Saturday, February 2, 2013

The Nutrition Debate #86: Beta Cell Function and Insulin Sensitivity

 I recently visited (as a new patient) an endocrinologist in Florida. My purpose was to find out what was going on with my glucose metabolism. Specifically, I was interested in knowing my % Beta cell function and my % Insulin Sensitivity (and its reciprocal, Insulin Resistance, or IR). I had read about a test that determines those values and wanted to be tested. The HOMA Assessment determines these values by formula. There is also a more sophisticated model that Oxford University developed called the HOMA2 that employs a “calculator.”

I haven’t been seen by an endo in more than 20 years (the last time to measure my testosterone, as I recall). Five years before that I consulted an old-timer who had me visit the out-patient department of a local hospital for a 4-hour glucose tolerance test. That test just confirmed the diagnosis that had been made a few years earlier that I was a Type 2 diabetic. That endo also upped my prescription for a sulfonylurea, the only oral diabetes med permitted in the U.S. at the time. Eventually I was maxed out at 20mg of glyburide (the sulfonylurea).

It would be another 10 years (in 1995) before my current doctor added metformin, which by then was finally allowed in the U. S. It had been in use in Europe for some time. But before long I was maxed out on that drug too and was then started on a TZD (Avandia). That is when my doctor suggested I try the Atkins Induction diet to lose weight. He had just read the Gary Taubes cover story, “What If is All Been a Big Fat Lie?” in the NYT Magazine on July 7, 2002. Within a few days on Atkins Induction, I was having frequent hypos. I called my doctor, and he told me to drop the Avandia. When the hypos continued, he cut the sulfonylurea and the metformin dosages in half, and then soon afterwards, in half again.

I lost 60 pounds on Atkins Induction but, after a few years of stable weight, I gained back 12. I then decided to try the Bernstein diet for diabetics. I lost 100 pounds in the next 50 weeks and eventually another 22 for a total loss of 170 pounds. Along the way, I weaned myself off the final 5mg of Micronase (the brand-name of the sulfonylurea), by halving it to 2½ and then halving it again (cutting the 2½ mg pill in half). I still take 500mg metformin once a day. But, all told, I figured I had been on a sulfonylurea, which pushes the pancreas to secrete more insulin in response to a glucose challenge, for the better part of 20 years. Remembering Dr. Ralph DeFronzo’s Banting Lecture at the 2008 ADA Convention in San Francisco, I figured I had lost 80% of my Beta cell function by the time I was diagnosed in 1986. He also said, at the end of the introduction to the full paper published in the ADA magazine “Diabetes,” and available here, “Sulfonylureas are not recommended because, after an initial improvement in glycemic control, they are associated with a progressive rise in A1C and progressive loss of β-cell function” (emphasis added).

Given my history on sulfonylureas and Dr. DeFronzo’s prognostications, the implications for my Beta cell function were not promising. So, my visit to the endo in Florida was for the specific purpose of testing my % Beta cell function and % (Insulin) Sensitivity. I was surprised with the test results: Beta Cell function = 68.2%; Sensitivity = 94.6%; and IR = 1.1 (1.057). I don’t have a follow-up visit scheduled with the endo for another 10 weeks, so I decided to do a little homework on my own. I would also like to put these results “out there” for comment by others. Has anyone out there ever had a HOMA assessment done? The endo’s nurse said she had been working with this doctor for about 10 years, and he had never ordered the test before. She knew, she said, because she’s the one who places the orders for tests.

The doctor said the test was mostly used in research, and he would have to look up the formula to apply it. Okay, but, I wondered, if not commonly used in clinical practice, does the test have clinical value? What can be learned from it? My first read is that I am not in as bad a shape as I thought I was. True, I have been eating VLC “on and off” for over 10 years, and now “totally on” for the last four and a half months. My last HbA1C was 5.7, down from recent low 6s. I expect the one from blood taken last week will be 5.6 or even 5.5. And I have been eating a very restricted ketogenic diet, recently under 1000 calories a day (without hunger), which is the direct consequence of being ketoadapted and in ketosis virtually all the time. My body is in balance and happy with my dietary intake, my supplements, and with the fatty acids, glycerol and ketone bodies it is making every day from the body fat it is breaking down for energy.

