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.

Great BLOGs

There are plenty of better BLOGs out there than this BLOG. Here’s some of the evidence based nutrition BLOGs run by some smart guys. As I find more I will add them to this list.

 

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 as Glucose (Fuel)

This article cites a number of studies which show the ways that fat gets converted to glucose on a Low Carb diet (We Really Can Make Glucose From Fatty Acids After All! O Textbook, How Thy Biochemistry Hast Deceived Me!).

The common objection to this is that insulin levels are low when eating fat.

Thus, when insulin levels fall and ketone levels rise, as occurs when our carbohydrate intake is low, our cells increase their supply of CYP2E1 and thereby activate the conversion of fatty acids to glucose.

And more details:

methylglyoxal inhibits the breakdown of glucose … when this pathway is activated, we not only convert fatty acids to glucose, but methylglyoxal concentrations rise and inhibit the breakdown of glucose.

Thus, when glucose runs low and we begin subsisting primarily on fatty acids for fuel, we have a coordinated effort to both spare glucose and to make more of it.

Here’s a study of the subject (

Christoph Kaleta, Luís F. de Figueiredo, Sarah Werner, Reinhard Guthke, Michael Ristow, and Stefan Schuster. In Silico Evidence for Gluconeogenesis from Fatty Acids in Humans. PLoS Comput Biol. 2011 Jul; 7(7): e1002116.). If we could not make glucose from fatty acids then we would not be able to survive long fasts because there are parts of our bodies which absolutely require glucose.

Analyzing evidence concerning the detected pathways lends support to their importance during times of starvation, fasting, carbohydrate reduced and ketogenic diets and other situations in which the nutrition is low on carbohydrates. Moreover, the energetic investment required for this pathway can help to explain the particular efficiency of carbohydrate reduced and ketogenic diets such as the Atkins diet.

More:

Although the brain can use ketone bodies in these situations, it still needs a certain amount of glucose, which has critical implications upon starvation and similar conditions.

Another Line of Evidence

An interesting writeup (Glucose from fatty acids: RQ of 0.454) on the generation of glucose from fatty acids(originally from Heinbecker. Studies on the Metabolism of Eskimos., 1928). The Eskimo woman has a very low RQ value on day 3.5 of her fast.

An RQ below 0.69 suggests the generation of oxygen rich molecules from fatty acids. An RQ of 0.454 suggests a huge amount of (probable) gluconeogenesis from fat is going on.

 

Low Carb Diet and Type 1 Diabetics – Part 2

Part 1 took a look at a Systematic Review of this subject.

A new study (May 2018) on the subject of Low Carb and Type 1 Diabetes (Leow ZZX1, Guelfi KJ1, Davis EA2,3,4, Jones TW2,3,4, Fournier PA1. The glycaemic benefits of a very-low-carbohydrate ketogenic diet in adults with Type 1 diabetes mellitus may be opposed by increased hypoglycaemia risk and dyslipidaemia. Diabet Med. 2018 May 8. doi: 10.1111/dme.13663.).

Abstract

AIMS:

To investigate whether very-low-carbohydrate high-fat diets, typical of ketogenic diets, can improve glycaemic control without causing any ill health effects in adults with Type 1 diabetes.

METHODS:

In this observational study, 11 adults with Type 1 diabetes (seven men, four women, mean ± sd age 36.1± 6.8 years, mean ± sd duration of diabetes 12.8 ± 10.3 years), who followed a ketogenic diet (< 55 g carbohydrate per day) for a mean ± sd of 2.6 ± 3.3 years (β-hydroxybutyrate 1.6 ± 1.3 mmol/l), underwent sampling and analysis of fasting blood, and were fitted with a blinded continuous glucose monitor for 7 days to measure glycaemic variability.

RESULTS:

The mean ± sd HbA1c levels were 35±4 mmol/mol (5.3±0.4%), and participants spent 74±20 and 3±8% of their time in the euglycaemic (4-8 mmol/l) and hyperglycaemic (>10 mmol/l) ranges, respectively, with little daily glycaemic variability (sd 1.5±0.7 mmol/l; coefficient of variation 26±8%). Blood glucose levels were <3.0 mmol/l for 3.6% of the time, and participants experienced a median (range) of 0.9 (0.0-2.0) daily episodes of hypoglycaemia.

Total cholesterol, LDL cholesterol, total cholesterol/HDL cholesterol ratio, and triglycerides were above the recommended range in 82%, 82%, 64% and 27% of participants, respectively; however, HDL cholesterol levels were within the recommended range for all participants. Participants displayed no or little evidence of hepatic or renal dysfunction.

CONCLUSION:

This study provides the first evidence that, ketogenic diets in adults with Type 1 diabetes are associated with excellent HbA1clevels and little glycaemic variability, but may also be associated with dyslipidaemia and a high number of hypoglycaemic episodes.

