The following cases and commentary, which focus on diabetes, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 18).
Case 1: Fasting with type 1
A 55-year-old man with type 1 diabetes mellitus was admitted to the hospital for management of a non-ST-elevation myocardial infarction. He is clinically stable and eating well. He will begin fasting at midnight in preparation for a cardiac catheterization tomorrow. His current fasting blood glucose values range from 70 to 80 mg/dL (3.9-4.4 mmol/L), and his premeal blood glucose values range from 140 to 160 mg/dL (7.8-8.9 mmol/L) on his home doses of basal insulin glargine and prandial insulin aspart. His last HbA1c value was 7.2%.
In addition to holding prandial insulin, which of the following is the most appropriate management for this patient's diabetes?
A. Continue basal insulin dose
B. Continue basal insulin dose and add correction insulin regimen
C. Decrease basal insulin dose and add correction insulin regimen
D. Hold basal insulin and add sliding-scale insulin regimen
Case 2: Nausea after med change
A 66-year-old man recently diagnosed with type 2 diabetes mellitus is evaluated in the emergency department for nausea, vomiting, and fatigue. He was diagnosed with type 2 diabetes 18 months ago. In the past month metformin was discontinued due to severe diarrhea, and glipizide and empagliflozin were initiated. In addition to type 2 diabetes, medical history is significant for coronary artery disease, hypertension, and dyslipidemia. Medications are aspirin, lisinopril, metoprolol, atorvastatin, glipizide, and empagliflozin.
On physical examination, temperature is normal, blood pressure is 90/60 mm Hg, pulse rate is 120/min, and respiration rate is 22/min. Dry mucous membranes are noted. There is diffuse abdominal tenderness to palpation without guarding. Other than tachycardia, the remainder of the examination is normal. Laboratory studies show sodium 133 mEq/L (133 mmol/L), bicarbonate 10 mEq/L (10 mmol/L), glucose 150 mg/dL (8.3 mmol/L), anion gap 17 mEq/L (17 mmol/L), and elevated β-hydroxybutyrate.
Which of the following is most likely responsible for the patient's findings?
B. Discontinuation of metformin
Case 3: Infected wound
A 58-year-old man is evaluated in the hospital for fever, hypotension, and altered mental status. He was hospitalized 2 days ago for an infected arm wound and was treated with intravenous piperacillin/tazobactam and vancomycin.
This morning he developed new pain in the middle of his back and difficulty urinating. His medical history is significant for type 2 diabetes mellitus treated with metformin.
On physical examination, temperature is 39.1 °C (102.4 °F), blood pressure is 83/48 mm Hg, pulse rate is 109/min, and respiration rate is 21/min. Oxygen saturation is 98% breathing 2 L/min of oxygen through nasal cannula.
He is somnolent but arousable and oriented when awake. There is erythema surrounding the wound on his right upper arm with no drainage or tenderness. There is tenderness to percussion in the middle of his back and a palpable bladder.
Laboratory studies reveal a blood serum leukocyte count of 22,000/µL (22 × 109/L), and plasma glucose of 160 mg/dL (8.88 mmol/L).
Chest radiograph is unremarkable.
Which of the following is the most appropriate next step in management?
A. Intravenous fluid bolus
B. Intravenous insulin
C. MRI of the spine
D. Surgical exploration of the arm wound
Case 4: Diabetic foot ulcer
A 67-year-old woman is hospitalized for an ulcer on the bottom of her right foot; it has expanded over the past 2 months. The patient has type 2 diabetes mellitus, hypertension, stage 3 chronic kidney disease, and peripheral neuropathy. Medications are insulin glargine, insulin lispro, lisinopril, and gabapentin.
On physical examination, temperature is 37.3 °C (99.1 °F); the remaining vital signs are normal. A deep 3- × 4-cm ulcer is located on the distal medial compartment of the plantar surface of the right foot. The base of the ulcer is necrotic and malodorous; a probe-to-bone test is negative. No surrounding erythema or increased warmth is noted. Both feet are warm with palpable pulses.
Erythrocyte sedimentation rate and C-reactive protein level are elevated. Results of a complete blood count are normal.
A plain radiograph reveals soft tissue swelling and ulceration; an MRI reveals findings consistent with osteomyelitis of the distal head of the first metatarsal.
Which of the following is the most appropriate management?
A. Bone biopsy and culture
B. Forefoot amputation
C. Swabbing and culture of wound base
D. Vancomycin and piperacillin-tazobactam
Case 5: Diabetic ketoacidosis
A 22-year-old man was admitted to the intensive care unit 24 hours ago with nausea, vomiting, and lethargy of 2 days' duration. Medical history is unremarkable, and he takes no medications. His admission laboratory values were consistent with diabetic ketoacidosis, and he was initiated on intravenous fluids and intravenous insulin therapy. After 24 hours, he is currently receiving 0.45% normal saline at 250 mL/h with 20 mEq (20 mmol) of potassium chloride per liter and an insulin drip at 5 U/h. His nausea continues, but his vomiting has ceased. He is unable to eat.
