Diabetes: where science, art and education meet

Louise Johnson explains that the art of living skilfully with diabetes in the new millennium is possible with your own skill, science and the help of a team.


The Oxford Dictionary defines art as “the creation of beautiful or significant things” and “a superior skill that you can learn by study and practice and observation.”

In the new millennium, diabetes patients can acquire this art or superior skill by diabetes education. This can be in any form of information from your diabetes nurse educator, doctor, internet support group or books on the subject.

Insulin saves lives

Historically, diabetes mellitus was a deadly disease in people living with Type 1 diabetes. Prior to 1921, when insulin was first given to Leonard Thompson, people living with Type 1 diabetes died.

There has been a radical change and growth in information and technology since 1921. People living with Type 1 diabetes now have basal and bolus analogue insulin.

An analogue is an insulin that works as close as possible to normal human insulin. Recently two new basal second-generation insulin were launched in 2018: Toujeo (glargine U300) and Tresiba (degludec).

Both have a working time of more than 24 hours. This is truly a once daily long-acting insulin without any peaks or intra patient variability. In practise, this mean that the sugar values will stay the same if you eat the same food every day. Thus, it allows for suitable background insulin to build on.

The short-acting analogues currently available are all very effective. NovoRapid, Humalog and Apidra all have a working time of approximately four hours and start to peak after 30 minutes. There is a new shorter-acting analogue in the pipeline and will be available later this year in South Africa.

Science and art meet at carb counting

Most people living with diabetes complain, from time to time, that they want to eat something ‘naughty’, without all the consequences of high sugars and feeling terrible.

The answer (if you don’t know it yet) is carbohydrate counting aka carb counting. This method calculates the carbohydrates per meal and establishes the correct amount of insulin via an easy mathematical calculation. Carb counting should be practiced by all diabetes patients on rapid insulin.

This scientific method both establishes the correct amount of insulin per carbohydrate meal as well as the correct dosage to correct sugar to a glucose target. Your doctor will determine this target value. The before meal and two-hour after meal values are important for good sugar control.

This art of food/insulin calculations are only possible with blood glucose values. Previously, the only method was finger prick. The more pricks and sugar measures, the better the sugar control.

The past few years have brought about five glucose sensors that can now do this for you. No more or very little finger pricking needed. This is made possible by continuous glucose monitoring.

It is a sensor that measures interstitial fluid sugar values every five minutes. This data is sent via a transmitter regularly. This data can be seen on cell phone apps or a reader specifically for this purpose.

The CGM system has arrows on the screen that gives an indication of sugars going up, down or staying stable. The real positive of this device is the reduction of finger pricking, accompanied with better hands on evaluation throughout a 24-hour period of the trend of the glucose.

All this technology is great but it is imperative to follow the correct procedure.

Insulin injection – the basics:

  1. Keep insulin in a cold area/fridge.
  2. Make sure it has not expired.
  3. Secure an insulin needle on a pen every second or third day. If you still use syringes then ensure you replace every second or third day. Blunt needles cause damage to the injected area. This can later lead to lipodystrophy (fat cells that are unresponsive and not functioning anymore, very lumpy).
  4. Rotate insulin injections areas every time to prevent this.
  5. Do not inject on scars or tattoos.
  6. Insert the needle at 90 degrees into fat tissue and not muscle. Be careful of upper arms and thighs if you are very thin. Make sure to pinch fat tissue between thumb and finger and not muscle.
  7. After the insulin dosage is injected, keep the plunger in for 10 seconds to get the whole dosage delivered.
  8. Do not clean with alcohol since this can interact with insulin. Soap and water is more than enough.

Glucose testing – the basics:

  1. Make sure your hands are clean.
  2. Check the machine and strips, to be sure they are the same brand, and that the strips are not expired.
  3. Replace lancets frequently to prevent damage to fingertips.
  4. Do not test on other sites than fingertips.
  5. Always keep a spare machine or battery at hand.

