Talk:Diabetic ketoacidosis/Archive 1

Comment

The section "Ketone body production" is very poor; it needs rewritten. Ketones needn't be desribed as "fuel for the brain" - they are used in the production of acetyl-CoA. —Preceding unsigned comment added by Dermotmallon (talk • contribs) 10:54, 10 June 2008 (UTC)

more re ketone bodies

The mechanism section does not clearly explain the pathophysiology of DKA. I am not an expert, but I believe the release of acidifying ketone bodies should be focused on.

name

Why does it say

and ketone bodies (acids)

Ketones aren't acids, are they? AxelBoldt 05:19 Feb 26, 2003 (UTC)

Ketone bodies include acetoacetate and b-hydroxybutyrate. Both of these compounds have acidic hydrogens on carbon 2, because of the adjacent carbonyl function. —The preceding unsigned comment was added by 137.53.182.171 (talk) 22:51, 27 April 2007 (UTC).

A ketone is a particular chemical type in biochemistry. The ketone bodies here are three chemicals, two of which are chemically ketones. One is not. Large quantities of these do acidify body fluids. The term comes from 'ketones of the body' and originated at a time at which the ketone breath, quite a distinct smell, was the distinguishing feature clinically. Hence the ketone 'bodies' terminology which is otherwise weird in biochemistry. Sorry it took me so long to notice this enquiry.

ww

Also, while ketone bodies are often considered acids, only two of the three are actually acidic: beta-hydroxybutyric acid and acetoacetic acid (acetone's only functional group is a ketone, so it isn't an acid). --David Iberri (talk) 20:21, 4 April 2007 (UTC)

reconciliation

This article needs to be reconciled with main diabetes mellitus article. Alex.tan 03:47, 5 Feb 2004 (UTC)

more on names

ww is incorrect here. They are called ketone bodies because they come from ketones. They are called ketoacids because they are both acid and ketone (well, beta-hydroxybutyrate is actually acid plus alcohol, but acetoacetate is both, and they're ketone bodies because they come from ketones.)

Devilbunny 22:02 18 Oct 2004 (UTC)

DB, The history is claimed to be as I suggested. The match between the chemistry and the terminology is the confusing bit.ww 21:42, 26 Nov 2004 (UTC)

Type 1 DKA episode

I've just returned from hospital aftr suffering dibetic ketoacidosis caused by insulin resistence due to a laceration infection (I've had type 1 diabetes for 20 years and have it under excellent control)... between 10am and 10pm i took 180 units of fast acting insulin into my body (Novorapid) on a normal day i take roughly 25-30 units of insulin. in less than 12 hours i went from having normal blood glucose range of 4mmol-7mmol to being seriously ill with ketoacidocis (dka). I don't have much background knowledge but as is written here type 2s can have dka, just not very often and it's also not unheard of for non diabetics to have a type of 'dka' (i'm aware that its often attributed to shock?) --this comment added 19 March 2007--

difficulties with recent edits

Recent edits have taken the position that lack of insulin causes DKA. And that the insulin/glucagon value is the key issue. And that glucagon affects cells generally and not merely those with mobilizable glycogen stores. etc All of these are questionable statements and should be reviewed. ww 21:42, 26 Nov 2004 (UTC)

I agree. For example, non-insulin dependent diabetics are initially insulin resistant and do not have an insulin deficiency. Such patient may also develop DKA, often precipitated by underlying infection. --Mvdw 15:30, 27 January 2007 (UTC)

WRONG. Type 2 diabetics do NOT develop DKA precicely because insulin is present. A complete lack of insulin is a requirement for DKA as even a tiny amount of serum insulin inhibits hepatic lipase, the enzyme which generates the acidic keytone bodies. Type 2 diabetics develop HONKC, which is a similar, but very different, clinical entity. —The preceding unsigned comment was added by 70.50.115.2 (talk) 00:24, 31 January 2007 (UTC).

Firstly, the term Type 2 diabetic is misleading, since many so-called Type 2 diabetics are insulin dependent. Secondly, a complete lack of endogenous insulin is virtually incompatible with life. The diagnosis of DKA rests upon hyperglycemia, acidosis and ketonuria. According to Kumar & Clarke, hyper-osmolar non-ketotic coma and diabetic keto-acidosis are two ends of a spectrum, rather than separate entities. Mvdw 15:31, 6 February 2007 (UTC)

Concur with Mvdw here. DKA is not unknown in Type 2, even some who still have some endogenous insulin production. ww 00:30, 8 February 2007 (UTC)

Everyone is a little wrong here. DKA is the direct result of both an insulin deficiency and glucagon excess. Conditions of hyperglycemia, acidosis, and ketonuria develop as a result of insulin deficiency. However, a complete lack of insulin is not a requirement for DKA. The very small % of Type 2 diabetics developing DKA will do so because of insulin deficiency. Please consult Harrison's if you are still unclear on the subject. glotris173 22:10, 22 February 2007 (UTC)

more trouble

I've just changed a sentence in the ketone body production section, as it was incoherent as it stands. Nevertheless, this section is still very dubious. It does not correspond to my understanding of the process (competitive inhibition of a step in the fat metabolism chain by a step in the protein degradation chain whilst making glucose from amino acids), but I hesitate to make canges when there are better infomred editors available. I invite them to step in and clean up what has become a most unsatisfactory article. ww 20:05, 24 April 2006 (UTC) hyerglycaemia and DKA are separate entities coexisiting due to inadequate insulin.130.209.6.40

Symptoms

There is no mentioning of the symptoms of DKA here, the article used to list them before though. I think it should be added as this article simply presents the pathophysiology of DKA. Jack Daw 19:45, 25 September 2006 (UTC)

Additionally, the section of symptoms that has been inputted is a complete mess. The syntax is terrible, and there are some major grammatical errors. I would attempt to change it, but some of the bullet points include contradictory statements and I don't know enough about DKA to know which parts to remove. Could somebody who is more knowledgeable please fix it?72.196.98.106 01:54, 28 June 2007 (UTC)

poor explanations

Some of the content is badly explained, irrelevant and even inaccurate, for example the last paragraph - the reason is not that the cell does not have enough glucose; it is that insulin inhibits hormone-sensitive lipase, the enzyme responsible for triglyceride breakdown in adipocytes, which results in release of fatty acids into the blood for subsequent oxidation in the tissues. Lack of this inhibition due to lack of insulin results in excessive triglyceride breakdown thus excessive fatty acids in the blood, and resultant ketoacidosis through mechanisms I unfortunately don't have time to go into - a well-informed person or expert is, I think, needed to clean up the article. Yazza 18:57, 14 November 2006 (UTC)