A failure of this abstract is that it was an observational study which didn’t have a control group. Hence, the objection about hypoglycemia lacks a comparison.

Yes, there is a chance of going too low but the very fact that the participants had “little glycaemic variability” reduces the chance of hypoglycemia rather than increases the chance. How were these participants trained? When the details of the study are released we may find out more.

Also, as I have noted on many occasions it is not unusual to have low blood sugar levels while on the ketogenic diet with no ill effects. The presence of ketone bodies as fuel reduces the dependence on blood glucose.

The other complication was the cholesterol numbers. The total cholesterol and total cholesterol to HDL ratio is a function of the LDL cholesterol so this is really one issue not two particularly since this was the value most affected. This BLOG has numerous articles about LDL cholesterol on the ketogenic diet. This is a well understood subject.

Overall, this is an encouraging study for Type 1 Diabetics who want to control their HbA1c values more closely.

 

Low Carb Diet and Type 1 Diabetics

Part 2 takes a look at newer studies.

Here’s a 2018 systematic review  which looked at Type 1 Diabetics and the Low Carb Diet (Jessica L. Turton, Ron Raab, Kieron B. Rooney. Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review. PLoS ONE 13(3): e0194987). They looked through a lot of studies and narrowed down to:

A total of nine studies were eligible and included for this review.

The nine studies were:

two randomised controlled trials , four pre-post intervention studies two retrospective case-series, and one case-report.

There was considerable differences between the nine studies:

Results for our primary outcome (HbA1c) were available from eight of nine studies reviewed. Results for secondary outcomes of interest were inconsistently reported. Two studies reported the effect of a low-carbohydrate diet on frequency of severe hypoglycaemia, five studies reported total daily insulin, three studies reported BMI, and one study reported mean daily blood glucose.

Here’s the detailed data (click to see large image).

The results were disappointing for HbA1C.

Four studies reported non-significant changes in HbA1c with a low-carbohydrate diet and three studies reported statistically significant reductions (P < 0.05).

However:

Of the five studies that reported daily insulin usage, two TLCD studies  demonstrated statistically significant reductions in total daily insulin within carbohydrate restriction groups (P < 0.05) with one study also reporting a statistically significant difference between the low-carbohydrate group and high-carbohydrate comparator (P < 0.05). Levels of significance could not be calculated or obtained in three studies due to inadequate sample size and lack of raw participant data.

The reduction in Insulin use is important since that could forestall Insulin Resistance in the Type 1 diabetic. It’s a serious problem when the Type 1 Diabetic becomes resistant to the very medication that they need to live. As the paper put it:

The excessive use of insulin that is often required to achieve glycaemic control in type 1 diabetes increases susceptibility to severe hypoglycaemia and may lead to some measure of hyperinsulinemia. Hyperinsulinemia is associated with; excessive weight gain, development of the metabolic syndrome, inflammation and atherosclerosis, Alzheimer’s Disease and cancer. Findings of the present review suggest that low-carbohydrate intakes may assist in reducing or preventing hyperinsulinemia in type 1 diabetes by decreasing the absolute amount of insulin required for tight glycaemic control.

The conclusion of the study was:

This systematic review presents all available evidence for low-carbohydrate diets in the management of type 1 diabetes mellitus. The existing body of evidence is limited and more primary studies evaluating the short and long-term effects of low-carbohydrate diets on type 1 diabetes management outcomes are necessary to support its use in practice.

 

 

Long Term Adherence to Low Carb for Diabetics?

I don’t personally find long term adherence to a low carb diet to be difficult. It will be two years next month for me on Low Carb. The rewards outweigh any desire to change away from the low carb diet. In fact, the only pressure has been to maintain my weight on Low Carb since I keep losing. I never thought I would weight 165 lbs and I’ve been in this range for months.

But, there is evidence that many people who are in trials are less motivated to keep the benefits of the low carb diet past a year. Here’s a study which makes that point (Ole Snorgaard, et.al. Systematic review and meta-analysis of dietary carbohydrate restriction in patients with type 2 diabetes. BMJ Open Diabetes Res Care. 2017; 5(1): e000354.).

We identified 10 randomized trials comprising 1376 participants in total. In the first year of intervention, LCD was followed by a 0.34% lower HbA1c (3.7 mmol/mol) compared with HCD (95% CI 0.06 (0.7 mmol/mol), 0.63 (6.9 mmol/mol)).

The greater the carbohydrate restriction, the greater the glucose-lowering effect (R=−0.85, p<0.01).

At 1 year or later, however, HbA1c was similar in the 2 diet groups.

The effect of the 2 types of diet on BMI/body weight, LDL cholesterol, QoL, and attrition rate was similar throughout interventions.

Does Low Carb Itself Only Work for a Year?

