The Diabetic Wounds Crisis

The number of people with diabetic wounds is large - an estimated 1.5 million American diabetics have wounds, often to the bone. These cost over $10 billion per year to treat, and they lead to approximately 200,000 amputations a year. 

The numbers get worse.  Diabetic wounds will multiply as the diabetes epidemic spreads, growing by 112 percent between 2015 and 2020 from 25+ million Americans to 55 million.

Yet, the current standard of care plus adjuvant therapies can heal only about 25 percent.  The reason is that most adjuvant therapies are not only complex and expensive but ineffective, with weak evidence for any substantial benefit.  They treat diabetic wounds topically, like other wounds, ignoring internal ischemic causes of the wounds.  That’s what makes Remote Ischemic Conditioning different.

Remote Ischemic Conditioning

Ischemia/reperfusion injuries (IRI), such as diabetic wounds, are among the most frequent causes of debilitating disease and death.  In addition to diabetic wounds, they include heart attack, TIA and stroke, and brain injury (TBI). Ischemia is inadequate blood supply to an organ.  It causes a shortage of the oxygen and glucose needed to keep tissue alive.  Reperfusion is the restoration of blood flow to an organ or tissue after having been blocked.  It can cause tissue damage when blood supply returns to the tissue.   

The body has an innate protection mechanism for defending itself from IRI.  The process, called ischemic conditioning, can be triggered by repeated short episodes of occlusion followed by comparable periods of blood flow.  When this is implemented on a limb, it’s called Remote Ischemic Conditioning (RIC). 

RIC therapy means four cycles of alternately stopping and restoring blood flow in an arm or leg for five minutes at a time in order to activate an innate process that makes remote tissues and organs resistant to IRI.


5 minutes on
5 minutes off
For 40 minutes

Produces resistance to IRI throughout the body


RIC is believed to signal through one or both of two potential pathways:  a humoral pathway, involving a blood-borne messenger molecule, and, a neural, parasympathetic pathway mediated by acetylcholine. Each pathway leads to the activation of cell-surface receptors that in turn leads to the activation of cytoprotective signaling. (1) 

See footnote for image credit.

See footnote for image credit.


RIC has been shown to enable innate protection from IRI but manual delivery is problematic for general use. The traditional blood pressure measuring device needs both hands to manage two of its three parts and calls for both a trained ear and a quiet room to listen for and hear the blood pulsing through the arteries. 

RIC then requires 5 minutes at a sustained pressure level alternating with 5 minutes of no pressure for 40 minutes.

Delivered manually, this becomes:

  • Erratic and difficult to sustain even in one place

  • Impossible to maintain as an emergency patient is moved

  • An obstacle to simultaneously monitoring blood pressure & heart rate

Widespread adoption of the therapy will require automated delivery.

Safety & Efficacy

A 2015 PubMed article states: “RIC is safe and effective, noninvasive, easily feasible, and inexpensive.” (2)

Clinical evidence is overwhelmingly positive.

  • 64 of 70 RIC studies with 5,769 patients were positive. No studies had negative results. The 8 studies that showed no effect involved the use of anesthesia known to counteract RIC.

  • Clinical trials – 30 years of more than 100 completed and ongoing trials with more than 20,000 patients throughout the world and zero negative results.

Click here to see a partial bibliography.

Click here to see selected published clinical studies and analyses. 

Key End Points Achieved

The open question has been how effective RIC can be in treating specific indications. High interest in RIC and its possible value for diverse indications has led to dozens of small studies, with larger studies conducted over the last 8 years. 

The most recent large heart attack study showed 33% fewer heart failures during hospitalizations, zero mortalities compared to 2% among untreated patients, and almost a 50% reduction in unsatisfactory heart function. This is shown below:

Remote Ischemic Conditioning in ST Elevation Myocardial Infarction as Adjuvant to Primary Angioplasty: One-Year Results of a Randomized Clinical Trial

Authors:  A Gaspar 1, A Lourenco 1, P Azevedo 2, M Pereira 2, J Marques 2, A LeiteMoreira

1, 1Faculty of Medicine

University of Porto, Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit Porto, Portugal,

2Hospital de Braga, Cardiology Braga, Portugal,

Topic(s):  Ischemia Reperfusion. Preconditioning.  Postconditioning

Citation:  European Journal of Heart Failure ( 2017 ) 19 ( Suppl. S1 ), 11

Funding Acknowledgements:  Portuguese Foundation for Science and Technology; European Commission Grant FP7Health2010; José de Mello Saúde.