Concur. This article contains a goodly amount of fact, some relevant and some irrelevant, and still more speculation as to causation (or implication as to causation). It is generally the latter which causes the problems with the article. It needs help badly. I will add a low quality tag to it shortly if we haven't done better. ww 21:42, 26 December 2006 (UTC)

type 2 DKA

There is an impression that Type 2 diabetics cannot experience DKA. This is an error. Quite a non-trivial number of Type 2 diabetics require insulin, and whatever the exact mechanism of DKA -- and will some informed person PLEASE go throuhg this article and clean it up in this respect) it is connected with lack of internal insulin production. It is a clinical fact, aside from anything else, that Type 2 diabetics do report to Emergency rooms with DKA.

This is the reason for the rollbakc made today. ww 13:29, 28 May 2007 (UTC)

It looks like someone has made the article go back to something along the lines of having no insulin is the reason for DKA. I disagree. I'm a newly diagnosed Type II. I presented DKA to the ER as my first diabetic episode. The endocrinologist consult informed me that it's quite common for Type II's to first present as DKA. From what the article says, type II's who have "lost their ability"--I was on insulin for a little over 2 months, and the endo had me cutting back weekly in order to not have persistant hypos, and am now off of it completely. So unless you can lose the ability to create insulin when your Type II and then regain it again I would think there was insulin in my system.

According to Dr. H. Peter Chase, M.D. (From his publication Understanding Insulin-Dependent Diabetes, 9th Edition)

Chapter 14 Ketonuria and Acidosis(Diabetic Ketoacidosis or DKA) bear with me as this material is dry and kind of long...

Taken verbatim:

" Causes of Ketonuria and Acidosis

One "emergency" in diabetes, low blood sugar(hypoglycemia), was discussed in chapter 5. The other emergency in ketonuria, the appearance of moderate or large ketones in the urine, which can lead to acidosis. The measurement of urine ketones is very easy(a dipstick) and was discussed in chpter 4. The lack of knowledge about when to measure urine ketones and what to do when they are positive, and and not having ketone sticks which have not expired available in the home, are the most common deficiencies in families referred to our center. These deficiencies can result in a serious episode of acidosis.

"Large" ketones are usually present in the urine for at least tour hours before the total body's acidity is increased (acidosis). Acidosis is very dangerous and people can go into a coma or die from it. It is the cause of 85% of hospitaliztions of children with known diabetes. The good news is that it is 98% preventable if people follow the instructions in this chapter and always remember to take their insulin shots. It is possible, with good knowledge and by following the instructions of this chapter, to never have a episode of acidosis.Acidosis can be prevented in a child who is known to have diabetes.

Ketonuria and acidosis are due to there not being enough insulin available to meet the body's needs. The three main causes are: 1)illnesses, 2)forgetting to take an insulin shot, 3)not enough insulin (see Table 1). With an illness, extra energy may be needed by the body. This cannot be made unless extra insulin is available to make the extra energy from sugar. If a shot is forgotten, insulin is not avaiable for the body. A lack of insulin could happen in a person coming out of the "honeymoon" period who has not had dosages adequately increased." -- This is the first three sections of Chapter 14, atarting on p. 137

I have had diabetes for 18 years and from my experince, you can indeed have DKA with insulin in your system and this seems to back me up. That diabetic kid 17:16, 8 June 2007 (UTC)

?? 'late symptoms'

If my blood sugar levels go higher than 12 sometimes I vomit, this is not only/always a symptom of late stage, life threatening ketoacidocis. You don't even have to be in diabetic ketoacidocis to vomit because of high BSL.

does anyone else agree that the 'signs and symptoms' refer to those of IDDM (type 1) and not DKA, which is an acute condition? ~~ —Preceding unsigned comment added by 130.209.6.40 (talk) 19:54, 25 October 2007 (UTC)

Stuff to do

I've not looked at this article closely before, but I can immediately see the obvious deficiencies. The most important document here is probably the ADA guideline (2006) doi:10.2337/dc06-9916. Much of what is written here can probably be sourced there, and anything that is not sourcable may actually not be worthy of inclusion. JFW | T@lk 12:31, 11 June 2009 (UTC)

This was in the article and should be reconsidered:

Management: refer to DKA flowchart in [1]. Also refer to full discussion in chapter in endotext.com ().

We don't "refer readers to" particular documents in such a fashion. JFW | T@lk 12:38, 11 June 2009 (UTC)

URL http://diabetesmanager.pbwiki.com/Hyperglycemic-Crises%253A-Diabetic-Ketoacidosis-%2528DKA%2529%252C-And-Hyperglycemic-Hyperosmolar-State-%2528HHS%2529-

Pushing this one further

I might just push this one as far as possible, having finally found some useful sources.

•  Done Signs and symptoms - try to avoid discussing treatment-related complications
•  Done Mechanism - this one needs shortening and may need some diagrams to make it all more informative; all the abnormalities are discussed in the ADA paper and Harrison's
•  Done Diagnosis - need to discuss the use of blood gases, U&E, and basic screening for sepsis and organ infarction; try to leave the more technical bits for the "mechanism" section
• Treatment - we need to discuss optimal rehydration strategies, bolus insulin versus no bolus, monitoring potassium and phosphate, lack of evidence for bicarbonate in most scenarios, and the complications associated with all of these
•  Done Prevention - consider starting a new section about "sick day rules" and so on
•  Done Epidemiology - there are probably numbers to be crunched here

This one should be up to GAC level fairly soon. JFW | T@lk 23:49, 14 June 2009 (UTC)

There might be a case for including the cost of DKA ($1 billion/year according to the ADA document). Could I ask everybody not to move the "criteria" section to the top (as WP:MEDMOS would demand) because it relies on concepts introduced in the previous paragraphs. JFW | T@lk 09:37, 5 July 2009 (UTC)

It sounds like the article needs a structural makeover. Pull those concepts out of their current locations and work them into the Criteria section, then put it earlier in the article. --Una Smith (talk) 17:30, 15 July 2009 (UTC)

