Identified biochemical hypoglycemia occurs more frequently in the inpatient population with insulin-treated CFRD than in the wider inpatient population with diabetes. In this study, 6.1% of the CBG measurements were in the hypoglycemic range, compared to 4.1% in a general diabetic population studied using the same methodology . The higher rate of hypoglycemia seen in this group is likely to be due to the insulin therapy which all patients entered into our study were receiving. Local standard practice consists of a basal bolus regime with basal and prandial insulin analogs, as guided by the CBG measurements. Hypoglycemia may also be more common in the CFRD group secondary to diminished exocrine pancreatic function, with malabsorption, loss of glucagon response, and reduced hypoglycemia awareness in patients with CFRD . As with the general population with diabetes, hypoglycemia is more frequent during the nighttime . This is potentially important as overnight CBG testing is often not part of routine diabetes management. It has previously been shown that a significant burden of nocturnal hypoglycemia is likely to be unrecorded secondary to the sporadic nature of overnight testing .
We have shown that hypoglycemia is associated with a significant increase in the rate of the composite endpoint of readmission and death over a 3.5-year follow-up period. With only one death occurring before the first readmission in this group, this finding is driven mainly by the increased rate of readmission. Hypoglycemia was associated with a non-significant increase in overall mortality. It is possible that episodes of hypoglycemia cause direct harm or predict a tendency for future deleterious hypoglycemic episodes causing adverse outcome. While no significant difference in available baseline characteristics or frequency of CBG testing were observed between those patients with and without hypoglycemia, it is likely that patients who are more ill and thereby readmitted more quickly have greater degrees of sepsis, liver disease, debility, and physiological derangement and are, therefore, more prone to hypoglycemia.
In our dataset, hyperglycemia and glucose variability did not show a significant association with readmission or mortality. In general, studies on diabetes inpatient populations have reported that hypoglycemia, hyperglycemia, and increased glucose variability are associated with excess morbidity and mortality [6–8]. It is likely that our dataset is underpowered to show any statistically significant increase in mortality associated with hypoglycemia, hyperglycemia, or glucose variability in this patient group.
Most of the hypoglycemic episodes were noted at the times when routine blood sugar monitoring was performed on the ward, which happens four times daily in our unit. This observation suggests that there may be a significant burden of hypoglycemia at other times of the day when CBG is not being tested. As hypoglycemia has been shown to confers excess mortality in the general inpatient population with diabetes, this possibility may be of clinical importance [6, 7].
This study had several limitations. Information gathering was difficult despite the introduction of electronic notes and the diabetes database (SCI-Diabetes). The dataset is quite small and heterogeneous, with patients having been started on insulin who have both impaired glucose tolerance and CFRD. We also lack data on other potential markers of poor outcome, such as sepsis, steroid use, enteral feeding, and transplantation. A larger, multi-center prospective study is required to determine whether the suspected trends of increased morbidity and mortality observed in this study are indeed significant. While individuals with CF are known to die earlier if they have diabetes, we do not have the data that would verify the benefit of tight glycemic control in CFRD or delineate fully the possible adverse outcomes .