How Fatty Liver Triggers Insulin Resistance, And What to Do About It

What You’ll Discover Inside:

• The silent organ shift that can signal metabolic trouble before blood sugar ever changes
  
• A hidden fat-making process your body might be running without your consent
  
• How a sweet addiction quietly derails liver function and energy production
  
• The overlooked lab markers that whisper metabolic distress long before diagnosis
  
• A little-known score that could change how you assess “normal” labs
  
• Simple but strategic actions that tip the scales from fatty liver to functional health
  
• How small shifts in timing and nutrients may unlock powerful liver regeneration
  
• Why stable glucose isn’t the full story, and the signal you might be missing

Resources and Links:

• See the Full Transcript here
• Download our FREE Metabolic Health Guide here.  
•  
• Here is a FIB-4 Calculator Tool 
• FIB-4 = (Age × AST) / (Platelets × √ALT)
• NAFLD fibrosis score (NFS) = -1.675 + (0.037 × age) + (0.094 × BMI) + (1.13 × hyperglycemia) + (0.99 × AST/ALT ratio) – (0.013 × platelet count) – (0.66 × albumin)

• Join the Next-Level Health Practitioner Facebook group here for free resources and community support
• Visit INEMethod.com for advanced health practitioner training and tools to elevate your clinical skills and grow your practice by getting life-changing results. 
• Check out other podcast episodes here

Transcript

Dr Ritamarie 

What if your liver is the first organ to break down in metabolic disease, even before blood sugar rises? What if insulin resistance quietly fuels liver fat buildup, setting the stage for metabolic storm? 

Today's episode is about the two-way street between fatty liver and insulin resistance, and how understanding this cycle could change the way you practice.

We're going to be exploring what non-alcoholic fatty liver really is and why it often goes undetected. How fatty liver contributes to insulin resistance and vice versa. The specific chemicals like sterile regulating element binding protein 1C, big mouthful, right, and protein kinase C epsilon that disrupt insulin signaling and promote liver fat accumulation.

We're going to look at how insulin resistance promotes liver fat via diet and lifestyle factors like fructose and uric acid, and what labs can reveal dysfunction before disease develops. A big task, we're going to handle it. So let's dive in.

Dr Ritamarie (01:35)

Non-alcoholic fatty liver disease is now more accurately called metabolic dysfunction-associated steatotic liver disease, M-A-S-L-D. It's a mouthful, I know. 

It's defined by excessive fat buildup in the liver in people who drink very little or don't drink any alcohol at all. It affects, get this, over 25% of adults, and up to 80% of those with type 2 diabetes and obesity. And the scary part is most people don't even know they have it. 

Over time, the silent fat buildup can cause inflammation, scarring, and severe metabolic dysfunction.

But here's the key, it doesn't always start with the liver. Sometimes fatty liver drives insulin resistance, and sometimes insulin resistance drives fatty liver. The relationship is bi-directional and understanding it helps us to get ahead of the disease. 

So let's start looking at how insulin resistance causes fatty liver. 

In an insulin resistant adipose tissue, fat cells become dysfunctional, and they release large amounts of free fatty acids into circulation. The liver pulls those free fatty acids and converts them into triglycerides and then stores them in liver cells. And on top of that insulin, even in the presence of insulin resistance, stimulates fat production in the liver through a pathway involving sterile regulating element binding protein 1C, aka SREPB-1C. 

This means that even when insulin can't lower blood sugar effectively, it still signals the liver to make and store more fat. 

So dietary and environmental factors can contribute to fatty liver by exacerbating insulin resistance and hepatic fat accumulation. 

These factors include fructose, which unlike glucose is primarily metabolized in the liver. High intake leads to de novo lipogenesis, which in English means fat creation from sugar. It can lead to increased uric acid buildup and triglyceride buildup.

 Uric acid is another factor which impairs mitochondrial function in liver cells when elevated, and that leads to fat storage and oxidative stress. And uric acid not only gets produced from fructose in the liver, but also can be found in certain foods that are high in purines like meats and beans and things like that. 

Overeating, poor sleep, and sedentary behavior all worsen insulin resistance and set up the liver for fat overload. 

In essence, even before blood sugar rises, diet and lifestyle factors can create the conditions for fatty liver to develop, and insulin resistance makes it worse. 

Dr Ritamarie (04:31)

Now let's flip the script and discuss how fatty liver drives insulin resistance. 

Once the liver accumulates fat, it begins to interfere with insulin signaling. Lipids like diacylglycerol, DAG, activate enzymes like PKC-Epsilon, which block insulin receptor signaling pathways.

This leads to hepatic insulin resistance, insulin resistance in the liver cells themselves, where the liver continues to pump out glucose even when insulin is present. And at the same time, the liver keeps producing and storing fat. This is a double-edged sword of selective insulin resistance. Fatty liver doesn't just reflect metabolic dysfunction, it drives it.

