Post transplant diabetes

Yesterday I saw a patient with post transplant diabetes. I guess this is a good time to share a presentation on this topic I did a while ago, when I was in final year DM. The purpose is to make it easier for those who make a presentation on this topic to get started and to give a brief 2 minute refresher for the time strapped DM/MD pg going for exam.

Here’s the link to download the presentation as a pptx file

Post transplant diabetes


Walking beer factories !

Let’s start with a fundamental question – do you need to drink to get drunk? The surprising answer is no. Our body can make ethanol, thus making us walking beer factories. This phenomenon of endogenous ethanol production is called Auto-Brewery.

Auto-brewery is fascinating and very few doctors would think about this when encountering a patient who they think is drunk. Imagine the plight of a teetotaler trying to persuade the doctor that he is drunk,but not because he drank 🙂

How does this happen?

While very little is known about the auto-brewery syndrome, the following are considered necessary for its development

  1. High carbohydrate intake
  2. Prolonged stay of the food in the gut due to
    1. Gut dysmotility
    2. Surgical alteration , creating a ‘vat’
  3. Colonization by organizations which cause fermentation of carbohydrates
    1. Candida spp
    2. Sacharomyces cerevisiae – both due to prolonged antibiotic therapy


  • Medical
    • Chronic -The above 3 conditions tend to coexist in one of the commonest patient groups- obese diabetics. They may have autonomic dysfunction leading to intestinal dysmotility. Many of these patients also have Non Alcoholic Fatty liver disease -NAFLD. If a subgroup of these patients have endogenous ethanol production, their liver disease may well be ‘alcoholic’. There is very little data to support or refute this claim. In a study of blood alcohol levels, the diabetic patients were found to have 5 times as much BAC (blood alcohol concentration) as non diabetics (1). While the authors conclude that this is not enough to be picked up in routine breath analyser tests, the implications of such long standing increased BAC on liver are intriguing, to say the least.
    • Acute- Acute alcohol intoxication has been reported in a patient who hasn’t touched alcohol in 30 years (2) ! Some cases of metabolic encephalopathy in which no apparent cause is forthcoming may be due to ethanol intoxication from endogenous production. However we must be careful to rule out the usual suspects and should only entertain this diagnosis if BAC is high in a teetotaler or abstinent patient.
  • Medico legal
    • It is unlikely that endogenous ethanol production is severe enough to cause positive breath analyser test in cases of drunken drive (3). This line of argument also doesn’t hold much water in the courts if the published medico legal literature is anything to go by.

To conclude auto-brewery is an interesting medical oddity. As the mechanistic insights are still not very clear, we must be cautious in making this diagnosis. Whether auto-brewery is the culprit in a subset of diabetic patients with neuropathy with NAFLD is not known.

Further reading

  1. Hafez EM, Hamad MA, Fouad M, Abdel-Lateff A. Auto-brewery syndrome: Ethanol pseudo-toxicity in diabetic and hepatic patients. Hum Exp Toxicol. 2017 May;36(5):445–50.

  2. Welch BT, Coelho Prabhu N, Walkoff L, Trenkner SW. Auto-brewery Syndrome in the Setting of Long-standing Crohn’s Disease: A Case Report and Review of the Literature. J Crohns Colitis. 2016 Dec;10(12):1448–50.

  3. Logan BK, Jones AW. Endogenous ethanol “auto-brewery syndrome” as a drunk-driving defence challenge. Med Sci Law. 2000 Jul;40(3):206–15.

Has my glucometer gone bonkers?

A common problem faced by many diabetic patients is the ‘perceived’ or real inaccuracy of their glucometer. This happens when the glucose reading on the meter is widely different from what is expected – say a very high value after a usual walk that is known to reduce blood glucose or a very low value in a patient who’s not experiencing any symptoms.

When such aberrations occur the common tendency is to blame the glucometer. Some people claim that their glucometer has gone bonkers!However that may not be a good idea.

