The Carbohydrate-Insulin Model of Obesity

Here’s a very fresh study published in JAMA (David S. Ludwig, MD, PhD; Cara B. Ebbeling, PhD. The Carbohydrate-Insulin Model of Obesity: Beyond “Calories In, Calories Out”JAMA Intern Med. Published online July 2, 2018.). From the abstract:

According to the carbohydrate-insulin model (CIM) of obesity, recent increases in the consumption of processed, high–glycemic-load carbohydrates produce hormonal changes that promote calorie deposition in adipose tissue, exacerbate hunger, and lower energy expenditure.

Basic and genetic research provides mechanistic evidence in support of the CIM. In animals, dietary composition has been clearly demonstrated to affect metabolism and body composition, independently of calorie intake, consistent with CIM predictions.

Meta-analyses of behavioral trials report greater weight loss with reduced-glycemic load vs low-fat diets, though these studies characteristically suffer from poor long-term compliance.

Feeding studies have lacked the rigor and duration to test the CIM, but the longest such studies tend to show metabolic advantages for low-glycemic load vs low fat diets.

Beyond the type and amount of carbohydrate consumed, the CIM provides a conceptual framework for understanding how many dietary and nondietary exposures might alter hormones, metabolism, and adipocyte biology in ways that could predispose to obesity.

Pending definitive studies, the principles of a low-glycemic load diet offer a practical alternative to the conventional focus on dietary fat and calorie restriction.

Here’s a good graphic from the paper:

Worth a read.


The Big Fat Hack – Day 4

Jimmy Moore is doing a big fat hack. He’s on day 4. And Jimmy is producing more drama than ketones at this point.

Jimmy’s claim to have developed glucagon resistance is a curious one. Jimmy may have actually dropped his glycogen stores down to where there’s not enough glycogen to convert to glucagon when needed. Since Jimmy eats low protein he lacks protein as a substrate for GNG.

We know that Jimmy does everything possible to keep GNG from refilling his glycogen stores (other than stop eating fat). Does Low Carb PLUS Low Protein create a problem in refilling glycogen? This article has the clues (Glycogen Stores in Low Carb).

If that’s the case it really could be true that Jimmy’s low blood sugar isn’t met by glucagon. Equally, I don’t know how someone could differentiate between glucagon resistance and a lack of production of glucagon.

Jimmy’s ketones and blood sugar were:

Here’s Jimmy’s recovery strategy. Note the strategic placement of the F-Bomb products (one of the products Jimmy Moore promotes).

Looks like the big fat hack may have stopped his big fat hack.

Lowering Fasting Insulin

If the Insulin Theory of Obesity is correct then my question for Richard Morris, Jimmy Moore, and other obese Low Carb luminaries is:

@richard I am curious about your podcast intro. You say that all signs of disease are gone but I’ve also heard you state that your Fasting Insulin is high. That would suggest that at least one of the markers of Insulin Resistance is still present. Is that a concern for you and what are you doing to try and reverse that? Would further weight loss help? (I know you and Carl both say weight loss isn’t necessarily your goal). I know you ride your bike quite a bit so that sort of intervention seems only so helpful in your case.

Two of the signs of metabolic syndrome are waist circumference and fasting insulin levels. Richard and Jimmy have both stated they have high fasting insulin levels and they both have substantial waist circumferences.

My contention is that weight loss is necessary in order to lower fasting insulin. And yes, it is true that higher fasting insulin levels make it much harder to lose weight. Note I did not say impossible, just much harder. But they also make it much more important to lose weight.

Here’s evidence that fasting Insulin correlates to BMI. A great place for an answer to this question to look is very young people. There was an interesting study which looked at seven year old children (Hrafnkelsson H1, Magnusson KT, Sigurdsson EL, Johannsson E. Association of BMI and fasting insulin with cardiovascular disease risk factors in seven-year-old Icelandic children. Scand J Prim Health Care. 2009;27(3):186-91.). Here’s what they learned in these young children:

Some 14% of the participating children were classified as overweight. Overweight children had higher fasting insulin, higher fasting glucose, and higher systolic and diastolic blood pressure. Furthermore, they had significantly lower total cholesterol (TC), lower high-density lipoprotein (HDL), and lower low-density lipoprotein (LDL) but a similar TC/LDL ratio to normal-weight children. The factors that were strongly associated with BMI were serum fasting insulin, systolic blood pressure (SBP), HDL and fasting glucose, while the sum of four skinfolds, triglycerides, glucose, and LDL were highly associated with fasting insulin.

The LDL part is interesting (but not the subject of this thread).

