What if the History of Diabetes Went Wrong?

In an interesting paper the question is asked what if the history of the development of our understanding of diabetes has it wrong? The paper (J. Denis McGarry. What If Minkowski Had Been Ageusic? An Alternative Angle on Diabetes. Science, Vol. 258, No. 5083 (Oct. 30, 1992), pp. 766-770).

Despite decades of intensive investigation, the basic pathophysiological mechanisms responsible for the metabolic derangements associated with diabetes mellitus have remained elusive. Explored here is the possibility that traditional concepts in this area might have carried the wrong emphasis. It is suggested that the phenomena of insulin resistance
and hyperglycemia might be more readily understood if viewed in the context of underlying abnormalities of lipid metabolism.
Some powerful food for thought in the paper. Another paper (Arius, Energy Metabolism) summarizes the argument as:
The author considers the possibility that the hyperinsulinemia of early non-insulin—dependent diabetes is coincident with hyperamylinemia, since insulin and amylin are cosecreted. Amylin would cause an increase in plasma lactate (Cori cycle); and lactate, a better precursor than glucose for fatty acid synthesis, would indirectly promote the production of very-low-density lipoproteins (VLDL). There would follow an increased flux of triglycerides from liver to muscle (and adipose tissue) and, as proposed and elaborated on, an increase in insulin resistance and production of many of the metabolic disturbances occurring in diabetes.
 The author of the paper draws heavily on the Randle Cycle.
The Randle cycle is a biochemical mechanism involving the competition between glucose and fatty acids for their oxidation and uptake in muscle and adipose tissue. The cycle controls fuel selection and adapts the substrate supply and demand in normal tissues. This cycle adds a nutrient-mediated fine tuning on top of the more coarse hormonal control on fuel metabolism. This adaptation to nutrient availability applies to the interaction between adipose tissue and muscle. Hormones that control adipose tissue lipolysis affect circulating concentrations of fatty acids, these in turn control the fuel selection in muscle. Mechanisms involved in the Randle Cycle include allosteric control, reversible phosphorylation and the expression of key enzymes.[5] The energy balance from meals composed of differing macronutrient composition is identical, but the glucose and fat balances that contribute to the overall energy balance change reciprocally with meal composition.
Interesting thoughts.
Fatty acids may act directly upon the pancreatic β-cell to regulate glucose-stimulated insulin secretion. This effect is biphasic. Initially fatty acids potentiate the effects of glucose. After prolonged exposure to high fatty acid concentrations this changes to an inhibition.[13] Randle suggested that the term fatty acid syndrome would be appropriate to apply to the biochemical syndrome resulting from the high concentration of fatty acids and the relationship to abnormalities of carbohydrate metabolism, including starvation, diabetes and Cushing’s syndrome.
My own weight had been in the 280 range for a long time. In the months before I was diagnosed as Type 2 Diabetic my weight dropped 50 lbs without any lifestyle changes. After I went on Metformin my weight was relatively lower for a while. When I eventually went on Insulin my weight went up 40+ lbs fairly quickly. It is well known that Insulin adds weight.
My own thought is that the Insulin is both the lock and the key. Increased levels of Insulin pushes glucose or fat into cells and decreased levels of Insulin allows fat to come out of cells. That’s why Intermittent Fasting is such a great bullet for Type 2 diabetics. It allows our fasting Insulin levels to drop. Add to that Low Carbohydrate diets and the perfect recipe for controlling Diabetes comes into play.
The problem never really was Insufficient Insulin. The problem was too much Insulin. And clearly it is a fat related problem.

mPSMF – Weight Loss Progress

My modified Protein Sparing Modified Fast is moving along very well. Here’s my weight loss chart (from Cron-o-meter):

I had a nice drop over the past couple of days. Note that I started teh food diary in Cron-o-meter on Oct 24th. That may contribute to the losses due to the increased attention to intake. Before that I was using my own spreadsheet to track diet.  Cron-o-meter may be making me more accurate with measuring food intakes.

Goals Changes?

My newly adjusted weight goal is 170 lbs. That’s 144.4 lbs of Lean Body Mass and 15% body fat. That’s in the middle of the athlete range of body fat and on the low end for an older man like myself.

