Prefer to listen without the ads? Become a Ben Bikman Insider.
A New Perspective on Type 1 Diabetes
For decades, the dominant narrative around type 1 diabetes (T1DM) has centered on one thing: insulin deficiency. But what if this isn’t the full picture? A growing body of evidence—rooted in the “bi-hormonal hypothesis” proposed by Dr. Roger Unger—suggests that the real issue may not be insulin alone, but also the unopposed action of glucagon.
In a healthy pancreas, insulin-producing beta cells sit right next to glucagon-secreting alpha cells. This arrangement allows insulin to suppress glucagon locally through a process called pericrine signaling. However, in type 1 diabetes, when the beta cells are destroyed, glucagon is no longer kept in check. The result? Even in the presence of high blood glucose, alpha cells keep releasing glucagon, promoting further glucose release from the liver and contributing to hyperglycemia and ketone production.
The Problem with Injected Insulin
While injected insulin is lifesaving, it doesn’t replicate the precise, localized insulin signal that naturally restrains glucagon. This mismatch may help explain why many people with T1DM need more insulin than expected and still struggle to maintain normal glucose levels. Injected insulin works systemically, not within the islet microenvironment where glucagon suppression matters most.
As a result, elevated glucagon can:
- Increase hepatic glucose output
- Stimulate ketone production, raising the risk of ketoacidosis
- Promote muscle breakdown for gluconeogenesis
- Drive further insulin demand, creating a frustrating feedback loop
New Therapeutic Strategies
With this new understanding, researchers are exploring ways to address the other side of the equation—glucagon. Drugs that block glucagon receptors or inhibit its secretion may provide additional support to people with T1DM.
Emerging strategies include:
- Glucagon receptor antagonists – directly block glucagon’s effects on the liver
- Somatostatin analogs – suppress multiple hormones including glucagon
- GLP-1 receptor agonists – shown to inhibit glucagon secretion and improve insulin sensitivity
- Amylin analogs – another hormone normally secreted with insulin that helps modulate glucagon
While none of these are stand-alone solutions, they represent a promising multi-hormonal approach to diabetes management.
Beyond Type 1: A Broader Model for Diabetes
Interestingly, this same glucagon-centric model may also apply to type 2 diabetes. Insulin resistance doesn’t just affect muscle and fat—it can impair insulin’s ability to suppress glucagon in alpha cells. This could explain why elevated glucagon is also common in type 2 diabetes, especially in the fasting state.
By shifting from an insulin-only view to a broader hormonal model, we may unlock better treatment strategies—not just for T1DM but for many forms of metabolic dysfunction.
10-Day Free Trial!
Start your journey toward better health today by taking control of your metabolic future, with the support you need for success.