Reversal a realistic goal?

[Lurch]

Just watched last night's Inside Out South West on iplayer (not aired in these parts) that included a bit (very short bit) on David Fitzgerald of the BBC doing the Newcastle Uni 600 kcal diet for 10 days. (I heard about the prog somewhere on here yesterday). Here's the iplayer link:

http://www.bbc.co.uk/iplayer/episode/b03nxjp2/Inside_Out_South_West_06_01_2014/

David's diet wasn't run by Newcastle Uni so seems the gospel's spreading that T2 can be reversed, but not 'cured' as they take care to say. In 10 days he lost 7 kilos, achieved fasting BS in the fours, and saw a three point fall in his A1C. The brain alone needs 600 kcals a day so the diet leaves nothing for the rest of the body!

I thought I was doing well on my self-created 11-1200 kcal intake because I've lost 11 kilos in 46 days. Paltry by comparison to David, but I'd never manage that 600 cal diet. I've seen only one under 5 fasting level so far, more usually 5.3 to 5.8. Since DX I've let my meter dictate my carb intake - 70g a day. Prof Jeff Volek (Art & Science of Low Carb Living etc) says an individual can be in ketosis at 70g CHO, and Jenny Ruhl's calculator certainly seems to think so, but I haven't bought urine strips to test if I am as it wasn't my plan to go ketogenic.

What interests me very greatly is whether the amazing results of the short VLCD can be achieved by a steadier decrease in weight? Prof Taylor says a weight loss of 15 kilos in 8 weeks should banish pancreatic and liver fat, which he now holds to be the reversal key, but I wonder if that time line is critical to the success or whether a slower reduction will get there just the same? I'm noticing that visceral fat is more reluctant to shift even while the shoulders are getting bony for the first time in many years.

Sorry to ramble but all the evidence tells me T2s have to act sooner than later after DX and whereas I can't face a 600 kcal diet, I'm hoping a more measured approach will still do the trick of reversing the beast. Can't see a doctor (if/when i see one) encouraging me to go ketogenic so it'll have to be my decision.

 

[DeusXM]

I always wonder about how the term 'reversal' is used in studies such as this.

I haven't seen the full results, but for me, 'reversal' indicates more than simply achieving normal blood sugar results. It means achieving those results regardless of the lifestyle of the person involved. Can those people on the Newcastle Diet eat a piece of cake, drink a glass of regular Coke and then sit in front of the TV for three hours and maintain blood sugars under 7mmol/l for the entire duration? I suspect probably not, although they may be able to eat managed quantities of carbohydrate without a need for medication.

My interpretation of the Newcastle Diet is that it simply confirms what everyone should know anyway - that T2 diabetes can be made easier to manage by losing weight and eating a diet lower in carbohydrates than in traditional. That in itself is an extremely positive result. But I'd very cautious about claiming a reversal of T2 on the basis that they don't need medication and maintain normal blood sugars. I know plenty of T2s who fit that category but certainly wouldn't consider their diabetes 'reversed', only 'controlled'.

 

[AlisonM]

Control yes, reversal? No, I don't think so. I find this whole thing highly suspect. I don't doubt the diet caused major changes in the test subject's health, but I have major reservations about the long term outlook for the participants. And it was such a small test group in th initial study that I doubt the results could be seen as definitive, or even significant.

 

[everydayupsanddowns]

In some senses I think this makes T1 easier. Aside from the relentlessly perky reports about 'the cure' for type 1 being only (an ever-shifting) 10 years away which are easy to ignore, we don't have to put up with this barrage of reporting that if we did x or y our diabetes would be 'reversed'.

There's no reversing my diabetes. That's for darned sure. So I just have to concentrate on effective management.

Incidentally some of the reporting around the initial study *did* seem to suggest a return of 'normal pancreatic function' (however that was defined), but the numbers in the study are so small... and the study so recent... there is absolutely no way of knowing whether or for how long any such improvement might last.

