I'll see your ketoacidosis and raise you a renal failure

A while back I posted on a paper that appeared in The Lancet about an obese woman who came to the emergency room with gastroenteritis and was misdiagnosed as being in diabetic ketoacidosis (a life-threatening disorder). She was misdiagnosed because the pinheads covering the ER couldn’t get past the fact that she had been on a low-carb diet. At the time I posted on this travesty I noted that this Lancet paper would from here on out be waved in the face of anyone who was following or advocated a low-carb diet as proof that such a diet is dangerous and can cause diabetic ketoacidosis (DKA). Well, now we’ve got an answer.
Next time someone tells you that it has been proven that low-carb diets are dangerous and can cause ketoacidosis, you can resort to poker terminology and reply that you’ll see their ketoacidosis and raise them a renal failure.
A few days ago I got wind of a paper published a few years ago that can be used as a counterpoint to the above mentioned idiotic paper in The Lancet that has given low-carbers such a bad time. This paper, published in the journal Renal Failure in 1998, is, like the other paper, a case report. The short version is as follows:
An obese young man arrived comatose in the emergency room. In an effort to lose weight he had been consuming a high-carbohydrate canned beverage as his sole source of nutrition for the two weeks prior. His blood sugar–at about 20 times normal–was extremely elevated and led to a diagnosis of diabetic ketoacidosis. The physicians on staff treated the patient appropriately, and he, over the next 20 hours or so, regained consciousness as his blood sugar levels and other lab parameters began to normalize. During a lab analysis 22 hours after admission the doctors found the patient to be breaking down and releasing into his blood huge amounts of muscle protein, a condition called rhabdomyolysis, which if severe enough can lead to kidney failure. Four days after admission the patient indeed developed renal failure, requiring multiple dialysis treatments. With judicious care at the hands of his physicians this patient recovered completely and was sent home on a diabetic diet 44 days later. At a follow-up visit five months later the patient was fine and all his lab values were normal.
So there you have it. Whenever an unenlightened person tells you low-carb diets are dangerous, say, Yeah, but so are high-carbohydrate diets and wave this horror story under their noses.
Before we try to make sense out of what all went on with this patient, let’s talk a little about what a case report is. When doctors encounter an unusual patient problem that they think might be of interest to other physicians, they often publish their findings as case reports. These case reports are not double blind, placebo controlled studies, they are simply presentations of interesting and unusual patient encounters. I emphasize the word unusual because no one would ever write up a case report on a typical, non-unusual, patient visit. The very nature of case reports are that they are so unusual that they are newsworthy; they are the man-bites-dog stories of the medical literature.. Typically anything found in a case report is not something that most physicians would likely ever encounter in the course of their normal practices, and for this reason, case reports should be taken as interesting observations, not as something to extrapolate to the patient population at large.
As you might imagine from my long rambling prologue on case reports that I have some problems with this one. Let’s take a look. (I’ve reproduced the entire paper at the bottom of this post, so that you can read it from beginning to end)
The first clue that the history might be a little off is found right off the bat.

A 23-year old obese man…was brought to the emergency room after being found in a unresponsive state at home by the relatives.

A couple of sentences down the report states:

On the morning of admission he suddenly felt dizzy and passed out in front of the family members.

So, was he found ‘in an unresponsive state’ implying that he had been unconscious for some period of time or did he “pass out in front of the family members”? You may think this is splitting hairs, but it speaks to how sloppily the case was written, and it calls into question (to me, at least) the accuracy of the whole thing.
At any rate the patient was definitely in a coma when he got to the ER. A Glasgow Scale of 3 is about as comatose as one can be, which is often how people who go into diabetic ketoacidosis are found. His blood sugar level was a whopping 1854 mg.dL, which is extremely high. His sodium was a little high, his potassium a little low, his bicarbonate a lot low. His picture looks fairly typical of someone in diabetic ketoacidosis. The only problem is that he doesn’t have diabetes. How do we know? Because he went home on a diabetic diet and did fine. People with type I diabetes have no insulin, which is what gets them in trouble with DKA in the first place, and when they get their DKA controlled, they still have no insulin and can’t go home on a diabetic diet. According to the authors of the case report, this patient suffers from insulin resistance and, therefore, one assumes, hyperinsulinemia. It would be virtually impossible to go into diabetic ketoacidosis with hyperinsulinemia, so I don’t really know what is going on here.
His history is that he had been drinking nothing but Ultra Slim Fast for the two weeks prior to his passing out, which the authors of the report blamed for his problem. Ultra Slim Fast is no longer available, so I can’t confirm what the nutritional content of the 15 ounce cans were. (If anyone has an old can laying around, send me the nutritional info and I’ll update this post.) According to the authors of this case report the drink contained 50 grams of carbohydrate per can, so the 6-8 cans the patient was purportedly drinking would provide him with about 400 grams of carbohydrate per day. 400 grams is a lot, but many obese people can put away a whole lot more than that; in fact, a glass of orange juice, a few bowls of breakfast cereal, sprinkled with sugar and consumed with milk (a common breakfast for many children) can provide more than 400 grams of carbs at one meal. The 400 grams in the 8 cans of Ultra Slim Fast aren’t much different than the amount of carb found in 8 cans of a regular softdrink or a couple of the supersized models, which many obese people consume regularly. As I said before, I don’t know what actually went on with this patient, but I don’t think it was driven by the fact that he consumed 6-8 cans of Ultra Slim Fast as his only source of nutrition.
Keeping his calories low–which would have been accomplished if he really did drink only the Ultra Slim Fast–should have improved his insulin sensitivity, making the development of diabetic ketoacidosis even more unlikely.
What’s not unlikely, however, is that this patient was in real trouble. He did indeed develop an acute breakdown of muscle tissue releasing protein into the blood that made its way to his kidneys where it basically gummed up the filtering mechanism and drove the kidneys to actually fail. The patient underwent multiple treatments of a couple of different types of dialysis to clear his blood and allow his kidneys to recover, which they ultimately did.
All in all this situation is a mystery to me. I don’t have the patient here to question, nor do I have his chart with all lab results to review, so I can’t speculate as to what happened. But, I’m pretty sure he didn’t have diabetic ketoacidosis just as I’m sure the woman in the other case report wasn’t driven into DKA by her low-carb diet. What it all boils down to is that we have two poorly written case reports (both of which require a lot of reading between the lines to figure anything out) in which the authors finger a particular nutritional regimen as the cause of the problem. In both cases I believe the authors are wrong, but at least now we have a ‘wrong’ high-carb paper to offset the equally ‘wrong’ low-carb paper. And when it gets to the dueling ‘wrong’ paper stage, we can sweeten the pot with a big dose of renal failure.
I’ve reproduced the body of the paper below:

