Percentage of Patients With DKA at Presentation

Report
Diagnosis of
Type 1 Diabetes
1
Classifying Diabetes
2
IAA, autoantibodies to insulin; GADA, glutamic acid decarboxylase;
IA-2A, the tyrosine phosphatase insulinoma antigen; ZnT8A, zinc transporter 8; T1aD, type 1a
(autoimmune) diabetes; T2D, type 2 diabetes.
*Needs to be refined for non-white population groups.
Rewers M. Diabetes Metab J. 2012;36:90-97.
A Growing Issue: Differentiating
T1DM and T2DM
3
Type 1 Diabetes
Type 2 Diabetes
Usual clinical course
Insulin-dependent
Initially non-insulin-dependent
Usual age of onset
<20 years (but ~50% over 20
years)
>40 years but
increasingly earlier
Body weight
Usually lean
Usually obese
Onset
Often acute
Subtle, slow
Ketosis prone
Yes
No
Family history
15% with 1st-degree relative
Common
Ethnicity
Predominantly white
More common in minorities
Frequency of HLA-DR3, DR4,
DQB1*0201, *0302
Increased
Not increased
Islet autoantibodies
(GADA, ICA, IA-2A, IAA)
Present
Absent
IAA, autoantibodies to insulin; GADA, glutamic acid decarboxylase; IA-2A, the tyrosine phosphatase
insulinoma antigen; ZnT8A, zinc transporter 8; T1aD, type 1a (autoimmune) diabetes; T2D, type 2 diabetes.
*Needs to be refined for nonwhite population groups.
Rewers M. Diabetes Metab J. 2012;36:90-97.
“Etiological” Classification of Diabetes
4
APS1, autoimmune polyendocrine syndromes 1;
IPEX, immunodeficiency, polyendocrinopathy, enteropathy, X-linked syndrome;
MODY, maturity-onset diabetes of the young.
Rewers M. Diabetes Metab J. 2012;36:90-97.
Other Specific Types of Diabetes:
Genetic Defects of Beta-Cell Function
•
•
•
•
Chromosome 12, HNF-1α (MODY3)
Chromosome 7, glucokinase (MODY2)
Chromosome 20, HNF-4α (MODY1)
Chromosome 13, insulin promoter factor-1
(IPF-1; MODY4)
• Chromosome 17, HNF-1β (MODY5)
• Chromosome 2, NeuroD1 (MODY6)
• Mitochondrial DNA
5
American Diabetes Association. Diabetes Care. 2013;36(suppl 1):S67-S74.
Symptoms and Severity of T1DM
at Presentation: EURODIAB
Presenting Symptoms:
Percentage of Patients
96%
Percentage of Patients
With DKA at
Presentation
42%
61%
52%
33%
with pH
7.1-7.3
9%
with pH
<7.1
Polyuria
Weight
Loss
Fatigue
DKA
6
DKA, diabetic ketoacidosis.
Levy-Marchal C, et al. Diabetol. 2001;44 (Suppl 3):B75-B80.
Markers of Immune Destruction of
the Beta Cell in T1DM
•
•
•
•
Islet cell autoantibodies
Autoantibodies to insulin
Autoantibodies to GAD (GAD65)
Autoantibodies to the tyrosine phosphatases
IA-2 and IA-2b
When fasting hyperglycemia is first detected, one and
usually more than one of these autoantibodies are
present in 85%-90% of individuals
7
American Diabetes Association. Diabetes Care. 2013;36(suppl 1):S67-S74.
Genetic Markers
• Strong HLA associations, with linkage to
the DQA and DQB genes
• Influenced by the DRB genes
• HLA-DR/DQ alleles can be either
predisposing or protective
8
American Diabetes Association. Diabetes Care. 2013;36(suppl 1):S67-S74.
Beta-Cell Destruction in T1DM
• Can be quite variable
– Rapid in some individuals (mainly infants and children)
– Slow in others (mainly adults)
• Children and adolescents often present with
ketoacidosis as the first manifestation of T1DM
• Other patients have modest fasting hyperglycemia
that can rapidly change to severe hyperglycemia
and/or ketoacidosis in the presence of infection or
other environmental triggers
9
American Diabetes Association. Diabetes Care. 2013;36(suppl 1):S67-S74.
Beta-Cell Destruction in T1DM
• Adults may retain residual β-cell function sufficient to
prevent ketoacidosis for many years
– These patients eventually become insulin-dependent and
are at risk for ketoacidosis
– They have low or undetectable levels of plasma C-peptide
• Immune-mediated diabetes commonly occurs in
childhood and adolescence but can occur at any age
10
American Diabetes Association. Diabetes Care. 2013;36(suppl 1):S67-S74.
T1DM and BMI
• Although T1DM patients are rarely obese
when they present, the presence of obesity is
not incompatible with T1DM
• These patients are also prone to other
autoimmune disorders
– For example, Addison’s disease, autoimmune
hepatitis, celiac sprue, Graves’ disease,
Hashimoto’s thyroiditis, vitiligo, myasthenia gravis,
pernicious anemia
11
American Diabetes Association. Diabetes Care. 2013;36(suppl 1):S67-S74.
T1DM: Clinical Course
• Typically characterized by the acute onset of the
classic symptoms of diabetes
– Polyuria, polydipsia, weight loss
• Course of autoimmune diabetes is characterized by
ongoing β-cell destruction
• Patients with T1DM require exogenous insulin for
survival and should be identified as soon as possible
to avoid high morbidity due to a delay in insulin
treatment
12
Idiopathic Diabetes
• Diabetes of “unknown etiology”
• Patients may have permanent insulinopenia and
are prone to ketoacidosis, but have no evidence
of autoimmunity
• Strongly inherited, lacks immunological
evidence for β-cell autoimmunity, and is not
HLA associated
– Most who fall into this category are of African or
Asian ancestry
13
• Often suffer from episodic ketoacidosis and
exhibit varying degrees of insulin deficiency
between episodes
American Diabetes Association. Diabetes Care. 2013;36(suppl 1):S67-S74.

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