Type 2 Diabetes: Beyond Remission to a Cure

Disclaimer: This post is not medical advice. At all times you should consult with your trusted health professionals. It is a self-reported case study with discussion of type 2 diabetes pathology, much of which is unsettled.

Foreword

About 500 million people have Type 2 Diabetes (T2DM), so it is likely that this case study will be useful for more than one person who is like me, and may have some use for a good many others. If you have T2DM or pre-diabetes, I hope that is you.

To the best of my knowledge, there isn’t a more detailed long-term case history with results and analysis of a cure of T2DM than in this blog. If there is, please let me know as I want to read it and learn. I’ve documented this truthfully with my lab results and tried to avoid my bias and enthusiasm for what worked for me and why.

If you are a clinician then there may be insights from my case to help the growing number of people who have achieved remission, but now wish to progress even further towards a completely normal metabolism.

Among other things, I think my success is because I took a metabolic health approach to my problem. This is a long post so I will put that detail in a separate ‘how-to/ what I did’ post, which needs to include metabolic testing and body composition. In full disclosure, convinced of the value of a metabolic approach, I now do work for Metabolic Health Solutions (MHS) after being a client.

I’d love your comments, improvement suggestions, or notification of any errors. Leave a comment here or have a discussion with me on Twitter.

My Type 2 Diabetes is Cured

It’s been about three years since my last post and my original one seeking to go beyond remission to a cure for T2DM. You might review these if you are unfamiliar with them. I have achieved my goal of curing T2DM with the proof of that coming about a year ago now, but I’ve taken my time to publish this as I wanted to get my ducks in a row.

When I say ‘cured’ what do I mean? Firstly, I have a non-(pre)-diabetic HbA1c that is now consistently less than 5%. That is better than most of the non-(pre)-diabetic population. Secondly, washed out of all medication, I passed a gold standard Oral Glucose Tolerance Test (OGTT) with a non-(pre-)diabetic result. There are no diagnostic criteria to say that I have either T2DM or pre-diabetes.

I challenge the belief that T2DM is a chronic progressive disease that has no cure, even though diabetes charities only allow you to be in remission (never cured). I challenge that T2DM is purely an unlucky genetic lottery. While genetics play their part in susceptibility, T2DM is an arbitrary diagnosis point of a condition that is actually a metabolic spectrum you are already on.

Without doubt, I have moved down that spectrum to be almost completely healthy. I don’t doubt that if I went back to the diet and lifestyle that led to it, it would come back, just as it develops in someone afresh. If I maintain a truly metabolically healthy lifestyle, I have every expectation that it will not.

T2DM as Metabolic Disease

To cure a disease, you’d better understand it’s nature. T2DM most likely starts with poor fat oxidation. If you are unable to use your body fat effectively for energy, it accumulates. Too much where it should be, then spilling to where it should not be. That includes in your liver, your adipocytes (fat cells), and in your pancreas. De Novo Lipogenesis (DNL or fat production from carbs) may be increased, exacerbating this process by depositing more fat in the liver which causes or aggravates Non-Alcoholic Fatty Liver Disease (NAFLD). One strong theory is that this fat spills over into the pancreas becoming T2DM (1). Dyslipidemia and inflammation from that are likely to be causal for cardiovascular disease (CVD). While the exact order and causation may be debated, one useful view of how all of these major conditions are linked from the same root cause is shown in Figure 1 below (2).

T2DM development is not completely understood, but in effect, because your metabolism is broken, insulin rises to high levels (hyperinsulinemia) often even without eating. Worsening insulin resistance means that more insulin is needed to hold blood glucose at desired levels. The same amount of insulin no longer produces the same lowering of glucose. As it’s governed by a control system, our pancreas obliges and puts out more insulin to try to keep blood glucose controlled. Eventually, our insulin-producing beta cells can not produce enough insulin and we get an Impaired Glucose Tolerance (IGT). When blood glucose rises past an arbitrary point, T2DM is diagnosed, however, you can see there is already a problem. Even if you’ve been to your doctor and told: “Everything is OK with your blood glucose, you don’t have (pre)-diabetes.”, you may have ‘diabetes in situ’ (3) or metabolic syndrome.

