Earlier today, I consulted on a patient in the hospital who was there because of recurrent hypoglycemia. It was an interesting problem. The patient was an 85-year-old man, with a 39-year history of insulin dependent diabetes, who had been on an external insulin pump for twenty-five years. During the past two years, he had been hospitalized four times, once for pneumonia, once for diabetic ketoacidosis, and twice for hypoglycemia. During this time, his estimated glomerular filtration rate dropped from 33ml/minute to 18ml/minute, and his A1C had gradually fallen at the same time from a mean of 7.3% to 6.8%.
On the surface it would seem straightforward to conclude that, as the renal clearance of insulin decreased, and the capability of the kidney for gluconeogenesis decreased, the patient’s risk for hypoglycemia would increase and may have been responsible for the problem. There is no question, in fact, that these factors played a role in increasing this patient’s risk for hypoglycemia. In general, not just chronic renal failure, but liver dysfunction and congestive heart failure may predispose patients to fasting hypoglycemia, and unsuspected endocrine disorders such as hypothyroidism, or primary or secondary adrenal insufficiency, should also be considered as potential causes of fasting hypoglycemia due to increased insulin sensitivity.
But the point of the editorial is not one of the well-studied causes listed above. The patient, once a very alert gentleman, could not remember any of the five basal insulin rates his pump was programmed to deliver. Neither could he explain the reasoning behind the doses of insulin he uses for treatment of hyperglycemia. At least one of his decisions to treat hyperglycemia appeared to be illogical and was followed by hypoglycemia. He was vague in his recollections regarding other historical events as well. It was clear that he had suffered considerable cognitive decline, a common finding in patients with diabetes over sixty-five years of age, and much more common as renal function declines to moderately severe levels. Also, he had been very depressed since the death of his wife of many years, from cancer, earlier this year. As for his physical condition, using the National Kidney Foundation terminology, he had gone from Stage III renal failure, to between 15-30ml/min creatinine clearance, Stage IV, the most severe stage of renal failure that is not routinely treated by dialysis.
It is likely that his increased frequency of hypoglycemia was related not just to the altered insulin kinetics, but to the cognitive dysfunction, which resulted in poorer decisions and frequent hypoglycemia. His depression almost certainly was a complicating factor as well. Further complexity is added by the fact that although the endocrinologist in the ambulatory care setting had been trying to encourage the patient to consider using multiple daily doses of subcutaneous insulin instead, the patient had resisted the physician’s efforts to discourage insulin pump use for him at this time.
The data available on cognitive decline shows that cognitive dysfunction is a common feature in type 2 and type 1 diabetes, and, depending upon the tools used to measure the cognitive dysfunction, many patients will show evidence of this finding if carefully tested. A careful analysis of type 1 patients without dementia will show a subtle cognitive decline in many patients, even in childhood and adolescence, but these are relatively minor changes and are usually not clinically significant, unlike the problems later in life that may lead to dementia. In all diabetic patients, some intermittent problems, such as hypoglycemia or ketosis in ketosis-prone patients, can cause short-lived, but important, dysfunction.
More important is the data that shows the close relationship between cognitive decline and the risk factors of: increased age, duration of diabetes, degree of control of glycemia long-term, hypertension, other forms of cardiovascular disease, and depression. Depression may confer up to a 2.5-fold increase in risk of cognitive decline (Katon 2009).
Should we not use the available tools to measure cognitive function prior to putting patients on a complex device such as an insulin pump? Should we do formal testing, as the French do, to ascertain whether the patient has retained what they have been taught related to the use of an insulin pump? Should we retest the patients periodically, especially after they reach the age of 60 or greater? It is likely that this patient needs a careful reassessment prior to restarting the insulin pump. But just as patients who have diabetes and drive automobiles fight fiercely to keep their license, so do some patients regarding their insulin pump.
Although there are insulin pumps that are better designed than others, there is no Consumer Reports information to guide the unwary patient or doctor. Many patients are placed on pumps without a careful evaluation by the physician who will be supervising their pump care. In many cases, neither the patient nor the physician is aware of more than a small fraction of the capabilities of the insulin pump, and neither is particularly well informed as to the full menu of functions and the sequences of activation of commands. Often, the only contact with a professional knowledgeable about the pump the patient encounters is the pump trainer of the of the pump manufacturer, a paid employee who would be unlikely to give the patient, the new pump user, a completely unbiased opinion regarding the relative value, comparative features and safety of their pump for that patient. We need more access to just-in-time comparative information about the pumps so the process of care can be more transparent, and the physicians and other staff who perform this task need to be reimbursed for their time and expertise.
This particular case illustrates a key issue in patient safety, the need to reevaluate our patients regularly, because as disease states change in severity, and the patient’s physical, mental and emotional states change, a most appropriate therapy may become dangerous, as it has here, due to combination of each of those factors.