No more cold feet – reflexology

For people with diabetes, winter can bring many battles, such as cold feet, that don’t need to be fought if reflexology is considered. Fiona Hardie tells us more.


Winter is slowly introducing herself through autumn colours and leaves falling from the trees. Heaters are being hauled out of storage and there is a decided increase in tea and coffee consumption, larger meals, as well as a deep need for thick socks and fluffy boots or slippers.

While this conjures up cosy images of comfort food and crackling fires, for people with diabetes this can spell trouble particularly with those who have peripheral neuropathy, the loss of feeling, numbness, or tingling one gets in the extremities due to high blood glucose levels. Burning soles and itchiness are another symptom of diabetic neuropathy caused by cytokines (proteins released by the immune system to regulate the inflammatory process).

Added to this, the cold weather also slows circulation as we tend to be somewhat more sedentary in the winter months. People with diabetes should definitely not resort to sitting too close to heaters or using hot water bottles which not only dries skin out, but can lead to blisters, ulcers and much worse if they have lost some sensation in their feet. Cooler weather also worsens neuropathy because blood vessels constrict when temperatures drop, resulting in less blood flow to the nerves. This can mean more pain and numbness.

Reflexology

Winter can bring many battles, for people with diabetes, that don’t need to be fought if reflexology as a therapeutic treatment is considered.

Reflexology is a blessing for numbness in the extremities because the reflexes are stimulated, which encourages blood flow to the nerves. This stimulation comes as a result of firm pressure exerted on the soles and tops of the feet, energising the corresponding organs in the body thus removing blockages in this flow of energy. Therefore, numbness is decreased, and mobility increased which lessens the chance of injury to the feet, loss of balance and overall feelings of discomfort. Additionally, swelling, pain, and the burning sensation respond favourably to reflexology treatments.

Reflexology can also work wonders in assisting in the maintenance of healthy blood glucose levels. HbA1c levels which are the average blood glucose levels also tend to rise during winter as exercise decreases and food consumption increases. This can weaken the immune system leading not only to colds and flu but also increases the risk of bacterial skin infections, such as Athlete’s foot.

The previously mentioned reflex stimulation can help in this dilemma. This is because the various glands responsible for producing white blood cells and building our immunity, as well as the organs involved in insulin regulation, such as the pancreas and liver, are stimulated, consequently helping to maintain the desired balanced blood glucose levels.1

Emotional and mental well-being

Beyond the physical, reflexology can have a profound impact on the emotional and mental states that are often accompanied by winter. It offers comfort because in the aforementioned stimulations, serotonin and oxytocin (feel good hormones) are increased.  Moreover, the firm confident pressure of the therapist during the treatment also lends a feeling of reassurance. Overall, a sense of relief is found not only in the extremities, thus rendering reflexology an all-encompassing therapy.

Spotting other health issues

Therapeutic reflexology can be a diabetic patient’s best friend during this cold season as the reflexologist does a thorough inspection of the condition of the nails and feet as this is how we can tell what is going on in the body. Each individual clients’ specific health issues and symptoms are taken into consideration allowing the therapy to be more personalised and efficient in its process.

Reflexology is not simply a foot massage but a systematic treatment that is incredibly powerful in assisting the body in healing itself by bringing about a profound feeling of relaxation during the cold months of winter.


References:

  1. Reflexology Association of Connecticut – 2007

MEET THE EXPERT


Fiona Hardie has owned her own Pilates studio for 18 years in Bryanston, Gauteng where she also does Bowen Therapy, Therapeutic Reflexology, Acudetox, and Bach Flower Remedies. She treats each client holistically taking into consideration their posture and physical state as well as their mental and emotional well-being. She has a special interest in natural pain management, particularly for diabetes and cancer related issues.

The rules for sick days

Diabetes nurse educator, Kate Bristow, outlines the rules for sick days and how to manage diabetes when you are sick.


COVID-19 has made the whole world sit up and take note but if you have diabetes, it is useful to know a bit more about handling sick days and the higher blood glucose readings that go with it, no matter what the cause of illness is.

When you are sick, your body will make a hormone called cortisol which is a stress hormone. Cortisol increases resistance to insulin which forces your liver to make more glucose, resulting in higher blood glucose levels. These signs are increased urination and thirst.

In some cases, the cells of your body will keep looking for something to give them energy and they will break down fat. Fat is converted to ketones by your liver. Ketones are toxic or poisonous to our bodies. Some signs of ketones can be tummy aches, nausea, and vomiting.

Which illnesses may affect your diabetes and your glucose levels?

  • Common colds/flu – this now includes COVID-19
  • A sore throat
  • Infections of the urinary tract
  • Chest infections/bronchitis/pneumonia
  • Gastric/stomach upsets
  • Skin infections e.g. abscesses

Be aware that certain medications used to treat infections may also impact the blood glucose levels. Cortisone treatment commonly used will cause the blood glucose levels to increase significantly.

