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 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. 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.
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. 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.
The original mission of this BLOG was to find a cure or at least a way of dealing with my own Insulin Resistance. A typical Type 2 Diabetic has Insulin Resistance. I knew that was what it was called but what is Insulin Resistance and how can someone tell if they have Insulin Resistance?
Plasma triglyceride concentration, ratio of triglyceride to high-density lipoprotein cholesterol concentrations, and insulin concentration were the most useful metabolic markers in identifying insulin-resistant individuals. The optimal cut-points were 1.47 mmol/L (130 mg/dL) for triglyceride, 1.8 in SI units (3.0 in traditional units) for the triglyceride-high-density lipoprotein cholesterol ratio, and 109 pmol/L for insulin. Respective sensitivity and specificity for these cut-points were 67%, 64%, and 57% and 71%, 68%, and 85%. Their ability to identify insulin-resistant individuals was similar to the ability of the criteria proposed by the Adult Treatment Panel III to diagnose the metabolic syndrome (sensitivity, 52%, and specificity, 85%).
To summarize (in US units):
Triglycerides > 130 mg/dL
Triglyceride to HDL ratio > 3.0 (using US units)
Insulin > 109 pmol/L
I haven’t ever had my Insulin measured so I don’t know what that number would be but I did have the other numbers done in 2015 and here are my numbers:
Triglycerides = 460 mg/dL
HDL Cholesterol = 36
Ratio = 12.7
Those numbers are well over the numbers that trigger the diagnosis of Insulin Resistance (aka Metabolic Syndrome). Check your own numbers to see where you are.
I did a previous Protein Experiment where I compared the response of my Blood Sugar to 50 grams of Whey Protein vs 50 grams of Casein Protein. Since both of those were “pure” Protein with very little fat, I was curious how those results would compare to animal protein which had fat.
For this experiment I chose Chicken Drumsticks. I weighed them amount of mean (total minus bones left at the end) and the nutritional information shows them to have been close to 50g of Protein:
Here is the Blood Glucose numbers (smoothed) over several hours added to the data from the original Whey/Casein test. The chicken drumsticks are in yellow.
Accounting for Differences
The drumsticks (in yellow) are lower overall because I have been on the PSMF longer and my blood sugar levels have dropped. This is evidence, at least to me, that the PSMF is doing good things for my metabolic health.
There was a dip at the start of the chicken wing experiment which was due to exercise. In this case it was a particularly grueling Saturday morning routine with a lot of lifting and burpees, etc. That explains the drop from 72 down to 64 at the start.
The highest number was very comparable to the Whey and Casein numbers in terms of rise from the minimum. The max rise in Blood Sugar in all of these cases was no more than 20 units.
The slope down with the animal Protein is longer and slower. That may explain less feelings of hunger as the consumption of the Protein ends.
The curve is longer than either of the “pure” Proteins. The fat may extend that longer than the pure proteins. I’d like to repeat the experiment with low fat chicken breasts and see if it’s the fat or if it is the animal Protein vs Milk Protein of the Whey/Casein choices that makes a difference.
50 grams of Protein is a decent serving size. It is more than enough to stimulate Protein Muscle Synthesis.
All in all, I see nothing to worry about with eating Protein even for Type 2 Diabetics like myself. With all of the “Protein turns into candy bars” fear mongering out there, some sanity needs to be applied to the subject.
Of course, I would encourage any diabetic to test to see where they are with this same test. At least this way they know what effect Protein would have on their body. If they are a Type 1 Diabetic this information could be helpful to determine what amount of Insulin they should add for Protein.
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.
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
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.
I got off Insulin a year ago so I haven’t needed to go to my MD in two years. I decided for the one year anniversary of starting ketogenic eating to go to my doctor and get my blood tests. So I anxiously checked my email for the results of my blood tests.
The number I was most interested in was the HbA1C number. That’s the measurement of the average blood sugar level of the past three months. The test showed my HbA1C to be 5.8. That is at the bottom of the Pre-Diabetic range. 5.6 or less is considered to be non-diabetic. The value of 5.8 is an average Blood Glucose value of 120. That matches pretty well what my meter shows.
