Protein and Gluconeogenesis

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.

Here’s a different article (Effect of long-term dietary protein intake on glucose metabolism in humans).

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.

How Much Protein?

Dr Fung has a great article on how much protein a person needs. The recommended amount was determined in a rather distorted manner.

In 1985, the WHO reviewed studies of daily obligatory losses of nitrogen, and found that an average is 0.61 g/kg/day (total). Presumable, the diet should replace (roughly) this 0.61 g/kg/day being lost. In order to make sure everybody was covered, the WHO added 25% (2 standard deviations) above the mean to get 0.75 g/kg/day which sometimes gets rounded up to 0.8 g/kg/day. For a standard 70-kg male this is 52.5 g/day. Remember this is for absolutely healthy adults, not gaining or losing weight and the amount needed to cover the average amino acid losses are only 42 g/day (0.6g/kg/day). Remember, that if you want to lose weight, you should be eating less protein so that you can break some down.

Considering that protein leads to gluconeogenesis in diabetics then excess protein is a bad thing. The Ketocalculator said that I need 100 grams of protein a day. Rerunning my numbers on the Ketocalculator:

  • 1301 kcal Goal, a 40% deficit. (546 min, 2169 max)
  • 25g Carbohydrates
  • 44g Protein (97g min, 160g max)
  • 114g Fat (30g min, 210g max)

 

Daily Status – 2016-08-29

Today is the third day I have been off Metformin. My Blood Glucose numbers have tended up but not horribly. About 10 increase. I am no longer seeing numbers from 95-115 and am now seeing numbers from 105-125 instead. Not too bad really. If the upward trend continues I will add back in Metformin. If it flattens out I will stick with removing Metformin. If Metformin reduces gluconeogensis by 33%, I really don’t see it in my own numbers. I should be seeing numbers that are 33% higher not 10% higher.

Work scale shows I am down 23 lbs since Aug 5th. I started about July 31 (four weeks now). Not sure what my initial weight was but my guess is that I am down about 30 lbs so far.

I am going out for dinner with the kiddos tonight so it will be out to somewhere that I can do LCHF easily. We have done Jimmy John’s (order the lettuce wrap and the JJ Gargantuan) as well as Five Guys Burgers and Fries (skip the fries and order the burger “bunless”). Harder to find suitable choices at places like Applebee’s.

Still doing the Intermittent Fasting (IF). Yesterday I ate from 5 PM to 6:30 PM with a final snack at 8:30 PM of some ParmCrisps.

 

Keto Calculator – Macronutrients

How many macronutrients do you need to do LCHF? There’s an on-line Keto Calculator.

KetoCalc

It projects your rate of weight loss based on the values you selected. You can even download this data as a CSV (EXCEL) file.

Here’s my daily macronutrient goals (yours will vary):

KetoCalc-Numbers

I have been shooting for a higher percentage from fat due to my Diabetes. I am too good at converting protein into glucose.

 

Fat Adapted Athletes

Here’s a great study on fat adapted athletes (Enhanced endurance in trained cyclists during moderate intensity exercise following 2 weeks adaptation to a high fat diet).

The study looked at five cyclists and compared them on a High Carb vs a High Fat diet.

Despite a lower muscle glycogen content at the onset of MIE [32 (SEM 7) vs 73 (SEM 6) mmol · kg −1 wet mass, HIGH-FAT vs HIGH-CHO, P < 0.01], exercise time to exhaustion during subsequent MIE was significantly longer after the HIGH-FAT diet [79.7 (SEM 7.6) vs 42.5 (SEM 6.8) min, HIGH-FAT vs HIGH-CHO, P<0.01]

Looks like they have an almost 2x advantage when it comes to endurance.

How long did it take to convert these athletes from Carb Adapted to Fat Adapted?

These results would suggest that 2 weeks of adaptation to a high-fat diet would result in an enhanced resistance to fatigue and a significant sparing of endogenous carbohydrate during low to moderate intensity exercise in a relatively glycogen-depleted state and unimpaired performance during high intensity exercise.

Only two weeks!

How much Insulin Does the Pancreas Produce?

According to (“Normal” Insulin Secretion: The Goal of Artificial Insulin Delivery Systems?).

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?

An interesting additional factor is the question of gluconeogenesis during fasting. There was a study done on this as well (Quantitative contributions of gluconeogenesis to glucose production during fasting in type 2 diabetes mellitus).

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.

 

Mayo Advice #5 – Don’t Stop the Insulin

Here’s where they are totally right and totally wrong at the same time. From the Mayo Clinic site (Avoid weight gain while taking insulin).

Take your insulin only as directed. Don’t skip or reduce your insulin dosages to ward off weight gain. Although you might shed pounds if you take less insulin than prescribed, the risks are serious. Without enough insulin, your blood sugar level will rise — and so will your risk of diabetes complications.

I get what they are saying. If you need insulin to regulate your blood sugar and you go off it then you’ve got serious problems up to death. The thing a diabetic should be watching isn’t the amount you were prescribed. It should be the amount needed to regulate your blood sugar. No more.

My doctor started me out by telling me that I needed to take 40 units of long-lasting insulin. When that led to a high HbA1C number he said that I needed to add meal-time insulin. I wish they would not call it that. So many false things there. He told me to use the 2nd Insulin and use 8 units before every meal. The diabetic nurse told me that was wrong and she had him fix the prescription.