It helps to think of the liver as a warehouse. Insulin is the manager and the manager has two key commands. One, stop making sugar, and two, store energy as fat. In insulin resistance, the stop making sugar order is ignored, the fat storing department is still wide open and still producing fat.

And sterile regulating element binding protein 1C, SREBP-1C, is the foreman of that department and keeps making fat, completely unaware that the shelves are overflowing from too much fat. This is how liver fat builds quietly, even when the blood sugar looks normal.

Fatty liver doesn't always stay simple. In some cases, the fat accumulation builds. In some cases, the fat accumulation leads to inflammation, and the inflammatory signals activate scar tissue formation.

This is known as fibrosis, and it's fibrosis, not fat. That's the biggest predictor of liver related illness. So those at highest risk include people with metabolic syndrome, diabetes, older age, and certain genetic traits. 

Because fatty liver is silent, early detection is key. 

And some of the markers to keep in mind as you're evaluating would be AST, ALT, GGT, early signs of liver stress, fasting insulin and HOMA-IR, which is calculated from insulin and blood sugar. They reveal early metabolic dysfunction. 

Fib4 is a score that estimates fibrosis risk using age, platelets, and liver enzymes, ALT and AST. I'll put the exact formula in the show notes, but what it basically is is Fib4 is the platelets times the ALT divided by the age times AST. 

If the Fib4 is less than 1.3, there's a very low risk of fibrosis. If it's greater than 2.67,

there's a high risk, and in between there's immediate risk, which really does require further investigation. The cutoffs may vary slightly based on the guidelines and the patient age. So you always need to interpret it in the context of the clinical picture and other labs. 

You can spot liver driven metabolic dysfunction long before glucose or A1C rise if you know where to look.

In a nutshell, we need to be aware of the two-way street between insulin resistance and fatty liver. And in a later episode, we're going to explore the liver-pancreas connection in detail, so you understand that more. 

So here are some action steps for clinical practice. Don't wait for high glucose. Test for early insulin resistance using insulin, C-peptide, and calculate the HOMA-IR ratio. Use triglyceride: HDL ratio and waist circumference as early metabolic flags.

Evaluate all the liver enzymes, ALT, AST, GGT, with suspicion, even if they're just mild elevations. They matter. And use non-invasive tools to access liver health. 

Calculate the FIB-4 that we explained earlier. Consider additional markers like ferritin, GGT, NAFLD fibrosis score. And for high-risk cases, recommend imaging like ultrasound or fibroscan.

And you must, must, address the root causes with lifestyle interventions, reduce fructose, reduce sugar alcohols, and all processed carbs, and support detox pathways with nutrients like choline and NAC and glutathione. 

Encourage circadian alignment, strength training, and gentle fasting. 

What do I mean by gentle fasting? Like not a 24 hour to 48 hour if nobody's used to that, but start with some intermittent fasting that gives this whole process a rest. 12 hours, 14 hours between the last meal and the first meal could be a great place to start that. 

And watch for hidden hyperinsulinemia. Insulin can be elevated for decades, before the glucose rises. 

And I tell people this all the time. It's a big mistake in medicine not to measure fasting insulin really early on. So a normal glucose with a high insulin is a metabolic dysfunction in progress. And it may be that way for a long time. And there's places we can intervene when we detect this early, which is why early, early, early, just as a routine test for fasting insulin. If it's looking good, maybe don't test it again for a few years, five years, but you must test it on a regular basis to detect this early, before somebody has damage to their liver. 

You want to educate clients that insulin and not glucose is often the first out of balance. And then reframe fatty liver as a functional alarm, not a diagnostic label. Avoid passive monitoring and act early, even when there's borderline labs. Investigate, look to see what the root causes are, and clean up the diet and lifestyle, because those are always modifiable factors that we can intervene with. 

Explaining the liver's central role in glucose, fat, and hormone balance, it has a critical role. It needs to be treated with care. Reinforce that liver function is dynamic and reversible with the right inputs. 

We have the ability to support people, before they develop dangerous consequences. Early detection, along with diet and lifestyle interventions, are key.

We're the future of healthcare, those of us committed to putting the care back in healthcare. This means going beyond symptom suppression and addressing the root causes of imbalance rather than just the symptoms. 

Fatty liver and insulin resistance are deeply connected. One drives the other and both respond to the same upstream interventions like food and movement and sleep and stress and targeted nutrients. 

I've dedicated my life to empowering people to take charge of their health and to mentoring practitioners who want to make a real difference using food, lifestyle, and functional insights to transform lives. 

If you're ready to take your practice to the next level, check out our other podcast episodes. Visit INEMethod.com for details about how we can support you.

And if you want to explore insulin resistance in more depth, head over to the show notes, and I'll have links there where you can have powerful tools to explore and to help clients with insulin resistance and metabolic dysfunction.

Together, let's continue the movement to reinvent healthcare. And until next time, shine on.