The Diabetologist #21

million people have T2D and more than 7 million of
them are unaware of their diagnosis. Characterized
by obesity, insulin resistance, dyslipidemia, hypertension,
microvascular and macrovascular complications,
and a predisposition in African Americans,
Hispanics, and Native Americans, T2D indirectly
accounts for nearly 1 in every 10 health care dollars.14
Given the tremendous burden T2D places
on the U.S. health care system, it is not surprising
that patients, health care providers, and researchers
often use the nonspecific termdiabetes when
referring to T2D. However, the practice of referring
to T2D as simply diabetes cultivates numerous
dangerous misconceptions regarding the etiology,
pathophysiology, and treatment of other subtypes
of diabetes.
In addition to T1D and T2D, a growing number
of Americans are diagnosed with diabetes during
pregnancy. Gestational diabetes mellitus
(GDM) currently affects ~7% of pregnancies
(200,000 cases annually) with
5–10% of affected women diagnosed
with T2D after delivery
(and some are diagnosed with
auto-immune T1D, as well).15
(See chapter 17 for more
details.) Even for those who
return to normal postpartum
glucose metabolism, the 20-
year risk of developing T2D
approaches 60% once GDM
has been diagnosed. Notably,
the screening and diagnostic
criteria for GDM are unique
from other forms of diabetes.
Cystic fibrosis–related diabetes
(CFRD) is another subtype of diabetes
requiring a unique therapeutic approach.
Named for the characteristic cyst and
fibrosis formation noted in the exocrine pancreas
of affected patients, cystic fibrosis (CF) is an autosomal
recessive disorder caused by a mutation
in a chloride transporter known as the cystic fibrosis
transmembrane conductance regulator. While
the primary complication in CF is chronic pulmonary
disease, up to 75% of adults with CF develop
glucose intolerance and nearly 15% have CFRD.
CFRD is unique in that it shares some pathophysiology
with both T1D and T2D. Namely, patients
with CFRD have a combination of 1) reduced β-cell
mass (a feature typically associated with T1D) secondary
to the chronic pancreatic inflammation and
2) severe insulin resistance (a feature associated
with T2D) as a result of chronic and often subclinical
pulmonary infections. Given the unique hypermetabolic
state associated with CF, patients with
CFRD require high-calorie diets and tight glycemic
control to avoid a catabolic state. As such, current
CFRD guidelines discourage the use of oral
hypoglycemics or calorie restriction and focus
instead on the use of insulin to manage glucose
abnormalities.16
Finally, clinicians should be aware of the monogenic
forms of diabetes. Accounting for only 1–5%
of all diabetes cases, monogenic diabetes results
from single gene mutations that are inherited in an
autosomal dominant fashion. These mutations do
not result in insulin resistance or autoimmunity but
instead induce diabetes by blunting the capacity
of otherwise normal β-cells to release insulin. The
two main forms of monogenic diabetes are neonatal
diabetes mellitus (NDM) and maturity-onset
diabetes of the young (MODY). NDM is a rare
condition and occurs in 1/100,000 to
1/500,000 newborns and is often
mistaken for T1D due to its association
with ketoacidosis and its
requirement for insulin therapy.
However, T1D is exceedingly
rare before 6 months of age
and any child diagnosed
with T1D before 9 months of
age should be screened for
monogenic diabetes. There
are two forms of NDM, transient
NDM, which resolves
within weeks to months, and
permanent NDM, which is
associated with a lifelong dependence
on insulin. Testing for
known diagnostic mutations allows
accurate differentiation of the two subtypes
of NDM and emphasizes the need for
clinicians to be aware of rare forms of diabetes. In
contrast to NDM, MODY is a mild form of diabetes
that is commonly, but not always, diagnosed
in adulthood. Patients initially diagnosed with T1D
who fail to demonstrate autoantibody positivity or
who persist with near normal glycemic control on
minimal insulin should be screened for MODY. Diagnosis
of MODY is especially important as some
forms of MODY may be controlled with oral hypoglycemic
agents. For a subset of patients, the
appropriate diagnosis can mean the difference
between a lifetime of insulin injections or effective
glycemic control with a sulfonylurea.17
issue 21 < May 2013
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