There’s nothing about the Low Carb diet itself which means that if you follow the Low Carb diet for a year the benefits end. My own HbA1C before Low Carb ranged from around 7-9 and now it is 5.2 at 18 months after I started Low Carb. Low Carb didn’t stop for me at a year.

My 90 day average blood sugar is 92 per my meter.

“Diet is Temporary”

Rather, it is lack of long term adherence to the diet which is the problem. If a diabetic thinks that they can do Low Carb and all their problems will go away without any potential for re-occurrence they are missing the point of how they got messed up to start with. Re-introduce a high carb load and the diabetic symptoms will quickly return.

Transition to Maintenance

People take the advice that they should increase their carbohydrates once the intervention ends and they just can’t do that. The Low Carb diet has to be followed for as long as a person wants to be non-diabetic. The transition strategy to higher carbs needs to be “just say no” rather than “try and find your carb tolerance”.

Motivated by a Study

On some level this is a problem with the nature of a study since the participants have a different set of motivations than someone who undertakes a Low Carb diet by their own choice. People who do a study are motivated by the study. A diabetic who finds low carb and reverses their diabetes has an entirely different motivation.

Study Participants

Many times these studies are very selective in the population they are studying.  Inclusion criteria is often to be newly diagnosed and un-medicated. That’s a less motivated crowd. They often have no serious symptoms (at least that they can see) and are less motivated to stay non-diabetic.

Study participants are rewarded for participating in studies not long term adherence. Once the study is over their motivation ends.

Too Easy to Pop a Pill

At the start of diabetes it is really simple to just pop a pill. And the HbA1c will react quite nicely to the pill. At least for a while.

What they don’t tell you is that you will eventually be on Insulin. I used to be in a small Bible study group with older men. There were around 6-8 of us and all of us except once guy were Type 2 diabetics. We all shared the same trajectory. We all started with Metformin which worked for a couple of years. Then our blood sugar numbers got worse. And we were prescribed additional oral medications. Eventually, we were all put on Insulin. Once of the guys commented one day that they never tell you when they put you on Metformin that it would eventually result in you getting put on Metform.

One Significant Takeaway

It seems obvious to me but the study found that the greater the carbohydrate restriction the greater the reduction in HbA1c value. This is worth noting all by itself. Here’s the figure from the study:

 

The cross over point is somewhere around 40% of energy. Assuming a 2000 calorie diet that’s 800 calories or 200 grams of carbohydrates. Above that point things get worse.

Equally the maximum benefit of around 0.8% reduction in HbA1c was found at 15% of energy from carbs. Again assuming a 2000 calorie diet that’s 300 calories or 75 grams of carbohydrates. That’s still high by my own standards.

 

Picking The Right Diet for Diabetics

The standard sort of recommendation for diets for diabetics is the “plate method”.

A 2017 new study compared the effectiveness of the “plate method” to a Very Low Carb diet (Laura R Saslow, PhD, et.al. An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial. J Med Internet Res. 2017 Feb; 19(2): e36.). The results were:

At 32 weeks, participants in the intervention group reduced their HbA1c levels more (estimated marginal mean [EMM] –0.8%, 95% CI –1.1% to –0.6%) than participants in the control group (EMM –0.3%, 95% CI –0.6% to 0.0%; P=.002). More than half of the participants in the intervention group (6/11, 55%) lowered their HbA1c to less than 6.5% versus 0% (0/8) in the control group (P=.02).

Participants in the intervention group lost more weight (EMM –12.7 kg, 95% CI –16.1 to –9.2 kg) than participants in the control group (EMM –3.0 kg, 95% CI –7.3 to 1.3 kg; P<.001). A greater percentage of participants lost at least 5% of their body weight in the intervention (10/11, 90%) versus the control group (2/8, 29%; P=.01).

Participants in the intervention group lowered their triglyceride levels (EMM –60.1 mg/dL, 95% CI –91.3 to –28.9 mg/dL) more than participants in the control group (EMM –6.2 mg/dL, 95% CI –46.0 to 33.6 mg/dL; P=.01).

Dropout was 8% (1/12) and 46% (6/13) for the intervention and control groups, respectively (P=.07).

  • Lower HbA1c = VLC win
  • Weight Loss = VLC win
  • Triglyceride reduction = VLC win
  • Dropout rate = VLC win

Here’s the link to the “plate method” in case anyone still wants to try the ADA recommended diet (demonstrated as ineffective to reverse diabetes above).

A critique of this study (Andrew Nathan Reynolds, BSc, MSc, PhD, et.al. Comment on “An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial”. J Med Internet Res. 2018 May; 20(5): e180.) was published which complained that the intervention counselled the Low Carb participants more than the ADA plate method. Since the ADA plate method was ineffective compared to the Low Carb diet, the correct critique of the study should not be against the Low Carb diet but against the ineffective4 plate method.