This study was designed to investigate the effects of heating the insulin injection site after prandial bolus delivery under conditions similar to real life. Subjects enrolled in this study were adult men and women with T1DM on CSII with moderate to good overall glycemic control. While previous studies used standardized liquid meals to investigate the effect of increased skin temperature,29
this study used continental breakfast and dinner meals in a structured clinical setting to investigate if the device also works in conditions similar to everyday use.
Postprandial AUC/t120 for capillary BG above baseline and the BG concentration 90 min after the start of the meal were significantly reduced and venous insulin concentrations were higher with heating than without. The number of hypoglycemic interventions appeared to be similar with and without local heat application.
The effect of heating on the AUC/t120
after the slowly absorbed dinner was about three times stronger than after the fast-absorbed breakfast (14% for breakfast and 40% for dinner). Raz and colleagues,29
who used a liquid meal tolerance test with 75% CHO content, reported a decrease of 33% in AUC/t120
when using the InsuPatch device. Postprandial glucose excursions are affected by several factors, such as meal composition34–36
and diurnal variations of the reaction to meal intake.37,38
Both are likely to have contributed to the larger effect observed after dinner.
Maximum venous insulin concentration was 27% higher with heating. Raz and colleagues,29
who also investigated the InsuPatch device, also found an increase in maximum insulin concentration, although the increase was somewhat larger than in this study. If patients want to increase the available insulin, a typical approach would be to increase the meal insulin dose, but this increases the risk of late postprandial hypoglycemia and also increases insulin consumption. An alternative might be the use of a local skin-heating device.
According to some studies, for rapid-acting insulin analogs, the time to insulin peak action can be up to 90 min and more.15,39,40
Although this time frame is short enough for many patients to manage their diabetes, faster insulin action is one major criterion in developing an artificial pancreas. The major problem of an artificial pancreas is in compensating for meals and exercise. Current insulin analogs still act too slowly and too long for optimal regulation.22
The data presented here suggest that an augmented insulin action may be achieved by local application of heat to the skin.
In a published study, compared to bolusing at meal time, a prebolusing of insulin glulisine 20 min before the meal resulted in reductions of BG after 60 min of approximately 40 mg/dl and after 120 min of approximately 30 mg/dl.17
This reduction is more pronounced than the effect of the local skin-heating device without using an injection–meal interval, which is presented here. Injection–meal intervals do not change insulin action; they just shift the action profile so that insulin peak action may overlap better with the postprandial glucose excursion. There are studies reporting that many diabetes patients use no or very short injection–meal intervals19
and that using no injection–meal interval increases flexibility at meal timing and quality of life.41
However, injection–meal intervals still are a beneficial therapy choice.17
Local skin-heating devices may offer an additional benefit when used in combination with injection meal intervals, but they could also be used by patients not able or willing to use injection–meal intervals.
Some technical issues with the heating device occurred during the 48 heating periods (2 days for each of the 24 subjects), especially with triggering of the heat application. However, these issues were resolved quickly, and use of the device was safe.
This study’s findings have some limitations. This feasibility study took place in a controlled clinical environment. However, a clear effect could be demonstrated for meals that were composed in a way similar to everyday life. As stated earlier, meal composition and time of day might influence the device’s effect. Lunch and snack meals were not investigated, but it seems likely that the heating device also has a beneficial effect on these kinds of meals. Although HbA1c was not investigated in this study, the observed change in glucose excursions might have an effect on HbA1c in a long-term study if the results are reproducible in a home-use setting.