Question 1#

A 75-year-old male with a history of hypertension, chronic renal insufficiency, and type 2 diabetes mellitus is admitted to the intensive care unit (ICU) with shock secondary to bowel perforation. His blood glucose is 304 mg/dL on presentation and 275 mg/dL on recheck an hour later.

hich of the following is the MOST appropriate for management of hyperglycemia?

A. Start insulin glargine 0.2 mg/kg/d and correction insulin with a sliding scale of regular insulin every 6 hours with a goal glucose target between 80 and 110 mg/dL

Correct Answer: D

A single center trial published in 2001 involving approximately 1,500 surgical ICU patients showed significantly decreased ICU mortality in patients who were managed with intensive glucose control (target blood glucose of 80-110 mg/dL) when compared to patients with conventional glucose control (target blood glucose of 180-200 mg/dL). Most of the patients in this trial had undergone cardiac surgery and the mortality benefit was in patients who were in the ICU for 5 days or longer. This mortality benefit was not seen in 1,100 critically ill medical patients from the same center. 

The subsequent Normoglycemia in Intensive Care Evaluation — Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial was a larger (approximately 6,000 patients), multicenter trial that showed that intensive glucose control (target blood glucose 81-108 mg/dL) was associated with higher mortality and increased risk of hypoglycemia when compared to conventional glucose control (target blood glucose <180 mg/dL). Furthermore, a post hoc analysis of the NICE-SUGAR database showed that hypoglycemia was associated with increased mortality. Based on these findings, the Surviving Sepsis guideline recommend a protocolized approach to glucose control targeting a blood glucose <180 mg/dL. Other experts recommend a target glucose between 140 and 180 mg/dL from the NICE-SUGAR trial (patients in the conventional glucose management group had a mean time-weighted glucose level of 144 ± 23 mg/dL). Although a basal/bolus insulin regimen is recommended for management of hyperglycemia in non-ICU patients, absorption of subcutaneously delivered medications can be variable because of shock or edema. Continuous intravenous insulin infusions are recommended for glucose management in ICU patients. The half-life of iv insulin is short (<15 minutes) and can be titrated to bring a patient’s blood glucose levels to targeted range more rapidly than subcutaneous insulin. Insulin infusions can also be adjusted quickly based on changes in the patient’s clinical status.

References:

1. Finfer S, Chittock DR, Blair D, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283- 1297.
2. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for the management of sepsis and septic shock: 2016. Crit Care Med. 2017;45:486-552.
3. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359-1367.
4. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449-461. 

Question 2#

Which of the following statements is FALSE regarding intensive glucose control (target blood glucose between 81 and 108 mg/dL) compared to conventional glucose control (target blood glucose <180 mg/dL) in critically ill patients.

A. Patients receiving intensive glucose control are 15 times more likely to develop hypoglycemia when compared to patients receiving conventional glucose control

Correct Answer: D

The NICE-SUGAR study was an international, multicenter trial involving 6,104 patients designed to test the hypothesis that intensive glucose control reduces mortality at 90 days. It found that intensive glucose control (target blood glucose between 81-108 mg/dL) was associated with a 2.6% increase in mortality at 90 days when compared to conventional glucose control (target blood glucose of <180 mg/dL). There were more hypoglycemic events in the intensive glucose control group. There was no difference between the two groups in overall length of stay, ICU length of stay, time on mechanical ventilation, time on renal replacement therapy, incidence of new organ failure, positive blood cultures, or red blood cell transfusions.

Although a previous trial showed intensive glucose control improved survival among surgical ICU patients, there was no difference in 90-day mortality in surgical and nonsurgical patients in the NICE-SUGAR trial.

References:

1. Finfer S, Chittock DR, Blair D, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283- 1297.
2. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359-1367.

Question 3#

Which of the following statements regarding agents used to treat Type 2 diabetes mellitus is FALSE?

A. Metformin is contraindicated in patients with an eGFR of less than 60 mL/min/1.73 m²

Correct Answer: A

Metformin is the first drug recommended when starting treatment for type 2 diabetes. It reduces hemoglobin A1c by 1% to 1.5% and is associated with decreases in both the microvascular and macrovascular complications of diabetes. Recommendations against the use of metformin in patients with mild to moderate chronic kidney disease were removed by the FDA, as recent studies did not show an increased risk of lactic acidosis in these patients. However, metformin is contraindicated in patients with an eGFR <30 mL/min/1.73 m².

