Diabetes Care Volume 48, Supplement 1, January 2025 S27

2. Diagnosis and Classification of American Diabetes Association

Professional Practice Committee*
Diabetes: Standards of Care in
Diabetes—2025
Diabetes Care 2025;48(Suppl. 1):S27–S49 | https://doi.org/10.2337/dc25-S002

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2. DIAGNOSIS AND CLASSIFICATION OF DIABETES
The American Diabetes Association (ADA) “Standards of Care in Diabetes” includes
the ADA’s current clinical practice recommendations and is intended to provide the
components of diabetes care, general treatment goals and guidelines, and tools to
evaluate quality of care. Members of the ADA Professional Practice Committee, an
interprofessional expert committee, are responsible for updating the Standards of
Care annually, or more frequently as warranted. For a detailed description of ADA
standards, statements, and reports, as well as the evidence-grading system for ADA’s
clinical practice recommendations and a full list of Professional Practice Committee
members, please refer to Introduction and Methodology. Readers who wish to com-
ment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Diabetes mellitus is a group of metabolic disorders of carbohydrate metabolism in

which glucose is both underutilized as an energy source and overproduced due to in-
appropriate gluconeogenesis and glycogenolysis, resulting in hyperglycemia (1). Diabe-
tes can be diagnosed by demonstrating increased concentrations of glucose in venous
plasma or increased A1C in the blood. Diabetes is classified conventionally into sev-
eral clinical categories (e.g., type 1 or type 2 diabetes, gestational diabetes mellitus,
and other specific types derived from other causes, such as monogenic diabetes, exo-
crine pancreatic disorders, and high-risk medications) (2).

DIAGNOSTIC TESTS FOR DIABETES

Diabetes may be diagnosed based on A1C or plasma glucose criteria. Plasma glucose
criteria include either the fasting plasma glucose (FPG), 2-h plasma glucose (2-h PG)
during a 75-g oral glucose tolerance test (OGTT), or random glucose accompanied by
classic hyperglycemic symptoms (e.g., polyuria, polydipsia, and unexplained weight
loss) or hyperglycemic crises (i.e., diabetic ketoacidosis [DKA] and/or hyperglycemic
hyperosmolar state [HHS]) (Table 2.1). *A complete list of members of the American
Diabetes Association Professional Practice Committee
Recommendations can be found at https://doi.org/10.2337/dc25-SINT.
2.1a Diagnose diabetes based on A1C or plasma glucose criteria. Plasma glucose Duality of interest information for each author is
criteria include either the fasting plasma glucose (FPG), 2-h plasma glucose (2-h PG) available at https://doi.org/10.2337/dc25-SDIS.
during a 75-g oral glucose tolerance test (OGTT), or random glucose accompanied Suggested citation: American Diabetes Association
by classic hyperglycemic symptoms/crises (Table 2.1). B Professional Practice Committee. 2. Diagnosis and
classification of diabetes: Standards of Care in
2.1b In the absence of unequivocal hyperglycemia (e.g., hyperglycemic crises), Diabetes—2025. Diabetes Care 2025;48(Suppl. 1):
diagnosis requires confirmatory testing (Table 2.1). B S27–S49
© 2024 by the American Diabetes Association.
Readers may use this article as long as the
work is properly cited, the use is educational
Screening and Diagnosis of Diabetes and not for profit, and the work is not altered.
FPG, 2-h PG during 75-g OGTT, and A1C are appropriate for screening and diagno- More information is available at https://www
sis. It should be noted that detection rates of different screening tests vary in both .diabetesjournals.org/journals/pages/license.
S28 Diagnosis and Classification of Diabetes Diabetes Care Volume 48, Supplement 1, January 2025

of random plasma glucose is sufficient

Table 2.1—Criteria for the diagnosis of diabetes in nonpregnant individuals
to diagnose diabetes (symptoms of hy-
A1C $6.5% ($48 mmol/mol). The test should be performed in a laboratory using a method perglycemia or hyperglycemic crisis plus
that is NGSP certified and standardized to the DCCT assay.* random plasma glucose $200 mg/dL
OR [$11.1 mmol/L]). In these cases, know-
FPG $126 mg/dL ($7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.* ing the plasma glucose level is critical be-
OR
cause, in addition to confirming that
symptoms are due to diabetes, it will in-
2-h PG $200 mg/dL ($11.1 mmol/L) during OGTT. The test should be performed as
form management decisions. Health care
described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous
glucose dissolved in water.*
professionals may also want to know the
A1C to determine the chronicity of hyper-
OR
glycemia. However, in an individual with-
In an individual with classic symptoms of hyperglycemia or hyperglycemic crisis, a random out symptoms, FPG or 2-h PG can be used

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plasma glucose $200 mg/dL ($11.1 mmol/L). Random is any time of the day without for screening and diagnosis of diabetes. In
regard to time since previous meal.
nonpregnant individuals, FPG (or A1C) is
DCCT, Diabetes Control and Complications Trial; FPG, fasting plasma glucose; OGTT, oral glu- typically preferred for routine screening due
cose tolerance test; NGSP, National Glycohemoglobin Standardization Program; WHO, World to the ease of administration (Table 2.3);
Health Organization; 2-h PG, 2-h plasma glucose. *In the absence of unequivocal hypergly- however, the 2-h PG (OGTT) testing pro-
cemia, diagnosis requires two abnormal results from different tests which may be obtained
at the same time (e.g., A1C and FPG), or the same test at two different time points.
tocol diagnoses more diabetes than the
other two tests and is preferentially rec-
ommended for screening for some condi-
populations and individuals. FPG, 2-h PG, clinical scenarios—in seemingly low-risk tions (e.g., cystic fibrosis-related diabetes
and A1C reflect different aspects of glu- individuals who happen to have glucose or posttransplantation diabetes mellitus).
cose metabolism, and diagnostic cut points testing, in individuals screened based on In the absence of classic hyperglycemic
for the different tests will identify groups diabetes risk assessment, and in symp- symptoms, repeat testing is required to
with incomplete concordance (3). Com- tomatic individuals. There is presently confirm the diagnosis regardless of the
pared with FPG and A1C cut points, the insufficient evidence to support the use test used (see CONFIRMING THE DIAGNOSIS,
2-h PG value diagnoses more people of continuous glucose monitoring (CGM) below).
with prediabetes and diabetes (4). More- for screening or diagnosis of prediabetes An advantage of glucose testing is that
over, the efficacy of interventions for pri- or diabetes. For additional details on the these assays are inexpensive and widely
mary prevention of type 2 diabetes (i.e., evidence used to establish the criteria available. Disadvantages include the high
preventing conversion of prediabetes to for the diagnosis of diabetes or prediabe- diurnal variation in glucose and fasting re-
type 2 diabetes) has been demonstrated tes, see the American Diabetes Associa- quirement. Individuals may have difficulty
mainly among individuals with prediabe- tion (ADA) position statement “Diagnosis fasting for the full 8-h period or may mis-
tes who have impaired glucose tolerance and Classification of Diabetes Mellitus” report their fasting status (Table 2.3). Re-
(IGT) with or without elevated fasting (2) and other reports (1,3,10,11). cent physical activity, illness, or acute
glucose, not for individuals with isolated stress can affect glucose concentrations.
impaired fasting glucose (IFG) or for Use of Fasting Plasma Glucose or
Glycolysis is also an important and under-
those with prediabetes defined by A1C 2-Hour Plasma Glucose for Screening recognized concern with glucose testing.
criteria (5–8). and Diagnosis of Diabetes Glucose concentrations will be falsely low
The same tests may be used to screen In the less common clinical scenario if samples are not handled properly and
for and diagnose diabetes and to detect where a person has classic hyperglyce- promptly prior to analysis (1).
individuals with prediabetes (9) (Table 2.1 mic symptoms (e.g., polyuria, polydipsia, People should follow a mixed eating
and Table 2.2). Diabetes may be identi- unexplained weight loss) or presents pattern with at least 150 g of carbohy-
fied anywhere along the spectrum of with hyperglycemic crisis, measurement drates on the 3 days prior to OGTT
(12–14). Antecedent carbohydrate re-
striction in the days prior to OGTT can
Table 2.2—Criteria defining prediabetes in nonpregnant individuals falsely elevate postchallenge glucose lev-
els, potentially resulting in a false-positive
A1C 5.7–6.4% (39–47 mmol/mol)
OGTT (12).
OR
FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (IFG) Use of A1C for Screening and
OR Diagnosis of Diabetes

2-h PG during 75-g OGTT 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) (IGT) Recommendations

For all three tests, risk is continuous, extending below the lower limit of the range and be-
2.2a The A1C test should be per-
coming disproportionately greater at the higher end of the range. FPG, fasting plasma glu- formed using a method that is certi-
cose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose fied by the National Glycohemoglobin
tolerance test; 2-h PG, 2-h plasma glucose. Standardization Program (NGSP) as
diabetesjournals.org/care Diagnosis and Classification of Diabetes S29

Table 2.3—Considerations related to the use and interpretation of laboratory measurements of glucose and A1C
Glucose A1C
Cost Inexpensive and available in most laboratories More expensive than glucose and not as
across the world widely available globally
Time frame of hyperglycemia Acute measure Chronic measure of glucose exposure over
the past 2–3 months
Preanalytic stability Poor; plasma must be separated immediately Good
or samples must be kept on ice to prevent
glycolysis
Sample Measurement can vary depending on sample Requires whole-blood sample
type (plasma, serum, whole blood) and
source (capillary, venous, arterial)

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Assay standardization Not standardized Well standardized
Fasting Fasting or timed samples required Nonfasting test; no participant preparation is
needed
Within-person variability High Low
Acute factors that can affect levels Food intake, stress, recent illness, activity Unaffected by recent food intake, stress,
illness, activity
Other individual factors that can affect test Diurnal variation, medications, alcohol, Altered erythrocyte turnover (e.g., anemia,
results smoking, bilirubin iron status, splenectomy, blood loss,
transfusion, hemolysis, glucose-6-
phosphate dehydrogenase deficiency,
erythropoietin), HIV, cirrhosis, renal failure,
dialysis, pregnancy
Test interferences Depends on specific assay: sample handling/ Depends on specific assay: hemoglobin
processing time, hemolysis, severe variants, severe hypertriglyceridemia,
hypertriglyceridemia, severe severe hyperbilirubinemia
hyperbilirubinemia

Data are from Selvin (217).

traceable to the Diabetes Control or erythropoietin therapy, plasma include specified personnel requirements
and Complications Trial (DCCT) ref- glucose criteria should be used to (including documented annual compe-
erence assay. B diagnose diabetes. B tency assessments) and participation three
2.2b Point-of-care A1C testing for dia- times per year in an approved proficiency
betes screening and diagnosis should testing program (15–18).
The A1C test should be performed using a A1C has several advantages compared
be restricted to devices approved for
method that is certified by the National with FPG and OGTT, including greater con-
diagnosis by the U.S. Food and Drug
Glycohemoglobin Standardization Program venience (fasting is not required), greater
Administration at Clinical Laboratory
(NGSP) (ngsp.org) and standardized or preanalytical stability, and fewer day-to-
Improvement Amendments–certified
traceable to the Diabetes Control and day perturbations during stress, changes
laboratories that perform testing of
Complications Trial (DCCT) reference assay. in nutrition, or illness. However, it should
moderate complexity or higher by
Outside the U.S., some assays are NGSP be noted that there is lower sensitivity
trained personnel. B
2.3 Evaluate for the possibility of a certified but many more are International of A1C at the designated cut point com-
problem or interference with either Federation of Clinical Chemistry (IFCC) cer- pared with that of 2-h PG as well as lim-
test when there is consistent and sub- tified (a similarly stringent process) (1). ited access in some parts of the world
stantial discordance between blood Point-of-care A1C assays may be NGSP (Table 2.3).
glucose values and A1C test results. B certified and cleared by the U.S. Food A1C reflects glucose bound to hemoglo-
2.4 In conditions associated with an and Drug Administration (FDA) for use in bin over the life span of the erythrocyte
altered relationship between A1C and monitoring glycemic management in peo- (120 days) and is thus a “weighted” av-
glycemia, such as some hemoglobin ple with diabetes in both Clinical Labora- erage that is more heavily affected by re-
variants, pregnancy (second and third tory Improvement Amendments (CLIA)– cent blood glucose exposure. This means
trimesters and the postpartum period), regulated and CLIA-waived settings. FDA- that clinically meaningful changes in A1C
glucose-6-phosphate dehydrogenase approved point-of-care A1C testing can can be seen in <120 days. A1C is an indi-
deficiency, HIV, hemodialysis, recent be used in laboratories or sites that are rect measure of glucose exposure, and fac-
blood loss or transfusion, hemolysis, CLIA certified, are inspected, and meet the tors that affect hemoglobin concentrations
CLIA quality standards. These standards or erythrocyte turnover can affect A1C
S30 Diagnosis and Classification of Diabetes Diabetes Care Volume 48, Supplement 1, January 2025

