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Key Features

Essentials of Diagnosis

  • Polyuria, polydipsia, and weight loss associated with random plasma glucose ≥ 200 mg/dL (11.1 mmol/L)

  • Plasma glucose ≥ 126 mg/dL (7.0 mmol/L) after an overnight fast, documented on more than one occasion

  • Ketonemia, ketonuria, or both

General Considerations

  • Caused by pancreatic islet B-cell destruction

  • Destruction autoimmune in > 95% of cases (type 1a) and idiopathic in the remainder (type 1b)

  • About 95% of type 1 patients possess either HLA-DR3 or HLA-DR4 compared with 45–50% of white controls. HLA-DQB1*0302 is an even more specific marker for susceptibility

  • Most patients have circulating antibodies to islet cells (ICA), glutamic acid decarboxylase (GAD65), insulin (IAA), and tyrosine phosphatase IA2 (ICA-512) and zinc transporter 8 (ZnT8) at diagnosis

  • The rate of pancreatic B-cell destruction ranges from rapid to slow

  • Prone to ketoacidosis

  • Plasma glucagon is elevated

  • C peptide levels do not reliably distinguish between type 1 and type 2 diabetes mellitus

Demographics

  • Occurs at any age but most commonly arises in children and young adults with a peak incidence before school age and again at around puberty

  • Incidence

    • Highest in Scandinavia

    • In Finland, yearly incidence in children 14 years old or younger is 40 per 100,000

    • Lowest incidence is < 1 per 100,000 per year in China and parts of South America

    • In the United States, average is 16 per 100,000

    • Incidences are higher in states densely populated with persons of Scandinavian descent such as Minnesota

    • The global incidence is increasing, with an annual increase of ~3%

  • An estimated 30.3 million Americans have diabetes mellitus, of whom ~1.5 million have type 1 diabetes

Clinical Findings

Symptoms and Signs

  • Increased thirst (polydipsia)

  • Increased urination (polyuria)

  • Increased appetite (polyphagia) with weight loss

  • Ketoacidosis

  • Paresthesias

  • Recurrent blurred vision

  • Vulvovaginitis or pruritus

  • Nocturnal enuresis

  • Postural hypotension from lowered plasma volume

Differential Diagnosis

  • Type 2 diabetes

  • Hyperglycemia resulting from other causes

    • Medications (high-dose corticosteroids, pentamidine)

    • Other endocrine conditions (Cushing syndrome, glucagonoma, acromegaly, pheochromocytoma)

  • Metabolic acidosis of other causes (alcoholic ketoacidosis)

  • Nondiabetic glycosuria (renal glycosuria)

Diagnosis

Laboratory Tests

  • Fasting plasma glucose > 126 mg/dL (7 mmol/L) or > 200 mg/dL (11.1 mmol/L) 2 h after glucose load (Table 27–4)

  • Hemoglobin A1c (HbA1c) of at least 6.5%

  • Ketonemia, ketonuria, or both

  • Urine glucose (Clinistix, Diastix)

  • Urine and blood ketones (Acetest, Ketostix)

  • Hemoglobin A1c reflects glycemic control over preceding 8–12 weeks

  • Serum fructosamine

    • Reflects glycemic control over preceding 2 weeks

    • Helpful in presence of abnormal hemoglobins or in ascertaining glycemic control at time of conception among diabetic women

  • Lipoprotein abnormalities; unlike in type 2 diabetes, moderately deficient control of hyperglycemia in type 1 diabetes is associated with only slight elevation of low-density lipoprotein (LDL) cholesterol and serum triglycerides and minimal change ...

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