There are several standards that a blood glucose meter should satisfy before coming to the market. You can access these ISO standards here. Specifically 99% of readings must fall within zones A and B of the Consensus Error Grid for type 1 diabetes. Let me explain further.

What is an error grid ?

When a glucometer is validated for clinical or regulatory purposes, the values measured by the glucometer is compared with a reference method (method comparison study). A scatter plot is drawn and a grid is superimposed on the scatter graph.

For example, a pair (300 mg/dl, 550 mg/dl) represents a large numerical discrepancy, but is unlikely to result in an adverse clinical outcome since in either case the patient will probably receive insulin. On the other hand, a discrepancy of 70 vs. 110 could have serious clinical consequences since hypoglycemic therapy may be administered in the former case, possibly erroneously.

An error grid basically gives clinical context to the discrepancy in measurement between the two methods. Two major systems are in use : Clarke’s error grid and Parke’s(consensus) error grid.Both systems place paired reference/test values into one of five zones – “A”, “B”, “C”, “D” or “E” based on the expected clinical impact of the discrepency.

This is how Clarke’s and Parke’s Error grids look like 




For regulatory clearance , 99 % of the values must fall within zone A or B. So glucometers from standard companies have a high bar to clear before they reach our hands.

In spite of all this, occasionally we get patients complaining of discrepant values. Let’s see what can be done if we get discrepant values. By going through a check list of questions, we can identify whether the reading is inaccurate and the source of inaccuracy. 

The inaccuracy can result from three sources – patient, glucose strip and glucometer

  1. Wrong technique of pricking – usually minor
    • Did you clean your fingers before pricking? This is common in children with type 1 diabetes/ the active type 2 diabetics who play/engage in outdoor activities. A finger that is covered with grime is unlikely to be accurate.Hence accurate cleaning is essential.
    • Did you squeeze your finger hard? Squeezing fingers is not recommended because it leads to estimation of blood glucose in the interstitial fluid, not the capillary blood(the one we want). Choose a lancet , or prick with the appropriate size needle to ensure you get enough blood.
  1. Problem with glucose strip – uncommon
    • Did you store the glucose strip properly? There is a reason glucostrips are packaged in black plastic containers. Exposure to excessive heat/moisture can lead to inaccuracy in glucose readings. Make sure that the glucose strip is stored correctly.
    • Have you used the correct code ? Most modern gluco meters don’t require you to set the code manually.In case you are using a older version of glucometer, it is important to input the correct code. Otherwise wrong readings are possible.
    • Has your strip expired? Glucose strips, like medicines, have expiry dates. It is important to make sure that the strip you are using is not an ancient one.
  2. Problem with glucometer
    • Did you drop the glucometer recently? Glucometers are sensitive devices which should be handled with care. Dropping the glucometer from a height , (like any other electronic device) can result in glucometer malfunction.
    • Water/heat or any other physical damage to the glucometer? Physical damage to the glucometer is easy to detect. You will have to replace the glucometer in this case.

    If you have done all the steps correctly, and still have abnormal values, you need to don the Sherlock Holmes hat and see why it is happening.

    Here are the steps to be followed

    1. Recheck again – this is the first step. If the second value is very similar to the first one, then perhaps error is not random. This of course, doesn’t mean that the value is correct. There could still be a systematic error (an example is a weighing machine that always shows you are 5 kg heavier:-)) . Systematic errors rarely happen in glucometers, but they are possible.
    2. If the repeat value is significantly different, (in spite of keeping all other conditions constant), then the technique is not the culprit. So the issue is with either the glucose strip or the glucometer.
    3. You have two optionscheck blood glucose with the nearby reliable lab or use a control solution. Control solutions contain a known amount of glucose and if the glucometer is working properly, it should be able to give the expected value. It is sort of like measuring a known 1 kg stone in an electronic weighing machine.If the machine shows abnormal reading, then something is wrong with the machine. However control solutions are not commonly used. Most pharmacies don’t event stock them and the glucometer doesn’t come with the control solution. The solution has to be purchased separately (can be got online) and once opened can be used for 3 months only. However they can be conveniently used at home.