(e.g., thalassemia or folate deficiency) If using samples at two different time metabolomic, and other characteristics
(Table 2.3). A1C may not be a suitable points, it is recommended that the sec- and pathophysiology (1):
diagnostic test in people with anemia, ond test, which may be either a repeat of
1. Type 1 diabetes (due to autoimmune
people treated with erythropoietin, or the initial test or a different test, be per-
b-cell destruction, usually leading to
people undergoing hemodialysis or HIV formed in a timely manner. For example, absolute insulin deficiency, including
treatment (1,19,20). Some hemoglobin if the A1C is 7.0% (53 mmol/mol) and a latent autoimmune diabetes in adults)
variants can interfere with A1C test re- repeat result is 6.8% (51 mmol/mol), the 2. Type 2 diabetes (due to a nonautoim-
sults, but this depends on the specific as- diagnosis of diabetes is confirmed. Two mune progressive loss of adequate
say. For individuals with a hemoglobin different tests (such as A1C and FPG) b-cell insulin secretion, frequently on
variant but normal red blood cell turn- both having results above the diagnostic the background of insulin resistance)
over, such as those with the sickle cell threshold when collected at the same 3. Specific types of diabetes due to other
trait, an A1C assay without interfer- time or at two different time points causes, e.g., monogenic diabetes syn-
ence from hemoglobin variants should would also confirm the diagnosis. On the

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dromes, diseases of the exocrine pan-
be used. An updated list of A1C assays other hand, if an individual has discor- creas, and drug- or chemical-induced
with interferences is available at ngsp dant results from two different tests, diabetes
.org/interf.asp. Another genetic vari- then the test result that is above the diag- 4. Gestational diabetes mellitus (diabe-
ant, X-linked glucose-6-phosphate dehy- nostic cut point should be repeated, with tes diagnosed in the second or third
drogenase G202A, carried by 11% of careful consideration of factors that may trimester of pregnancy that was not
African American individuals in the U.S., is affect measured A1C or glucose levels. The clearly overt diabetes prior to gesta-
associated with a decrease in A1C of diagnosis is made based on the confirma- tion or other types of diabetes occur-
about 0.8% in homozygous men and tory screening test. For example, if an indi- ring throughout pregnancy, such as
0.7% in homozygous women compared vidual meets the diabetes criterion of A1C type 1 diabetes).
with levels in individuals without the vari- (two results $6.5% [$48 mmol/mol]) but
ant (21). Type 1 diabetes and type 2 diabetes are
not FPG (<126 mg/dL [<7.0 mmol/L]),
There is controversy regarding racial dif- heterogeneous diseases in which clinical
that person should nevertheless be consid-
ferences in A1C. Studies have found that presentation and disease progression
ered to have diabetes.
African American individuals have slightly may vary considerably. Classification is
If individuals have test results near
higher A1C levels than non-Hispanic White important for determining personalized
the margins of the diagnostic threshold,
or Hispanic people (22–25). The glucose- therapy, but some individuals cannot be
the health care professional should edu-
independent racial difference in A1C is clearly classified as having type 1 or type 2
cate the individual about the onset of
diabetes at the time of diagnosis. The tra-
small (0.3 percentage points) and may possible hyperglycemic symptoms and
ditional paradigms of type 2 diabetes
reflect genetic differences in hemoglobin repeat the test in 3–6 months.
having onset only in adults and type 1 di-
or red cell turnover that vary by ances- Consistent and substantial discor-
abetes having onset only in children are
try. There is an emerging understanding dance between glucose values and
not accurate, as both diseases occur in
of the genetic determinants of A1C (21), A1C test results should prompt addi- all age-groups. Children with type 1 dia-
but the field lacks adequate genetic tional follow-up to determine the un- betes often present with the hallmark
data in diverse populations (26,27). derlying reason for the discrepancy symptoms of polyuria/polydipsia, and
While some genetic variants might be (including evaluation for the possibility approximately half present with DKA
more common in certain race or an- of a problem or interference with either (30–32). The onset of type 1 diabetes
cestry groups, it is important that we test) and whether it has clinical implica- may be more variable in adults; they
do not use race or ancestry as proxies tions for the individual (Table 2.3). In addi- may not present with the classic symp-
for poorly understood genetic differ- tion, consider other biomarkers, such as toms seen in children and may progress
ences. Reassuringly, studies have shown fructosamine and glycated albumin, which to insulin replacement more slowly (33–35).
that the association of A1C with risk for are alternative measures of chronic hy- The features most useful in determination
complications appears to be similar in perglycemia that are approved for clinical of type 1 diabetes include younger age at
African American and non-Hispanic White use for monitoring glycemic management diagnosis (<35 years) with lower BMI
populations (28). in people with diabetes. (<25 kg/m2), unintentional weight loss, ke-
toacidosis, and plasma glucose >360 mg/dL
Confirming the Diagnosis CLASSIFICATION (>20 mmol/L) at presentation (36) (Fig. 2.1).
Unless there is a clear clinical diagnosis Other features classically associated with
Recommendation
(e.g., individual with classic symptoms of type 1 diabetes, such as ketosis without
2.5 Classify people with hyperglycemia
hyperglycemia or hyperglycemic crisis and acidosis, osmotic symptoms, family history,
into appropriate diagnostic categories
random plasma glucose $200 mg/dL to aid in personalized management. E or a history of autoimmune diseases, are
[$11.1 mmol/L]), confirmation is neces- weak discriminators. Occasionally, people
sary to establish the diagnosis. This can be with type 2 diabetes may present with
accomplished by two abnormal screening Diabetes is classified conventionally into DKA (37), particularly members of certain
test results, measured either at the same several clinical categories, although these racial, ethnic, and ancestral groups (e.g.,
time (29) or at two different time points. are being reconsidered based on genetic, African American and Hispanic/Latino
diabetesjournals.org/care Diagnosis and Classification of Diabetes S31

Flowchart for investigation of suspected type 1 diabetes in newly

diagnosed adults, based on data from White European populations

Adult with suspected type 1 diabetes1

Test islet autoantibodies2

Islet autoantibody negative

Islet autoantibody positive
(5–10% of adult-onset type 1 diabetes)

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Type 1 diabetes Age

<35 years >35 years

Are there features of monogenic diabetes?3 Unclear classification7

Make clinical decision as to
how person with diabetes
should be treated
Trial of noninsulin therapy
Yes No may be appropriate 8

Yes

Are there features of Consider C-peptide4 test

Test C-peptide4
type 2 diabetes?5 after >3 years' duration

>200 pmol/L <200 pmol/L No <200 pmol/L 200–600 pmol/L >600 pmol/L

Indeterminate 9
Genetic testing for monogenic Type 1 Type 2
diabetes where available6 Consider repeat
diabetes C-peptide at >5 years diabetes

Figure 2.1—Flowchart for investigation of suspected type 1 diabetes in newly diagnosed adults, based on data from White European populations.
1
No single clinical feature confirms type 1 diabetes in isolation. 2Glutamic acid decarboxylase (GAD) should be the primary antibody measured
and, if negative, should be followed by islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) where these tests are available. In indi-
viduals who have not been treated with insulin, antibodies against insulin may also be useful. In those diagnosed at <35 years of age who have no
clinical features of type 2 diabetes or monogenic diabetes, a negative result does not change the diagnosis of type 1 diabetes, since 5–10% of peo-
ple with type 1 diabetes do not have antibodies. 3Monogenic diabetes is suggested by the presence of one or more of the following features: A1C
<58 mmol/mol (<7.5%) at diagnosis, one parent with diabetes, features of a specific monogenic cause (e.g., renal cysts, partial lipodystrophy,
maternally inherited deafness, and severe insulin resistance in the absence of obesity), and monogenic diabetes prediction model probability >5%
(diabetesgenes.org/exeter-diabetes-app/ModyCalculator). 4A C-peptide test is only indicated in people receiving insulin treatment. A random sam-
ple (with concurrent glucose) within 5 h of eating can replace a formal C-peptide stimulation test in the context of classification. If the result is
$600 pmol/L ($1.8 ng/mL), the circumstances of testing do not matter. If the result is <600 pmol/L (<1.8 ng/mL) and the concurrent glucose is
<4 mmol/L (<70 mg/dL) or the person may have been fasting, consider repeating the test. Results showing very low levels (e.g., <80 pmol/L
[<0.24 ng/mL]) do not need to be repeated. Where a person is insulin treated, C-peptide must be measured prior to insulin discontinuation to ex-
clude severe insulin deficiency. Do not test C-peptide within 2 weeks of a hyperglycemic emergency. 5Features of type 2 diabetes include increased
BMI ($25 kg/m2), absence of weight loss, absence of ketoacidosis, and less marked hyperglycemia. Less discriminatory features include non-White
ethnicity, family history, longer duration and milder severity of symptoms prior to presentation, features of metabolic syndrome, and absence of a
family history of autoimmunity. 6If genetic testing does not confirm monogenic diabetes, the classification is unclear and a clinical decision should
be made about treatment. 7Type 2 diabetes should be strongly considered in older individuals. In some cases, investigation for pancreatic or other
types of diabetes may be appropriate. 8A person with possible type 1 diabetes who is not treated with insulin will require careful monitoring and
education so that insulin can be rapidly initiated in the event of glycemic deterioration. 9C-peptide values 200–600 pmol/L (0.6–1.8 ng/mL) are
usually consistent with type 1 diabetes or maturity-onset diabetes of the young but may occur in insulin-treated type 2 diabetes, particularly in
people with normal or low BMI or after long duration. Reprinted and adapted from Holt et al. (36).

adults), who may present with ketosis- HLA associated. An absolute requirement for for health care professionals to realize
prone type 2 diabetes (30). This form of insulin replacement therapy in affected indi- that classification of diabetes type is not
diabetes is strongly inherited and is not viduals may be intermittent. It is important always straightforward at presentation
S32 Diagnosis and Classification of Diabetes Diabetes Care Volume 48, Supplement 1, January 2025

and that misdiagnosis is common and can (e.g., glucagon-like peptide 1 receptor ago- Diagnostic accuracy may be improved
occur in 40% of adults with new type 1 nist [GLP-1 RA] or sodium–glucose cotrans- by using higher-specificity tests, using
diabetes (e.g., adults with type 1 diabe- porter 2 [SGLT2] inhibitor therapies for confirmatory testing for other autoanti-
tes misdiagnosed as having type 2 dia- potential weight and other cardiometa- bodies, and restricting testing to those
betes). In comparison, individuals with bolic benefits) and monitoring systems. with clinical features suggestive of au-
maturity-onset diabetes of the young Characterization of the underlying toimmune diabetes (48).
(MODY) may be misdiagnosed as having pathophysiology is more precisely de- The paths to b-cell demise and dys-
type 1 diabetes (36). Although difficul- veloped in type 1 diabetes than in type 2 function are less well defined in type 2
ties in distinguishing diabetes type may diabetes. It is clear from prospective diabetes, but deficient b-cell insulin
occur in all age-groups at onset, the di- studies that the persistent presence of secretion, frequently in the setting of
agnosis generally becomes more obvious two or more islet autoantibodies is a insulin resistance, appears to be the
over time in people with b-cell deficiency near-certain predictor of clinical diabe- common denominator. Type 2 diabe-
as the degree of b-cell deficiency be- tes (40). In at-risk cohorts followed from tes is associated with insulin secretory