On physical examination, vital signs are normal. He is alert and oriented, and the remainder of his physical examination is unremarkable.
Laboratory studies show sodium 141 mEq/L (141 mmol/L), potassium 4.0 mEq/L (4.0 mmol/L), chloride 104 mEq/L (104 mmol/L), bicarbonate 20 mEq/L (20 mmol/L), glucose 180 mg/dL (10 mmol/L), and pH 7.32.
Which of the following is the most appropriate management?
A. Continue current insulin drip rate
B. Decrease insulin drip rate and add intravenous dextrose
C. Discontinue intravenous potassium
D. Transition insulin drip to subcutaneous insulin regimen
Case 6: Hyperglycemia in CAP
A 66-year-old woman was admitted to the hospital 24 hours ago with community-acquired pneumonia (CAP). Since admission, she has been confused and her oral intake has been poor. Appropriate antibiotics, intravenous fluids, and oxygen have been initiated. She has no other known medical problems.
On physical examination, temperature is 39 °C (102.2 °F), blood pressure is 142/88 mm Hg, pulse rate is 98/min, and respiration rate is 20/min. Oxygen saturation is 98% on oxygen, 2 L/min by nasal cannula. Crackles are evident in the right posterior thorax.
Laboratory studies show glucose values of 185 to 215 mg/dL (10.3-11.9 mmol/L) and a hemoglobin A1c level is 5.5%.
A chest radiograph demonstrates a right lower lobe infiltrate.
Which of the following is the most appropriate management of this patient's hyperglycemia?
A. Empagliflozin and sliding-scale insulin
B. Metformin and sliding-scale insulin
C. Scheduled basal insulin and correction insulin
D. Sliding-scale insulin only
Answers and commentary
Correct answer: C. Decrease basal insulin dose and add correction insulin regimen.
The most appropriate management of this patient's type 1 diabetes mellitus is to decrease basal insulin dose by 10% to 20% and add correction insulin regimen. This patient's fasting blood glucose values were already low on his home basal insulin doses, thus it is most appropriate to continue his basal insulin but at a reduced dose to avoid diabetic ketoacidosis (DKA) and hypoglycemia. Correction insulin with basal insulin will treat hyperglycemia while he is fasting. Patients with type 1 diabetes must have continuous insulin therapy, particularly basal insulin, to avoid the development of DKA. Because of the requirement of continuous insulin, prolonged fasting in a patient with type 1 diabetes can be complicated by hypoglycemia. Proactive adjustments to insulin doses are required to avoid extreme fluctuations in glycemic control while in the fasting state.
This patient's fasting blood glucose value of 70 mg/dL (3.9 mmol/L) on the current basal insulin dose meets the American Diabetes Association's threshold value for downward titration of insulin doses to avoid hypoglycemia. The basal insulin dose should be decreased in addition to holding the prandial insulin in the fasting state. A correction insulin regimen should also be added to the basal insulin to help manage hyperglycemia that may occur while fasting.
Efficient glucose utilization is impaired when continuous insulin therapy, such as basal insulin, is held in type 1 diabetes. This may cause the development of DKA as a result of increased glycogenolysis and gluconeogenesis for fuel production. A sliding-scale insulin regimen alone is not physiologic and may cause large fluctuations in the blood glucose levels owing to the inherent reactive nature of its dosing, coupled with the near universal lag time between measurement of glucose and injection of insulin that occurs in most hospitals.
- In fasting hospitalized patients with type 1 diabetes mellitus, the basal insulin dose should be decreased, the prandial insulin held to avoid hypoglycemia, and a correction insulin regimen should be added to help manage hyperglycemia.
Correct answer: C. Empagliflozin.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors (canagliflozin, dapagliflozin, and empagliflozin) improve glycemia by increasing excretion of glucose by the kidney. SGLT2 is expressed in the proximal tubule and mediates reabsorption of approximately 90% of the filtered glucose load. SGLT2 inhibitors promote excretion of glucose by the kidneys and thereby modestly lower elevated blood glucose levels in patients with type 2 diabetes. Euglycemic diabetic ketoacidosis (DKA) has been reported in patients with type 2 diabetes taking SGLT2 inhibitors. Because of this, the FDA issued a Drug Safety Communication that warns of an increased risk of DKA with uncharacteristically mild to moderate glucose elevations (euglycemic DKA) associated with the use of all the approved SGLT2 inhibitors. SGLT2 inhibitors should be discontinued in patients who develop acidosis on these agents.
