Position Statement Executive Summary: Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

Abstract

Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially.
An expert committee compiled evidence-based recommendations for the use of laboratory analysis in patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. A draft of the guidelines was posted on the Internet, and the document was modified in response to comments. The guidelines were reviewed by the joint Evidence-Based Laboratory Medicine Committee of the AACC and the National Academy of Clinical Biochemistry and were accepted after revisions by the Professional Practice Committee and subsequent approval by the Executive Committee of the American Diabetes Association.
In addition to the long-standing criteria based on measurement of venous plasma glucose, diabetes can be diagnosed by demonstrating increased hemoglobin A(1c) (HbA(1c)) concentrations in the blood. Monitoring of glycemic control is performed by the patients measuring their own plasma or blood glucose with meters and by laboratory analysis of HbA(1c). The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed.
The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.

Full text

Position Statement Executive Summary:
Guidelines and Recommendations for
Laboratory Analysis in the Diagnosis and
Management of Diabetes Mellitus
DAVID B. SACKS
1
MARK ARNOLD
2
GEORGE L. BAKRIS
3
DAVID E. BRUNS
4
ANDREA RITA HORVATH
5
M. SUE KIRKMAN
6
AKE LERNMARK
7
BOYD E. METZGER
8
DAVID M. NATHAN
9
BACKGROUND—Multiple laboratory tests are used in the diagnosis and management of
patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these
assays varies substantially.
APPROACH—An expert committee compiled evidence-based recommendations for the use
of laboratory analysis in patients with diabetes. A new system was developed to grade the overall
quality of the evidence and the strength of the recommendations. A draft of the guidelines was
posted on the Intern et, and the document was modified in response to comments. The guidelines
were reviewed by the joint Evidence-Based Laboratory Medicine Committee of the AACC and the
National Academy of Clinical Biochemistry and were accepted after revisions by the Professional
Practice Committee and subsequent approval by the Executive Committee of the American
Diabetes Association.
CONTENT—In addition to the long-standing criteria based on measurement of venous plasma
glucose, diabetes can be diagnosed by demonstrating increased hemoglobin A
1c
(HbA
1c
) con-
centrations in the blood. Monitoring of glycemic control is performed by the patients measuring
their own plasma or blood glucose with meters and by labora tory analysis of HbA
1c
. The potential
roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies,
urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed.
SUMMARY—The guidelines provide specific recommendations based on published data or
derived from expert consensus. Several analytes are found to have minimal clinical value at the
present time, and measurement of them is not recommended.
Diabetes Care 34:1419–1423, 2011
Diabetes mellitus is a group of met-
abolic disorders of carbohydrate
metabolism in which glucose is
underutilized and overproduced, leading
to hyperglycemia. Diabetes is a common
disease. The current worldwide preva-
lence is estimated to be approximately
250 310
6
and is expected to reach 380 3
10
6
by 2025 (1). The most recent data,
derived from the 2005–2006 National
Health and Nutrition Examination Sur-
vey, show a prevalence of diabetes in the
U.S. in persons $20 years of age of 12.9%
(equivalent to approximately 40 310
6
people) (2), 40% (approximately 16 3
10
6
) of whom are undiagnosed. The prev-
alence of diabetes has also increased in
other parts of the world. Recent estimates
suggest 110 x 10
6
diabetic individuals in
Asia in 2007 (3), but the true number is
likely to be substantially greater, because
China alone was thought to have 92.4 3
10
6
adults with diabetes in 2008 (4).
The worldwide costs of diabetes in 2007
were approximately $232 billion and are
likely to be $302 billion by 2025 (1). The
mean annual per capita healthcare costs
for an individual with diabetes are ap-
proximately 2.3-fold higher than those
for individuals who do not have diabetes
(5). The high costs of diabetes are attrib-
utable to care for both acute conditions
(such as hypoglycemia and ketoacidosis)
and debilitating chronic microvascular
and macrovascular complications (6). To-
gether, they make diabetes the fourth
most common cause of death in the de-
veloped world (7).