Blood glucose can be managed with lifestyle and medication but this almost certainly continues as a chronic progressive disease. It continues to rise and insulin production falls further and eventually, injected (exogenous) insulin may be needed. Unfortunately, high insulin and high blood glucose cause diabetic complications, some of which we see above. Along with CVD, you can risk blindness, kidney disease, and poor circulation with nerve damage that leads to amputation.

The T2DM Spectrum

This diagram from doctors Kushner & Johnson’s article (4) illustrates this kind of progression which occurs over many years. In my case, it was over about a decade- perhaps more.

This picture exposes that we have created a problem because we have a binary view T2DM. “You have it or you don’t.” this leads people to think “You have the bad genes or you don’t” or some other factor. While computer numbers are binary, metabolic processes rarely are. If fact, the very existence of pre-diabetes (which precedes T2DM and can also be reversed and prevented from proceeding to T2DM) shouts out to us that T2DM is not a binary condition.

Instead, we should view T2DM as a condition of extended metabolic illness where everyone is on its spectrum. Consistent with Kushner & Johnson’s view, and while not really new, I propose Figure 3 showing T2DM on a spectrum.

Accepting that spectrum is reversible, then we need to find the things that will move us left. You will note that in figure 1, I have added “poor fat oxidation and poor metabolic flexibility”. That corresponds with figure 2’s meal size, composition, timing, and low activity. If that is driving the process, it’s no surprise then that changing meal size, composition, timing, and activity to achieve better fat oxidation and metabolic flexibility would be a great place to start to move left. High insulin is a major problem, so continuing to keep that as low as possible also seems wise.

T2DM as Insulin Resistance of the Pancreas

The latest research into diabetes indicates that a problem of T2DM may be insulin resistance of the pancreas itself. This leads to the related problem that alpha cells that make glucagon (the hormone that makes your body produce glucose) make too much of that (5) because they do not react properly to high insulin, so the liver overproduces glucose.

This seemed to be my main problem. My glucose was low most of the time, but would still be high in the morning even before I’d eaten. This had improved but appeared to be why my HbA1c wouldn’t drop below my target of 5.1%. Instead it hovered around 5.6%.

Let’s summarise some important points from this discussion of T2DM.

1. T2DM is characterised by hyperinsulinemia, with insulin resistance affecting tissues in the body differently, including, but not limited to, muscle, kidneys, liver, and (it seems) the pancreas itself.
2. Both insulin and blood glucose levels are high. Both will be exacerbated by lifestyle and in particular by foods that raise blood glucose and promote insulin secretion.
3. While the focus is often on the problems with the insulin-producing beta cells, both the alpha and beta cells do not function normally. Especially if there is no severe damage to them, this may be reversible. Even if there is some damage, it might be possible to regain function or possibly repair them.
4. T2DM is actually a spectrum condition that has hyperinsulinemia and insulin resistance to varying degrees. Before pre-diabetes, we have “sub-clinical diabetes” or T2DM that has not yet passed its clinical diagnosis points. You may also hear this called ‘diabetes in situ’.
5. Reversal can target hyperinsulinemia by lowering insulin and improving insulin sensitivity (reducing insulin resistance) until we have moved to the left, subject to any lasting damage to tissues and organs which then may or may not heal over time.
6. If we just try to control blood glucose without addressing high insulin, we have a chronic progressive disease. We can ‘rob Peter (increase insulin) to pay Paul (reduce glucose)’. This is, unfortunately, often the outcome of standard diabetes management.
7. If insulin resistance and hyperinsulinemia are the real problem, making the pancreas produce more insulin or supplementing insulin to keep it high by injecting it, is unlikely to fix the problem.
8. Striving for excellent metabolic health, by moving to the left in figure 3, appears to be the real goal for a cure. 

Moving Towards a Cure

One interesting aspect of my case is that it was almost only a diet approach for the first years. I did little exercise and was on a fairly small dose of metformin (500mg) for most of the time. This means my case study largely isolates diet (with a small metformin dose) from other factors like exercise.