BMI and fasting insulin are clearly correlated. Does one cause the other? Probably.  Does it actually matter? If lazy ket0 isn’t working then look around. Protein Sparing Modified Fasts are a special case of keto with low fat and low carbs. But the high fat kings won’t try them (recent pictures of Left to Right Richard Morris, Carl Franklin, and Jimmy Moore). As far as I know none of these guys will post their food diaries. In fact, they seem to not track their food intake.


Again, this is not intended to ridicule any of these men. Rather, it is to question their dietary advice. They are all low protein and high fat advocates. And it worked for them. Until it didn’t work.


Jimmy’s Big Fat Experiment

Jimmy Moore has been covered here a couple of times (Fat Jimmy and Jimmy Does PSMF – Sorta).

Jimmy’s Current Drama/Experiment

Now Jimmy is going to do an experiment to show the effect of eating 90% of his calories from fat. This is designed to contrast with Jimmy’s “failed” protein experiment. Remember that? It was the experiment which dropped Jimmy’s fasting Insulin in half but Jimmy considered it a failure.

Jimmy is going to eat 1900 calories for a week. Let me make a radical set of predictions (actually not radical at all).

  1. Jimmy will lose weight.
  2. Jimmy weighs north of 300 lbs so he must be taking in like 3500 calories a day.
  3. Dropping his calories to 1900 will create a deficit of around 1600 calories a day which should come from body fat.
  4. Jimmy should lose about 3-4 lbs of fat over the week.
  5. If Jimmy loses more 3-4 lbs that will be interesting since it will create a real mystery as to what he is eating prior to the diet since he would have to be at a large surplus prior to the experiment.
  6. Certainly Jimmy has enough fat on his body to support a long fast so this high fat diet will just supplement his body fat stores.
  7. Jimmy will proclaim fat the winner over protein.
  8. Jimmy is doing 1900 calories with 190 calories from protein or 47.5 grams of protein a day.
  9. If Jimmy currently weighs 300 lbs, that’s 136 kg. Jimmy will be taking in 0.35 g per kg of body weight.
  10. The DRI (Dietary Reference Intake) is 0.8 grams of protein per kilogram of body weight so Jimmy will be under half the DRI for protein.
  11. Jimmy’s cholesterol will go up since he’s going hypocaloric (See Dave Feldman).

Jimmy’s diet will be fat bombs.

Jimmy’s High Protein Experiment

What was Jimmy’s so-called High Protein diet? 1900 calories with 90% from protein is 1710 calories from protein or 427.5 grams of protein. That’s an extreme amount of protein. If Jimmy bothered to look at Ted Naiman’s graphic he would have seen:

TedTed Naiman’s graphic shows the ratio of protein to non-protein energy in grams. To maintain eat as many grams of fat as protein. To lose eat more protein and less fat. To gain weight eat less protein and more fat. Jimmy has been in that diet as he has gotten fatter.

Jimmy would do better to listen to Arnold.

Hyperinsulemia and Weight Loss

Interesting line of evidence as to why insulinemia may cause obesity (rather than the reverse). The evidence is based on a 5-6 week long water-only fast (Fasting insulin and weight loss on a water fast). In the study referenced, the fasting insulin of the individuals was measured as they progressed on the fast.

On a water fast the higher your starting weight (surrogate for “fed” fasting insulin, remote surrogate for “starvation” fasting insulin), the less weight you lose over 5-6 weeks.

Elevated insulin is associated with obesity BECAUSE it inhibits lipolysis.


Fat and Insulin Resistance at Insulin Injection Sites

I had an insulin pump for over four years. I learned a lot about Insulin from using the pump.

One of the things that I learned about Insulin injection is that insulin injection points need to be moved after a while. The reason is that the area around the injection becomes Insulin Resistant and insulin isn’t as effective in that area. Eventually, a whole part of the body becomes unusable and may remain that way for years.  I could no longer pump into the area to the sides of my navel. It gets harder and harder to find a place to pump Insulin. There are limited areas to pump. Some are pretty hard to reach, uncomfortable or just plain impractical.

The other thing I learned is that there’s localized fat deposited in the same area as the Insulin injection point was placed. This fact has been noted in the literature for almost 70 years (Renold AE, Marble A, Fawcett DW. Action of insulin on deposition of glycogen and storage of fat in adipose tissue. Endocrinology. 1950;46(1):55–66.).

SOON after the discovery of insulin, clinical observers reported the occurrence … hypertrophies (Eeg-Olofsson, 1930; Rowe and Garrison, 1932) of subcutaneous adipose tissue at the site of repeated insulin injections. A number of case reports and statistical studies have since been published. … lipodystrophy without evidence of inflammation has not been reported following injection of substances other than insulin. The production of insulin lipodystrophies in animals has been attempted by Reed, Anderson, and Mendel (1930), Marble and Smith (1942), Goldner (1943) and Oesterreicher (1947) with conflicting results.

