Saturday, February 23, 2013

The Nutrition Debate #89: “Reversal of Type 2 Diabetes” Revisited

“Reversal of Type 2 Diabetes,” published online in Diabetologia 09 June 2011, was the subject of last week’s blog (#88) here. In the course of doing “due diligence,” my brilliant on-line editor, found a companion piece in Diabetic Medicine: a Journal of the British Diabetic Association dated 2013 January 15 by two of the authors, E. L Lim and R. Taylor, plus S. Steven, also of Newcastle. It is titled, “Population Response to Information on Reversibility of Type 2 Diabetes.” She also found a related link that particularly impressed me: One of the authors of both papers, R. Taylor, presented “The 2012 Banting Lecture” at the American Diabetes Association annual meeting. His subject: “Reversing the Twin Cycles of Type 2 Diabetes,” the very same stuff! The lecture is given by the winner of the Banting Medal for Scientific Achievement Award, the highest scientific award of the American Diabetes Association. About finding this current paper, my editor commented: I mostly wanted to see what areas of expertise these authors had…! I think (they) are on to something important and also wanted to see what they were up to currently. There's an ongoing effort to shorten the time between research and clinical practice. So their reporting on people trying out their ideas was especially interesting to me. In the med world, this is pretty fast turnaround.” What a consummate professional my editor is!  How lucky I am to have her!

The balance of this post will be verbatim extracts of the abstracts of both the “Population Response…” and the “2012 Banting Lecture.” Both are copyrighted as noted. Note also: authors’ names are hyperlinked to their work in PubMed.

"Population response to information on reversibility of Type 2 diabetes."


Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon, Tyne, UK.



Following publication of the Counterpoint Study (on the reversibility of Type 2 diabetes using a very low energy diet), the extent of public interest prompted the authors to make available, on a website, general information about reversing diabetes. Shortly thereafter, individuals began to feed back their personal experiences of attempting to reverse their diabetes. We have collated this information on the effects of energy restriction in motivated individuals with Type 2 diabetes that has been achieved outside a research setting.


Emails, letters and telephone communications received between July 2011 and September 2012 were evaluated (n = 77: 66 men, 11 women). Median diabetes duration was 5.5 years (3 months-28 years). Reversal of diabetes was defined as achieving fasting capillary blood glucose < 6.1 mmol/l and/or, if available, HbA(1c) less than 43 mmol/mol (6.1%) off treatment.


Self-reported weight fell from 96.7 ± 17.5 kg at baseline to 81.9 ± 14.8 kg after weight loss (P < 0.001). Self-reported fasting blood glucose levels fell from 8.3 mmol/l (5.9-33.0) to 5.5 mmol/l (4.0-10.0) after the weight loss period (P < 0.001). Diabetes reversal was considered to have occurred in 61% of the population. Reversal of diabetes was observed in 80, 63 and 53% of those with > 20, 10-20 and < 10 kg weight loss, respectively. There was a significant correlation between degree of weight loss and reported fasting glucose levels (Rs -0.38, P = 0.006). Reversal rates according to diabetes duration were: short (< 4 years) = 73%, medium (4-8 years) = 56% and long (> 8 years) = 43%.


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. © 2013 The Authors, Diabetic Medicine © 2013 Diabetes UK.

"The 2012 Banting Lecture Reversing the twin cycles of Type 2 diabetes."


Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, UK.


