Healthier hearts in Type 2 diabetes

Dr Angela Murphy educates us about new drugs that treat Type 2 diabetes and decrease the risk of heart disease.


I asked several of my patients what concerns them most about having diabetes. The answers were fairly consistent: high sugar levels, losing vision, amputations, kidney failure and needing dialysis, and dying early.

However, cardiovascular disease (CVD) which consists of heart attacks, heart failure and stroke is the cause of complications and death in two-thirds of patients with Type 2 diabetes. It would make sense to have treatment for diabetes that not only decreased the blood sugar but also the risk of heart disease.

In 2008, the Federal Drug Administration (FDA) in the USA stipulated that all new diabetic agents would need to prove that they do not increase the risk of CVD. This was in the wake of a medication (Rosiglitazone – insulin sensitiser) that had to be withdrawn due to adverse cardiac effects. Only Pioglitazone remains available from that group.  

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The first of the new medications to market – the gliptins or DPP1V inhibitors – showed they were safe but did not improve cardiac outcomes. However, two new agents have, remarkably, done just that: empagliflozin (Jardiance) and liraglutide (Victoza).

1.Empagliflozin

This is a sodium glucose transport receptor (SGLT)-2 inhibitor. It acts by stopping the reabsorption of glucose in the kidney. Excess glucose is excreted in the urine which results in the lowering of blood glucose levels. This is accompanied by an estimated loss of 280kcal/day which contributes to a decrease in weight. There is also fluid and sodium losses resulting in blood pressure lowering and improvement in heart function.

The excellent results from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose (EMPA-REG OUTCOME) trial, allowed the FDA to add another indication for treatment with Empagliflozin.  Empagliflozin is now registered:

  1. as an adjunct to diet and exercise to improve glycaemic control in adults with Type 2 diabetes mellitus.
  2. to reduce the risk of cardiovascular death in adult patients with Type 2 diabetes mellitus and established CVD.

In this ground-breaking trial, over 7000 patients with Type 2 diabetes were shown to have had a 38% relative risk reduction (RRR) in cardiovascular death with empagliflozin compared with placebo. There was also a statistical reduction in hospitalisation for heart failure, as well as a drop in all causes of death.

CANVAS programme

There are two other drugs in the SGLT-2 inhibitor class, viz. dapagliflozin (Forxiga) and canagliflozin (Invokana). The recent CANagliflozin CardioVascular Assessment Study (CANVAS) programme also reported a significant reduction in cardiovascular disease and hospitalisations for heart failure.

Over 10 000 patients with Type 2 diabetes were enrolled in the study with a third of the patients not yet having documented heart disease but they had to have two or more risk factors (hypertension, hyperlipidaemia or obesity).

This is exciting to know that the protection is also for patients who have not developed heart disease.

A concern with the use of Invokana was the reported increase in amputations, mainly of the toes but some leg amputations too. Patients with diabetic foot problems should probably not receive Invokana.

CVD-REAL study

It is possible that the SGLT-2 inhibitors as a class will be cardioprotective. The Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL) study shows just that.

This is a study that looked at 154 528 patients who received a SGLT-2 inhibitor from their own doctor for the first time. The results were compared with other classes of glucose-lowering drugs. Again, there was a significant improvement in hospitalisation for heart failure and reduction in all cause of deaths.

Only 13% of the patients had established cardiovascular disease which implies a benefit for the broader Type 2 diabetes population. In the USA, canagliflozin was the drug most used whereas in Europe it was dapagliflozin. This supports the idea of a class effect.

2.Liraglutide

This is the second diabetic drug to receive cardiovascular approval from the FDA. Liraglutide is a glucagon like peptide-1 (GLP-1) agonist.

GLP-1 is a hormone released in the gut in response to food. GLP-1 then stimulates the pancreas to produce insulin. In Type 2 diabetes, this system is sluggish so a great deal of research has focussed on restoring this important system.

Liraglutide is a synthetic version of GLP-1 and when given (via subcutaneous injection), it raises the GLP-1 levels to above normal. In addition to the glucose lowering effects from stimulating the pancreas, liraglutide slows down gastric emptying, dampens the appetite centre and protects the heart muscle from damage in the event of a heart attack.