The National Academy of Clinical
Biochemistry (NACB) issued its “Guide-
lines and Recommendations for Labora-
tory Analysis in the Diagnosis and
Management of Diabetes Mellitus”in
2002 (8). These recommendations were
reviewed and updated by a multidisciplin-
ary guideline team using an evidence-based
approach, especially in key areas in which
new evidence has emerged since the pre-
vious edition. The guideline committee,
whose membership was mostly from the
U.S., included clinical, laboratory, and
ccccccccccccccccccccccccccccccccccccccccccccccccc
From the
1
Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland; the
2
De-
partment of Chemistry, University of Iowa, Iowa City, Iowa; the
3
Department of Medicine, Hypertensive
Disease Unit, Section of Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, Illinois;
the
4
Department of Pathology, University of Virginia Medical School, Charlottesville, Virginia; the
5
Screening and Test Evaluation Program, School of Public Health, University of Sydney, SEALS Department
of Clinical Chemistry, Prince of Wales Hospital, Sydney, Australia; the
6
American Diabetes Association,
Alexandria, Virginia; the
7
Department of Clinical Sciences, Lund University/CRC, Skane University Hos-
pital Malmö, Malmö, Sweden; the
8
Division of Endocrinology, Northwestern University, The Feinberg
School of Medicine, Chicago, Illinois; and the
9
Massachusetts General Hospital and Harvard Medical
School, Diabetes Center, Boston, Massachusetts.
Corresponding author: David B. Sacks, sacksdb@mail.nih.gov.
Received 11 February 2011 and accepted 25 February 2011.
DOI: 10.2337/dc11-9997
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.
2337/dc11-9997/-/DC1.
This article is simultaneously published in Clinical Chemistry and Diabetes Care, under joint copyright, and by
the National Academy of Clinical Biochemistry.
© 2011 by the American Diabetes Association and the American Association for Clinical Chemistry. Readers
may use this article as long as the work is properly cited, the use is educational and not for profit, and the
work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
See accompanying article, p. e61.
care.diabetesjournals.org DIABETE S CARE,VOLUME 34, JUNE 2011 1419
Reviews/Commentaries/ADA Statements
POSITION STATEMENT EXECUTIVE SUMMARY

evidence-based guideline methodology
experts. Members of the guideline com-
mittee have disclosed any financial, per-
sonal, or professional relationships that
might constitute conflicts of interest
with this guideline and have received no
direct funding related to the development
of the recommendations. The perspec-
tives and views of various international
and national organizations, as well as
other potential stakeholders (e.g., health-
care providers, patients, policy makers,
regulatory bodies, health insurance com-
panies, researchers, and industry) were
taken into account during the public-
consultation process. A new system was
developed to grade both the overall qual-
ity of the evidence (Table 1) and the
strength of recommendations (Table 2).
The process of updating guideline recom-
mendations followed the standard oper-
ating procedures for issuing NACB
laboratory medicine practice guidelines,
and the key steps are detailed in the
guideline and accompanying supple-
ments available in the Supplementary
Data that accompanies the online version
of this report.
This guideline focuses on the practi-
cal aspects of care in order to assist with
decisions related to the use or interpreta-
tion of laboratory tests while screening,
diagnosing, or monitoring patients with
diabetes. It covers the rationale and pre-
analytical, analytical, postanalytical, and,
where applicable, emerging consider-
ations, the last of which alert the reader
to ongoing studies and potential future
aspects relevant to each analyte. The
recommendations intend to supplement
the American Diabetes Association guide-
lines and thus do not address any issues
related to the clinical management of
patients. The full version of this guideline
and its accompanying supplements are
available in the Supplementary Data that
accompanies the online version of this
report. Key recommendations are sum-
marized below.
