The Diabetologist #21

12 In the absence of unequivocal hyperglycemia,
results should be confirmed by repeat testing of
the initially positive criteria as discordance between
the different diagnostic criteria is not uncommon.
Further, as the ADA/WHO diagnostic
criteria are heavily influenced by the overwhelming
burden of T2D worldwide (>90% of diabetes
cases), clinicians must recall that these criteria
are not T1D-specific and do not always provide
optimal sensitivity for the diagnosis of T1D....
An NGSP method, standardized or traceable to
the DCCT reference assay, for A1C should be
used at diagnosis and for ongoing monitoring.
The recent assimilation of A1C as a diagnostic
standard for diabetes exemplifies the challenges
of the diagnostic criteria when evaluating patients.
Because A1C can be performed in the
nonfasting state, has less day-to-day variability,
and does not require stringent patient participation
when measured for diagnostic purposes,
A1C has several desirable qualities of a diagnostic
tool. However, A1C may not provide optimal
sensitivity when evaluating patients with diverse
disease processes culminating in hyperglycemia.
In patients who rapidly develop the disease, A1C
may not rise above current diagnostic criteria despite
marked hyperglycemia. Similarly, in patients
known to be at increased risk for T1D, serial fasting
and OGTT-stimulated glucose concentrations
are likely a more sensitive diagnostic test than
A1C when using a cutoff of 6.5%13. Given the
need to prevent the serious morbidity and mortality
of DKA at diagnosis, ongoing efforts to develop
cost-effective screening or case-finding strategies
in high-risk patients may eventually lead to
diagnostic criteria more specific to T1D.13
Table 1.1 Diagnostic Criteria of Diabetes Fasting
plasma glucose >126 mg/dl (7.0 mmol/L) or 2-h
plasma glucose >200 mg/dl (11 mmol/L) during
OGTT or Clinical symptoms Polyuria, polydipsia,
weight loss, and random plasma glucose >200
mg/dl orHemoglobin A1C >6.5%* *A1C should
be performed using a method that is NGSP-certified
and standardized to the DCCT assay.
DIABETES SUBTYPES
ADA and WHO criteria are used to broadly diagnose
diabetes, however, a combination of immunologic,
genetic, and phenotypic features must
be used to differentiate among the different forms
of diabetes. A brief review of other forms of diabetes
is necessary to frame our ongoing discussion
of T1D. (See chapter 2 for further discussion
of T1D diagnosis.)
T1D has at least two broad subcategories: type
1a diabetes and type 1b diabetes. Type 1a diabetes,
the primary focus of the T1D Sourcebook,
refers to diabetes that is autoimmune in its etiopathogenesis.
Type 1b diabetes results from nonimmune-mediated
β-cell loss (pancreatic agenesis,
pancreatectomy, etc.). In addition to these broad
subtypes, the inherent heterogeneity of T1D has
necessitated additional monikers for patients within
the broad framework of T1D. Some patients, classified
as having fulminant T1D, experience rapid
β-cell destruction; they present with DKA despite
near normal A1C. Conversely, patients labeled as
Latent Autoimmune Diabetes of Adulthood (LADA)
develop T1D over many years, with gradual β-cell
decline that may not be recognized as immunemediated
for years (and sometimes decades) after
the development of hyperglycemia.
Given the growing epidemic of obesity, physicians
must also remember that autoimmune diseases do
not spare those who are overweight or obese. As
such, when an obese patient presents with polyuria,
polydipsia, and hyperglycemia, careful consideration
should be given to making a diagnosis of
T1D versus T2D. A missed or delayed diagnosis
of T1D could result in rapid development of DKA.
Moreover, because patients with T2D can develop
glucose toxicity and a severe enough β-cell deficiency
to cause DKA, clinicians must also be careful
not to label all new-onset patients who present
with DKA as having T1D. Ketonemia and ketonuria
are not typically seen in T2D, but may be present.
They more commonly occur in teens with newonset
T2D than in adults with T2D. Pancreatic islet
autoantibodies are generally absent in T2D but
have been reported in patients with a T2D phenotype.
These cases emphasize the heterogeneity
and crossover of these two distinct diseases.
Some groups have used labels such as double diabetes
or type 1.5 diabetes to describe children with
characteristics of both diseases. Our preference is
to not use such terms. Instead, we consider all patients
with evidence of autoimmunity to have T1D,
while acknowledging the presence of a T2D phenotype
(also thought of as T1D plus the metabolic
syndrome) and emphasizing the importance of
monitoring for and treating associated comorbidities.
In such cases, the presence of autoantibodies
can be helpful. Definitive classification of diabetes
as type 1 or type 2 can be delayed, but treatment
with insulin should always be initiated.
Beyond our focus on T1D we must acknowledge
that T2D accounts for the overwhelming majority
of the world’s diabetes. In the U.S. alone, over 25
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issue 21 < May 2013