Modified Protein Sparing Modified Fast (PSMF)

I am calling what I am doing a Modified Protein Sparing Modified fast (PSMF) since the classical PSMF does not factor in fat oxidation rates.

I think it’s useful to factor in fat oxidation rates since that’s the maximum amount of fat a person can pull from their body per day. See my post, “Hypophagia – How much fat can I lose in a day?” for details.

Lyle McDonald’s Rapid Fat Loss Book

Lyle McDonald’s book “Rapid Fat Loss” (RFL) simply puts people on a particular amount of protein depending upon what stage of the diet a person is on. As the diet goes on and a person loses body fat their protein amount increases on Lyle’s method. So basically, his method is Very Low Carbs (except certain unlimited green veggies).

I think the fault in Lyle’s method isn’t so much that it leads to excessive protein consumption. Some would say that there’s no such thing as too much protein and within limits they could be right.

I think the fault in Lyle’s method is not factoring in the limits of hypophagia. Drop your calorie intake too low (below what the body can provide) and something has to give. If you can’t lose more than a particular amount of fat per day then why would you eat at a lower calorie amount than that?

 

PSMF – A Day’s Food/Supplements/Exercise/Biometrics

I’ve completed a day of logging everything with CRON-o-meter. Here’s the data entry part:

Bio-metrics were Weight, Body Fat percentage (from the scale), Body Temperature (used to determine if metabolism has dropped) and Blood Glucose.

Exercise was logged (CrossFit with warm-up and the resistance training portions).

Finally, the food I ate was carefully and completely logged. So how did I do compared to my goals? For overall calories I overshot by 2%. That’s great since I should never go under with PSMF.

The overall breakdown was also pretty good. I went under on my fat and over on my protein which balanced each other out. I did not exceed the carbohydrate number (net grams less than 20). That put me at a net deficit of 1131 calories. That would be about 2 lbs per week of loss.

 

Intermittent Fasting and Insulin Resistance

Long-time readers of this BLOG may remember that the initial seed of a thought here was to reduce Insulin Resistance. To that end, I found Dr Fung videos and decided to start Intermittent Fasting (IF). Here’s a study which returns back to that theme (Effect of intermittent fasting and refeeding on insulin action in healthy men; Nils Halberg, Morten Henriksen, Nathalie Söderhamn, Bente Stallknecht, Thorkil Ploug, Peter Schjerling, Flemming Dela; ).

 

Lessons from 100 Years Ago

An effective treatment for Type 2 diabetes has been known for over 100 years. It was described in (Steiner, 1916; The Starvation Treatment of Diabetes Mellitus). Since there were no medicines for Diabetes 100 years ago, this treatment was completely a dietary intervention.

The Protocol

Patients were fasted until their high blood sugars dropped to “normal” levels. This took anywhere from one to four days. They were then introduced to increasing amount of carbohydrates until a carbohydrate limit was determined. They were then put on a diet of half of that amount of carbohydrates. Protein was then added and the process repeated to find the limit and then reduced to half. Finally, fat was added and the process was again repeated. At the end, patients had a workable diet to leave the hospital and maintain their health. Patients also did a full fast for one day per week.

Patients that returned home and stuck to the diet stayed well and those that didn’t follow the diet got worse.

Their Macros and Averages

Case Gender Age Carbs Protein Fat Total Cals Notes
1 Female 59 45.0 73.5 120.0 1554.0
2 Female 55 65.7 82.0 58.0 1112.8
3 Female 55 49.0 72.0 156.0 1888.0
4 Female 35 25.0 75.0 100.0 1300.0
5 Female 49 58.8 66.0 120.5 1583.5
6 Female 56 10.0 46.0 47.5 651.5 (Plus
Whiskey)
7 Male 58 25.0 78.0 100.0 1312.0
8 Male 42 25.0 75.0 100.0 1300.0
Avg 51 37.9 70.9 100.3 1337.7

This diet was effective for treatment of Type 2 diabetes. It is still effective. Doctors have just forgotten their history. The availability of medications has made it easy to take a pill or a shot and not deal with the underlying problem.

 

One Year on the scale

I found my scale numbers from a year ago. This was about 10 weeks after I started Keto so it doesn’t show my full weight drop. But it does show some great trends.

