Insulin resistance

Why it is important and what you can do about it, Op. 105


This post was largely inspired by a recent manuscript by Chris Gardner.  He’s an outside-the-box thinker and if you haven’t heard of him, check out this YouTube video: The Battle of the Diets: Is Anyone Winning (At Losing?)

Part I.  

Type II diabetes is the clinical manifestation of insulin resistance.  It is preceded by obesity (except in the cases of MONW & NOD), and caused by poor nutrition.  Markers of insulin resistance are: 1) impaired fasting glucose; 2) impaired glucose tolerance; and 3) elevated HbA1c.  THIS is why it is important: in 2009, Barr and colleagues showed a linear relationship between all three of these risk factors and all-cause mortality in the AusDiab study.  All.  Cause.  Mortality.

>10,000 people, 7 years of follow-up.  And this remained true when the data were statistically controlled for age, sex, CVD, smoking, blood pressure, waist-to-hip ratio, etc., etc.  In other words, guns don’t kill people, people high glucose kills people.

From the Funagata Diabetes study (Tominaga et al., 1999):

From a multi-country study by Doehner and colleagues (2005):

Hyperinsulinemia, an early marker of insulin resistance, on all-cause mortality in the Helsinki Policeman Study (Pyorala et al., 2000):

Convinced yet?  Insulin resistance, regardless of how it is measured or expressed, bodes poorly for survival.

Part II.

What can you do about it?  Insulin resistance is universally attenuated by weight loss.  And while some people can lose weight by simply reducing calorie intake, insulin resistant people in particular are most benefitted by carbohydrate restriction…  (unfortunately most overweight/obese people are insulin resistant.)

Exhibit A.  A low-glycemic load diet facilitates greater weight loss in overweight adults with high insulin secretion but not in overweight adults with low insulin secretion in the CALERIE Trial (Pittas et al., 2005)

Pittas took 32 overweight people and divided them up by insulin values 30 minutes after consuming a sugar-sweetened beverage.  In other words, insulin sensitive (“Low INS-30”) or insulin resistant (High INS-30).  Then he randomly put half of the people in each group on either a high glycemic load (“high GL” = high carb) or low glycemic load (“low GL” = low carb), moderately calorie restricted diet (~ 2,000 kcal/d) for 6 months.

Here’s where it gets good.  The insulin sensitive people (Low INS-30) lost slightly more weight on the high GL diet (“HG” in the figure below) compared to the Low GL diet (“LG” in the figure below), although this wasn’t statistically significant (p = 0.31).  But the insulin resistant people (High INS-30) lost significantly more weight on the low GL diet (“LG” in the figure below) relative to the high GL diet (p = 0.047).  Furthermore, insulin resistant people on a low carb diet lost more weight than any other group.

Insulin resistance is carbohydrate intolerance.  It means that more insulin is needed to metabolize carbs.  A side effect of more insulin is increased fat storage.  Lowering insulin by reducing carb intake leads to fat loss.  Food intake was controlled in these studies.

how do you treat lactose intolerance?

The authors prudently concluded [sic]: “Our results require confirmation in further studies …”  I’m here to say their results have received said confirmation.

Exhibit B.  Insulin sensitivity determines the effectiveness of dietary macronutrient composition on weight loss in obese women (Cornier et al., 2005)

Cornier took 21 ovese women and divided them up by fasting insulin values.  Then he randomly put half of the people in each group on either a high carb or low carb, moderately calorie restricted diet (-400 kcal/d) for 4 months.

Look familiar?Insulin sensitive obese women lost more weight on low fat while insulin resistant lost more on low carb.  All food was provided by the researchers; the insulin sensitive people on low carb and the insulin resistant people on high carb lost the expected amount of weight.  But the people with diets specifically tailored to their respective sensitivity to insulin lost significantly more weight.  It’s not about calories (food intake was controlled!), it’s about how your body responds to the nutrients that make up the calories.  Carbohydrate intolerance is more effectively treated by reducing carbohydrate intake than by simply reducing calories.  Calories in don’t equal calories out.  Nutrition matters.

Exhibit C.  (yes, there’s more)  Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial (Ebbeling et al., 2007)

Ebbeling took 73 obese adults and divided them up by insulin values 30 minutes after consuming a sugar-sweetened beverage, similar to Pittas.  Then she randomly put half on a low glycemic-load (low carb) or low-fat (high glycemic-load) non-calorie restricted diet for 18 months. 

