Diabetes Mellitus, Type 1

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

• Islet autoantibodies are frequently present

General Considerations

• Catabolic disorder in which

  • Circulating insulin is virtually absent

  • Plasma glucagon is elevated

  • Pancreatic B cells fail to respond to all insulinogenic stimuli

• Caused by autoimmune destruction of pancreatic islet B cells

• About 95% of patients with type 1 diabetes 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

• 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 at age 10–14 years

• Incidence

  • Highest in Scandinavia and northern Europe

  • In Finland, yearly incidence in children ≤ 14 years 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 37.3 million Americans (10.5%) have diabetes mellitus, of whom ∼5–10% have type 1 diabetes

CLINICAL FINDINGS

Symptoms and Signs

• Increased thirst (polydipsia)

• Increased urination (polyuria)

• Usual or increased appetite (polyphagia) with weight loss

• Ketoacidosis

• Paresthesias

• Altered level of consciousness

• Recurrent blurred vision

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 29–3)

• Hemoglobin A_1c (HbA_1c) of at least 6.5% (48 mmol/mol); reflects glycemic control over preceding 8–12 weeks

• Ketonemia, ketonuria, or both

• Urine glucose (Clinistix, Diastix)

• Urine and blood ketones (Acetest, Ketostix)

• Serum fructosamine

  • Reflects glycemic control over preceding 1–2 weeks

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