The Metabolic Engine: Understanding Insulin Resistance

Type 2 diabetes, heart disease, fatty liver, dementia. We treat those as separate problems, and underneath most of them is the same process, insulin resistance, working on you for years before it earns a name.

That is why we go looking for it early at Fishtown Medicine. By the time your blood sugar breaks, the process has had a decade to run, and caught before that it is still fully reversible. So when someone tells me they are wiped out by 3 PM, hungry again an hour after lunch, or carrying more around the middle than they used to, I do not file it under getting older. Your metabolism is talking. We try to listen earlier than most.

What is insulin resistance?

Insulin is a key. It opens your cells so glucose can get in and be burned for energy, and when things are working, a small amount of that key does the whole job.

In insulin resistance, the lock is jammed. Your cells stop answering the signal, so your pancreas does what any hard-working organ does: it makes more key, then more again, and your blood sugar stays where it belongs. That is why a standard panel reads fine year after year. Your glucose is normal because your pancreas is buying it, and almost nobody measures what it is paying.

What it pays is insulin. High circulating insulin is inflammatory, it tells your body to store fat around the middle, and that abdominal fat feeds the same cycle back on itself.

What are the early signs of metabolic stagnation?

These all have an innocent explanation, which is how they get past a 12-minute visit one at a time. Alone, any of them is nothing much. Together they make a pattern I recognize before the labs come back:

• The 3 PM crash: You hit a wall in the afternoon and need coffee or something sweet to climb back out. People describe this to me apologetically, as though it were a discipline problem, and it is a fuel problem.
• A thickening middle: Fat gathering at your abdomen while nothing about the way you eat has changed.
• Hunger soon after eating: You finish lunch, often a carb-heavy one, and you are hungry again inside the hour.
• Skin tags or darkened skin: Velvety dark patches at the neck or the armpits, called acanthosis nigricans, usually with skin tags in the same spots. Nobody ever brings these up, so I go looking for them.
• Brain fog: Your concentration falls apart after you eat, sometimes with a wave of sleepiness you cannot argue with.

You do not need a lab test to suspect your metabolism is struggling. You need one to prove it, and the proof is what lets us do something about it.

How do we diagnose insulin resistance properly?

Most panels stop at Hemoglobin A1c and fasting glucose. Both are honest tests, and both come in late, because neither one moves until your pancreas has already lost the fight. By the time either number reads high, you have likely been insulin resistant for a decade, and a decade is a long stretch to spend being told your labs look normal.

We use a higher-resolution approach:

1. Fasting insulin: The earliest warning we have, and it is cheap. Under 7 mIU/L is where we want you.
2. HOMA-IR: A short calculation that sets your insulin next to your glucose and shows how hard your body is working to keep that glucose where it is.
3. Continuous glucose monitoring (CGM): A Dexcom or Libre sensor for a couple of weeks. We get to watch what a Wawa hoagie, a Federal Donuts run, or a Reading Terminal lunch does to you while it happens, and people learn more from 2 weeks of their own data than from anything I can say in an exam room.
4. ApoB and triglyceride-to-HDL ratio: Lipid patterns that point at insulin trouble before your glucose ever drifts.

Guidance from the clinic

"Insulin is the most powerful anabolic hormone you have, and when it runs high all day, your body is in storage mode 24/7. I have watched people white-knuckle their way through that and get nowhere, because the problem was the signal itself. So we fix the signaling first. Once your baseline insulin comes down, your body composition follows as a side effect of being healthier instead of a grueling chore."

How does Fishtown Medicine fix insulin resistance?

No single lever does much on its own, so we pull them together and let them compound into metabolic flexibility:

• Nutrition design: A protein-forward, fiber-rich way of eating that holds your glucose steady from one meal to the next, built around food you already like.
• Movement strategy: Zone 2 cardio plus resistance training. Muscle is where glucose goes, and the more of it you carry, the more sensitive to insulin you become.
• Sleep and stress repair: One rough night can make a healthy person look briefly diabetic on a CGM, so we treat your sleep with the same seriousness as anything we prescribe.
• Strategic therapeutics: Metformin, or a GLP-1 agonist like semaglutide or tirzepatide when it is clinically indicated, to give the healing a head start while the rest of the work catches up.

Scientific References

1. Reaven GM. "Banting Lecture 1988. Role of insulin resistance in human disease." Diabetes. 1988.
2. Lustig RH, et al. "Obesity I: Overview and molecular and biochemical mechanisms." Biochemical Pharmacology. 2022.
3. Donga E, et al. "A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects." Journal of Clinical Endocrinology & Metabolism. 2010.
4. Frias JP, et al. "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes." New England Journal of Medicine. 2021.

Dr. Ash is a board-certified internal medicine physician specializing in preventive medicine and healthspan optimization at Fishtown Medicine in Philadelphia.