Curing Diabetes

I wrote the following to respond to a post about Jason Fung on Carb Sane (Diabetes Un-Funged). Her central thesis is that exogenous Insulin doesn’t cause Insulin Resistance.

I was a T2DM for 13 years (and probably undiagnosed for 8 years before that).

Two years ago, I went from 100 units a day of Insulin (Medtronics Pump) to zero in two weeks following Fung’s methods (Low Carb and Intermittent Fasting) with great blood sugar levels. I did Low Carb in the past and it helped me get a decent HbA1C but not out of the diabetic range. Fast forward 22 months and I am down 120 lbs (current weight is 165). My HbA1C was 5.2 a few months ago. No longer on HBP meds (I was on them for 20 + years). All of this while following Fung’s methods (Low Carb and Intermittent Fasting).

As to the progression of Insulin and loss of blood sugar control points in your article. In my own case I went from 40 units of Insulin with good control to 100 units with poorer control (higher HbA1C) in 4.5 years. The more I tried to control my blood sugar with Insulin the higher the amount of Insulin I required kept getting.

Worse yet the real surrogate of Insulin Resistance is the ratio of grams of carbs to units of Insulin. Anyone who has been on Insulin for a long time can testify that this ratio degrades with time. At the start, 1 unit of Insulin would cover 15 grams of carbohydrates and 4.5 years later one unit would only cover 4 grams of carbs. Clearly (at least to me) this is evidence of progressive insulin resistance).

Even if you don’t agree with Fung’s reasons his method is essentially the same as yours (Low Carb). Problem for me was that without having an intermittent fasting window I would have just had lower Insulin requirements – not a cure, but a decent treatment. I got to HbA1C of 6.6 with Low Carb and Insulin.

And it wasn’t about weight loss since most of what someone loses in the first week or two is water weight. I think it was more about leaning out the liver and then leaning out the fat around the pancreas than anything else…

Incidentally, this wasn’t about titrating the dosage of Insulin over the four and a half years. The “honeymoon period” is well known among people who start using diabetes meds – including Insulin. It isn’t long until more is required as the body becomes more resistant to the insulin.

Another line of evidence is the studies showing that hyperinsulinemia precedes diabetes and obesity often by decades.

Burn Fat Fast

The top rates of fat oxidation (fat burning) are around 1.5 g/min at high intensity levels. At that level an hour would burn 90g of fat or 810 calories. Marathon runners are said to expend about 1,000 calories an hour but that might be largely carbohydrates (around 75%).

Lightly active fat oxidation rates are 31 g/lb of fat mass per day (Hypophagia – How much fat can I lose in a day?). Assuming a 170 lb person with 10% body fat that’s 17 lbs times 31g/lb = 527 cals a day. At that body fat it would take a week to lose a lb. This also means that the diet can’t be at a larger caloric deficit than that amount (exercise as above is the exception).

Assuming that the 170 lb person expends about 12 calories per lb of body weight that’s a daily caloric expenditure of 2040 calories. Cutting calories for a caloric deficit to around 1500 would result in maximum fat loss.

But this is only true if the person gets enough protein. Ideally, that would be around 0.8 g per lb of lean body mass for a lightly active person. This person would need to eat 136g of protein a day.

Eating the protein in four meals of at least 30 grams of protein would spare the most muscle mass while rapidly losing weight.

Macros would then be:

  • 136 g protein
  • 20 g carbs
  • 97 g fat

It might be tempting to drop fat or protein but that would be a mistake since it would not result in larger losses.

Combine that with intense activity (as noted) a greater weight of loss can be achieve.

I have a calculator for this at Keto Calculator.

Low Fat Vs Low Carb

Interesting one year long study to compare low fat and “low-carb” diets points out the effect of individual variability on dietary results (Gardner CD, Trepanowski JF, Del Gobbo LC, Hauser ME, Rigdon J, Ioannidis JPA, Desai M King AC. Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial. JAMA. 2018 Feb 20;319(7):667-679.). The study was a

…randomized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40

The study looked at the two diets with respect to three categories:

weight change

genotype pattern

insulin secretion

The results were surprising (from my perspective).