DIABETIC KETOACIDOSIS AND RHABDOMYOLYSIS FOLLOWING EXCESSIVE INTAKE OF A WEIGHT REDUCING DIET

ABSTRACT

Click here.

INTRODUCTION

Ultra Slim Fast is a popular weight reducing meal supplement with a high carbohydrate content (50 gm per 15 oz. can). According to the manufacturer’s instructions it is supposed to be taken as a shake for breakfast and lunch followed by a healthy dinner. We describe a case of a young obese man who developed diabetic ketoacidosis (DKA) after he had been on Ultra Slim Fast as the only source of nutrition for two weeks prior to presentation. The patient subsequently developed acute renal failure from rhabdomyolysis which is an uncommon completion of DKA.

CASE REPORT

A 23-year old obese man with no significant medical illness was brought to the emergency room after being found in an unresponsive state at home by the relatives. The patient had been ingesting 6-8 15 oz. cans of Ultra Slim Fast per day for two weeks prior to admission. There was no history of illicit drug use of significant alcohol intake. The patient had been vomiting 2-3 times a day for three days prior to presentation. On the morning of admission he suddenly felt dizzy and passed out in front of the family members. He was immediately intubated by paramedics and was resuscitated with intravenous fluids. On admission to the emergency room, physical examination revealed an obese 320 pound man on mechanical ventilation with a pulse rate of 120 beats/minute, blood pressure of 90/60 mm Hg. and temperature of 95 degrees F, in a state of dehydration and a glasgow coma scale of 3. There were no other significant clinical findings. Laboratory data revealed: sodium 151 mmole/L, potassium 3.7 mmole/L, glucose 1854 mg/dL, blood urea nitrogen (BUN) 63 mg/dL, creatinine 5.7 mg/dL, chloride 104 mmol/L, bicarbonate 8 mmol/L calculated anion gap 39, calculated serum osmolality was 427 mOsmol/L and serum acetone was positive at a titre of 1:1. Serum lactic acid was 1.5 mEq/L ad CPK was 84 U/L. Urine toxicology screen was negative and showed absence of oxalate crystals. Electrocardiogram showed sinus tachycardia and a chest roentgenogram was normal.

The patient was managed with intravenous fluids in the form of 0.9% sodium chloride solution, intravenous insulin, intravenous potassium chloride and hemodynamic monitoring with a subsequent improvement in the mental status, hemodynamic parameters, acidosis and electrolyte imbalances. Twenty-two hours after admission an increase CPK to 20,922 U/L with a negative CK-MB fraction was noted associated with a 4+ heme on urinalysis. At this time the serum phosphorus was 2.5 mg/dL, potassium 3.2 mmol/?, sodium 145 mmol/L, calculated serum osmolality 340 mOsmol/L and arterial pH was 7.32 with an anion gap of 22. By the fourth day the patient’s CPK had gone up to 44,672 U/L and he had developed progressive non-oliguric renal failure with necessitated peritoneal and hemodialysis on a total of five occasions. He also developed stress induced gastritis, enterococcus faecium bacteremia and staphylococcal pneumonia which responded to broad spectrum antibiotics. The renal function improved with judicious volume replacement and dialysis and the patient was discharged on the 44th hospital day (BUN 13 mg/dL, creatinine 2.2 mg/dL) on a diabetic diet. During an outpatient clinic visit five months after the initial episode of DKA, the patient was asymptomatic with a BUN of 16 mg/dL, creatinine of 1.8 mg/dL and had good glycemic control on a diabetic diet.

DISCUSSION

The probable mechanism of DKA in the above case was physical stress from hypertonic dehydration due to a combination of poor fluid intake, vomiting and hyperglycemia from the high carbohydrate meal supplement in the setting of insulin resistance due to obesity. The rhabdomyolysis was secondary to a combination of severe metabolic acidosis and severe hyperosmolality. Metabolic acidosis can reduce the rate of glycolysis and reduce intracellular stores of ATP to a critical level which can lead to accumulation of intracellular calcium and activation of lytic cellular and membrane enzymes leading to rhabdomyolysis. Severe hyperosmolality and hypernatremia are known to cause muscle injury by increasing intracellular sodium in muscle cells and decreasing the total body potassium level.

In conclusion, physicians should be aware of the potential development of DKA and serious metabolic derangement from the excessive consumption of weight reducing meal supplements which have become very popular since the awareness of health problems related to obesity. These supplements should never be taken as the sole source of nutrition especially in obese persons who have underlying insulin resistance.