These recommendations primarily
target laboratory professionals, general
practitioners, physicians, nurses, and
other healthcare practitioners involved
inthecareofdiabeticpatients.The
guidelines can be used by patients
(where relevant, e.g., self-monitoring of
blood glucose [SMBG]), policy makers,
and payers for healthcare, as well as by
researchers and manufacturers. Al-
though the recommendations were de-
veloped for national and international
use and were intended to be generic,
certain recommendations may not reflect
views that are universally held or may
have limited applicability in healthcare
settings with differing organizational,
cultural, and economic backgrounds.
The guideline committee therefore advises
users to adapt recommendations to local
settings.
The next review of this guideline is
planned in 5 years, unless substantial new
evidence emerges earlier for high-priority
areas in the laboratory management of
patients with diabetes mellitus.
RECOMMENDATIONS—Capital
letters denote the grade of recommenda-
tions, and categories in brackets refer to
the quality of the underlying body of
evidence supporting each recommenda-
tion. The grading system is described in
Tables 1 and 2.
1. Glucose
a. When glucose is used to establish the
diagnosis of diabetes, it should be mea-
sured in venous plasma. A(high)
b. When glucose is used for screening
of high-risk individuals, it should be
measured in venous plasma. B(moder-
ate)
c. Plasma glucose should be measured in
an accredited laboratory when used for
diagnosis of or screening for diabetes.
GPP (good practice point)
d. Outcome studies are needed to de-
termine the effectiveness of screening.
C(moderate)
e. Routine measurement of plasma glu-
cose concentrations in an accredited
laboratory is not recommended as the
primary means of monitoring or evaluat-
ing therapy in individuals with diabetes.
B (low)
f. Blood for fasting plasma glucose anal-
ysis should be drawn in the morning after
the individual has fasted overnight (at
least 8 h). B(low)
g. To minimize glycolysis, one should
place the sample tube immediately in an
ice–water slurry, and plasma should be
separated from the cells within 30 min. If
that cannot be achieved, a tube containing
a rapidly effective glycolysis inhibitor,
such as citrate buffer, should be used for
collecting the sample. Tubes with only
enolase inhibitors, such as sodium fluo-
ride, should not be relied on to prevent
glycolysis. B (moderate)
h. On the basis of biological variation,
glucose measurement should have an an-
alytical imprecision #2.9%, a bias #2.2%,
and a total error #6.9%. To avoid mis-
classification of patients, the goal for glu-
cose analysis should be to minimize total
analytical error, and methods should be
without measurable bias. B (low)
2. Glucose meters
a. There are insufficient published data to
support a role for portable meters and
skin-prick (finger-stick) blood samples in
the diagnosis of diabetes or for population
screening. C(moderate)
b. The imprecision of the results, coupled
with the substantial differences among
meters, precludes the use of glucose meters
from the diagnosis of diabetes and limits
their usefulness in screening for diabetes.
A(moderate)
Table 1—Rating scale for the quality of evidence
High: Further research is very unlikely to change our confidence in the estimate of effect. The body of evidence comes from high-level individual
studies that are sufficiently powered and provide precise, consistent, and directly applicable results in a relevant population.
Moderate: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate and the
recommendation. The body of evidence comes from high-/moderate-level individual studies that are sufficient to determine effects, but the
strength of the evidence is limited by the number, quality, or consistency of the included studies; generalizability of results to routine practice; or
indirect nature of the evidence.
Low: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate and
the recommendation. The body of evidence is of low level and comes from studies with serious design flaws, or evidence is indirect.
Very low: Any estimate of effect is very uncertain. Recommendation may change when higher-quality evidence becomes available. Evidence is
insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct,
gaps in the chain of evidence, or lack of information.
1420 DIABETES CARE,VOLUME 34, JUNE 2011 care.diabetesjournals.org
Position Statement Executive Summary

c. SMBG is recommended for all insulin-
treated patients with diabetes. A (high)
d. In patients with type 2 diabetes treated
with diet and oral agents, SMBG may help
achieve better control, particularly when
therapy is initiated or changed. Data are
insufficient, however, to claim an associ-
ated improvement of health outcomes.