Having now identified the EPSE and ADA documents concerning children I may need to update other sections as well. I try to spend as little time as possible on making distinctions between adults and children as the mechanism is essentially the same. We will need to discuss cerebral oedema in more detail and I need better references (see below). JFW | T@lk 00:30, 13 July 2009 (UTC)

Responding to a request for feedback from WP MED, my main thought is that diabetic ketoacidosis is not distinguished from ketoacidosis until rather late in the article, in the Criteria section. That should happen much earlier, so that readers read about signs and symptoms with the understanding that most are signs and symptoms of ketoacidosis, not necessarily diabetic ketoacidosis. Also, I am left wondering if someone who is diabetic can have an episode of simple ketoacidosis? I would like a clearer explanation of how treatment differs (if it differs) between ketoacidosis and diabetic ketoacidosis. The article states an episode of ketoacidosis sometimes leads to the diagnosis of diabetes; more explanation about that would be helpful. What fraction of people who experience ketoacidosis subsequently are diagnosed with diabetes? --Una Smith (talk) 17:27, 15 July 2009 (UTC)

Thanks for your feedback Una. There are only two other causes of ketoacidosis, which I will expand on earlier in the article. It is unknown how many people with ketoacidosis have DKA, but it is probably the majority. The high glucose levels usually lead to the diagnosis of diabetes (the other forms tend to cause low-normal glucose levels). The other forms of ketoacidosis are discussed on ketoacidosis, but they tend to respond to supportive treatment. JFW | T@lk 22:04, 15 July 2009 (UTC)

Cerebral oedema

There must be more content about cerebral oedema, which causes a full one-fifth of all deaths in children with DM1. I identified this paper, but I can't find it free and am not keen to fork out for it...

Glaser N (2006). "New perspectives on the pathogenesis of cerebral edema complicating diabetic ketoacidosis in children". Pediatr Endocrinol Rev. 3 (4): 379–86. PMID 16816806. {{cite journal}}: Unknown parameter |month= ignored (help)

I will ask the author if she could send me a copy. JFW | T@lk 17:28, 12 July 2009 (UTC)\

I can get the paper. I know the author. —Preceding unsigned comment added by Nimzodisaster (talk • contribs) 04:09, 23 October 2009 (UTC)

She has sent me the paper. Could I persuade you to read WP:SYNTH and WP:MEDRS? Your contribution has been temporarily removed because of issues. In general I don't think we should cite studies directly. JFW | T@lk 09:59, 23 October 2009 (UTC)

I am new to the Wiki editing process. What I attempted to do was provide background information on what is known about cerebral swelling in DKA without overt cerebral edema, then provide two independent references of observed cognitive deficits in children with a history of DKA. While it is true that these are not prospective studies that directly link a DKA event with the emergence of cognitive deficits, it seems not outrageous that an edit of the proposed text that retains the information, but in a way that does not push a causal mechanism, would be of ethical benefit to the Wiki's audience. --The observed deficits in children with a history of DKA is fact, and confirmed independently. How can we get this valid information out, without violating those principles of Wiki editing that you graciously pointed me to. Thanks. --Nimzodisaster (talk) 18:07, 23 October 2009 (UTC)

If a finding or theory is not discussed in a secondary source (such as the review mentioned above) it is probably not going to be appropriate to be discussed here on this general purpose encyclopedia page. I can't see the ethical angle here, to be frank. JFW | T@lk 19:38, 25 October 2009 (UTC)

doi:10.1007/s00247-007-0536-8 may be what you're looking for. JFW | T@lk 20:29, 26 October 2009 (UTC)

Insulin therapy

Comments: This below sentence is not a contrast of an arguenment but to seperate points:

´´Some guidelines recommend a bolus (initial large dose) of insulin of 0.1 unit of insulin per kilogram of body weight,[1] while others delay the initiation of insulin until fluids have been administrered´´ The other point is that usually once starts with fluids and holds off on insulin until the potassium is known. There have been a number of deaths were insulin was given before a potassium was known the patient become more hypok and died. Far from home therefore unable to get refs.--Doc James (talk · contribs · email) 19:32, 15 July 2009 (UTC)

I agree, but a guideline is a guideline. Most modern arterial blood gas machines will give potassium levels, therefore this is becoming less of a problem. Let me know if you find a good source.

Thanks for your other edits. I felt the content of "causes" had already been discussed elsewhere. Moreover, the reference (Eledrisi) was duplicated. JFW | T@lk 21:55, 15 July 2009 (UTC)

Yes agree. What was written under signs and symtoms is much better worded. Split it off. I will see what I can find. I know that this is the advice I have heard at confrences. It is not the high BS that kills you but low fluids and low K.--Doc James (talk · contribs · email) 02:44, 16 July 2009 (UTC)

The ADA guidelines say: ¨In adult patients, once hypokalemia (K+ < 3.3 mEq/l) is excluded, an intravenous bolus of regular insulin at 0.1 unit/kg body wt¨ Therefore added.--Doc James (talk · contribs · email) 19:03, 17 July 2009 (UTC)

The guidelines for insulin therapy in DKA point to an initial bolus of insulin being contraindicated due to increased risk of cerebral edema and lack of benefit. The most recent guidelines seem to point to 0.05-0.1 U/kg/hr IV insulin following the initial fluid bolus. Source: the 2nd one for the article and Dunger et al, 2004 Naranoth (talk) 23:32, 27 July 2010 (UTC)

GA Review

This review is transcluded from Talk:Diabetic ketoacidosis/GA1. The edit link for this section can be used to add comments to the review.

Did a review made a few corrections and I think this article passes. Congratualtions.

