I have a 40-year-old patient who has been an insulin-dependent diabetic for 20 years and is currently blind and on dialysis for 18 months. In spite of this typical medical history of type 1 diabetes, he has high levels of C peptide (3 ng/mL and other dosage with 7 ng/mL).
Do you think his high level of C peptide excludes him from simultaneous pancreas-kidney transplantation (SKPT), or is kidney transplantation alone indicated? If SKPT is indicated for this patient, what is the rationale since they already have insulin production? Do you think he might benefit and become insulin-free after SKPT?
Marcelo Perosa, MD
In the recent past, type 2 diabetes was considered a contraindication to pancreas transplantation. However, based on anecdotal, then single-center, and now International Pancreas Transplant Registry (IPTR) data, type 2 diabetes is no longer an exclusionary criterion for pancreas transplantation. According to IPTR data, 231 SKPTs were performed in "type 2" diabetics in the United States and reported to the Registry between January 1, 1999 and May 15, 2003. This cohort of patients was compared with 3479 SKPTs performed in "type 1" diabetics during the same time period. The 1-year patient survival rates (95% type 1 vs 93% type 2) and graft survival rates (84.8% type 1 vs 85.2% type 2) were not significantly different, and the 3-year survival rates were virtually identical. Consequently, the "type" of diabetes did not appear to have a significant effect on short- or intermediate-term outcomes after SKPT. However, long-term data are not available, and reporting of Registry data suffers from the lack of strict criteria (ie, C-peptide production) with respect to the definition of type 1 vs type 2 diabetes.
In a previous Registry analysis, the 1-year mortality risk was 5% in type 1 and 10% in type 2 diabetics undergoing SKPT, although the 1-year graft survival rates were similar. In other words, death with a functioning graft was more prevalent in type 2 diabetics undergoing SKPT, although the difference was not statistically significant (but one could argue that such a difference is clinically significant). Suffice it to say that the type of diabetes is less important in recipient selection compared with other variables, such as physiologic age, obesity, severity of atherosclerosis, and degree of insulin resistance.
In general, type 2 diabetic patients are older (often older than 45 years), have a higher body mass index (BMI > 30 kg/m), have more advanced atherosclerosis, and have higher insulin requirements than type 1 diabetic patients. Recipient selection is paramount when considering type 2 diabetic patients for pancreas transplantation. We consider type 1 diabetic patients younger than 40 years to be transplant candidates until proven otherwise. Conversely, a type 2 diabetic patient, defined as having normal or supranormal C-peptide production, is considered "not to be a transplant candidate until proven otherwise." A diabetic individual needs to be insulin-requiring for at least 5 years to be considered for pancreas transplantation. In addition to advanced renal insufficiency, the diabetic patient needs to have evidence either of 1 or more progressive diabetic complications (proliferative retinopathy, symptomatic peripheral or autonomic neuropathy, vasculopathy) or of hyperlabile diabetes (episodes of diabetic ketoacidosis or hypoglycemia unawareness) leading to a significant impairment in quality of life in order to qualify for pancreas transplantation.
Age older than 60 years, a BMI > 30 kg/m, daily insulin requirement > 1 unit/kg, fasting C-peptide > 10 ng/mL, bilateral amputations, active smoking, and left ventricular hypertrophy with an ejection fraction below 40% are considered contraindications to transplantation in the type 2 diabetic patient. In general, selection criteria for SKPT are similar for type 1 and type 2 diabetic patients. However, greater attention must be directed towards identifying atherosclerosis, especially peripheral vascular disease. In this particular case, I would consider a person who is 40 years old, blind, diabetic, insulin-requiring for 20 years despite C-peptide production, and on dialysis for 18 months to be a potential SKPT candidate provided that the above criteria are met. For whatever reason, limited pretransplant C-peptide production does not appear to have an influence on short-term outcomes following SKPT in appropriately selected type 2 diabetics, as these patients are reliably and reproducibly rendered insulin-free by the transplant procedure, and do not appear to be at higher risk in the short term for type 2 diabetes or insulin resistance posttransplantation.