Date Weight BMI Body Fat % Total Body Water % Muscle Mass % Body Fat lbs Body Water lbs Muscle Lbs
2016-10-11 248.2 34.0 40.3 28.0 21.1 100.0 69.5 52.4
2017-09-29 197.2 27.0 30.9 38.0 28.4 60.9 74.9 56.0
Difference -51.0 -7.0 -9.4 10.0 7.3 -39.1 5.4 3.6

Weight is down 51 lbs. That’s a lb a week. A decent number.

Body fat dropped by almost 40 lbs of the 51 lbs lost. That’s a great result.

Water lbs is up! That’s really good and signals a recomposition.

Equally important is that my muscle lbs has gone from 53 to 56 lbs. Not huge but definitely my muscle mass has not suffered from a year of keto and fasting.

 

Protein Sparing Modified Fast (PSMF) – Two Weeks In

I am two weeks into this Protein Sparing Modified Fast. How do the results stack up so far? My current Scale (vs Original scale) numbers are:

  • Weight: 198.6 (203.3) 4.7 lbs down, Predicted Weight: 197.5 lbs.
  • Body Fat: 31.2 (32)%. down 1.6% of body weight (-3.2 lbs), Predicted Body fat loss: -5.02 lbs.
  • Muscle:  28.2 (27.6)%, down -0.2 lbs.

That’s pretty good. 6.3% of loss was muscle loss, 93.7% of loss was fat loss. So this WOE is definitely protein sparing. Just not hitting the amount of body fat loss that the table predicts. Will need to scale the time to achieve my goals. Interestingly enough the protein loss was very similar to the number reported by Yang on a water-only fast. Still it’s hard to draw a definitive conclusion from a bathroom scale.

Water retention has been relatively good with my %H2O going up from 36.9% to 37.7% (which correlates to an actual weight drop of 0.26 lbs). This isn’t a diet which dumps a lot of water plus I had just been on a loss before starting this WOE. Also, I’ve been able to keep up with needed electrolytes. I may even be overdoing them. In PSMF it seems easier to take care of electrolytes than a water-only fast. The Whey Protein Powder has a lot of the electrolytes in them plus vitamins. Protein itself may help and the fiber in green vegetables probably contributes. I’ve been eating Chia Seeds to keep up the fiber as well.

Dietary compliance has been pretty good/easy. I have been consistently hitting or slightly exceeding my daily macros within a few percentage points. It’s a bit of a juggling act and some pain to do daily tracking of the macros, but my spreadsheet makes it easier.

Exercise (CrossFit) has been varied but well tolerated. I am mostly in the phase of neurological adaptations now and on occasion I do something right enough to not be told to change it. Not putting on muscle mass isn’t all that big of a deal in this phase of my adaptation. I don’t see myself becoming a body builder and I don’t want too much muscle mass anyway. But I can imagine that doing body weight things like chinups and pushups will be a heck of a lot easier with 28 less lbs of fat. Running is already getting easier.

Sticking with my initial goal of 15% body fat. Scale says 31.2% which is significantly different than the USN calculator value of 24.1%. This article suggests that bathroom scales include the water that is in fat cells in their water results. That may give a clue as to why the fat number and water numbers are not quite what is expected. Particularly if some fat is being replaced by water (See the Whooosh Effect).

Update (2017-09-28): Link to Lyle McDonald’s article on the whooosh.

Blood Sugar Response to Proteins

I bought some Casein Protein and consumed a test of a mixture of 25g of Casein and 25g of Whey Protein powders. Here’s the blood sugar response to that 50%-50% mixture as compared to my previous test with 50g of Whey only Protein powder:

In both tests I fasted for at least 16 hours before taking the Protein Powders. The standard information is that Whey is a fast acting protein and Casein is a slow acting protein. My starting and ending numbers today are lower than the previous test since I am farther into my Protein Sparing Modified Fast (PSMF).

I don’t have a mechanism to measure my Insulin levels.

 

Yang – Part 1 – What is Lost During a Diet or Fast?

There was an interesting study done back in the mid 1970’s. The study may not be possible today since there may now be ethical issues about starving people. We seem to have a fear of fasting that fails to take into account our human history of long fasts and famines.

