Diagnosis of Diabetes: Putting it All Together
Today I had the opportunity to review posts from fellow bloggers on this site. Natalie's blog "A1c is not enough" specifically caught my attention as she noted that her diabetes would not have been diagnosed simply by a hb A1c initially but rather by review of fasting and post-prandial blood sugars. As such, I would like to review the criteria currently used to diagnose diabetes (all types, except gestational diabetes, which has different criteria).
- Fasting blood sugar > 126 mg/dl on two separate occasions.
- Random blood sugar > 200 mg/dl along with symptoms associated with diabetes including increased urination, increased drinking, increased appetite, fatigue, weight loss, etc. (These criteria are typical of those children/teens/adults who are diagnosed with type 1 or insulin dependant diabetes.)
- Oral glucose tolerance test (75 grams of anhydrous carbohydrates) with a 1-2 hour post prandial blood sugar > 200 mg/dl.
- Hb A1c >/= 6.5% (newest diagnostic criteria and still controversial). A hb A1c of 6.5 reflects a 3-month estimated blood sugar of 138.85 mg/dl in people that glycate the hemoglobin molecule normally. The hb A1c reflects the binding (or glycation) of the glucose molecule to the hemoglobin molecule that resides in the red blood cell. Due to the fact that red blood cells turn over approximately every 3 months, we are able to use the hb A1c to reflect blood sugar control every 3-4 months.
Generally, any one of these 4 criteria may be used to diagnose diabetes when reviewing the entire picture. However, one must be extraordinarily cautious when actually making the diagnosis definitively. Several cases in point:
- Diagnosis of diabetes by blood sugar alone:
a. High blood sugar, sick kid! A 5-year old presents to the local Emergency Department with a fever of 105 degrees in association with vomiting and lethargy. Laboratory evaluation reveals a very high white blood cell count indicating a suspected infection and a blood sugar of 362 mg/dl. The serum blood sugar is repeated and confirmed. When the mother is questioned further about associated symptoms of increased urination, increased drinking, etc., she is not sure but it could be possible. Does this child have diabetes? Maybe or maybe not. Further evaluation is necessary by the healthcare team to determine if, indeed, this child has newly diagnosed diabetes versus stress-induced hyperglycemia secondary to a significant infection! A hb A1c may help to confirm or rule out the diagnosis.
b. High blood sugar, child with asthma on prednisone: A 10-year old presents to the Emergency Department with wheezing after beginning Prednisone prescribed by his primary care practitioner several days ago. He is given nebulizer treatments and his blood sugar is noted to be 202 mg/dl. Does he/she have diabetes? Is the diagnosis new onset type 1 diabetes versus steroid induced hyperglycemia? Once again, a hb A1c may help to clarify the situation.
c. High blood sugar, hb A1c is the normal range: A 14-year old presents to his or her pediatrician for a routine school physical and a urine sample is positive for glucose. The primary care provider obtains a fasting blood sugar of 196 mg/dl. A follow-up fasting blood sugar is 163 mg/dl. Upon further history, the mother notes that "yes, indeed, he has been drinking huge amounts of water and going to the bathroom frequently and appears to be getting taller despite no change in weight." He is referred to the diabetes specialist for further evaluation. A hb A1c of 5.3% is obtained that would normally represent a 3-month average blood sugar of 105.41 mg/dl. Does this child have diabetes? Aware that a hb A1c is affected by multiple variables, our team runs a serum fructosamine ( a test that reflects glucose binding to a protein-not the hemoglobin molecule) and notes that it is extremely elevated indicating that the hb A1c was not accurate.
What are the factors that may determine the accuracy of the hb A1c in the diagnosis of diabetes and reflecting hyperglycemia? And, what conditions prevent the use of the hb A1c as a reliable predictor of glycemic control?
1. Racial differences may predispose affected individuals to have higher or lower hb A1c's. Such research has been published in several Diabetes Care papers.
2. People that have hemolytic anemia in which there is rapid red blood cell turnover typically have low hb A1c's and thus do not accurately indicate glycemic control. Some examples include sickle cell disease (hb SS or hb SC etc.) and G6PD hemolytic anemia. There are other types of hemolytic anemia that may result in lower hb A1c's as well.
3. People that have different permutations of hemoglobin strands instead of the usual hemoglobin A/hemoglobin A. (Sometimes fetal hemoglobin may persist and not cause any obvious problems.)
4. People that are "low glycators." For some unknown reason serum glucose is unable to bind to the hemoglobin molecules residing in the red blood cell and the hb A1c measurement is falsely low.
5. People who have chronic illnesses such as Cystic Fibrosis Related Diabetes in which hb A1c levels are typically on the low side. (Measuring changes from one visit to another will at least give trend information.)
6. Other unknown causes of low hb A1c's
Let's put it all together!
Relying on only one criterion without the substantiation of the history, physical examination and additional laboratory evaluation is not in your best interests. Of most importance, the experience of your diabetes healthcare team in regard to diagnosis, education, and management is critical to navigate through the labyrinth of information that may lead to the diagnosis (or not) of a chronic illness such as diabetes.