College of American Pathologists



Hemoglobin A1C and Microalbuminuria: What Physicians Need to Know

Posted November 1, 2010

Kristin A. Olson, MD

Diabetes mellitus encompasses a spectrum of abnormal carbohydrate metabolism diseases associated with serious microvascular, macrovascular, and neurologic complications. Clinicians have long sought simple, reproducible means of assessing diabetic patients for their risk of progressive disease, with hemoglobin A1C (HbA1C) and microalbuminuria testing frequently employed for this purpose.

Hemoglobin A1C is a measure of glycated hemoglobin that estimates the mean blood glucose concentration over the life span of the red blood cell (normally 120 days). Most commonly, HbA1C is used to evaluate long-term glycemic control in diabetic patients. In June 2009, an International Expert Committee (IEC) issued a recommendation that HbA1C > 6.5% be used to diagnose diabetes mellitus.1,2 This recommendation was based on increased patient convenience, the strong correlation between HbA1C and retinopathy, and multiple technical advantages of newer HbA1C assays over fasting plasma glucose (FPG) testing.3,4 The National Health and Nutrition Examination Survey (NHANES), conducted from 1999 to 2004, demonstrated that an HbA1C of 5.8% had the highest sensitivity and specificity (86% and 92%, respectively) for the diagnosis of diabetes mellitus; Buell et al proposed that those individuals with HbA1C > 5.8% return for a fasting plasma glucose test for confirmation of the diagnosis.5 Other studies have had comparable results, suggesting that HbA1C and FPG are similarly useful in the detection of diabetes mellitus.6

Another issue of significant concern in the diabetic population is the prospect of renal damage, as measured by increased urinary protein excretion. Albumin excretion of 30–300 mg/day (with < 20 mg/day considered normal) is termed microalbuminuria. When persistent, microalbuminuria is considered indicative of early diabetic nephropathy. Type 2 diabetes mellitus patients with microalbuminuria face increased long-term mortality and an increased risk of developing macroalbuminuria.7 It is important to recognize that negative urine dipstick urine proteins and even negative chemistry urine total proteins do not exclude microalbuminuria. Currently, the preferred means of screening for microalbuminuria is measurement of the urine albumin-to-creatinine ratio in an untimed urine specimen, thereby avoiding the confounding effect of urine volume variability on urine albumin concentration and/or the need to collect a 24-hour urine.8,9 With this method, urine albumin-to-creatinine values of 30–300 mg/g correspond to albumin excretion of 30–300 mg/day, suggesting that microalbuminuria is likely present. Once the albumin-to-creatinine excretion exceeds 300 mg/g, macroalbuminuria is diagnosed.

General points in the use of HbA1C and microalbuminuria testing for diabetes mellitus:

  • Hemoglobin A1C is typically used to evaluate long-term glycemic control.
  • An International Expert Committee recently recommended that HbA1C > 6.5% be used to diagnose diabetes mellitus.
  • Microalbuminuria is indicative of early diabetic nephropathy and is defined as albumin excretion between 30–300 mg/day (or urine albumin-to-creatinine values of 30–300 mg/g).
  • Measurement of urine albumin-to-creatinine ratio in an untimed urine specimen is the preferred means of screening for microalbuminuria.
  • At most hospitals, clinical pathologists are readily available for consultation regarding the use of HbA1C and microalbuminuria in the evaluation and management of diabetes mellitus.


  1. International Expert Committee. International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32(7):1327–1334.
  2. American Diabetes Association. Executive summary: standards of medical care in diabetes—2010. Diabetes Care. 2010;33(Suppl 1):S4–S10.
  3. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977–986.
  4. Tapp RJ, Tikellis G, Wong TY, et al. Longitudinal association of glucose metabolism with retinopathy: results from the Australian Diabetes Obesity and Lifestyle (AusDiab) study. Diabetes Care. 2008;31(7):1349–1354.
  5. Buell C, Kermah D, Davidson MB. Utility of A1C for diabetes screening in the 1999-2004 NHANES population. Diabetes Care. 2007;30(9):2233–2235.
  6. Bennett CM, Guo M, Dharmage SC. HbA(1c) as a screening tool for detection of Type 2 diabetes: a systematic review. Diabet Med. 2007;24(4):333–343.
  7. Newman DJ, Mattock MB, Dawnay AB, et al. Systematic review on urine albumin testing for early detection of diabetic complications. Health Technol Assess. 2005; 9(30):iii–vi, xiii–163.
  8. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139(2):137–147.
  9. Eknoyan G, Hostetter T, Bakris GL, et al. Proteinuria and other markers of chronic kidney disease: a position statement of the National Kidney Foundation (NKF) and the National Institute of Diabetes and Digestive and Kidney diseases (NIDDK). Am J Kidney Dis. 2003;42(4):617–622.

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NewsPath® Editor: C. Leilani Valdes, MD
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