LEADER trial

The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results—A Long Term Evaluation (LEADER) trial showed a 13% reduction in the combined endpoint of heart attack, stroke and cardiovascular death compared with placebo.

The official FDA approved package leaflet now reads that liraglutide is indicated:

  • as an adjunct to diet and exercise to improve glycaemic control in adults with Type 2 diabetes mellitus.
  • as an adjunct to standard treatment of cardiovascular risk factors to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal heart attack, or non-fatal stroke) in adults with Type 2 diabetes mellitus and high cardiovascular risk.

Current label indications

It is important to note that at this time the FDA label indications for these two drugs, Jardiance and Victoza, is for those people with diabetes and current heart disease.

The results of the CANVAS trials, as well as other ongoing trials, will allow the FDA to consider indications in the future for these medications to help reduce heart complications in those people with diabetes who have risk factors for but no known cardiovascular disease.

Should a Type 2 diabetes patient change his/her medications?

It is always important to review a prescription, especially with patients with diabetes. If sugar control is poor, if more cardiovascular risk factors have been identified, or if a patient has had a heart attack, stroke or been hospitalised for heart failure, it would be very valuable to consider changing or adding these new classes of medications.

Availability

Liraglutide, empagliflozin and dapagliflozin are available in South Africa. However, they are not available in the public sector and medical aids may not always fund them. Hopefully, as evidence continues to build of the importance of the extra benefits of these glucose lowering medications, they will become more accessible for all patients with Type 2 diabetes.

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 as well as a specialist with the Centre for Diabetes Excellence (CDE) network.


Agents for Change by Noy Pullen

Happier healthier lunch boxes for children

Why does a 30-second video called Japanese school lunches puts the rest of the world to shame have more than 42 million likes in a few days? What is the project The Grab 5 doing right when they can claim: ‘There definitely has been an improvement in behaviour and children are healthier now than they were a year ago’? Lunch boxes are changing. Lunch time is seen as part of education, not a break from it. Will South African schools join in happier healthier lunch boxes?


Criteria

The World Health Organisation and the Basic Dietary Guidelines recommends that at least five portions of rainbow coloured food are consumed every day as part of a balanced diet. This advice is easy to understand and remember in theory, and psychologically strengthening, because it does not ask us to give something up. But, sadly, this is not happening.

The Diabetes South Africa (DSA) Agents for Change team knows that in the rural areas, most meals consist of brown and white (very little colour). According to a British project, The Grab 51, some children do not even have one coloured piece of fruit or vegetable per day.

Agents for Change model

We, at Agents for Change, target health providers, patients and families living with and working with diabetes and share creative ideas for changing habits. At a recent site visit with our international funders, World Diabetes Foundation, their project manager, Hanne Strandgaard, accompanied us to the Red Cross War Memorial Children’s Hospital in Rondebosch, Cape Town. We interacted with parents and children at the diabetes clinic and demonstrated simple effective ways of presenting healthy, economical and enticing food options.

Dr Steve Delport, the consulting endocrinologist, told us that his little patients kept darting in and out of his rooms to fetch another snack. The snacks definitely passed the taste test, especially the green grapes which Hanne placed on tooth picks and called green balloons. Her ‘boiled egg mice’ were also popular.

Happier healthier lunch boxes
‘Boiled egg mice’ with Vienna or ham slices for ears and chive tails prepared by Hanne Strandgaard from World Diabetes Foundation, Denmark.
Happier healthier lunch boxes
Noy Pullen replenishing a platter for the food demonstration of healthier snacks at the Diabetes Clinic at Red Cross War Memorial Children’s Hospital in Cape Town.

The fathers were most interested in tasting all snacks and finding out how to make them. Those who took part in this demonstration also had fun choosing from the available variety of tomatoes, cheese blocks, Vienna rounds, grapes, pawpaw, apple slices, and building their own ‘toothpick towers’. They were overjoyed at being given a copy of the booklet Rainbow in my kitchen14, which contains ideas of how to shop for a basic pantry, and recipes using whatever you have.

Self-feeding vs spoon-feeding

According to recent studies on eating habits of babies, nutritional ‘schooling’ starts long before schoolgoing age. Early healthy nutrition develops healthy balanced thinking processes and develops the subtle sense of knowing when you have had enough to eat.

