Category: 2018 Autumn – Diabetes Focus eMag

Targets and therapies

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Diabetes management is all about targets. It is of cardinal importance to know what these targets are and to work diligently to reach them. The outcome of your diabetes and diabetes-related complications are balanced finely on these values.

The targets in a diabetic patient’s life are:

1. Correct weight and body mass index (BMI)

BMI should be between 18,5 and 24,9. If it is too low or too high, it may increase mortality.

Obesity is commonly associated with Type 2 diabetes. The South African National Health and Nutrition Examination Survey (SANHANES -1) data showed that one third of South African men and two thirds of South African women are obese (BMI >30) or overweight (BMI >25)10.

 The aim in the overweight patient is to lose 5-10% of their body weight as this has shown to reduce cardiovascular risk factors.

Data showed that 15% of weight loss has been proven to even reverse Type 2 diabetes8. The remission of diabetes was associated with the Very Low Carb Diet (VLCD), which consists of less than 800 calories/day. This should be prescribed and monitored by a healthcare team.

2. Cholesterol

A cholesterol test has three important components that should all be in the target range.

  1. Low-density lipoprotein (LDL), also known as the bad cholesterol, causes atherosclerosis in the arteries. This measurement should be equal or less than 1,8 mmol/L. The increase in LDL is the cause of heart attacks and strokes. South Africans are prone to higher LDL levels due to genetic predisposition. The only way to get your LDL in target is with a statin (cholesterol lowering drug).
  2. High-density lipoprotein (HDL) is known as the good cholesterol as it is protective. This value should be more than 1,0 mmol\L in men and 1,2 mmol\L in women. The only way to increase your value if it is too low (as is often the case in Type 2 diabetes), is with exercise or mild alcohol use. (Females – one unit per day; males – two units per day. A unit is a single 200ml glass of dry red or white wine, or a single shot of hard liquor).
  3. Trygliseride is the fat count and can be decreased with a low-fat diet and medication if needed. The target should be less than 1,7 mmol/L.

 

3. Blood pressure

This is the most important goal to achieve first. In diabetic patients, blood pressure should not be above 130/80mmHg. If you have kidney impairment, blood pressure should not be above 120/80mmHg12.

The best method to measure an accurate value is to get an upper arm electronic blood pressure measure. Sit down in a quiet room and do three measures, five minutes between each measurement and take the lowest value. This was proven to be as effective as a 24-hour ambulatory blood pressure measurement (test where one wears a portable blood pressure monitor for 24 hours). The three intermittent measures compare well with risk of complications as seen in the Systolic Blood Pressure Intervention Trial (SPRINT) trial2.

Hypertension (high blood pressure) is the most common non-communicable disease (NCD) in the world, with a prevalence of 40%. It is also the number one cause of mortality in the world4. Worldwide it is poorly treated, and 70% of all people do not reach the target. In this evaluation, the target for blood pressure was 140/90mmHg.

Why the big drive to get to blood pressure targets?

If you have uncontrolled blood pressure (not on target) in your 40s and 50s, the risk of dementia increases three-fold in your 60s and 70s.

In South Africa, 195 people die daily due to heart disease associated with hypertension11. Cardiovascular mortality risk doubles with each 20/10 mmHg increase in the systolic/diastolic blood pressure. For example, a blood pressure of 155/95 mmHg will have a four-fold increased risk of cardiovascular mortality, and a blood pressure of 175/105 will have an eight-fold increased risk7.

The smallest amount of blood pressure reduction can make a difference. It was proven that a decrease of systolic blood pressure of 2mmHg decreases the risk of cardiovascular events by 7-10%. The risk for ischemic heart disease decreased by 7% and the risk for stroke mortality reduce by 10%7.

4. HbA1c

This is the most targeted and talked about value in diabetes treatment. This is the average three-month glucose value that can predict the possible development of both microvascular and macrovascular complications. It is important to remember that it is an average and not a hard value.

HbA1c is the measurement of how the red blood cells and glucose stick together in the previous 120 days. The lifespan of a red blood cell is only 120 days. It will also show if there is red cell loss (anaemia or bleeding) as this will affect HbA1c.

To get a calculated value of your estimated average glucose from your HbA1c value, this tool can be used – https://www.diabetes.co.uk/hba1c-to-blood-sugar-level-converter.html The shortened table inserted can also be of use.

To get a better impact of your diabetes control a continuous glucose monitoring (CGM) is of much more value, since the measurement shows the fluctuations of both high and low glucose values effectively.

How often should I test my blood glucose?