I stress “non-calorie restricted” because it’s important; people naturally eat less when they’re being monitored, so we expect weight loss despite this.  The effect of the observer on the observed (Margaret Mead):

N.B.  This is a long study with a lot patients.In contrast to the earlier studies, weight loss was similar in insulin sensitive people on either diet; in other words, the rare, yet seemingly lucky, insulin sensitive obese person can lose weight by cutting calories alone.  But insulin sensitivity is rare in obesity.  Insulin resistant people, on the other hand, lost significantly more weight on the low carb diet… and they kept it off for 18 long months!  The people assigned to low fat were eating slightly fewer calories than those on low carb, but the low carb dieters (at least the insulin resistant ones) lost significantly more weight.

Actually, by the end of the study, the insulin resistant people on a low carb diet lost over twice as much body fat than any other group.  It didn’t matter what diet the insulin sensitive people ate; they are tolerant to a wide range of carbohydrate intakes and thus only require a simple calorie deficit. 


Part III.

In general, and most unfortunately, overweight/obese people are insulin resistant with few exceptions (those who engage in regular high intensity exercise, for example)

I humbly submit Exhibit D.  The point of this is simple: overweight/obese people are insulin resistant and respond better to carbohydrate restriction.  Enter montage music or soundtrack of your choice.  With no further ado,

Brehm et al., 2003


Foster et al., 2003 


Maki et al., 2007


McAuley et al., 2005 


Samaha et al., 2003

Stern et al., 2004 


Yancy et al., 2004  


Gardner et al., 2007 


Shai et al., 2008   


Hussain et al., 2012


calories proper

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  • Guido Vogel

    Hi Bill,

    Gerald Reaven concludes: “y. Finally, and most importantly, not all overweight/obese individuals are insulin-resistant,”

    On which data do you conclude that almost all obese people are insulin-resistant?

    • William Lagakos

      Hi Guido,

      Funny, Reaven was one of my mentor’s mentor… small world :-)

      Obese people who are exercise-tolerant, younger, “fit,” and otherwise healthy tend to be more insulin sensitive… Reaven’s data show that only after these variables are controlled for, the amount of insulin resistance attributable to excess adiposity declines (he mentions this in the paper you linked).

  • Marty Kendall

    Great post. Thanks Bill.

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  • Thomas Hemming Larsen

    I understand the conclusion that lean, active people should generally eat high carb and overweight, sedentary should eat high fat.
    But what is the physiological mechanism/explanation behind this? Just looking at insulin, it seems like there is no benefit excreting it (even as an insulin sensitive person). What am I missing here?

    • Bill Lagakos

      Obese, insulin resistant: does better w/ LC.

      Obese, insulin sensitive: does better w/ LF.

      • Bill Lagakos

        I got dis:

        Subconsciously, no one likes hyperglycemia but everyone likes high carb.

        insulin sensitive = no hyperglycemia, so can enjoy tasty high carb.

        insulin resistant = can’t eat high carb bc enjoyment of diet is cancelled by dislike of hyperglycemia.


        • Thomas Hemming Larsen

          Yes, I get that.

          But why is it that insulin sensitive people can get away with eating so many carbs without getting fat? If you eat far beyond your carb needs, why aren’t the excess converted to fat?
          Can you also make the argument that insulin sensitive are more prone to gain fat by overeating fat?
          I guess this also relates to why some studies show that carb overfeeding is less prone to promote weight gain.

          Sorry for being a pain. I just feel that there is something missing.

  • Thomas Hemming Larsen

    Inspired by this post, I had to try it out myself. I switched my macros so that the majority were carbs. Within a few weeks I lost ~2kg, I’m noticeably leaner (especially my thighs and arms) and I’m stronger. The latter doesn’t say much as I’ve been following the same training program the whole time.
    Moreover, I feel better and have more energy.

    Just wanted to share this n=1.

    • Bill Lagakos


      • Thomas Hemming Larsen

        Indeed. Only problem is that its difficult to eat the volume of food to get in ~300g carbs from tubers, rice, legumes and oats (yes, I’ve started eating legumes and oats – I hope we can still be friends). I’ve also noticed that I can’t eat that much protein, it simply makes me sick.

        • Bill Lagakos

          “I’ve started eating legumes and oats – I hope we can still be friends”

          I fully support this! :-)

          • Thomas Hemming Larsen

            The last point I forgot to mention is that in this period I’ve increased my calories. This makes me believe that I’ve increased my NEAT and been able to train harder – hence the body composition results.

          • Dan Ordoins

            Many of people have built fabulous bodies and performance levels on many ways of eating….. Perhaps its just not all about the macros. Context and stimulus matter…. Also what are the long term effects as well?

          • Bill Lagakos


          • Thomas Hemming Larsen

            Totally agree. There is no magic formula that necessarily works for everyone.

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