Pathophysiology of Pancreatic Insufficiency

The primary defect in DM is a relative deficiency of insulin for regulation of blood and tissue glucose levels. Two forms of the disease are recognized: type 1 DM, which is characterized by a significant deficiency in insulin production by the islet cells of the pancreas, possibly from autoimmune destruction, and type 2 DM, in which insulin levels may be normal but patients have a relative resistance to the action of the hormone. Type 1 diabetics are more likely to require daily administration of exogenous insulin, to be prone to ketosis, and to have wide fluctuations in blood sugar levels. The symptoms can be completely relieved by successful pancreas transplantation, but it is still uncertain whether the progression of comorbidities in all organ systems is abated.

DM severely affects the cardiovascular system by accelerating atherosclerotic vascular disease. Accelerated atherosclerosis and autonomic nervous system dysfunction are the major cardiovascular changes present in diabetic patients. If ESRD is also present, the cardiovascular risk rises dramatically. Diabetic patients with severe CAD may not recognize anginal symptoms caused by dysfunction of the autonomic nervous system. Autonomic dysfunction can also limit control of the cardiovascular reflexes and result in increased lability of blood pressure and heart rate. One index of autonomic dysfunction that has been studied is a decrease in heart rate variability, which reflects a defect in the autonomic nervous system. These defects may give rise to dysrhythmias and put patients at increased risk for sudden death during pancreas transplantation.^[149]

Patients with ESRD superimposed on DM will be subject to the same hemodynamic, fluid, volume, and electrolyte problems as those with renal failure alone. They will probably be maintained on some form of dialysis to manage fluid overload and accumulation of electrolytes. They may well have significant systemic hypertension for the reasons discussed in the kidney transplant section. Finally, they may also have the same problems of chronic anemia and uremic coagulopathy as those with renal failure alone.

After successful SPK, pathologic cardiac changes such as diastolic dysfunction and LV hypertrophy can improve or stabilize.^[150] It has not been proved whether other manifestations of DM, such as accelerated atherosclerosis, neuropathy, or vascular insufficiency, will improve or stabilize.