How to deal safely with sick days

  • Know your targets – expect an increased blood glucose level and discuss how to handle this in advance with your healthcare team. Elderly patients with diabetes will have slightly higher targets – targets are individualised with your diabetes nurse educator and your doctor.
  • Understand how to adjust your medication and when to call the healthcare team for help.
  • Test your glucose levels more regularly. It’s recommended every two to four hours, including during the night. This applies to patients taking tablets and those on insulin and/or tablets.
  • If you take insulin you may need to test for ketones as well. Your healthcare team will help with this.
  • There is no need to eat when you are sick, but it is important to stay hydrated. High blood glucose levels will make you thirsty and urinate more often, this can lead to dehydration which is equally bad for your system. So, drink more often, even just small sips.
  • Keep taking your insulin as normal, you may need more not less.
  • Some medications may be stopped in infections, these include metformin and SGLT2 inhibitors. Discuss this with your healthcare professional.
  • Check all over-the-counter medications with your pharmacist but they are generally okay, even if they contain a bit of sugar.
  • If you have ketones, anti-nausea medications may not be effective.
  • If you have extremely high blood glucose levels and are on insulin, know the symptoms of ketone build up: tummy ache, nausea and vomiting.
  • Rapid breathing with no cough or fever as well as vomiting without diarrhoea could indicate an increase in ketones.
  • If you can’t keep fluid down or have anything that makes you worried, call for help. A lot of assistance can be given on the phone.
  • Have the contact details for your healthcare team on the fridge and easily accessible to your family/support system. It is okay to ask for help.

DKA

High ketone levels are called diabetic ketoacidosis or DKA.

High ketone levels are called diabetic ketoacidosis or DKA.

Essential supplies to manage your glucose levels

  • Blood glucose test kit
  • Glucose test strips
  • Basal and rapid-acting or mixed insulins (as prescribed)
  • Oral medications (as prescribed)
  • Quick-acting carbs/sugars to treat a low if necessary
  • Ketone test kit and ketone strips
  • Glucagon
Sister Kate Bristow is a qualified nursing sister and certified diabetes educator.

MEET THE EXPERT


Kate Bristow is a qualified nursing sister and certified diabetes educator. She currently runs two diabetes clinics as well as consults with patients privately, on a one-on-one basis via their medical aids, providing the network support required and on-going assistance and education to assist them with their self-management of their diabetes.


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Latent autoimmune diabetes in adults (LADA)

Dr Louise Johnson explains why the correct diagnosis can prevent unnecessary complications, especially in latent autoimmune diabetes in adults (LADA).


Diabetes is the world’s fastest growing non-communicable (non-infectious) disease. Diabetes is more diverse than the crude subdivision into Type 1 and Type 2 diabetes.4

LADA, or latent autoimmune diabetes in adults, is a common hybrid form of diabetes with features of both Type 1 and Type 2 diabetes. The incidence of LADA is 2-12% of all cases of diabetes in the adult population.

LADA is a diverse disease characterised by a less intensive autoimmune (antibodies against the pancreas) process than Type 1 diabetes and sharing features of Type 2 diabetes, such as abnormal cholesterol, higher blood pressure and a wider waist circumference.

Autoimmune diabetes is characterised by the presence of specific autoantibodies directed against pancreatic beta cells and initial requirement of insulin therapy.This condition is as prevalent in adulthood as in childhood.

In 1977, Irvine showed that 11% of individuals initially diagnosed as Type 2 diabetes had antibodies against the beta cells.The term LADA was introduced in 1993 and described as a subset of diabetes sharing the autoantibodies of Type 1 diabetes and the phenotype (look like) of Type 2 diabetes.

The diagnosis of LADA is based on three criteria

  1. Adult age of onset of diabetes. Usually older than 30 years of age. The person can have the phenotype (look like) of Type 2 diabetes but there tends to be fewer signs of the metabolic syndrome, such as healthier lipids, lower BMI and better blood pressure profiles.
  2. Autoantibodies against the beta cells of the pancreas, called GAD antibodies.
  3. Insulin requirements within six months after diagnosis.

The early detection of LADA among newly diagnosed Type 2 diabetes patients seems crucial since the autoimmune process against the beta cells of the pancreas can cause rapid beta cell loss if treated wrong. Treatment to prevent beta cell failure is needed and should be implemented early.

Autoantibodies and C-peptide

It is very difficult to distinguish Type 1 diabetes from LADA on a blood test. The antibody load against the beta cell of the pancreas is larger in Type 1 diabetes than in LADA.

The functionality of the beta cell of the pancreas that produce insulin can be measured by C-peptide. This is a blood test that can be done in South Africa. In Type 1 diabetes, the C-peptide is very low or absent where in LADA the C-peptide is low.

The antibody that can be measured to confirm LADA is called glutamic acid decarboxylase autoantibody (GAD). A regular laboratory in South Africa can measure this and if this is positive, it confirms the presence of autoimmunity (antibodies against the pancreas) and if diabetes is also present then this person has LADA.

