"Anything Meds Can Do, You Can Do Better" Part 8 of 12 - Alpha Cell Dysfunction

Alpha Cell Dysfunction: Why Blood Sugar Rises When You Don’t Eat

In this episode of the Diabetes Podcast, Richie and Amber unpack Alpha Cell Dysfunction—the last stop in DeFronzo’s “ominous octet.” We explain why your blood sugar can rise overnight, what alpha cells do in a healthy body, how things go wrong in type 2 diabetes, and what you can do—today—to take back control. We also cover meds that target this defect and the simple “non‑prescription prescription” of food and movement.

If you’ve wondered why fasting blood sugar is high even when you skip a snack, this one is for you.

Episode at a glance

• What alpha cells do and how glucagon works with insulin
• What goes wrong in Alpha Cell Dysfunction (glucagon “gone rogue”)
• Why fasting and after‑meal sugars run high
• Where it fits on the timeline from insulin resistance to type 2 diabetes
• Meds that can help: GLP‑1s, SGLT‑2s, and DPP‑4s (who, how, and cautions)
• Food moves: fiber-rich carbs, intact grains, pairing, and what to limit
• Movement that helps your liver and hormones: walking, aerobic, and strength
• Simple action steps to start today

Chapter markers

• 00:00 Welcome + why Alpha Cell Dysfunction matters
• 01:20 What alpha cells do in a healthy body
• 03:30 What goes wrong in type 2 diabetes
• 06:00 When Alpha Cell Dysfunction shows up in the timeline
• 10:45 Medications that can help
• 14:00 Food strategies that support balance
• 18:00 Movement that fixes the signal
• 22:00 The “non‑prescription prescription”
• 23:30 Closing and next steps

What is Alpha Cell Dysfunction?

• Alpha cells live in your pancreas.
• They make a hormone called glucagon.
• Glucagon tells your liver to release stored sugar (glycogen).
• This helps during fasting, exercise, and when blood sugar drops.
• Insulin and glucose normally “turn down” glucagon after a meal.
• Think of a seesaw: insulin on one side, glucagon on the other. That balance keeps your blood sugar steady.

What goes wrong in type 2 diabetes?

With Alpha Cell Dysfunction, the alpha cells stop listening. They become resistant to the normal “slow down” signal from insulin and glucose. So:

• After you eat, insulin rises…but glucagon does not fall like it should.
• The liver keeps making and releasing sugar even when blood sugar is already high.
• Fasting sugars rise. After‑meal sugars rise too.

It feels like your pancreas is pressing the gas and the brake at the same time. Your liver gets mixed messages and keeps dumping sugar. Not helpful!

When does Alpha Cell Dysfunction show up?

It starts before diagnosis. Here’s the simple flow:

1. Insulin resistance shows up first (muscle, liver, fat). Blood sugar may still be normal.
2. The pancreas makes more insulin to keep sugars in range (compensation).
3. Impaired glucose tolerance: after‑meal sugars start to spike. Early alpha cell issues can show here (glucagon not suppressed well after meals).
4. Impaired fasting glucose: fasting sugars rise. Alpha Cell Dysfunction is now clear.
5. Type 2 diabetes: fasting ≥126 mg/dL or random ≥200 mg/dL with symptoms.

Nerve damage and other changes can start years before diagnosis. So if you have prediabetes or type 2 diabetes, it’s safe to say your liver may be “not helping” and Alpha Cell Dysfunction is likely part of the picture.

Medications that help Alpha Cell Dysfunction

Talk to your clinician to see what is right for you. Here’s what we covered:

GLP‑1 receptor agonists

• Examples: Ozempic, Trulicity; higher‑dose versions for weight loss include Wegovy.
• Also: Mounjaro and Zepbound (work on similar hormone pathways).
• How they help: they lower glucagon when sugars are high, in a glucose‑dependent way. They do not block glucagon when sugars are low.
• Common side effects: nausea, vomiting, diarrhea.
• Do not use if you or your family have a history of medullary thyroid C‑cell tumors.

SGLT‑2 inhibitors

• May help overall control. Evidence on glucagon effects is mixed. Still can be useful for many people for other benefits.

DPP‑4 inhibitors (for example, Januvia)

• Help preserve your own GLP‑1 activity so glucagon drops after meals.
• Often work better in earlier stages.
• Do not combine a DPP‑4 with a GLP‑1 since they act on the same pathway.

Meds can help. But lifestyle still moves the needle the most and fixes many defects at once.

Food strategies to calm Alpha Cell Dysfunction

Focus on simple changes you can keep doing.

• Eat fiber‑rich, minimally processed carbs
  • Beans, lentils, peas
  • Non‑starchy veggies (broccoli, cauliflower, peppers, greens, mushrooms, onions