SGLT2 inhibitors & euDKA risks…why?

AusDoc reports a bunch of people saying watch out for DKA in patients on SGLT2 inhibitors who may be having surgery or are unwell. You know those tongue twisters dapagliflozin, empagliflozin, ertugliflozin, etc. These drugs block sodium-glucose cotransporter 2 in the kidney to inhibit renal glucose reabsorption through an insulin-independent mechanism, which in turn lowers glucose levels through increased urinary glucose excretion. More details on the pharmacology can be found here. Thus SGLT2 inhibitors helps control diabetes type 2.

Now if you believe the pharmaceutical industry hype these drugs will prevent diabetic patient from having heart attacks and keep them off dialysis. For more useful information on this have a read of this post on BroomeDocs by Casey Parker.

These drugs have had their problems. After overcoming my fears of bladder cancer and concerns about increasing toe amputations and Fourniers gangrene, this new hazard may reduce my enthusiasm for these drugs.

So how does a drug which works to make you pee out sugar cause DKA? It would seems that this is a different type of DKA, and as none of the warning letters satisfied my curiosity for Why, I’d thought I’d hunt for a theory or two.

I am used to managing DKA in DMT1. You know, the teen who thinks that 24 beers on a Saturday night is cool and forgets to take his insulin for the next 2 days. Gets dumped in ED by his concerned mates, looking very sick (abdominal pain, shortness of breath, fatigue, nausea, and vomiting) with a glucose of 30 and pH of 6.9. Or, a young 5 year old whose parents have missed the gradual weight loss, drinking lots, peeing lots and then turns up with belly pain. This kind of DKA happens because there is no insulin to help metabolise sugar so the body switches over to fatty acid metabolism with ketoacids (eg., acetoacetate and β-hydroxybutyrate) being produced. The result is metabolic acidosis.

DKA caused by SGLT2 inhibitors is a little bit different. Glucose levels decrease with SGLT2 inhibition because you pee it out. Because glucose triggers the release of insulin, the drop in glucose levels results in less insulin production. This is good, and helps explain the drugs beneficial effect on weight unlike diabetes drugs which just make the pancreas work harder, like sulphonylureas. SGLT2 inhibitors also act independently on pancreatic alpha cells, further increase plasma glucagon levels and stimulate hepatic ketogenesis. It has also been speculated that they may decrease renal clearance of ketone bodies (making a urine dipstick for ketones less reliable), further increasing the concentration of ketones in the body. Thus a new acronym arises to describe euglycaemic or euDKA. This paper explains more of the science of this problem.

There is a also a case report of empagliflozin unmasking type 1 diabetes in someone who was originally thought to have type 2 diabetes. In such a person, positive GAD antibodies would change the diagnosis to LADA.

So, now I need to tell my patient who are on these drugs to come in for a checkup when they are sick and not eating or drinking well and to make sure their surgeon and anesthetist know what they are taking.

Finally for all you herbal fans, the first non selective SGLT inhibitor was extracted from unripe apples and the bark of apple trees way back in 1835. Unfortunately, it is broken down in the stomach and one if its metabolites causes severe diarrhoea making it not very useful to treat diabetes.

Shingle me this, shingle me that….no thank you!

Singles is caused by the same virus which caused chickenpox in children, varicella zoster virus. Once that illness is completed, the virus lays dormant in the nerve cells. When you get older or your immune system is compromised by illness or medication,  the virus reactivates and travels along nerve to cause the classic skin disease of shingles,

In last few weeks I have seen a number of patients with shingles were there has been a delay in diagnosis.

This may not surprising as the first signs of the illness may be headache, fever or fatigue. Sometimes it may be prickly, burning, throbbing, or stabbing sensation in a patch of skin anywhere on the body.

The first rash may look quite innocuous as in this photo below.

The classic description of the progression of shingles rash is from small red bumps (erythematous papules) to clear blisters (vesicles) to small pimples (pustules) which break open and crust over, usually over seven to ten days.

The rash often follows a specific pattern on the skin, and often stop in the midline. It follows the dermatomes for the right or left side of the body. If you want to learn more about dermatomes watch this video.

Shingles can be very painful, it may threaten sight and other senses depending on the affected nerves.

Anyone who has shingles will tell you how uncomfortable it is. Actually, uncomfortable may be an understatement. The bad new is that the pain may persist even when the rash has healed. This is known as post herpetic neuralgia which may perists for several months, and require medication to keep under control. Other complications of shingles include pneumonia, a stroke or brain infection called encephalitis which may be fatal. Some people go on to have recurrent shingles.

