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July 26, 2009

Diagnosis and Symptoms

Question from Allentown, Pennsylvania, USA:

I took my four and a half-year-old daughter to our family doctor because she was having "strange" episodes. Early in the morning, around 6 a.m., she would wake up pale, shaky, thirsty and weak. After about an hour, she would vomit a few times then go back to sleep until about 11 or 12. When she would wake, she would be fine, like nothing ever happened and she would have a voracious appetite. A week or two would pass with no problems and, suddenly, it would happen again. The episodes are always exactly the same. The doctor sent her for blood work to rule out diabetes. Her A1c was fine (5.2), and her fasting blood sugar was 75 mg/dl [4.2 mmol/L], but her C-Peptide levels came back low (0.6 with normal ranging from 0.8 to 3.2). My doctor seemed very concerned and referred me to an endocrinologist. He said it was very important to catch it early. Unfortunately, I am finding it nearly impossible to get her an appointment with an endocrinologist because her A1c is normal, so her case is not considered urgent. The earliest I could get her an appointment was in three months, with some practices refusing to take me at all. I am very concerned because I have suspected something was wrong since birth. She was barely gaining weight as a baby, I had to take her every couple days for weight checks for her first three or four weeks. She had thrush in her mouth and a horrible diaper rash that would bleed even with yeast medication applied regularly. She would vomit excessively and had frequent diarrhea. She has always been below the 10th percentile for her weight and height and she recently lost 6 pounds (down to 36 pounds from 42) despite having an enormous appetite for a little girl. She has a sore under her eye that seems never to heal and frequent yeast infections. She also seems easily fatigued, taking a two to three hour nap every day and constantly needs to be carried because her "legs are tired" as she says. She also has a first cousin with type 1 diabetes (diagnosed at five years old). At the same time, she does not seem to urinate excessively and her fasting and random sugar tests are rarely and not excessively high. I have only gotten two high fasting readings, both around 6 a.m. One was 151 mg/dl [8.4 mmol/L] and another was 117 mg/dl [6.5 mmol/L]. She has not gotten sick since acquiring a meter, so I have not been able to check her during an episode. She is always well within normal the rest of the time. So, in light of all this, I am wondering how aggressively I should pursue this. Should I wait three months for an endocrinologist to see her or should I keep looking for a practice that will take her sooner? I know they will test for antibodies next, but is there any rush to do so? Aside from low doses of insulin, which she doesn't appear to need currently, how would an early diagnosis improve her outcome since there doesn't seem to be any way to halt the progress of type 1, if that is indeed what she has?


I know that it is difficult and frustrating when you request a referral to a subspecialist and you are then asked to wait for an appointment. The good news is what this means is that, based on the information your doctor provided, the subspecialist believes that there is not something urgent probably going on and that the issue is probably not serious.

Based on what you’ve written, I doubt your daughter has diabetes mellitus at present.

Your doctor apparently is concerned – and has passed this on to you – that the child’s C-Peptide is “low.” C-Peptide reflects the amount of insulin available. Mature, active insulin is composed of two different pieces (or “chains”) of protein, called “peptides”; one is the “A” chain and the other is the “B” chain. When insulin is being manufactured, these two chains have a third component called the “C” chain (or C-Peptide), which becomes detached as the insulin becomes mature. Active mature insulin does not last long so is quickly used by the body. On the other hand, the C-Peptide does circulate a bit longer. It is also important to understand that the manufacturing of insulin is very dependent upon the blood glucose concentration. After a normal, non-diabetic consumes food and the blood glucose begins to increase, the pancreas begins to release some stored insulin and manufacture new insulin. But when the blood glucose is low, there is not supposed to be much stored or manufactured insulin (and therefore C-Peptide) around.

So, I am not surprised and not in any way concerned right now that when the fasting serum glucose was 75 mg/dl [4.2 mmol/L], the C-Peptide was “only” 0.6 ng/mlL. The endocrinologists contacted probably reached the same conclusion. I fear that your doctor may be reacting more to a laboratory test value rather than how that value “fits” into the clinical situation described. Frankly, I am not certain why the C-Peptide was even measured.

Now, as to your daughter’s symptoms:

I have pictured a thin, perhaps “sickly” little girl who, as an infant, gained weight poorly and had recurrent bouts of vomiting with diarrhea. She’s had recurrent or persistent yeast infections and has recently lost 6 pounds (or a whopping 14%) of her previous body weight. I’d be concerned that your daughter is malnourished in one way or another – perhaps overall calories, perhaps a specific nutrient and her “voracious” appetite is a compensation mechanism to try to self-correct it. Poor nutrition would also explain poor wound/sore healing. I would first worry about some intestinal disorder preventing optimal digestion and absorption of nutrients. This could be something serious or easier to address such as a chronic food allergy.

The morning episodic symptoms you describe bring to mind a condition sometimes called “ketotic hypoglycemia” – a kind of LOW blood glucose (whereby again the insulin level would be expected to also be LOW.) You might discuss this with your family doctor. You might ask for a referral to a good general pediatrician for a consultation.

On mornings of these spells, the child’s blood (or even urine) could be screened with simple, inexpensive home test strips to screen for the presence of ketones which you should be able to get from your health care provider.

Given the more complex history you describe, I’d start with a visit for a formal consultation with a board-certified pediatrician.

Good luck and please let us know what, if anything, is found. I’d take solace that the issue of possible diabetes mellitus and urgent referral to an endocrinologist is not pressing at this time.