This study is (Yang, Composition of Weight Lost during Short-Term Weight Reduction: METABOLIC RESPONSES OF OBESE SUBJECTS TO STARVATION AND LOW-CALORIE KETOGENIC AND NONKETOGENIC DIETS)

The six subjects in the study were each given one of three different diets for ten days each. Over the course of the thirty days they ate either a ketogenic diet, a mix fat/carbohydrate diet, or they were fasted.
This is a pretty unique study since it provides the opportunity to see what effects fasting has vs other means of weight loss. Perhaps most interestingly is that they looked at what was lost during each of the three diets. Here’s the results of the losses from each in table form (with percentage of the total weight loss):
Diet/Intervention Weight Loss Water Loss Fat Loss Protein Loss
Ketogenic Diet 466 g/day 61.20% 35.00% 3.80%
Mixed diet 278 g/day 37.10% 59.50% 3.40%
Fasting 751 g/day 60.90% 32.40% 6.70%
Here is the same data in grams per day:
Diet/
Intervention
Weight Loss Water Loss Fat Loss Protein Loss
Ketogenic Diet 466.6 g/day 285.6 163.3 17.7
Mixed diet 277.9 g/day 103.1 165.4 9.4
Fasting 750.7 g/day 457.2 243.2 50.3

Ketogenic vs Mixed Diet

Once again the Ketogenic diet is shown to be more effective at weight loss than a mixed diet. However, the different is almost entirely made up of a much larger water loss on the keto diet than on the mixed diet. Looking at the grams per day of fat loss (the only thing that really matters in weight loss) the keto diet and the mixed diet are almost identical. Protein losses were equivalent on both the Keto and Mixed diets so there’s not much of an advantage to either. In the case of Keto vs Mixed it might just come down to which diet is easier to comply with and Keto wins that hands down for most people.

Fasting vs Ketogenic Diet

The results here show that a person can lose more weight fasting than they can even with either a ketogenic or a mixed diet. After all, they are eating nothing while fasting. Fasting produced almost three times the weight loss of the mixed diet. And when it comes to fat loss, fasting also wins hands down with a 1/3 greater amount of fat lost.

However, protein losses while fasting are almost twice those of the ketogenic diet on a percentage basis. The loss of 50g of Protein a day is almost two ounces of protein per day. That could be a significant amount for someone and is not a great preservation of Lean Body Mass.

The answer here may be found in the subjects themselves. They were six grossly obese males. The mean weight was 140 kg (308 lbs). They were great subjects for fasting since they had more than enough fat mass to support a ten day fast.

Fasting was slightly better about not having as much water loss as the Keto diet but Fasting was not as effective for weight loss as a percentage of weight lost.

What Does This Study Say About Fasting?

  1. Fasting produces the quickest weight loss of any of these three methods.
  2. Over 60% of the weight lost during a fast was water weight. This was the same for the Ketogenic diet. A mixed diet with carbohydrates is better at holding onto water. Much, it not all, of water weight is quickly regained after leaving the any diet.
  3. Fasting does not spare Protein as well as the Ketogenic diet. In fact, it is about twice as bad at preserving Protein.

 

Another Bone to Pick with Dr Fung

Another point I disagree with Dr. Fung is on the subject of Electrolytes. Dr Fung’s book, The Complete Guide to Fasting, leads many people to think that they don’t need electrolytes while doing Extended Fasting. They reach that conclusion from soundbites like the chapter heading:

Electrolytes Remain Stable (TCGtF, p 49)

And

Prolonged studies of fasting have shown no evidence of electrolyte imbalances…

This is led many to conclude that they don’t need to be concerned about electrolytes during extended fasting.

This is further exacerbated by Dr Fung being a clinician, IE, Dr Fung runs a weight loss clinic. He has thousands of patients and if he says that electrolytes are not needed then they are not needed… Or so the logic goes.

However, there are many others in the keto community who will tell you that they got into serious trouble by ignoring electrolytes. In particular, they had to end fasts due to electrolyte levels being way too low and some have ended up in the ER getting electrolytes via IV bags.

