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.
GargSK. New insulin analogues. Diabetes Technol Ther.2005;7 (5): 813–7.
2.
BolandEMonsodTDeluciaMBrandtCAFernandoSTamborlaneWV. Limitations of conventional methods of self-monitoring of blood glucose: Lessons learned from 3 days of continuous glucose sensing in pediatric patients with type 1 diabetes. Diabetes Care.2001;24 (11): 1858–62.
3.
HeptullaRAAllenHFGrossTMReiterEO. Continuous glucose monitoring in children with type 1 diabetes: Before and after insulin pump therapy. Pediatr Diabetes.2004;5 (1): 10–5.
4.
GargSZisserHSchwartzSBaileyTKaplanREllisSJovanovicL. Improvement in glycemic excursions with a transcutaneous, real-time continuous glucose sensor: A randomized controlled trial. Diabetes Care.2006;29 (1): 44–50.
5.
CobryEMcFannKMesserLGageVVanderWelBHortonLChaseHP. Timing of meal insulin boluses to achieve optimal postprandial glycemic control in patients with type 1 diabetes. Diabetes Technol Ther.2010;12 (3): 173–7.
6.
HeinemannL. Variability of insulin absorption and insulin action. Diabetes Technol Ther.2002;4 (5): 673–82.
7.
BookbinderLHHoferAHallerMFZepedaMLKellerGALimJEEdgingtonTSShepardHMPattonJSFrostGI. A recombinant human enzyme for enhanced interstitial transport of therapeutics. J Control Release.2006;114 (2): 230–41.
8.
SteinerSHompeschMPohlRSimmsPFlackeFMohrTPfutznerAHeinemannL. A novel insulin formulation with a more rapid onset of action. Diabetologia.2008;51 (9): 1602–6.
9.
CicconeCD. Basic pharmacokinetics and the potential effect of physical therapy interventions on pharmacokinetic variables. Phys Ther.1995;75 (5): 343–51.
10.
DillonRS. Improved serum insulin profiles in diabetic individuals who massaged their insulin injection sites. Diabetes Care.1983;6 (4): 399–401.
11.
MinsonCTBerryLTJoynerMJ. Nitric oxide and neurally mediated regulation of skin blood flow during local heating. J Appl Physiol.2001;91 (4): 1619–26.
12.
KelloggDLJr.In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges. J Appl Physiol.2006;100 (5): 1709–18.
13.
MagerlWTreedeRD. Heat-evoked vasodilatation in human hairy skin: Axon reflexes due to low-level activity of nociceptive afferents. J Physiol.1996;497 (Pt 3): 837–48.
14.
KoivistoVA. Sauna-induced acceleration in insulin absorption from subcutaneous injection site. Br Med J.1980;280 (6229): 1411–3.
15.
DanonABen-ShimonSBen-ZviZ. Effect of exercise and heat exposure on percutaneous absorption of methyl salicylate. Eur J Clin Pharmacol.1986;31 (1): 49–52.
16.
AshburnMAOgdenLLZhangJLoveGBastaSV. The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat. J Pain.2003;4 (6): 291–7.
17.
SindelkaGHeinemannLBergerMFrenckWChantelauE. Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects. Diabetologia.1994;37 (4): 377–80.
18.
RazIWeissRYegorchikovYBittonGNagarRPesachB. Effect of a local heating device on insulin and glucose pharmacokinetic profiles in an open-label, randomized, two-period, one-way crossover study in patients with type 1 diabetes using continuous subcutaneous insulin infusion. Clin Ther.2009;31 (5): 980–7.
19.
DeFronzoRATobinJDAndresR. Glucose clamp technique: A method for quantifying insulin secretion and resistance. Am J Physiol.1979;237 (3): E214–23.
20.
RazIYegorchikovYBittonGPesachBNagarRWeissR. Improving pharmacokinetic and pharmacodynamic profiles of rapid-acting insulin analogs using the InsuPatch device. J Diabetes Sci Technol.2009;3 (2): 384, A138.
21.
CengizETamborlaneWSherrJMartinMCarriaLSikesKUrbanABittonGWeinzimerS. O-11 Effect of a novel warming device on pharmacodynamics (PD) of rapid acting insulin in youth with type 1 diabetes (T1D). Abstracts. Diabetes Technol Ther.2011;13 (2): 173–293.
22.
FreckmannGPleusSWesthoffAKrinelkeLGBuhrAJendrikeNHaugC. Clinical performance of a device that applies local heat to the insulin infusion site: A crossover study. J Diabetes Sci Technol.2012;6 (2): 320–7.
23.
PetersALDavidsonMB. Protein and fat effects on glucose responses and insulin requirements in subjects with insulin-dependent diabetes mellitus. Am J Clin Nutr.1993;58 (4): 555–60.
24.
ServiceFJRizzaRAHallLDWestlandREO'BrienPCClemensAHHaymondMWGerichJE. Prandial insulin requirements in insulin-dependent diabetics: Effects of size, time of day, and sequence of meals. J Clin Endocrinol Metab.1983;57 (5): 931–6.
25.
BeckerRHFrickADNosekLHeinemannLRaveK. Dose-response relationship of insulin glulisine in subjects with type 1 diabetes. Diabetes Care.2007;30 (10): 2506–7.
26.
PetrofskyJPalusoDAndersonDSwanKAlshammariFKatrakVMurugesanVHudlikarANChindamTTrivediMLeeHGorakshNYimJE. The ability of different areas of the skin to absorb heat from a locally applied heat source: The impact of diabetes. Diabetes Technol Ther.2011;13 (3): 365–72.