The role of SMBG in patients with stable
type 2 diabetes controlled by diet alone is
not known. C(high)
e. Patients should be instructed in the
correct use of glucose meters, includ-
ing quality control. Comparison between
SMBG and concurrent laboratory glucose
analysis should be performed at regular
intervals to evaluate the performance of the
meters in the patient’s hands. B (moderate)
f. Multiple performance goals for portable
glucose meters have been proposed. These
targets vary widely and are highly contro-
versial. Manufacturers should work to im-
prove the imprecision of current meters,
with an intermediate goal of limiting total
error for 95% of samples to #15% at
glucose concentrations $5.6 mmol/L (100
mg/dL) and to ,0.8 mmol/L (15 mg/dL) at
glucose concentrations ,5.6 mmol/L (100
mg/dL). Lower total error would be desir-
able and may prove necessary in tight
glucose-control protocols and for avoiding
hypoglycemia in all settings. C(low)
g. Meters should measure and report
plasma glucose concentrations to facilitate
comparison with assays performed in ac-
credited laboratories. GPP
h. Studies are needed to determine the
analytical goals (quality specifications) for
glucose meters in SMBG and in intensive
care units. C (moderate)
i. Recommendations for future research:
Important end points in studies of SMBG
should include, at a minimum, hemoglo-
bin A
1c
(HbA
1c
) and frequency of hypo-
glycemic episodes to ascertain whether
improved meters enable patients to achieve
better glucose control. For studies of meter
use in intensive or critical care, important
end points include mean blood glucose,
frequency of hypoglycemia, and variation
of glucose control. Ideally, outcomes (e.g.,
long-term complications) should also be
examined. GPP
3. Continuous minimally invasive
glucose analyses
a. Real-time continuous glucose moni-
toring (CGM) in conjunction with in-
tensive insulin regimens can be a useful
tool to lower HbA
1c
in selected adults
Table 2—Grading the strength of recommendations
A. The NACB strongly recommends adoption
Strong recommendations for adoption are made when
cThere is high-quality evidence and strong or very strong agreement of experts that the intervention improves important health outcomes
and that benefits substantially outweigh harms; or
cThere is moderate-quality evidence and strong or very strong agreement of experts that the intervention improves important health
outcomes and that benefits substantially outweigh harms.
Strong recommendations against adoption are made when
cThere is high-quality evidence and strong or very strong agreement of experts that the intervention is ineffective or that benefits are closely
balanced with harms, or that harms clearly outweigh benefits; or
cThere is moderate-quality evidence and strong or very strong agreement of experts that the intervention is ineffective or that benefits are
closely balanced with harms, or that harms outweigh benefits.
B. The NACB recommends adoption
Recommendations for adoption are made when
cThere is moderate-quality evidence and level of agreement of experts that the intervention improves important health outcomes and that
benefits outweigh harms; or
cThere is low-quality evidence but strong or very strong agreement and high level of confidence of experts that the intervention improves
important health outcomes and that benefits outweigh harms; or
cThere is very low–quality evidence but very strong agreement and very high level of confidence of experts that the intervention improves
important health outcomes and that benefits outweigh harms.
Recommendations against adoption are made when
cThere is moderate-quality evidence and level of agreement of experts that the intervention is ineffective or that benefits are closely balanced
with harms, or that harms outweigh benefits; or
cThere is low-quality evidence but strong or very strong agreement and high level of confidence of experts that the intervention is ineffective
or that benefits are closely balanced with harms, or that harms outweigh benefits; or
cThere is very low–q uality evidence but very strong agreement and very high levels of confidence of experts that the intervention is ineffective
or that benefits are closely balanced with harms, or that harms outweigh benefits.
