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.

https://www.thinkingparticle.com/image/unripe-apple-banjar-valley

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.

https://bpac.org.nz/BPJ/2014/March/herpes.aspx

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.