…weight change over 12 months was not significantly different for participants in the HLF diet group (−5.3 kg) vs the HLC diet group (−6.0 kg),

there was no significant diet-genotype interaction

[there was no significant ] diet-insulin interaction

Genetic Distribution in this Study Population

This may be the most interesting result from this large population group. The distribution of low-fat and low-carb genotypes were 40% vs 30%.

  • 244 [40%] had a low-fat genotype;
  • 180 [30%] had a low-carbohydrate genotype

The genetic tests were for  (Dieting With A New Twist — A Double Helix):

3 genes (PPARG, ADRB2, and FABP2)  that are involved with fat and carbohydrate metabolism

Here is a critique of the genes that the study selected by the Genetic testing company (Arivale responds to DIETFITS study in Journal of American Medical Association (JAMA)).

The DIETFITS study considered three genetic variants in their analysis: FABP2 (rs1799883), PPARG (rs1801282), and ADRB2 (rs1042714). It is unclear why the investigators chose these specific genetic variants given that other variants also had evidence of gene/diet interaction at the time the study was designed.

Further, it appears that the investigators weighted each variant equally in their genetic model, regardless of the strength of the evidence or other factors. This may have affected the study outcomes, as which genetic variants are included in a genetic risk profile and how they are individually weighted is likely to play a role in what findings emerge.

Dietary Macronutrient Contents

This was not a ketogenic diet study by any stretch of the imagination.

In the HLF vs HLC diets, respectively, the mean 12-month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45% for fat, and 21% vs 23% for protein.

A well formulated ketogenic diet would have had 5% of calories from carbohydrates 20-30% from protein and the remainder 65-75% from fat.

[2018-06-20: Interesting commentary here – Registered Dietitian Health Educators: how fat do you want to get?].

Insulin Sensitivity

Insulin sensitivity was done with an Oral Glucose Tolerance Test (Dieting With A New Twist — A Double Helix).

…the study participants were administered an oral glucose tolerance test*, and their patterns and amounts of insulin secreted in response to a 75-gram glucose challenge were determined — the 30-minute response was used as an indicator of carbohydrate sensitivity

Not a surprise that there was no correlation of insulin sensitivity levels and weight loss. This was due to the high level of the low-carbohydrate diet. Assuming 2,000 calories and 30% of calories from carbs would have been 600 calories from carbs or 150 grams from carbohydrates. This is too high of a level to be all that effective in dropping Insulin levels.

Insulin Sensitivity and Diet Type

Another study specifically looked at Insulin Sensitivity vs diet type (Cornier MA1, Donahoo WT, Pereira R, Gurevich I, Westergren R, Enerback S, Eckel PJ, Goalstone ML, Hill JO, Eckel RH, Draznin B. Insulin sensitivity determines the effectiveness of dietary macronutrient composition on weight loss in obese women. Obes Res. 2005 Apr;13(4):703-9.).

Obese nondiabetic insulin-sensitive (Si) (fasting insulin < 10 microU/mL; n = 12) and obese nondiabetic insulin-resistant (fasting insulin > 15 microU/mL; n = 9) women (23 to 53 years old) were randomized to either a high carbohydrate (CHO) (HC)/low fat (LF) (60% CHO, 20% fat) or low CHO (LC)/high fat (HF) (40% CHO, 40% fat) hypocaloric diet. Primary outcome measures after a 16-week dietary intervention were: changes in body weight (BW), Si, resting metabolic rate, and fasting lipids.

The results were interesting:

Insulin-sensitive (Si) women on the HC/LF diet lost 13.5 +/- 1.2% (p < 0.001) of their initial BW, whereas those on the LC/HF diet lost 6.8 +/- 1.2% (p < 0.001; p < 0.002 between the groups). In contrast, among the insulin-resistant women, those on the LC/HF diet lost 13.4 +/- 1.3% (p < 0.001) of their initial BW as compared with 8.5 +/- 1.4% (p < 0.001) lost by those on the HC/LF diet (p < 0.04 between two groups).

The state of Si determines the effectiveness of macronutrient composition of hypocaloric diets in obese women. For maximal benefit, the macronutrient composition of a hypocaloric diet may need to be adjusted to correspond to the state of Si.

The Great Noakes-McDonald Debate

One of my new favorite podcasts is the Sigma Nutrition Radio Podcast.