C. The NACB concludes that there is insufficient information to make a recommendation
Grade C is applied in the following circumstances:
cEvidence is lacking or scarce or of ver y low quality, the balance of benefits and harms cannot be determined, and there is no or very low level
of agreement of experts for or against adoption of the recommendation.
cAt any level of evidence—particularly if the evidence is heterogeneous or inconsistent, indirect, or inconclusive—if there is no agreement of
experts for or against adoption of the recommendation.
GPP. The NACB recommends it as a good practice point
GPPs are recommendations mostly driven by expert consensus and professional agreement and are based on the information listed below and/or
professional experience, or widely accepted standards of best practice. This category applies predominately to technical (e.g., preanalytical,
analytical, postanalytical), organizational, economic, or quality-management aspects of laboratory practice. In these cases, evidence often comes
from observational studies, audit reports, case series or case studies, nonsystematic reviews, guidance or technical documents, non–evidence-
based guidelines, personal opinions, expert consensus, or position statements. Recommendations are often based on empirical data, usual
practice, quality requirements and standards set by professional or legislative authorities or accreditation bodies, and so forth.
care.diabetesjournals.org DIABETE S CARE,VOLUME 34, JUNE 2011 1421
Sacks and Associates

(age .25 years) with type 1 diabetes.
A(high)
b. Although the evidence for lowering
HbA
1c
is not as strong for children, teens,
and younger adults, real-time CGM may
be helpful in these groups. Success corre-
lates with adherence to ongoing use of the
device. B (moderate)
c. Real-time CGM may be a supplemental
tool to SMBG in individuals with hypo-
glycemia unawareness and/or frequent
episodes of hypoglycemia. B(low)
d. Patients require extensive training in
using the device. Available devices must
be calibrated with SMBG readings, and
the latter are recommended for making
treatment changes. GPP
4. Noninvasive glucose analysis
a. No noninvasive sensing technology is
currently approved for clinical glucose
measurements of any kind. Major tech-
nological hurdles must be overcome be-
fore noninvasive sensing technology will
be sufficiently reliable to replace existing
portable meters, implantable biosensors,
or minimally invasive technologies.
C(verylow)
5. Gestational diabetes mellitus
a. All pregnant women not previously
known to have diabetes should undergo
testing for gestational diabetes mellitus
(GDM) at 24–28 weeks of gestation.
A(high)
b. GDM should be diagnosed by a 75-g
oral glucose tolerance test according to
the IADPSG (International Association
of the Diabetes and Pregnancy Study
Groups) criteria derived from the HAPO
(Hyperglycemia and Adverse Pregnancy
Outcome) study. A (moderate)
6. Urinary glucose
a. Semiquantitative urine glucose testing
is not recommended for routine care of
patients with diabetes mellitus. B(low)
7. Ketone testing
a. Ketones measured in urine or blood in
the home setting by patients with diabetes
and in the clinic/hospital setting should be
considered only an adjunct to the diagnosis
of diabetic ketoacidosis (DKA). GPP
b. Urine ketone measurements should not
be used to diagnose or monitor the course
of DKA. GPP
c. Blood ketone determinations that rely
on the nitroprusside reaction should be
used only as an adjunct to diagnose
DKAandshouldnotbeusedtomonitor
DKA treatment. Specific measurement of
b-hydroxybutyric acid in blood can be
used for diagnosis and monitoring of
DKA. B (moderate)
8. HbA
1c
a. HbA
1c
should be measured routinely in
all patients with diabetes mellitus to doc-
ument their degree of glycemic control.
A (moderate)
b. Laboratories should use only HbA
1c
assay methods that are certified by the
National Glycohemoglobin Standardiza-
tion Program (NGSP) as traceable to the
DCCT (Diabetes Control and Complica-
tions Trial) reference. The manufacturers
of HbA
1c
assays should also show trace-
ability to the IFCC reference method.
GPP
c. Laboratories that measure HbA
1c
should participate in a proficiency-testing
program, such as the College of American
Pathologists (CAP) HbA
1c
survey, that
uses fresh blood samples with targets set
by the NGSP Laboratory Network. GPP
d. Laboratories should be aware of po-
tential interferences, including hemoglo-
binopathies, that may affect HbA
1c
test
results, depending on the method used.
