Diabetes Mellitus, Type 1

SOURCE

Source: Triplitt CL, Repas T, Alvarez C. Diabetes mellitus. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146065891. Accessed March 9, 2017.

CONDITION/DISORDER SYNONYMS

• Juvenile-onset diabetes mellitus (DM)

• Insulin-dependent DM

DEFINITION

• Disorder of carbohydrate regulation caused by absolute deficiency of insulin production by pancreas.

ETIOLOGY

• Autoimmune disorder usually developing in childhood or early adulthood probably initiated by exposure of genetically susceptible individual to unknown environmental agent.

• Idiopathic type 1 DM is nonimmune form often seen in minorities, especially Africans and Asians, with intermittent insulin requirements.

PATHOPHYSIOLOGY

• Immune-mediated destruction of pancreatic β-cells usually resulting in absolute deficiency of insulin.

• A genetically susceptible individual must be exposed to a trigger that initiates the autoimmune process and destruction of pancreatic β-cells.

• β-Cell destruction thought to occur during long preclinical period (9–13 years) associated with presence of immune markers.

• Hyperglycemia occurs when 80–90% of β-cells are destroyed.

• A transient remission (“honeymoon phase”) may precede established disease with associated risks for complications and death.

• Factors initiating the autoimmune process unknown, but process mediated by macrophages and T lymphocytes with autoantibodies to β-cell antigens (eg, islet cell antibody, insulin antibodies)

EPIDEMIOLOGY

• Accounts for 5–10% of all cases of DM

• Prevalence of type 1 DM is increasing.

PREVENTION AND SCREENING

• Presently no means of prevention.

• Routine screening not recommended; screening for islet autoantibody status in high-risk family members may be appropriate in context of clinical trials.

RISK FACTORS

• Parent or sibling with type 1 DM

• Mother who had preeclampsia during pregnancy.

• Respiratory infection shortly after birth.

CLINICAL PRESENTATION

SIGNS AND SYMPTOMS

• Onset: usually abrupt, <30 years old.

• Patients often thin and prone to develop diabetic ketoacidosis (DKA) if insulin withheld or under conditions of stress.

• 20–40% of patients present with DKA several days of.

  • Polyuria.

  • Polydipsia.

  • Polyphagia.

  • Weight loss.

DIAGNOSIS

LABORATORY TESTS

• Criteria for diagnosis of DM include any one of the following:

  • A1C ≥6.5%

  • Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L)

  • 2-hour plasma glucose ≥200 mg/dL (111.1 mmol/L) during oral glucose tolerance test (OGTT) using 75 g anhydrous glucose in water.

  • Random plasma glucose concentration ≥200 mg/dL (111.1 mmol/L) with symptoms of hyperglycemia.

• In absence of unequivocal hyperglycemia, confirm criteria 1 through 3 by repeat testing.

• Normal fasting plasma glucose (FPG) <100 mg/dL (5.6 mmol/L)

• Impaired fasting glucose defined as FPG of 100–125 mg/dL (5.6–6.9 mmol/L)

• Impaired glucose tolerance diagnosed when 2-hour postload sample of OGTT is between 140 and 199 mg/dL (7.8 and 11.0 mmol/L).