Statins may cause myopathy and liver aminotransferase elevations and are associated with an increased risk of diabetes and, possibly, cognitive dysfunction. The incidence of these adverse effects ranges from 1% to 10%, but permanent disability related to statin intolerance is rare. Statin therapy is not associated with ketoacidosis.
According to labeling guidelines, initiation of metformin therapy is not recommended if the estimated glomerular filtration rate (eGFR) is between 30 and 45 mL/min/1.73 m2 and is contraindicated if the eGFR is less than 30 mL/min/1.73 m2 due to the risk of lactic acidosis. Metformin should be used cautiously in patients with heart failure or hepatic impairment. The discontinuation of metformin is not associated with the development of lactic acidosis or ketoacidosis.
Glipizide is a sulfonylurea. Sulfonylurea agents work by stimulating insulin secretion. Sulfonylurea agents are associated with weight gain, and they can cause hypoglycemia. They are not, however, associated with the development of ketoacidosis in patients with type 2 diabetes.
A common adverse effect of ACE inhibitors is a dry, nonproductive cough. Other common adverse effects include hyperkalemia and, occasionally, worsening kidney function. ACE inhibitors can cause life-threatening angioedema but not ketoacidosis.
- An increased risk of diabetic ketoacidosis with mild to moderate glucose elevations has been associated with the use of all the approved sodium-glucose transporter-2 (SGLT2) inhibitors (canagliflozin, dapagliflozin, and empagliflozin).
Correct answer: A. Intravenous fluid bolus.
The most appropriate management is an intravenous fluid bolus of 30 mL/kg of body weight. Successful treatment of severe sepsis and septic shock depends on the rapid institution of hemodynamic support, empiric treatment of infection, and infection control. Crystalloid infusion (normal [0.9%] saline or lactated Ringer solution) to support circulating intravascular volume should be administered to all patients with severe sepsis and septic shock. The 2016 update to the Surviving Sepsis Guidelines recommends using an initial bolus of 30 mL/kg of body weight.
The 2018 American Diabetes Association Standards for Care recommend that insulin therapy be initiated for treatment of persistent hyperglycemia starting at a threshold of 180 mg/dL (10.0 mmol/L). Once insulin therapy is started, a target glucose range of 140 to 180 mg/dL (7.8–10.0 mmol/L) is recommended for most critically ill and noncritically ill patients. This patient's plasma glucose is not so high that it is an emergency; therefore, administration of insulin is a lower priority than treatment of shock.
This patient may have also have developed a paraspinous abscess (fever, new-onset back pain, difficulty urinating). This patient may need spine imaging but the more urgent priority is his hemodynamic instability, which requires fluid resuscitation before he can undergo any diagnostic imaging study.
Before this patient can be evaluated for surgical source control, he needs to be resuscitated. He is not showing signs of necrotizing fasciitis, which would be a surgical emergency, but even if he were suspected of this diagnosis, he would need aggressive fluid resuscitation while arrangements were made for urgent surgical debridement.
- Patients with hypoperfusion due to sepsis should be managed with aggressive crystalloid fluid resuscitation using an initial bolus of 30 mL/kg of body weight.
Correct answer: A. Bone biopsy and culture.
A bone biopsy and culture is the next step in the management of osteomyelitis for this patient. Biopsies can be accomplished by open surgical procedure or percutaneously. Confirming a microbiologic diagnosis is needed before antibiotics can be administered.
Indications for amputation include persistent sepsis, inability to tolerate antibiotic therapy, progressive bone destruction despite therapy, and bone destruction that compromises the mechanical integrity of the foot. None of these indications are present in this patient. Surgical debridement of the ulcer may be needed to remove the necrotic tissue, but this can be done at the time of bone biopsy.
With the exception of Staphylococcus aureus, microorganisms isolated from culture samples obtained from superficial wounds or sinus tracts correlate poorly with deep cultures from bone; therefore, this practice is of limited value. Bone biopsy with histopathologic assessment and full microbiologic studies is important for diagnosing osteomyelitis, excluding other entities (such as neoplasm), and isolating the causative pathogen(s).
Because the patient has no signs of skin or soft tissue infection or of sepsis, antibiotics are not immediately needed; furthermore, the provision of empiric antibiotics would also decrease the yield of a subsequent bone biopsy. Vancomycin and piperacillin-tazobactam might be indicated in the future, pending the results of the bone biopsy. However, a histologic and microbiologic diagnosis confirmation is needed before antibiotics can be administered.
- Osteomyelitis in a patient with a diabetic foot infection and no evidence of skin or soft tissue infection or sepsis requires a bone biopsy before antibiotics are administered.
Correct answer: B. Decrease insulin drip rate and add intravenous dextrose.
