C h a p t e r 3 3
Diabetes Mellitus and the Metabolic Syndrome
801
quite variable, being rapid in some individuals (mainly
infants and children) and slow in others (mainly adults).
Some individuals, particularly children and adoles-
cents, may present with diabetic ketoacidosis (DKA) as
the first manifestation of the disease (to be discussed).
Others may have modest elevations in FPG that can
rapidly change to severe hyperglycemia and DKA in the
presence of stress and infection. Still others, particularly
adults, may retain sufficient beta cell function to delay
onset of clinical diabetes for many years.
The destruction of beta cells and absolute lack of
insulin in people with type 1 diabetes mellitus mean that
they are particularly prone to the development of DKA.
One of the actions of insulin is the inhibition of
lipolysis
(i.e., fat breakdown) and release of free fatty acids (FFAs)
from fat cells. In the absence of insulin, ketosis devel-
ops when these fatty acids are released from fat cells and
converted to ketones in the liver. Because of the loss of
insulin response, all people with type 1A diabetes require
exogenous insulin replacement to reverse the catabolic
state, control blood glucose levels, and prevent ketosis.
Type 1A Immune-Mediated Diabetes.
Type 1A dia-
betes, commonly referred to as
type 1 diabetes
, is char-
acterized by immune-mediated destruction of beta cells.
This type of diabetes, formerly called
juvenile diabetes,
occurs more commonly in children and adolescents. In
fact, three quarters of all cases of type 1 diabetes occur
in individual younger than 18 years of age.
11
Type 1A diabetes is an autoimmune disorder
that is thought to result from a genetic predisposition
(i.e., diabetogenic genes); an environmental triggering
event, such as an infection; and a T-lymphocyte–medi-
ated hypersensitivity reaction against some beta cell
antigens. Much evidence has focused on the inherited
major histocompatibility complex (MHC) genes on
chromosome 6 that encode human leukocyte antigen
(HLA)-DQ and HLA-DR, especially DR-3 and DR-4.
3
In addition to the MHC susceptibility genes on chromo-
some 6, an insulin gene regulating beta cell replication
and function has been identified on chromosome 11.
Type 1A diabetes–associated autoantibodies may exist
for years before the onset of hyperglycemia. There are
two main types of autoantibodies: insulin autoantibodies
(IAAs) and islet cell autoantibodies, including antibodies
directed at other islet autoantigens, including glutamic
acid decarboxylase (GAD) and the protein tyrosine phos-
phatase IA-2.
3,11
Testing for antibodies to GAD or IA-2
and for IAAs using sensitive assays can be used to iden-
tify new cases of type 1 diabetes when diagnostic confu-
sion between type 1 and type 2 diabetes occurs or there is
future risk of type 1 diabetes (e.g., in siblings of a person
with type 1).
1
These persons also have increased predis-
position to other autoimmune disorders such as Graves
disease, rheumatoid arthritis, and Addison disease.
The fact that type 1 diabetes is thought to result from
an interaction between genetic and environmental fac-
tors led to research into methods directed at prevention
and early control of the disease. These methods include
the identification of genetically susceptible persons and
early intervention in newly diagnosed persons with
type 1 diabetes. After the diagnosis of type 1 diabetes,
TABLE 33-3
Normal and Increased Fasting Plasma Glucose (FPG), Oral GlucoseToleranceTest
(OGTT), and Hemoglobin A
1c
(A1C) for Categories of Increased Risk for Diabetes and
Criteria for Diagnosis of Diabetes
Test
Normoglycemia
Categories of Increased
Risk for Diabetes*
Criteria for Diagnosis of
Diabetes
†
FPG
‡
<100 mg/dL(5.6 mmol/L)
Impaired fasting glucose
(IFG)100 mg/dL (5.6 mmol/L)
to125 mg/dL (6.9 mmol/L)
≥
126 mg/dL (7.0 mmol/L)
or
2-h plasma glucose in 75-g
OGTT
<140 mg/dL(7.8 mmol/L)
Impaired glucose tolerance
(IGT)140 mg/dL (7.8 mmol/L)
to199 mg/dL (11.0 mmol/L)
≥
200 mg/dL (11.1 mmol/L)
or
A1C
§
3.9%–5.6%
5.7%–6.4%
≥
6.5%
or
Other
Classic symptoms of
hyperglycemia or
hyperglycemic crisis and a
plasma glucose
≥
200 mg/dL
(11.1 mmol/L)
*
For all three tests, risk is continuous below the lower limit of the range and becomes disproportionately
greater at higher ends of the range.
†
Diagnosis of diabetes can be based on criteria 1 (FP), 2 (OGTT), 3 (A1C), or 4 (Other). In the absence of
unequivocal hyperglycemia, criteria for 1–3 should be confirmed by repeat testing.
‡
Fasting is defined as no caloric intake for at least 8 hours.
§
A1C should be performed using a method that is certified by the National Glycohemoglobin
Standardization Program and standardized or traceable to the Diabetes Control and ComplicationsTrial
reference assay.
Developed from American Diabetes Association. Diagnosis and classification of diabetes mellitus—2010.
Diabetes Care. 32(Suppl 1):S62–S69.