Self-monitoring blood glucose (SMBG):

  1. Individuals on insulin injections two to four times a day should test three times a day at least.
  2. Individuals on a one per day basal insulin should test first thing in the morning. Should this fasting glucose value be above 4-7mmol/L then a second glucose test two hours after the largest meal should be done. This value should be below 10mmol/L13, or below 9,0mmol/L14.
  3. SMBG should only be done in individuals that were trained on how to adjust medication and/lifestyle accordingly.
  4. SMBG should be done more frequently when:
  • Acute illness
  • Periods of poor glycaemic control
  • Frequent hypoglycaemic events
  • Pregnancy
  • Adjustments to therapy, either old or new additions.

 HbA1c target

The target value for HbA1c is 7% but this should be as low as 6% in pregnancy, and can increase slightly to 7,1 to 8.5% in the elderly, chronic kidney impairment, limited life expectancy and patients that are staying alone and are hypoglycaemic unaware. This needs to be discussed with your healthcare provider15.

The HbA1c as a target is important to predict microvascular complications. By the time the HbA1c exceeds 7,5%, the risk of microvascular disease (diabetic eye problems, diabetic kidney impairment and feet problems, such as burning feet) is increased by 2,5 to five-fold6.

In Type 2 diabetes, there is also a strong risk factor (two to four-fold increased risk for macrovascular complications (development of cardiovascular disease – heart attack and heart failure). This risk can already be present in the pre-diabetic phase in Type 2 diabetes5.

It is very good news to know from trial data that intensive glucose control can reduce microvascular disease even in older individuals with long-standing diabetes.

The legacy effect

The ‘legacy effect’ should be remembered in managing diabetes. This is where, the body remembers the early days of treatment, where there was good control, even when, later, the glucose control deteriorates9.

Severe hypoglycaemia is a strong risk factor for cardiovascular mortality in patients that are:

  • Older than 60 years of age
  • Diabetes duration longer than eight years
  • Cardiovascular risk factors, such as smoking, high cholesterol, and hypertension3.

Smoking

Smoking increases the risk of atherosclerosis and can deteriorate and advance the onset of macrovascular complications (heart attack and stroke) in diabetes. It should be stopped and not substituted for the e-cigarette since this is not proven safe.

Exercise

People with Type 2 diabetes should be advised to perform at least 150 minutes of exercising per week. This should be of aerobic nature i.e. walking, cycling, swimming and should aim to increase the heart rate by 50-70% of the maximal heartbeat.

Final thought

In conclusion, it is of importance to remember that there are many drugs both old and new that can help with achieving most of these goals. Speak to your healthcare professional and acquire the correct combination of drugs for your diabetes. You are the leader of this diabetes team and are the most important player in securing long-term success.

References:

  1. American Diabetes Association. Standards of Medical Care in diabetes.(2017) (Suppl 1) 40 p1-142
  2. Andreadis eA et. al. (2012) Am J Hypertension ,25
  3. Duckworth W, Abraira C, Moritz T et. al. (2009) ‘Glucose control and vascular complications in Veterans with type 2 Diabetes.’ N Engl J Med., 360(2) p129-139
  4. Ezzati et.al. (2012) Lancet, 360 p1347-60
  5. Gerstein HC, Pogue J, Mann JFE et. al. (2005) ‘ The relationship between dysglycaemia and cardiovascular and renal risk in the diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis.’ Diabetologia,48(9) p1749-1755
  6. Heine RJ, Balkau B, Ceriello A et. al. (2004) ‘ What does postprandial hyperglycemia mean?” Diab Med’ 21(3) p208-213
  7. Lewington et. al. (2002) Lancet,360 p1903-13
  8. Lim EL, Hollingsworth KG, Aribisala Bs et. al. (2011) ‘Reversal of type 2 diabetes: normalization of beta cell function in association with decreased pancreas and liver triacylglycerol.’ Diabetologia ,54 p2506-2514
  9. Orchard TJ, Nathan DM, Zinman B et. al. (2015) ‘Association between 7 years of Intensive treatment of type 1 diabetes and Long Term Mortality.” JAMA, 313(1)p45
  10. Shisana O, Labadarios D, Rehle T et. al. (20140 ‘South African National Health and Nutrition Examination Survey (SANHANES-1),Cape town HSRC Press
  11. Steyn et. al. Heart disease in South Africa,2007
  12. AHA guidelines 2017
  13. ADA guidelines 2017
  14. IDF guidelines
  15. SEMDSA guidelines2017

MEET OUR EXPERT

Dr Louise Johnson
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.

Should I have a flu vaccine?

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Dr Angela Murphy explains why and how a flu vaccine can save millions of lives.    

Every year more than 6000 people die from influenza (flu) in South Africa. Thousands more are hospitalised and many lose income from being absent from work.

What is influenza?

It’s a viral illness which has a sudden onset, causing fever, sore throat, body pains and a headache. In most otherwise healthy adults, it will be an uncomplicated illness and the person will recover within a week.