Looking at What Fung Actually Says

Fung’s book has different messages on electrolytes depending upon the fasting length.

p.48-49 During short-term fasts, salt depletion is not a concern.

p. 49 During prolonged fasting (more than a week) the kidneys are able to reabsorb and retain most of the salt needed by the body. However, some salt supplementation may be required.

People seem to miss the second part (on Extended Fasting).

There very little guidance on supplementation in the book, but several examples are found in the book (p. 240):

Dizziness
If you experience dizziness during your fast, most likely, you’re becoming dehydrated. Preventing this requires both salt [ed: Sodium and Chloride are two electrolytes] and water.

The same advice is given for headaches on the same page.

Also (p 241):

Muscle Cramps
Low magnesium, which is particularly common in diabetics, can cause muscle cramps. You may take over-the-counter magnesium supplement.

Facts Keep Getting in the Way

I have a serious concern with Dr. Fung’s method when it comes to Extended Fasts and the evidence against needing electrolytes. On p 50, Dr. Fung has Figure 1.4 which states in the legend:

Figure 1.4 Electrolytes remain stable during extended fasting

The book shows charts for Chloride, Potassium and Sodium.

But what is missing from these charts? What is in the charts themselves? And, who is the subject of the charts?

The charts are from the Guiness Book record holder for longest extended fast, Angus Barbieri. I have written about Angus’ fast. His fast was medically covered in this study (Stewart, Features of a successful therapeutic fast of 382 days’ duration).

Angus was a big man

There are some significant things of note. Angus was 456 lbs at the start of his fast. To use his extreme situation as evidence that electrolyte supplements are not needed during an extended fast is sketchy at best since he had so much available substrate to draw from during his fast.

Missing Data?

Further, Dr Fung omits in his book Angus’ Magnesium (Mg) levels which were published in the study and did show him with low Mg levels for much of the fast. The Normal range is clearly marked and the points are below that line. This is the figure from the study itself.

As you can see Angus’ Magnesium levels did drop during his fast very quickly and were on the low range of normal for almost the entire fast.

Fung doubles down with the statement (p 228):

While monitoring the world-record-breaking 382 day fast, researchers measured the magnesium content within the cells, which remained firmly in the normal range.

Dr Fung does go on to note (p 229) something ignored by many:

Nevertheless, we often supplement patients with magnesium to be on the safe side.

Did Angus Get Supplements?

The study also clearly notes that Angus was given supplements for the entire duration of his fast:

During the 382 days of his fast, vitamin supplements were given daily as ‘Multivite’ (BDH), vitamin C and yeast for the first 10 months and as ‘Paladac’ (Parke Davis), for the last 3 months.

I am not sure if the formula for Multivite has changed between the mid 1960’s and today, but the current formula is:

As you can see, Angus was actually given Magnesium, Potassium, Calcium and Phosphorus during his fast in the form of a supplement. Not in high dosage but not ZERO either.

Did Angus Receive Other Electrolytes?

The most serious issue with respect to Dr Fung’s claims about Angus’ fast however, is the study indicates that Angus actually did receive additional electrolytes during the fast.

From Day 93 to Day 162 only, he [sic: Angus] was given potassium supplements (two effervescent potassium tablets BPC supplying 13 mEq daily) and from Day 345 to Day 355 only he was given sodium supplements (2.5 g sodium chloride daily).

Here’s the chart from Dr Fung’s book which clearly shows Angus’ Potassium levels dropping below normal to the point where he was given potassium supplements (day 93 in the study). They went up to normal after Angus was given the Mg supplements and even after he discontinued the supplements.

Conclusions

Angus Barbieri is an example where electrolyte supplementation was required which is the exact opposite of what Dr Fung says in his book. Angus Barbieri was not only given Potassium when his levels fell, he was also given Sodium Chloride for another portion of his fast. He also had a daily vitamin which contained these elements.

Angus Barbieri was medically monitored and tested during his extended fasts. The doctors could tell when to supplement and when it was unnecessary.

It is a serious mistake to use Angus Barbieri as evidence that electrolyte supplementation doesn’t need to be done in Extended Fasting. Fung’s book on this subject is sloppy and ignores the evidence in the study. It sends a mixed message in the practical advice section later in the book from what it sent in the earlier part of the book.