Insulin Resistance is believed by some to progress in a particular order. But I couldn't find anything to actually back that up. However, since insulin resistance in the liver is characterized by insulin's inability to turn off glucose production (Gluconeogensis), it does make sense that Insulin Resistance would begin with the liver.
Since glucose production no longer shuts off, both obese and Lypodystrophic patients (those with no adipose tissue for storage purposes) with Insulin Resistance have an increased amount of fat hidden in the liver. Liver cells, as well as the spaces in the liver fill with fat, so the liver becomes enlarged and heavier. Plus you may also have gallstones composed of cholesterol and bile salts.
When the liver is full of fat, it can't filter and cleanse the blood as efficiently, so the bloodstream becomes clogged with toxins and excess fatty acids (Triglycerides). The liver will also overproduce most of the known cardiovascular risk factors such as VLDL, glucose, CRP (C-reactive Protein), PAI-1 (Plasminogen Activator Inhibitor-1), fibrinogen, and coagulation factors. Poor liver function can also lead to autoimmune issues and Diabetes.
Fatty liver is the most common cause of increased liver enzymes, a sign of inflammation and liver damage. And among the obese, fatty liver is seen in 90% of adults and 53% of children. However, while 90% shows the magnitude of the problem of Insulin Resistance, at least at beginning levels of the syndrome, it also shows that for 10% of the obese population there is no fatty liver, and therefore no Insulin Resistance. Those 10%, even though obese, are actually Insulin Sensitive.
Development of fatty liver comes from an imbalance between the influx and production of fatty acids, and the use of those fatty acids for oxidation or the secretion as VLDL Triglycerides. There is a strong relationship between increased liver fat and the overproduction of large VLDL particles, since insulin is unable to regulate their production. So while large, fluffy VLDL particles are a good thing as far as not being able to slip underneath blood vessel linings, a large amount of them circulating in the bloodstream is a sign of fatty liver disease.
Excess glucose produced in the liver is not the only source of excess Triglyceride. Alcohol, sugar/fructose, high-fat foods (especially red meat and dairy), all play a role. So do birth control pills, steroids, and diuretics, as well as medical conditions like hypothyroidism and kidney disease.
Even the fat that is stored in your adipose tissue is Triglycerides, so the more body fat you have, the higher your overall Triglyceride levels will be. Plus, they also tend to increase the older you get.
And let's not forget heredity.
The good thing is that in addition to weight-bearing exercise and aerobic activity, a low carb diet is set up in such a way as to help you burn a lot of those excess, damaging Triglycerides. So blood Triglyceride numbers tend to improve greatly once you enter into a low carb diet, without having to do anything else.
The bad news is it's extremely hard to burn liver fat. Making complete liver Insulin Resistance reversal hard, but not impossible if you take your total body fat stores down low enough. Plus, when the body is burning viseral fat, it doesn't always show up on the scale, or in inches, so there's the temptation to abandon the diet, even though it's actually working.
Not everyone is willing to do what it takes to reverse Insulin Resistance. But for those of us who are, it's very important to work on making our current dietary lifestyle a way of life, rather than something we plan on doing just for the short term. Because if we return to our old ways and habits, the Insulin Resistance will also return.