It was a low carbohydrate approach which has the advantage of also minimising the insulin my pancreas produces. This is because carbohydrates stimulate insulin the most, then protein (but also much less in the near absence of carbohydrates) and fat the least. Logically too, if I had a pancreas overworked from six years of being unable to keep up with insulin production, it makes sense to give it a holiday from that.

After 18 months (see my 18-month post), I had markedly better health. My HbA1c was consistently below 6%, but I wanted it lower than 5.1%. My weight was now about 96kg, but I wanted to be around 80kg. Both seemed to be stuck. I toyed with options like keto (higher fat), exercise (but what kind?) and further intermittent fasting as discussed in my previous 18-month post.

I did persist for about another 10 months with just diet. Strictly two meals a day (16:8 fasting). I tried more keto but my blood glucose and weight did not seem to shift. Control chart theory (and common sense) indicated that if I wanted my system to change, I needed to do something different.

Metabolic testing from MHS (the subject of my next post) showed that my metabolism was far from optimal and this provided evidence for the lifestyle interventions. With my doctor’s support, I also increased my metformin dose.

Inflammatory Hysteresis

Inflammation can be caused by high blood glucose and high insulin. Neither my blood glucose nor (fasting) insulin was springing back to a level normal for the general population. Why was that and how could I shift it?

Nick Paterson who writes this blog from Finland, coined the term ‘inflammatory hysteresis’ to describe a phenomenon he saw in his own journey and people he worked with. Hysteresis is an engineering term and it made some sense to me so what does it mean?

Take a paperclip and straighten it out. Now deform the straight end slightly with a bit of pressure then let go. The clip springs back a bit like a spring. If you flex it much further, it will stay bent and if you deform it further in the same direction it will not return to the original position. It will bend further until it breaks. The inability of a system to return to normal shows that a system can hold a different persistent state. Simplistically, this is hysteresis. To straighten the clip, we need to actively deform it in the opposite direction to take it past its normal position.

The bent spring is a pretty good analogy for diabetes. You have bent your metabolism and pancreas so far that it will not snap back to normal. Hopefully, it’s not permanently damaged, but you need to ‘bend’ in the opposite direction so that it might settle back to normal again.

Increasing Metformin

Diet and exercise interventions are tools, but could I somehow bend my metabolism further? Nick was doing an experiment with metformin to see if that could help. I also remembered the comment in my previous post from Dr Lance De Foa about metformin.

Most doctors would not prescribe metformin for T2DM with an HbA1c of about 5.6% if it is only to manage blood glucose. At 5.6% blood glucose is already non-diabetic and metformin will likely not lower it much further.

Clinical practice might need to be rethought for T2DM in remission. Metformin should improve insulin resistance and reduce gluconeogenesis (caused by my alpha cells) to promote further recovery ‘bending the spring’ a bit further using medication. Patients may have a goal to be medication free (I did), but metformin is not the same as insulin or sulphonylureas which may make T2DM progression worse (6) and increase the risk of cancer (7) and CVD (8). In fact, metformin is likely to improve those risks and others (9).

Changes

At about month 58 in figure 3, I began deeper fasting, resistance training, and I took my increased metformin dose. It worked almost like magic. Over the next year, my HbA1c crashed through the 5.1% barrier to 4.6%, my weight dropped 18kg to 78kg, and my fasting insulin dropped from about 12 to 6. 

These were great results, but could I say I was cured? A great HbA1c on a low carbohydrate diet is often dismissed because you have just ‘hidden the problem’ by avoiding carbohydrates, however, my fasting insulin had also fallen from 26 to 6. On a low carbohydrate diet it turns out that for me HbA1c (in %), is a pretty good proxy for fasting glucose (in mmol/L) so this would indicate that my HOMA-IR (insulin resistance) had fallen from about 6.7 to 1.3. Generally, between 0.5 to 1.5 is regarded as the healthy range but this was when my pancreas was not being worked hard (during fasting).