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comes clear (Fig. 2.1). One useful clinical birth or a very young age, seroconver- defects related to genetic predisposi-
tool for distinguishing diabetes type is sion rarely occurs before 6 months of tion, epigenetic changes, inflammation,
the AABBCC approach: Age (e.g., for indi- age and there is a peak in seroconver- and metabolic stress. Future classifica-
viduals <35 years old, consider type 1 sion between 9 and 24 months of age tion schemes for diabetes will likely focus
diabetes); Autoimmunity (e.g., per- (41–43). The rate of progression is de- on the pathophysiology of the underlying
sonal or family history of autoimmune pendent on the age at first detection of b-cell dysfunction (38,49–52).
disease or polyglandular autoimmune an autoantibody, number of autoanti-
syndromes); Body habitus (e.g., BMI bodies, autoantibody specificity, and au- TYPE 1 DIABETES
<25 kg/m2); Background (e.g., family his- toantibody titer. Glucose and A1C levels
tory of type 1 diabetes); Control (pre- may rise well before the clinical onset Recommendations
ferred term is “goal,” i.e., the inability to of diabetes (e.g., changes in FPG and 2.6 Screening for presymptomatic
achieve glycemic goals on noninsulin ther- 2-h PG can occur about 6 months be- type 1 diabetes may be done by de-
apies); and Comorbidities (e.g., treatment fore diagnosis) (44), making diagnosis tection of autoantibodies to insulin,
with immune checkpoint inhibitors for feasible under ideal situations of serial glutamic acid decarboxylase (GAD),
cancer can cause acute autoimmune monitoring of individuals at high risk of islet antigen 2 (IA-2), or zinc trans-
type 1 diabetes) (36). type 1 diabetes before the onset of porter 8 (ZnT8). B
In both type 1 and type 2 diabetes, DKA. Three distinct stages of type 1 di- 2.7 Autoantibody-based screening for
genetic and environmental factors can abetes have been defined (Table 2.4) presymptomatic type 1 diabetes should
result in the progressive loss of b-cell and serve as a framework for research be offered to those with a family his-
mass and/or function that manifests and regulatory decision-making (38,45). tory of type 1 diabetes or otherwise
clinically as hyperglycemia. Once hyper- There is debate as to whether slowly known elevated genetic risk. B
glycemia occurs, people with all forms progressive autoimmune diabetes with 2.8 Having multiple confirmed islet
of diabetes are at risk for developing an adult onset should be termed latent autoantibodies is a risk factor for clin-
the same chronic complications, although autoimmune diabetes in adults (LADA) ical diabetes. Testing for dysglyce-
rates of progression may differ. The iden- or type 1 diabetes. The clinical priority mia may be used to further forecast
tification of individualized therapies for with detection of LADA is awareness near-term risk (Table 2.4). When mul-
diabetes in the future will be informed that slow autoimmune b-cell destruc- tiple islet autoantibodies are identi-
by better characterization of the many tion can occur in adults, leading to a fied, referral to a specialized center
paths to b-cell demise or dysfunction long duration of marginal insulin secre- for further evaluation and/or consid-
(38). Across the globe, many groups are tory capacity. For this classification, all eration of a clinical trial or approved
working on combining clinical, patho- forms of diabetes mediated by autoim-
therapy to potentially delay develop-
physiological, and genetic characteristics mune b-cell destruction independent of
ment of clinical diabetes should be
to more precisely define the subsets of age of onset are included under the ru-
considered. B
diabetes that are currently clustered bric of type 1 diabetes. Use of the term
2.9 Standardized islet autoantibody
into the type 1 diabetes versus type 2 LADA is common and acceptable in clini-
tests are recommended for classifica-
diabetes nomenclature with the goal of cal practice and has the practical impact
tion of diabetes in adults who have
optimizing personalized treatment ap- of heightening awareness of a popula-
phenotypic risk factors that overlap
proaches (39). A diagnosis of type 1 dia- tion of adults likely to have progressive
with those for type 1 diabetes (e.g.,
betes does not preclude also having autoimmune b-cell destruction (46), thus
younger age at diagnosis, uninten-
features classically associated with type 2 accelerating insulin initiation prior to de-
diabetes (e.g., insulin resistance, obe- terioration of glucose management or tional weight loss, ketoacidosis, or
sity, and other metabolic abnormalities), development of DKA (34,47). At the short time to insulin treatment). E
and until more precise subsets are used same time, there is evidence that ap-
in clinical practice, it may be appropriate to plication of only a single imperfect au-
categorize such an individual as having fea- toantibody test for determining LADA Immune-Mediated Diabetes
tures of both type 1 and type 2 diabetes to classification may lead to misclassification Autoimmune type 1 diabetes accounts
facilitate access to appropriate treatment of some individuals with type 2 diabetes. for 5–10% of diabetes and is caused by
diabetesjournals.org/care Diagnosis and Classification of Diabetes S33

Table 2.4—Staging of type 1 diabetes

Stage 1 Stage 2 Stage 3
Characteristics • Autoimmunity • Autoimmunity • Autoimmunity
• Normoglycemia • Dysglycemia • Overt hyperglycemia
• Presymptomatic • Presymptomatic • Symptomatic
Diagnostic criteria • Multiple islet autoantibodies • Islet autoantibodies (usually multiple) • Autoantibodies may become absent
• No IGT or IFG, normal A1C • Dysglycemia: • Diabetes by standard criteria
8 IFG: FPG 100–125 mg/dL (5.6–6.9 mmol/L)
or
8 IGT: 2-h PG 140–199 mg/dL
(7.8–11.0 mmol/L) or
8 A1C 5.7–6.4% (39–47 mmol/mol) or
$10% increase in A1C

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Adapted from Skyler et al. (38). FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; 2-h PG, 2-h plasma
glucose. Alternative additional stage 2 diagnostic criteria of 30-, 60-, or 90-min plasma glucose on oral glucose tolerance test $200 mg/dL
($11.1 mmol/L) and confirmatory testing in those aged $18 years have been used in clinical trials (84). Dysglycemia can be defined by one
or more criteria as outlined in the table.

autoimmune destruction of the pancre- should be monitored in individuals with disease, Addison disease, vitiligo, auto-
atic b-cells. Autoimmune markers include presymptomatic type 1 diabetes (57). immune hepatitis, myasthenia gravis,
islet cell autoantibodies and autoantibod- The rate of b-cell destruction is quite and pernicious anemia (see Section 4,
ies to glutamic acid decarboxylase (GAD) variable, being rapid in some individuals “Comprehensive Medical Evaluation and
(such as GAD65), insulin, the tyrosine (particularly but not exclusively in infants Assessment of Comorbidities”). Type 1
phosphatases islet antigen 2 (IA-2) and and children) and slow in others (mainly diabetes can be associated with monogenic
IA-2b, and zinc transporter 8 (ZnT8). Nu- but not exclusively adults) (44,58). Chil- polyglandular autoimmune syndromes,
merous clinical studies are being conducted dren and adolescents often present with including immune dysregulation, polyen-
to test various methods of preventing or DKA as the first manifestation of the dis- docrinopathy, enteropathy, and X-linked
delaying type 1 diabetes in those with ev- ease, and rates in the U.S. have in- (IPEX) syndrome, which is an early-onset
idence of islet autoimmunity (trialnet.org/ creased over the past 20 years (30–32). systemic autoimmune, genetic disorder
our-research/prevention-studies) (40–42, Others have modest fasting hyperglyce- caused by mutation of the forkhead box
47,53,54). The disease has strong HLA as- mia that can rapidly change to severe protein 3 (FOXP3) gene, and another dis-
sociations, with linkage to the DQB1 and hyperglycemia and/or DKA with infection
DRB1 haplotypes, and genetic screening order caused by the autoimmune regula-
or other stress. Adults may retain suffi- tor (AIRE) gene mutation (61,62).
has been used in some research studies cient b-cell function to prevent DKA for
to identify high-risk populations. Specific Introduction of immunotherapy, spe-
many years; such individuals may have cifically checkpoint inhibitors, for cancer
alleles in these genes can be either pre- remission characterized by decreased in-
disposing (e.g., DRB1*0301-DQB1*0201 treatment has led to unexpected adverse
sulin needs for months or years, eventu- events, including immune system activa-
[DR3-DQ2] and DRB1*0401-DQB1*0302
ally become dependent on insulin for tion precipitating autoimmune disease.
[DR4-DQ8]) or protective (e.g., DRB1*1501
survival, and are at risk for DKA (33–35, Fulminant onset of type 1 diabetes can
and DQA1*0102-DQB1*0602). Stage 1 of
59,60). At this later stage of the disease, occur, with DKA and low or undetectable
type 1 diabetes is defined by the presence
there is little or no insulin secretion, as levels of C-peptide as a marker of endog-
of two or more of these autoantibodies
and normoglycemia (Table 2.4). At stage 1,
manifested by low or undetectable levels enous b-cell function (63–65). Fewer than
of plasma C-peptide. Immune-mediated half of these individuals have autoanti-
the 5-year risk of developing symptomatic
type 1 diabetes is 44% overall but varies diabetes is the most common form of bodies that are seen in type 1 diabetes,
considerably based on number, titer, and diabetes in childhood and adolescence, supporting alternate pathobiology. This
specificity of autoantibodies as well as age but it can occur at any age. Autoimmune immune-related adverse event occurs in
of seroconversion and genetic risk (45). destruction of b-cells has multiple ge- just under 1% of checkpoint inhibitor–
Stage 2 includes individuals with multiple netic factors and is also related to envi- treated individuals but most commonly
islet autoantibodies and dysglycemia not ronmental factors that are still poorly occurs with agents that block the pro-
yet diagnostic of diabetes (dysglycemia defined. Although individuals did not clas- grammed cell death protein 1/programmed
can be defined by one or more criteria as sically have obesity when they presented cell death ligand 1 pathway alone or in
outlined in Table 2.4). At stage 2 of the with type 1 diabetes, obesity is increas- combination with other checkpoint in-
disease, there is 60% risk by 2 years ingly common in the general population; hibitors (66). To date, the majority of im-
and 75% risk within 5 years of develop- as such, obesity should not preclude mune checkpoint inhibitor–related cases
ing a clinical diagnosis of type 1 diabetes testing for type 1 diabetes. People with of type 1 diabetes occur in people with
(55,56). A consensus guidance provides type 1 diabetes are also prone to other high-risk HLA susceptibility haplotype for
expert recommendations on what should autoimmune disorders, such as Hashi- type 1 diabetes; however, people with
be monitored and how often these factors moto thyroiditis, Graves disease, celiac either a neutral or typically protective
S34 Diagnosis and Classification of Diabetes Diabetes Care Volume 48, Supplement 1, January 2025

HLA haplotype for type 1 diabetes can with high genetic risk (73) can identify Screening programs are available in
also develop checkpoint inhibitor–asso- many individuals who will develop type 1 Europe (e.g., Fr1da and gppad.org),
ciated type 1 diabetes (67). To date, risk diabetes. A study reported the risk of pro- Australia (e.g., type1screen.org), and the
cannot be predicted by family history or gression to type 1 diabetes from the time U.S. (e.g., trialnet.org, askhealth.org, and
autoantibodies, so all health care profes- of seroconversion to autoantibody posi- cascadekids.org). General population-based
sionals administering these medications tivity in three pediatric cohorts from screening programs may offer broader
or caring for people who have a history Finland, Germany, and the U.S. Of the testing where high-quality, validated assays
of current or past exposure to these 585 children who developed more than and resources for appropriate follow-up of
agents should be mindful of this adverse two autoantibodies, nearly 70% devel- results are available, with several coun-
effect and educate and monitor individ- oped type 1 diabetes within 10 years tries considering making such testing part
uals appropriately. and 84% within 15 years (40). These of standard care. In 2023, Italy introduced
A number of viruses have been associ- findings are highly significant, because nationwide screening for type 1 diabetes
ated with type 1 diabetes, including enter- while the German group was recruited and celiac disease in the general popula-