But I have not been satisfied with my fasting blood glucose readings these last 4 months. I no longer have weekly averages around 90. I have to work hard to get them under 100, and they should never be higher than 95. My daily FBG readings should never be above 100. I am very careful to eat VLC and to never eat too much protein.

So, what does my HOMA assessment test reveal? If my Type 2 diabetes is in “clinical remission,” is it attributable solely to my VLC diet? If my diet has “reversed” my Type 2 diabetes, has it also “normalized” my Beta Cell function and improved my insulin sensitivity? If Beta Cells can regenerate themselves, can they do this over and over, year after year?

I hope to learn the answers to these questions from my new endo in my follow-up appointment. I can hardly wait.
© Dan Brown 2/2/13


  1. Thank you for this. I have a quite similar history and have been wondering what's going on with my body. My A1Cs are always under 5.4, but my fasting blood glucose, which used to be between 85 and 90, is consistently between 95 and 105 now. My doctor gave me metformin, 1000 mgs at night. When I take 1000 mg, my blood sugar is higher in the morning. When I take 500 mg it is lower, though not where I want it. I've been on a very strict low carb diet that's below 1200 calories a day, trying to lose weight. (I was at 167 at one point and have gained to 195 in 2 years, even on low carb and low calorie.) I am beginning to wonder if my liver isn't sensing a lack of glucose and is trying to make up for it. I have no access to testing through my doctor at Kaiser because my A1Cs are "too low" for them to allow me to see an endocrinologist. I wonder if I can arrange and pay for my own testing. It is encouraging to me that my pancreas may not be failing, and that I may have improved my insulin sensitivity, that isn't something I would ever have suspected to happen. I'll be interested to see what your endo comes up with...or more likely, what YOU come up with in your own studies.

    1. Thanks for commenting, Jan. Most people don't know much about their glucose metabolism, and most doctors don't either; and if they do (and I sincerely believe that is a BIG IF), they can't be bothered to share it or delve into any interesting aspect of it BECAUSE OF THE INSURANCE SYSTEM, not only Kaiser but also Medicare and the supplementals since the supplementals will only pay the balance of what Medicare covers. Therefore, if Medicare won't cover it, you are on your own.

      Yes, you can have a lot of testing done yourself. I don't know about this one, but all you have to do is Google it, and the offers (with prices) will appear.

      Most people don't care enough to track postprandials over long periods, and everyone's function and response is different, as is the content of foods, both quantifies and component macronutrients. So, its difficult to do comparisons in a non-research setting where there are no real controls.

      One thing I have noticed from discussions on the Bernstein Forum, where many people are well-informed and serious about these issues, is that there are unexplained excursions in bs that could be attributable to many things. One of the things that was recently suggested is that most all of us T2s have lost our first stage response and so our pancreas gets "surprised" by the need when glucose is sensed in the digestion/absorption process and overcompensates.

      Another factor I am just getting interested in is the fasting insulin level. This is not a "standard test" done in periodic doctor's visits, but an endo could do it. It is necessary for the HOMA test, apparently, as my new endo told his nurse he would need it and she ordered it. Mine was 7.8 with a range of 3.0-25.0 mU/L. Two others on the Forum recently said theirs was 4.0. I do not know yet what this portends, but I will be investigating.

      The most vexing thing for me (besides the creep up of my FBG) is how when it goes up it doesn't come down more than a few points a day for many days. Why does it hang up there for days when I am eating <15g of carbs a day and no more than 65 or 75g of protein.

      Yes, I think your liver is sensing the need for glucose and making it (gluconeogenesis). It can make is from protein, as we all know, but I think from fat as well. The formula for ketogenesis allows 10% of every triglyceride to be converted to glucose. When a triglyceride is broken down, whether dietary or stored belly fat), it becomes 3 molecules of free fatty acids and 1 molecule of glycerol (plus ketone bodies as byproducts). Two glycerol molecules get together to form a glucose molecule. I read somewhere recently that a 1,200 calorie diet that is 65% fat will make over 100g of glucose from the fat alone. This is of course necessary for red blood cells (that have no mitochondria), certain cells in the eye, and of course the brain. But I think the brain prefers ketone bodies, if it can get it.