C-peptide values can be used to help in determining the treatment of LADA patients:

  1. Below 0,3nmol/L – This group needs insulin and can be treated according to the guidelines for Type 1 diabetes with insulin at bedtime and before meals.
  2. More than 0,3 and less than 0,7nmol/L -This is a grey area and it’s suggested to treat this group at first with therapy that preserve beta cells. The classes of medication considered would be: DPP4i (sitagliptin, saxagliptin, vildagliptin) or GLP1-receptor agonist, such as liraglutide, exenatide or dulaglutide. The newer class of SGLT2 inhibitors empagliflozin or dapagliflozin can also be considered in some patients.
  3. C-peptide levels of more than 0,7 nmol/L needs to be treated as insulin resistant patients with metformin and the above-mentioned therapy in 2. Their antibodies need to be repeated to make sure it wasn’t a false positive and their C-peptide levels need to be followed-up.

Treatment strategies for LADA

It’s important to evaluate all newly diagnosed Type 2 diabetes patients with a test for antibodies as to not miss the diagnosis of LADA.

The reason why this is important is that certain Type 2 diabetes drugs can worsen the autoimmunity in the pancreas and accelerate the loss of beta cells. The drugs that should be avoided in LADA patients are sulfonylureas. Drugs such as gliclazide, diaglucide, glimepiride and the rest of the class.

Insulin

This is essential in all people where the C-peptide level is very low or undetectable. Insulin administration supports the declining beta cells and improves the attack of antibodies against the pancreas. This process is called insulinites.

 DiPeptidyl Peptidase 4 (DPP4) inhibitors

This is a class of drugs that work in the gut by inhibiting the enzyme DPP4 that is responsible for secretion of insulin, inhibition of glucagon and production of incretin. Incretin helps to keep the satiety level up and prevent weight gain. In LADA patients, the DPP4 inhibitors protect against beta cell loss. Drugs in this class are vildagliptin, sitagliptin and saxagliptin.

Glucagon Like Peptide Receptor Agonist (GLP RA)

This group of drugs works like the DPP4 inhibitors but are injectable and more potent. They cause weight loss of 4-5kg and a greater reduction in glucose if that is needed. They are also protective against heart disease. Drugs in this class are liraglutide, exenatide and dulaglutide.

The overlap

Patients with LADA show midway features between Type 1 and Type 2 diabetes. Although adults with high GAD antibody tests are clinically closer to Type 1 diabetes than Type 2 diabetes, an overlap does exist. The overlap causes a misdiagnosis of 5-10%. This is the reason that we recommend the testing of antibodies in new type 2 diabetes.5

It’s important to remember that the misdiagnosis of LADA in Type 2 diabetes can lead to an increase of complications due to the fact that glucose control is a lot more difficult in this group, if not treated correctly.

In the new millennium that we are living with available technology, all newly diagnosed Type 2 diabetes patients should have a GAD antibody test. Type 2 diabetes patients that are struggling to control glucose on tablets should also be evaluated. The correct diagnosis can prevent unnecessary complications. Remember information can save a life riddled with complications.


References:

  1. Pieralice S et. al. “Latent autoimmune diabetes in adults: A review on clinical implications and management Diab Metab J 2018;42:451-464
  2. Bluestone JA et. al. Genetics, pathogenesis and clinical interventions in type 1 diabetes” Nature 2010 ;464: 1293 -300
  3. Buzetti et al. Management of Latent autoimmune diabetes I adults: A consensus statement from an International expert panel. Diabetes oct 2020 vol 69
  4. Tuomi T et. al. The many faces of diabetes: a disease with increasing heterogeneity. Lancet 2014, 383;1084
  5. Mishra et. al. 2018 
Dr Louise Loot

MEET THE 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.


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The importance of clinical trials

Amina Goondiwala, a principal study coordinator, explains the importance and benefits of clinical trials.


The World Health Organisation has defined clinical trials as: “A type of research that studies new tests and treatments and evaluates their effects on human health outcomes. People volunteer to take part in clinical trials to test medical interventions, including drugs, cells and other biological products, surgical procedures, radiological procedures, devices, behavioral treatments and preventive care.”

Authorities of clinical trials

A clinical trial is carefully designed, reviewed and submitted to South African Health Products Regulatory Authority (SAHPRA) and ethics committees prior to being implemented at different sites. Updates during a study and at the end are also submitted to these regulatory bodies to ensure proper conducts of these studies are completed.

The Food and Drug Authority (FDA) has overall authority on trials for drugs and biologics and medical device products regulated by the agency. The purpose of an Institutional Review Board (IRB) review is to ensure that appropriate steps are taken to protect the rights and welfare of participants in the research. If the risks to participants are found to be too great, the IRB will not approve the research, or it will specify changes that must be made before the research can be done. As part of their review, IRBs consider participant inclusion and exclusion requirements to be sure that appropriate people have been identified as eligible for the trial. They often look at how and where recruitment for clinical trials will occur.

Patients’ medical records are reviewed for consideration on who can participate in a clinical trial. All patients are given an Informed Consent where the benefits and possible side effects of the medication is described. It is on a voluntary basis and a patient may stop at any time and continue with their previous treatment regime with their primary healthcare provider.