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oviruses such as Coxsackievirus B. During from offspring of parents with type 1 di- tion aged 1–17 years (83). Individuals who
the coronavirus disease 2019 (COVID-19) abetes, the Finnish and American groups test autoantibody positive should be
pandemic, numbers of cases of hypergly- were recruited from the general popula- provided with or referred for counseling
cemia, DKA, and new diabetes increased, tion. Remarkably, the findings in all three about the risk of developing diabetes,
groups were the same, suggesting that diabetes symptoms, and DKA prevention
suggesting that severe acute respiratory
the same sequence of events led to clini- and should be given consideration for
syndrome coronavirus 2 (SARS-CoV-2) is a
trigger for or can unmask type 1 diabetes cal disease in both “sporadic” and famil- referral to a specialized center for further
ial cases of type 1 diabetes. Indeed, the evaluation and/or consideration of a clini-
(68). Possible mechanisms of b-cell dam-
risk of type 1 diabetes increases as the cal trial or approved therapy to potentially
age include virus-triggered b-cell death,
number of relevant autoantibodies de- delay development of clinical diabetes (84).
immune-mediated loss of pancreatic
b-cells, and damage to b-cells because tected increases (53,74,75). In The Envi-
ronmental Determinants of Diabetes in PREDIABETES AND TYPE 2
of infection of surrounding exocrine
the Young (TEDDY) study, type 1 diabetes DIABETES
cells. The cytokine storm associated
developed in 21% of 363 subjects with
with COVID-19 infection is a highly inflam- Recommendations
at least one autoantibody at 3 years of
matory state that could also contribute. 2.10 Screening for risk of prediabe-
age (76). Such testing, coupled with edu-
To better characterize and understand the tes and type 2 diabetes with an as-
cation about diabetes symptoms and
pathogenesis of new-onset COVID-19– sessment of risk factors or validated
close follow-up, has been shown to en-
related diabetes, a global registry, CoviDIAB, risk calculator should be done in
able earlier diagnosis and to prevent
has been established (69). asymptomatic adults. B
DKA (77,78). In several cohort studies,
2.11a Testing for prediabetes or type 2
up to 50% of children with only a single
Idiopathic Type 1 Diabetes diabetes in asymptomatic people
autoantibody revert to being islet au-
Some forms of type 1 diabetes have no should be considered in adults of
toantibody negative during follow-up
known etiologies. Individuals have perma- any age with overweight or obesity
(79,80). Therefore, it is recommended
nent insulinopenia and are prone to DKA who have one or more risk factors
that the first autoantibody-positive test
but have no evidence of b-cell autoimmu- be confirmed with a second test within
(Table 2.5). B
nity. However, only a minority of people 2.11b For all other people, screen-
3 months, preferably in a laboratory that
with type 1 diabetes fall into this category. ing should begin at age 35 years. B
meets the performance standards set by
2.11c In people without prediabetes
the Islet Autoantibody Standardization
Screening for Type 1 Diabetes Risk or diabetes after screening, repeat
Program (IASP) (57).
The incidence and prevalence of type 1 screening recommended at a mini-
Type 1 diabetes genetic risk scores
diabetes are increasing (70). People with mum of 3-year intervals is reasonable,
have been used in newborn screening
type 1 diabetes often present with acute sooner with symptoms or change in
to identify those at risk for future pre-
symptoms of diabetes and markedly ele- risk (e.g., weight gain). C
sentation of the disease. In a simulation
vated blood glucose levels, and 25–50% 2.12 To screen for prediabetes and
using one such genetic risk score, the
are diagnosed with life-threatening DKA type 2 diabetes, FPG, 2-h PG during
majority of those who would go on to
75-g OGTT, and A1C are each appro-
(30–32). Family history of type 1 diabetes develop type 1 diabetes, >77%, could
increases the risk of developing type 1 priate (Table 2.1 and Table 2.2). B
be identified within just 10% of the gen-
diabetes compared with the general pop- 2.13 When using OGTT as a screen-
eral population, identifying a subset who
ulation, but the majority, 90%, of indi- ing tool for prediabetes or diabetes,
may most benefit from autoantibody
adequate carbohydrate intake (at least
viduals who develop type 1 diabetes do testing (81). As many genetic risk studies
150 g/day) should be assured for 3 days
not have a known relative with the dis- have been performed in populations of
prior to testing. E
ease. Multiple studies indicate that mea- European ancestry and discriminatory
2.14 Risk-based screening for predia-
suring islet autoantibodies in relatives of ability may differ in those of different
betes or type 2 diabetes should be
those with type 1 diabetes (45), in chil- ancestry, more large case-control co-
considered after the onset of puberty
dren from the general population (71,72), horts from non-European populations
or after 10 years of age, whichever
or in children from the general population are still needed (82).
diabetesjournals.org/care Diagnosis and Classification of Diabetes S35

Prediabetes
Table 2.5—Criteria for screening for diabetes or prediabetes in asymptomatic
Prediabetes is the term used for individ-
adults
uals whose glucose or A1C levels do not
1. Testing should be considered in adults with overweight or obesity (BMI $25 kg/m2 or meet the criteria for diabetes yet have
$23 kg/m2 in individuals of Asian ancestry) who have one or more of the following risk abnormal carbohydrate metabolism that
factors:
results in elevated glucose levels (dysglyce-
 First-degree relative with diabetes
 High-risk race, ethnicity, and ancestry (e.g., African American, Latino, Native American, mia) intermediate between normoglycemia
Asian American) and diabetes (28,85). People with predia-
 History of cardiovascular disease betes are defined by the presence of IFG
 Hypertension ($130/80 mmHg or on therapy for hypertension) and/or IGT and/or A1C 5.7–6.4% (39–47
 HDL cholesterol level <35 mg/dL (<0.9 mmol/L) and/or triglyceride level >250 mg/dL mmol/mol) (Table 2.2). As prediabetes is
(>2.8 mmol/L) an intermediate state between normo-
 Individuals with polycystic ovary syndrome
 Physical inactivity
glycemia and diabetes, it is a significant

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 Other clinical conditions associated with insulin resistance (e.g., severe obesity, risk factor for progression to diabetes
acanthosis nigricans, metabolic dysfunction–associated steatotic liver disease) as well as cardiovascular disease and
2. People with prediabetes (A1C $5.7% [$39 mmol/mol], IGT, or IFG) should be tested yearly. several other cardiometabolic outcomes.
Criteria for screening for diabetes or pre-
3. People who were diagnosed with GDM should have testing at least every 1–3 years.
diabetes in asymptomatic adults are out-
4. For all other people, testing should begin at age 35 years. lined in Table 2.5. Prediabetes is associated
5. If results are normal, testing should be repeated at a minimum of 3-year intervals, with with obesity (especially abdominal or
consideration of more frequent testing depending on initial results and risk status. visceral obesity), dyslipidemia with
high triglycerides and/or low HDL cho-
6. Individuals in other high-risk groups (e.g., people with HIV, exposure to high-risk medicines,
evidence of periodontal disease, history of pancreatitis) should also be closely monitored lesterol, and hypertension. The presence
of prediabetes should prompt compre-
GDM, gestational diabetes mellitus; IFG, impaired fasting glucose; IGT, impaired glucose tolerance. hensive screening for cardiovascular risk
factors.

occurs earlier, in children and adoles- 2.15b In people who are prescribed Diagnosis of Prediabetes
cents with overweight (BMI $85th second-generation antipsychotic medi- IFG is defined as FPG levels from 100 to
percentile) or obesity (BMI $95th cations, screen for prediabetes and 125 mg/dL (from 5.6 to 6.9 mmol/L)
percentile) and who have one or diabetes at baseline and repeat 12– (78,84) and IGT as 2-h PG levels during
more risk factors for diabetes. (See 16 weeks after medication initiation 75-g OGTT from 140 to 199 mg/dL
Table 2.6 for evidence grading of or sooner, if clinically indicated, and (from 7.8 to 11.0 mmol/L) (10). It should
risk factors.) B annually thereafter. B be noted that the World Health Organi-
2.15a Consider screening people for 2.16 People with HIV should be zation and a number of diabetes organ-
prediabetes or diabetes if they are screened for diabetes and prediabetes izations define the IFG lower limit at
on certain medications, such as glu- with an FPG test before starting anti- 110 mg/dL (6.1 mmol/L). The ADA also
cocorticoids, statins, thiazide diuretics, retroviral therapy, at the time of initially endorsed this IFG lower limit in
some HIV medications, and second- switching antiretroviral therapy, and 1997 (10). However, in 2003 the ADA
generation antipsychotic medica- 3–6 months after starting or switch- adopted the new range of 100–125 mg/dL
tions, as these agents are known ing antiretroviral therapy. If initial (5.6–6.9 mmol/L) to better define IFG so
to increase the risk of these condi- screening results are normal, FPG that the population risk of developing dia-
tions. C should be checked annually. E betes with IFG would be similar to that
with IGT (11).
As with the glucose measures, several
Table 2.6—Risk-based screening for type 2 diabetes or prediabetes in prospective studies that used A1C to pre-
asymptomatic children and adolescents in a clinical setting dict the progression to diabetes demon-
Screening should be considered in youth* who have overweight ($85th percentile) or strated a strong, continuous curvilinear
obesity ($95th percentile) and who have one or more additional risk factors: association between A1C and subsequent
 Maternal history of diabetes or GDM during the child’s gestation diabetes. In a systematic review of 44,203
 Family history of type 2 diabetes in first- or second-degree relative individuals from 16 cohort studies with
 High-risk race, ethnicity, and ancestry (see Table 2.5) a follow-up interval averaging 5.6 years
 Signs of insulin resistance or conditions associated with insulin resistance (acanthosis
(range 2.8–12 years), those with A1C be-
nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, large- or small-for-
gestational-age birth weight)
tween 5.5% and 6.0% (between 37 and
42 mmol/mol) had a substantially in-
GDM, gestational diabetes mellitus. *After the onset of puberty or after 10 years of age, creased risk of diabetes (5-year incidence
whichever occurs earlier. If tests are normal, repeat testing at a minimum of 3-year intervals
from 9% to 25%). Those with an A1C
(or more frequently if BMI is increasing or risk factor profile is deteriorating) is recom-
mended. Reports of type 2 diabetes before age 10 years exist, and this can be considered range of 6.0–6.5% (42–48 mmol/mol)
with numerous risk factors. had a 5-year risk of developing diabetes
between 25% and 50% and a relative risk
S36 Diagnosis and Classification of Diabetes Diabetes Care Volume 48, Supplement 1, January 2025

20 times higher than that with A1C of who generally have relative (rather than reduction, physical activity, and/or pharma-
5.0% (31 mmol/mol) (86). In a commu- absolute) insulin deficiency and have insu- cologic treatment of hyperglycemia but is
nity-based study of African American and lin resistance (i.e., decreased biological re- seldom restored to normal. Recent inter-
non-Hispanic White adults without di- sponses to insulin). ventions with intensive nutritional changes
abetes, baseline A1C was a stronger There are various causes of type 2 dia- and exercise, newer pharmacological agents
predictor of subsequent diabetes and betes. Although the specific etiologies (e.g., GLP-1 RAs), or surgical weight loss can
cardiovascular events than fasting glu- are not known, individuals do not have lead to diabetes remission (91–94) (see
cose (87). Other analyses suggest that any of the other known causes of diabe- Section 8, “Obesity and Weight Manage-
A1C of 5.7% (39 mmol/mol) or higher tes. Most, but not all, people with type 2 ment for the Prevention and Treatment of
is associated with a diabetes risk simi- diabetes have overweight or obesity. Ex- Type 2 Diabetes”).
lar to that of the high-risk participants cess weight itself causes some degree of The risk of developing type 2 diabetes
in the Diabetes Prevention Program insulin resistance. Individuals who do not increases with age, obesity, and lack of
(DPP) (88), and A1C at baseline was a have obesity or overweight by traditional physical activity (95,96). It occurs more