The doctor told me he has never seen this before or heard of this happening to anyone. I told him how I did it (documented in this BLOG). How I took off a week from work and decided I was going to figure out how to Hack my Type 2 Diabetes.
I recommended that the doctor look up Jason Fung and find some of his videos on Diabetes. Here’s one that YouTube has:
Results After 6 months on the HP diet, 100% of the subjects had remission of their pre-diabetes to normal glucose tolerance, whereas only 33.3% of subjects on the HC diet had remission of their pre-diabetes. The HP diet group exhibited significant improvement in (1) insulin sensitivity (p=0.001), (2) cardiovascular risk factors (p=0.04), (3) inflammatory cytokines (p=0.001), (4) oxidative stress (p=0.001), (5) increased percent lean body mass (p=0.001) compared with the HC diet at 6 months.
A dialog in the 2KetoDudes Facebook group has me thinking more deeply about Gluconeogenesis (GNG). One of the folks there challenged my belief that GNG is a culprit with respect to Protein consumption. The person pointed me to a site which had a couple of articles, but this was the key one to represent his POV (Protein, Gluconeogenesis, and Blood Sugar).
It is the contention of the article that for a Keogenic (LCHF) diet the effects of Gluconeogensis from protein consumption are not significant to blood glucose levels. In fact, the article argues GNG and blood glucose levels are negatively correlated.
We haven’t found any solid evidence to support the idea that excess protein is turned into glucose.
Another interesting quote:
On the input side, blood sugar can come from three sources:
– We can eat carbohydrates, and have sugar enter the blood through digestion.
– We can make glucose out of glycogen (the limited amount of glucose stored in persistent form in the liver). This process is called glycogenolysis.
– Thirdly, we can produce new glucose by GNG.
Here’s where it gets even more interesting:
Even on a keto diet, there is still a substantial proportion of glucose production from glycogenolysis. Ultimately, of course, the glycogen in keto dieters also comes from GNG that happened previously.
Glucose-stimulated insulin secretion was increased in the high protein group “516 45 pmol/l vs 305 32,p = 0.012) due to reduced glucose threshold of the endocrine beta cells “4.2 0.5 mmol/l vs 4.9 0.3, p = 0.031). Endogeneous glucose output was increased by 12% “p = 0.009) at 40 pmol/l plasma insulin in the high protein group, but not at higher insulin concentration whereas overall glucose disposal was reduced.
In the present study, we have determined prehepatic insulin production in six normal men throughout a day that included three typical 750-cal meals. Total insulin secretion for the 24 h was 45.4 ∪, secreted as 10.6 ∪ with breakfast, 13.4 ∪ with lunch, and 13.8 ∪ with dinner. The remaining 7.6 ∪ was secreted during the 9 h night at a rate of 0.85 ∪/h.
This may be why the transition down from 20 units a day to 8 units a day has been a more stressful one (with a couple of “higher” Blood Glucose levels) than any of the previous steps. I am now down into the range my body needs as a baseline.
If my LC-HF diet is keeping me from needing mealtime insulin then the remaining rate of approx .85 U/h would mean approx 20 U/day are needed for the background rate. I am far from a normal man (in so many ways) but I have to imagine that these were people substantially smaller than myself. Maybe 2/3 my weight so my requirements should be proportionately higher. Not a biologist so who knows?
Contributions of gluconeogenesis to glucose production were determined between 14 to 22 hours into a fast in type 2 diabetics (n = 9) and age-weight-matched controls (n = 7); ages, 60.4 ± 2.3 versus 55.6 ± 1.2 years and body mass indices (BMI) 28.6 ± 2.3 versus 26.6 ± 0.8 kg/m2.
The results were interesting.
Thus, gluconeogenesis contributed more to glucose production in the diabetic than control subjects. Production and the contribution of gluconeogenesis declined more in the diabetic subjects during the fast.