It has become widely accepted that type 2 diabetes is inevitably life-long, with irreversible and progressive beta cell damage. However, the restoration of normal glucose metabolism within days after bariatric surgery in the majority of people with type 2 diabetes disproves this concept. There is now no doubt that this reversal of diabetes depends upon the sudden and profound decrease in food intake, and does not relate to any direct surgical effect. The Counterpoint study demonstrated that normal glucose levels and normal beta cell function could be restored by a very low calorie diet alone. Novel magnetic resonance methods were applied to measure intra-organ fat. The results showed two different time courses: a) resolution of hepatic insulin sensitivity within days along with a rapid fall in liver fat and normalization of fasting glucose levels; and b) return of normal beta cell insulin secretion over weeks in step with a fall in pancreas fat. Now that it has been possible to observe the pathophysiological events during reversal of type 2 diabetes, the reverse time course of events which determine the onset of the condition can be identified. The twin cycle hypothesis postulates that chronic calorie excess leads to accumulation of liver fat with eventual spill over into the pancreas. These self-reinforcing cycles between liver and pancreas eventually cause metabolic inhibition of insulin secretion after meals and onset of hyperglycaemia. It is now clear that Type 2 diabetes is a reversible condition of intra-organ fat excess to which some people are more susceptible than others. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes. (link to full text here)

Saturday, February 16, 2013

The Nutrition Debate #88: “Reversal of Type 2 Diabetes”

This column is about an open access article published online in Diabetologia 09 June 2011. I found it in my search for answers to questions I raised in #86, “Beta Cell Function and Insulin Sensitivity,” here. Unfortunately, I will not learn the answers from my new endo since he fired me as reported here in #87, “Optimal Blood Lipid Levels.” The Diabetologia article is “Reversal of type 2 diabetes: normalization of beta cell function in association with decreased pancreas and liver triacylglycerol.” The authors, E. L Lim, K. G Holingsworth, B. S. Aribisala, M. J. Chen, J. C. Mathers and R. Taylor, all of whom are associated with institutes at Newcastle University in the UK, begin their abstract thus:

Aims/hypothesis Type 2 diabetes is regarded as inevitably progressive, with irreversible beta cell failure. The hypothesis was tested that both beta cell failure and insulin resistance can be reversed by dietary restriction of energy intake.”

The plot thickens, however, with an exposition of this theme in the “Introduction,” from which I delete only footnotes:

“Type 2 diabetes has long been regarded as a chronic progressive condition, capable of amelioration but not cure. A steady rise in plasma glucose occurs irrespective of the degree of control or type of treatment. Beta cell function declines linearly with time, and after 10 years more than 50% of individuals require insulin therapy. The underlying changes in beta cell function have been well described, and beta-cell mass decreases steadily during the course of type 2 diabetes. Overall, there is strong evidence that type 2 diabetes is inexorably progressive, with a high likelihood of insulin therapy being eventually required to maintain glycaemic control.

However, type 2 diabetes is clearly reversible following bariatric surgery. The normalization of plasma glucose concentration follows within days of surgery, long before major weight loss has occurred, and it has become widely assumed that the protective effects of gastrointestinal surgery are mediated by altered secretion of incretin hormones. Improved control of blood glucose in type 2 diabetes by moderate energy restriction has been demonstrated by others. We have hypothesized that the profound effect of a sudden negative energy balance on the metabolism could explain the post-bariatric surgery effect and, specifically, that the decrease in the intracellular fatty acid concentrations in the liver would lead to a lower export of lipoprotein triacylglycerol [i.e., TG or triglycerides] to the pancreas, with the release of beta cells from the chronic inhibitory effects of excess fatty acid exposure.

This study was designed to test the hypothesis that acute negative energy balance alone reverses type 2 diabetes by normalizing both the beta cell function and insulin sensitivity. We examined the restoration of first-phase and total insulin response as well as hepatic and peripheral insulin sensitivity. Additionally, to examine the mechanistic basis of observed outcomes, we quantified the changes in fat content in the pancreas and liver.”

This last paragraph is particularly notable for the word “alone,” and even more so when you consider the study participants’ diet. It was basically 2.1 MJ/day (510 kcal/day for non-Brits) of Optifast, which is a “liquid diet formula” manufactured by Nestlé Nutrition. This was supplemented with “three portions of non-starchy vegetables” such that total energy intake was about 2.5 MJ (600kcal)/day. The authors aver that “Nestlé UK provided the Optifast on request but had no other input into the research.” The authors declare “no duality of interest.” And I believe them.