The goal of a trial is to answer specific questions on new therapies and medications. These studies are conducted in three phases and may take about 10 to 15 years before a product is approved for use in a country.

Diabetes clinical trials

Many studies have been completed for diabetes and many new trials are available for participation, not because of a last resort but to help pharmaceutical industries develop better-suited medication to control diabetes and avoid complications.

Patients with elevated glucose levels may be considered for these trials and not only will they receive medication but also have frequent clinic visits with regular blood tests and ECG monitoring. Patients may also be included in Oral Diabetic Studies or Insulin Controlled Studies.

These patients will also be contacted regularly during their scheduled visits to ask how they are feeling, and should any new symptoms develop that need to be monitored. Nurses or site staff spends time with each patient addressing their concerns regarding their conditions. Social and economic factors may also be addressed with patients having a difficult time maintaining their glucose levels. All patients are encouraged to engage in some form of exercise or activities to ensure a healthier outcome.

Benefits of participating in a clinical trial

There are many benefits to enrolling on a clinical trial. For example, you can take a more active role in your healthcare, such as learning the importance of taking your medication on time and how to deal with a hypoglycemic episode; gain access to optimal medical treatment and adherence to standard of care; get expert advice at these facilities and help others by contributing to medical research.

You may also involve your primary care provider on your achievements during a trial. At some facilities, they also invite family members to each appointment, so they may also learn on how to help you manage your diabetes. Eating plans where portion sizes and choosing the healthier option, specifically for diabetes, are discussed. Patients may receive glucose monitoring devices and shown how to take their glucose levels daily.

Patients are reminded that medication is not to be shared between friends and family as other diabetic patients may have other conditions as well and the prescribed medication may only be suitable to you.

Inform your treating doctor

Please speak to your primary healthcare provider prior to enrolling in any clinical trial or changing your diabetic medications. It is best to seek medical advice first before making any decisions.

Amina Goondiwala

MEET THE EXPERT


Amina Goondiwala is the senior study coordinator at Soweto Clinical Trials. She has 19 years’ experience in clinical trials, having participated in over 110 trials since 2002, and was awarded Study Coordinator of the Year in 2010 by the South African Clinical Research Association.


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The measure of it – Time in range

Dr Angela Murphy discusses diabetes control in the 21st century, specifically time in range.


After the discovery of insulin in 1922, people with diabetes (PWD) were living longer and, thus, diabetic complications started to emerge. The goal in managing diabetes started to focus on preventing these complications and improving overall quality of life. With the advent of large-scale clinical trials, the relationship between glucose levels and risk of complications was revealed.

The Diabetes Control and Complications Trial (DCCT), which involved Type 1 diabetes patients, released its results in 1990. It conclusively showed that improved glucose control reduced the risk of microvascular (small blood vessel) complications of the eyes, kidneys, and nerves.

Large trials done in Type 2 diabetes patients, such as the United Kingdom Prospective Diabetes Study (UKPDS), confirmed these reductions in microvascular complications with good diabetes control.

Initially, the data didn’t show the same benefit in macrovascular (large blood vessel) complications, viz: coronary artery disease, stroke, and peripheral vascular disease where blood supply to the feet is blocked. However, trials that followed-up patients beyond 15 years did show that there was indeed benefit. We now had proof that good glucose control prevented complications. So, what constitutes good diabetes control?  How do we measure that?

Blood glucose measurement

The impetus to test glucose in the early days of diabetes was centred on diagnosis. Hence, initial urine test kits would just have established if glucose was present or not.

Then PWD wanted to assess the degree of improvement in their glucose levels using the different treatment regimens available. Another strong reason to test would have been to establish hypoglycaemia.

Blood glucose testing was greatly improved in the mid 1960s with the invention of the Ames dextrostix and gradually home glucose testing kits became available.

When continuous glucose monitoring (CGM) devices were released, even more accuracy was expected. Blood glucose targets were partly determined from knowing what the non-diabetic blood glucose range is, but also from the data of the trials. There are three parameters that are used for these targets: fasting blood glucose, post-prandial (two hours after a meal) blood glucose, and HbA1c.

HBA1C – glycated haemoglobin

In 1968, Iranian born Samuel Rahbar started studying the haemoglobin (Hb) molecule (which carries iron and oxygen in our blood). By chance he came across an unusual variant in diabetic blood and went on to work at the Albert Einstein College of Medicine with Helen Ranney. They found that their diabetic Hb matched the previously described subtype of HbA and so was named HbA1c.

HbA1c is formed when excess glucose in the blood attaches to the haemoglobin molecule, a process called glycation. Red blood cells are renewed on average every three months, so HbA1c is regarded as an average of blood glucose control over a three-month period. In fact, it was HbA1c that was used in the DCCT and UKPDS trials to show that good glucose control prevented diabetes complications. Without HbA1c, this would have been nearly impossible to demonstrate.