Recent UK studies show that spoon-fed babies are more likely to become obese children6. If someone else shovels in the food (with the best motives), this bypasses this subtle sense. Let the children guide the way to what and how much they want to eat. The study shows that the self-feeders had a lower obesity rate than the spoon-fed children. Allowing them to choose from a selection of finger foods means they learn to regulate the amount they eat and are less likely to become overweight. They are also more likely to opt for healthier options than spoon-fed babies, who tend to favour sweet things.

The study suggests infants weaned through the baby-led approach learn to regulate their food, resulting in lower body mass index and a preference for healthy foods. This has implications for combating the well-documented rise in obesity in society. Tam Fry, from the National Obesity Forum, said, “Babies have this wonderful rapport with their mother when breastfeeding and indicate how much milk they want and when they are ready to go on to solids.” Adding, “It is important they experience all five food groups and experiment with variety as much as possible. If half of it finishes on the floor, so be it – the value of experimentation in the early months of nutrition is incalculable and babies won’t willingly starve themselves.”

The study comprised 92 children who had been weaned on finger foods and 63 who were traditionally spoon-fed. Parents filled in questionnaires on how their children had been weaned, including how often they ate certain foods when they were aged six months and six years.

The Grab 5 project research

Aiming for a holistic approach to school lunches and healthy tuck shop, they found:

  • Well-fed pupils are calmer and concentrate better.
  • Well-fed pupils have fewer days off due to illness.
  • School food activities, such as tasting events and playground markets, are good ways to involve parents and community groups in school life.
  • School food activities, such as cooking, growing and tasting, are often good ways to engage children that are otherwise reluctant to get involved in school life.
  • Serving meals and snacks increases school revenue and children develop a positive attitude towards what they eat.
  • Curriculum links with food projects and events bring subjects alive and are responsible for healthier more socialised children1.

How can we change the school food environment?

  • Free fresh fruit and vegetable food tasting tables offered to pupils at the tuckshop. This would be a gradual means of finding out what they like and introducing them to new foods textures, colours and combinations.
  • Integrating talks on nutrition about all food groups and their service to the body – energy foods (carbohydrates), protection foods (vegetables and fruit), nutrients (milk products), building foods (meat and other protein) and food that protects our nerves (fats)4. Tasting tables prepared by children in the classroom.
  • A visit to a fruit and veg shop or food farmer.
  • Introducing practical demonstrations of how to put food together in balanced, fun healthy and economical combinations. This could be done in the form of fund raising projects, and help to wean children off the unhealthy options offered in tuck shops.

  • Introducing all aspects of food into the curriculum in each age group. This would involve maths – budgeting, ordering and invoicing, being able to apply the concept of a planned balanced meal; science – cooking, processes of heating and freezing; biology – learning the various components of hygiene, digesting and nutrition, portion sizes etc.; life-skills – co-operation through supervised preparation of and cooking of simple dishes and clearing up; geography – cultural differences in serving and eating; horticulture – encouraging children to ‘grow their own’ simple bean or spinach plants and to demonstrate sprouting of various pulses and seeds for immediate micro-nutrients.
  • Developing new standards for the tuck shop stock e.g. practical fruit and vegetables options, bread sticks, plain popcorn or sprinkled with healthy herb salts, crumpets with honey, natural yoghurt with chopped fruit and toasted snacks5,6,7,8,9,10..
  • The more children taste different kinds of fruit and vegetables, prepared in different kinds of ways, the more they will learn to like them. It is a learning curve for children to try new foods. Exploring new tastes is an educational adventure in itself.

A working model for schools

In Japan, children’s lunch time is part of the curriculum, where fresh simple meals are made from scratch by pupils in rotation for less than $2,50 (roughly R35) per day. They study the menu and cultural history, and assess the nutritional value. The children prepare, cook and serve the meal and then clear up. This teaches cooperation and manners. They harvest from their own gardens where possible. It is no wonder that they have one of the lowest obesity rates in the world.

As the first verse of the song The Greatest Love of All says:

I believe the children are our future
Teach them well and let them lead the way
Show them all the beauty they possess inside
Give them a sense of pride to make it easier
Let the children’s laughter remind us how we used to be

Please contact Noy Pullen if you would like more information on her resources: linoia@web.co.za or 072 258 7132.