缅北禁地

Background

All this work has depended upon a breakthrough in understanding

We now know that type 2 diabetes is caused by excess fat inside liver and pancreas.

It all started with sudden coming together of research results from 缅北禁地 and elsewhere. The Twin Cycle Hypothesis described how it might be possible to explain the cause of type 2 diabetes in a very simple way. reversing the twin cycles of type 2 diabetes to read the description of this once the story could be told of what happened next. The highest scientific award from Diabetes UK – The Banting Lecture – was awarded for this, and this paper described what was said in the lecture, delivered at the Annual Professional Conference of Diabetes UK in 2012.

In 2008, Diabetes UK had given a grant to test the twin Cycle Hypothesis of the cause of type 2 diabetes. Proof of the hypothesis was published in 2011 as the study Counterpoint. The slides you will see on clicking the Counterpoint link show the data both from this, the most important study on what causes type 2 diabetes as well as the following study.

It was clear from that time onwards that type 2 diabetes is caused by too much fat building up within liver, then overspilling to the rest of the body - including the pancreas. This starts up a second vicious cycle inside the pancreas, with the fat actually switching off normal insulin production.

This second study – CounterBalance - showed that once the vicious cycles of type 2 diabetes had been reversed, the remission of diabetes was durable – as long as weight was not regained. Here is the scientific paper, published in 2016 in Diabetes Care: 

One of the most important discoveries is that of the Personal Fat Threshold. Type 2 diabetes is not caused by ‘obesity’. Different people have different levels of tolerance of fat within liver and pancreas. But if you have type 2 diabetes, you have crossed your ‘personal fat threshold’. This has been tested in the ReTUNE study which found that weight loss in people of normal or near normal BMI brought about exactly the same changes in liver and pancreas to that in heavier people. At an average threshold of 6.5% weight loss in this group of people with BMI 21-27, 70% went into remission. This was maintained throughout the one-year study on a normal diet but avoiding weight regain.

Your Personal Fat Threshold (PFT) can only be identified by weight loss. If you lose weight and go below your own PFT, type 2 diabetes is likely to disappear - providing that you have not had diabetes for too long. Most people can get back to normal in the first 6 years after diagnosis, but it is never too late to try. But even if remission of diabetes does not happen, less medication will be needed, and your health will improve massively. Importantly, you will also feel better.

‌Watch Professor Taylor's  on reversing type 2 diabetes (4th November 2014).

DiRECT

Diabetes REmissions Clinical Trial

Understanding why significant weight loss results in remission of Type 2 diabetes is at the heart of DiRECT.

Once we had shown that type 2 diabetes was a simple condition of too much fat inside liver and pancreas, we needed to move on to discover whether this knowledge could be used for routine treatment of the condition. Professor Roy Taylor collaborated with Professor Mike Lean, University of Glasgow to carry out the Diabetes Remission Clinical Trial (known as DiRECT). It showed:

One third of all people taking part were free of diabetes at 2 years.

Around three quarters of everyone who were in remission at 1 year stayed in remission at 2 years.

The group who embarked on rapid weight loss had fewer serious medical problems in the second year of DiRECT.

At 5 years, those who avoided weight regain continued to be in remission. Even though the whole weight loss group remained over 6kg below their starting weight, the majority did gain some weight. Despite this, the number of serious medical events was halved in the entire weight loss group.

DiRECT results: DiRECT results at 2 years  full paper and the online DiRECT appendix  are now available. 

View details at:

• the DiRECT study protocol
• Taylor et al: Who was studied in DiRECT at Diabetologia (2018)
• Taylor et all: Substantial weight loss can reverse the processes underlying type 2 diabetes at Taylor et al Cell Metabolism 2018‌
• Al-Mrabeh et al: Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss (Cell Metabolism, Dec 2019)

Watch Professor Taylor’s interview:  (Medscape, 8 March 2019) 

Scientific information

The information on this page is for doctors and scientists

It includes slides on various aspects of the reversal of Type 2 diabetes as well as published papers.

缅北禁地 research has established that type 2 diabetes is caused by excess fat in liver and pancreas.

If this fat is removed in the first ~6 years of diabetes, functional beta cell mass gradually returns to a completely normal level over 12 months in most people.