Antiviral drugs may help hasten the recovery from shingles, but need to be started early in the course of the illness to be effective, ideally within the first 72 hours of the onset of the rash.

A vaccination (Zostervax) is available which costs about $180 but is subsided by for those between 70 and 79 years. It is recommended for anyone over 60. Vaccination reduced the herpes zoster by 51%, post herpetic neuralgia by 66% and reduces the severity of the pain.

Zostevax is a live vaccination and should not be used if you are immunocompromised. To do so risks a potentially fatal disseminated zoster infection. A potentially safer inactive, recombinant vaccine called Shingrex maybe marketed in Australia in the next few years.

The fluid that leaks from the vesicles does contain the virus, so it may cause infection in those who have no immunity to shingles, that is those who haven’t had chickenpox as a child or been vaccination. Pregnant women, newborns babies and immunocompromised people are particularly at risk. Until the rash has crusted over, it is considered infectious. Keeping the rash covered and washing hands helps reduce the spread of the virus.

If you think you have shingles, see your doctor as soon as possible. You can find out more information about shingles here.



Warning: This website and the information it contains is not intended as a substitute for professional consultation with a qualified practitioner.

It may not come as a surprise but as a doctors I use Google quite a bit. There are of course other alternative search engines; “Just Google it” has been adopted into our lexicon, whilst “DuckDuckGo it”  or “Dogpile it” doesn’t have the same ring, although some would argue they are better. But getting back to the topic.

During a consultation, I may turn to my computer and search Google for a picture to illustrate a point, for example, I think you have measles – see here is a picture of the rash in question. My consulting room is set up so we can both see the computer screen. That makes it hard to surreptitiously do a quick search as you talk. Don’t ask what happens when the computer isn’t working! My doodles are not art, but I do have books!

When it comes to making a diagnosis, I haven’t yet had to enter “headache, fever, rash and cold hands”, well at least not in front of a patient. By the way if you do, you get a screen full of sites suggesting you have meningitis. In fact you get 10 million results. There is a lot of information out there in the Internet. When I was a younger my Mum would probably resort to her nursing text book to work out what was ailing us kids. Life was so much simpler there – books, libraries…

Obviously there will be a lot of duplication of information on the Internet. Some information will be country specific. For example, an American website may suggest taking two acetaminophen for a headache, which translated into Australian is take two paracetamol.  Of course, there is nothing wrong at looking at health resources based in other countries. But remember, different countries have different disease prevalence. If you plus headache, fever and rash into a health site based in the Congo you may diagnose yourself with Ebola or Malaria.

The challenge is quickly access reliable and easy to understand medical information that doesn’t lead to a site trying to sell you something, or one that makes unproven claims or is just plain wrong.

If you have seen this image at the bottom of a website, usually right down the bottom, with lots of other small print, it may provide you with some degree of veracity. Health on the Net certification offers a compliance certificate for websites that goes a way to reassure the reliability of the website.

Logo certificat HONCode


Here are my suggestions for reputable health care information

For general health

Health Direct is a government-funded service, providing quality, approved health information and advice. It has links to many other resources. It also has a Symptom Checker Tool (not a real doctor) which when I put it to the test with my headache, fever and rash, did advise I call an ambulance, use a cold compress and lie down quietly. Thankfully, it didn’t tell me I was going to die from meningitis so I didn’t have to panic. Each State Health Department has its own website offering health advise.

The Department Of Health has a webpage which links to a wide variety of health concerns for consumers.

For children’s health problem, here a couple of that are useful, Children’s Health Queensland Hospital and Health Service and The Royal Children’s Hospital Melbourne

I think the Royal Women’s Hospital Melbourne has a good website for pregnancy and women’s health questions. Jean Hailles is another good site for women’s health.

For parents try the The Australian Parenting Website

For skin problems, I think Dermnet a great website from New Zealand is very comprehensive.

The Cancer Council which has been around since 1961 providing education and support.

For Men’s health problems, Healthy Male is a good starting point.

For contraception advise, each state has its own Family Planning organisation. In Queensland this is named True. Marie Stopes is also a useful source of information.

Now I could go through each body part and nominate a site to access. For example,

Hearts at The Heart Foundation

Lungs at the Lung Foundation Australia

Bowel and liver at Gastrointestinal Society of Australia

Kidneys at Kidney Health Australia 

Allergies at Australasian Society of Clinical Immunology and Allergy

Eyes at Vision Initiative

Brains at The Brain Foundation and if it isn’t working well Dementia Australia

Pancreas (okay diabetes) at Diabetes Australia

For infectious diseases, I like to head to the US to look at the Centre for Disease Control website

For information on Mental health problems there are a number of websites. Beyond Blue, Black Dog Institute, Sane, and Headspace, just name a few. Head to Head is a Government website that tries to help people through the information overload.