My Pancreas at Wide Open Throttle

The gold standard test for diabetes is an Oral Glucose Tolerance Test (10). I decided to do this in month 89. You can see my preparation and the test results I took alongside the lab measurements on Twitter, which was tweeted in real-time. I ceased taking metformin for two weeks prior so that it was not a factor affecting the result. The official result confirmed that I was neither diabetic nor pre-diabetic.

The C-Peptide result shows that my pancreas still produces adequate insulin despite six years of quite bad T2DM. It was almost in the middle of the normal range. My HbA1c was 4.6% so it was below the population average of about 5.1%. Everything looks pretty good but the pass or fail isn’t really enough to assess where I am on the T2DM spectrum. Metabolism testing was also good (to be the subject of another post). To assess further we need a little detective work and this paper (11), particularly figure one in it, as provides us with a useful yardstick. Here is that figure reproduced with my results added to it in yellow.

Analysing my Oral Glucose Tolerance Test

Analysing the insulin, it’s a shame that I don’t have a 30-minute insulin value to compare (it was not part of the standard test that is done in Australia) but otherwise, the insulin response is fairly close to the average value for an insulin sensitive person with normal glucose tolerance.

Looking at the glucose curve, we can see that while I passed the test threshold at 2 hours, the peak is higher than would be expected for an insulin sensitive person with normal glucose tolerance. I speculate that for some reason (that may or may not be damage to my pancreas from T2DM) my first phase insulin response is still slow or low which leads to an excessive glucose peak. This might have been seen if I had an insulin measurement at 30 minutes.

What does that mean for me? Probably that it is best to still avoid food that is like 75g of glucose in one hit. Slow, complex carbs should not be as bad. Aren’t we all told to do that anyway to avoid T2DM? I’ll still generally restrict carbohydrates in my diet until I can see this improve too. It’s easy for me to repeat this test yearly myself to see how the glucose peak changes.

This may be due to a (genetic?) metabolic abnormality that I have always had or developed as I aged. If so it may be the reason I was more susceptible to developing diabetes (12). It is also possible that this is just the last thing needed to fixed before becoming completely normal. Interesting questions for me and perhaps for others.

We know from Prof. Roy Taylor’s work that first phase insulin response can improve with effective reversal or remission and this is more likely if you reverse T2DM after less than six years. It may be that six years of diabetes has left my first phase response more damaged. If that’s the case, maybe it can’t be improved or fixed, but then that’s what they’ve told us about T2DM for decades and so far ‘they’ haven’t been right for me.

There is also another possible explanation. These were the first substantial carbohydrates that I had eaten for 3.5 years. The OGTT protocol requires that you eat 150g of carbs a day for three days. I did that for four days but I cannot rule out that I might actually need longer to adapt given my very long time without them. It is fairly uncharted territory, but if anyone knows of a study that resolves this possibility or can otherwise explain this, then let me know.

“Just Losing Weight Cured You.”

I have been told this by some folks on social media. Usually, they don’t like low carb diets and/or fasting and think that a caloric deficit and weight loss are all that is needed. It’s sometimes from some who really should know better.

At 78kg down from 109kg it’s clear that I have healthier adipose tissue but there are also obese people that don’t have T2DM and thin people that do. If you consider that and now appreciate the complexity of T2DM a bit better, then you will know that saying that T2DM reversal is purely about weight loss is an oversimplification. It is as wrong as saying that weight loss has nothing to do with it. I note:

• We’ve been telling people with T2DM to lose weight for decades. It hasn’t made much difference to the remission rate. Most health professionals don’t even bother to try with patients because losing weight is hard if you are unable to utilise your body fat- which is likely to be why the whole problem started. They just put them straight onto medication.
• How do thin people with T2DM reverse it if excess body mass is wholly causative and remission is achieved just by losing 15kg? The answer is that they do this with a metabolic diet and don’t try to lose weight unhealthily to reverse it like this poor fellow (13).
• Specifically, though, diabetes is most believed to be exacerbated by ectopic and visceral fat accumulation around and in the liver and pancreas (14). Liver fat may be reduced without a significant change in weight (15).
• Metabolism is complex. A recent review (16) of the evidence supports that the relationship between weight loss and glycaemia (hence remission) is not as straightforward as might first be thought.
• My particular case shows that weight loss is not the only thing happening in remission if therapy is sustained. For me, a very modest weight loss of about 1.5kg dropped my fasting insulin from 26 to 12. Insulin resistance was more than halved and there was no exercise to confound this! That is easily seen between months 38 and 51 in figure 3.