Sulfonylureas also decrease hemoglobin A1c by 1% to 1.5% and have been shown to reduce long-term macrovascular and microvascular events. Adverse effects include weight gain and hypoglycemia.

GLP-1 receptor agonists also lower hemoglobin A1c by 1% to 1.5% and are associated with weight loss. They are associated with a reduced risk of cardiovascular mortality. Adverse effects include nausea, vomiting, diarrhea, acute renal failure due to volume depletion from vomiting and diarrhea, and acute pancreatitis. 

DPP-4 inhibitors produce a small reduction in hemoglobin A1c (0.5%-1%). It has been associated with acute pancreatitis as well as hypersensitivity reactions.

SGLT2 inhibitors also produce a small reduction in hemoglobin A1c (0.5%-1%) and are also associated with a small decrease in systolic blood pressure and weight loss. Because SGLT2 inhibitors also increase sodium excretion, acute renal injury due to hypovolemia can occur.

References:

1. Drugs for type 2 diabetes. Med Lett Drugs Ther. 2017;59(1512):9-18.
2. Qaseem A, Barry MJ, Humphrey LL, et al. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(4):279- 290.

Question 4#

All of the following contribute to the development of diabetic ketoacidosis (DKA) EXCEPT: 

A. Insulin deficiency

Correct Answer: C

DKA results from insulin deficiency and increased levels of glucagon. In addition, there is increased secretion of catecholamines, cortisol, and growth hormone, which counteract the action of any residual insulin. Absolute insulin deficiency results in increased lipolysis resulting in increased free fatty acids that are oxidized to ketone bodies in the liver. Increased levels of catecholamines, cortisol, and growth hormone result in increased gluconeogenesis and glycogenolysis, and hyperglycemia. 

References:

1. Hirsch IB, Emmett M. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: epidemiology and pathogenesis. In: Nathan DM, Wolfsdorf JI, eds. UpToDate. Waltham, MA: UpToDate, Inc. http://www.uptodate.com. Accessed August 28, 2018.
2. Umpierrez G, Korykowski M. Diabetic emergencies – ketoacidosis, hyperglycemic hyperosmolar state, and hypoglycemia. Nat Rev Endocrinol. 2016;12:222-232. 

Question 5#

A 27-year-old man with a history of obesity and substance abuse is found obtunded. His laboratory findings are:

Chemistry:

• Sodium 135 mmol/L
• Potassium 3.0 mmol/L
• Chloride 105 mmol/L
• CO₂ 10 mmol/L
• Blood Urea Nitrogen 42 mg/dL
• Creatinine 2.1 mg/dL
• Glucose 570 mg/dL

Arterial Blood Gas:

• pH 7.21
• PaCO₂ 24
• PaO₂ 95
• Serum ketones positive

Initial treatment for him should include all of the following EXCEPT:

A. Normal saline at 500 to 1,000 mL/h during the first 1 to 2 hours

Correct Answer: B

Diagnostic criteria for DKA consist of the triad of hyperglycemia (serum glucose >250 mg/dL), acidemia (pH <7.3), and ketonemia. The osmotic diuresis associated with glycosuria results in total body water, sodium, potassium, and phosphate deficits. Initial treatment consists of administration of normal saline to restore intravascular volume and renal perfusion. If the serum potassium is less that 3.3 mmol/L, potassium should be repleted before starting insulin as correction of volume depletion and acidosis, and insulin can all worsen hypokalemia. Once the serum sodium is greater than 3.3 mmol/L, insulin should be started. The recommended dose for regular intravenous insulin is a bolus of 0.1 U/kg followed by a continuous infusion at 0.1 U/kg/h. In patients with mild to moderate DKA, subcutaneous rapid-acting insulin analogues can also be considered. 

A search for a precipitating event should be initiated. The most common associated events are infection and inadequate insulin therapy. Other precipitating factors include medications that affect carbohydrate metabolism (glucocorticoids, thiazide diuretics, sympathomimetic agents), SGLT2 inhibitors, cocaine use, and malfunction of continuous subcutaneous infusion devices.

References:

1. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patient with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(12):2739-2748.
2. Umpierrez G, Korykowski M. Diabetic emergencies – ketoacidosis, hyperglycemic hyperosmolar state, and hypoglycemia. Nat Rev Endocrinol. 2016;12:222-232.