Other artful skills to learn:

  1. Adopting a diabetic diet.
  2. Regular aerobic exercises, such as walking, swimming, or running.
  3. Yearly visit to the eye specialist for a retina examination.
  4. Yearly visit to the podiatrist to examine feet and help with removing of corns, calluses, and abnormal nails.
  5. Visit a specialist physician once a year for heart and kidney evaluation. This is important to ensure all your values are on target.

Targets to achieve:

  1. Normal weight with a waist circumference below 80cm for a woman and 98cm for a male.
  2. Blood pressure equal to or below 130/80 mmHg.
  3. HbA1c below 7% (people with heart and kidney problems can have a value up to 8% but your doctor will establish your correct value).
  4. Triglycerides less than 1,2 mmol/L.
  5. LDL (bad cholesterol) less than 1,8 mmol/L.
  6. HDL (good cholesterol) more than 1,0 for a male and 1,2 mmol/L for a female.
  7. Urine albumin: creatinine ratio less than 30 mg/min. 

Type 2 diabetes

The tablet arena has increased dramatically over the past five years. The basis to all Type 2 diabetes treatment protocols should still be metformin.

The options in cases where metformin is not sufficient depend on the patient’s risk factors for heart attack, weight problems and cost.

  • DPP4i (Galvus, Onglyza, Januvia)

These dipeptidyl peptidase-4 inhibitor (DPP4i) drugs work on the incretin in the gut of diabetics and cause food to stay in the stomach. This causes increased satiety. In addition, the liver and pancreas secrete less glucose. The pancreas secretes the correct amount of insulin. This group of drugs makes patients sensitive to their own insulin.

  • GLP-1RA (Victoza, Byetta)

This glucagon-like peptide-1 receptor agonists (GLP-1RA) class of drugs are injectable incretins. They work the same way as the DPP4i but cause a greater loss of weight.

  • SGLT2i (Forxiga, Jardiance)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) is the newest class of drugs, especially for type 2 diabetes. They work in the top part of the kidney loop and prevent the reabsorption of sugar. This causes more sugar in the urine as well as lower blood sugar, lower blood pressure and 3 to 6kg weight loss.

In both Forxiga and Jardiance, there is sufficient data that showed improvement in mortality (risk to die) to both diabetics with previous heart attacks, strokes and heart failure and the group that only have the risk factors.

Dr Louise Loot

MEET OUR EXPERT


Dr Louise Johnson is a specialist physician passionate about diabetes and endocrinology. She enjoys helping people with diabetes live a full life with optimal quality. She is based in Pretoria in private practice.


Emerging science of probiotics in diabetic foot ulcers

Anette Thompson explains the use of probiotics in diabetic foot ulcer treatment.


Treating diabetic foot ulcers

Diabetic foot wound care practitioners understand that the three pillars of foot ulcer healing consist of: tight blood glucose control; offloading of pressure on the wound; and optimum care of the wound itself (ensuring good blood supply to assist the wound healing process).

Good blood supply delivers nutrition to the wound, although the word nutrition in diabetes has other dietetic connotations. In the past decade, emerging research into the specifics of the wound bed environment has brought further understanding of such entities: wound biofilm; proteases (protein destroying enzymes); colonisation by microorganisms and antibiotic resistance.

Wound dressing companies have developed specialised dressings to address each wound scenario, bringing in different approaches to break down biofilm, reduce the harmful bacterial load and stimulate tissue growth.

Biofilms

Biofilms are complex microbial communities containing bacteria and fungi. The microorganisms produce and secrete a protective matrix that attaches the biofilm firmly to a living surface, such as in a wound, or a non-living surface, such as an instrument7.

Biofilms are dynamic heterogeneous communities that are continuously changing3. They may consist of a single bacterial or fungal species, or may be polymicrobial, i.e. contain multiple diverse species9.

In a wound, you can imagine the biofilm as a densely-packed colony of bacteria embedded in a thick, slimy barrier of sugars (polysaccharides) and proteins. The biofilm barrier protects the harmful microorganisms beneath from external threats.

Probiotics

Most people will have heard of probiotics (a substance which stimulates the growth of microorganisms, especially those with beneficial properties) as a supportive treatment to gastrointestinal disorders. The human gut is naturally populated with millions of beneficial bacteria which in healthy individuals exist in balanced colonies, collectively called our gut microbiome.