In the search for an explanation of the effect of insulin on the adipose tissue of diabetics, various factors not concerned with the actual metabolic action of insulin have been suggested but supporting experimental evidence has been lacking (Marble and Smith, 1942).

This is interesting to me because of excess skin. My fat was enlarged by Hyperinsulinemia both from diet and exogenous Insulin.


HyperInsulinemia – Finding the Moving Target

My BLOG posts on hyperinsulinemia.

A related BLOG post by an MD (Hyperinsulinemia: Should You Be Tested?).

My initial target was hacking my diabetes. That was even the subtitle of my original BLOG (Hacking my T2DM). For years, I took the medications that the doctors gave me and my diabetes got worse. In the end I was on 100+ units Insulin delivered via a pump and I was getting worse. I thought there must be a better target since the doctor’s approach wasn’t helping me.

Diabetes and Insulin Resistance

In seeking answers, I found that the diabetes related to Insulin Resistance. So I chased after curing my Insulin Resistance via the Low Carb diet. In doing so my diabetes was apparently cured.

Certainly the low carb diet has greatly helped my Insulin Resistance, but the question remained of whether my diet has cured my Insulin Resistance and there’s indications that I am not completely cured (Insulin Resistance Test).

Aspects of Insulin Resistance

Turned out that Insulin Resistance has a bunch of subtle aspects. There’s hepatic (in your liver) Insulin Resistance, peripheral (in your muscles) insulin resistance, physiological insulin resistance, etc. Each of these play a role in diabetes and each are affected in various ways by the Low Carb diet.

Somebody may have written a good write-up on all of this but I haven’t yet seen it. Everyone seems to have a piece of the story. Perhaps a BLOG post sorting it out would be helpful?

Fatty Liver and Diabetes

Recently, I’ve been circling around a more nuanced view of the problem and have been looking more closely at the role of the fatty liver and glycogen stores.

Your body stores glucose in the liver as glycogen. Once those glycogen stores are filled, excess carbohydrates then fill up the liver fat. . Fat then overflows into other internal organs, particularly the pancreas. Eventually the pancreas isn’t able to make enough Insulin to keep up with the resistant areas. That’s when you end up on insane levels of Insulin.

How Does a Low Carb Diet Work?

Low carb reverses fatty liver quickly by first dropping glycogen stores. It only takes a day or two of eating very low carbs to reduce your glycogen stores to minimal levels.  The liver then mobilizes its own fat for energy. This leads to a leaned liver within a week or less. This leads to less fat in the pancreas and restores normal insulin production in the pancreas.

In addition, the reduction in carbohydrates leads to a reduction in blood glucose and insulin levels. The lower glucose load allows the pancreas to keep up. This is part of why the Low Carb diet is effective with diabetes so quickly.

Obesity fits into this in a strange way since increasing insulin sensitivity (decreasing Insulin Resistance) allows cells to take up more glucose. But a low carb diet reduces the glucose from the diet. Under a low carb diet most of the glucose the body needs comes from Gluconeogenesis (GNG) (glucose made by the liver from stuff other than glucose). So GNG which is a problem under a high carb diet because it contributes to the amount of glucose in the body, then becomes what provides the necessary glucose to survive under a low carb diet.

What Causes What?

But all of this raises the question of what causes what. Current dogma mostly blames energy surplus as the problem. You are fat because you eat too much and getting fat makes you Insulin Resistant, diabetic, etc.

Since the Low Carb cure reduces weight it’s hard to tease out which effect leads in terms of the effectiveness of the cure. I know in my own case that I got off all Insulin within two weeks and I hadn’t lost much weight yet.

The Real Target

I’ve come to view Hyperinsulinemia as the central issue in the development of the cluster of issues known as Metabolic Syndrome (hypertension, hyperlipidemia, obesity, Type 2 Diabetes).  Others have recently presented the same insight. One crucial paper on the subject is (Erion, K.A. & Corkey, B.E. (2017). Hyperinsulinemia: a Cause of Obesity? Curr Obes Rep (2017) 6: 178.).

Purpose of Review

This perspective is motivated by the need to question dogma that does not work: that the problem is insulin resistance (IR).

The prequel to severe metabolic disease includes three interacting components that are abnormal: (a) IR, (b) elevated lipids and (c) elevated basal insulin (HI). HI is more common than IR and is a significant independent predictor of diabetes.