Figure 1 demonstrates the concept of a lower HbA1c, <7,0%, being good, so it’s green, whereas a higher HbA1c is dangerous and thus, is in red. HbA1c can be affected by several conditions that may make it less reliable, such as kidney failure, pregnancy, smoking and ethnicity.

Home glucose monitoring

In this era of data overload, it’s truly useful to be reminded why we advocate blood glucose testing in the management of diabetes. It should not just be about going through a routine to provide the doctor with readings at the consultation, but also to empower the PWD.

In 2011, the Structured Testing Program Study showed that getting PWD to do structured testing in the three days before their doctor’s visit improved their HbA1c by 0,3%. There was no medication change, just behavioural change.

The participants in the study used the AccuCheck 360’ tool (below) and did a seven-point profile for those three days. This involved testing before each meal, two hours after each meal and at bedtime. I have adapted this tool for my clinical practice and use it frequently. It helps me advise patients with medication changes, but it’s just as valuable for the patient to see what else influences the glucose levels. This can range from food to medication, activity, illness and even stress. It is particularly useful when patients are new to the practice and their diabetes regimen needs to be assessed.

Continuous glucose monitoring

The first generations of CGMs approved by the Food and Drug Administration (FDA), beginning in 1999, were able to provide significant clinical benefits as an adjunct to standard self-monitoring of blood glucose.  These are the machines of many a PWD’s dreams: a way of seeing the blood glucose at any time of day or night without having to open a conventional glucometer and prick a finger.

As the CGM devices became more advanced, they not only showed the current glucose reading, and of course the tracing of where the glucose had been but could predict where the glucose would go. In this way, PWD could be forewarned of a hypoglycaemia or hyperglycaemia and take appropriate action to avoid these. When this type of CGM technology works in tandem with insulin pumps, we see the makings of an artificial pancreas.

Time in range

What data from CGM showed acutely is that we cannot always rely on average blood glucose levels, even HbA1c, to fully assess overall diabetic control. Averages do not show the extent of the high and low glucose readings.

Let me explain. If there are three blood glucose values of 6,0mmol/L, then obviously the average blood glucose is 6,0mmol/L. However, three readings of 12mmol/L, 2mmol/L and 5mmol/L will also give an average of 6,0mmol/L and yet only one reading is in the target range.

Figure 3 shows how all HbA1c’s are truly not equal. The same HbA1c of 7,0% can have completely different glucose profiles. This variation in glucose levels is called glucose variability. CGM demonstrates patterns of glucose over a 24-hour period in detail so the swings in blood glucose levels are easily seen. There is strong evidence to show that increased glucose variability predicts the risk of hypoglycaemia. Specifically, it predicts severe hypoglycaemia in Type 1 diabetes and non-severe in Type 2 diabetes.

Severe hypoglycaemia is defined as low blood glucose <4mmol/L and the PWD requires assistance to treat the low glucose. The more frequently the blood glucose levels swing from highs to lows, the higher the glucose variability. There is concern that this variability can damage blood vessels and thus, may be implicated in diabetic complications.

Glucose targets

Based on data from all the large diabetes trials over the years, we can set targets for good diabetes control. This is not a one-size fits all range. Age, duration of diabetes, presence of complications, risk of hypoglycaemia and pregnancy all affect the target blood glucose levels.

In older PWD who have diabetic complications, particularly of the heart and kidneys, glucose levels are slightly higher than a young, newly diagnosed PWD. Table 1 shows advised targets for FBG, PPG, HbA1c.

TABLE 1 – BLOOD GLUCOSE TARGETS FROM SOCIETY OF ENDOCRINOLOGY AND METABOLISM SOUTH AFRICA 2017

 

 

HbA1c FBG (fasting blood glucose)mmol/L PPG (2-hour post prandial blood

glucose)mmol/L

     YOUNG <6.5% 4-7 4.4-7.8
     MOST <7.0% 4-7 5-10
     ELDERLY <7.5% 4-7 <12

In 2019, the International Consensus in Time in Range (TIR) was released and defined the concept of the time spent in the target range between 4 and 10mmol/L while reducing time in hypoglycaemia, for patients using CGM.

Several studies have now shown a good correlation of TIR with HbA1c. In one, more than 90% participants with a TIR of >80% has HbA1c values of ≤ 7.0%.

At present, TIR is only verified with the use of CGM. Intermittent testing, even doing seven-point profiling does not seem to be as predictable. Several medical aids will now consider reimbursement for CGM devices for Type 1 diabetes patients, which will significantly increase the use of CGM in South Africa.

Summary

To achieve good diabetes control, we try to get as close to physiological glucose levels as is safe which has been proven to decrease both microvascular and macrovascular complications. Good control is not only a good average but also stability of glucose levels over time. It is this latter attribute which is measured with Time in Range and which may become the most important of all glucose measurements in the future.


