In an interesting paper the question is asked what if the history of the development of our understanding of diabetes has it wrong? The paper (J. Denis McGarry. What If Minkowski Had Been Ageusic? An Alternative Angle on Diabetes. Science, Vol. 258, No. 5083 (Oct. 30, 1992), pp. 766-770).
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.
Here are my blood glucose numbers over the past three months. I have been fasting the last week so the number are lower during the fast. This is an average of 113, and a HbA1c of 5.7. The normal range for level for hemoglobin A1c is less than 6%. Note that I am still taking Metformin. I am also doing High Carb, Healthy Fats plus Intermittent Fasting.
I started a new fast on Sunday so I am at day 4 now. So far it is going very well. Not very hungry and not too grouchy (that I can tell). I’ve dropped off half the weight I regained over the four days of eating.
Stopped taking Metformin on the third day of this fast. My blood sugar numbers are up a bit but still on the low end. By dinner time last night my Blood Sugar was 88.
Considering starting up some exercise. Not for weight loss, it might in fact hinder some weight loss. More to work on my Blood Pressure. I have had a nice mountain bike since 2007 but I rarely ever ride the bike. So I bought a trainer which is attaches to the rear tire and turns the bike into a stationary bike.
One of my Keto/fasting heros, Tom, uses an ap called Kinomap. It lets you ride in different places in the world where people have recorded videos of their rides.
I pulled the bike out of the basement, cleaned it off and pumped up the tires. Hopefully I will be in riding shape by Spring. There’s a great bike trail very near to here,
I’ve noticed that every so often I get a blood sugar reading in the 120’s. Nothing to be alarmed about but when you’ve gotten used to being in the 90’s mostly it seems out of place. I’ve also started to wash my hands and retest after the number. I’ve noticed that the second reading is quite a bit lower.
For instance, when I woke up at 6:41 I tested and got 122. I then got up washed my hands and retested at 6:52 and my number was 109. Two hours later my number is 93. The 93 may be partly attributable to the Metformin I took when I got up.
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.
I am now at my 1992 weight. I remember the weight very well since I had started a new job with a very tight deadline. It meant I worked 60 hours a week for the first six weeks of the job. The company brought in pizza for us every night and I gained weight. When I got around to weighing myself that meant I was up. That’s the number that I remember. The good news is that I am at that weight now. Not too bad to be at the same weight I was at 24 years ago.
Wish I had weighed myself at the start of this. I am down more than 20 lbs so far for sure.
Didn’t take Metformin yesterday. My waking Blood Sugar was 101 which is a bit higher than yesterday. I am going to try this out for a couple of days to see if there’s a change.
Still doing LCHF+IF (of course).
I’ve been off Insulin for a full week now.
So why am I still alive? After all, I needed 100 units a day on the average just one month ago. But here I am. Still Alive!
So did I just decide to ignore my Blood Glucose levels and am I on the edge of dying? Hardly. I’m still checking multiple times a day – mostly now in disbelief at how well my blood sugar is being regulated by my body. My high today was 124 and my low so far today is 109. I never got numbers like that before day after day on Insulin.
For dinner last night I took the kids out to Five Guys Burgers and Fries. I skipped the fries. I ate a bunch of peanuts and more importantly had my burger “bunless”. The choice to replace the bun with lettuce was a good one since it took away about 40 grams of carbs and left about 1 gram. The fat ratio was good and the jalapenos, etc didn’t add much to the carb count but they did add to the flavor.
All of that made my Blood Sugar at 103 around bedtime.
Addendum : Still taking Metformin. Not out of the T2D woods yet.
I shut off my Insulin Pump 36 hours ago.
My Blood Glucose numbers have been great.
This will be my last Insulin dosage chart since I am no longer on Insulin. I am still on Metformin.
I will probably post numbers like these:
7 day average – 123
14 day average – 124
30 day average – 137
The LC-HF plus IF dieting has been going great. Easy to do. I don’t get hungry until after 2 PM which is when my blood sugar goes down to around 104 or so.
Noticed this morning that my body was out of ketosis. My detection method is the metallic taste in my mouth when I am in ketosis. Now, 2 hours later I am back in Ketosis. My pump delivers .5 U/hr between 4 AM and 12 PM. The rest of the time I am pumping .25 U/hr.
I am not adding any bolus today so that I can try to understand the effects. I took a Metformin 850 mg when I got up so part of the following effect may be from the Metformin. Numbers were up early on but I am watching the numbers over the day.
- 7:20 – 130
- 8:20 – 154
- 9:20 – 130
- 10:20 – 116
- 11:20 – 118
- 12:30 – 127 (physically active – working in the kitchen)
- 1:20 – 118
- 2:20 – 108
- 3:20 – 111
- 5:40 – 113
I have gotten pretty much the same response when I used Insulin so why use Insulin?
Here’s the full text of this next piece of advice (Avoid weight gain while taking insulin) from the Mayo Clinic website.
Ask your doctor about other diabetes medications. Some diabetes medications that help regulate blood glucose levels — including metformin (Fortamet, Glucophage, others), exenatide (Byetta), liraglutide (Victoza) and pramlintide (Symlin) — may promote weight loss and enable you to reduce your insulin dosage. Ask your doctor if these or other medications would be appropriate as part of your diabetes treatment plan.
I like the goal – reducing Insulin dosage. When I started Insulin my doctor wanted to take me off Metaglip. Only part of that made sense. The Glipizide part of Metaglip is a Sulfonylurea which stimulates the release of more insulin from the pancreas. But we’ve already determined that too much insulin is the problem. Sulfonylurea drugs also decrease insulin resistance which they would pretty much have to do in order to help the extra insulin work.
The diabetic care nurse knew more about the drug than the doctor did. I was able to convince the doctor to prescribe Metformin which the doctor was convinced could not help since my pancreas (he said) no longer produces insulin. He clearly had the meds mixed up. But he has told me since then that as long as it is working for me (and it is) that he will keep prescribing it.
I was on Byetta (Exenatide) which was getting decent results when the diabetic nurse recommended I go to the “gold standard” of care which is insulin with the pump. The mechanism of Byetta is (wikipedia source).
- Exenatide augments pancreas response…
- Exenatide also suppresses pancreatic release of glucagon in response to eating…
- Exenatide helps slow down gastric emptying…
- Exenatide has a subtle yet prolonged effect to reduce appetite…
- Exenatide reduces liver fat content…
Byetta has some side effects that bother people enough to get them to stop taking it. It’s a shot, like Insulin, so there’s that inconvenience.
I have no experience with the other classes of drugs but if the drug’s net effect is to increase the level of insulin in your blood then it’s bad. Good that it is reducing your blood sugar. Bad that the insulin is what does the damage.
From what I can tell, Metformin is one of the best and it only gets you half way to normal. So yes, ask your doctor about these drugs but focus on the question of whether or not the drug increases the insulin level in your blood. If so, be skeptical.