Hyperglycemia After Pancreas Transplantation?
How often is late hyperglycemia after pancreas transplantation ascribed to tacrolimus (TAC) use; does it resolve with switch to cyclosporine (CsA) or sirolimus?

Factors influencing long-term glycemic control after pancreas transplantation include functioning beta cell mass relative to body mass index, pancreatic graft denervation, hyperinsulinemia, renal function, drug-induced insulin resistance, direct beta cell toxicity (decreased insulin secretion), and beta cell apoptosis due to either immunologic or nonimmunologic factors. Causes of long-term pancreas graft loss include rejection (either acute or chronic), vascular stenosis/thrombosis, infection, chronic pancreatitis, recurrent autoimmunity, metabolic (beta cell) exhaustion, and drug toxicity manifesting either as insulin resistance or decreased insulin secretion.

TAC has been implicated in contributing both to insulin resistance and direct beta cell toxicity. Both of these side effects appear to be dose related, and can be distinguished by measuring fasting and stimulated C-peptide levels. There are little data on the actual incidence of late hyperglycemia related to TAC, although I suspect that the true incidence is low because drug doses and levels are usually lowered over time. With the availability of rapamycin and other, newer immunosuppressants, however, the potential may exist to convert patients to less diabetogenic immunosuppression in the long term, similar to what is being done for nephrotoxicity/chronic allograft nephropathy in kidney transplantation. Such an approach may illuminate the pathophysiology of (chronic) drug-induced glucose intolerance and provide insight into the true incidence and importance of this entity. Metabolic testing before and after pharmacologic conversion can be used in this setting to determine the effect, if any, of long-term drug toxicity on beta-cell function.

My experience has been that cyclosporine causes less glucose intolerance post pancreas transplantation, so I suspect that conversion to either rapamycin or CsA may play a role in managing the pancreas transplant recipient with progressive beta-cell dysfunction in the absence of rejection, infection, vascular insufficiency, or chronic pancreatitis.