For the health and computer literate, to search medical information on a specific problem, Google Scholar in conjunction with US National Library of Medicine Pubmed, are useful to find journal articles that may be useful.

If you want to test the information found in your search result, you can always see if it has been mentioned in Quack Watch!

Now I haven’t mentioned searching for answering using Web 2.0, where you throw your question or rash photo out to the crowd, hoping that someone will come up with a sensible answer. OMG that’s absolutely syphilis, may not be what you want to hear about the red spot on your hand! I use Web 2.0 a bit when I’m stuck and it has been quite useful. I am connected to doctors through Facebook and Twitter around Australia and the world.

So for your next consultation, come along better prepared, use Google by all means for I may learn something too.


What is Vaccine Hesitancy?

Parents care about their children. I care for mine. That is why my children are immunised.

With immunisation uptake in Northern Queensland for 1-5 year old between 92 and 95%, I don’t often meet parents who decline to immunise their children.

In our modern society we are mostly detached from life threatening complications of common vaccine preventable illnesses. It was our great-grandparents generation who were more used to seeing small children dying from diphtheria, tetanus, or measles. Most Australian have no fear of smallpox or polio because we don’t see these illnesses anymore in our community. This edition of Ockham’s Razor talked about the early attempts to control infectious disease in Australia.

Only a small percentage of parents out rightly declined to vaccinate their children. Others have heard the charismatic social media gurus, fear adverse effects, mistrust the motives of government and the influence of pharmaceutical companies.

There are who those who don’t wish to engage in a discussion, and those who are hesitant about making a commitment to immunise. I would like to think as a GP, I have time to explore concerns and provide information that may provide reassurance.

I have put together this post to enable a more informed discussion and open the door to immunisation.

Here is a link to three video resources which I have found helpful.



The Australian Academy of Science produced this document in 2016 to help to improve community understanding of the principles of immunisations. This addresses the science, safety and efficacy of immunisations.

“Immunisation Myths and Realities” is another useful resource. It helps to address certain questions raised by those who are opposed to immunisations.

Questions answered include

  • Vaccines are unsafe
  • Vaccines are not adequately tested
  • Vaccines contain foreign proteins
  • Vaccines are contaminated with foreign viruses
  • Vaccines contain toxic additives

Another Australian resource on vaccine safety is Are vaccines safe?

Many studies have been completed which investigated the link measles, mumps and rubella vaccination and thiomersal to autism. The good thing about these studies is that the data show no relationship between vaccines and autism. The Autism Science Foundation has an extensive list of resources.

I hope this takes away the hesitancy.




Mandatory Reporting Deters Health Practitioners Seeking Mental Health Help

This is a copy of letter I have sent to support removing mandatory reporting from Queensland Health Practitioner legislation.

Mr Aaron Harper MP
Chair, Health, Communities, Disability Services and Domestic and Family Violence Prevention Committee

I believe that the proposed Health Practitioner Regulation National Law and Other Legislation Amendment Bill 2018 still fails to meet the stated purpose of ensuring that health practitioners have confidence to seek treatment. Rather than clarifying the matter, the ill defined “substantial risk of harm” potential creates more confusion. Who defines this, and if I were to define it as not “substantial” who is to say a lawyer or politician may define it otherwise. This lack of clarity continues to be a barrier to Health practitioners seeking effective treatment. This lack of clarity may cause more harm as earlier interventions may be deferred out of fear of reporting.

I believe that Western Australian model should be sufficient for all of Australia. That is, voluntary reports based on their professional and ethical obligations to report matters that may place the public at risk of harm.

There should be no distinction between the treatment of a registered health practitioner and that of a patient from any other occupation. Just like all other people in Australia, any health practitioner who becomes a patient should be entitled to discuss their health with their doctor in a strictly confidential environment.

A report to AHPRA can lead to a lengthy and stressful wait even if finds no case needs to be answered. Whilst awaiting the result of an investigation and determination, the burden of stress only increases on the health practitioner.