    • Standard glucometers go through stringent quality checks
    • Whenever a discrepant glucose measurement is seen, think of the different levels where things can go wrong – patient, strip or glucometer
    • When in doubt measure in a standard lab or use a control solution.
    • As usual, proper patient education can avoid unnecessary confusion 

    Further reading

    1. Parkes, J. L., S. L. Slatin, S. Pardo, and B.H. Ginsberg. “A New Consensus Error Grid to Evaluate the Clinical Significance of Inaccuracies in the Measurement of Blood Glucose.” Diabetes Care 23, no. 8 (August 2000): 1143-48
    2. Pfutzner, Andreas, David C. Klonoff, Scott Pardo, and Joan L. Parkes. “Technical Aspects of the Parkes Error Grid.” Journal of Diabetes Science and Technology 7, no. 5 (September 2013): 1275-81


Hope for the “helmet” times

I have shared this one before in social media. Luckily Journal of Social Health and Diabetes was willing to publish it. If you haven’t read about the heroic work of my friends in managing a patient with unusual features of Type 1 Diabetes, you can read it in the link below.

Hope for the “helmet” times

Sweet, naturally

Diabetic patients can have a a hard time getting used a life without their favorite sweets. Sweeteners aim to circumvent this perplexing problem by delinking sweet taste from calories. Ironically artificial sweeteners became popular much before the natural ones. The belief was that if the substance can taste sweet and has no calories, it was a godsend. Unfortunately that claim proved too good to be true for many artificial sweeteners.

Just because they didn’t have calories didn’t mean the artificial sweeteners were safe. Paradoxically they have been found to be linked with obesity in some cases. Even though these no calorie sweeteners aren’t metabolised by our body, the gut microbiome can metabolize it and the end products are toxic to the “good bacteria”. This eventually leads to “dysbiosis” (a change in the composition of bacteria in our gut) and defeats the purpose of taking sweeteners.

Stevia Saccharin
Monk fruit Acesulfame
Miracle berry Aspartame
Kateme fruit Cyclamate
Licorice root Neohesperidin
HFCS (high fructose corn syrup)

With continuing demand for low colorie/non nutritive sweeteners, the natural ones have become more popular. Some of the main ones are

  1. Stevia
  2. Monk fruit (only extracted active ingredient can be used)
  3. Kateme fruit (probably not available in India)


This is the most well known of the natural sweeteners and the best studied. Stevia is a plant native to Paraguay and Brazil and is intensely sweet – 250 times sweeter than sugar. The glcosides – stevioside and rebaudioside are responsible for this sweetness.Unlike other natural sweeteners stevia is easy to cultivate in urban homes and its leaves can be used fresh , without the need for industrial processing. Also because of its low cost, stevia has the potential to be the most popular natural sweetener.

In fact Stevia was featured in a recent TV show. (the video is in Tamil, but the visuals are fairly self explanatory)

The two important questions are

  1. Is this safe?
  2. Is this effective? ( for reducing weight/ reducing blood sugar/reducing cardiovascular risk)


  • Stevia started off on a bad note, with concerns of carcinogenecity, but the concerns were later found to be baseless. Consequently FDA has given it a GRAS status (Generally recognized as safe). In India, FSSAI has approved the use of stevia in various food products.
  • Like any other plant, stevia has a lot of other ingredients and the safety label given by FDA is for purified rebaudioside.
  • Data on pregnant women and children with type 1 diabetes are scarce – thus caution must be exercised.


  • Stevia has mixed reports of efficacy, but in reality it has not been studied as extensively as prescription drugs or even artificial sweeteners.
  • While the short term studies don’t show great benefit with Stevia in terms of glucose reduction, the longer term studies (>40 weeks) tend to show reduction in weight.

