HbA1C no doubt reflects the past status of blood glucose level but when it is not detectable then fasting blood glucose shoukld be checked twice in a week.

May wish to do an oral glucose tolerance test. Although it would be unusual not see some elevation in HbA1c, if the fasting abnormality is isolated and generally minimally elevated, the HbA1c may underestimate the severity of the dysglycemic condition. (The positive predictive value is low). It may be worthwhile obtaining a fructosamine and a hemoglobin electrophoresis, CBC (anemia may obscure the HbA1c level as well), metabolic panel (renal function).

As you have affirmed, the HbA1c is an average indicator of the blood glucose for the past 120 days (approx). But, in the medical case you have mentioned, the following issues need to be addressed i) the patient has to clarify that neither health drinks nor any confectioneries were not taken in the morning before test. ii). Whether, both the FPG and the HbA1c test was repeated for confirmation. iii) Whether, the patient is having the normal RBC life span of 120 days and the patient had not undergone any surgery that incurred a heavy blood loss iv) The observed value of the HbA1c was not given in this case, as per the diagnostic criteria set by the ADA it should >= 6.5% for diabetes. v) Further, in this medical case, the gender and age of the patient was not given; if the patient was female and aged around 45 years, there could be a sudden onset of the diabetes due to significant hormonal disturbances at the menopause stage.

There are clear differences in the rate of hemoglobin glycosylation in some populations and individual patients (i.e. rapid or slow glycosylators). Although the ADA adapted 6.5% as a diagnostic criteria for patients to have diabetes clinical findings from that time have clearly shown that some patient do not follow the mathematical models correlating HbA1c to blood sugar and in these patients the blood glucose should be monitored. If closely followed the HbA1c correlation for these patients and there average glycemic control can be assessed and the A1c then followed. The reason for rapid and slow glycators is uncertain at this time, but likely represents very subtle variations in the hemoglobin molecule that have no other clinical effect.

It is also not described what the surgery was for an the one time elevated blood sugar could be secondary to significant physiological stress, emotional stress, medication, a laboratory error or anyone of a number of factors and the first step would be repeating the HgbA1c, fasting glucose and considering a 2 hour OGTT and Fructosamine could be helpful to confirm whether there have been new stable increases in sugars.

All of the above answers are also applicable.

Repeat test for HbA1c showed same result, i,e, undetectable

If the HbA1c is truly undetectable or extremely low in this patient there is most likely either an interfering substance in the blood which can sometimes resolve or a there subtle variant hemoglobin. You should look for other underlying medical conditions and consider appropriate referral to specialists. You now need to use the blood glucose and can utilize the Fructosamine test for following glycemic control.

It is reasonable to occasional measure the HbA1c in the event there is an interfering substance causing the issue. Additionally, if the HbA1c is extremely low but detectable and there is a stable defect in this patient's hemoglobin the average blood glucose values from a CGMS could be compared to the A1c on several occasions and curve correlating A1c to glycemic control created for this individual patient.

An undetectable HbA1c clearly indicates either a faulty laboratory test (highly unlilkely in case of repeated tests) or an underlying hemoglobinopathy. As no human being is able to survive without physiological concentrations of glucose in the blood it is an undeniable fact that part of HbA is glycated during the lifetime of the erythrocyte. In sickle cell disease it is reported that depending on the laboratory method used results may range from undetectable to encreased. Whithout hemoglobinopathy high erythrocyte turnover or increased erythropoesis may lead to false low HbA1c levels but not to undetectable results. Even after mass transfusion you would expect the blood of the donor to contain normal HbA1c levels.

In the presence of hemoglobinopathy, anemia or other identified interferences HbA1c cannot be used to indicate glycemic control. You will have to refer to fructosamin or regular blood glucose testing.

Hypoglcemia risk is the main problem if you want to know the patients profile during

the last 2 months. All the above answers are useful, but the risk of hypoglycemia during nigth hours may be one of the important issues in diabetes care. Many trials including HbA1C show the limitations of HbA1C as a only marker of diabetes good control.

1) Yes, it does in untreated or inadequately treated established diabetes. By the term established diabetes, I mean confirmed by oral glucose tolerance test with 1-h level and 2-h level >_ 200 mg/dL (>_ 11.1 mmol/L).

2) In condition of elevated glucose associated with thiazide diuretic, beta blocker or other anti-hypertensive therapy, HbA1c may not reflect past glycemic status.

3) HbA1c is unlikely to reflect glycemic control in anemia due to diverse etiology. More importantly, anemia associated with real failure when insulin level rises giving rise to misleading information of glycemic control.

4) Similarly in chronic liver disease when glycogen storage is defective, relationship between glycemic control and HbA1c may be erroneous.

What method was used for A1c (glycated HbA on the 1st amino-terminal valine residue of the beta chain) assessment? Was HPLC? If it was HPLC, at least 2-3% should have been detected IF THE PATIENT HAS HbA...For a glucose level of 139 mg/dl, you should not expect a A1c too high, anyway :

Estimated average glucose (eAG):

eAG (mg/dl) =28.7 X A1C –46.7

If the patient does NOT have HbA (e.g. HbS/S, S/C, C/C, etc) no A1c would be detected. However, as glucation of Hb does still occur, the glycated Hb (in this case S1c, C1c, etc) can be assessed with immunoassay, not with HPLC...Nevertheless, in the case of HbSS (or other homozygote Hb variants) patients which are transfustion dependent, the glycated Hb level would NOT reflect the reality of glucose and glycated Hb concentration in patient's blood, as the patient has in circulation the donor's blood as well. In this situation, fructosamine (glycated albumin) assessment and quantitative determination of glycated serum protein (GSP) would be recommended. In this case, fructosamine would reflect the average glucose level in the last 2-3 weeks (vs 2-3 months in the case of HbA1c) in patient's blood.

I hope thiswould help.

If you have further question and/or need more help you can contact me even directly.

Alina G. Sofronescu PhD, MSc

Clinical Chemist

Technical Director Clinical Chemistry Laboratory

Assistant Professor

983135 University Nebraska Medical Center

Omaha, Nebraska 68198-5520

Ph: (402) 559-8335

Email: [email protected]

One more thing...There is, most likely nothing wrong with lal, lab's method or instrumentation! (if you have repeted the glucose tests and the level was similar...) Do NOT blame on this! Dig more in to Hb...Assess Hb variants (HPLC)...I'm almost sure that the patient does not Have HbA, but he/she is homozygote for Hb variants (No HbA, no HbA1c)...Let me know if you need further help.

In my opinion HbA1c always reflect past status of glucose level in diabetes mellitus and corresponds also with diabetic retinopathy severety.