Podcast 210 was a debate between Dr. Tim Noakes and Martin McDonald. It was conducted in a gentlemanly way. Given the personality of Tim Noakes it is hard to imagine it not being handled that way.

The subject was Insulin Resistance and the effectiveness of the Low Carb diet compared to other interventions. Both sides had good points but to my way of thinking Dr. Noakes clearly won the debate.

Both sides pointed to studies (linked on the page above).

How Type 2 Diabetics Gain Weight on Insulin

This study looks at how a Diabetic is affected strongly by taking Insulin (A. Franssila-Kallunki, L. Groop. Factors associated with basal metabolic rate in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia; October 1992, Volume 35, Issue 10, pp 962–966.). The study looked at:

66 Type 2 (non-insulin-dependent) diabetic and 24 healthy age- and weight-matched control subjects…

The interesting part is that some of the diabetics were looked at both before and after insulin therapy.

Eight Type 2 diabetic patients were re-studied after a period of insulin therapy.

In the following analysis, take note that the group put on Insulin therapy was a subset of the original group of Diabetics so their numbers were different (more exaggerated) from the rest of the Diabetics group.

Weight Gain on Insulin

The group on the Insulin treatment saw their BMI increase from 28.2 to 29.6 kg/m^2.

Basal Metabolic Rate

The control and Diabetics groups were weight matched. Surprisingly, the BMR in the Diabetics was 13% higher than the control group:

Basal metabolic rate was higher in Type 2 diabetic patients than in control subjects (102.8 ± 1.9 J · kg LBM−1-min−1 vs 90.7 ± 2.8 J · kg LBM−1;min−1; p<0.01)

Insulin treatment reduced the BMR of the Diabetics (115.5 ± 5.6 to 103.1 ± 5.7). It is question begging whether the lowered BMR caused the BMI increase with Insulin.

Diabetics Produce More Glucose

Not surprisingly the Type 2 Diabetics were producing glucose from their livers at significantly higher rates than the control group.

 The basal rate of hepatic glucose production was higher in Type 2 diabetic patients than in control subjects (1044.0 ± 29.9 vs 789.3 ± 41.7 μmol/min; p <0.001)

Insulin therapy decreased glucose production (1133 ± 92 to 983 ± 80). In theory this is good. A possible explanation of the effect of Insulin is that it took more insulin to overcome the Insulin Resistance of the liver. Insulin therapy isn’t a great long term solution, though, since the liver will eventually become even more Insulin Resistant and require ever increasing levels of exogenous Insulin.

Insulin Therapy Reduced Fat Oxidation Rate

The fat oxidation of the Diabetics was reduced when Insulin therapy was added:

Lipid oxidation was increased in Type 2 diabetic patients compared with control subjects (1.68 ± 0.05 vs 1.37 ± 0.08 μmol · kg LBM−1 · min−1‘; p <0.01) and decreased significantly after insulin therapy (p<0.05).

The lipid oxidation rate fell from 2.1 ± 0.1 to 1.4 ± 0.1 with the addition of Insulin therapy. A key phrase in the discussion section is:

lipid oxidation accounted for the major part of the BMR

So, putting someone on Insulin reduces their fat oxidation rate. If Type 2 Diabetes is a problem of fat build-up then Insulin therapy isn’t helping. It’s making Diabetics fatter. Yes, it is driving down Serum Glucose levels in the short term.

Fasting Insulin

Of note is the difference in the Fasting Serum Insulin levels between the Diabetics (64 ± 5) and the control group (37 ± 4).

The subset of the Diabetics put on Insulin therapy had higher Fasting Insulin levels than the lumped group of all diabetics. With the addition of exogenous Insulin therapy the Fasting Serum Insulin levels in the Diabetic (subset) increased from 84 to 132.

That would, of course, indicate that the part of the Diabetics group that was not put on Insulin had a much lower fasting Insulin level. This is interesting given that the error bar was ±5 so the group put on Insulin therapy at 84 +± 11 was many standard deviations out of the entire group.

The paradox here is that even with higher fasting insulin levels the fat oxidation rate in the diabetics indicates that the additional fasting insulin levels didn’t seem to stop the diabetics from being able to burn fat. The paradox is that the fat oxidation rate decreased with Insulin Therapy which would indicate the opposite conclusion.