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strong predictor of the development weight criteria may have an increased per- frequently in individuals with prediabetes,
of glucose-defined diabetes during the centage of body fat distributed predomi- prior gestational diabetes mellitus, or
DPP and its follow-up (7). nantly in the abdominal region, including polycystic ovary syndrome. It is also more
An A1C range of 5.7–6.4% (39– sites involved in metabolic dysfunction– common in people with hypertension or
47 mmol/mol) identifies a group of indi- associated steatotic liver disease (MASLD) dyslipidemia and in certain racial, ethnic,
viduals at high risk for diabetes and car- and/or ectopic sites (e.g., skeletal muscle). and ancestral subgroups (Table 2.5). It is
diovascular outcomes. These individuals DKA seldom occurs spontaneously in often associated with a strong genetic
should be informed of their increased type 2 diabetes (30); when seen, it usually predisposition or family history in first-
risk for diabetes and cardiovascular dis- arises in individuals who are insulinopenic degree relatives (more so than type 1 dia-
ease and counseled about effective strat- and already treated with insulin (e.g., betes). However, the genetics of type 2
egies to lower their risks (see Section 3, missed or inadequate doses); in people diabetes are poorly understood and under
with ketosis-prone type 2 diabetes; in as- intense investigation in this era of preci-
“Prevention or Delay of Diabetes and
sociation with the stress of another illness sion medicine (50). The composition of
Associated Comorbidities”). Similar to glu-
such as infection (e.g., COVID-19) or myo- the gut microbiome may also affect the
cose measurements, the continuum of
cardial infarction; in association with illicit likelihood of developing type 2 diabetes
risk is continuous and curvilinear: as A1C
drug use (e.g., cocaine); in association (97). In adults without traditional risk fac-
rises, the diabetes risk rises disproportion-
with certain social determinants of health; tors for type 2 diabetes and/or of younger
ately (86). Aggressive interventions and
or with the use of certain medications age, consider islet autoantibody testing
vigilant follow-up should be pursued for
such as glucocorticoids, second-generation (e.g., GAD autoantibodies) to exclude the
those considered at very high risk (e.g.,
antipsychotics, or SGLT2 inhibitors (89,90). diagnosis of type 1 diabetes (36) (Fig. 2.1).
those with A1C >6.0% [>42 mmol/mol]
HHS is more typically associated with type
and individuals with both IFG and IGT).
2 diabetes (existing or new diagnosis) and Screening and Testing for
Table 2.5 outlines the criteria for
is characterized by severe hyperglycemia, Prediabetes and Type 2 Diabetes in
screening for prediabetes. The ADA risk hyperosmolality, and dehydration in the Asymptomatic Adults
test is an additional option (i.e., an absence of significant ketoacidosis. Peo- Screening for prediabetes and type 2 dia-
awareness tool for the layperson and ple with diabetes can also have mixed betes risk through a targeted assessment
the health care professional) for assess- clinical features of both DKA and HHS of risk factors (Table 2.5) or with an as-
ment to determine the appropriateness (30). sessment tool, such as the ADA risk test
of screening for diabetes or prediabetes Type 2 diabetes frequently goes un- (Fig. 2.2) (diabetes.org/diabetes-risk-test),
in asymptomatic adults (Fig. 2.2) (dia- diagnosed for many years, because hy- is recommended to guide health care
betes.org/diabetes-risk-test). For addi- perglycemia develops gradually and, at professionals on whether performing a di-
tional background regarding risk fac- earlier stages, is often not severe enough agnostic test (Table 2.1) is appropriate.
tors and screening for prediabetes, see for the individual to notice the classic dia- Prediabetes and type 2 diabetes meet cri-
screening and testing for prediabetes betes symptoms caused by hyperglyce- teria for conditions in which early detec-
and type 2 diabetes in asymptomatic mia, such as dehydration or unintentional tion via screening is appropriate. Both
adults and screening and testing for weight loss. Nevertheless, even undiag- conditions are common and impose sig-
prediabetes and type 2 diabetes in chil- nosed people with diabetes are at in- nificant clinical and public health burdens.
dren and adolescents, below. For details creased risk of developing macrovascular There is often a long presymptomatic
regarding individuals with prediabetes and microvascular complications. phase before the diagnosis of type 2 dia-
most likely to benefit from a formal be- People with type 2 diabetes early in betes. Simple tests to detect preclinical
havioral or lifestyle intervention, see Sec- the disease course may have insulin levels disease are readily available (98). The du-
tion 3, “Prevention or Delay of Diabetes that appear normal or elevated, yet the ration of glycemic burden is a strong pre-
and Associated Comorbidities.” failure to normalize blood glucose reflects dictor of adverse outcomes. There are
a relative defect in glucose-stimulated in- effective interventions that prevent pro-
Type 2 Diabetes sulin secretion that is insufficient to com- gression from prediabetes to diabetes. It
Type 2 diabetes accounts for 90–95% of all pensate for insulin resistance. Insulin is important to individualize the risk-to-
diabetes. This form encompasses individuals resistance may improve with weight benefit ratio of formal intervention for
diabetesjournals.org/care Diagnosis and Classification of Diabetes S37

Are you at risk for type 2 diabetes?

WRITE YOUR SCORE
Diabetes Risk Test IN THE BOX.
Height Weight (lbs.)

1. How old are you? 4´ 10˝ 119–142 143–190 191+

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Less than 40 years (0 points) 4´ 11˝ 124–147 148–197 198+
40–49 years (1 point) 5´ 0˝ 128–152 153–203 204+
50–59 years (2 points)
5´ 1˝ 132–157 158–210 211+
60 years or older (3 points)
5´ 2˝ 136–163 164–217 218+
2. Are you a man or a woman? 5´ 3˝ 141–168 169–224 225+
Man (1 point) Woman (0 points) 5´ 4˝ 145–173 174–231 232+

5´ 5˝ 150–179 180–239 240+

3. If you are a woman, have you ever been diagnosed
with gestational diabetes? 5´ 6˝ 155–185 186–246 247+

5´ 7˝ 159–190 191–254 255+

Yes (1 point) No (0 points)
5´ 8˝ 164–196 197–261 262+
4. Do you have a mother, father, sister or brother 5´ 9˝ 169–202 203–269 270+
with diabetes?
5´ 10˝ 174–208 209–277 278+
Yes (1 point) No (0 points)
5´ 11˝ 179–214 215–285 286+

5. Have you ever been diagnosed with high 6´ 0˝ 184–220 221–293 294+
blood pressure? 6´ 1˝ 189–226 227–301 302+
Yes (1 point) No (0 points) 6´ 2˝ 194–232 233–310 311+

6´ 3˝ 200–239 240–318 319+

6. Are you physically active?
6´ 4˝ 205–245 246–327 328+
Yes (0 points) No (1 point)
1 point 2 points 3 points
7. What is your weight category? If you weigh less than the amount
in the left column: 0 points
See chart at right.
Adapted from Bang et al., Ann Intern Med
151:775–783, 2009 • Original algorithm was validated
without gestational diabetes as part of the model
If you scored 5 or higher: ADD UP
YOUR SCORE
You are at increased risk for having type 2 diabetes. Lower your risk:
However, only your doctor can tell for sure if you do
Diabetes Risk Test | American Diabetes Association®

The good news is you can manage

have type 2 diabetes or prediabetes, a condition in
your risk for type 2 diabetes. Small
which blood glucose levels are higher than normal but steps make a big difference in helping
not yet high enough to be diagnosed as diabetes. Talk you live a longer, healthier life.
to your doctor to see if additional testing is needed.
If you are at high risk, your first step is
Type 2 diabetes is more common in African Americans, to visit your doctor to see if additional
Hispanic/Latino individuals, Native Americans, Asian testing is needed.
Americans, and Native Hawaiians and Pacific Islanders. Visit diabetes.org or call
1–800–DIABETES (800–342–2383) for
Higher body weight increases diabetes risk for
information, tips on getting started,
everyone. Asian Americans are at increased diabetes and ideas for simple, small steps you
risk at lower body weight than the rest of the general can take to help lower your risk
public (about 15 pounds lower).

Learn more at diabetes.org/diabetes-risk-test | 1-800-DIABETES (800-342-2383)

Figure 2.2—ADA risk test (diabetes.org/diabetes-risk-test).

people with prediabetes and consider highest risk (99) (see Section 3, “Prevention “Cardiovascular Disease and Risk Man
person-centered goals. Risk models have or Delay of Diabetes and Associated agement,” Section 11, “Chronic Kidney
explored the benefit, in general finding Comorbidities”) and reduced risk of diabe- Disease and Risk Management,” and Sec-
higher benefit of intervention in those at tes complications (100) (see Section 10, tion 12, “Retinopathy, Neuropathy, and
S38 Diagnosis and Classification of Diabetes Diabetes Care Volume 48, Supplement 1, January 2025

Foot Care”). In the National Institutes of People With HIV follow-up testing and care. However, in spe-
Health (NIH) Diabetes Prevention Program People with HIV are at higher risk for de- cific situations where an adequate referral
Outcomes Study (DPPOS) report, preven- veloping prediabetes and diabetes. In ad- system is established beforehand for posi-
tion of progression from prediabetes to di- dition, some antiretroviral (ARV) therapies tive tests, community screening may be
abetes (101) resulted in lower rates of may further increase the risk. Therefore, a considered. Community screening may also
developing retinopathy and nephropathy screening protocol for prediabetes and be poorly targeted; i.e., it may fail to reach
(102). Similar impact on diabetes com- type 2 diabetes is recommended (106). As the groups most at risk and inappropriately
plications was reported with screening, the A1C test may underestimate glycemia test those at very low risk or even those
diagnosis, and comprehensive risk factor in people with HIV, plasma glucose criteria who have already been diagnosed (110).
management in the U.K. Clinical Prac- are preferred to diagnose prediabetes and
tice Research Datalink database (100). diabetes (20). Screening in Dental Practices
In that report, progression from predia- Diabetes risk is increased with certain Because of the bidirectional relationship
betes to diabetes augmented risk of protease inhibitors (PIs) and nucleoside/ between periodontal disease and diabetes,