Final GA review (see here for criteria)

1. It is reasonably well written.

   a (prose):Very well written b (MoS (Med)): No important MoS ommissions

2. It is factually accurate and verifiable.

   a (references): Very well referenced b (citations to reliable sources): c (OR): The sources are reliable

3. It is broad in its coverage.

   a (major aspects): Yes b (focused): Remains focused

4. It follows the neutral point of view policy.

   Fair representation without bias: Yes

5. It is stable.

   No edit wars etc.: Yes

6. It is illustrated by images, where possible and appropriate.

   a (images are tagged and non-free images have fair use rationales): b (appropriate use withsuitable captions):

7. Overall:

   Pass/Fail:

--Doc James (talk · contribs · email) 04:54, 4 August 2009 (UTC)

Triglycerides

Using heparin to reduce triglycerides - not sure if this is actually common, let alone whether we should mention it! http://archinte.ama-assn.org/cgi/content/full/169/15/1439 JFW | T@lk 23:35, 13 August 2009 (UTC)

Mortality

The source for the "less than 5%" mortality figure gives the qualification "in experienced centers". The only reason for that qualification is that the overall mortality is higher. The true overall mortality would be better, but this is what we have now. If you quote that source, you need the qualifier. - JeffJonez (talk) 01:37, 15 March 2010 (UTC)

The figure <5% is mentioned in numerous other sources without the qualifier "in experienced centers". The Harrison's section mentions it without the qualifier. Why exactly are you making such heavy weather out of this? JFW | T@lk 03:05, 15 March 2010 (UTC)

I haven't seen any other unqualified numbers. Please change the ref to an unqualified percentage. As I said, the qualifier makes it appear as if the overall mortality metric is higher, otherwise the qualifier wouldn't be there. The quote should reflect the source... it's that simple. - JeffJonez (talk) 03:30, 15 March 2010 (UTC)

DKA is a poorly studied condition, despite the high numbers. Hence the statistics are going to be unreliable. The paediatric reference (Dunger et al) has much more precise figures with regards to children, which are <1% and fairly constant. There is no source available to support the implied claim by Kitabchi et al that non-experienced centres somehow attract a mortality of >5% - it's a bit of an enigma why they actually make that claim. As I said, other sources carry the <5% figure without the putative qualifier. I don't think I'm going to change my mind over this; as the primary author of much of article I don't want to exhibit WP:OWN though so please ask other editors to weigh in and develop consensus here. JFW | T@lk 20:16, 15 March 2010 (UTC)

Then this is simple: cite a better source. You can't site a source, then not fully represent the source's findings. - JeffJonez (talk) 00:58, 16 March 2010 (UTC)

I have already provided a source without a qualifier. I suggest you stop changing it. By the way, boldface as a surrogate for shouting is really quite unnecessary here. JFW | T@lk 14:59, 16 March 2010 (UTC)

Bolding was for emphasis, as you seemed to be missing that particular point. You've now referenced a source that I am unable to verify, which gives me pause, as your previous attempts to source the figure you're defending were incomplete at best. I'd prefer to see a consensus on a proper morality figure and source before I acquiesce to your demand to stop editing this article. - JeffJonez (talk) 18:50, 16 March 2010 (UTC)

Another British guideline

The Joint British Diabetes Societies Inpatient Care Group, a body with representations from several British diabetes societies, has authored a DKA guideline for NHS Diabetes. It does not grade the evidence and is mostly experience-based with some recommendations based on ancient papers, but it is clearly the best available.

Joint British Diabetes Societies Inpatient Care Group (March 2010). "The Management of Diabetic Ketoacidosis in Adults" (PDF). Retrieved 2010-06-06.

I will need to identify any discrepancies with the current article and cite it where necessary. Very similar protocols have already been circulating (but I'm unsure on their provenance), but this clearly is a standard of care. JFW | T@lk 12:58, 6 June 2010 (UTC)

Unsourced content

Gaussgauss (talk · contribs) added content to the "mechanism" section about catecholamines playing a significant role in DKA, and that strenuous exercise can precipitate DKA in type 2 diabetics. Most of this is not discussed in my sources and I wonder how much of it is speculative. I have asked the editor to advise on this talk page. JFW | T@lk 11:43, 4 July 2010 (UTC)

Response to assertions made by Jfdwolff (talk · contribs) Nowhere did I state that exercise precipitates DKA. Please retract your claim. And, an apology would be appropriate for impugning me with such fiction.

None of I wrote is speculative. It is fundamental, rather basic, early undergraduate level physiology.

The critical role of counterregulatory hormone excess in the pathophysiology of DKA is textbook stuff. It is so basic that finding journal citations for the notion would be a challenge, i.e. one would need to go back fifty or more years. Will you accept e-medicine and medscape as references (at least for our discussion here, but not for the DKA article itself, of course)? Please look at 1. http://emedicine.medscape.com/article/766275-overview (the pathophysiology section of the article) and 2. http://www.medscape.com/viewarticle/713278 (see figure 1 which is as good a summary as one will find).

For the important point that catecholamines suppress insulin secretion (which, again, is basic textbook type stuff), you can look at the abstract of the following article by Ralph DeFronzo where it is stated explicitly http://www.ncbi.nlm.nih.gov/pmc/articles/PMC371414/

I trust these examples satisfy your demands and that you will now undo your edit of my contribution. And, again, you should acknowledge that nowhere do I state the exercise, strenuous or otherwise, precipitates DKA.

Thank you. Gaussgauss (talk) 13:06, 4 July 2010 (UTC)

Apologies for misreading "extreme physical stress" as exertion. I have never heard of type 2 diabetics developing DKA in the setting of MI or sepsis, and given that it is not mentioned in my sources (Kitabchi, Harrisson's etc) I would like a good source (see WP:MEDRS) that will support your additions. Just calling it "textbook stuff" does not replace the need to thoroughly source everything we write to reliable sources. The DeFronzo reference is interesting, but probably does not reflect normal epinephrine levels in man and cannot really be used to support any claims about DKA pathophysiology. JFW | T@lk 18:52, 4 July 2010 (UTC)

Gaussgauss responds: This is very silly. Again, I know this will sound hostile, but you do not seem to have sufficient familiarity with glucose homeostasis and counterregulation to be suppressing other people's contributions. I'm not saying you don't make valid and valuable contributions yourself, only that you should probably not act as a judge and censor of things about which you are, perhaps, well-versed, but not expert. So, for example, please look at this 30-year-old reference (from two 'heroes' of glucose/insulin pathophysiology): http://diabetes.diabetesjournals.org/content/51/suppl_1/S271.long Right there in the abstract, the authors state, "During such exercise, insulin secretion is inhibited by beta-cell alpha-adrenergic receptor activation." This should dispel any remaining doubts you have as to the effect of adrenergic control of insulin secretion, including in vivo and in day-to-day life. That being said, the effect is exaggerated in type II DM where there is already compromise of the pancreatic beta-cells. Hence, in type II DM in the setting of high catecholamine states such as MI and major trauma, etc, insulin secretion may be totally suppressed for some time (although it recovers as the stress recedes). But, again, bottom line: Insulin secretion is inhibited by the alpha effect of catecholamines.