References:

  1. Parkin G, Zhihong Jelsovsky, Bettina Petersen, Matthias Schweitzer, Robin S. Wagner. Structured Self-Monitoring of Blood Glucose Significantly Reduces A1C Levels in Poorly Controlled, Noninsulin-Treated Type 2 Diabetes. Diabetes Care Feb 2011, 34 (2) 262-267; DOI:2337/dc10-1732 
  1. Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, Bosi E, Buckingham BA, Cefalu WT, Close KL, Cobelli C. Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range. Diab Care. 2019;1(42):1593–603.
  1. Gabbay, M.A.L., Rodacki, M., Calliari, L.E. et al.Time in range: a new parameter to evaluate blood glucose control in patients with diabetes. Diabetol Metab Syndr 12, 22 (2020)
  1. Hirsch IB, Welsh JB, Calhoun P, Puhr S, Walker TC, Price DA. Associations between HbA1c and continuous glucose monitoring-derived glycaemic variables. Diabet Med. 2019;36:1637–42.

MEET THE 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.


The great power of insulin

As we celebrate the centenary of insulin therapy, Dr Angela Murphy reflects on what a change it has made in the management of diabetes. It’s a life-saving medication.

A telegram to Dr Robert Lawrence: “I’ve got insulin – it works – come back quick.”

In May 1923, Dr Robert Lawrence was in Florence, Italy, far from his family home in Scotland, preparing to die from Type 1 diabetes.  A telegram from his colleague urged him to return to London and on 31 May 1923, Lawrence received his first injection of insulin. His life was saved! Lawrence went on to become a leading diabetologist and help found the British Diabetes Association. He lived almost 50 productive years thanks to insulin.

Present day

Yet today, insulin is frequently not seen as life-saving but rather as a harbinger of the end of the road. People with Type 1 diabetes require insulin injections from diagnosis as they lose the ability to secrete insulin from the beta-cells in the pancreas.

In Type 2 diabetes, insulin deficiency only develops after several years.  A healthy lifestyle, as well as oral medications, is prescribed to bring glucose levels under control. It’s important to remember that diabetes is, by nature, a progressive disease.

Initial treatments aim to improve insulin sensitivity and improve endogenous insulin secretion. At some point, the insulin secreting cells of the pancreas struggle to keep up with demands and start to shut down. When glucose control can’t be achieved with the body’s own insulin then it’s time to start insulin injections.

Incredibly, sometimes this seems to trigger a partial recovery of some beta-cells. It turns out that they had not died, merely gone on strike as the work became too hard. When reinforcements arrive in the form of an insulin injection, they decide to return to work. This is the reason people with diabetes often manage with just one injection daily, in combination with their tablets, for many years.

How does insulin work?

Insulin is needed to open the glucose channel into the cell so that glucose from the blood can enter the cell. If there is not enough insulin, or the cell resists the action of the insulin, blood glucose levels will rise.

In the 1920s, insulin was derived from animals and only lasted in the body for several hours. In the 1950s, modifications were made to allow the insulin to be absorbed more slowly into the body. Over the next decades more advances where made with the introduction of human insulin, insulin analogues, improved delivery devices (pens and pumps) and non-injectable insulin (not available in SA). However, the precept of the purpose of insulin has not changed: it functions to move glucose from the blood into the cells where glucose is used to produce energy.

Patients often ask me how the morning blood glucose can be high when they have not eaten for 10 hours. Glucose enters the body directly from food and from stored glucose in the liver and muscle, particularly the liver. In the fasting state, such as being asleep overnight, the liver not only releases stored glucose but also manufactures glucose. One of the earliest features of insulin resistance occurs when the production of glucose in the liver is not kept in check, resulting in a rise in fasting glucose. At this point people with diabetes may be advised to start a night-time insulin.

Insulins available in SA

With such a plethora of insulins on the market, it’s no wonder insulin use can seem overwhelming and confusing. To better understand how the different insulins are used, I will explain the various insulin regimens that people with diabetes may be started on.

BASAL INSULIN

Regular insulins: Humulin N; Protophane; Biosulin N

Analogue Insulins: Basaglar; Levemir; Lantus and Optisulin; Tresiba; Toujeo

Most people with diabetes who are initiated on insulin will start with one daily injection, usually at bedtime. The efficacy of this insulin is determined by the fasting blood glucose reading: i.e. the blood glucose measured on waking in the morning before eating or drinking. If this fasting blood glucose is not at the target range (see Table 2 for your target range as per our South African guidelines), then the evening insulin is adjusted accordingly. The important points about bedtime insulin dose adjustment are:

  • Adjustments are NOT made according to the bedtime glucose
  • Adjustments are made according to the average fasting blood glucose values over a 3-7-day period (your HCP will determine this time frame).

Thus, adjustments are not made up and down daily. Rather they are based on the trend of the averages. Sometimes, the HCP may suggest using the basal insulin twice daily if they feel it would benefit daytime control. The titration of the morning dose will then be determined by the evening glucose reading, as explained below in the Pre-Mix Insulins.