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complications. nucleotide reverse transcriptase inhibitors the utility of screening in a dental setting
Despite the numerous benefits of screen- (NRTIs). New-onset diabetes is estimated and referral to primary care as a means to
ing and early diagnosis for prediabetes or to occur in more than 5% of individuals improve the diagnosis of prediabetes and
diabetes, unfortunately many people in infected with HIV on PIs, whereas more diabetes has been explored (111,112). For
the U.S. and globally either remain un- than 15% may have prediabetes (107). example, one study estimated that 30% of
diagnosed or are diagnosed late, when PIs are associated with insulin resistance individuals $30 years of age seen in gen-
complications have already arisen. and may also lead to apoptosis of pan- eral dental practices (including both peo-
Additional considerations regarding creatic b-cells. NRTIs also affect fat distribu- ple with and without periodontal disease)
testing for type 2 diabetes and prediabe- tion (both lipohypertrophy and lipoatrophy), had newly diagnosed dysglycemia (112).
tes in asymptomatic individuals are de- which is associated with insulin resistance. Further research is needed to demon-
scribed below. For people with HIV and ARV-associated strate the feasibility, effectiveness, and
hyperglycemia, it may be appropriate cost-effectiveness of screening in this
Age to consider discontinuing the problem- setting. For additional background on
Age is a major risk factor for diabetes. atic ARV agents if safe and effective alter- oral health in relation to prediabetes
Testing should begin at no later than age natives are available (108). Before making and type 2 diabetes, see Section 4,
35 years for all people (103). Screening ARV substitutions, carefully consider the “Comprehensive Medical Evaluation and
should be considered in adults of any age possible effect on HIV virological control
Assessment of Comorbidities.”
with overweight or obesity and one or and the potential adverse effects of new
more risk factors for diabetes. ARV agents. In some cases, antihypergly- Screening and Testing for
cemic agents may still be necessary. Prediabetes and Type 2 Diabetes in
Medications
Children and Adolescents
Certain medications, such as glucocorti- Testing Interval The epidemiologic studies that formed
coids, statins (104), thiazide diuretics, The appropriate interval between screen- the basis for the recommendations to use
some HIV medications (19), and second- ing tests is not known (109). The ratio- A1C and plasma glucose criteria to diag-
generation antipsychotic medications nale for the 3-year interval is that with nose prediabetes and diabetes included
(105), should be considered when de- this interval, the number of false-positive only adult populations (113). However,
ciding whether to screen for prediabe- tests that require confirmatory testing ADA clinical guidance concluded that A1C,
tes or diabetes, as these medications will be reduced, and individuals with FPG, or 2-h PG also could be used to test
are known to increase the risks of these false-negative tests will be retested before
conditions. for prediabetes or type 2 diabetes in chil-
substantial time elapses and complications
For example, people taking second- dren and adolescents (114).
develop (109). In especially high-risk indi- In the last decade, the incidence and
generation antipsychotic medications re- viduals such as those with previous val-
quire greater monitoring because of an in- prevalence of type 2 diabetes in children
ues nearer to the diabetes diagnostic cut
crease in risk of type 2 diabetes associated and adolescents has increased dramati-
point, shorter intervals between screen-
with this medication (105). There is a cally, especially in certain high-risk racial,
ings may be useful.
range of effects on metabolic parame- ethnic, and ancestral subgroups (115).
ters (e.g., hyperglycemia, dyslipidemia, See Table 2.6 for recommendations on
Community Screening
and weight gain) across second-generation Ideally, screening should be carried out risk-based screening for type 2 diabetes
antipsychotic medications. People treated within a health care setting (including ap- or prediabetes in asymptomatic children
with these agents should be screened for propriately resourced pharmacies) because and adolescents in a clinical setting (114).
prediabetes or diabetes at baseline, re- of the need for follow-up and treatment. See Table 2.1 and Table 2.2 for the cri-
screened 12–16 weeks after medication Community screening outside a health teria for the diagnosis of diabetes and
initiation, and screened annually thereaf- care setting is generally not recommended prediabetes, respectively, that apply to
ter (105). Repeat testing can occur sooner because people with positive tests may children, adolescents, and adults. See Sec-
if clinically warranted. not seek, or have access to, appropriate tion 14, “Children and Adolescents,” for
diabetesjournals.org/care Diagnosis and Classification of Diabetes S39

additional information on type 2 diabetes considered. In the context of pancreatec- diabetes before the age of 10 years can
in children and adolescents. tomy, islet autotransplantation can be identify risk for progression to CFRD in
considered for selected individuals with those with abnormal glucose tolerance,
PANCREATIC DIABETES OR medically refractory chronic pancreatitis in no benefit has been established with
DIABETES IN THE CONTEXT OF specialized centers to preserve endoge- respect to weight, height, BMI, or lung
DISEASE OF THE EXOCRINE nous islet function and insulin secretion function. OGTT is the recommended
PANCREAS (123,124). In some cases, autotransplant screening test for CFRD. Not unexpect-
can lead to insulin independence. In edly, annual OGTTs are perceived as bur-
Recommendation others, it may decrease insulin require- densome, and engagement in current
2.17 Screen people for diabetes within ments (125). CFRD screening guidelines is poor, with
3–6 months following an episode of
only 30% of adults with cystic fibrosis
acute pancreatitis and annually there- Cystic Fibrosis–Related Diabetes having annual OGTTs (128). A1C is not
after. Screening for diabetes is rec-
Recommendations recommended for screening due to low

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ommended annually for people with
2.18 Annual screening for cystic fi- sensitivity; however, a value of $6.5%
chronic pancreatitis. E
brosis–related diabetes (CFRD) with ($48 mmol/mol) is consistent with a
an OGTT should begin by age 10 years diagnosis of CFRD and reduces patient
Pancreatic diabetes (also termed pan- in all people with cystic fibrosis not screening burden (129–131). Regardless
creatogenic diabetes or type 3c diabetes) previously diagnosed with CFRD. B of age, weight loss or failure of expected
includes both structural (e.g., destruction 2.19 A1C is not recommended as a weight gain is a risk for CFRD and should
or removal of normal pancreatic tissue) screening test for CFRD due to low prompt screening (129,130). The Cystic
and functional loss of glucose-normalizing sensitivity. However, a value of $6.5% Fibrosis Foundation Patient Registry
insulin secretion in the context of exo- ($48 mmol/mol) is consistent with a (132) evaluated 3,553 people with cystic
crine pancreatic dysfunction and is com- diagnosis of CFRD. B fibrosis and identified 445 (13%) with
monly misdiagnosed as type 2 diabetes. 2.20 Beginning 5 years after the di- CFRD. Early diagnosis and treatment of
The diverse set of etiologies includes agnosis of CFRD, annual monitoring CFRD was associated with preservation
pancreatitis (acute and chronic pancre- for complications of diabetes is rec- of lung function. The European Cystic Fi-
atic inflammation and associated fibrosis ommended. E brosis Society Patient Registry reported
leading to loss of functional exocrine and an increase in CFRD with age (10% in-
endocrine pancreatic function), trauma crease per decade), genotype, decreased
Cystic fibrosis is a multisystem condition
or pancreatectomy, neoplasia, cystic fibrosis lung function, and female sex (133). CGM
arising from recessive mutations in the
(addressed later in this section), hemochro- or HOMA of b-cell function (134) may be
gene encoding the cystic fibrosis trans-
matosis, fibrocalculous pancreatopathy, membrane conductance regulator (CFTR)
more sensitive than OGTT to detect risk
rare genetic disorders, and idiopathic forms for progression to CFRD; however, evi-
protein. Pancreatic exocrine damage,
(2); as such, pancreatic diabetes is the pre- which can begin as early as infancy, ulti- dence linking these results to long-term
ferred umbrella term (116). mately leads to pancreatic exocrine insuf- outcomes is lacking, and these tests are
Acute (even a single bout) and chronic ficiency (126). Cystic fibrosis–related not recommended for screening outside
pancreatitis can lead to postpancreatitis diabetes (CFRD) is a common comorbid- the research setting (127). There is inade-
diabetes mellitus (117). A distinguishing ity in people with cystic fibrosis, occur- quate evidence presently to alter CFRD
feature is concurrent pancreatic exocrine ring in about 20% of adolescents and screening based on use of highly effec-
insufficiency (consider screening individ- 40–50% of adults (127). The relevance of tive CFTR modulator therapy, which uses
uals with acute and chronic pancreatitis CFRD is highlighted by its association small-molecule compounds that directly
for exocrine pancreatic insufficiency by with increased morbidity, mortality, and correct the basic defect of the CFTR chan-
measuring fecal elastase), pathological patient burden. Diabetes in this popula- nel and restore channel function (127).
pancreatic imaging (endoscopic ultra- tion, compared with individuals with CFRD mortality has significantly de-
sound, MRI, and computed tomography), type 1 or type 2 diabetes, is associated creased over time, and the gap in mortal-
and absence of type 1 diabetes–associated with worse nutritional status, more se- ity between people with cystic fibrosis
autoimmunity (118–122). There is loss of vere inflammatory lung disease, and with and without diabetes has consider-
both insulin and glucagon secretion and greater mortality. Insulin insufficiency is ably narrowed (135). There are limited
often higher-than-expected insulin re- the primary defect in CFRD. Genetically clinical trial data on optimal therapy for
quirements. Risk for microvascular com- determined b-cell function and insulin CFRD. People with CFRD should be treated
plications appears to be similar to that resistance associated with infection and with insulin to attain individualized glyce-
of other forms of diabetes. inflammation may also contribute to mic goals. See Section 9, “Pharmacologic
For people with pancreatitis and diabe- the development of CFRD. Approaches to Glycemic Treatment,” for
tes, therapy should be advanced if A1C Milder abnormalities of glucose toler- further information.
goals are not met. Glucose-lowering ance are even more common and occur Additional resources for the clinical man-
therapies potentially associated with at earlier ages than CFRD. Whether indi- agement of CFRD can be found in the posi-
increased risk of pancreatitis (i.e., incretin- viduals with IGT should be treated with tion statement “Clinical Care Guidelines for
based therapies) should be avoided. Early insulin replacement has not currently Cystic Fibrosis-Related Diabetes” (136) and
initiation of insulin therapy should be been determined. Although screening for in the International Society for Pediatric
S40 Diagnosis and Classification of Diabetes Diabetes Care Volume 48, Supplement 1, January 2025

and Adolescent Diabetes (ISPAD) 2022 clin- risks (such as age, family history of diabe- genetics is recommended to under-
ical practice consensus guidelines (127). tes, and obesity) and transplant-specific stand the significance of genetic mu-
factors, such as use of immunosuppres- tations and how best to approach
sant agents (144–146). Whereas post- further evaluation, treatment, and
POSTTRANSPLANTATION
DIABETES MELLITUS
transplantation hyperglycemia is an genetic counseling. E
important risk factor for subsequent
Recommendations PTDM, a formal diagnosis of PTDM is
2.21 After organ transplantation, optimally made once the individual is stable Monogenic defects that cause b-cell dys-
screening for hyperglycemia should be on maintenance immunosuppression (usu- function (e.g., neonatal diabetes and
done. A formal diagnosis of posttrans- ally at least 45 days) and in the absence of MODY) or insulin resistance syndromes
plantation diabetes mellitus (PTDM) is acute infection (138,142–144,147). (e.g., monogenic lipodystrophies) are pre-
best made once the individual is stable The OGTT is recommended for the di- sent in a small fraction of people with dia-
on an immunosuppressive plan and in agnosis of PTDM (1 year posttransplant) betes (<5%) (152). Table 2.7 describes