For the sake of people with T2DM, we need to challenge the “it’s just weight loss” paradigm, not the least because it just has not worked as a goal in itself for remission for 40 years or more. A good approach instead is a focus on overall metabolic health. That means healthy adipose tissue, healthy mitochondria, visceral fat reduction, metabolic flexibility, improved fat oxidation, increased muscle mass, total fat mass reduction and (naturally) involves weight loss.

What I Have Learned

Reflecting on my journey:

1. Diet is the primary intervention for T2DM, but metabolic health, which can include sleep, sunlight, exercise, and supplements (sometimes medications), is the real aim. Nonetheless, while it’s not all about diet, a low carb/ keto diet (with intermittent fasting) is a powerful metabolic tool.
2. Even if a dietary guidelines diet is healthy for everyone already healthy, it is an inappropriate diet for someone with T2DM wishing to be in remission or cured. It is unlikely to therapeutically address the underlying pathology, but also how could any health professional recommend an eating pattern to achieve remission that has no evidence for delivering remission?
3. It’s not all about weight loss. Your metabolism is complicated and T2DM puts you at the far end of a spectrum of a metabolic problem. That said, significant weight loss is a likely part of the journey if you are overweight or obese with T2DM. Losing excess fat mass improves your metabolic health, but the relationship is complex because sustained weight loss is also an outcome from an improved metabolism.
4. It’s much more about lowering insulin than managing glucose but we manage best what we measure. It’s easy to measure blood glucose and as it’s associated with complications so it’s the therapeutic goal, but it is not the only or best therapeutic goal. A focus on blood glucose has allowed us to mistreat T2DM with exogenous insulin, sulphonylureas, and now SGLT2’s (which are better but still not great). Evidence shows that a therapeutic diet can obviate or reduce the need for medications for many people.
5. Patience and persistence are important. It took me 3.5 years to reverse my metabolism to a non-(pre)-diabetic state after a decade of NAFLD and 6 years of poorly controlled T2DM. If one of the factors in reversal and cure is simply time, that’s unlikely to happen if you can’t sustain the therapeutic lifestyle needed and go back too early to a diet that may actually have caused progression. If I had tried to cure my T2DM using shakes for rapid weight loss, followed by a high carb dietary guidelines eating pattern, the result would likely have been quite suboptimal.

From here I’m going to continue my health journey. My weight hovers between 78kg and 82kg quite reliably. It’s unlikely that a decade of fatty liver and six years of poorly controlled T2DM has left me with no problems or health risks, but I’m a hell of a lot better than I would have been with a decade of T2DM.

Research Reflections

Everyone should think about where they are on the T2DM Spectrum. I would hope if you have T2DM and are not in remission, you might now be inspired you to set that as a goal. If you are in remission, I hope it would show you there is a further path to travel, but that is also true whether you are pre-diabetic or have insulin resistance or metabolic syndrome.

For self-managing patients and clinicians, I think there are a few concepts here (and also in my next post) useful to continue to assess progress and work beyond remission.

Of course, my case can’t prove repeatability for someone else; however, it’s a more useful scientific resource than me filling in a lifestyle (food frequency) questionnaire only to have it mixed with 100,000 others, so you can look for an association with the foods to eat for a T2DM cure!

Maybe you can dismiss it as an anecdote and close your browser tab? I hope not as wisdom suggests an n=1 helps you understand a disease. Noting that I had diet as the main intervention for the first years, I think my case provides some interesting separation of the effects of those interventions for you to ponder.

I expect there are a few hypotheses in this post worth testing. 4.5 years is a long time to live without carbs and I’d like to put a few back at some point and expect I will after seeing my one hour OGTT normalise and HOMA-IR improve further. It’d be nice that if repeatable, the process heal can be sped up for others.

