A 37-year-old woman presents with difficult-to-control diabetes. The diabetes developed 3 years prior to this visit, when the patient began to notice fatigue, nocturia, and visual blurriness. She has been placed on metformin, glyburide, and finally pioglitazone at maximal doses, and yet her hemoglobin A1C is still above target at 8.2. She has compliant with her medical regimen and is concerned about her health status. There is no family history of diabetes. On examination, her BP is 126/80, BMI is 23.7, and general physical examination is normal. She has no evidence or retinopathy or peripheral neuropathy. Anti-islet cell autoantibodies, including anti-glutamic acid decarboxylase (GAD) antibodies, are positive. What is the likely diagnosis?
A. Cushing syndromeClassically, you think of type 1 diabetes as immune-mediated destruction of beta cells leading to insulin-dependent disease in children or adolescents, and type 2 diabetes as a disease of insulin resistance in obese adults with positive family history of the disease—but reality is more complex. Lateonset autoimmune diabetes of adults (LADA) typically occurs in nonobese adults, often without a family history of diabetes. It is slower in onset and less ketosis prone than type 1 diabetes, but responds poorly to agents such as metformin that improve insulin sensitivity. Autoantibodies (anti-GAD antibodies being the most sensitive and specific) characterize LADA as well as type 1 DM. An important aspect of LADA is that early use of insulin is necessary to adequately control the blood glucose levels. Maturity-onset diabetes of young is the opposite of LADA, that is, that is, a condition resembling type 2 diabetes (ie, often associated with obesity and a positive family history) yet occurring before the age of 20. This patient’s autoantibodies, thin body habitus, and unresponsiveness to oral hypoglycemic would not go with MODY. Cushing syndrome is often associated with hyperglycemia due to the insulin counter-regulatory effect of cortisol, but this patient does not have the other clinical features that almost always accompany cortisol excess. Glucagonomas are rare islet cell tumors that produce weight loss, malabsorption, and a severe skin rash. The patient in question has none of the features of this rare syndrome.