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the absence of an acute infection. B (138,139,148). However, screening people the most common causes of monogenic
2.22 The OGTT is the preferred test with FPG and/or A1C can identify high-risk diabetes. For a comprehensive list of
to make a diagnosis of PTDM. B individuals who require further assess- causes, see Genetic Diagnosis of Endo-
2.23 Immunosuppressive plans shown ment and may reduce the number of crine Disorders (153) and ISPAD 2022 clin-
to provide the best outcomes for indi- overall OGTTs required. ical practice consensus guidelines (152).
Few randomized controlled studies have
viduals and graft survival should be
reported on the short- and long-term use
used, irrespective of PTDM risk. E Diagnosis of Monogenic Diabetes
of antihyperglycemic agents in the setting
The diagnosis of monogenic diabetes
of PTDM (144,149,150). Most studies have
Several terms are used in the literature should be considered in children and adults
reported that transplant individuals with
to describe the presence of diabetes diagnosed with diabetes in early adulthood
hyperglycemia and PTDM after transplan-
following organ transplantation (137). with the following findings:
tation have higher rates of rejection, infec-
New-onset diabetes after transplanta- tion, and rehospitalization (142,144,151).
tion (NODAT) is one such designation Insulin therapy is the agent of choice for • Diabetes diagnosed within the first 6
that describes individuals who develop the management of hyperglycemia and months of life (152,154)
diabetes in the hospital setting and can • Diabetes without typical features of
new-onset diabetes following transplant.
be continued postdischarge. Noninsulin type 1 or type 2 diabetes (negative
NODAT excludes people with pretrans-
glucose-lowering therapies can also be diabetes-associated autoantibodies,
plant diabetes that was undiagnosed as
used for long-term management. The no obesity, and lacking other metabolic
well as posttransplant hyperglycemia that
choice of agent is usually made based features, especially strong family his-
resolves by the time of discharge (138).
on the side effect profile of the medica- tory of diabetes)
Another term, posttransplantation diabe-
tion, possible interactions with the indi- • Stable, mild fasting hyperglycemia
tes mellitus (PTDM) (138,139), describes
vidual’s immunosuppression plan, and (100–150 mg/dL [5.6–8.5 mmol/L]),
the presence of diabetes in the post-
potential cardiovascular and renal ben- stable A1C between 5.6% and 7.6%
transplant setting irrespective of the
efits in individuals with PTDM (144). (between 38 and 60 mmol/mol), es-
timing of diabetes onset (140). The clini-
See Section 9, “Pharmacologic Approaches pecially if no obesity
cal importance of PTDM lies in its impact
to Glycemic Treatment,” for further
as a significant risk factor for cardiovas- information. Neonatal Diabetes
cular disease and chronic kidney disease Diabetes occurring under 6 months of
in solid-organ transplantation (137). MONOGENIC DIABETES age is termed neonatal diabetes, and
Hyperglycemia is very common during SYNDROMES about 80–85% of cases can be found to
the early posttransplant period, with 90% have an underlying monogenic cause
of kidney allograft recipients exhibiting Recommendations
(36,154–157). Neonatal diabetes occurs
hyperglycemia in the first few weeks 2.24a Regardless of current age, all much less often after 6 months of age,
following transplant (138,139,141,142). people diagnosed with diabetes in the
whereas autoimmune type 1 diabetes
In most cases, such stress- or steroid- first 6 months of life should have ge-
rarely occurs before 6 months of age.
induced hyperglycemia resolves by the netic testing for neonatal diabetes. B
Neonatal diabetes can either be transient
time of discharge (142,143). Although 2.24b Children and young adults who
or permanent. Transient diabetes is most
the use of immunosuppressive thera- do not have typical characteristics of
often due to overexpression of genes on
pies is a major contributor to the devel- type 1 or type 2 diabetes and family
chromosome 6q24, is recurrent in about
opment of PTDM, the risks of transplant history of diabetes in successive gen-
half of cases, and may be treatable with
rejection outweigh the risks of PTDM, erations (suggestive of an autosomal
medications other than insulin. Perma-
and the role of the diabetes health care dominant pattern of inheritance) should
nent neonatal diabetes is most commonly
have genetic testing for maturity-
professional is to treat hyperglycemia due to autosomal dominant mutations in
onset diabetes of the young (MODY). B
appropriately regardless of the type of the genes encoding the Kir6.2 subunit
2.24c In both instances, consultation
immunosuppression (138). Risk factors for (KCNJ11) and SUR1 subunit (ABCC8) of the
with a center specializing in diabetes
PTDM include both general diabetes b-cell KATP channel.
diabetesjournals.org/care Diagnosis and Classification of Diabetes S41

Table 2.7—Most common causes of monogenic diabetes

Gene Inheritance Clinical features
MODY HNF1A AD HNF1A-MODY: progressive insulin secretory defect with presentation in
adolescence or early adulthood; lowered renal threshold for glucosuria;
large rise in 2-h PG level on OGTT (>90 mg/dL [>5 mmol/L]); low
hs-CRP; sensitive to sulfonylureas
HNF4A AD HNF4A-MODY: progressive insulin secretory defect with presentation in
adolescence or early adulthood; may have large birth weight
(macrosomia) and transient neonatal hypoglycemia; sensitive to
sulfonylureas
HNF1B AD HNF1B-MODY: developmental renal disease (typically cystic); genitourinary
abnormalities; atrophy of the pancreas; hyperuricemia; gout
GCK AD GCK-MODY: higher glucose threshold (set point) for glucose-stimulated
insulin secretion, causing stable, nonprogressive elevated fasting blood

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glucose; typically does not require treatment; microvascular
complications are rare; small rise in 2-h PG level on OGTT (<54 mg/dL
[<3 mmol/L])
Neonatal diabetes KCNJ11 AD Permanent or transient: IUGR; possible developmental delay and seizures;
responsive to sulfonylureas
INS AD Permanent: IUGR; insulin requiring
ABCC8 AD Permanent or transient: IUGR; rarely developmental delay; responsive to
sulfonylureas
6q24 (PLAGL1, AD for paternal Transient: IUGR; macroglossia; umbilical hernia; mechanisms include
HYMA1) duplications UPD6, paternal duplication, or maternal methylation defect; may be
treatable with medications other than insulin
GATA6 AD Permanent: pancreatic hypoplasia; cardiac malformations; pancreatic
exocrine insufficiency; insulin requiring
EIF2AK3 AR Permanent: Wolcott-Rallison syndrome: epiphyseal dysplasia; pancreatic
exocrine insufficiency; insulin requiring
EIF2B1 AD Permanent diabetes: can be associated with fluctuating liver function
(154)
FOXP3 X-linked Permanent: immunodysregulation, polyendocrinopathy, enteropathy
X-linked (IPEX) syndrome: autoimmune diabetes, autoimmune thyroid
disease, exfoliative dermatitis; insulin requiring
Adapted from Carmody et al. (153). AD, autosomal dominant; AR, autosomal recessive; IUGR, intrauterine growth restriction; OGTT, oral glu-
cose tolerance test; UPD6, uniparental disomy of chromosome 6; 2-h PG, 2-h plasma glucose.

The ADA-European Association for the action (in the absence of coexistent obe- monogenic diabetes has been reported.
Study of Diabetes type 1 diabetes consen- sity). It is inherited in an autosomal domi- Individuals in whom monogenic diabetes
sus report recommends that regardless of nant pattern with abnormalities in at least is suspected should have genetic testing.
current age, individuals diagnosed under 14 genes on different chromosomes iden- Genetic screening (i.e., next-generation
6 months of age should have genetic test- tified to date (152). The most commonly sequencing) is increasingly available and
ing (36). Correct diagnosis has critical im- reported forms are GCK-MODY (MODY2), cost-effective (152). Consultation with a
plications, because 30–50% of people with HNF1A-MODY (MODY3), and HNF4A- center specializing in diabetes genetics is
KATP-related neonatal diabetes will exhibit MODY (MODY1). recommended to understand the signifi-
improved blood glucose levels when Correct diagnosis of monogenic forms cance of genetic mutations and how best
treated with high-dose oral sulfonylureas of diabetes is critical because people to approach further evaluation, treatment,
instead of insulin. Insulin gene (INS) mu- who have them may be incorrectly diag- and genetic counseling. Genetic counsel-
tations are the second most common nosed with type 1 or type 2 diabetes, ing is recommended to ensure that af-
cause of permanent neonatal diabetes, leading to suboptimal, even potentially fected individuals understand the patterns
with insulin therapy being the preferred harmful, treatment plans and delays in of inheritance and the importance of a
treatment strategy. diagnosing other family members (152). correct diagnosis and to address compre-
A diagnosis of MODY should be consid- hensive cardiovascular risk.
Maturity-Onset Diabetes of the ered in individuals who have atypical dia- A diagnosis of one of the three most
Young betes and multiple family members with common forms of MODY, HNF1A-MODY,
MODY is frequently characterized by on- diabetes not characteristic of type 1 or GCK-MODY, and HNF4A-MODY, allows for
set of hyperglycemia at an early age (clas- type 2 diabetes (155–162) (Fig. 2.1). In more cost-effective personalized therapy
sically before age 25 years, although most cases, the presence of autoantibod- (i.e., no therapy for GCK-MODY and sulfo-
diagnosis may occur at older ages). MODY ies for type 1 diabetes precludes further nylureas as first-line therapy for HNF1A-
is characterized by impaired insulin secre- testing for monogenic diabetes, but the MODY and HNF4A-MODY). See Section 9,
tion with minimal or no defects in insulin presence of autoantibodies in people with “Pharmacologic Approaches to Glycemic
S42 Diagnosis and Classification of Diabetes Diabetes Care Volume 48, Supplement 1, January 2025

Treatment,” for further information. Ad- definition facilitated a uniform strategy If early screenings for undiagnosed dia-
ditionally, diagnosis can lead to identifica- for detection and classification of GDM, betes or early abnormal glucose metabo-
tion of other affected family members but this definition has limitations (163). lism were negative, individuals should be
and can indicate potential extrapancreatic First, the best evidence reveals that rescreened for GDM between 24 and 28
complications in affected individuals. many cases of GDM represent preexist- weeks of gestation and individuals not
ing hyperglycemia that is detected by previously screened should be screened
GESTATIONAL DIABETES routine screening in pregnancy, as rou- for GDM at the same time point (see
MELLITUS tine screening is not widely performed in Section 15, “Management of Diabetes in
nonpregnant individuals of reproductive Pregnancy”). The GDM diagnostic criteria
Recommendations age. The ongoing epidemic of obesity for the 75-g OGTT from the International
2.25 In individuals who are planning and diabetes has led to more type 2 dia- Association of the Diabetes and Preg-
pregnancy, screen those with risk fac- betes in people of reproductive age, with nancy Study Groups (IADPSG) and the
tors (Table 2.5) B and consider testing an increase in the number of pregnant indi- GDM screening and diagnostic criteria

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all individuals of childbearing potential viduals with undiagnosed type 2 diabetes with the two-step approach were not
for undiagnosed prediabetes or diabe- in early pregnancy (164–166). Ideally, un- derived from data in the first half of
tes. E diagnosed diabetes should be identified pregnancy and should not be used for
2.26a Before 15 weeks of gesta- preconception in individuals with risk fac- early screening (179). Most randomized
tion, test individuals with risk fac- tors or in high-risk populations (167–172), controlled trials of treatment of early ab-
tors (Table 2.5) B and consider testing as they are likely to benefit from precon- normal glucose metabolism have been
all individuals E for undiagnosed diabe- ception care. The preconception care of underpowered for outcomes. One random-
tes at the first prenatal visit using stan- people with known preexisting diabetes ized controlled trial performed at 17 centers
dard diagnostic criteria if not screened results in lower A1C and reduced risk of administered early screening (mean 15.6 ±
preconception. birth defects, preterm delivery, perinatal 2.5 weeks) for GDM with a 75-g OGTT. Indi-
2.26b Before 15 weeks of gestation, mortality, small-for-gestational-age birth viduals who met World Health Organization
screen for abnormal glucose metabo- weight, and neonatal intensive care unit
criteria for GDM were randomized to re-
lism to identify individuals who are at admission (173). If individuals are not
ceive early treatment or a repeat OGTT at
higher risk of adverse pregnancy and screened prior to pregnancy, universal
24–28 weeks (with deferred treatment if in-
neonatal outcomes, are more likely early screening at <15 weeks of gestation
dicated). The first primary outcome mea-
to need insulin, and are at high risk for undiagnosed diabetes may be consid-
sure was an adverse neonatal composite
of a later gestational diabetes melli- ered over selective screening (Table 2.5),
outcome including birth <37 weeks, birth
tus (GDM) diagnosis. B particularly in populations with high prev-
weight $4.5 kg, birth trauma, neonatal
2.26c Screen for early abnormal glu- alence of risk factors and undiagnosed di-
respiratory distress within 24 h of birth,
cose metabolism with dysglycemia abetes in people of childbearing age.
phototherapy, stillbirth neonatal death,
using FPG 110–125 mg/dL (6.1– Strong racial and ethnic disparities exist in
or shoulder dystocia. Early GDM treat-
6.9 mmol/L) or A1C 5.9–6.4% (41– the prevalence of undiagnosed diabetes.
ment resulted in a modest improvement
47 mmol/mol). B Therefore, early screening provides an ini-
tial step to identify these health dispar- in the composite adverse neonatal out-
2.27 Screen for GDM at 24–28 weeks come (24.9% early treatment vs. 30.5%
of gestation in pregnant individuals ities so that they can begin to address
them (169–172). Diagnostic criteria for control treatment, relative risk 0.82
not previously found to have diabe- [0.68–0.98]), although this was driven pri-
tes or high-risk abnormal glucose me- identifying undiagnosed diabetes in early
pregnancy are the same as those used in marily by differences in rates of neonatal
tabolism detected earlier in the current respiratory distress between groups that
pregnancy. A nonpregnant individuals (Table 2.1). In-
dividuals found to have diabetes should included neonates requiring $4 h of sup-
2.28 Screen individuals with GDM for plemental oxygen who may not have re-
be classified as having diabetes compli-
prediabetes or diabetes at 4–12 weeks quired a higher level of respiratory care.
cating pregnancy (most often type 2 dia-
postpartum, using the 75-g OGTT and There was also a suggestion of more ben-
betes, rarely type 1 diabetes or monogenic
clinically appropriate nonpregnancy di- efit (per prespecified subgroup analyses)
diabetes) and managed accordingly.
agnostic criteria. B among individuals who had the OGTT at
Early abnormal glucose metabolism,
2.29 Individuals with a history of GDM <14 weeks and among those with OGTT
defined as a fasting glucose threshold of
should have lifelong screening for the glycemic values in higher ranges (180).
110 mg/dL (6.1 mmol/L) or an A1C of
development of prediabetes or diabe- Therefore, the benefits of treatment of
5.9% (41 mmol/mol), may identify indi-
tes every 1–3 years. B early abnormal glucose metabolism re-
viduals who are at higher risk of adverse
pregnancy and neonatal outcomes (pre- main uncertain. Nutrition counseling and
eclampsia, macrosomia, shoulder dysto- periodic testing of glucose levels weekly
Definition cia, and perinatal death), are at high risk to identify individuals with high glucose
For many years, gestational diabetes mel- of a later GDM diagnosis, and are more levels are suggested. Testing frequency
litus (GDM) was defined as any degree of likely to need insulin treatment (174–176). may proceed to daily, and treatment may
glucose intolerance that was first recog- An A1C threshold of 5.7% (39 mmol/L) has be intensified, if the FPG is predominantly
nized during pregnancy (86), regardless not been shown to be associated with ad- >110 mg/dL (>6.1 mmol/L) prior to
of the degree of hyperglycemia. This verse perinatal outcomes (177,178). 18 weeks of gestation.
diabetesjournals.org/care Diagnosis and Classification of Diabetes S43

