Diabetes Mellitus Type 1 vs Pancreatogenic Diabetes Mellitus after Total Pancreatectomy: Who is at higher risk for Hypoglycemia?

Insulin therapy is the mainstay of treatment for both type 1 diabetes mellitus (T1DM) and pancreatogenic diabetes mellitus (PDM) after total pancreatectomy. Because insulin lowers blood glucose, both groups of patients are at risk of developing hypoglycemia.

However, the risk of clinically significant hypoglycemia differs between these two forms of diabetes. Do you know, who is at higher risk for hypoglycemia?

Patients with pancreatogenic diabetes after total pancreatectomy are at higher risk.

To understand why, we need to recall how the body normally responds to falling blood glucose.

1. Immediate Response (within minutes)

The goal is to halt further glucose decline and restore hepatic glucose output.

• Decreased Insulin secretion: Reduces peripheral glucose uptake, preserving circulating glucose. Lower insulin levels allow for an increase in hepatic glucose production (through gluconeogenesis and glycogenolysis).

• Increased Glucagon secretion: Stimulates hepatic glycogenolysis and gluconeogenesis.

2. Delayed (Secondary) Response (minutes to hours)

These mechanisms sustain glucose production if hypoglycemia persists.

• Increased Epinephrine (adrenaline) secretion: Enhances hepatic glucose production, inhibits insulin secretion, and mobilizes substrates für gluconeogenesis (e.g. lactate, amino acids).

• Increased Cortisol and growth hormone secretion: Act over hours to support gluconeogenesis and reduce peripheral glucose utilization.

After total pancreatectomy, both β-cells and α-cells are absent.
This means patients lack not only insulin but also glucagon, the key immediate counterregulatory hormone.
In contrast, individuals with type 1 diabetes retain α-cell function and can still mount a glucagon response (at least early in the disease).

Furthermore, exogenous insulin continues to act even as glucose levels fall, because, unlike endogenous insulin, its secretion from the subcutaneous tissue cannot be physiologically reduced in response to hypoglycemia. This persistent insulin action prevents the body from counterbalancing falling glucose levels, amplifying the risk of severe or prolonged hypoglycemia.

Therefore, patients with pancreatogenic diabetes lack both mechanisms of the first line of defense against falling glucose, making them more prone to severe or prolonged hypoglycemia compared to patients with type 1 diabetes mellitus, and intact glucagon secretion.

Additional factors such as insulin sensitivity, dietary intake, alcohol consumption, and insulin dosing technique further modulate individual risk.

Note: Cell distribution in pancreas is illustrative and does not represent real histology accurately