#7 The Liver Issue.

Welcome

In this issue, we explore one of the central control hubs in your metabolism and metabolic health: your lovely, lively liver. An insight into your liver will make sense of many aspect of type-2 diabetes and things like high morning glucose, bursts of hunger that won’t go away and stubborn symptoms like waking to urinate three times a night.

But, while the liver is vital to understand, there’s no denying that it is a complex organ. So, what follows is my attempt to walk the line between enough detail to be useful and not so much that it is info/mechanism overload.

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Right, let’s get into the thick of it!

How A Fatty Liver Keeps Blood Glucose High

Your liver has thousands of jobs and it is central to the control of your whole metabolism. For us, a key function is to act as a buffer for fuels. After eating, influenced by insulin released by your pancreas, your liver captures circulating glucose and converts some of it into long chains of a storage form called glycogen (which means "glucose generator", as that is what it does when blood glucose falls). Then, between meals and overnight, as insulin and blood glucose falls, glycogen is chopped up by enzymes back into glucose and released slowly into your bloodstream to keep your blood glucose level constant.

So, the liver's night job is to keep blood sugar steady. While you sleep, it reaches into its storage depot, and drips glucose into your bloodstream by breaking down glycogen as I just mentioned and also by making new glucose from other circulating fuels such as amino acids, lactate, and glycerol.

Your internal plumbing streams your pancreas output directly into your liver, so a gentle pulse of insulin should keep your liver's output under tight control. But, when fat starts building up inside the liver's cells, that message doesn't have its full effect. The signal that says "enough glucose, stop now" is still there, but your liver doesn't hear it very well. The liver keeps pumping glucose into the blood, and this is called hepatic insulin resistance. ['hepatic' = liver-related]

Studies have shown this clearly. In people with fatty liver, overnight glucose output can be two to three times higher than in those with lean livers, even when body weight and muscle insulin sensitivity are identical (Korenblat et al., J Clin Invest 2008). This bathes your tissues in glucose as you sleep, which damages tissues directly and keeps your HbA1c higher than you might expect from your daytime readings.

Even worse, this resistance is selective. The same insulin signal that fails to suppress glucose production in the liver (and your pancreas keeps on trying all night!) still drives fat creation and particularly visceral and ectopic fat - the most harmful kinds.

So the liver keeps doing both, exporting sugar and making fat at the same time.

That's why you might see higher than expected morning blood glucose despite making healthy changes in your diet and lifestyle. And it's why an improvement in your morning readings is a good indication of progress in clearing the harmful fat.

I'll share some good ways to speed up the clearance of liver fat later in this issue.

How a Short Binge Tricks Your Brain Into Overeating

Short bursts of overeating do more than add a few pounds. They can very quickly increase liver fat and distort how the brain senses hunger, reward, and fullness.

A 2025 study in Nature Metabolism asked healthy young men to eat about 1,500 extra calories per day of sweet, fatty snacks for just five days. Liver fat rose significantly, even though body weight and peripheral insulin sensitivity didn't change by a measurable amount. Then, using intranasal insulin (which delivers insulin directly to the brain), the researchers saw something extraordinary on their brain scans: the participants' brain insulin responses in reward circuits changed, and their food-reward learning worsened. They became less sensitive to reward and more sensitive to punishment.

One week after returning to a normal diet, the brain changes were still there. The rise in liver fat predicted how much the brain's insulin response had shifted.

The authors concluded that "short-term overeating triggers liver-fat accumulation and disrupted brain-insulin action that outlasted the time-frame of its consumption."

In plain terms: even a few days of excess calories can make the liver fatter and the brain hungrier, before any weight change is visible. Insulin normally calms the appetite centres of the brain. But, when the liver becomes engorged with fat, that calming signal misfires. You feel hungrier, you crave more energy-dense foods, and you overeat again, the cycle tightening with each round.

This is worth bearing in mind when you overeat at holidays, festivals or "cheat weeks". The effect on your eating (and the drive to eat) can keep acting against you for a long time after you stop. And the reverse of this can be used to your advantage, as I will show you below.