A 36-year-old man with type 1 diabetes mellitus comes to the office due to recurrent hypoglycemic episodes. He previously had difficulty controlling his high blood glucose levels, but over the past several weeks his blood glucose has intermittently dropped to

Question

A 36-year-old man with type 1 diabetes mellitus comes to the office due to recurrent hypoglycemic episodes.  He previously had difficulty controlling his high blood glucose levels, but over the past several weeks his blood glucose has intermittently dropped to <50 mg/dL with accompanying symptoms of tremulousness and headache.  There have been no recent changes in his diet, activity level, insulin dosage, or other medical therapy.  The patient's other medical conditions include chronic kidney disease from diabetic nephropathy.  His estimated glomerular filtration rate has declined to 20 mL/min in recent months, and he is under consideration for initiation of hemodialysis.  Physical examination findings are unchanged from the previous office visit 3 months ago.  Which of the following is most likely contributing to this patient's current glycemic disturbances?

Quizplus · Accepted Answer

Insulin is a peptide hormone that has both renal and hepatic clearance. Degradation of circulating insulin in the kidneys is dependent on an adequate glomerular filtration rate (GFR), which allows for delivery of insulin to the proximal tubule cells where it is broken down. Chronic kidney disease (CKD) causes decreased GFR, which impairs insulin clearance. In patients with normal pancreatic function, hypoglycemia is avoided because pancreatic insulin production decreases and circulating insulin levels rapidly return to baseline. However, patients taking exogenous insulin are at increased risk of hypoglycemia if there is no decrease in dosage to compensate for renal failure. In light of this patient's worsening CKD, his symptomatic hypoglycemia is likely due to reduced renal insulin clearance and a prolonged insulin effect. (Choice A) Advanced CKD leads to reduced gluconeogenesis in the kidney, not the liver. Hepatic gluconeogenesis is inhibited by inflammatory cytokine release (eg, sepsis), heavy alcohol use, and beta blockers. (Choice C) Patients with type 1 diabetes typically have minimal to no secretory reserve and cannot increase insulin in response to physiologic stimuli. (Choice D) Increased renal glucose excretion can cause glucosuria; however, this occurs in the setting of significant hyperglycemia (not hypoglycemia). In addition, this patient's low glomerular filtration rate would be expected to reduce renal glucose excretion. (Choice E) Insulin sensitivity is decreased (not increased) in CKD due to the accumulation of urea and other metabolic toxins. Educational objective: Insulin has both renal and hepatic clearance. In patients with advanced chronic kidney disease and diabetes mellitus, decreased renal clearance of insulin can lead to symptomatic hypoglycemia if exogenous insulin doses are not adjusted based on the change in renal function. __________ References: Pathophysiology and management of hypoglycemia in end-stage renal disease patients: a review. (http://www.ncbi.nlm.nih.gov/pubmed/27967230)

A 36-Year-Old Man with Type 1 Diabetes Mellitus Comes to the Office