The most appropriate management for this patient is to decrease the insulin drip rate and add intravenous (IV) dextrose. This patient continues to have anion gap acidosis and should remain on IV insulin therapy to suppress ketogenesis until this resolves. His current blood glucose level below 200 to 250 mg/dL (11.1-13.9 mmol/L) increases his risk for hypoglycemia with continued IV insulin therapy. This risk can be mitigated by transitioning his IV fluids to 5% dextrose with 0.45% normal saline at 150 to 250 mL/h to maintain his glucose between 150 and 200 mg/dL (8.3-11.1 mmol/L) until his diabetic ketoacidosis resolves. Reducing the insulin drip rate to maintain his blood glucose between 150 and 200 mg/dL (8.3-11.1 mmol/L) will also decrease the risk of hypoglycemia while still suppressing ketogenesis.
If he continues at the current insulin drip rate or if he does not have the addition of IV dextrose, he has an increased risk of developing hypoglycemia now that his blood glucose is less than 200 mg/dL (11.1 mmol/L).
Insulin deficiency and urinary potassium losses induce shifts in potassium from the intracellular to extracellular compartments. This can result in low or normal serum potassium levels in the setting of depleted potassium stores. Potassium shifts back from the extracellular to intracellular compartments with resultant hypokalemia as insulin administration corrects the hyperglycemia, anion gap acidosis, and hyperosmolality associated with diabetic ketoacidosis. To avoid cardiac complications, serum potassium must be greater than 3.3 mEq/L (3.3. mmol/L) before initiating IV insulin. Once potassium is 3.3 mEq/L (3.3 mmol/L) or higher and IV insulin has been initiated, 20 to 30 mEq (20-30 mmol/L) of potassium chloride will usually need to be added to each liter of IV fluid to maintain a serum potassium level of 4.0 to 5.0 mEq/L (4.0-5.0 mmol/L). He is at risk of developing hypokalemia if his potassium supplementation is discontinued at this time.
Although subcutaneous insulin would provide insulin to suppress ketogenesis, the IV insulin drip provides greater flexibility in dose adjustments than subcutaneous insulin. Once the patient's anion gap acidosis has resolved, transitioning from the insulin drip to a subcutaneous insulin regimen should occur.
- In patients with diabetic ketoacidosis, intravenous insulin therapy should be continued until complete resolution of the anion gap acidosis; as acidosis improves, it may be necessary to reduce the insulin infusion rate and add intravenous dextrose to prevent hypoglycemia.
Correct answer: C. Scheduled basal insulin and correction insulin.
The most appropriate management of this patient's hyperglycemia is to initiate scheduled basal insulin and correction insulin. Inpatient hyperglycemia, defined as consistently elevated plasma glucose values above 140 mg/dL (7.8 mmol/L), is associated with poor outcomes. Attempts to decrease morbidity and mortality with tight glycemic control (80-110 mg/dL [4.4 6.1 mmol/L]) have not consistently demonstrated improvements in adverse outcomes and, in some settings, have shown increased rates of severe hypoglycemic events and mortality. As a result, revised inpatient glycemic targets are less stringent than outpatient glucose targets to avoid both hypoglycemia and severe hyperglycemia that can lead to volume depletion and electrolyte abnormalities. Dietary modifications should be made once glucose levels exceed 140 mg/dL (7.8 mmol/L). At persistent glucose levels of 180 mg/dL (10.0 mmol/L) and higher, the American Diabetes Association recommends initiation of scheduled insulin with a blood glucose target of 140 to 180 mg/dL (7.8-10.0 mmol/L) for most critically ill and noncritically ill patients to decrease the risk of adverse outcomes. Scheduled basal insulin or basal insulin plus correction insulin is appropriate for patients who are fasting or who have poor oral intake, such as this patient, with frequent bedside point-of-care monitoring every 4 to 6 hours for insulin adjustments. Scheduled basal and prandial insulin plus correction insulin are appropriate for patients who are eating.
The safety of oral antihyperglycemic agents, including empagliflozin, in the hospital setting has not been fully studied or established. In addition, sodium-glucose transporter-2 (SGLT2) inhibitors have been associated with diabetic ketoacidosis and should be avoided in situations that may produce ketone bodies, such as severe illness or prolonged fasting. Scheduled insulin therapy is the recommended treatment regimen for hyperglycemia in the hospital setting.
The safety of oral antihyperglycemic agents, including metformin, in the hospital setting has not been fully studied or established. Scheduled insulin therapy is the recommended treatment regimen for hyperglycemia in the hospital setting.
The sole use of correction insulin for the management of hyperglycemia is not recommended. It is a reactive approach to hyperglycemia that can lead to large fluctuations in glucose levels coupled with the near universal lag time between measurement of glucose and injection of insulin that occurs in most hospitals.
- To manage inpatient hyperglycemia, scheduled basal insulin or basal insulin plus correction insulin is appropriate for patients who are fasting or who have poor oral intake.