A 63-year-old man comes to the office for follow-up after abnormal test results. He was found to have a blood glucose level of 255 mg/dL during a recent outpatient visit. The patient had previous normal blood glucose levels, except during a hospital admission for abdominal pain 9 months ago when he briefly required insulin for hyperglycemia. He currently feels well except for dry mouth and frequent urination, and has experienced a weight loss of 10.4 kg (23 lb) in the last 6 months. The patient has a history of obesity, hypertension, chronic pancreatitis due to alcohol abuse, obstructive sleep apnea, chronic kidney disease (estimated glomerular filtration rate 28 mL/min/1.73 m²), and heart failure with reduced ejection fraction (ejection fraction 35%). He quit drinking alcohol a year ago and does not use tobacco or illicit drugs. Both of his parents had type 2 diabetes mellitus; his father died of a massive myocardial infarction at age 58 and his mother died due to metastatic breast cancer. Blood pressure is 132/80 mm Hg and pulse is 76/min. BMI is 31 kg/m². Physical examination shows mild bilateral pedal edema. Repeat blood glucose level is 250 mg/dL, and hemoglobin A1c is 9%. Which of the following medications is most appropriate for treatment of diabetes mellitus in this patient?

Question

Quizplus · Accepted Answer

Explanation: 11ec2b69_beb3_135e_8f63_479d05de59fb_MD0005_00 This patient has symptomatic hyperglycemia likely due to pancreatogenic diabetes mellitus (PD). Chronic pancreatitis can cause islet cell damage, leading to insulin deficiency with progressive glucose intolerance and eventually overt diabetes. The risk of PD increases with longer duration of chronic pancreatitis and is more common in patients with other risk factors for diabetes such as a family history of diabetes. Mild hyperglycemia in PD can be treated initially with metformin. However, more severe insulin deficiency with symptomatic hyperglycemia, as in this patient, requires insulin therapy. Patients with PD are prone to developing hypoglycemia due to loss of glucagon-producing alpha cells in addition to the loss of beta cells. (In type 1 diabetes, there is loss of beta cells, but alpha cells are largely intact and can secrete glucagon in response to hypoglycemia). However, due to loss of glucagon secretion, diabetic ketoacidosis is rare in PD despite insulin deficiency. (Choice A) Insulin secretagogues (eg, glipizide) are often ineffective in PD due to decreased pancreatic beta cell reserve. (Choices C and D) Incretin-based therapy, such as dipeptidyl peptidase-4 inhibitors (eg, linagliptin, sitagliptin) and glucagon-like peptide-1 receptor agonists (eg, liraglutide, exenatide, dulaglutide), is associated with an increased risk of pancreatitis and should be avoided in patients with a history of pancreatitis. (Choice E) Metformin is contraindicated in patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² and should be used with caution in those with eGFR 30-45 mL/min/1.73 m². Educational objective: Pancreatogenic diabetes mellitus is associated with destruction of both islet alpha cells and beta cells. Mild hyperglycemia in pancreatogenic diabetes can be treated initially with metformin, but more severe insulin deficiency with symptomatic hyperglycemia requires insulin therapy. References: Pancreatogenic diabetes: special considerations for management. (http://www.ncbi.nlm.nih.gov/pubmed/21757968)

A 63-Year-Old Man Comes to the Office for Follow-Up After