Where Does Type 2 Come From?

Last Friday, I went to a seminar on a new kind of surgery for weight loss. The talk was held at the Center for Obesity Assessment, Study, and Treatment (COAST) at the University of California, San Francisco. At the end of the seminar, Robert Lustig, MD, said, “This surgery [vagotomy, or cutting the vagus nerve] won’t work for the kind of overweight that contributes to Type 2 diabetes. This is for the other kind of obesity.”


Kinds of obesity? Causing Type 2? So I started wondering, what does cause Type 2? We know that insulin resistance plays a role in Type 2 diabetes. But what causes insulin resistance (IR)? Is it a germ, an autoimmune response, the body’s response to fat, or what? For three days, I got lost in the wilds of biochemistry, only to realize with a shock that I knew the answer already. Here’s what I found.

Types of Insulin Resistance
There are several types of IR. All of them involve cells refusing to open up for the glucose that insulin is transporting. Many different proteins are involved in helping insulin transport glucose into cells. Problems with any of them can cause resistance.

Several of these proteins and hormones are mentioned in this study from Japan. Other scientists report that the resistance that happens in muscles is different from what happens in an insulin-resistant liver. At the cellular level, IR sounds very complicated.

But how do cells become insulin-resistant? Some IR is inherited. Scientists at Yale found changes in the mitochondria of insulin-resistant children. Mitochondria are our cells’ “power plants.” They are where the glucose gets used for energy. The insulin resistance in these children is a kind of genetic insulin resistance.

Diet can also contribute to IR, sometimes in surprising ways. Salt intake may increase IR, as indicated by this Tokyo study. The same study cited evidence that high blood pressure (hypertension) promotes IR. The insulin resistance connection may be why hypertension often predicts future Type 2.

But the belief in medical circles now says that fat in the cells causes the most IR. A widely-cited article entitled “Etiology [Cause] of insulin resistance” by two Yale scientists claims strong evidence that “insulin resistance is a result of accumulation of intracellular lipid metabolites [fatty acids]… in skeletal muscle and [liver cells].” This explanation seems to be gaining wider acceptance as the general panic over obesity spreads, and it seems to be true in some cases. Confused? Well that’s not all. Inflammation and “oxidative stress” have also been blamed for IR in many studies. And inflammation and oxidation each have several different molecular pathways.

What’s the Real Cause, Then?
But actually, when you look at all the dizzying research on IR at the cellular level, none of it is that impressive. Scientists are certainly gaining more biochemical knowledge, but what does it have to do with what is really making people sick? I was getting more and more confused.

After two days looking at molecular chemistry, I found this study from Boston University. Called “Physical Inactivity Rapidly Induces Insulin Resistance and Microvascular Dysfunction in Healthy Volunteers,” it reports on 20 healthy young people who were restricted to bed rest for 5 days. The article states that, “Bed rest led to a 67% increase in the insulin response” — that’s right, 67% in five days — “to glucose loading, suggesting increased insulin resistance, and produced increases in total cholesterol and triglycerides.” The authors also found that arteries became tighter and systolic blood pressure (the top number, representing the pressure when the heart contracts) increased with bed rest.

In my book, Diabetes: Sugar-Coated Crisis, I wrote that insulin resistance is sometimes just a fancy word for physical inactivity. Glucose is fuel. If your muscles aren’t using the fuel, of course they won’t want any more. It’s like trying to pump gas into your car when the tank is already full. The gas spills all over the place. Before you can pump more gas, you have to drive the car.

But physical inactivity isn’t the only cause with striking supporting evidence. There is also stress. A 2006 study from The Cleveland Clinic found that “Hostility and stress [predict] insulin resistance.” “Hostility” was measured on a psychological scale including cynicism, hostile attitudes, and aggressive behaviors. “Stress” was measured by the amount of stress hormones found in the urine.

Lead author Jiangping Zhang, MD, said that “people with higher hostility don’t always have worse insulin resistance, but they do when they are under stress, especially high levels of chronic stress.” But even without “hostility,” stress has been linked to IR in dozens of studies.

Somehow I got so lost in the biochemistry that I forgot what was really important for most people with Type 2 or prediabetesstress reduction and physical activity. But that is the same path to nowhere that our entire medical system has been on for decades. They hunt down the molecular targets so they can develop new drugs. But there are so many proteins and hormones involved in insulin function that we could never cover them all. The important things are to relax and to move our bodies when we can.

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7 thoughts on “Where Does Type 2 Come From?

  1. Dear David.

    Insulin resistance appears to have a multitude of causes and We cannot expect a quick cure in our lifetimes. Without G.B. we might of had techniques to regenerate our pancreases and not depend on injected insulin. My present obesity is mainly due to the necessity to eat more than I would like to correct lows or impending lows but also due to a much reduced level of activity compared to 10 years ago. a high degree of insulin resistance combined with external insulin makes weight loss difficult, I was going to try cutting the insulin dose a lot. Did any papers or people address this issue? Heredity may also have a lot to do as my father-in-law does not move if he can avoid it and is a super healthy 85 year old.

