Increasing local blood flow by warming the application site: beneficial effects on postprandial glycemic excursions.

The absorption profile of rapid-acting insulin analogs delivered subcutaneously is slow compared with physiological insulin. Shorter time to peak and shorter duration of insulin action are important steps toward reducing high postprandial blood glucose concentrations in diabetes therapy and are critical for the development of a closed-loop insulin delivery system. Many attempts have been made to develop more rapid-acting insulins. Since the 1950s, different approaches, such as jet injectors and sprinkler needles, which try to increase the absorption areas of injected insulin, have been developed; however, none of them are commonly used in diabetes therapy. Massage and heat increase tissue blood perfusion and, thereby, the absorption of subcutaneously applied insulin. The main focus of this article is a novel device that allows local application of heat to human skin. The device can be connected to a regular insulin pump. This device could demonstrate a significant effect on insulin absorption and postprandial glucose excursions in multiple clinical trials.

Clinical performance of a device that applies local heat to the insulin infusion site: a crossover study.

BACKGROUND: Fast-acting insulin analogs have been available since 1996. The absorption rate of these insulins is still too slow to mimic the physiological insulin action in healthy subjects. This study investigates the clinical performance of InsuPatch™, a local skin-heating device, on postprandial glucose excursion. METHODS: Twenty-four type 1 diabetes mellitus subjects on continuous subcutaneous insulin infusion were included in this crossover study [10 male, 14 female, age: 43.5 ± 11.3 years, diabetes duration: 18.3 ± 10.5 years, glycosylated hemoglobin: 7.4 ± 0.8%, body mass index: 25.0 ± 3.0 kg/m(2) (mean ± standard deviation)]. The impact of local skin heating was measured by dividing the two-hour area under the curve by integration time (AUC/t(120)) for blood glucose (BG) above baseline after two standardized breakfast and dinner meal pairs (with and without heating) per subject. For the first breakfast pair, venous insulin concentration was also measured. RESULTS: A significant reduction was found for the AUC/t(120) after breakfast and after dinner meals (42 breakfast meal pairs, AUC/t(120) not heated 66.4 ± 32.8 mg/dl vs heated 56.8 ± 34.0 mg/dl, p = .017; 38 dinner meal pairs, AUC/t(120) not heated 30.8 ± 31.0 mg/dl vs heated 18.4 ± 23.9 mg/dl, p = .0028). The maximum venous insulin concentration with heating was 27% higher than without heating (n = 23). The number of hypoglycemic events on days with heating (n = 9) was similar to the number of days without heating (n = 13). CONCLUSIONS: Local heating of the skin around the infusion site significantly reduced postprandial BG by enhancing insulin absorption. The heating device was well tolerated, and it could facilitate development of closed-loop systems.