This fits the hypothesis that Insulin Resistance in the liver is a primary driver rather than insulin resistance in adipose cells.

Calories out is much more complicated than just a number on a paper.

 

Exogenous Ketones Inhibit Fat Loss

Contrary to much of the marketing hype, exogenous ketones inhibit fat loss. Ketones generated from the person have the following characteristics (Brianna J. Stubbs, Pete J. Cox, Rhys D. Evans, Peter Santer, Jack J. Miller, Olivia K. Faull, Snapper Magor-Elliott, Satoshi Hiyama,3 Matthew Stirling, and Kieran Clarke. On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 2017; 8: 848.):

The metabolic phenotype of endogenous ketosis is characterized by lowered blood glucose and elevated Free Fatty Acid (FFA) concentrations, whereas both blood glucose and FFA are lowered in exogenous ketosis. During endogenous ketosis, low insulin and elevated cortisol increase adipose tissue lipolysis, with hepatic FFA supply being a key determinant of ketogenesis.

Ketone bodies exert negative feedback on their own production by reducing hepatic FFA supply through βHB-mediated agonism of the PUMA-G receptor in adipose tissue, which suppresses lipolysis (Taggart et al., 2005).

Exogenous ketones have similar effects.

Exogenous ketones from either intravenous infusions (Balasse and Ooms, 1968; Mikkelsen et al., 2015) or ketone drinks, as studied here, inhibit adipose tissue lipolysis by the same mechanism, making the co-existence of low FFA and high βHB unique to exogenous ketosis.

If your goal is weight loss from your body, exogenous ketones are probably a poor choice.

 

MCT Oil and Liver Size

A rat study showed MCT Oil increased liver size (Shannon L. Kesl,corresponding author Angela M. Poff, Nathan P. Ward, Tina N. Fiorelli, Csilla Ari, Ashley J. Van Putten, Jacob W. Sherwood, Patrick Arnold, and Dominic P. D’Agostino. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats. Nutr Metab (Lond). 2016; 13: 9.).

MCT supplemented animals had significantly larger livers compared to their body weight (p < 0.05).

The study offered a possible explanation for the larger liver size.

The ratio of liver to body weight was significantly higher in the MCT supplemented animals (Fig. 5). MCTs are readily absorbed in the intestinal lumen and transported directly to the liver via hepatic portal circulation. When given a large bolus, such as in this study, the amount of MCTs in the liver will likely exceed the β-oxidation rate, causing the MCTs to be deposited in the liver as fat droplets. The accumulated MCT droplets in the liver could explain the higher liver weight to body weight percentage observed with MCT supplemented rats.

The rats were fed a large amount of MCT Oil.

It should be emphasized that the dose in this study is not optimized in humans. We speculate that an optimized human dose would be lower and may not cause hepatomegaly or potential fat accumulation.

Another study indicates positive results when MCT Oil replaces Corn Oil (Ronis MJ, Baumgardner JN, Sharma N, Vantrease J, Ferguson M, Tong Y, Wu X, Cleves MA, Badger TM. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease. Exp Biol Med (Maywood). 2013 Feb; 238(2):151-62.).

These data suggest that replacing unsaturated fats like corn oil with MCT oil in the diet could be utilized as a potential treatment for NAFLD.

This could be something that people who love their Bulletproof Coffee might want to pay attention to.

 

Maintenance – One Month In

I’m doing pretty well with my Low Carb maintenance at least from a weight perspective. I have been weight stable over the past four weeks at around 166 +/- 4 lbs:

I hit a new low at 162 lbs two weeks ago and used a lot of salt to increase my water weight and level out the fluctuations by adding electrolytes (Messing Around With Electrolytes).

My [food] macros were set to:

  • Protein : 165-174g
  • Carbs: < 20
  • Fat: 145-155

Here’s how I did over the past week (Cronometer Gold would provide a larger window of time but it costs money).

I’ve gone over on my Protein by about 10% (from the lower limit). My Protein at 183 were matched by my carbs plus fat grams of 183g. That is the maintenance plan of Dr Ted Naiman.

My blood sugars have been good over this time period although they were messed up a bit when I got a cortisone shot in my shoulder.