They got me nutritional training and told me to count carbs. Not count as in limit, but to bolus for the amount of grams of carbs in what I was eating. Good advice for high carb meals. Not great when you consider gluconeogenesis. That all got me to a decent point of glucose control but was about 60 units a day (40 of basal and 20 of “meal-time” (fast acting) Insulin. In the last 5 years I have progressed to around 100 units a day (varies by my carb intake). It’s only now that I am getting lower than when I was diagnosed.

I am using less by doing LCHF (really mostly LC) and Intermittent Fasting (IF). Yesterday I used a total of 47 units of Insulin. I will lower my basal (constant) Insulin rate tomorrow to drive my Insulin levels even lower.

 

What I wish I knew about Metformin back then

From Wikipedia, here’s why Metformin is a good drug for dealing with Insulin Resistance and, for me, worked well for years.

Gluconeogenesis is also a target of therapy for type 2 diabetes, such as the antidiabetic drug, metformin, which inhibits glucose formation and stimulates glucose uptake by cells.

The phrase “stimulates glucose uptake by cells” is equivalent to “helps lower insulin resistance”. From this NIH paper (2000), you can see why Metformin works and how it doesn’t quite work well enough in a diabetic person.

The rate of glucose production was twice as high in the diabetic subjects as in control subjects (0.70 ± 0.05 vs. 0.36 ± 0.03 mmol · m−2 · min−1, P < 0.0001). Metformin reduced that rate by 24% (to 0.53 ± 0.03 mmol · m−2 · min−1, P = 0.0009) and fasting plasma glucose concentration by 30% (to 10.8 ± 0.9 mmol/l, P = 0.0002).

So diabetics produced 2x the insulin of non-diabetics (100%) but Metformin only reduced that rate by 24%. Better than nothing but not nearly enough to make the diabetic person “normal”. And insulin resistance is a progressive disease by which the cells get better and better at not unlocking for insulin.

Going on in the paper.

The rate of gluconeogenesis was three times higher in the diabetic subjects than in the control subjects (0.59 ± 0.03 vs. 0.18 ± 0.03 mmol · m−2 · min−1) and metformin reduced that rate by 36% (to 0.38 ± 0.03 mmol · m−2 · min−1, P = 0.01). By the 2H2O method, there was a twofold increase in rates of gluconeogenesis in diabetic subjects (0.42 ± 0.04 mmol · m−2 · min−1), which decreased by 33% after metformin treatment (0.28 ± 0.03 mmol · m−2 · min−1, P = 0.0002).

It keeps getting better. A diabetic person is 3x better at gluconeogenesis but Metformin ws only able to reduce that so that the diabetic person was at 2x the normal person.

And note, Metformin is about as good as it gets in that category of drug. Looks like it can help, but not solve the issues with gluconeogenesis. Something is better than nothing but don’t get lulled (like I was) into assuming all is well. If we keep filling up those protein stores than the same problem which happened to us with carbs will also happen to us with proteins.

 

LCHF Personal Observations

I like the Low Carb High Fat diet. The 18 months I spent on it nearly 20 years ago probably put off my becoming a diabetic by several years. I was at a good weight while on the diet – down from 260 lbs to 225 lbs. The only thing that got me to stop was the feeling that my heart wasn’t doing well on the diet. I had no numbers to back up that opinion. Just felt like I was having some arrhythmia on the diet. And that was after a long time on the diet.

When I did it a couple of years ago I had good results. HbA1C numbers were great (6.4). Triglycerides and other blood numbers were excellent. Doctor was amazed. I was one of the few patients he had who was doing well. However, the diet wasn’t a cure but needs to be kept as a permanent way of life. When I went off the diet the weight came back on quickly and with a vengeance.

Problem is that LCHF only works so well for me now and I think I understand why – at least partly. It has to do with the way the body converts protein to glucose in a process called Gluconeogenesis.

The body doesn’t do nearly as good of a job of converting protein to glucose as it does of converting carbs to glucose. It does it much slower. So if I eat a dozen chicken wings at night my morning blood sugar is up from if I eat nothing or something with carbs instead. The glucose from carbs was gone hours before. Meat was still digesting and being turned into glucose hours later. The problem for me with a LCHF diet over time is that my body got really, really good at Gluconeogenesis.

Wikipedia describes the process as:

In vertebrates, gluconeogenesis takes place mainly in the liver and, to a lesser extent, in the cortex of the kidneys

To put it in personal terms, my liver is really good at converting protein from food into glucose. It would much rather take it from what I eat than take it from me. And LCHF puts no restrictions on when you should eat so for me this means I can no longer get a good blood sugar level from eating LCHF. I can get a better blood sugar but I can’t lose much weight and I am stuck with that demanding diet for the rest of my life. I already feel defeated since I’ve done this before and was only able to do it for 18 months.

I don’t feel this reduced my insulin resistance much either. Sure it must have helped some since the body doesn’t convert protein to glucose as quickly but the other edge of that sword was the longer hours that the glucose was in my bloodstream.

So far I have dodged many of the more severe issues related to T2D. I got a nerve conduction test which indicated very mild neuropathy but my eyes and kidneys have been doing well.

What I have been searching for is something to reset my body’s insulin resistance. Metformin is the oral med which helps me with that but doesn’t work well enough to keep my blood sugar regulated on its own.

I am sure someone will tell me that I didn’t eat enough fats and ate too much protein and that is why I have failed to achieve healing with LCHF. I am sure that’s true.