Diagnosis
Elevated HbA1c levels (5.7% to 6.4%) had
low accuracy for diagnosing prediabetes
Mann DM, Carson AP, Shimbo D, et al. Impact of A1C screening
criterion on the diagnosis of pre-diabetes among U.S. adults.
Diabetes Care. 2010;33:2190-5.
Clinical impact ratings: F ★★★★★★✩ e ★★★★★★✩
Question
Commentary
In patients without diabetes, what is the agreement of hemoglobin
(Hb) A1c and fasting plasma glucose (FPG) tests and what is the
accuracy of elevated HbA1c levels (5.7% to 6.4%) for diagnosis of
prediabetes?
Prediabetes is typically diagnosed by FPG or a 2-hour poststandard
oral glucose tolerance test. Compared with FPG, HbA1c is costly;
may not be available or standardized around the world; and may
vary by age, race, or coexistence of anemia and hemoglobinopathies
(1). Conversely, HbA1c registers glycemia over a longer time,
making it more robust than glucose measures, which are susceptible to recent changes. The study by Mann and colleagues adds
that HbA1c also identifies a different set of people as having prediabetes from that identified by FPG.
Methods
Design: Comparison of elevated HbA1c levels (5.7% to 6.4%)
with FPG test results.
Setting: USA.
Patients: 7029 noninstitutionalized civilian adults ≥ 20 years of
age (mean age 45 y, 52% women) who participated in the National
Health and Nutrition Examination Survey between 1999 and
2006 (inclusive). Exclusion criteria included previous diabetes
diagnosis, FPG ≥ 126 mg/dL (6.99 mmol/L), HbA1c ≥ 6.5%, and
missing FPG or HbA1c measurements.
Description of test: HbA1c measured with high-performance
liquid chromatography.
Diagnostic standard: Prediabetes was defined as FPG levels of
100 to 125 mg/dL (5.5 to 6.9 mmol/L) measured in the morning
after a 9- to 24-hour fast.
Outcomes: Included agreement of HbA1c and FPG results and
sensitivity and specificity of HbA1c.
Main results
HbA1c and FPG results were in agreement for diagnosis of
prediabetes in only 7.7% of patients; 20.5% of patients were
diagnosed with prediabetes by the FPG test but not the HbA1c
test and 4.9% by the HbA1c test only. Sensitivity of elevated
HbA1c levels was 27%, and specificity was 93% (Table).
We question the wisdom of diagnosing a predisease. If therapeutic
interventions were deemed necessary and helpful to treat the
large populace with predisease, there would also be real health
risks to individuals and substantial economic impact. Evidence
suggests that prediabetes has a high rate of conversion to overt
type 2 diabetes (2) and is independently linked to increased
prevalence of macrovascular disease (3). Weight loss of 4% to
7% as a result of lifestyle changes in the Diabetes Prevention Program reduced progression of prediabetes to overt type 2 diabetes
by 58% (4). While lifestyle changes also improve general health,
blood pressure, lipids, and mechanical arthropathy and limit
medication-related expenses (5, 6), 2 key questions remain. First,
does reduction in diabetes risk translate to a reduction in morbidity and mortality associated with type 2 diabetes? Second,
does labeling a patient as having prediabetes promote the uptake
of therapeutic lifestyle changes or cause adverse effects as has
been found for other asymptomatic conditions? (7)
We are asking more of HbA1c than it has been shown to deliver.
Glucose measurement should remain the cornerstone for diagnosing prediabetes in patients who might benefit from this
label—and the promise of diabetes avoidance—by initiating
or sustaining lifestyle changes.
Yogish C. Kudva, MD
Ananda Basu, MD
Mayo Clinic
Rochester, Minnesota, USA
Conclusions
In patients without diabetes, agreement between hemoglobin A1c
and fasting plasma glucose tests for diagnosis of prediabetes was
very low. The accuracy of the hemoglobin A1c range of 5.7% to
6.4% had low sensitivity and high specificity for diagnosis of
prediabetes.
Source of funding: National Institute of Diabetes and Digestive and
Kidney Diseases.
For correspondence: Dr. D. Mann, Boston University School of
Medicine, Boston, MA, USA. E-mail [email protected]. ■
Diagnostic properties of elevated hemoglobin A1c
(5.7% to 6.4%) for diagnosing prediabetes*
Sensitivity
27%
Specificity
+LR
−LR
93%
3.9
0.78
*Diagnostic terms defined in Glossary. LRs calculated from data in article.
References
1. Cohen RM, Haggerty S, Herman WH. HbA1c for the diagnosis of
diabetes and prediabetes: is it time for a mid-course correction?
J Clin Endocrinol Metab. 2010;95:5203-6.
2. Perreault L, Bergman BC, Playdon MC, et al. Impaired fasting glucose
with or without impaired glucose tolerance: progressive or parallel states of
prediabetes? Am J Physiol Endocrinol Metab. 2008;295:E428-35.
3. Meigs JB, Nathan DM, D’Agostino RB Sr, Wilson PW; Framingham
Offspring Study. Fasting and postchallenge glycemia and cardiovascular
disease risk: the Framingham Offspring Study. Diabetes Care. 2002;25:
1845-50.
4. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the
incidence of type 2 diabetes with lifestyle intervention or metformin.
N Engl J Med. 2002;346:393-403.
5. Gallego PH, Craig ME, Duffin AC, et al. Association between
p.Leu54Met polymorphism at the paraoxonase-1 gene and plantar fascia
thickness in young subjects with type 1 diabetes. Diabetes Care. 2008;
31:1585-9.
6. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a
multifactorial intervention on mortality in type 2 diabetes. N Engl J Med.
2008;358:580-91.
7. Stewart-Brown S, Farmer A. Screening could seriously damage your
health. BMJ 1997;314:533-534.
15 March 2011 | ACP Journal Club | Volume 154 • Number 3
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