Ultimately, the suicide of a untreated health practitioner fearful of a mandatory report, who does not seek help becomes a tragedy for the person, the community, colleagues and the practitioner’s family. This is a real problem in Australia with both young and old doctors taking their lives because of mental health problems. As you maybe aware you cannot always tell a person is struggling or considering suicide by just looking at them. They have to feel that they are in a safe and confidential position to ask for help. This applies to the butcher, baker or the neurosurgeon.
Health professional suicide is a world wide problem. Canada, UK, USA, South Africa …. As you may be aware between 2001 and 2012, 369 suicides by health professionals were recorded in Australia. Drs John Moutzouris, Chloe Abbott and Andrew Bryant are just three doctors who took their own life since that data was collected. Tragically there are more.

Beyond Blue in 2013 surveyed 12,000 doctors and one third were concerned about seeking treatment that may have an adverse effect on their registration and ability to continue to work in the field they were trained. Half suggested lack of confidentiality was a barrier to seeking help.

I again ask Mr Harper that Queensland adopt the Western Australian model to protect the health professionals who serve our community. I am not aware that this model has put the public at risk of harm in that state.

Let me share this link to Dr Pamela Wible’s Ted Talk on doctor suicide in the US

The photo above is a new Dad hugging the doctor who delivered his baby.

But I think it shows how much we are all human and we all need the freedom to have a hug and not get reported if we are not OK. 

If you are in an emergency, or at immediate risk of harm to yourself or others, please contact emergency services on 000, or Lifeline Australia 13 11 14. 

Coronor reports

Reading a Coroner report, I sometimes feel part voyeur with a macabre interest but feeling guilty about invading someone’s death. However, I reconcile that by using a Coroner’s report as a way of learning. With my medical education, as I read the story unfolding, I sometimes think to myself. “no, no no, check the blood pressure”, or “He is clearly septic and the temperature means nothing. Give the antibiotics, Get him to ICU – now!” It is like when you watch a horror movie and the teenagers split up look around the haunted house alone. “No you stupid fools stay together”, except these are real people falling through the gaps and being harmed. I sometimes place myself in the deceased story and think would I have done that, omitted this? “If only…”

The office of the coroner dates from approximately the 12th century under the English judicial system. In its early years, the coroner’s duties were mainly administrative. The coroner kept the king’s records, and collected revenue. Over the years the role expanded to include investigating deaths. If a person was found dead the coroner was notified and a jury was assembled where the jury examined the body. Evidence was heard and the jury’s verdict taken. If a verdict of murder or manslaughter was returned the coroner seized his property for the king. For a discussion of the the early history of the coroner, this article by Charles Gross is informative. In Australia, the Coroner’s jurisdiction has been in place since the foundation of the NSW colony. In his commission of 2 April 1787 Governor Phillip was granted power to ‘constitute and appoint Justices of the Peace, Coroners Constable and other necessary officers’. The earliest recorded inquest in New South Wales dates from 1796 in which three magistrates including Samuel Marsden inquired into the death of a convict who had been shot.

Today, a Coroner investigates a death in order to determine the identity of the deceased and the date, place, circumstances and medical cause of death. It is stated that the Coroner’s role is to find out what happened, not to point the finger or lay blame.  To assist a Coroner will call upon experts in the field, police, and witnesses, including doctors and nurses who may have been involved in a deceased person’s care. Importantly, not all people who die are investigated by the Coroner. And sometimes findings are not disclosed to the general public. The Coroner after deliberation will makes recommendations to prevent the same think happening again, that is to avoid a preventable death. In the past I have seen arguments about how impractical some of these recommendations are. For example,  one Coroner suggested GP’s should not prescribe fentanyl, which was an interesting statement to make when an non-GP had prescribed the medication that lead to the person’s death. Some reports are more controversial than others. Newspapers have the habit of summarising a Coroner’s report to sell a story, so journalist’s reports should never relied upon to make an opinion without reading the original report. The Inquest into the death of Hamid Khazaei recently completed by the Queensland Coroner, Terry Ryan provides so much more than what can be gleaned from various newspapers. As there is a delay between death and the Coroner’s recommendation, the media may speculate all sorts of stories. A Coroner report can provide closure to family and friends of the dead person.

I have been involved in the death of a number of patients whilst working within the hospital system and had to present evidence to the Coroner in one case. That information is all on public record. Back in October 2002, a man fell from his bed in hospital and died shortly afterwards from a massive intracranial haemorrhage. I was the intern on the team looking after him on that final admission. Reading back through the Coroner’s report today, I can see essentially how all the holes in the Swiss cheese lined up which lead to a preventable death.