I would suggest it is better to concentrate efforts on ongoing BG control rather than hoping for reversal (and possibly being ultimately disappointed if it does not emerge)

 

[Redkite]

I agree with all the other comments. It's only truly reversed if you can eat what you like when you like without a care in the world, and still have normoglycaemia.

As for type 1 cures, I have been happily informed by well-meaning people on more than one occasion that they know of someone who carefully manages their diet and no longer has to use insulin, and is therefore a cured type 1! Meaning a well-managed type 2 I suppose.

 

[cherrypie]

Take it from a very skinny Type 2.
My diabetes is under control and has been since diagnosis, 2002.
I cannot reverse or cure it as if I decide to have a day where I eat what I want then the meter tells me that I am still diabetic.
Control is possible, reverse or cure it, I don't think so.

I think the subjects in the trial, all 11 of them, had been diagnosed no longer than 4 years. There is a larger trial coming up to see if it works for people who have had Type 2 for a longer duration.

I think words like reversal and cure give people false hope.

 

[LeeLee]

Complete and permanent reversal may not be possible, but after weight loss, diet and exercise I can now get away with the odd day off sainthood. Yes, I do know how lucky I am - I just wish there was a way to share my forgiving pancreas with all those who are still struggling. 🙂

 

[Lurch]

Yes, the huge question is the meaning of the word "reversed". As you probably know Newcastle Uni also carried out a further study of self-reporting to their website. Just found that pdf, so sorry for being slow. 😱

The report is titled: "Counterpoint reflections", about a population response to information on reversibility of Type 2 diabetes. Method: Emails, letters and telephone communications received between July 2011 and September 2012 were evaluated (n=77: 66 men, 11 women).

Quote: "Reversal of diabetes was observed in 80% of those with >20 kg weight loss, 63% of those with weight loss 10?20 kg and in 53% of those with<10 kg weight loss."

Quote: "These data demonstrate that intentional weight loss achieved at home by health-motivated individuals can reverse Type 2 diabetes. Diabetes reversal should be a goal in the management of Type 2 diabetes in these individuals."

So constant use of the word "reverse". But what they are not meaning by this word long-term is then revealed: "The durability of the effect on glucose metabolism requires further study. Long-term avoidance of weight gain must be the top priority after reversal of diabetes, and the dietary regimen best able to achieve this must now be established."

So the quick 'fix' is not a reversal as such, just a jump start. I guess the word "reversal" means different things to different folks including scientists?

But I found the answer to my question in the same pdf:

"...it is explained that a very low energy diet was chosen in the
research study to mimic the effects of gastric bypass surgery. However, steady but substantial weight loss achieved by reducing portion size was recommended as the preferred method. The focus was on the need to achieve substantial and sustainable weight loss through the best approach for that individual."

Come to think of it, I'm feeling I've seen that exact quote here recently, but there's nothing like learning at your own pace! 😱

 

[yorksman]

Hi Lurch,

A couple of points, firstly, you don't need the crash diet. In fact Roy Taylor recommends substantial weight loss of a period of time, 5 - 6 months. Secondly, reversal doesn't mean going back to the way you were before diagnosis, it means reversing the 'inevitable progression of the disease'.

Regarding the first point, this is what Taylor says in his FAQ:

• "The particular diet used in the study was designed to mimic the sudden reduction of calorie intake that occurs after gastric bypass surgery."
  
• "The essential point is that substantial weight loss must be achieved. The time course of weight loss is much less important."
  
• "It is also very important to emphasise that sustainability of weight loss is the most important thing to ensure that diabetes stays away after the initial weight loss. Previous research has shown that steady weight loss over a 5 – 6 month period is more likely to be successful in keeping weight down in the long term. For this reason, ordinary steady weight loss may be preferable."

The full FAQ are available online.

Regarding the second point about reversal, you really need to read it in the context of Taylor's Twin Cycle Hypothesis in Type 2 Diabetes: Etiology and Reversibility but they do measure more than blood glucose concentrations. They also measure the improvement in insulin response.

