In this analysis of patients with T1D transitioning from multiple daily injections to insulin pump therapy, higher HbA1c and not being treated with statins were independent predictors of improvement of HbA1c without worsening hypoglycemia. Higher baseline HbA1c and family history of diabetes were independent predictors of reduction of HbA1c. And higher baseline HbA1c, family history of diabetes and not being treated with statins were independent predictors of improvement in HbA1c. Having hypoglycemia before insulin pump therapy was a predictor of severe hypoglycemia after starting this treatment, and family history of diabetes, higher HbA1c and psychological/psychiatric disorders were predictors of diabetic ketoacidosis after therapy with insulin pump.
Insulin pump therapy has several advantages over multiple daily injections that have been already highlighted in previous studies [20, 17, 21]. This therapy allows more flexible, programmable and customizable basal insulin rates, with downloadable records and easy adjustment of insulin doses with physical activity. The possibility of using different types of boluses adjusted to the type of meal is also an advantage of insulin pump therapy. In addition, the increased flexibility improves the feeling of well-being and motivation of patients, improving their adherence to therapy [22, 23, 15]. Although more expensive, previous studies have shown that insulin pump therapy is more cost-effective than multiple daily injections [24]. Insulin pump therapy also have disadvantages that may justify why some patients have poorer glycemic control with this therapy. The disadvantages include the risk of potential infection of the site, occlusion of the catheter, or the cosmetic impact of the device, which can be discouraging for patients [22, 23, 25].
Our results are in agreement with previous reports evidencing an improvement in HbA1c levels after start therapy with insulin pump [18, 21, 19]. The association of higher baseline HbA1c values with greater reduction of HbA1c is also in agreement with other studies [26]. This association is probably explained by the greater margin to improve that patients with higher HbA1c have in comparison with patients with HbA1c closer to the target.
In our study, family history of diabetes was a predictor of reduction and improvement of HbA1c after insulin pump therapy. Other studies suggested that having a family history of diabetes may be associated with worse glycemic control and higher HbA1c levels [27–29]. As higher levels of HbA1c are associated with a greater improvement in HbA1c, this may partially explain this finding. However, in the adjusted analysis, family history of diabetes was an independent predictor of reduction of HbA1c, suggesting that additional mechanisms are involved. Having a family history of diabetes is associated with a greater awareness of the disease [30]. Family members with diabetes may be more prepared to help managing the insulin pump system, which may contribute to the improvement of HbA1c [31, 32]. The presence of a family history was also a predictor of diabetic ketoacidosis after insulin pump therapy. This may be justified by the higher levels of HbA1c found in these patients. This finding is in agreement with the study by Vakharia J et al. that found an association between family history of diabetes and a higher risk for diabetic ketoacidosis recurrence in youth with T1D [33, 29].
Patients not treated with statins were more likely to improve HbA1c levels after transitioning to therapy with insulin pump. While several studies have shown an association of treatment with statins and increased HbA1c levels and risk of diabetes in the general population and in type 2 diabetes, [34–36] few studies assessed this association in T1D. In the Thousand & 1 Study, use of statins was independently associated with increased HbA1c in patients T1D. It is uncertain whether the association of statins with HbA1c is causal or simply a marker for another mechanism such a dietary or lifestyle factor.
The improvement in HbA1c was independent of several factors including sex, age, duration of the disease and education level. Most previous studies also reported similar benefits for men and women [37, 38]. Concerning age, previous studies found discordant results. While some studies also found no difference according to age, [39, 38] other studies showed that an younger age at insulin pump initiation was associated with better glycemic controls [40, 37, 41]. Although the education level was not associated with improvement in HbA1c in our study, it should be noted that the population included in our study had higher education levels that the general Portuguese population. This suggests that people with higher education are being more frequently treated with insulin pumps, which was also reported in previous studies [42].
Regarding the safety outcomes, we found that hypoglycemia before therapy with insulin pump was a predictor for severe hypoglycemia after starting this therapy. Previous studies have shown that the main predictor of future severe hypoglycemia is previous occurrence of severe hypoglycemia or the occurrence of frequent hypoglycemia. Our results highlight that preventive measures to avoid severe hypoglycemia with insulin pump therapy are particularly relevant among patients that had hypoglycemia before starting this therapy [43, 33, 18, 44]. Due to the low number of severe hypoglycemias, our study may have been underpowered to identify other predictors. Previous reports have also identified long-standing type 1 diabetes, peripheral neuropathy and smoking as predictors of severe hypoglycemia [45, 46].
One of the most dreaded complications of T1D is diabetic ketoacidosis. As insulin pump therapy uses only fast acting insulins, failure of the device may lead to diabetic ketoacidosis in a few hours if no appropriate intervention is performed [47]. In our study, 4.5% of the population had ketoacidosis during the 3 years of follow-up. Higher baseline HbA1c levels and the presence of psychological/psychiatric disorders was a predictor of having diabetic ketoacidosis after insulin pump therapy, which is in agreement with other studies [48, 49]. This relationship can be attributed to the negative impact of psychopathology on diabetes, since it may influence blood glucose levels indirectly through lower adherence to therapy and directly increasing by promoting the release of catecholamines and corticosteroids [48].
Other studies found other predictors of improvements in HbA1c that were not assessed in our study including increased frequency of blood glucose monitoring [40] and using the bolus calculator feature [41].
Our study has limitations, including the retrospective design which limited our analysis to predictors that are routinely assessed during clinical practice. Furthermore, the study was carried out in a single center and only included adult participants, which may decrease the generalizability of our findings. Our analysis did not include patients with sensor-augmented pump therapy and, as such, our conclusions may not be applicable to this type of pump.
The strengths of our study include the specific questions that we addressed. Although several studies evaluated factors associated with outcomes during treatment with insulin pumps, few studies assessed which baseline predictors were associated with glycemic control and acute complications after transitioning to insulin pump. The identification of predictors of HbA1c improvement and predictors of severe hypoglycemia and ketoacidosis after starting insulin pump therapy is of clinical relevance as it will help to guide clinical practice. This allows a better selection of patients that most benefit from insulin pump therapy and those that are at increased risk of complications during treatment with insulin pumps.
In conclusion, insulin pump therapy was associated with improvement of glycemic control in most patients and a low risk of acute complications of diabetes. Higher baseline HbA1c, family history of diabetes and not being treated with statins were predictors of improvement of HbA1c, while hypoglycemia before insulin pump therapy was a predictor of severe hypoglycemia after starting this therapy. Family history of diabetes, higher HbA1c and psychological/psychiatric disorders were predictors of diabetic ketoacidosis after starting therapy with insulin pump. Future studies evaluating strategies to improve results in patients at risk of worse results after transitioning to insulin pump therapy are warranted.