The immediate loss of fat from the pancreas following weight loss is from a labile pool, and this is observed only in those with type 2 diabetes and not non-diabetic people.

The small, irregular pancreas typical of type 2 diabetes returns towards normal volume, and returns to completely normal shape over 2 years of remission.

Provided weight loss is maintained, beta cell function does not decline over the following years.

The UK consensus definition of  is an HbA1c <48mmol/mol (<6.5%) off all diabetes medication, achieved by weight loss and maintained for 6 month

Download our slides on:

• Counterpoint
• Counterbalance 
• pancreas fat
• the DiRECT study 
• personal fat thresholds
• Physiological mechanisms lecture to ADA
• Insulin secretion recovery during remission
• Pancreas volume during remission
• ReTUNE study slides

Further information

In 2008, we published the Twin Cycle Hypothesis to explain the cause of Type 2 diabetes. This hypothesis predicted that diet could entirely reverse Type 2 diabetes. Read the scientific review, Pathogenesis of type 2 diabetes on the US National Library of Medicine website.

The Counterpoint study designed to test the hypothesis was funded by Diabetes UK. The results were very clear. Weight loss averaging 15kg (2 stone 5lb) achieved over 8 weeks caused two distinct sets of changes. Within seven days, liver fat had fallen by 30%, liver insulin sensitivity had returned to normal and fasting blood glucose had become normal. By eight weeks, pancreas fat content had returned to normal and insulin secretion by the pancreas had returned to normal. Read the full scientific paper, Reversal of Type 2 diabetes and the related 缅北禁地 Press Release, Diet Reverses Type 2 Diabetes.

This new understanding of what causes Type 2 diabetes and how it can be completely reversed has been used by individuals worldwide, a report has been published documenting practical management of Type 2 diabetes in respect of reversal.  A review describing the beta cell de-differentiation explains why the condition is reversible. Under the endoplasmic reticulum stress caused by excess intracytoplasmic fat, the cell goes into a survival mode and switches off specialised gene expression. Removal of the fat permits re-differentiation.  Scientists and doctors with access to the journal Diabetes Care, can read a full review of the science underlying this matter: Type 2 diabetes: etiology and reversibility. See the more recent reviews:   a discussion of practical aspects of achieving remission. The most recent reviews are in  and in  

Professor Taylor was awarded the 2012 Banting Lectureship of Diabetes UK. Read his lecture reversing the twin cycles of type 2 diabetes.

The pathophysiological basis of reversal of type 2 diabetes is described in 9 major papers:

• Lim EL, et al. Reversal of type 2 diabetes: Normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011; 54: 2506-2514. PMID 21656330.
• Steven S, et al. Weight loss decreases excess pancreatic triacylglycerol specifically in type 2 diabetes. Diabetes Care 2016 Jan;39(1):158-65. doi: 10.2337/dc15-0750.
• Steven S, et al. Very low-calorie diet and 6 months of weight stability in type 2 diabetes: Pathophysiologic changes in responders and nonresponders. Diabetes Care 2016 May 39(5):808-15. doi: 10.2337/dc15-1942.
• Taylor R et al. Remission of human type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for beta cell recovery. Cell Metabolism 2018. Aug 2. pii: S1550-4131(18)30446-7. doi: 10.1016/j.cmet.2018.07.003. Taylor et al Cell Metabolism 2018.
• Rehackova L et al. . Diabetic Medicine 2018. Nov;34(11):1554-1567. doi: 10.1111/dme.13426.
• Taylor et al. . Lancet Diabetes Endocrinology 2019. May 13, pii: S2213-8587(19)30076-2. doi: 10.1016.
• Al-Mrabeh et al. Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss. Cell Metabolism 2019. Dec 19, doi.org/10.1016/j.cmet.2019.11.018.
• Al-Mrabeh A, Hollingsworth KG. Shaw JAM, McConnachie A, Sattar N; Lean MEJ, Taylor R. 2-year remission of type 2 diabetes and pancreas morphology: a post-hoc analysis of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol 2020; Dec 8; doi: 10.1016/S2213-8587(20)30303-X.
• Taylor R, et al. . Clin Sci (Lond) (2023) 137: 1333–1346

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