A 34-year-old man comes to the office for a follow-up visit. The patient has had type 1 diabetes since age 12 and is diligent in taking insulin to achieve good glycemic control. Over the past few months, he has had more frequent episodes of hypoglycemia despite no changes in his treatment, diet, or physical activity, but the episodes have been associated with less severe hypoglycemic symptoms compared to prior episodes. Physical examination is unremarkable. Laboratory results show normal basic metabolic panel and serum TSH level. Hemoglobin A1c is 7.0%. Which of the following factors is primarily responsible for this patient's increased frequency of hypoglycemia?

Question

A 34-year-old man comes to the office for a follow-up visit.  The patient has had type 1 diabetes since age 12 and is diligent in taking insulin to achieve good glycemic control.  Over the past few months, he has had more frequent episodes of hypoglycemia despite no changes in his treatment, diet, or physical activity, but the episodes have been associated with less severe hypoglycemic symptoms compared to prior episodes.  Physical examination is unremarkable.  Laboratory results show normal basic metabolic panel and serum TSH level.  Hemoglobin A1c is 7.0%.  Which of the following factors is primarily responsible for this patient's increased frequency of hypoglycemia?

Quizplus · Accepted Answer

11ec160b_3cb1_33da_9249_bdc57c23548c_MD0001_00 As blood glucose levels fall through the physiologic range, insulin secretion by pancreatic beta cells decreases, leading to reduced peripheral uptake and utilization of glucose. At the same time, alpha cells increase secretion of glucagon, which is the primary counterregulatory hormone to insulin and acts on the liver to rapidly increase glycogenolysis and gluconeogenesis and decrease glycolysis. Patients with type 1 diabetes mellitus are at increased risk of hypoglycemia because exogenous insulin is not subject to the same regulation as endogenous insulin and will continue to be absorbed from the injection site despite falling glucose levels. Those with long-standing diabetes (ie, >5 years) frequently also have alpha cell failure with decreased glucagon secretion and therefore have an even greater risk of rapid hypoglycemia. Patients with pancreatogenic diabetes (eg, secondary to chronic pancreatitis) also typically have inadequate alpha cell reserve and can experience frequent hypoglycemia. (Choice A) Progressive hypoglycemia prompts a catecholamine (eg, epinephrine) surge, which increases hepatic glucose production and triggers many of the characteristic hypoglycemic symptoms (eg, arousal, tremor). Patients with long-standing diabetes often have a blunted autonomic response to hypoglycemia, with reduced hypoglycemic awareness, but catecholamines are less important than glucagon in raising blood glucose levels. (Choice C) Prolonged hypoglycemia can stimulate secretion of cortisol and growth hormone, which increase glucose levels. These hormones typically act over longer timescales (eg, days/weeks) and are less important than glucagon in preventing acute hypoglycemia. (Choice D) Chronic exposure to high circulating insulin levels leads to downregulation of insulin receptors and reduced insulin sensitivity. This effect promotes hyperglycemia, not hypoglycemia. (Choice E) Repeated hypoglycemia causes downregulation of beta-adrenergic receptors, which contributes to reduced hypoglycemic awareness. Depending on the systems involved, upregulation of beta-adrenergic receptors would generally reduce hypoglycemia and increase awareness. Educational objective: Patients with type 1 diabetes mellitus are at increased risk of hypoglycemia because exogenous insulin will continue to be absorbed from the injection site despite falling glucose levels. Those with long-standing diabetes may also have decreased glucagon secretion and therefore have an even greater risk of rapid hypoglycemia. __________ References: Mechanisms of hypoglycemia-associated autonomic failure in diabetes. (http://www.ncbi.nlm.nih.gov/pubmed/23883381)

A 34-Year-Old Man Comes to the Office for a Follow-Up