Background: Despite a significant improvement in STEMI care, mortality and morbidity remain high. One of the possible reasons is that reperfusion itself may paradoxically cause additional myocardial injury, through the so-called ischemia/reperfusion injury (IRI). Remote cardiac ischemic conditioning (RCIC) has shown encouraging results in reducing IRI.

Purpose: To evaluate the clinical impact of RCIC as an adjuvant to primary angioplasty in STEMI.

Methods: We conducted a randomized clinical trial to evaluate RCIC versus no intervention in patients with  STEMI with <12 h of symptom evolution (exclusion criteria: shock, post-cardiorespiratory arrest status or indication for surgical revascularization rather than angioplasty). RCIC consisted of intermittent left thigh ischemia through three cycles of 5 min inflation followed by 5 min deflation of a blood pressure cuff. The primary endpoint was a combined endpoint of cardiac death or hospitalization for heart failure (including device

implantation: implantable cardioverter defibrillator, cardiac resynchronization, or left ventricular assist device). We report an interim evaluation at one year follow-up.

Results: 516 patients were randomized, of which 448 were retained for analysis (231 in the RCIC group and 217 in the no-intervention group). There were no differences in baseline characteristics between the 2 groups. 

Patients without RCIC evolved more frequently with heart failure during the initial hospitalization (24.4% vs.  16.9%, p=0,06). There were also more in-hospital deaths of cardiac cause among patients not submitted to RCIC (1.8% vs. 0%, p=0.05).   At follow-up,  patients not submitted to RCIC had more frequently an Ejection Fraction <40% (18.8% vs. 10.1%, p=0.03). At one year follow-up, the combined endpoint was more frequent in nonconditioned patients (8.2% vs. 2.3%, p=0.007).

Conclusion: In this randomized study, RCIC as an adjuvant to primary angioplasty was associated with a better prognosis.


The First RIC Study of Diabetic Foot Ulcers

The first RIC study of diabetic foot ulcers also had encouraging results and has become the baseline for LifeCuff Technologies studies. Patients treated only 3 times over 6 weeks had 41% complete healing of chronic diabetic wounds versus 0% in a standard of care control with sham therapy.

 Intermittent cycles of remote ischemic preconditioning augment diabetic foot ulcer healing

Gad Shaked, MD1; David Czeiger, MD PhD1; Anwar Abu Arar, MD1; Tiberiu Katz, MD2;

Ilana Harman-Boehm, MD3; Gilbert Sebbag, MD1

1. Department of General Surgery B,

2. Department of Orthopedics,

3. Department of Internal Medicine C and the Diabetes Unit, Soroka University Medical Center and Ben-Gurion University, Beer Sheva, Israel


The morbidity and mortality caused by diabetic foot ulcer (DFU) are still significant. Conservative treatment of DFU is often ineffective. Treatment modalities using stem cells directly into the DFU or systematically have been introduced recently. Ischemic preconditioning (IPC) has been proved to be a cheap, simple, and safe method which can augment stem cells number in the peripheral blood circulation. This study’s purpose was to test whether IPC can improve DFU healing.

Forty diabetic patients were enrolled and divided into study and control groups. All patients received their regular treatment. The study group patients received in addition brief, transient cycles of IPC while the control group patients received a sham procedure only. The procedure was repeated every 2 weeks to complete a follow-up period of 6 weeks. The ulcers were photographed to measure wound area, and the degree of granulation tissue was assessed. No serious adverse events were noted. Twenty-two patients from the study group and 12 from the control group completed the entire follow-up. The ratio of patients who reached complete healing of their ulcer was 9/22 (41%) in the study group compared with 0/12 (0%) in the control group, p50.01. Furthermore, the mean remaining ulcer area at the end of the follow-up was significantly smaller in the study group, 2566% of the initial area vs. 61610% in the control group, p50.007. The degree of granulation increased after one cycle of treatment in 8/24 (33%) study patients compared to 3/16 (19%) in the control group, p50.47.  Remote, repeated IPC significantly improves the healing of DFU. This simple, safe, inexpensive treatment method should be considered to be routinely applied to diabetic patients with DFU in addition to other regular treatment modalities. 

For the full study, see




(2) Reproduced from Robert M. Bell et al. Remote Ischaemic Conditioning: Building Evidence of Efficacy. EHJ (2014) 35 (3): 138-140 (Fig. 1). By permission of Oxford University Press on behalf of the European Society of Cardiology. Published at