In selecting assay methods, laboratories
should consider the potential for interfer-
ences in their particular patient popula-
tion. In addition, disorders that affect
erythrocyte turnover may cause spurious
results, regardless of the method used.
GPP
e. Desirable specifications for HbA
1c
mea-
surement are an intralaboratory CV ,2%
andaninterlaboratoryCV,3.5%. At
least two control materials with different
mean values should be analyzed as an in-
dependent measure of assay performance.
B(low)
f. Samples with HbA
1c
results below the
lower limit of the reference interval
or .15% HbA
1c
should be verified by re-
peat testing. B(low)
g. HbA
1c
values that are inconsistent with
the clinical presentation should be inves-
tigated further. GPP
h. Treatment goals should be based on
American Diabetes Association recommen-
dations, which include generally maintain-
ing HbA
1c
concentrations at ,7% and
more-stringent goals in selected individual
patients if they can be achieved without
significant hypoglycemia or other adverse
treatment effects. Somewhat higher inter-
vals are recommended for children and
adolescents and may be appropriate for pa-
tients with limited life expectancy, exten-
sive comorbid illnesses, a history of severe
hypoglycemia, or advanced complications
(note that these values are applicable only if
the NGSP has certified the assay method as
traceable to the DCCT reference). A (high)
i. HbA
1c
testing should be performed at
least biannually in all patients and quar-
terly for patients whose therapy has
changed or who are not meeting treat-
ment goals. B(low)
j. HbA
1c
may be used for the diagnosis of
diabetes, with values $6.5% being diag-
nostic. An NGSP-certified method should
be performed in an accredited laboratory.
Analogous to its use in the management of
diabetes, factors that interfere with or ad-
versely affect the HbA
1c
assay will pre-
clude its use in diagnosis. A (moderate)
k. Point-of-care HbA
1c
assays are not suf-
ficiently accurate to use for the diagnosis
of diabetes. B (moderate)
9. Genetic markers
a. Routine measurement of genetic mark-
ersisnotofvalueatthistimeforthe
diagnosis or management of patients with
type 1 diabetes. For selected diabetic syn-
dromes, including neonatal diabetes,
valuable information can be obtained
with definition of diabetes-associated mu-
tations. A(moderate)
b. There is no role for routine genetic
testing in patients with type 2 diabetes.
These studies should be confined to the
research setting and evaluation of specific
syndromes. A (moderate)
10. Autoimmune markers
a. Islet cell autoantibodies are recom-
mended for screening nondiabetic family
members who wish to donate part of their
pancreas for transplantation into a relative
with end-stage type 1 diabetes. B(low)
b. Islet cell autoantibodies are not recom-
mended for routine diagnosis of diabetes,
but standardized islet cell autoantibody
tests may be used for classification of
diabetes in adults and in prospective
studies of children at genetic risk for
type 1 diabetes after HLA typing at birth.
B(low)
c. Screening patients with type 2 diabetes
for islet cell autoantibodies is not recom-
mended at present. Standardized islet cell
autoantibodies are tested in prospective
clinical studies of type 2 diabetic patients
to identify possible mechanisms of sec-
ondary failures of treatment of type 2
diabetes. B(low)
d. Screening for islet cell autoantibodies
in relatives of patients with type 1 di-
abetes or in persons from the general
population is not recommended at pres-
ent. Standardized islet cell autoantibodies
1422 DIABETES CARE,VOLUME 34, JUNE 2011 care.diabetesjournals.org
Position Statement Executive Summary

are tested in prospective clinical studies.
B(low)
e. There is currently no role for measure-
ment of islet cell autoantibodies in the
monitoring of patients in clinical practice.
