) Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause. Diabetologia 51:1781–1789
Ref 14: Bauman WA, Schwartz E, Rose HG, Eisenstein HN, Johnson DW. Early and long-term effects of acute caloric deprivation in obese diabetic patients. Am J Med 1988
Ref 15: Unwin D, Unwin J. Low carbohydrate diet to achieve weight loss and improve HbA1c in type 2 diabetes and pre-diabetes: experience from one general practice. Practical Diabetes 2014.
Ref 16: Unwin DJ, Cuthbertson DJ, Feinman R, VS S. A pilot study to explore the role of a low-carbohydrate intervention to improve GGT levels and HbA1c. Diabesity in Practice 2015.
Ref 17: http://bernews.com/2017/05/argus-offering-diabetes-reversal-programme/