Now, with respect to the role of counterregulatory hormones in the pathogenesis of DKA, here is a free full-text reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874999/?tool=pubmed While not the most prestigious reference, it is clearly and unambiguously stated therein that, "The role of counterregulatory hormones in the pathogenesis of diabetic ketoacidosis is considerable". Considerable! Of course, the pathophysiology underlying this statement (paraphrased from the abstract actually) is elucidated in some detail in the body of the article under the section entitled 'Pathogenesis of Diabetic Ketoacidosis". Please look at it. Among other things it explains how in the absence of various counterregulatory hormones, ketoacidosis cannot occur, e.g. the essentiality of glucagon in the process.

Unfortunately, the article does not reference a more clinically relevant point - that even in type I diabetics who abstain from insulin (i.e. as part of an experimental protocol), so long as one gives them IV saline to replace urine losses (and thereby prevents the volume depletion usually caused by osmostic diuresis), ketoacidosis does not develop or does so very, very slowly. Why? Because maintenance of blood volume in this way prevents the rise in counterregulatory hormones normally prompted by volume depletion. If nothing else, this realization (and more generally the realization of the profound role of the counterregulatory hormones in DKA and their stimulation by volume depletion and hypotension), serves to emphasize the essential role of volume replacement during the treatment of DKA. Giving insulin without concomitant volume support, will not succeed in clearing the DKA. In fact, that is why I am so dedicated to having it included in the article - so that medical students will appreciate the fact and remember it when they treat people with DKA (yes, alas, many med students use Wiki; I see it happening every day at work). I will keep looking for the reference for that study (done in the days before ethics committees!), but it is a very old one and is probably not on-line.

As my tone no doubt reveals, I was more than frustrated by your actions and, I think, frankly, your arrogance. Your decision to delete my contributions flies in the face of the references I've provided. But, that you were not aware of them (and all the others) not only explains why you did not believe me (that is excusable), it more importantly gives testimony that you don't know the subject well enough to sit in judgment of others (which is not permissible).

Beyond all this, though, you were holding me to a standard that is much, much higher than the vast majority of Wiki articles (where unreferenced statements are routinely noted but not unilaterally deleted). I am sorry to sound so angry but I love to teach. However, it really takes the joy out of contributing, out of teaching, when I have to teach the arbiters as well.Gaussgauss (talk) 01:32, 5 July 2010 (UTC)

I would like you to moderate your tone and take my requests at face value. I have spent a lot of time on the DKA article and pushed it to GA status, and you are only an occasional editor. I thought it was therefore safer to temporarily remove the content in question while we sorted out the sourcing. I do not question your expertise or even claim particular expertise myself, but much of what you have said is not reflected by the sources that I am familiar with and that represent the best and most recent sources available to us. Could you please have a look at WP:MEDRS, which outlines the kind of source that I would like to be using. Please have some patience, try to understand my perspective, and focus on the issues. JFW | T@lk 07:43, 5 July 2010 (UTC)

Possible Additions for You to Consider

Not criticisms, just some suggestions, but there are a number of points about DKA and its treatment which are not yet included in the article or that might be expanded upon. For example, no mention is made of hypophosphatemia, and the discussion of potassium changes during the course of DKA seems somewhat incomplete (and currently contains at least one misconception). Further, there is little or no attention paid to some of the mid-term biochemical consequences of DKA such as the development of non-anion gap metabolic acidosis or persistent/increasing ketonemia despite appropriate therapy. Another area to consider changing has to do with blood testing during DKA. As it stands, the section is a bit scattered and not as relevant clinically as it could be (e.g. no talk of amylase elevation, use of anion gap to monitor acidosis, distinguishing "stress leukocytosis" from that due to sepsis, misleading hyponatremia due to hyperglycemia, etc.). Of course, and as you know it's my opinion that the critical role of counterregulatory hormones in DKA could be emphasized a a bit more. Finally, although not only germane to this particular subject, you may also wish to consider some discussion of "dehydration" versus "volume depletion". All this is simply for your consideration. The article is quite fine at present even without making any changes. Still, at least in my opinion, addressing any of these things would enhance the article.Gaussgauss (talk) 11:11, 5 July 2010 (UTC)

The Kitabchi guideline states that routine phosphate correction is not beneficial. Hence I left it out (although it is touched on in the "history" section).

With regards to the potassium, please state what the misconception is rather than making me guess.

We can put in loads of information about saline-induced non-anion gap acidosis (as indeed the JBDS source discusses), but in my mind there is a limit to what we need to discuss for the article to be useful for the average reader. For the same reason I left out the perennial debate whether Hartmann's solution or saline is the appropriate fluid.

You are free to make any addition/change you wish as long as it is properly sourced to high-quality reviews (see WP:MEDRS). JFW | T@lk 18:41, 5 July 2010 (UTC)

Regarding the amount of detail, whose call is that? In many of the math and physics Wiki articles, NO attempt is made to aim for the "average reader". So, why not refrain here as well from talking down to your audience (as is the philosophy apparently in the physics articles)?

The reference for the potassium error dates to the 1970's. I will look for a more contemporary source. Gaussgauss (talk) 22:17, 5 July 2010 (UTC)

I find it troubling that the physics and maths articles make no attempt to make things comprehensible for the layperson.

With regards to potassium, it has now gone from a "misconception" to an "error". Can you please state clearly what is wrong so I can correct the factual error? JFW | T@lk 22:53, 5 July 2010 (UTC)

Yes, of course. I am not trying to withhold anything.

In the 'potassium' subsection of the management section it says, "Serum potassium levels are initially often mildly raised even though total body potassium is depleted - as potassium from the intracellular space would have been shifted to the extracellular space in an exchange for hydrogen ions that accumulate extracellularly in acidosis of DKA."

I wasn't trying to be coy. The quoted sentence above is based on a misconception and is erroneous. Why? Although it is often taught that when hydrogen ions enter the cell to be buffered there is a corresponding exit of potassium (to maintain electric neutrality), this is not (usually) the case and is a misconception. Such a phenomenon is true when the anion associated with the proton is inorganic, as occurs, say, after hydrochloric acid ingestion (or infusion). In that instance, the potassium leaves the cell because the chloride ion cannot enter the cell with the proton. In other words, there is no other choice for the maintenance of electric neutrality.