Islet cell autoantibodies are measured in
research protocols and in some clinical
trials as surrogate end points. B(low)
f. It is important that islet cell autoanti-
bodies be measured only in an accredited
laboratory with an established quality-
control program and participation in a
proficiency-testing program. GPP
11. Albuminuria (formerly
microalbuminuria)
a. Annual testing for albuminuria in pa-
tients without clinical proteinuria should
begin in pubertal or postpubertal indi-
viduals 5 years after diagnosis of type 1
diabetes and at the time of diagnosis
of type 2 diabetes, regardless of treatment.
B (moderate)
b. Urine albumin at concentrations $30
mg/g creatinine should be considered as a
continuous risk marker for cardiovascular
events. B (moderate)
c. The analytical CV of methods to mea-
sure albuminuria should be ,15%.
B (moderate)
d. Semiquantitative or qualitative screen-
ing tests should be positive in .95% of
patients with albuminuria to be useful for
screening. Positive results must be con-
firmed by analysis in an accredited labo-
ratory. GPP
e. Currently available dipstick tests do not
have adequate analytical sensitivity to
detect albuminuria. B(moderate)
f. Acceptable samples to test for increased
urinary albumin excretion are timed collec-
tions(e.g.,12or24h)forthemeasurement
of albumin concentration and timed or
untimed samples for measurement of the
albumin–creatinine ratio. B (moderate)
g. The optimal time for spot urine collec-
tion is the early morning. All collections
should be at the same time of day to min-
imize variation. The patient should not
have ingested food within the preceding
2 h, but should be well hydrated (i.e., not
volume depleted). GPP
h. Low urine albumin concentrations
(i.e., ,30 mg/g creatinine) are not associ-
ated with high cardiovascular risk if the
estimated glomerular filtration rate (eGFR)
is .60 mL zmin
21
z(1.73 m
2
)
21
and
the patient is normotensive. If the eGFR
is ,60 mL zmin
21
z(1.73 m
2
)
21
and/or
the level of albuminuria is $30 mg/g cre-
atinine on a spot urine sample, a repeat
measurement should be taken within the
year to assess change among people with
hypertension. A (moderate)
12. Miscellaneous potentially
important analytes
a. There is no role for routine testing for
insulin, C-peptide, or proinsulin in most
patients with diabetes. Differentiation be-
tween type 1 and type 2 diabetes may be
made in most cases on the basis of the
clinical presentation and the subsequent
course. These assays are useful primarily
for research purposes. Occasionally, C-
peptide measurements may help distin-
guish type 1 from type 2 diabetes in
ambiguous cases, such as patients who
have a type 2 phenotype but present in
ketoacidosis. B (moderate)
b. There is no role for measurement of
insulin concentration in the assessment of
cardiometabolic risk, because knowledge
of this value does not alter the manage-
ment of these patients. B (moderate)
c. Because current measures of insulin are
poorly harmonized, a standardized insu-
lin assay should be developed to encour-
age the development of measures of
insulin sensitivity that will be practical
for clinical care. GPP
d. There is no published evidence to
support the use of insulin antibody test-
ing for routine care of patients with di-
abetes. C(verylow)
Acknowledgments—Upon manuscript sub-
mission, all authors completed the Disclosures
of Potential Conflict of Interest form. D.B.S.
and D.E.B. reported employment or leader-
ship positions with Clinical Chemistry, AACC.
M.A. reported employment or leadership
positions with, research funding from, and
stock ownership in ASL Analytical, Inc. G.L.B.
reported consultant or advisory role for
Novartis, Takeda, Johnson & Johnson, and
Merck and received research funding from
GlaxoSmithKline, Forest Laboratories, and
Novartis. D.E.B. received research funding
from Abbott Diagnostics, Siemens, and BD.
A.R.H. reported honoraria from MediLab Ltd.
(Hungary) and received other remuneration
from Diagon Ltd. Hungary, Roche Diagnostics
(Hungary), and Becton Dickinson.A.L. reported
consultant or advisory role for Diamyd Medical
AB and Probi AB. No other potential conflicts
of interest relevant to this article were reported.
The funding organizations played no role in
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