High Blood Sugar Without Side Effects?

There’s a small set of people who have a genetic defect (GCK-MODY) which gives them high blood sugar levels but they have no diabetic side effects. This paper looks at this group (Ali J. Chakera, Anna M. Steele, Anna L. Gloyn, Maggie H. Shepherd, Beverley Shields, Sian Ellard, Andrew T. Hattersley. Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation. Diabetes Care Jul 2015, 38 (7) 1383-1392).

Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population.

They don’t treat these people since they don’t respond to medications.

Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications.

These people don’t get extra high levels of blood sugar but they are in the range diagnosed for pre-diabetic up to diabetic.

People with GCK-MODY have an HbA1c between 5.8 and 7.6%.

It seems to me that this might be evidence of something other than the blood sugar being the cause of damage in diabetics. Could it be the higher Insulin levels (hyperinsulinemia)? The paper presents some possibilities.

This is likely to be due to a number of factors: the hyperglycemia is mild, stable, and under homeostatic regulation; the hyperglycemia is often lower than the threshold above which the risk of diabetes complications increases; and people with GCK-MODY do not have the additional burden of the metabolic syndrome, with weight, lipid profile, and blood pressure being comparable with the general population 

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.

 

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.

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.

 

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.

 

Taxonomy of Low Carb Studies

I’ve been collecting studies for a while and hosting them on GitHub at OpenKeto/KetoStuff. Here’s the structure of the studies.

Some of the studies can be put into multiple places so I picked one or the other place to put them without much pattern as to why. Classifying the LC Diet as Energy Input is possibly the key insight into this pattern. Also, the Effect of the Ketogenic Diet on Diabetes is under MetS.

With GitHub Desktop you can replicate the entire repository onto your computer or select individual files to download. Copyrights are the individual holders. Studies are reproduced here and were found on the Internet in general.

 

 

Messing Around With Electrolytes

I also do this to prevent calf cramps which I get when I don’t supplement electrolytes. I am putting 1 teaspoon of NoSalt or Morton Lite Salt plus one teaspoon of Sea Salt into 16 ozs of water and adding that water to my coffee during the day. This also tends to stabilize my water weight swings which I think is important in determining day-to-day weight fluctations.

  • 1 tsp Lite Salt has 290(*4) mg of Sodium and 350(*4) mg of Potassium.
  • 1 tsp of Sea Salt has 560(*4) mg of Sodium.
Totals
Sodium 4 g
Potassium 1.4 g
Chloride 5.8 g

Here’s the KetoGains recommendations.

Totals (2t-Lite Salt, 1t-Sea Salt)
Sodium 6 g
Potassium 2.8 g
Chloride 8 g
Totals (1t-NoSalt, 2t-Sea Salt)
Sodium 4 g
Potassium 2.6 g
Chloride 9.8 g
Totals (1t-Lite Salt, 1t-Sea Salt)
Sodium 4 g
Potassium 1.4 g
Chloride 5.8 g

Type 2 Diabetes Cured in Less Than Two Months

An interesting small study which fed subjects a very low fat diet and reversed their Type 2 Diabetes in a couple of months (Kitt Falk Petersen, Sylvie Dufour, Douglas Befroy, Michael Lehrke, Rosa E. Hendler, Gerald I. Shulman. Reversal of Nonalcoholic Hepatic Steatosis, Hepatic Insulin Resistance, and Hyperglycemia by Moderate Weight Reduction in Patients With Type 2 Diabetes. Diabetes Mar 2005, 54 (3) 603-608).

To examine the mechanism by which moderate weight reduction improves basal and insulin-stimulated rates of glucose metabolism in patients with type 2 diabetes, we used 1H magnetic resonance spectroscopy to assess intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) content in conjunction with hyperinsulinemic-euglycemic clamps using [6,6-2H2]glucose to assess rates of glucose production and insulin-stimulated peripheral glucose uptake.

The participants were fed a low calorie, low fat diet.

Eight obese patients with type 2 diabetes were studied before and after weight stabilization on a moderately hypocaloric very-low-fat diet (3%).

These were full blown diabetic patients.

The diabetic patients were markedly insulin resistant in both liver and muscle compared with the lean control subjects. These changes were associated with marked increases in IHL (12.2 ± 3.4 vs. 0.6 ± 0.1%; P = 0.02) and IMCL (2.0 ± 0.3 vs. 1.2 ± 0.1%; P = 0.02) compared with the control subjects.

IHL is fat in the liver. The IHL went from 12.2% to 0.6% in the diabetics with the treatment.