  2. Inside those tiny mitochondria where that complex energy production goes on,the biochemical pathway or the “all important cycle” which makes use of carbohydrates (be it simple or complex sugars) what is it called? the Krebs Cycle?
    Anyway – at just about every step along the way
    in that cycle, is the NEED for oxygen. Such a simple thing – oxygen. Now – you take a good long look at the patient suffering from obstructive sleep apnea. On & off, perhaps hundreds of times every night this individual stops breathing for
    varying lengths of time until their body does
    eventually sound that warning bell telling their body that the oxygen levels have dropped so very drastically that if it keeps up,they’ll die.
    Not ONLY does this explain our patient’s tough and inexplicable inability to lose weight; no matter how hard they try…I’ve starved myself into a state of pure malnutrition while weighing in at 205lbs.
    But at the SAME TIME – we can see how insulin resistance is building & building. And how that
    little glucose molecule simply CANNOT BE USED NOR UTILIZED RIGHTLY – NOT WITHOUT OXYGEN present. Meanwhile this disorder destroys the normal sleep pattern of our patient, so our patient tries to sleep more & longer hours just TRYING to get any rest, meanwhile they’re unwittingly making every aspect of their condition TEN TIMES WORSE by
    increasing the # of hours they’re sleeping-trying desperately to get enough rest that the daytime hypersomnolence doesn’t completely disrupt their entire life!! I have heard and firmly believe that EVERY SINGLE TYPE II DIABETIC OUGHT TO BE
    TESTED FOR OBSTRUCTIVE SLEEP APNEA. The damage done to a human body deprived of such an essential ingredient as oxygen can’t even begin
    to be measured.

  3. David,

    Yes, of course, inactivity is a major cause of insulin resistance. And yes, of course, genetics, and some foods, and high stress in the form of hostility or fear or anger of other illness can contribute to insulin resistance. But even though that is already a complex picture, I am convinced that reality is much more complex than that.

    My observation of myself indicates that it’s likely that insulin resistance is also a major cause of inactivity and appetite disregulation. I noticed that when my own insulin resistance began, I felt I had much less energy, so I exercised less; and I was hungrier. This makes sens when you consider that my cells probably were not getting the fuel they needed when they needed it. So insulin resistance — inactivity — lack of exercise is really a never-ending cycle where the causes move in all directions making it all worse unless something interrupts the process.

    I am also quite convinced that there are environmental pollutants that cause insulin resistance. We know there is more type 2 diabetes in areas with high air pollution. And we know agent orange caused insulin resistance. What other agricultural chemicals currently in use do the same?

  4. These are several great comments, and I’m sure there is a lot of truth in all of them. I totally agree about the sleep apnea and the environmental chemicals. I hadn’t thought about insulin resistance causing inactivity, but it makes sense.

    Perhaps it’s my prejudice, but I still think that stress is a greatly underestimated cause of diabetes. See this week’s blog for more.

  5. David:
    All my life I have wondered about a problem in my youth that I seemed to always encounter even though I was in peak physical condition. For many years of my youth, I loved being active. I played many different sports in junior high, high school and in college, as well as just the usual fun stuff like skiing, tennis, jogging, biking, handball, raquetball, etc. I am now older (52) and seriously overweight (5-10 and 260 lbs) and seriously sedentary, with Type II and quite a number of complicating factors including about 30 years worth of slowly progressing degenerative disk and joint disease, pain, surgical hypothyroidism, sleep apnea, heart valve issues, and so on.
    The problem I first alluded to above was that whenever I did weighlifting, as part of an athletic training regimen, at anything other than a fairly leisurely pace, I would often be overcome with nausea, strong enough to cause me to quit and go sit or lie down. Your comments about “cells refusing to open up for the glucose that insulin is transporting” and “[o]ther scientists report that the resistance that happens in muscles is different…” have made a light go on now. Back then, within a year after I left school for the workforce, with a commensurate decline in physical activity, I started to notice that I couldn’t even eat a bowl of Wheaties and milk in the morning — by itself, nothing else eaten — without suffering a blood sugar plunge within a couple hours, followed by the shakes. Even so, for over 20 years I was still healthy enough to pass the Navy’s semi-annual physical fitness tests. And though I regularly complained to my doctors about the blood sugar plunge, the simple glucose tolerance tests administered were never sufficient to point to any kind of clinical problem, let alone a diagnosis.
    There is a lot more to this story, but I think I’ll stop here. I don’t exactly know what that light that I said went on for me will be illuminating. But thank you for a few more bits of light and info in a life-long journey of discovery. I still hold out hope for a return someday to my “old” activity-loving self.

  6. Hi Jon,

    It sounds like you are going through a tough time. Your story about the nausea makes me wonder if you might have a gluten intolerance or some other digestive problem. As I mentioned in my blog on new food discoveries, gluten intolerance has been linked to Type 1 diabetes — maybe you have a bit of that process going on. Might not hurt to check.

  7. im currently on this type of thing in my grade 11 biology class. I never understand anything but i like how you explain it 🙂 thank you i totally understand it way better now

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