"The extent of weight loss required to reverse type 2 diabetes is much greater than conventionally advised. A clear distinction must be made between weight loss that improves glucose control but leaves blood glucose levels abnormal and weight loss of sufficient degree to normalize pancreatic function. The Belfast diet study provides an example of moderate weight loss leading to reasonably controlled, yet persistent diabetes. This study showed that a mean weight loss of 11 kg decreased fasting blood glucose levels from 10.4 to 7.0 mmol/L but that this abnormal level presaged the all-too-familiar deterioration of control."

Implication for Management of Type 2 Diabetes (ibid)

You can improve blood glucose control by watching what you eat but to normalise your pancreatic function requires a loss of liver fat content. Without the latter, the former becomes more difficult to achieve in time because of the way the liver and pancreatic interact, according to his Twin Cycle Hypothesis (ibid).

Weight loss required is just a mean weight loss, observed in the sample set. There is a wide range and it is the age old question about why one person eats what they want and remains skinny whilst others look at a bag of chips and gain two pounds. He doesn't look into the hows and whys of weight loss but just asserts that, it you lose enough, you can loose enough in your liver and pancreas to restore function and stop the decline.

This leads to the question of what does restore mean? The main problem is that as the pancreatic islets get clogged up, the insulin beta cells die off. We never know how many have died by the time of diagnosis. There is no way of telling without slicing the patient open and all tests, other that a couple of dozen post mortem investigations on humans, have been on force fed rats. Often the figure of a '50% loss of the beta cell mass' is quoted, but this is little more than a guess. Some may have lost 25% whilst others 60% or 70%. The initial study was for people who had been diagnosed within 4 years and a follow up study showed that 49% of people who had diabetes of more than 4 years could still halt the decline. Crucially, Taylor argues that there is a stage when some beta cells are not dead but simply 'metabolically inhibited'. But, it is important that people understand that some beta cell mass has been permanently lost and so they can turn diabetic again but this time, with a lower tipping point than before. People are not returned to the initial condition, only the progression has been halted. Be careful though.

"Within 7 days, liver fat decreased by 30%, becoming similar to that of the control group, and hepatic insulin sensitivity normalized. The close association between liver fat content and hepatic glucose production had previously been established. Plasma glucose normalized by day 7 of the diet."

"Pancreas fat content decreased gradually during the study period to become the same as that in the control group, a time course matching that of the increase in both first phase and total insulin secretion."

Reversal of Type 2 Diabetes by Diet Alone (ibid)

You may have to register to see the articles but you can simply choose 'other' when it asks for profession. There is no restricttion that I am aware of and no subscription is required.

 

[yorksman]

I agree with all the other comments. It's only truly reversed if you can eat what you like when you like without a care in the world, and still have normoglycaemia.

Without a care in the world is often what turns non diabetic people into type 2 diabetics in the first place. But, moderation is possible. Yesterday I had a portion of sticky toffee pudding with custard after dinner and a few chocs whilst watching TV. I went to bed with a 6.4 and woke up to to a 5.2. But, I am not going to make a habit of it. It will return if I do. I have lost an undefined amount of my beta cell mass and cannot afford to lose any more. You still have to look after what you have got left.

How the researchers define it is illustrated in the graphs below. Graphs A and B show the improved insulin responses whilst Graph C shows the correlation with the reduction in pancreatic triaglyceride content.

Effect of an 8-week very-low-calorie diet in type 2 diabetes on arginine-induced maximal insulin secretion (A), first phase insulin response to a 2.8 mmol/L increase in plasma glucose (B), and pancreas triacylglycerol (TG) content (C). For comparison, data for a matched nondiabetic control group are shown as ◯. Replotted with permission from Lim et al.

It is not just measured by the improvement in the blood glucose, which correlates with a reduction in liver triaglycerides:

Effect of a very-low-calorie diet in type 2 diabetes on fasting plasma glucose level (A), basal hepatic glucose production (HGP) (B), and hepatic triacylglycerol content (C). For comparison, data for a matched nondiabetic control group are shown as ◯. Reproduced with permission from Lim et al.