TABLE 2: Target range (2017 SEMDSA GUIDELINES)

HbA1c FBG (mmol/L) PPG (mmol/L)
YOUNG <6.5% 4-7 <8
MOST <7,0% 4-7 <10
ELDERLY <7,5% 4-7 <12

TWICE DAILY PRE-MIX INSULIN

Regular insulins: Actraphane; Humulin 30/70; Insuman; Biosulin 30/70

Analogue insulins: NovoMix 30; Humalog Mix 25; Humalog Mix 50; Ryzodeg

When good glucose control can’t be maintained throughout the day with tablets alone, then insulin must be given to allow glucose absorption from meals. Pre-mix insulin consists of a mixture of short and intermediate insulin in the same pen. Some important points to remember:

  • This insulin will replace the basal insulin.
  • It’s essential to remember that a pre-mix insulin must be given BEFORE meals. I have often come across patients switched from basal to premix insulin and continued to give the evening insulin dose before bedtime, i.e. several hours after supper. This is extremely dangerous as the short-acting component can cause low blood glucose during the night.
  • Adjusting the dose of pre-mix insulin can seem quite complex. As with basal insulin, this must be done according to trends and not according the reading on hand.
  • The dose of morning insulin is determined by how well the glucose readings are controlled during the day, so we look at the pre-dinner reading to decide.
  • The dose of the evening insulin is determined by the control of glucose overnight, so we use the morning reading to decide (similar to titrating basal insulin).

Insulin diary log

I ask my patients to keep a diary and send it in every week so that I can help with these dose adjustments until we have reached the target glucose levels.

BASAL BOLUS INSULIN

Basal insulins as described above.

Bolus insulins:

Short-acting regular insulins: Humulin R; Actrapid; Biosulin R

Rapid-acting analogue insulins: Humalog; NovoRapid; Apidra

This regimen aims to mimic the normal function of the pancreas: intermediate or long-acting insulin provides the background insulin needed and then short-acting insulin is given before each meal (but not with snacks).

This short-acting insulin can be adjusted at every injection according to the pre-meal glucose reading and food being eaten. People with diabetes on this regimen are often taught carbohydrate counting. This is a method of quantifying how much carbohydrate is in a meal.

The HCP works out a ratio of insulin dose per carbohydrate portion and this is calculated at each meal. In addition, high glucose readings need to be corrected, so people with diabetes are taught a correction formula to bring the blood glucose back to an average of 6mmol/l (see calculation below). This sounds much more complicated than it is.

With some practice, people with diabetes can use this skilfully. It’s mainly used in Type 1 diabetes but is appropriate for anyone using a basal bolus regimen.

CALCULATION OF A BOLUS INSULIN DOSE

Pre-meal dose of insulin = food dose + correction dose, where

Food dose = (total carbohydrate portion) ÷ carbohydrate insulin ratio

Correction dose = (blood glucose – 6) ÷ sensitivity factor

The carbohydrate insulin ratio and sensitivity factor will be provided by the healthcare provider.

Constant communication with doctor

At my practice, we would not expect patients with diabetes to adjust their own insulins in those first weeks. They are asked to send readings in regularly, weekly to begin. We often revert to recording the readings the old-fashioned way with a diabetic diary as seen above and the patient can email or text that to me or the diabetic nurse educator (DNE). Some patients are using newer glucometers with Apps that can be uploaded and sent in.

HbA1c readings

Overall diabetes control is assessed with an HbA1c measurement every three to six months. HbA1c is a complex of glucose attached to haemoglobin in the red blood cell. This allows us to see what the average glucose is over the previous three months and gives a more comprehensive idea of control compared to the glucometer.

If the HbA1c and glucometer readings don’t correlate, then we must look at where in the day the blood glucose is increasing. To do this, patients will be asked to do 360’ testing or seven-point profile testing. For three days, they must test before and two hours after each meal as well as before going to bed (seven readings). This can help decide the next step in insulin management.

Getting the best response from insulin therapy

Up to this point, emphasis has been made on the choice of insulin and finding the correct dose. However, it’s important to remember the following when aiming to get the best response from insulin therapy:

  1. Timing of the insulin injection
    1. Basal insulin should be given at the same time every day. There is only a leeway of an hour either way.
    2. Pre-mix insulin should be given 30 minutes BEFORE breakfast and dinner.
    3. Bolus insulin should be given 15-30 minutes BEFORE each meal. No insulin will work in time if given at or after the meal.
  2. Changing of needles used to inject insulin should be done every THIRD injection. If looked at under a microscope after three injections, the needle has a barb on it and can cause significant trauma to the skin and subcutaneous tissue.
  3. Rotation of sites is essential. Repeatedly using the same site will result in a condition called lipohypertrophy, the accumulation of fat at the injection site causing a lump.

If your healthcare provider suggests it’s time to start insulin, do not see this as a negative in your diabetes journey but as a tool to continue in good health in your life journey.

MEET THE 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.


Insulin pump therapy in SA

Dr Louise Johnson gives us a breakdown of the insulin pump therapy available in South Africa.