In organic acidosis on the other hand, the organic ion (such as ketoanion) can enter the cell together with the proton. Hence, there is no need for potassium to exit. Indeed, entrance of the proton with the organic ion is essentially the only mechanism for intracellular acid buffering in organic acidosis. Little, if any, potassium leaves. As a result, there is no hyperkalemia.

The first reference I am aware for this process is: http://ajprenal.physiology.org/cgi/content/abstract/235/4/F345. The abstract reads as follows:

"Metabolic acidosis is known to be associated with increased blood potassium and phosphorus concentrations but the influence of mineral versus nonmineral acids on these variables remains undefined. Therefore, we infused anesthetized mongrel dogs with 0.45% saline (controls), the mineral acids HCl and NH4Cl, and the nonmineral acids lactic, beta-hydroxybutyric and methyl malonic for 1-3 h. Administration of both mineral acids was associated with significant increases in plasma potassium. In contrast, infusion of the three monmineral acids did not result in increases in plasma potassium; in fact, the levels decreased initially in the majority of the dogs. Phosphorus concentrations were increased by lactic and beta-hydroxybutric acids, were unchanged by NH4Cl and HCl, and were decreased by methyl malonic acid. Although the mechanisms responsible for these changes remain to be elucidated, the findings indicate that short-duration infusion of mineral and nonmineral acids has substantially different effects on plasma concentrations of these predominantly intracellular ions."

Subsequently, the authors' conclusion in this regard and its implication for human acidoses has been incorporated into standard textbooks. Thank you. Gaussgauss (talk) 00:43, 6 July 2010 (UTC)

I will clarify the content in question, although the source itself is probably inadequate from a WP:MEDRS perspective. JFW | T@lk 15:17, 6 July 2010 (UTC)

To Close Out DKA vis a vis Counterregulatory Hormones

I present here two of the early papers emphasizing the role of counterregulatory hormones (CRH) in the pathogenesis of DKA. Both articles (from David Schade and Phillip Eaton in New Mexico) attest to the primary, essential role of CRH in the development and perpetuation of DKA. In fact, as I recall, it was these researchers who put the concept 'on the map'. Although there may be earlier references, I suspect that these are among the earliest in the clinical journals.

Schade DS, Eaton RP. The controversy concerning counterregulatory hormone secretion. A hypothesis for the prevention of diabetic ketoacidosis? Diabetes. 1977;26:596-9.

Diabetic ketoacidosis is characterized by an excess secretion of counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Experimental evidence obtained in both diabetic man and animals suggests that elevation of the plasma concentration of these hormones is necessary to initiate excess hepatic production of ketone bodies. This increase in hepatic ketogenesis in concert with inability of peripheral tissues to completely utilize ketone bodies results in clinical ketoacidosis. This hypothesis would suggest that pharmacologic control of excess counterregulatory hormone secretion would be a rational therapeutic modality to prevent diabetic ketoacidosis.

Schade DS, Eaton RP. Prevention of diabetic ketoacidosis. JAMA. 1979;242:2455-8.

Absolute deficiency of insulin no longer is considered the principal cause of ketoacidosis. A combination of pathogenic mechanisms includes (1) relative insulin deficiency, (2) stress hormone excess, (3) fasting, and (4) dehydration. Prevention of any one or more of these mechanisms will reverse or lessen the rate of metabolic decompensation. Several important metabolic parameters must be monitored at frequent intervals to permit rational, preventive therapy. The flow sheet to be maintained by the patient should include body weight, temperature, respiratory rate, level of consciousness, degree of ketonuria, and degree of glycosuria. If the patient exhibits decreased mental status, more than 5% loss of body weight, or respirations more than 36/min, hospitalization is indicated.

I believe these references serve to establish the role CRH excess in the pathogenesis of DKA. If nothing else, I draw your attention to the first line of the second article's abstract. It states, "Absolute deficiency of insulin no longer is considered the principal cause of ketoacidosis."

I trust this is satisfactory. Thank you. Gaussgauss (talk) 16:23, 5 July 2010 (UTC)

The references are over 30 years old and may have been supplemented by more recent experimental data. This is why WP:MEDRS advises that recent, high-quality reviews are used for medical articles. JFW | T@lk 18:41, 5 July 2010 (UTC)

I agree with Jfd WRT the importance of using uptodate sources. A review from the last 10 years would be better. Doc James (talk · contribs · email) 21:47, 5 July 2010 (UTC)

The problem, the one I noted back at square one, is that these things are old. No one publishes on stuff that's 30 years old. It goes into textbooks. But, do you really want me to cite a textbook when I've already provided the references that the textbooks themselves will cite? Or, look at it this way: You agree that what I said about CRH is true, no? The references, however old, bear that out. So, there is no danger that the article will contain falsehoods in this regard. Are you going to omit "the truth" until I come up with a textbook reference? In the meantime, readers will miss out on said "truths". I'm sure you see what I'm getting at. Your call, though. Gaussgauss (talk) 22:12, 5 July 2010 (UTC)

I did not comment on the CRH issue at all, because it does not appear in recent sources (and not in Harrison's as far as textbooks go) and I can therefore not say how widely this has been reproduced etc. Not exactly my call if you are able to produce the kind of source I mentioned. JFW | T@lk 22:52, 5 July 2010 (UTC)

Here is a recent review on hyperglycemic crises by a fellow by the name of Kitabchi: http://care.diabetesjournals.org/content/32/7/1335.full It came out in 2009 which is recent. So, I am not sure why you say "CRH issues . . . (do) not appear in recent sources". In any case, in the section entitled "Pathogenesis" (third section of the article), Kitabchi states at least twice that it is the combination of insulin deficiency and increased CRH which leads to DKA. When coupled with the more historical references I noted earlier, this reference should finally make it clear that insulin deficiency per se, in the absence of elevated CRH, is not the cause of DKA. Rather, as Kitabchi emphasizes, it is the combination of insulin lack and elevated CRH levels that leads to DKA (which was all I was trying to say with my contribution in the first place). This is a clinically critical point since it underscores the need for vigorous volume replacement in the treatment of DKA in order to turn off the stimulus for CRH release (i.e. to correct the inevitable volume depletion of the DKA state) without which the DKA will be more protracted and refractory.

