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Mrs. D is a 50-year-old African American woman who is worried she has diabetes.

image What is the differential diagnosis of diabetes? How would you frame the differential?


The differential diagnosis of diabetes mellitus (DM) is actually a classification of the different causes of diabetes:

  1. Type 1 DM

    1. Of the persons with DM in Canada, the United States, and Europe, 5–10% have type 1.

    2. Caused by cellular-mediated autoimmune destruction of the pancreatic beta cells in genetically susceptible individuals, triggered by an undefined environmental agent

      1. Some combination of antibodies against islet cells, insulin, glutamic acid decarboxylase (GAD65), or tyrosine phosphatases IA-2 and IA-2beta are found in 85–90% of patients.

      2. Strong HLA association

      3. Risk is 0.4% in patients without family history, 5–6% in siblings and children, and 30% in monozygotic twins.

      4. Patients are also prone to autoimmune thyroid disease, Addison disease, vitiligo, celiac sprue, autoimmune hepatitis, myasthenia gravis, and pernicious anemia.

    3. Occasionally occurs without a defined HLA association or autoimmunity in patients of African or Asian ancestry

    4. Insulin therapy is always necessary.

    5. Patients are at high risk for diabetic ketoacidosis (DKA).

  2. Type 2 DM

  3. Other, less common causes of diabetes

    1. Genetic defects of beta cell function or insulin action

    2. Exocrine pancreatic diseases (pancreatitis, trauma, infection, pancreatectomy, pancreatic carcinoma)

    3. Endocrinopathies (acromegaly, Cushing syndrome, glucagonoma, pheochromocytoma)

    4. Medications (especially corticosteroids)

    5. Infections

  4. Gestational diabetes

Type 1 DM generally occurs in children, although approximately 7.5–10% of adults assumed to have type 2 DM actually have type 1, as defined by the presence of circulating antibodies. Type 2 DM is becoming more prevalent in teenagers and young adults, presumably related to the increased prevalence of obesity.

In most patients, the distinction between type 1 and type 2 DM is clear. Thus, the primary tasks of the clinician are to determine who should be tested for diabetes, who has diabetes, which complications to monitor, and how to treat the patient.


Mrs. D has worried about having diabetes since her father died of complications from the disease. Over the last couple of weeks, she has been urinating more often and notes larger volumes than usual. She is aware that excess urination can be a symptom of diabetes, so she scheduled an appointment.

image At this point, what is the leading hypothesis, what are the active alternatives, and is there a must not miss diagnosis? Given this differential diagnosis, what tests should be ordered?


Mrs. D’s pretest probability of diabetes is high because of 2 pivotal points in her history, the polyuria and the positive family history. Excess fluid intake and diseases that cause true polyuria, defined as urinary output of > 3 L/day, should also be considered. Bladder dysfunction and urinary tract infection generally cause frequent, small volume urination. Since patients sometimes have trouble ...

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