What is the role of islet cell transplantation in managing type 1 diabetes?

Islet Cell Transplantation in Type 1 Diabetes

Islet cell transplantation is indicated specifically for adults with type 1 diabetes who experience problematic hypoglycemia—defined as recurrent severe hypoglycemic events (seizure or loss of consciousness) despite optimal insulin management—and should be performed only after structured education programs have failed to control these life-threatening episodes. 1

Primary Indication and Patient Selection

The most critical indication for islet transplantation is problematic hypoglycemia with severe hypoglycemic events that persist despite optimized insulin therapy and structured education. 1 This represents a specific subset of type 1 diabetes patients where quality of life and mortality risk justify the burden of lifelong immunosuppression.

Specific Criteria for Consideration

Patients must meet all three criteria before islet transplantation is appropriate: 1

• History of frequent, acute, and severe metabolic complications (hypoglycemia, marked hyperglycemia, ketoacidosis) requiring medical attention
• Clinical and emotional problems with exogenous insulin therapy that are so severe as to be incapacitating
• Consistent failure of insulin-based management to prevent acute complications

First-Line Therapy Must Be Attempted First

Structured education programs (such as DAFNE or BGAT) must be tried before considering transplantation, as these programs reduce severe hypoglycemia by 50-70% and restore hypoglycemia awareness in up to 40% of patients. 1, 2 Only after documented failure of these educational interventions should islet transplantation be considered.

Clinical Outcomes and Efficacy

Hypoglycemia Prevention (Primary Benefit)

The elimination of severe hypoglycemia is the primary clinical benefit and approved indication for islet transplantation. 1 Clinical trial data demonstrate:

• 82% of patients achieve HbA1c <7.0% with elimination of severe hypoglycemia at 1 year 1
• 70% maintain this dual goal at 2 years post-transplant 1
• Even partial islet graft function (requiring continued insulin) provides >90% reduction in severe hypoglycemia incidence 1

The mechanism is restoration of endogenous glucose production response to insulin-induced hypoglycemia, which protects against problematic hypoglycemia even when patients still require exogenous insulin. 1

Glycemic Control

Near-normal glycemic control is achieved in the majority of recipients, with continuous glucose monitoring studies showing near absence of time at glucose <70 mg/dL. 1 The most recent comparative data from 2025 shows that 71-80% of islet transplant recipients achieve HbA1c <7.0% without severe hypoglycemia over 5 years, compared to only 21-33% with standard care. 3

Insulin Independence

Insulin independence at 5 years is maintained in 50% of recipients, though this is now considered a secondary outcome rather than the primary goal. 1 Even insulin-requiring recipients experience similar reductions in mean glucose, glucose variability, and hypoglycemia compared to insulin-independent recipients. 1

Patient Population and Advantages Over Whole Pancreas

Islet transplantation is a minimally invasive procedure that allows inclusion of older patients and those with coronary artery disease who would be ineligible for whole-pancreas transplant. 1 The target patient population includes:

• Non-obese recipients (target islet dose ≥5,000 islet equivalents/kg can be isolated from a deceased donor pancreas) 1
• Nonuremic patients with T1D and problematic hypoglycemia (most common scenario) 1
• Patients with previous kidney transplant (islet-after-kidney transplantation) 4

Islet recipients experience significantly fewer operative complications compared to whole pancreas transplant, which has a reoperation rate as high as 40%. 1

Critical Risks and Trade-offs

Immunosuppression Burden

Lifelong immunosuppression is required, with side effects that are frequent and severe enough to restrict use to patients with serious progressive complications or unacceptable quality of life. 1 This is the primary limiting factor for broader application.

Kidney Function Decline

The most significant adverse outcome is accelerated decline in kidney function. The 2025 comparative study demonstrates that estimated glomerular filtration rate declined by 8.8-20 mL/min/1.73m² over 5 years in islet transplant recipients versus only 1.3-6.5 mL/min/1.73m² in standard care patients. 3 This represents a critical trade-off that must be weighed against the mortality risk of recurrent severe hypoglycemia.

Mortality Considerations

The procedure carries a small but not negligible mortality risk, though it is unclear whether this exceeds the inherent mortality in the patient population with years of chronic diabetes, extreme glycemic swings, and poor quality of life. 1

Regulatory Status and Reimbursement

Islet transplants are now approved and reimbursed in several countries for treatment of problematic hypoglycemia in type 1 diabetes. 1 In the United States, a phase 3 trial has been completed, and FDA approval was recently granted for adults with type 1 diabetes complicated by recurrent severe hypoglycemic events. 3

Where to Perform the Procedure

Islet transplantation should only be performed in tertiary care centers with an active kidney transplant program that are equipped to handle the complex medical and psychosocial needs of transplant patients long-term. 1 Program guidelines for objective multidisciplinary evaluation must be established and followed.

Common Pitfalls to Avoid

• Do not consider islet transplantation for general glycemic control in type 1 diabetes—the indication is specifically for problematic hypoglycemia after failure of education and optimized insulin therapy 1
• Do not skip structured education programs—these must be attempted first as they are highly effective and avoid immunosuppression 1, 2
• Do not overlook kidney function monitoring—the accelerated decline in renal function is a significant long-term complication that requires careful surveillance 3
• Do not assume insulin independence is required for benefit—even partial graft function with continued insulin requirement provides substantial protection from hypoglycemia 1