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Diagnosis of Type 1 Diabetes

Diagnosis of Type 1 Diabetes. Classifying Diabetes. 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.

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Diagnosis of Type 1 Diabetes

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  1. Diagnosis of Type 1 Diabetes

  2. Classifying Diabetes 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.

  3. A Growing Issue: Differentiating T1DM and T2DM 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.

  4. “Etiological” Classification of Diabetes 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.

  5. 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.

  6. Symptoms and Severity of T1DM at Presentation: EURODIAB DKA, diabetic ketoacidosis. Levy-Marchal C, et al. Diabetol. 2001;44 (Suppl 3):B75-B80.

  7. 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 American Diabetes Association. DiabetesCare. 2013;36(suppl 1):S67-S74.

  8. 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. DiabetesCare. 2013;36(suppl 1):S67-S74.

  9. 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. DiabetesCare. 2013;36(suppl 1):S67-S74.

  10. 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. DiabetesCare. 2013;36(suppl 1):S67-S74.

  11. 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. DiabetesCare. 2013;36(suppl 1):S67-S74.

  12. 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

  13. 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 • Often suffer from episodic ketoacidosis and exhibit varying degrees of insulin deficiency between episodes American Diabetes Association. DiabetesCare. 2013;36(suppl 1):S67-S74.

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