Monk Fruit


Monkfruit(Siraitia grosvenorii) is a subtropical melon grown in South East Asian countries. Legend has it that the fruit derives its moniker by virtue of having been cultivated by Chinese monks more than 800 years ago. Since the fruit is hard to store, it is usually not used in the fresh form. It becomes brown on drying. From the dry fruit, its active ingredient is extracted. These are glycosides – mainly mogrosides.(siamenoside and neomogroside are other glycosides)

Safety :

Rigoroussafety studies have not been carried out – partly because of the difficulty instandardizing the production of monk fruit extract. US FDA has given a GRAS-Generally recognized as safe (3)notice about its safety.


There aren’t any long term studies on the efficacy of monk fruit, perhaps due to the difficulty in cultivation and the expense of import.

Katemfe fruit


This is much less popular than the other two natural sweeteners. Very few long term studies exist. I am not sure if this is even available in India.

The following table compares the common natural sweeteners

Availability Better Difficult to obtain
Cost $ $$
Safety GRAS (generally regarded as safe) GRAS
Efficacy Short term : no benefits/ harms Limited data, but not much different from stevia
Long term : weight reduction
Use Fresh leaves can be used Fresh fruit cannot be consumed
Ease of growing Easy Difficult
Other uses Purified stevia extract doesn’t have other uses Purified form doesn’t have other uses

Things to remember

  • Just because something is natural doesn’t mean it is safe (even strychnine is natural). While occasional use of sweetener , for example in a family function , is likely to be safe, usage in pregnant women or children should not be encouraged
  • Taste matters – all natural sweeteners , to varying extent, produce some aftertaste. Ultimately long term use hinges heavily on taste and you can only experiment to see which taste you like
  • Purity and standardization – just like any plant product, it is very hard to standardize purity and manufacturing practices. Since the commercial products are not as well regulated as drugs, you might be getting stevia laced with glucose or other sweeteners too. Read the label, but don’t fully trust it if the company is unknown. You might be better off using the fresh leaves
  • “Side effects” – purified extracts are safe for consumption because they are predictable. But the plants has several other active ingredients which have not been well studied, even though they have been in use for centuries. While the modern reductionist approach is one we are used to, I wouldn’t discount the advantage /disadvantage of consuming the whole leaves/fruit products. Consider this – if you analyze Coke/Pepsi, you will get sugar as the main ingredient, and a variety of others in tiny quantities. Perhaps even the order of adding these ingredients matter, which is why their formula is a closely guarded secret. Just by extracting the main ingredient(sugar), we won’t get Coke/Pepsi. In the same way, the complex interactions between the ingredients in a plant can have unpredictable good /bad effects. Being alert is the prudent option.

Non nutritive sweeteners may never become mainstream. But for the diabetic with a sweet tooth, they may be a godsend. By following common sense, we can avoid the bitter aftertaste, in more ways than one.

5 Rupees medicines and diabetes


Story time.
Once upon a time, there lived a conman. He decided to make some quick buck. He sold 1000 lottery tickets, each at a price of  $ 5. The bumper prize was $1000. So you could buy a ticket for 5 and if you are lucky , get $1000. He marketed it, saying if you lost, you just lost 5 $. But think of what you will get if you win – $1000. 200 times your initial investment. Or an insane profit of close to 20000%. There was  a mad rush to buy the lottery. The numbers on the ticket were 8 digits long and were alphanumeric. It was a clever ploy. Had he numbered the tickets sequentially from 1 to 1000, people would easily remember that. His alphanumeric system precluded that possibility. A few days later, the results were released. Photos were flashed of the winner getting a cheque.Many who had bought the tickets were disappointed. But they went about their lives as usual. After all, the loss was tiny. One of the guys who lost it was a little suspicious. No one he knew had won the prize. He decided to dig deeper. When he confronted the conman with questions, he was told to prove his theory in court ( a legal battle that would ruin him financially) or take his $5 as refund. The poor guy got his $ 5, while the conman made  $ 4995. No one actually won the lottery.

Recently I was asked by a patient about the  effectiveness and side effects of two drugs  called BGR -34 and IME-9. I must admit I hadn’t heard of those drugs.As an allopathic doctor and an endocrinologist, the name sounded odd to me. Such names are reminiscent of  candidate molecules being tested. Nevertheless I decided to dig deeper and find out more.