Another reason why this is notable is that the formulation of Optifast used in this study was 46.4% carbohydrate, 32.5% protein and 20.1% fat. And that was before the 3 servings (0.4 MJ or +/-90 calories) of vegetables, essentially all carbs, was added. So the results of this study are all the more striking since the participants during the 8 week duration of the program ate a high carb, high protein, low fat mostly liquid diet. Type 2s take note. The paradox is about to get starker.

Eleven people with type 2 diabetes (aver. age 49.5, BMI 33.6) were studied before and after 1, 4, and 8 weeks. An age-, sex-, and weight-matched group of eight non-diabetic participants was studied also. Key metrics were taken using state-of-art measurement techniques (e.g. magnetic resonance imaging) and study practices. All the protocols for exclusion, ethics, etc. were followed. The results (selected only to omit arcane statistics):  “After 1 week of restricted energy intake, fasting plasma glucose normalized in the diabetic group from 9.2 to 5.9mmol/l (166 to 106mg/dl US). Insulin suppression of hepatic glucose output improved from 43% to 74% vs. 68% for the control group. Hepatic triacylglycerol (TG) content fell from 12.8% in the diabetic group to 2.9% by week 8; The first-phase insulin response increased during the study period…and approached control values; Maximal insulin response became supernormal at 8 weeks vs. controls; pancreatic triacylglycerol decreased from 8.0% to 6.2%, compared to 6.0% in the control group.

Conclusions/interpretation Normalization of both beta cell function and hepatic insulin sensitivity in type 2 diabetes was achieved by dietary energy restriction alone (emphasis mine). This was associated with decreased pancreatic and liver triacylglycerol stores. The abnormalities underlying type 2 diabetes are reversible by reducing dietary energy intake.”

The implications of this are still reverberating in my brain. This paper is pretty “brainy” and certainly way above my pay grade, but I wonder why many others who are qualified to discuss it aren’t.  Could it be a “duality of interest”? Or maybe our clinicians are too busy figuring out the latest medical reimbursement rules and insurance regulations. Who knows!!!

Saturday, February 9, 2013

The Nutrition Debate #87: Optimal Blood Lipid Levels

Be warned! This is a very hot topic, particularly if you are as intemperate as I can be (am?). I recently refused the recommendation of an endocrinologist given to me over the phone by his nurse, saying to her “the doctor really should be ashamed of himself” for suggesting I “try” a certain statin drug. The next morning the doctor called me at 7:30 AM, saying I had hung up on his nurse. Not true, she hung up on me after I made that comment.

Apparently she hadn’t told him what I’d said, leaving it to me to tell him directly. It definitely added fuel to the fire. He then calmly told me that the LDL value in my Lipid Panel was high and that both the ADA and the AHA guided that my LDL should be below 100mg/dl. I told him that I didn’t care what the ADA and the AHA guidelines said. I then went into a bit of a harangue about Ancel Keys, and suggested the doctor really should “go back to school.” That did it. He declared, “You need to find a new doctor. I’m not going to treat you.” And then he hung up. Two hang-ups in a row! But I don’t blame him. I was rude – really rude. Maybe even hostile? Perhaps a “little” angry? But I think mostly just disappointed.

But I don’t apologize for what I said. I had high hopes that I would find an endo who was enlightened. I haven’t seen any endo in over 20 years, seeing only an internist/cardiologist 3 or 4 times yearly, and I wanted to establish a relationship with an endo in the community near our winter home. I failed, and it was my fault. Of course, I could have accepted the prescription he offered and then refused to fill it. Then the doctor could simply have written in my chart that, like all the other old people (his PA told me) who “don’t care about their health,” I was just “non-compliant.” She told me that when I asked her why other patients didn’t follow her recommendation to eat Low Carb. She eats about 60 carbohydrate grams a day. I eat about 15, for glucose control. I am a 26-year-long Type 2 diabetic who is carb intolerant.

