Insulin Resistance and the Liver

Few middle-aged men realize that it is very likely their liver is under assault. NAFLD (non-alcoholic fatty liver disease) affects a huge percentage of the population over 40 and can lead, literally, to a "hardened liver". No, that's not a good thing.

This is something that every male over 40 (and some under) needs to watch carefully.  One study of 503 consecutive car accident fatalities - pretty morbid, eh? - found that 24 percent of all victims had fatty liver disease and 40 percent that were over the age of 60. [1] And don't forget that men have a much higher prevalence than women, so "epidemic" is no exagerration: it is very likely that a third of the men reading this site have non-alcoholic fatty liver disease of one stage or another (and many do not even know it yet). Somewhat similar results were found in a study of Japanese adults and the National Liver Foundation estimates about a quarter of the U.S. has NAFLD. [2][3]

What makes NAFLD particularly worrisome is the fact that it exists for months or even years with no real symptoms or issues.  So then who cares if your liver is a little chunky, right?  Well, eventually you will care if that is your condition:  fat stored in the liver triggers a cascade of nasty hormonal and endocrinological changes, which we will cover below. Even worse, fat in the form of triglycericdes builds up in the liver - thus the name - and, in some cases, leads to cirrhosis, i.e. actual organ damage occurs.

In fact, in many patients, the patient eventually ends up with NASH (non-alcoholic steatohepatitis), which is a polite way to say "scarred and damaged liver". Everyone fears hepatitis, but NASH leads to some of the same issues:  inflammation and cirrhosis of the liver that can lead to permanent damage.  And NASH, by the way, is not uncommon:  estimates are between 1-3% of the general population at any given time. [8] But, again, it is likely much more common in men over 40 and, undoubtedly, many reading this page are afflicted with it.  Furthermore, it has been estimated that about 20%of those with NAFLD will progress to NASH and that is also likely to be much higher in middle-aged and older males. [9]

Some of the symptoms of low testosterone and chronic fatigue can tie with the early stages of NASH, including fatigue, mental fog and memory issues.  So get tested! (You can also experience fluid retention and swelling of the extremeties.)

CAUTION:  There is a related disease called alcoholic fatty liver disease. This is yet another reason not to drink more than 1-2 drinks per day.

So what causes this type of fatty liver disease?

Insulin resistance. Insulin resitance. Insulin resistance.

Yes, genetics plays a role, but so far the #1 factor that shows up in the research is insulin resistance, which you'll remember is the hallmark of Metabolic Syndrome and prediabetes. Insulin resistance leads to elevated triglycerides and other changes that literally send fats into the liver like a guided muscle.  Your liver is packed with insulin receptors and when these get "out of whack", things get ugly very quickly.

Evidence of this theory is backed up by the fact that prediabetes, the other name for Metabolic Syndrome, can eventually lead to full-fledged type II diabetes if not stopped in its tracks.  And 70% of diabetics have been found to have fatty livers! [6]

So, of course, to avoid non-alcoholic fatty liver disease, one should avoid insulin resistance (and diabetes).  Let's start with the four big guns of Insulin Resistance Avoidance:

1) Exercise.  This is king.  Nothing unlocks insulin resitance like exercise.  Physical activity forces your body to utilize both glucose and insulin and, once again, I state, "We were born to move." This is yet another example as to why Sitting Is So Deadly.

2) Proper Weight.  A huge risk factor for Metabolic Syndrome, insulin resistance and NAFLD (non-alcoholic fatty liver disease) is being overweight. About three quarters of the obese have fatty liver disease. [7] One study found that reducing weight by as little as 5 percent can substantially improve fatty liver disease. [4]

3)  Sleep.  One recent study found that reducing patients sleep from 8 hours to 5.5 hours substantially increased insulin resistance.  [5] And, of course, we know that lack of sleep is extremely common in modern societies with TVs, computers and a hundred other things to distract us from our pillow time.

4) Testosterone. It is not that well-known that low testosterone generally raises insulin levels and predisposes men to insulin resistance, Metabolic Syndrome and Type II Diabetes.  For more details, see my book Low Testosterone by the Numbers. Researchers recently found in mice that low testosterone + insulin resistance = NAFLD. [10] More remarkably, when they gave the (castrated) mice testosterone, it eliminated the liver disease.

Wait!  There are many, many other ways to avoid insulin resistance as well.  In fact, I cover over 20 of them in my link on Metabolic Syndrome Solutions. If you can't solve the problem naturally, the doctor may put you on Metformin, a diabetes medication that can help with NAFLD in some cases.

So, again, the picture is this:  insulin resistance (prediabetes) sets in, due to lifestyle factors primarily, which then sets off a cascade of nasty medical conditions including non-alcoholic fatty liver disease, heart disease, erectile dysfunction and dementia. And it is also associated with low testosterone: see my link on Insulin Resistance, Metabolic Syndrome and Testosterone for more information. And, it it develops into full-blown diabetes, then aging accelerates and a whole host of other major issues begin to take over.


1)   Scand J Gastroenterol, 1977, 12(5):593-7, "Liver histology in a 'normal' population--examinations of 503 consecutive fatal traffic casualties"

2) J Gastroenterol Hepatol, 2002 Oct, 17(10):1098-105, "Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics"


4) Journal of Hepatology, Dec 2005, 43(6):1060–1066, "Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease"

5) J of Clin Endocrin & Metab, Nedeltcheva, A.V. , published online ahead of print, June 30, 2009


7) European Review for Medical and Pharmacological Sciences, 2005; 9:273-277, " The natural history and risk factors for progression of non-alcoholic fatty liver disease and steatohepatitis"

8), HEPATOLOGY, 2010, 52:1836-1846, "Evolution of Inflammation in Nonalcoholic Fatty Liver Disease: The Multiple Parallel Hits Hypothesis"


10) Metabolism, 2013 Jun, 62(6):851-60, "Testosterone deficiency induces markedly decreased serum triglycerides, increased small dense LDL, and hepatic steatosis mediated by dysregulation of lipid assembly and secretion in mice fed a high-fat diet"