References

(1) Taylor R. Type 2 diabetes: etiology and reversibility. Diabetes Care. 2013 Apr;36(4):1047-55. doi: 10.2337/dc12-1805. PMID: 23520370; PMCID: PMC3609491.

(2) Lomanaco, R. & Cusi, N., Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?, Chapter 21, Evidence-based Management of Diabetes

(3) Joseph R. Kraft, M.D., Detection of Diabetes Mellitus In Situ (Occult Diabetes), Laboratory Medicine, Volume 6, Issue 2, 1 February 1975, Pages 10–22, https://doi.org/10.1093/labmed/6.2.10

(4) Johnson, JD & Kushner, JA. Endogenous insulin: its role in the initiation, progression and management of diabetes, The Endocrinologist, ISSUE 129 AUTUMN 2018

(5) Muhmmad Omar-Hmeadi, Per-Eric Lund, Nikhil R. Gandasi, Anders Tengholm, Sebastian Barg. Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-15717-8

(6) Genuth S. Should sulfonylureas remain an acceptable first-line add-on to metformin therapy in patients with type 2 diabetes? No, it’s time to move on! Diabetes Care. 2015 Jan;38(1):170-5. doi: 10.2337/dc14-0565. PMID: 25538314.

(7) Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 2006 Feb;29(2):254-8. doi: 10.2337/diacare.29.02.06.dc05-1558. PMID: 16443869.

(8) O’Brien MJ, Karam SL, Wallia A, et al. Association of Second-line Antidiabetic Medications With Cardiovascular Events Among Insured Adults With Type 2 Diabetes. JAMA Netw Open. 2018;1(8):e186125. doi:10.1001/jamanetworkopen.2018.6125

(9) Campbell JM, Bellman SM, Stephenson MD, Lisy K. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis. Ageing Res Rev. 2017 Nov;40:31-44. doi: 10.1016/j.arr.2017.08.003. Epub 2017 Aug 10. PMID: 28802803.

(10) Phillips, PJ,. Oral glucose tolerance testing, Emergency Care, Volume 41, No.6, June 2012 Pages 391-393

(11) Wang, Q., Jokelainen, J., Auvinen, J. et al. Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals: an interventional study. BMC Med 17, 217 (2019). https://doi.org/10.1186/s12916-019-1440-4

(12) Gerich JE. Is reduced first-phase insulin release the earliest detectable abnormality in individuals destined to develop type 2 diabetes? Diabetes. 2002 Feb;51 Suppl 1:S117-21. doi: 10.2337/diabetes.51.2007.s117. PMID: 11815469.

(13) Odhaib S A, Mansour A A (June 03, 2019) A Patient Loses 18 kg and Type 2 Diabetes Mellitus: The Challenge of Complete Remission. Cureus 11(6): e4817. doi:10.7759/cureus.4817

(14) Sattar N, Gill JM. Type 2 diabetes as a disease of ectopic fat? BMC Med. 2014 Aug 26;12:123. doi: 10.1186/s12916-014-0123-4. PMID: 25159817; PMCID: PMC4143560.

(15) A. Mardinoglu, H. Wu, E. Bjornson, C. Zhang, A. Hakkarainen, S.M. Rasanen, S. Lee, R.M. Mancina, M. Bergentall, K.H. Pietilainen, S. Soderlund, N. Matikainen, M. Stahlman, P.O. Bergh, M. Adiels, B.D. Piening, M. Graner, N. Lundbom, K.J. Williams, S. Romeo, J. Nielsen, M. Snyder, M. Uhlen, G. Bergstrom, R. Perkins, H.U. Marschall, F. Backhed, M.R. Taskinen, J. Boren
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(16) Fridman M, Lucas ME, Paprocki Y, Dang-Tan T, Iyer NN. Impact of Weight Change in Adults with Type 2 Diabetes Mellitus: A Literature Review and Critical Analysis. Clinicoecon Outcomes Res. 2020;12:555-566. Published 2020 Sep 29. doi:10.2147/CEOR.S266873