Anyway, in reaching my latest level of self-assurance (expressed as arrogance or ignorance or both, depending on your perspective) about the optimal blood lipid levels, I had a fresh recollection of Chapter 41, “Blood Lipids,” in “Perfect Health Diet” (Scribner, 2012), the new book by Paul and Shou-Ching Jaminet (both PHDs). It’s a very good book, even if I recommend it only for “background” for most Type 2s. They do get “into the weeds” a bit, but explain everything very well, and I really like their approach to healing – finding the root causes rather than treating the symptoms.

Chapter 41 has the following sub-sections: “Optimal HDL Levels,” “How to Raise HDL Levels,” “The Immune Functions of LDL,” “Optimal Blood Lipid Levels,” and “Troubleshooting Blood Lipids.” I will discuss only the section “Optimal Blood Lipid Levels” in this missive and then relate it to my own test results from the lipid panel performed by my “new” (and now former) endo. For the other sections of this chapter and the rest of the book, you should buy the book. I regard it as an essential reference and a must for any nutrition “library.”

“The ideal serum lipid profile – the one that produces the best health and minimizes mortality – looks like this:” (pg 366)

·         Total Cholesterol level between 200 and 260 milligrams per deciliter

·         LDL Cholesterol level above 100 milligrams per deciliter

·         HDL Cholesterol level above 60 milligrams per deciliter

·         Triglyceride level around50 to 60 milligrams per deciliter

How did my profile compare to the Jaminet’s ideal? Here is the endo’s lab report for my serum lipid profile:

·         Total Cholesterol level = 245

·         LDL Cholesterol level = 176

·         HDL Cholesterol level = 58

·         Triglyceride level = 54

Okay, I missed the HDL target by 2. But, this was the lowest HDL I have had in over 4 years (12/08 = 57) and the average of my last 15 HDLs going back to July 2007 is 75. But, in all other respects my scores appear to fit the Jaminet’s ideal.

My LDL (176) was high – the highest it has ever been (since 1992, when my lab reports first starting calculating LDLs). And my Total Cholesterol, at 245, was the highest ever, and my Total Cholesterols go back almost 40 years to 1974. So, I am intrigued and will look forward with some anticipation to my next “home” doctor’s appointment on 4/22/13.

I am comforted somewhat, however, by the knowledge that my TG/HDL ratio = 0.93, which is <1.0 and therefore “ideal.” In my column #27, a 2008 paper published in Clinics and available though PubMed (2008 August 63(4) 427-432) here, the conclusion is that this ratio is “…the single most powerful predictor of extensive coronary heart disease among all the lipid variables examined.” I would like to have known, though, what my hs C-Reactive Protein score was. Oh, well.

© Dan Brown 2/9/13

Saturday, February 2, 2013

The Nutrition Debate #86: Beta Cell Function and Insulin Sensitivity

 I recently visited (as a new patient) an endocrinologist in Florida. My purpose was to find out what was going on with my glucose metabolism. Specifically, I was interested in knowing my % Beta cell function and my % Insulin Sensitivity (and its reciprocal, Insulin Resistance, or IR). I had read about a test that determines those values and wanted to be tested. The HOMA Assessment determines these values by formula. There is also a more sophisticated model that Oxford University developed called the HOMA2 that employs a “calculator.”

I haven’t been seen by an endo in more than 20 years (the last time to measure my testosterone, as I recall). Five years before that I consulted an old-timer who had me visit the out-patient department of a local hospital for a 4-hour glucose tolerance test. That test just confirmed the diagnosis that had been made a few years earlier that I was a Type 2 diabetic. That endo also upped my prescription for a sulfonylurea, the only oral diabetes med permitted in the U.S. at the time. Eventually I was maxed out at 20mg of glyburide (the sulfonylurea).