A weight loss of only ∼8 kg resulted in normalization of fasting plasma glucose concentrations (8.8 ± 0.5 vs. 6.4 ± 0.3 mmol/l; P < 0.0005), rates of basal glucose production (193 ± 7 vs. 153 ± 10 mg/min; P < 0.0005), and the percentage suppression of hepatic glucose production during the clamp (29 ± 22 vs. 99 ± 3%; P = 0.003).

That is a fairly small weight loss but it shows that loss of fat from the liver drops the production of glucose from the liver significantly.

These improvements in basal and insulin-stimulated hepatic glucose metabolism were associated with an 81 ± 4% reduction in IHL (P = 0.0009)

These diabetics lost 81% of their liver fat!

but no significant change in insulin-stimulated peripheral glucose uptake or IMCL (2.0 ± 0.3 vs. 1.9 ± 0.3%; P = 0.21).

This showed it wasn’t peripheral Insulin Resistance that was the problem, but rather fat in the liver. It also wasn’t other fat (IMCL).

In conclusion, these data support the hypothesis that moderate weight loss normalizes fasting hyperglycemia in patients with poorly controlled type 2 diabetes by mobilizing a relatively small pool of IHL, which reverses hepatic insulin resistance and normalizes rates of basal glucose production, independent of any changes in insulin-stimulated peripheral glucose metabolism.

The average course of treatment was 7 weeks. After the treatment their Fasting Insulin levels were almost 1/3 of the original numbers.

Low carb, of course, can quickly achieve the same results but this does point to the liver fat as the root cause of diabetes. I did this in two weeks with Low Carb and Intermittent Fasting.

Bariatric patients who are scheduled surgery are often told that they need to lose liver fat before their surgery. From (How to Shrink Your Liver Before Weight Loss Surgery).:

Studies have shown that losing weight before surgery and avoiding carbohydrates and fats in the weeks leading up to surgery can reduce the size of your liver through a process known as “ketosis,” which is when your body starts to use its fat stores because it has run out of fuel (calories). Excess fat in the liver appears to be one of the first places the body turns to for this added fuel.

Or you can just stay on the Low Carb diet…

A Second Related Study

Here’s a second related study (Noud A. van Herpen Vera B. Schrauwen-Hinderling Gert Schaart Ronald P. Mensink Patrick Schrauwen. Three Weeks on a High-Fat Diet Increases Intrahepatic Lipid Accumulation and Decreases Metabolic Flexibility in Healthy Overweight Men. The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 4, 1 April 2011, Pages E691–E695).

Twenty overweight men were randomly allocated to low- or high-fat groups (age, 54.0 ± 2.3 and 56.4 ± 2.5 yr; body mass index, 29.3 ± 0.6 and 28.3 ± 0.5 kg/m2, respectively). Both groups started with a 3-wk low-fat diet [15% energy (En%) as protein, 65 En% as carbohydrates, 20 En% as fat], after which half of the subjects switched to a 3-wk isocaloric high-fat diet (15 En% protein, 30 En% carbohydrates, 55 En% fat). After 3 and 6 wk, IHL and IMCL content were assessed by 1H magnetic resonance spectroscopy and a muscle biopsy, and insulin sensitivity was studied using a hyperinsulinemic-euglycemic clamp. An additional liver scan was performed after 1 wk in the high-fat group.

Note this was not a low carb study because both diets were relatively high in carbohydrates. However, the results are interesting.

IHL decreased by 13% in the low-fat group and increased by 17% in high-fat group (P = 0.047). IMCL content was unaffected (P = 0.304). Insulin sensitivity was unaffected. At wk 3, IHL correlated negatively with insulin sensitivity (r = −0.584; P = 0.009, all subjects combined). Metabolic flexibility, defined as change in respiratory quotient upon insulin stimulation, was decreased after 3 wk of the high-fat diet (change in respiratory quotient was +0.02 ± 0.02 vs.−0.05 ± 0.1 in low-fat vs. high-fat group, P = 0.009).

The change in RQ was very small which shows that the carb/fat burning mixture was not much changed. There was enough carbs present to cause the liver to get fatter.

 

Believing You Can Get Well

It all starts with a belief that you can get well

I used to be on Facebook groups for Diabetics. I had to leave the groups. They were just too depressing and there was no hope. Many of the people were lamenting their issues with getting on welfare, etc. They had basically already checked out of life due to complications from Diabetes.

If you tell people who believe they are just going to get worst that there is hope for something better they just don’t believe it.

It all starts with believing you can get well. You don’t have to progress down the road of chronic disease, particularly Type 2 Diabetes. You can improve and be healed.

A Low Carb diet can get you there.