A while ago Michael and I were discussing future article topics. There are truly a plethora of avenues to go down in this area of research and there is no lack of things to research and comment on. But even though I have a couple of pretty cool MCT articles sitting around on my desk, I want an interesting topic. I want something new. Something challenging. Besides, everyone is drinking the MCT koolaid these days. It’s become passe. (Also, it upsets my stomach and I have a personal vendetta against it. So there.)
What’s new? There has to be something new!
Michael pointed me to one of his old articles on physiological insulin resistance as an idea. I brushed it off at first. Dismissed it as a quirk.
But then I thought about it. WHY does blood glucose rise in response to a low carb diet? It truly is an interesting question. What does it say about low carb diets if they induce an almost diabetic effect on circulating glucose?
Thus my research began. This short abstract confirmed that it is normal for people on low carb diets to experience a rise in blood glucose levels. Because it’s a non-open journal (shame!), there’s a one-sentence explanation given:
A decrease in first-phase insulin secretion may partially contribute to the short-term LC/HFD-induced increase in postprandial plasma glucose levels.
First phase insulin secretion? There’s a first phase? So… There’s more than one phase to insulin secretion? I had no idea. Call me ignorant but I had no idea until this point that there was more than one phase to insulin secretion.
This article delves deeper into the signaling involved in (what I learned is called) biphasic insulin secretion. The first phase of insulin secretion lasts approximately 10 minutes, and the second phase of insulin secretion picks up after the first and lasts for several hours. This is initiated by the influx of glucose into the beta cells of the pancreas, leading to an eventual depolarization and activation of calcium channels that regulate insulin release.
Type 2 diabetes is associated with a shift from biphasic, to monophasic insulin release, and it is therefore important to establish the cell biology of insulin release kinetics.
O rly? This is where I become instantly hooked… Their experiment involved a particular calcium channel and studying a mouse knockout version of it, which was heavily responsible for the second phase of insulin release. The first and second phases are related, yet separate processes, it turns out.
The conclusion we can now make in low carb dieters: a similar process is happening. People become monophasic in their insulin releasing, like diabetics. Let’s tease out the particulars now…
When sugar is ingested, there are two very important proteins that are released: GIP and GLP-2. These two work in a similar manner, acting on the beta cells to release insulin. I would like to add now that GIP is also released in response to fat intake. We’ll come back to that point.
While infusions of GLP-1 seem to increase the insulin release in diabetics significantly (source), Lewis et al. argue that the rise in GIP levels following glucose is greater in magnitude and appears to be more insulinotropic than GLP-1 (source).
Indeed, it has recently been suggested that the primary physiological role of GLP-1 may be inhibition of upper gastrointestinal motor and digestive functions rather then potentiation of meal-induced insulin secretion.
I will let Ehses and Lewis duel that battle out. At any rate, the article goes on to find that GIP is very important to a rapid beta cell response to glucose, and it increases absorption of glucose in the intestines. Interestingly enough, neither acute nor chronic impairment of GIP seems to alter fasting plasma glucose levels, but in mice with disrupted GLP-1 receptors, they are often accompanied by fasting hyperglycemia. Even the null mutation in the GLP-1 receptor will exhibit high blood glucose levels.
Therefore, while GIP appears to act as an acute insulinotropic hormone in order that β-cells may anticipate the absorption of glucose from the gut, GLP-1 signaling appears to be additionally important for the maintenance of normoglycemia, irrespective of the site of glucose entry into the circulation. This ability to promote glucose disposal makes GLP-1 a candidate therapeutic for the treatment of the abnormal glucose homeostasis associated with diabetes mellitus.
Follow me here for a little bit: If low carb dieters are not intaking glucose (for the very purpose of reducing an insulin response!) and not activating GIP accordingly, possibly not activating a second phase insulin response (depending on the genetic variant), then according to science, the absolute natural reaction of the body would be to have higher blood sugar levels. While diabetics and ketogenic dieters have the same symptom, one is a purposeful manipulation of the chemical signaling in the body, and the other is a distinct disregulation caused by a complicated clusterfuck of issues (diabetes).
So that solves that question! Now to return to GIP, because I stumbled across something truly fascinating here: GIP is released from glucose…but also from fat consumption. Ah hah! Interesting!
In this article (http://ajcn.nutrition.org/content/95/2/506.short) the researchers examine the relationship between genetic variants of the GIP receptor in response to different diets (low carb, low fat, and low/high protein). If you have ever hated someone for their ability to lose weight on a low fat diet, if you have ever wondered why such huge gaps in beliefs and attitudes exist towards low fat and low carb diets, here’s why: different people respond (metabolically) differently to different diets.
Sometimes in papers, the graphs are worth a million words. Essentially if you have a certain allele (also depending on if you’re heterozygote or homozygote), it can dramatically shift weight loss, fasting glucose, fasting insulin, and insulin resistance (HOAM-IR) in response to fat and carbohydrate metabolism.
So in conclusion, having higher blood sugar levels on a low carb diet is a consequence of killing the insulin response, which looks similar to diabetics but is actually far, far different.
Also, there are some people who can eat nothing but oatmeal and potatoes and lose lots of weight, and it’s not their fault that they’re mutants. I’m quite sure there will be many more future studies showing other genotypes that affect fat and carbohydrate metabolism, but we can now all agree there is no one best diet for everyone.
- CaV2.3 calcium channels control second-phase insulin release, Jink, Li et al. The Journal of Clinical Investigation, 2005;115(1):146–154. | doi:10.1172/JCI22518.
- Differential Effects of Acute and Extended Infusions of Glucagon-Like Peptide-1 on First- and Second-Phase Insulin Secretion in Diabetic and Nondiabetic Humans, Quddusi, Vahl et al. Diabetes Care March 2003 vol. 26 no. 3 791-798 | doi: 10.2337/diacare.26.3.791
- Glucose-Dependent Insulinotropic Polypeptide Confers Early Phase Insulin Release to Oral Glucose in Rats: Demonstration by a Receptor Antagonist, Lewis, Dayananden et al. Endocrinology October 1, 2000 vol. 141 no. 10 3710-3716 | doi: 10.1210/en.141.10.3710
- Physiological Insulin Resistance, O’Neill. Ketopia, December 17, 2012.
- Short-term low carbohydrate/high-fat diet intake increases postprandial plasma glucose and glucagon-like peptide-1 levels during an oral glucose tolerance test in healthy men, Numao, Kumano et al. European Journal of Clinical Nutrition 66, 926-931 (August 2012) | doi:10.1038/ejcn.2012.58
- Weight-loss diets modify glucose-dependent insulinotropic polypeptide receptor rs2287019 genotype effects on changes in body weight, fasting glucose, and insulin resistance: the Preventing Overweight Using Novel Dietary Strategies trial, Qi, Bray et al. American Journal of Clinincial Nutrition, February 2012 vol. 95 no. 2 506-513