Diabetes is rapidly becoming a major health epidemic in most regions of the world. All Type 1 diabetes patients and a significant number of Type 2 diabetes patients require the use of insulin for controlling blood glucose.

There are several varieties of insulin and many different injection regimes that can be used. Despite the availability of insulin vials and pens, the acceptability for patients and the glucose readings that are obtained with single or multiple injections regimens is not to the desired level.

This is where insulin pump therapy also known as continuous subcutaneous insulin infusion (CSII) comes in.

Continuous subcutaneous insulin infusion

Insulin pumps were introduced half a century ago. They utilise short- or rapid-acting insulin types only. This minimises variability of administration and reduces the chances of glucose fluctuations. Pump therapy has progressed to the level of mimicking physiological demands.

Pumps are programmed to deliver basal or background insulin. This is usually the same as the previous long-acting insulin. Basal insulin delivery happens automatically. It delivers a programmable dosage per hour every 24 hours; it’s tailored according to the glucose profile of the person.

The insulin requirements may be affected by a person’s physiology, exercise, work schedule, concomitant medications, and illness.

Most patients utilise multiple basal rates over a 24-hour period. There are some that only uses one rate. Most pumps have the capability of programming basal rates that can be used in special situations as a temporary basal rate. Your physician will determine all this.

There is also a bolus function. This is calculated according to the carbohydrate ratio used for carb counting. The person should administer the correct amount of total carbohydrates consumed to the pump and it will then automatically calculate the exact number of insulin and deliver it. This will be administered over minutes to a few hours. Insulin boluses cover meals and correct high blood glucose levels.

How is insulin delivered?

This happens via a plastic cannula connected to the pump on the one side and a single subcutaneous site with a connection on the other side.

The subcutaneous site is the same as a person would inject insulin in the fat tissue on the abdomen. The site needs to be changed every three to four days to prevent infection or inflammation.

Only rapid-acting insulin can be put into a pump. Usually the analogues work best (Novorapid, Humalog and Apidra).

Advantages

  1. Programmable insulin delivery allows closer match with physiologic needs.
  2. Uses only short- or rapid-acting insulin. This minimises peaks and absorption related variability.
  3. Use one injection site every three to four days. This reduces variation in absorption and treatment burden from multiple injections.
  4. Reduction in glucose variability and improve glucose control.
  5. Decrease the risk of severe hypoglycaemia
  6. Improved quality of life and treatment satisfaction.

Type 1 ideal candidate

The ideal candidate for initiation of pump therapy is a motivated patient who is knowledgeable in the important aspects of diabetes self-care and desires better glucose control.

The patient should be familiar with carbohydrate counting and have knowledge about pump technology.

However, a pump is neither a cure for diabetes nor does it function autonomously without intervention or input.

Patients should be clear about the fact that the pump is a highly-specialised gadget. It requires constant interaction from the wearer.

It’s important to regular monitor blood glucose and communicates with a professional pump team. This will predict long-term success.

Indications for insulin pump therapy

  1. Suboptimal glucose control despite multiple daily injections. You do not reach your target HbA1c.
  2. Frequent or unpredictable hypoglycaemia and hypoglycaemia unawareness.
  3. Dawn phenomenon. That is the early rising of blood glucose between 2am and 8am.
  4. An active lifestyle with strenuous physical activities.
  5. Children and young adults who typically desire fewer restrictions and more flexibility.
  6. Growth spurt of adolescents.
  7. Preconception planning and pregnancy
  8. The presence of gastroparesis. (Abnormal slow movement of food from stomach to the rest of the bowel).
  9. Hectic lifestyle with frequent travel between time zones.
  10. Shift work.
  11. Need for flexibility in the amount and timing of meals.
  12. Patients that are sensitive to insulin and need very small dosages.
  13. Type 2 diabetes patients with increased insulin requirements.

Types of pumps in South Africa

We currently have three different companies with have a variety of pumps. Each have its own pros and cons. It’s important that your medical team is familiar with your pump. Medical aids sometimes prefer to pay for certain pumps.

Medtronic 780 G is the newest of the Medtronic pumps and is a hybrid close loop system.

Tandem T slim 2 is the newest of the Tandem pumps and is also a hybrid close loop system pump.

Roche Accucheck Combo is a traditional pump.

Understanding hybrid close loop pump systems

In this type of system, the insulin pump “talks” to a continuous glucose sensor. The pump has a built-in algorithm; this allows the insulin to increase or decrease according to the blood glucose to attain the target. The only interaction the patient has with the pump is the input of carbohydrates consumed. Currently this is the ‘top’ pump to have if possible.

Disadvantages

  • Pumps are technology and they can break or malfunction
  • Cannulas can kink and this will stop insulin delivery.
  • Infusion sites can get infection or inflammation. This will cause rapid development of extreme hyperglycaemia, especially in Type 1 diabetes patients.

Pumps are not yet perfect but they are very close to it. Safeguards, such as alarms that warn of delivery problems or low amount of insulin in the pump reservoir are now standard features of insulin pump.

Dr Louise Loot

MEET THE 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.