A 54-year-old man comes to the physician for a follow up appointment. He has no complaints. His medical problems include type 2 diabetes mellitus, hyperlipidemia, and hypertension. His current medications include metformin, glyburide, lovastatin, and lisinopril. He was diagnosed with type 2 diabetes mellitus 6 years ago and at the time had a BMI of 31 kg/m². He has since employed significant lifestyle changes to decrease his blood glucose levels and has lost 10 lbs (4.5 kg) . Both of his parents have type 2 diabetes and hypertension. He works as a supervisor in a grocery store. He walks 3 miles five times per week. He denies tobacco or alcohol use.
His physical examination is unremarkable, except for a BMI of 29 kg/m².
His hemoglobin A1C trend is shown below.

Anti-glutamic acid decarboxylase (anti-GAD) antibody is not detected.
Which of the following is the most likely explanation for this patient's worsening glycemic status?

Question

A 54-year-old man comes to the physician for a follow up appointment. He has no complaints. His medical problems include type 2 diabetes mellitus, hyperlipidemia, and hypertension. His current medications include metformin, glyburide, lovastatin, and lisinopril. He was diagnosed with type 2 diabetes mellitus 6 years ago and at the time had a BMI of 31 kg/m². He has since employed significant lifestyle changes to decrease his blood glucose levels and has lost 10 lbs (4.5 kg) . Both of his parents have type 2 diabetes and hypertension. He works as a supervisor in a grocery store. He walks 3 miles five times per week. He denies tobacco or alcohol use.
His physical examination is unremarkable, except for a BMI of 29 kg/m².
His hemoglobin A1C trend is shown below.

Anti-glutamic acid decarboxylase (anti-GAD) antibody is not detected.
Which of the following is the most likely explanation for this patient's worsening glycemic status?

Quizplus · Accepted Answer

11ec193a_97b0_16c1_853d_239f1aeb23e5_MD0002_00 Type 2 diabetes mellitus (T2DM) is a complex interplay of multiple pathophysiologic factors, including insulin resistance and progressive beta cell failure (relative insulin deficiency). Patients predisposed to developing T2DM are generally insulin resistant, causing their pancreatic beta cells to overproduce insulin to compensate. These patients transition from normoglycemia to hyperglycemia when their relative insulin deficiency is unable to overcome their insulin resistance. As a result, most T2DM patients require additional anti-diabetic therapies to maintain normoglycemia. Current anti-diabetic drugs do not completely prevent T2DM beta cell functional decline. Large studies (e.g., UKPDS) have shown that T2DM controlled with one medication usually requires additional therapy after a few years to maintain glycemic control. This patient has the typical T2DM course (i.e., requiring additional therapy with disease progression) and now likely has relative insulin deficiency. (Choice A) The patient has insulin resistance, but it is unlikely that the insulin resistance has increased given his lifestyle changes and 10 lb weight loss. (Choice B) Approximately 10% of patients with T2DM have an indolent form of type 1 diabetes (LADA), which usually presents in thin individuals with positive anti-GAD antibodies and no significant family history. However, this patient is overweight without anti-GAD antibodies. In addition, his strong family history of T2DM and good initial glycemic response to anti-diabetic medications makes LADA less likely. (Choice C) Medication non-compliance is a major reason for uncontrolled T2DM, but this patient appears to be compliant with a good initial response to medications and a gradual worsening of glycemic control. (Choice E) Statins have a minimal hyperglycemic effect and it is somewhat controversial if they cause worsening hyperglycemia or development of T2DM. Educational objective: Progressive insulin deficiency plays a very important role in the pathophysiology of diabetes and is one of the main reasons for failure of anti-diabetic therapy over time despite good initial response. __________ References: Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. (http://www.ncbi.nlm.nih.gov/pubmed/10359389) Beta-cell failure in type 2 diabetes mellitus (http://www.ncbi.nlm.nih.gov/pubmed/18625113)

A 54-Year-Old Man Comes to the Physician for a Follow