To ensure that the as many as possible are informed of coroner recommendations, many reports are available for reading. Of course, some of these reports pertain to deaths due to violence, misadventure and have no medical staff intervention at all.

If you have an interest, here are the links to public Coroner reports.


(to see coroner reports, type “coroner” into text search)

New Zealand

Northern Territory



South Australia




edit 9/10/18

The Clinical Communiqué is an electronic publication containing narrative case reports about lessons learned from Coroners’ investigations into preventable deaths in acute hospital and community settings. The Clinical Communiqué is written, edited, published and distributed by the Department of Forensic Medicine, Monash University and the Victorian Institute of Forensic Medicine.

cfDNA, ala NIPT

Oh no another acronym change!

Technically non-invasive prenatal testing aka NIPT was always a misnomer as a needle into your arm is still invasive. Now it seems we need to get used to cell free DNA testing or cfDNA. Again  technically the test is done on circulating cell-free fetal DNA which is really ccffDNA, but lets keep it shorter. An important consideration is most of the DNA comes from dead placental cells which means a discordant NIPT  oops cfDNA, may arise with mosaicism.

For a great update on what this tests and what it does have a look at this ANZJOG paper published this month.

Some highlights for cfDNA:

  • screening is suitable as a primary screening test for all women – if they can afford it (see below)
  • screening has a sensitivity of ~99% and specificity of >99% for trisomy 21 ie.,  very high detection rate and very low false positive rate (0.1%). It is only marginally less sensitivity for trisomy 18 and 13
  • sensitivity and specificity are less precise for twin pregnancies
  • does not correct guarantee correct gender and may not be as useful for sex chromosome aneuploidy
  • less sensitive for microdeletions and trisomies
  • is a screening test, it is not diagnostic. Victorian women with a high probability cfDNA result, fetal aneuploidy was confirmed by invasive fetal testing in 64%, with 36% of results being false positives
  • is useful as follow‐up screening following non-reassuring combined first trimester screen (CFTS) prior to an invasive diagnostic testing, ie. amniocentesis
  • first trimester ultrasound has benefits in addition to aneuploidy detection, including confirmation of dates, viability, number of fetuses and detection of structural anomalies. Although many women will have an ultrasound prior to paying for the cfDNA test to ensure accurate dates.
  • the required fetal fraction threshold for cfDNA ranges from 2–4%. The higher the fetal fraction the more accurate the test, hence the test is recommended after 10 weeks. Maternal weight may reduce the fetal fraction (7% in women over 100 kg and 50% over 160 kg)
  • delaying cfDNA until 12 weeks will reduce the costs of screening aneuploid pregnancies that are destined to miscarry eg., 6% of trisomy 21 pregnancies
  • cfDNA screening performs better than CFTS for aneuploidy detection thus CFTS is not recommended as this increases the false positive rate but not the detection rate
  • ultrasound ‘soft markers’ of aneuploidy need no longer be considered indications for invasive testing if the woman has had a low probability cfDNA result
  • meta‐analysis has shown procedure‐related miscarriage risks following invasive as 0.11% (one in 909) for amniocentesis and 0.22% (one in 454) for chorionic villus sampling. If doing an invasive test, I would always ask the doctor doing it what their own rates are.

Cost for the basic NIPT/cfDNA test do vary a little but have become a lot less expensive since they were introduced into Australia.

Percept from Victorian Clinical Genetic Service $449 (but needs to be done as a specific collection centre, so travelling to the collection centre needs to be factored in)

Harmony from Sonic Genetics (and 12 affiliated pathology labs) $425

Generation from Dorovitch/Laverty/QML/Western Pathology $395

Panorama from IVF Australia and (affiliated IVF services in NSW, Qld and Victoria) $450

The expanded tests for each of these assessing gender and microdeletion etc, obviously cost more. None offer a money back guarantee for errors in gender assessment! Some offer a free retest if fetal fraction is too low and no result can be give.

The cost of a cfDNA is however a considerable expense for many patient. For example, Lisa Hui has has shown that over 90% of referrals for an NIPT in 2013 were from private practice. Susan Maxwell in an editorial in the ANZJOG has called for consideration of public funding for NIP/cfDNA testing.  MBS provides a subsidy for maternal serum screening and combined first trimester screening as well as invasive prenatal diagnostic procedures and karyotyping. Although, as many families may discover there may be a considerable gap to these tests too.

I do wonder given there are 300,000 successful pregnancies in Australia each year, what cost the various pathology labs would charge if there was public funding available. Economy of scales that work for pizza should provide a more equitable solution to providing a better quality test to Australian families.