We hypothesize that

(1) the initiating defect is HI that increases nutrient consumption and hyperlipidemia (HL);

(2) the cause of HI may include food additives, environmental obesogens or toxins that have entered our food supply since 1980; and

(3) HI is sustained by HL derived from increased adipose mass and leads to IR.

We suggest that HI and HL are early indicators of metabolic dysfunction and treating and reversing these abnormalities may prevent the development of more serious metabolic disease.

Not only are high levels of Insulin the key driver in the processes related to the development of Metabolic Syndrome but they are the key drivers in reversing Metabolic Syndrome.

Taking exogenous Insulin drives hyperinsulinemia.

Eating too many carbs drives hyperinsulinemia like nothing else can do.

Reversing hyperinsulinemia via a combination of low carb diets and fasting does the best possible of any treatment.

Another view showing evidences on both sides (Shanik MH1, Xu Y, Skrha J, Dankner R, Zick Y, Roth J. (2008). Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse? Diabetes Care. 2008 Feb;31 Suppl 2:S262-8.).

We examine situations where insulin itself appears to be a proximate and important quantitative contributor to insulin resistance.

1) Mice transfected with extra copies of the insulin gene produce basal and stimulated insulin levels that are two to four times elevated. The mice are of normal weight but show insulin resistance, hyperglycemia, and hypertriglyceridemia.

2) Somogyi described patients with unusually high doses of insulin and hyperglycemia. Episodes of hypoglycemia with release of glucose-raising hormones, postulated as the culprits in early studies, have largely been excluded by studies including continuous glucose monitoring.

3) Rats and humans treated with escalating doses of insulin show both hyperinsulinemia and insulin resistance.

4) The pulsatile administration of insulin (rather than continuous) results in reduced requirements for insulin.

5) Many patients with insulinoma who have elevated basal levels of insulin have reduced (but not absent) responsiveness to administered insulin.

In summary, hyperinsulinemia is often both a result and a driver of insulin resistance.


Hyperinsulinemia – Chicken or Egg?

Which comes first – obesity or Hyperinsulinemia? Does fat get locked in our cells due to higher fasting insulin levels? Or is it the fact that we are fat that raises our fasting insulin levels?

From (Crofts, C., Zinn, C., Wheldon, M., Schofield, G. 2015. Hyperinsulinemia: A unifying theory of chronic disease?. Diabesity 1(4): 34-43.):

It is agreed that hyperinsulinemia precedes hyperglycemia, by up to 24 years. There is a strong argument that hyperglycemia indicates pancreatic β-cell attrition; essentially end-stage organ damage.We contend that the under-recognition of hyperinsulinemia is an important clinical issue because there are no standard diagnostic reference values, is most accurately diagnosed with dynamic glucose and insulin testing, and has few (pharmaceutical) management options.

One of the posited reasons for hyperinsulinemia is fructose.

Fructose is metabolized in liver into ATP and/or triglycerides in a process that is competitive with, and preferential to, glucose. If excessive fructose is consumed, glucose will not be metabolized causing hyperglycemia and subsequent hyperinsulinemia.

A helpful insight:

Hyperinsulinemia is independent to insulin resistance: Hyperinsulinemia is excessive insulin secretion, while insulin resistance is impaired glucose uptake.

Given the intertwined nature between insulin resistance and hyperinsulinemia as depicted above, it can be assumed that the majority of people with insulin resistance are also hyperinsulinemic.

Here’s another subject that is interesting:

There is debate as to whether hyperinsulinemia precedes, or are a consequence of fatty liver

From the citation noted (Dig Liver Dis. 2010 May;42(5):320-30.  From the metabolic syndrome to NAFLD or vice versa? Vanni E,

Recent data indicate that hyperinsulinemia is probably the consequence rather than cause of NAFLD and NAFLD can be considered an independent predictor of cardiovascular disease. Serum free fatty acids derived from lipolysis of visceral adipose tissue are the main source of hepatic triglycerides in NAFLD, although hepatic de novo lipogenesis and dietary fat supply contribute to the pathogenesis of NAFLD.

Here’s more on the fat question:

Hypertrophic adipose tissues activate inflammatory and stress pathways and decreases insulin response. This results in increased cytokine production including TNF-α, vascular endothelial growth factor and leptin, while adiponectin expression is decreased. These actions contribute to decreased glucose and lipid uptake, leading to further reductions to adiponectin secretion and adipogenesis as well as contributing to further insulin resistance. Decreased glucose uptake means there is less glycerol within the adipocyte to esterify free fatty acids, allowing them to infiltrate and accumulate in other tissues.

Sounds like a viscous cycle!