Both the FPG and A1C are low-cost

Table 2.8—Screening for and diagnosis of GDM
tests. An advantage of the A1C test is its
convenience, as it can be added to the One-step strategy
prenatal laboratories and does not re- Perform a 75-g OGTT, with plasma glucose measurement when an individual is fasting and at
1 and 2 h, at 24–28 weeks of gestation in individuals not previously diagnosed with diabetes.
quire an early-morning fasting appoint- The OGTT should be performed in the morning after an overnight fast of at least 8 h.
ment. Disadvantages include inaccuracies The diagnosis of GDM is made when any of the following plasma glucose values are met or
in the presence of increased red blood exceeded:
cell turnover and hemoglobinopathies  Fasting: 92 mg/dL (5.1 mmol/L)
(usually reads lower) and higher values  1 h: 180 mg/dL (10.0 mmol/L)
 2 h: 153 mg/dL (8.5 mmol/L)
with anemia and reduced red blood cell
turnover (181). A1C is not reliable for Two-step strategy
screening for GDM or for preexisting di- Step 1: Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h, at
24–28 weeks of gestation in individuals not previously diagnosed with diabetes.
abetes at 15 weeks of gestation or later

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If the plasma glucose level measured 1 h after the load is $130, 135, or 140 mg/dL (7.2,
in part from the higher red blood cell 7.5, or 7.8 mmol/L, respectively),* proceed to a 100-g OGTT.
turnover in pregnancy but also from Step 2: The 100-g OGTT should be performed when the individual is fasting.
the unknown diabetes status prior to The diagnosis of GDM is made when at least two† of the following four plasma glucose
pregnancy, which could help distin- levels (measured fasting and at 1, 2, and 3 h during OGTT) are met or exceeded
guish new-onset diabetes from preex- (Carpenter-Coustan criteria [208]):
 Fasting: 95 mg/dL (5.3 mmol/L)
isting diabetes.
 1 h: 180 mg/dL (10.0 mmol/L)
GDM is often indicative of underlying  2 h: 155 mg/dL (8.6 mmol/L)
b-cell dysfunction (182), which confers  3 h: 140 mg/dL (7.8 mmol/L)
marked increased risk for later develop-
GDM, gestational diabetes mellitus; GLT, glucose load test; OGTT, oral glucose tolerance
ment of glucose intolerance and diabetes test. *American College of Obstetricians and Gynecologists (ACOG) recommends any of the
in the mother after delivery (183–185). commonly used thresholds of 130, 135, or 140 mg/dL for the 1-h 50-g GLT (204). †ACOG
As effective prevention interventions are notes that one elevated value can be used for diagnosis (204).
available (186,187), individuals diagnosed
with GDM should receive lifelong screen-
ing for prediabetes to allow interventions Different diagnostic criteria will identify increased body fat, suggesting that the
to reduce diabetes risk and for type 2 dia- different degrees of maternal hypergly- group identified as having GDM by the
betes to allow treatment at the earliest cemia and maternal/fetal risk, leading one-step approach would benefit from
possible time (188). experts to debate optimal strategies for the increased screening for diabetes and
the diagnosis of GDM. prediabetes after pregnancy (193). The
Diagnosis ADA recommends the IADPSG diagnostic
GDM carries risks for the mother, fetus, One-Step Strategy criteria to optimize gestational outcomes,
and neonate. The Hyperglycemia and Ad- The IADPSG examined data from the because these criteria are the only ones
verse Pregnancy Outcome (HAPO) study HAPO study and defined diagnostic cut based on pregnancy outcomes rather
(189), a large-scale multinational cohort points for GDM as the average fasting, than end points such as prediction of
study completed by more than 23,000 1-h, and 2-h PG values during a 75-g subsequent maternal diabetes.
pregnant individuals, demonstrated that OGTT in individuals at 24–28 weeks of Expected benefits of using IADPSG
risk of adverse maternal, fetal, and neo- gestation, wherein the cut points were criteria for offspring are inferred from in-
natal outcomes continuously increased those at which odds for adverse outcomes tervention trials focusing on individuals
as a function of maternal glycemia at reached 1.75 times the estimated odds. with lower levels of hyperglycemia than
24–28 weeks of gestation, even within This one-step strategy was anticipated to those identified using older GDM diag-
ranges previously considered normal for significantly increase the incidence of nostic criteria. Those trials found modest
pregnancy. For most complications, there GDM (from 5–6% to 15–20%), primarily benefits, including reduced rates of large-
was no threshold for risk. These results because only one abnormal value, not for-gestational-age births and preeclamp-
have led to careful reconsideration of the two, became sufficient to make the diag- sia (194,195). Of note, 80–90% of partici-
diagnostic criteria for GDM. nosis (191). Many regional studies have pants being treated for mild GDM in
GDM diagnosis (Table 2.8) can be ac- seen a roughly one- to threefold increase these two randomized controlled trials
complished with either of two strategies: in GDM cases using the IADPSG criteria could be managed with lifestyle therapy
(192). A study of pregnancy OGTTs with alone. The OGTT glucose cutoffs in these
1. The “one-step” 75-g OGTT derived glucose levels blinded to caregivers found two trials overlapped the thresholds rec-
from the IADPSG criteria, or that 11 years after their pregnancies, in- ommended by the IADPSG, and in one trial
2. The older “two-step” approach with a dividuals who would have been diagnosed (195), the 2-h PG threshold (140 mg/dL
50-g (nonfasting) screen followed by a with GDM by the one-step approach, as [7.8 mmol/L]) was lower than the cutoff
100-g OGTT for those who screen posi- compared with those without GDM, were recommended by the IADPSG (153 mg/dL
tive based on the work of Carpenter- at 3.4-fold higher risk of developing pre- [8.5 mmol/L]).
Coustan’s interpretation of the older diabetes and type 2 diabetes and had No randomized controlled trials of treat-
O’Sullivan and Mahan (190) criteria. children with a higher risk of obesity and ing versus not treating GDM diagnosed by
S44 Diagnosis and Classification of Diabetes Diabetes Care Volume 48, Supplement 1, January 2025

different criteria have been published to a two-step approach to screening that lower diagnostic thresholds, as shown
date. However, a randomized trial of test- used a 1-h 50-g glucose loading test (GLT) in step 2 in Table 2.8.
ing for GDM at 24–28 weeks of gestation followed by a 3-h 100-g OGTT for those
by the one-step method using IADPSG who screened positive. The American Col- Future Considerations
criteria versus the two-step method by lege of Obstetricians and Gynecologists Data exist to support each strategy, as
Carpenter-Coustan criteria identified twice (ACOG) recommends any of the com- demonstrated by conflicting recommen-
as many individuals with GDM using the monly used thresholds of 130, 135, or dations by expert groups. A systematic re-
one-step method. Despite treating more 140 mg/dL for the 1-h 50-g GLT (204). A view of economic evaluations of GDM
individuals for GDM using the one-step 2021 U.S. Preventive Services Task Force screening found that the one-step method
method, there was no difference in systematic review concluded that one- identified more cases of GDM and was
pregnancy and perinatal complications step versus two-step screening is associ- more likely to be cost-effective than the
(196), though concerns were raised about ated with increased likelihood of GDM two-step method (211). The decision of
sample size estimates and unanticipated (11.5% vs. 4.9%) but without improved which strategy to implement must there-

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suboptimal engagement with the screen- health outcomes (205). The use of A1C at fore be made based on the relative val-
ing and treatment protocol. For example, 24–28 weeks of gestation as a screening ues placed on factors that have yet to
in the two-step group, 165 participants test for GDM does not function as well as be measured (e.g., willingness to change
not counted as having GDM were treated the GLT (206). practice based on correlation studies
for isolated elevated FPG >95 mg/dL Importantly, the NIH panel noted the rather than intervention trial results,
(>5.3 mmol/L) (197). lack of clinical trial data demonstrating available infrastructure, and importance
The one-step method identifies long- the benefits of the one-step strategy and of cost considerations).
term risks of maternal prediabetes and di- the potential negative consequences of The IADPSG criteria (one-step strategy)
abetes as well as offspring glucose intol- identifying a large group of individuals have been adopted internationally as the
erance and adiposity. Post hoc GDM in with GDM, including medicalization of preferred approach. Data that compare
individuals diagnosed with this method in pregnancy with increased health care uti- population-wide outcomes with one-step
the HAPO cohort was associated with lization and costs. Moreover, screening versus two-step approaches have been
higher prevalence of IGT; higher 30-min,
with a 50-g GLT does not require fasting inconsistent to date (196,212–214). Preg-
1-h, and 2-h glucose levels during the
and therefore is easier to accomplish for nancies complicated by GDM per the
OGTT; and reduced insulin sensitivity and
many individuals. Treatment of higher- IADPSG criteria, but not recognized as
oral disposition index in their offspring at
threshold maternal hyperglycemia, as iden- such, have outcomes comparable to preg-
10–14 years of age compared with off-
tified by the two-step approach, reduces nancies with diagnosed GDM by the more
spring of mothers without GDM. Associa-
rates of neonatal macrosomia, large-for- stringent two-step criteria (215,216). There
tions of mother’s fasting, 1-h, and 2-h
gestational-age births (207), and shoulder remains strong consensus that establishing
values on the 75-g OGTT were continuous
dystocia without increasing small-for- a uniform approach to diagnosing GDM
with a comprehensive panel of offspring
gestational-age births. ACOG currently will benefit people with GDM, caregivers,
metabolic outcomes (198,199). HAPO
supports the two-step approach but and policymakers. Longer-term outcome
Follow-up Study (HAPO FUS) data demon-
strate that neonatal adiposity and fetal notes that one elevated value, as op- studies are currently underway.
hyperinsulinemia (cord C-peptide), both posed to two, may be used for the diag-
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