I believe I have now fulfilled the criteria you spelled out earlier and hope and trust you will therefore see fit to include my earlier contributions (which were deleted). Gaussgauss (talk) 14:33, 7 July 2010 (UTC)

I managed to misread CRH as corticotropin stimulating hormone, rather than counterregulatory hormones. Still, close reading of Kitabchi (which is the main source for the article) does not really state that CRH activation is a sine qua non for DKA. It is just mentioned side by side and relative prominence of CRH and insulin resistance is probably one of those unknown unknowns. JFW | T@lk 19:36, 7 July 2010 (UTC)

Well, that is not my take on the article at all. I can't conceive that one will ever find a more unequivocal contemporary statement attesting to the combined role of counterregulatory hormones and insulin lack in the genesis of DKA. If you disagree, so be it, but this will be my last post here. Still, as a courtesy to someone who wanted to help, and tried to help, I beseech you to read this and the following abstract: http://www.ncbi.nlm.nih.gov/pubmed/804137 The first is from a 35-year-old New England Journal of Medicine article that says, "insulin lack per se does not lead to fulminant diabetic ketoacidosis in man and that glucagon, by means of its gluconeogenic, ketogenic, and lipolytic actions, is a prerequisite to the development of this condition.". And, from the same group, here: http://www.ncbi.nlm.nih.gov/pubmed/829924 an even more explicit statement, "insulin deficiency is necessary, but is in itself not sufficient, to cause fulminant diabetic ketoacidosis". Kitabchi says the same thing, in different language, without mentioning glucagon by name (with glucagon, of course, being a counterregulatory hormone). That you repudiate this established (patho)physiologic result, I cannot explain. As requested, I have provided modern references to complement the historic ones I dug up. But, you seem to change and interpret your own rules in a capricious fashion that I can't keep up with. Indeed, it was you who said, "Not exactly my call if you are able to produce the kind of source I mentioned". But, when I gave you Kitabchi himself as the source, you refused to budge.

I hope it is evident how much work (finding references if nothing else) that I put into this pursuit so that is equally evident that I am no "fly-by" poster who's here just to cause trouble. I can only hope you will leave this, and all the other dialogue on this page, stay in place where it can be reviewed objectively by all. But for now, I rest my case.Gaussgauss (talk) 20:49, 7 July 2010 (UTC)

Again you have cited primary physiological studies, which we cannot therefore use as evidence. How about you change the content the way you think is correct, using appropriate references (Kitabchi is the best by far), and we'll see how it goes. JFW | T@lk 22:12, 8 July 2010 (UTC)

Brain does not need insulin!

"β-Hydroxybutyrate can serve as an energy source for the brain in absence of insulin-mediated glucose delivery,"

Insulin-mediated action has nothing to do with the brain. The BBB uses GLUT1 transporters and thus insulin is not needed for glucose delivery at all! —Preceding unsigned comment added by Smodtactical (talk • contribs) 00:08, 11 November 2010 (UTC)

Edited mechanism and clinical resolution

Added some fairly detailed/advanced level stuff in both sections, but that is still relevant to DKA. Also contributed under an anonymous IP accidentally. Please revise if the content is beyond the scope of the article. — Preceding unsigned comment added by Jimhsu77479 (talk • contribs)

Most of the edits to "mechanism" are not supported by the references that we currently provide (e.g. the mitochondrial conversion of FFA to ketones). I have removed this pending discussion; I'm not 100% sure whether the finer details of this process are useful for the reader.

The suggestion that anion gap measurements are used to check resolution is very novel to me. Neither Kitabchi or any of the British guidelines recommends this. I believe that direct measurement of ketones is much more useful, and of course the clinical state of the patient. JFW | T@lk 23:13, 15 November 2010 (UTC)

For the mechanism part, here is the reference: http://www.jbc.org/content/270/29/17513.full

For the anion gap at least, many US sources mention it (ex. http://www.merckmanuals.com/professional/sec12/ch158/ch158c.html ) and I believe it is a routine measurement. Thought it should at least be included for completion. Jimhsu77479 (talk) 01:22, 16 November 2010 (UTC)

The JBC paper is not quite the kind of source I would use to support medical content. Similarly, I'd appreciate if you could provide a source compliant with MEDRS for the anion gap statement; don't you agree that direct measurement of ketones is much more useful than the proxy measure of anion gap? Also, anion gap calculations may be clouded by lactate. JFW | T@lk 09:54, 16 November 2010 (UTC)

Ok, after some more discussion, I agree with your points, and do not really have the time to edit the article further and/or clarify.

One thing though: the mechanism part should mention that the "absolute lack of insulin" is not totally required for DKA, as evidenced by certain T2 patients that progress to DKA. "Lack" in this case implies there is no significant amount of insulin in circulation. Can you clarify that part -- maybe "deficiency"? Don't know. Jimhsu77479 (talk) 17:15, 16 November 2010 (UTC)

Will look at this. Thanks for your contributions. JFW | T@lk 23:03, 16 November 2010 (UTC)

I still do not understand your near exclusive reliance on Kitabchi. Physicians familiar with DKA and its treatment could note that there are many authorities beyond good Doctor Abbas. In any case, from the horse's mouth (Kitabchi, A, Rose B. Treatemnt of diabetic ketoacidosis and hyperglycemic hyperosmolar states in adults. UpTo Date online edition 18.3, 2010), we have:

". . . an alternative to monitoring venous pH and serum beta-hydroxybutyrate is monitoring the serum bicarbonate concentration (to assess correction of the metabolic acidosis) and the serum anion gap (to assess correction of the ketoacidemia).

The serum anion gap provides an estimate of the quantity of unmeasured anions in the plasma, such as albumin and, in DKA, ketoacid anions. It is calculated by subtracting the major measured anions (chloride and bicarbonate) from the major measured cation (sodium).

Monitoring the anion gap will give a good estimate of serum ketoacid levels in DKA. Normalization of the anion gap reflects disappearance of ketoacid anions in the serum and correction of the ketoacidosis. However, ketonemia and ketonuria may persist for more than 36 hours due to the slower removal of acetone, in part via the lungs."