BGR -34 is an ayurvedic medicine developed jointly by National Botanical Research Institute (NBRI) and Central Institute for Medicinal and Aromatic Plant (CIMAP) — both funded by government. BGR 34 stands for Blood Glucose Regulator with 34 active phyto ingredients. The NBRI website unfortunately doesn’t give much details. The drug is touted as having 67 % ‘success rate’ based on animal studies. No human data are available. The senior principal scientist AK Rawat has said, “The drug has extracts from four plants mentioned in Ayurveda and that makes it safe”. I have no idea how that will make a drug safe ! Tell me if you do.

IME 9 stands for Insulin Management Expert. It’s  developed by another government body called CCRAS (Central Council for Research in Ayurvedic Sciences). This one doesn’t have much information listed either.
I decided to check for any publications on BGR 34 and IME 9. Unfortunately I coudn’t find one. Next I proceeded to the AIMIL pharmaceuticals page( the company that is licensed for manufacturing and marketing this drug). When I tried to see the products page, it told me helpfully that I was not authorized to view that page and that I should login! Why should I login to view a company’s drug landing page? I ve never had to ‘login’ to see the details of any drug in the past!


Even more brazenly, the privately owned entity has used DRDO logo in its website to give itself an ‘official’ veneer. In an event attended by Dr Man Mohan Singh and JP Nadda, the company has also been awarded the AYUSH company of the year!


So I turned to the mother of all search engines, Google for help. There were a few blog posts. One of them had lamented that the drug had actually increased the blood glucose in his mother ! Now the ridiculousness of checking blog posts for evidence of efficacy is an injury. To watch youtube videos on the same topic is insult to that injury. Nevertheless, I did that too. The comments on the YouTube videos were mostly negative[There are tools to make formal ‘Sentiment Analysis’, though I haven’t done here]. Yet one common thread was the feeling that native medicines were side effect free. How many more years will it take for people to understand that there is no such thing as a drug without side effects? (Paracelsus said this thousands of years back)

All drugs are poisons. Only dose makes the difference.

                                                                   – Paracelsus

Curiously these drugs are marketed as 5 rupee medicines for diabetes. Metformin and sulphonylureas, the two most commonly used diabetes medications with a huge evidence base, cost much less than 5 rupees. Yet no one had ever marketed them as 5 rupee wonder drugs! There’s  even a Facebook page for this drug with a rating of 4.5 ! Ever seen Facebook pages for drugs before? Me neither. It is available in Amazon, Ebay and Snapdeal, not to mention some less well known online retailers.
Just like we can’t accept anecdotal evidence for the efficacy as valid, we can’t accept anecdotal evidence for the lack of efficacy as valid too. As much as I would hate it, I was forced to say that this drug’s efficacy was ‘unknown’.More importantly the safety was questionable too.
We have no data at all.So who is tasked with regulating this market? Why is our tax money used to fund such projects incompletely? What prevents them from testing the drugs? How are they made to trend in pill selling apps like 1 mg? Why are they marketed as government approved drugs? Why are these drugs marketed to patients directly?Too many questions , too few answers.
At the end of the day, diabetes is as much a disease of behaviour as it is of beta cells. The lure of a cheap drug without side effects with no need for any pesky life style changes , becomes irresistible to the common man. Thus clever marketing always works (just like it works for pharma on doctors). Direct to consumer marketing must be banned, regardless of the system of medicine practiced. For the simple reason that the patient isn’t qualified to make an informed choice. Otherwise we will always have the lottery tickets and dubious drugs.

Science shouldn’t be sacrificed at the altar of business.