Losing liver fats will improve blood glucose concentrations but, unless pancreatic fats are lost too, which takes longer, liver fats will again accumulate and blood glucose concentrations will again rise.

 

[cherrypie]

We first heard of this diet in 2011. Seven of the 11 subjects completed the course.

We are now into 2014 and unless we know what has happened to the subjects since then we can speculate all we like.
I think that if you do follow this diet then the proof that it works will be after the diet finishes. I wonder why there has been no follow up published? I know we heard after 2 0r 3 months but that is hardly a follow up.

 

[yorksman]

I wonder why there has been no follow up published? I know we heard after 2 0r 3 months but that is hardly a follow up.

There is continuing work. Have a look at the Mag Res website and follow the links. In particular, keep a future eye open for the project, Characterisation of the principle determinants of long term reversal of type 2 diabetes and also dig out the 2013 study from Stevens et al Population response to information on reversibility of Type 2 diabetes. Lim, who did the 2011 study is co author here. Press coverage is not very good. This weekend the Sunday times were still reporting the 2011 study as if it were 'news'. Richard Doughty's experience though did recieved some press attention, primarily because he wrote the articles.

The Guardian
Daily Mail

 

[everydayupsanddowns]

Thanks for digging out those graphs Yorksman - very interesting.

 

[Lurch]

Thanks for excellent info. Have registered with Medscape. Didn't know a non-medic could. Nothing like reading the facts.

I prefer to hope this research and others like it is onto something regarding liver and pancreatic fat. May be 'fools gold' but life is all about hope.

Strikes me its unlikely T2s will be offered 'fat scans' on the NHS to confirm their visceral fat levels, so I suppose the only realistic plan is to get weight substantially down and if the midriff is stubborn do the boring belly exercises to push it off. At the end of the day, a low-carb diet along with exercise and routine testing is now a life-long pursuit anyway. It's just nice to hope. 🙂

Great to have access to Medscape.

 

[yorksman]

I prefer to hope this research and others like it is onto something regarding liver and pancreatic fat. May be 'fools gold' but life is all about hope.

The Counterpoint Study was designed to test the theory which resulted because of the observation that people who underwent bariatric surgery appeared to have their diabetes reversed. Two large scale studies showed this, Pories et al. 1995, Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus and Schauer et al. 2003, Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery.

The twin cycle hypothesis, which the Counterpoint Study tests, is an attempt to explain the observation.

 

[Lurch]

Hi Yorksman,

Have now studied the full eight page report you linked, and it was well worth reading in full instead of the media reports. Even through all the science I found it compelling as a new T2. Almost 90% of T2s who underwent bariatric surgery remained free of diabetes 10 years later, unless substantial weight gain occurred. That has to count for something, research-wise, so was a solid hypothesis to start with.

I liked...

"The accepted view has been that the β-cell dysfunction of established diabetes progresses inexorably, whereas insulin resistance can be modified at least to some extent. However, it is now clear that the β-cell defect, not solely hepatic insulin resistance, may be reversible by weight loss at least early in the course of type 2 diabetes."

And finally...

"Formal recommendations on how to reverse type 2 diabetes in clinical practice must await further studies. In the meantime, it will be helpful for all individuals with newly diagnosed type 2 diabetes to know that they have a metabolic syndrome that is reversible. "

That's not what the NHS says but I'm a believer. Losing 17% off my dx weight was my personal target to reach my healthy BMI upper limit and I have 6 kilos to go. I will demand a good response from my liver and pancreas. 5.1 this morning...gotta see some fours soon or I'm buying a different meter. Or maybe a magnet? 😡

Lurch

 

[Andy HB]

My take on this, based on my journey so far following diagnosis in October 2009......

In 2009 my BG response to any carb load was not good! I was probably in the late teens and twenties all the time (I certainly was when I was able to test).

