A 64-year-old woman is brought to the emergency department due to confusion and lethargy. The patient was asymptomatic when her husband left for work in the morning, but when he arrived home, he found her in bed weak and disoriented. The patient's medical conditions include type 2 diabetes mellitus and hypertension, for which she takes multiple medications. She does not use tobacco, alcohol, or illicit drugs. Temperature is 37 C (98.6 F), blood pressure is 140/70 mm Hg, pulse is 74/min, and respirations are 18/min. On physical examination, the patient is somnolent but withdraws all extremities to pain. Laboratory testing shows an elevated serum C-peptide level. If her current condition is due to an antidiabetic drug, which of the following is the most likely culprit agent?

Question

A 64-year-old woman is brought to the emergency department due to confusion and lethargy.  The patient was asymptomatic when her husband left for work in the morning, but when he arrived home, he found her in bed weak and disoriented.  The patient's medical conditions include type 2 diabetes mellitus and hypertension, for which she takes multiple medications.  She does not use tobacco, alcohol, or illicit drugs.  Temperature is 37 C (98.6 F), blood pressure is 140/70 mm Hg, pulse is 74/min, and respirations are 18/min.  On physical examination, the patient is somnolent but withdraws all extremities to pain.  Laboratory testing shows an elevated serum C-peptide level.  If her current condition is due to an antidiabetic drug, which of the following is the most likely culprit agent?

Quizplus · Accepted Answer

11ec160b_3bb0_daea_9249_9186658ebdf4_MD0001_00 This patient with type 2 diabetes mellitus has acute confusion and lethargy, which is consistent with symptomatic hypoglycemia, a common adverse effect of antidiabetic medications. Her elevated C-peptide level is further indicative of a medication that stimulates pancreatic insulin secretion independent of blood glucose levels, such as sulfonylureas (eg, glyburide) or meglitinides. Insulin is synthesized in pancreatic beta cells as preproinsulin, which is guided by a signal peptide into the rough endoplasmic reticulum during translation. The signal peptide is then removed, converting preproinsulin to proinsulin. Protein folding and disulfide bond formation take place as proinsulin traverses the rough endoplasmic reticulum. Proinsulin is then transported to the Golgi apparatus, where it is packaged with proteolytic enzymes into insulin secretory granules and cleaved into mature insulin and C-peptide. C-peptide and insulin are then co-secreted from pancreatic beta cells in equimolar amounts. When hypoglycemia is due to excessive endogenous insulin production (eg, sulfonylureas, meglitinides, insulinoma), C-peptide levels are elevated. In contrast, exogenous insulin and insulin analogs (ie, insulin-like polypeptides with alterations in the amino acid sequence to optimize pharmacokinetic properties) do not contain C-peptide. When hypoglycemia is induced by these agents, endogenous insulin secretion is suppressed and C-peptide levels are low (Choices D and G). (Choice A) Acarbose inhibits alpha-glucosidase in the intestinal brush border, impairing the hydrolysis of polymeric carbohydrates and leading to decreased postprandial glucose absorption. Acarbose indirectly decreases endogenous insulin (and C-peptide) secretion by reducing postprandial hyperglycemia. (Choices B, E, and F) Sodium-glucose cotransporter-2 inhibitors (eg, canagliflozin, dapagliflozin) act in the kidney to decrease the reabsorption of filtered glucose. Major side effects include hypotension and urinary tract infection. Metformin is a biguanide that decreases hepatic glucose production, decreases intestinal glucose absorption, and increases peripheral glucose uptake and utilization. Thiazolidinediones (eg, pioglitazone) increase insulin sensitivity by increasing glucose utilization and decreasing glucose production in adipose tissue, muscle, and liver. These agents have a low risk of hypoglycemia and do not increase endogenous insulin secretion. Educational objective: Proinsulin is cleaved into mature insulin and C-peptide, which are co-secreted from pancreatic beta cells in equimolar amounts. Circulating levels of C-peptide can be used as a marker of endogenous insulin secretion. Sulfonylureas and meglitinides lower blood glucose by stimulating pancreatic insulin secretion; hypoglycemia due to these agents is associated with elevated C-peptide levels. __________ References: Regulation of insulin synthesis and secretion and pancreatic beta-cell dysfunction in diabetes. (http://www.ncbi.nlm.nih.gov/pubmed/22974359)

A 64-Year-Old Woman Is Brought to the Emergency Department Due