So, not only is Kitabchi saying one can dispense with blood gas measurements in favour of electrolyte (i.e. anion gap) measurements in most patients with DKA, but that "real world" measurement of serum ketones is actually misleading! (i.e. the predominant endogenous acid ketone (beta-OH-butyrate; B-OH-B) is not measured by most labs, whereas the non-acidic, clinically inconsequential metabolite of B-OH-B, acetone, is. Gaussgauss (talk) 00:19, 25 January 2011 (UTC)

As an aside, I will use this opportunity to point out that Kitabchi himself, in the same article from UpToDate, states, "acidemia alone probably does not play a major role in the elevated serum potassium associated with DKA. The greater importance of insulin deficiency and hyperosmolality is illustrated by the observation that hyperkalemia also occurs in HHS despite the absence of ketoacidosis [2]". In other words, elevated potassium levels in DKA are not due the acidemia. This is precisely what I tried to include previously previously (and even gave the original reference for the phenomenom- vide supra) but had stricken from the text. Gaussgauss (talk) 00:34, 25 January 2011 (UTC)

Oh, you're back?

UpToDate is not a source that I like to use, because it is stuffed with original research and anecdotal reports. Unless we can find reliable medical sources saying the same thing, it will be inappropriate to cite this content.

Clearly, if the ADA wanted to mute Abbas Kitabchi they wouldn't have published the guideline that we are citing extensively.

We don't say anywhere that the hyperkalaemia is driven by acidosis.

Please stick to the right kind of sources, because that's what's at the root of our disagreements. JFW | T@lk 01:02, 25 January 2011 (UTC)

In 2019, do you still impugn UpToDate as not "the right kind of source"?Gaussgauss (talk) —Preceding undated comment added 21:12, 3 March 2019 (UTC)

Yah Uptodate is not a great source for Wikipedia as one cannot reference a specific version.

Using 40 year old sources is not appropriate. http://diabetes.diabetesjournals.org/content/26/6/596.long

Doc James (talk · contribs · email) 04:47, 4 March 2019 (UTC)

JBDS

The JBDS guideline has been summarised here doi:10.1111/j.1464-5491.2011.03246.x. I think we should still reference the full guideline rather than the summary in Diab Med. JFW | T@lk 22:53, 21 August 2011 (UTC)

Have just discovered that the ADA updated their guideline in 2009 (just after the GA!) - doi:10.2337/dc09-9032. Must read and update. JFW | T@lk 20:50, 22 August 2011 (UTC)

Another try at rectifying the potassium error

Please see the following reference from the Merck online. Frankly, it's not the type of reference I would want to use but you have disqualified the other references I've dug up with respect to this issue (vide supra).

Reference: Disorders of Potassium Regulation (Merck)

From that source, we have the following quotes:

1. "Low concentrations of insulin, as in diabetic ketoacidosis, cause K to move out of cells, thus raising serum K, sometimes even in the presence of total body K deficiency."

2. "metabolic acidosis due to accumulation of organic acids (increased anion gap acidosis) is not associated with hyperkalemia." I presume you will agree that ketones are organic acids. Ergo, hyperkalemia in DKA is not from the acidosis.

Taken together, these statements should dispel the notion that in DKA, it is the acidemia which leads to the elevated potassium levels. Accordingly, no review of DKA should persist in attributing the tendency towards hyperkalemia in DKA to acidemia. Indeed, I am surprised that not only did you discount my earlier references attesting to this fact, but you evidently were neither curious enough or motivated in any other way to check things out for yourself. As the author of an article receiving the designation of "Good Article" (or whatever the proper phrase is) you demonstrated a remarkable lack of interest in actually making it "good". Notwithstanding having the error it contained pointed out to you (more than once), you have allowed it to remain in place for over a year.

I will not bring up the additional references which document the other point I have attempted to make repeatedly concerning the essential role of counterregulatory hormone excess in the pathogenesis of DKA, i.e. even in the absence of insulin, DKA will not supervene in the absence of counterregulatory hormone excess. This is no mere (patho)physiologic curiosity. Rather, this fact underscores and rationalizes the critical, nay, essential, role of volume repletion (to reduce counterregulatory hormone levels) in the treatment of DKA. As such, it plays an important part in medical trainees' (and other interested individuals') understanding of DKA and its management. Without such understanding, the practitioner is more of a technician than a physician.

If you detect a note (and probably) several of frustration in my 'voice' at this time, it is only because I cannot fathom why you have resisted all my previous (and well referenced) attempts to correct things. And, frankly, as a Professor of Medicine^§ at one of the most highly ranked medical schools in North America (by various metrics including research productivity, external assessment, etc.), whose area of expertise is endocrinology and metabolism (yes), it is, indeed, extremely frustrating to be thwarted at every step. But most of all, I find it unconscionable that you would choose to allow errors of fact to remain in article that is used, at least in part, for the education of the uninitiated (and yet permit the "Good Article" star to remain attached).

Best regards Gaussgauss (talk) 17:16, 19 October 2011 (UTC)

§ Ever since I first started in my attempts to edit this article, I have been tempted to mention my academic position but felt it would appear immodest or that I was saying, "Trust me, I know about these things". I have resisted until now. At this time, though, in light of my attempt to 'pull out all the stops' and finally get this fixed, I have mentioned it.

Leaving apart problems with your accusatory tone and pulling rank, I have temporarily removed the offending sentence until we can resolve this.

The single sentence that seems to have raised your ire is: "Serum potassium levels are initially often mildly raised even though total body potassium is depleted—as potassium from the intracellular space would have been shifted to the extracellular space in an exchange for hydrogen ions that accumulate extracellularly in acidosis of DKA." The perception that acidosis can drive hyperkalaemia is extremely widespread, and bicarbonate solutions are used widely in the treatment for severe hyperkalaemia (despite the fact that this is not very effective, as per doi:10.1097/CCM.0b013e31818f222b). If I erred, I did so in commission.

Please could you now propose a better wording for this sentence, as well as a secondary source that meets the criteria set out in WP:MEDRS? JFW | T@lk 22:18, 22 October 2011 (UTC)

After a long day, my eyes glazed over about halfway through the sentence, but on the sourcing issue: Isn't this the kind of stuff that ought to be described in some decent med school textbook? That would be a great source for physiology information. WhatamIdoing (talk) 02:33, 25 October 2011 (UTC)