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

• Caused by autoimmune destruction of pancreatic islet B-cells

• 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

• Altered level of consciousness

• 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 27–3)

• Hemoglobin A_1c (HbA_1c) of at least 6.5%; 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 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 ...