It would be another 10 years (in 1995) before my current doctor added metformin, which by then was finally allowed in the U. S. It had been in use in Europe for some time. But before long I was maxed out on that drug too and was then started on a TZD (Avandia). That is when my doctor suggested I try the Atkins Induction diet to lose weight. He had just read the Gary Taubes cover story, “What If is All Been a Big Fat Lie?” in the NYT Magazine on July 7, 2002. Within a few days on Atkins Induction, I was having frequent hypos. I called my doctor, and he told me to drop the Avandia. When the hypos continued, he cut the sulfonylurea and the metformin dosages in half, and then soon afterwards, in half again.

I lost 60 pounds on Atkins Induction but, after a few years of stable weight, I gained back 12. I then decided to try the Bernstein diet for diabetics. I lost 100 pounds in the next 50 weeks and eventually another 22 for a total loss of 170 pounds. Along the way, I weaned myself off the final 5mg of Micronase (the brand-name of the sulfonylurea), by halving it to 2½ and then halving it again (cutting the 2½ mg pill in half). I still take 500mg metformin once a day. But, all told, I figured I had been on a sulfonylurea, which pushes the pancreas to secrete more insulin in response to a glucose challenge, for the better part of 20 years. Remembering Dr. Ralph DeFronzo’s Banting Lecture at the 2008 ADA Convention in San Francisco, I figured I had lost 80% of my Beta cell function by the time I was diagnosed in 1986. He also said, at the end of the introduction to the full paper published in the ADA magazine “Diabetes,” and available here, “Sulfonylureas are not recommended because, after an initial improvement in glycemic control, they are associated with a progressive rise in A1C and progressive loss of β-cell function” (emphasis added).

Given my history on sulfonylureas and Dr. DeFronzo’s prognostications, the implications for my Beta cell function were not promising. So, my visit to the endo in Florida was for the specific purpose of testing my % Beta cell function and % (Insulin) Sensitivity. I was surprised with the test results: Beta Cell function = 68.2%; Sensitivity = 94.6%; and IR = 1.1 (1.057). I don’t have a follow-up visit scheduled with the endo for another 10 weeks, so I decided to do a little homework on my own. I would also like to put these results “out there” for comment by others. Has anyone out there ever had a HOMA assessment done? The endo’s nurse said she had been working with this doctor for about 10 years, and he had never ordered the test before. She knew, she said, because she’s the one who places the orders for tests.

The doctor said the test was mostly used in research, and he would have to look up the formula to apply it. Okay, but, I wondered, if not commonly used in clinical practice, does the test have clinical value? What can be learned from it? My first read is that I am not in as bad a shape as I thought I was. True, I have been eating VLC “on and off” for over 10 years, and now “totally on” for the last four and a half months. My last HbA1C was 5.7, down from recent low 6s. I expect the one from blood taken last week will be 5.6 or even 5.5. And I have been eating a very restricted ketogenic diet, recently under 1000 calories a day (without hunger), which is the direct consequence of being ketoadapted and in ketosis virtually all the time. My body is in balance and happy with my dietary intake, my supplements, and with the fatty acids, glycerol and ketone bodies it is making every day from the body fat it is breaking down for energy.

But I have not been satisfied with my fasting blood glucose readings these last 4 months. I no longer have weekly averages around 90. I have to work hard to get them under 100, and they should never be higher than 95. My daily FBG readings should never be above 100. I am very careful to eat VLC and to never eat too much protein.

So, what does my HOMA assessment test reveal? If my Type 2 diabetes is in “clinical remission,” is it attributable solely to my VLC diet? If my diet has “reversed” my Type 2 diabetes, has it also “normalized” my Beta Cell function and improved my insulin sensitivity? If Beta Cells can regenerate themselves, can they do this over and over, year after year?

I hope to learn the answers to these questions from my new endo in my follow-up appointment. I can hardly wait.
© Dan Brown 2/2/13