Antibiotics destroy both beneficial and harmful bacteria, hence one should administer probiotics with a course of antibiotics (but not to be taken at the same time of the day). An imbalanced microbiome or dysbiosis is related to both gastrointestinal problems, such as diarrhoea and inflammatory bowel disease but also, outside the gut, such as obesity, allergy and skin disorders 12.

Most early studies in the literature regarding skin outcomes were those in which probiotics were taken orally. Newer studies are investigating topical application but there are limitations due to a lack of regulatory consensus in different parts of the world.

2010 research

In 2010, medical researchers, in Tucuman, Argentina, tested bacteriotherapy with lactobacillus plantarum (probiotic) on infected chronic leg ulcers6.

They produced a culture of the probiotic and applied it to the wounds of 14 diabetic patients and 20 non-diabetic patients. Wound debridement (clearing of dead tissue), granulation tissue formation (healthy new tissue containing new blood supply) and total healing after 30 days were found in 43% of diabetics and in 50% non-diabetics.

When the researchers looked at cells from the wounds after 10 days, they found that there was a decrease in the percentage of diseased and necrotic (dead) cells and an enhancement of interleukin-8 production.

Interleukin-8 (IL-8), now renamed CXCL8, is an important mediator of the immune reaction in one’s immune system response. It has two main functions:

  • It is the primary cytokine (messenger protein) involved in the recruitment of neutrophils (white blood cells that fight infection) to the site of damage or infection – in a process called chemotaxis4. This causes target cells, primarily neutrophils but also other granulocytes, to migrate toward the site of infection. It induces phagocytosis (engulfing of the bacteria to destroy them) once they have arrived.
  • It is also known to be a potent promoter of angiogenesis (formation of new blood vessels).

Probiotic strains

There are hundreds of different probiotic strains. Even within the genus lactobacillus, there are more than 150 different species, such as L plantarum, L acidophilus, L reuteri and L rhamnosus to name a few.

Many of these are found in fermented food items, such as yoghurt, kefir, kimchi, sauerkraut and salt-pickled vegetables. Within each species, there are further hundreds of strains which are numbered, such as Lp299v.

Probiotics can strengthen the immune system, reduce inflammation and promote wound healing through an array of mechanisms, such as the production of inhibitory substances like acids or bacteriocins; excretion of natural antibiotics; blockage of pathogen adhesion; nutrient competition and antioxidant activity8. Painstaking research is required to pinpoint the exact effect of each strain on the body before any claims can be made.

Latest research

In 2016, continuing research, at the national university in Tucuman, Argentina,1 designed two pharmaceutical dosage forms by using lactobacillus plantarum culture supernatants (clear liquid left above the solids after spinning in a centrifuge to concentrate the cells). These formulations have been cleared for use in clinical trials on chronic wounds that lack good blood supply (ischemic wounds).

Animal studies

Animal studies have been used to investigate the efficacy of probiotics, such as L brevis, L fermentum, L plantarum and L reuteri, as treatment for skin wounds. A meta-analysis of animal studies performed, in early 2017,10 found that probiotics administration is an effective pharmacological treatment of cutaneous animal wounds but further research is required.

Diabetic foot ulcer study

Late last year, a study at Babol University of Medical Sciences in Iran, tested the benefits of probiotic administration in patients with diabetic foot ulcers5. Patients with a diabetic foot ulcer who received probiotic supplementation for 12 weeks experienced faster wound healing coupled with an improved glycaemic and lipid profile compared with patients who had been assigned a placebo, according to findings from a randomised double-blind, placebo-controlled trial.

The probiotic capsules contained L acidophilus, L casei, L fermentum and Bifidobacterium bifidumAll participants also underwent standard treatment for wound care.

Probiotic supplementation also influenced lipid profile and inflammatory markers when compared with placebo. The researchers noted that information was not collected on faecal bacteria loads before and after probiotic administration, or on the characterisation of the microbiome at baseline, during and after therapy and bacterial cultures were not taken (a shortcoming of the study).

