Transcript Percentage of Patients With DKA at Presentation
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Diagnosis of Type 1 Diabetes
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.
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A Growing Issue: Differentiating T1DM and T2DM
Usual clinical course Usual age of onset Body weight Onset Ketosis prone Family history Ethnicity Frequency of HLA-DR3, DR4, DQB1*0201, *0302 Islet autoantibodies (GADA, ICA, IA-2A, IAA)
Type 1 Diabetes
Insulin-dependent <20 years (but ~50% over 20 years) Usually lean Often acute Yes 15% with 1 st -degree relative Predominantly white Increased Present
Type 2 Diabetes
Initially non-insulin-dependent >40 years but increasingly earlier Usually obese Subtle, slow No Common More common in minorities Not increased 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.
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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 American Diabetes Association.
Diabetes Care.
2013;36(suppl 1):S67-S74.
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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 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 7 When fasting hyperglycemia is first detected, one and usually more than one of these autoantibodies are present in 85%-90% of individuals American Diabetes Association.
Diabetes Care
. 2013;36(suppl 1):S67-S74.
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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 American Diabetes Association.
Diabetes Care
. 2013;36(suppl 1):S67-S74.
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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 American Diabetes Association.
Diabetes Care
. 2013;36(suppl 1):S67-S74.
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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 American Diabetes Association.
Diabetes Care
. 2013;36(suppl 1):S67-S74.
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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 American Diabetes Association.
Diabetes Care
. 2013;36(suppl 1):S67-S74.
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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
Idiopathic Diabetes
13 • 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 • 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.