However, certain high-risk groups, as discussed below, are at risk of more severe infection. Although flu can be treated, it is much better to prevent it. The most effective prevention available is the flu vaccination.

Flu vaccination

A vaccination is designed to get the body to produce an immune response so that when an infection occurs, the body can easily fight against it.

The flu vaccination is an inactivated vaccine i.e. there is no live virus so it is impossible for the vaccine to cause flu.

The flu virus is constantly changing and so the vaccine must be updated every year. The current vaccine contains three different strains of flu which the World Health Organization has predicted will cause this season’s outbreak.

Getting vaccinated

Flu season in South Africa runs from May to September. Ideally vaccination should be done in April as it takes around two weeks for immunity to develop. If during this period, a person is exposed to flu, they may indeed get ill as they would not yet be immune. This illness is not due to the flu vaccine.

It is possible to give the vaccine later in the year, especially in the high-risk groups mentioned below. Preferably, everyone over the age of six months should receive the vaccine, but due to resource constraint the Department of Health has highlighted high-risk groups who are a priority for flu vaccination.

High-risk groups:

  • Pregnant women.
  • Patients infected with HIV.
  • Patients with underlying chronic disease, especially diabetes, lung diseases and heart disease.
  • People > 65 years of age.

Department of Health’s goal

If resources allow, the Department of Health would also like healthcare workers, residents of Old Age Homes, Institutions and Rehabilitation Centres as well as children on Aspirin therapy, aged between six and 18 months, to receive the vaccine.

The dose of flu vaccine recommended by the National Health Laboratory Services is as follows:

  • Adults 0.5ml IMI single dose
  • 3 years – 8 years   0.5ml IMI 1 or 2 doses*
  • 6 months-2 years-0.25ml IMI 1 or 2 doses*

*Two doses should be administered ≥ 1 month apart during first year of vaccination, thereafter one dose.

Side effects of flu vaccine

The vaccine is safe to take in most people but should be avoided if there is a history of severe allergic reaction. Most flu vaccines today are produced using an egg-based manufacturing process and thus contains a small amount of egg protein, called ovalbumin. The Centre for Disease Control in Atlanta, USA recommends the flu vaccine to be safe for most patients with history of egg allergy unless the reaction was life-threatening, i.e. an anaphalaxic reaction. They found in a recent study that the anaphylaxis rate after all vaccines is 1,31 per one million vaccine doses given.

It also better to recover from any flu-like symptoms before receiving the vaccine. Most people will experience little more than the discomfort of the injection. Sometimes there may be a more significant local skin reaction, hoarseness, red eyes, aches and pains, itching and headache. These side effects should not last longer than two days.

How a flu epidemic starts

The flu virus often mutates and different strains arise. When populations are not immune to these new strains, then epidemics arise.

Less commonly, a new strain appears to which most people around the world have no immunity. In this instance, a pandemic arises. The worst of these pandemics started 100 years ago in March 1918 where the Spanish flu killed millions. With today’s improved medical care and availability of vaccines that type of tragedy should not be seen.

Flu vaccine studies

A recent study at Bergen University, in Sweden, confirmed that having the flu vaccine annually improved immunity in the body. The investigators, led by Rebecca Cox, showed that people who had repeated annual flu vaccines had much greater disease-fighting capability than those who did not get the vaccine.

The effects of flu on a diabetes patient

People living with diabetes will know how infection can cause a significant deterioration in their sugar control. Having flu elevates blood sugars due to increased resistance to insulin, and with dehydration it is possible to develop a diabetic ketoacidosis. Paradoxically, hypoglycaemia may also be a feature of flu because of high fevers, sweating, poor appetite and vomiting.

Flu vaccination remains the most effective way to prevent all of this. There are 80% less hospital admissions in diabetic patients who get flu if they have also had the flu vaccine.

Remember, by being vaccinated and becoming immune to the flu, you cannot pass it on. Vaccinate today and keep healthy this winter.

REFERENCES:

http://www.nicd.ac.za/index.php/influenza/

https://www.cdc.gov/flu/protect/vaccine/egg-allergies.htm

https://www.aaaai.org/conditions-and-treatments/library/allergy-library/egg-allergy-and-the-flu-vaccine

http://www.uib.no/en/news/111513/annual-influenza-vaccination-does-not-prevent-natural-immunity

MEET OUR EXPERT

Dr Angela Murphy is a specialist physician working in the field of Diabetes and Endocrinology in Boksburg. She is part of the Netcare Sunward Park Bariatric Centre of Excellence and has a busy diabetes practice.

Emerging science of probiotics in diabetic foot ulcers

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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 bifidum. All 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.