Lactic acid bacteria

Most recently, Dr David Armstrong reports, from the USA, that researchers are showing faster wound healing following the administration of lactic acid bacteria into wounds.

He refers to a study by Vågesjö et al., published online in the Proceedings of the National Academy of Sciences of the United States of America, that used a mice model to show wound healing.

Researchers transformed lactobacilli with a plasmid encoding chemokine 12 (CXCL12), noting that this enhanced wound closure via proliferation of dermal cells and macrophages. It also resulted in more transforming growth factor-beta (TGF-β) expression in macrophages. The study notes that bacteria-produced lactic acid reduced the local pH, which inhibited the peptidase CD26 and facilitated a higher availability of bioactive CXCL12.

The authors also note that lactobacilli delivering CXCL12 improved wound closure in mice with hyperglycaemia or peripheral ischemia, conditions associated with chronic wounds. The study adds that the treatment showed macrophage proliferation on human skin in an in vitro model of wound epithelialisation.

Final note

This is exciting news—although admittedly in early days—that we can use a probiotic (lactobacillus species) that is already a part of our beneficial bacterial microbiome2 and enable it to produce, in this case, CXCL12, which may have positive wound healing attributes.


REFERENCES

  1. Cabrera CA, Ramos AN, Loandos M del H, Valdez JC, Seso Cabral ME. Novel topical formulation for ischemic chronic wounds -Technological design, quality control and safety evaluation. Pharm Dev Technol 2016;21(4):399-404.
  2. Dixit N, Simon SI (2012). Chemokines, selectins and intracellular calcium flux: temporal and spatial cues for leukocyte arrest. Frontiers in Immunology. 3: 188. doi:10.3389/fimmu.2012.00188. PMC 3392659 Freely accessible. PMID 22787461.
  3. Hall-Stoodley L, Stoodley P. Evolving concepts in biofilm infections. Cell Microbiol 2009; 11(7): 1034-43.2.
  4. Modi WS, Dean M, Seuanez HN, Mukaida N, Matsushima K, O’Brien SJ (1990). “Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily”. Hum. Genet. 84 (2): 185–7. doi:10.1007/BF00208938. PMID 1967588.
  5. Mohseni S, Bayani M, Bahmani F, et al. The beneficial effects of probiotic administration on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. Diabetes Metab Res Rev. 2017;e2970.
  6. Peral MC, Rachid MM, Gobbato NM, Human Martinez MA and Valdez JC. Interleukin-8 production by polymorphonuclear leukocytes from patients with chronic infected leg ulcers treated with Lactobacillus plantarum. Clin Microbiol Infect 2010 Mar; 16(3):281-6
  7. Stoodley P, Sauer K, Davies DG, Costerton JW. Biofilms as complex differentiated communities. Annu Rev Microbiol 2002; 56:187-209.
  8. Tavaria F Topical use of probiotics: the natural balance. Porto Biomed J. (Portugal) 2017:2(3):69-70.
  9. Trengove NJ, Stacey MC, McGechie DF, Mata S. Qualitative bacteriology and leg ulcer healing. J Wound Care 1996; 5(6): 277-80.
  10. Tsiouris, Christos G., Martha Kelesi, Georgios Vasilopoulos, Ioannis Kalemikerakis, and Effie G. Papageorgiou. 2017. “The efficacy of probiotics as pharmacological treatment of cutaneous wounds: Meta-analysis of animal studies”. European Journal of Pharmaceutical Sciences. 104 (8): 230-239.
  11. Vågesjö E, Öhnstedt E, Mortier A, et al. Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria. Proc Natl Acad Sci USA. 2018;115(8):1895-1900.
  12. Vandenplas,Y, Huys G, Daube G. Probiotics: an update. J Pediatr (Rio J Brazil) 2015;91:6-21).

MEET OUR EXPERT

Anette Thompson
Anette Thompson (M Tech Podiatry (UJ) B Tech Podiatry (SA)) is the clinical director at Anette Thompson & Associates, Incorporated, a multi podiatrist practice in KwaZulu-Natal. Tel: 031 201 9907. They run a member service for Diabetes SA members at their Musgrave consulting rooms as a service to the community.