Further reading


Light pollution: the silent pandemic

I got up last night and was amazed to find my room awash with light. The photons were blazing in from the cracks of the window. There was enough light to read a news paper, but I didn’t feel like doing it. There was a time in the past when our nights weren’t this illuminated. There were no skyscrapers spewing light or an avalanche of insomnia inducing mobile phones or tablets. Early to bed and early to rise was a virtue. Unfortunately, that habit has all but disappeared from our lives.
I know parents who feel proud that their 3 year old can navigate an iPad like a pro. Some lament about the need for YouTube to feed their children. Social media sites are flooded with questions like “I am still a sperm which has just started swimming. Is it too late to learn programming?”. The biggest boon of our generation has also become our biggest bane. We have literally made day out of our nights.
Light pollution is the phenomenon of excessive exposure to light(predominantly the blue end of the spectrum) in the night.While mobile addiction contributes to light pollution, it is a much larger problem, involving excessive lighting even outside our homes.

Light intensity is measured in lux – the number of photons per second that strike our retina. Natural background night light is 0.1 to 0.3 lux. A typical shopping mall emits 20 to 30 lux ! That’s about 200 to 300 times the background light. A mobile phone has an even bigger impact -because unlike a shopping mall, we directly stare at the mobile phone.(or tablet). Nocturnal creatures are most affected by this phenomenon – there are instances of birds being stunned by bright lights in the buildings,hitting them and falling to their deaths. Even the bats, which use echolocation to move about tend to avoid well lit areas.
Our rods and cones are overstimulated by exposure to light in the night , sending our circadian rhythm into a tailspin. This results in suppression of melatonin, a hormone produced by the pineal gland. While our body is resilient enough to handle occasional sleeplessness, it is ill equipped to deal with constant light in the night. After all our cave dwelling ancestors too got up in the night for various reasons, but they never switched on their phones to check the twitter feed. Research shows we have intrinsically photosensitive ganglion cells that contain melanopsin, whose only job is to tell the brain the ambient light levels in the night. These are affected mainly by blue light – the kind emitted by our beloved gadgets.
Sleep fragmentation doesn’t affect melatonin levels, but exposure to light does. Not only does it affect melatonin, but also a host of other hormones ranging from growth hormone to cortisol.
But do these biochemical effects have any lasting impact? Yes they do. This light induced disruption of our serene hormonal milieu has been linked to obesity,diabetes, depression and cancer. The data are sparse in Indian context(much like any other problem) but there is no reason to believe that Indians are resistant to the effects of light pollution. If anything, because of our higher background genetic risk of diabetes and metabolic syndrome, light pollution may pose a greater risk to us!

So what can we do to cut down the risk?

  • Learn more about light pollution to realize how serious the problem is.
  • Enforce a lights out policy with your children. Early to bed and early to rise has a sound scientific basis!
  • Avoid bringing laptops/iPads/mobiles into bedroom. Bedroom is meant for sleeping, not playing with mobiles.
  • For patients in ‘hyperlit’ hospital wards, advise eyemasks. Try and dim the light as much as possible. The nurses may not be comfortable at first, but a little cajoling might work.
  • If you live in apartments (better still as some secretary ), lobby for lights out during bird migration periods.
  • If working with computer in the night is something you can’t avoid , install F.lux in your computer. It is free, open source and is available for Windows,Mac ,Linux and all major mobile operating systems. It warms up the color display of your monitor, shifting it from blue light to a more orangish hue. Reduce the brightness of your laptop to the lowest possible level at nights.
  • Create awareness about FOMO – the fear of missing out. The notifications you receive on your phones are engineered to get you hooked. Never sleep with a mobile phone near your pillow, unless you are on duty.
  • On a lighter note,be a stargazer and encourage it in your children. You could buy a telescope and teach kids about the various constellations.Make sure you learn them first 😉 just kidding.Beyond the health benefits, there is a certain magic in gazing at the spangled heavens from your terrace with kids. If not the starry sky, they will love you for it.

Like many people, I have struggled with implementing some or many of these. As a borderline laptop junkie myself, it was hard to avoid my machine, but I have somehow managed it ! Anyone can do it with some effort and you will get to sleep better.

There’s no simpler way to put this – we are meant to sleep in the night.