I lost weight steadily and slowly (averaging around 1lb/week) and now I very rarely exceed 7mmol/L no matter what I eat.

I am still a type 2 diabetic, but I would say that my BG levels have been reversed in that for the same carb load, my BG levels are significantly better now. However, it is also true to say that I don't consistently eat as much carbohydrate as I used to.

Andy 🙂

 

[everydayupsanddowns]

And finally...

"Formal recommendations on how to reverse type 2 diabetes in clinical practice must await further studies. In the meantime, it will be helpful for all individuals with newly diagnosed type 2 diabetes to know that they have a metabolic syndrome that is reversible. "

I've never liked hearing that people are told their diabetes is inevitably going to get worse and worse and require inexorably greater and more powerful medication - hardly seems to encourage positive patient interaction with their condition.

However it is also important to recognise (in a way that the quote seems to fail to do) that not *everyone* diagnosed with Type 2 diabetes is overweight at diagnosis. I believe something like 20% aren't. Some people simply do not have the weight to lose. I suppose others may be TOFI (thin outside, fat inside), but I don't think it would be helpful, given the current level of Type-2-bashing that prevails in the media, and to some extent among HCPs themselves for the standpoint to become even more, "it's all your own fault in the first place, and if you put some effort in and stopped being such a lardy it would simply go away".

The fact that symptoms and reactions to foods might be much improved with careful carb reduction/management and weight loss will not surprise anyone here I suspect. But I'm still cautious about the term 'reversible' being bandied about so freely. The researchers may know what they mean by it. But I don't think others (including patients themselves) necessarily think of it meaning the same thing.

 

[yorksman]

Yes, it is important to remember what this research was all about. It wasn't about a cure for type 2 diabetes but an attempt to better understand an unexpected observation, namely that obese patients who underwent bariatric surgery appeared to have a reduction in their fasting blood glucose levels. It's quite different.

The research mimicked the effect of the gastric band by use of a hypocalorific diet, again on obese patients, and then measured their insulin levels as well as their BG levels.

It makes no attempt to explain why some people with relatively low BMIs develop diabetes whereas some with very high BMIs do not. Roy Taylor simply suggests that other factors are involved of which genetics might be one of them.

Why people put on weight in certain places but not others, or, when they lose weight through diet never seem to be able to lose it in this or that place remains a mystery. It is as big a mystery as to the observation that identical twins, who are born of the same original cell and who share the same genes, start to look different to those who spend time with them. You do not even need to have a trained eye. Schoolkids can spot the differences between identical twins in their classes. Other developmental processes come into play to make a person individual in a physical manner.

 

[MargB]

I am fascinated by this discussion. I was diagnosed T2 in March 2010 and accepted it, partly because of family history and just accepted it was inevitable. Immediately put on Metformin but also decided to lose weight. Lost just under 4 stone and my Hba1C results have gone down, down, down. When they recorded 36 mmol twice I asked if I could come off or cut down the Metformin and the doc agreed I could stop the tabs. Did well for a few months but then the weight started to creep back on and my diet was more relaxed. Know I have to lose weight again but thought I would check out the next HbA1C results and was astounded that they have gone down again, to 33 mmol. At that stage, I asked my doc if it was possible I was not and never had been diabetic but mis-diagnosed. Maybe I had been pre-diabetic and the weight loss and been enough to delay it.

Still not sure. Mis-diagnosis or reversal? The longest I could have been diabetic before diagnosis was 6 months as I have had regular blood tests for years. There again, my next HbA1C is in March so there is only a 3 month gap this time and that should tell us more.

It is actually heartening to know that even if I am diabetic then it is not just going to deteriorate and all I can do is try to slow the disease down.

By the way, I have never displayed any symptoms. I have to drink a lot of water for a bowel condition so there is nothing strange about sometimes needing to go to the loo during the night. I could make things fit it I put my mind to it. I don't have a meter so don't monitor. All I go off is the blood tests.

Mmmmmmm, a lot to think about about.