Case 1: Congestive heart failure
A 71-year-old woman with type 2 diabetes is hospitalized with new congestive heart failure. She had an inferior-wall myocardial infarction treated with percutaneous coronary intervention three years ago. A recent echocardiogram showed a left ventricular ejection fraction of 35%. A stress myocardial perfusion scan demonstrates a large, fixed inferior defect and a small, reversible anterolateral defect. Her cardiovascular disease is treated medically with furosemide, lisinopril, a statin, aspirin and metoprolol. Her diabetes regimen is glyburide, 10 mg twice daily, and metformin/rosiglitazone, 1,000 mg/4 mg twice daily. Capillary blood glucose values have recently been in the 140 to 180 mg/dL range, with an occasional result in excess of 200 mg/dL. Her hemoglobin A1c level has recently climbed to 7.6%. Combination therapy with metformin/rosiglitazone is stopped in the hospital.
Which of the following would be the most appropriate discharge antihyperglycemic regimen for this patient?
A. Continue glyburide alone
B. Continue glyburide and add acarbose
C. Stop glyburide and begin insulin therapy
D. Continue glyburide and begin metformin; add insulin
E. Continue glyburide and begin rosiglitazone; add insulin
Case 2: Progressive claudication
A 68-year-old woman is scheduled for arteriography of the lower extremities for progressive claudication. She has type 2 diabetes that is well controlled (hemoglobin A1c level, 6.4%) with rosiglitazone, metformin and glipizide. On the day of the procedure she is to receive nothing by mouth all morning except for medications until after the procedure.
Which of the following would be the most appropriate oral regimen on the day of the procedure?
A. Continue all medications
B. Hold metformin, continue glipizide and rosiglitazone
C. Hold glipizide and metformin, continue rosiglitazone
D. Hold glipizide and rosiglitazone and decrease metformin dose by half
E. Hold metformin and rosiglitazone, continue glipizide
Case 3: Obtundation
A 78-year-old woman with a 10-year history of type 2 diabetes mellitus is hospitalized with obtundation. She developed a fever and dyspnea three days before admission. Her antihyperglycemic regimen consists of glipizide and pioglitazone; her hemoglobin A1c level is usually in the 7.5% to 8.5% range. Her blood glucose levels are in the 200 to 350 mg/dL range.
On physical examination, blood pressure is 80/50 mm Hg and pulse rate is 122 beats/min. Serum sodium level is 143 mEq/L, and plasma glucose level is 1,245 mg/dL; the serum bicarbonate is normal and urinary ketones are absent.
Which of the following is the most appropriate therapy for this patient?
A. IV normal saline (0.9% NaCl), followed by insulin infusion
B. IV insulin infusion, followed by normal saline
C. IV half-normal saline, followed by IV insulin infusion
D. IV half-normal saline (0.45% NaCl) and insulin infusion simultaneously
E. IV insulin infusion
Case 4: Postprocedure fever
A 57-year-old man develops fever two days after prosthetic mitral valve replacement. He remains intubated and requires pressors. Medications include epinephrine, dexamethasone and famotidine. Other than a history of mitral valve stenosis, the patient had been previously healthy.
On examination, he has a rectal temperature of 38.5 °C (101.3 °F) and crackles in the left lung; leukocyte count is 12,600 cells/µL, and plasma glucose level is 178 mg/dL; chest radiograph shows an infiltrate in the left lower lobe. Antibiotic therapy is started for suspected pneumonia.
Which of the following is the most appropriate management for this patient's hyperglycemia?
A. IV insulin infusion
B. Regular insulin by sliding scale
C. Insulin glargine, 10 units in the evening
D. Glyburide, 5 mg/d
Answers and commentary
Correct answer: C. Stop glyburide and begin insulin therapy
The management of the patient with both diabetes and heart failure is particularly challenging. The insulin-sensitizing drugs metformin and the thiazolidinediones are contraindicated in patients with advanced heart failure. Metformin should not be used in patients whose heart failure is advanced to a degree that requires drug therapy. This caution emerges from the observation that a significant proportion of the lactic acidosis cases reported in postmarketing surveys involved patients with underlying heart failure. The mechanism likely pertains to hemodynamic impairment and resultant decreased tissue perfusion and increased lactate production. Potentially, decreased renal blood flow in such patients may also decrease metformin elimination, heightening the risk of lactic acidosis.
The thiazolidinediones are not indicated in patients with New York Heart Association class II–IV heart failure. This caution results from this class of drug's known side effect of increasing fluid retention. Case reports of worsening heart failure or new heart failure have emerged, although a recent observational study suggested that mortality was actually reduced in heart failure patients treated with thiazolidinediones (with a similar observation in patients treated with metformin). However, until further data become available—preferably in the form of a randomized clinical trial—it is prudent to continue to avoid these medications in such patients.
This patient's glucose levels are elevated on her current therapy, and they will certainly worsen upon discontinuation of metformin and rosiglitazone. Continuing glyburide alone is therefore inappropriate. Acarbose is a relatively weak antihyperglycemic agent and will probably not adequately reduce glucose levels. Changing the patient to insulin is the intervention most likely to improve her glycemic control and decrease the risk of future complications.
- The insulin-sensitizing drugs metformin and the thiazolidinediones are contraindicated in advanced heart failure.
Correct answer: C. Hold glipizide and metformin, continue rosiglitazone
Metformin accumulates in renal insufficiency, which may lead to lactic acidosis. Therefore, because of the potential nephrotoxicity of radiocontrast agents, the current prescribing guidelines for metformin include strict precautions when radiographic procedures employing an IV contrast agent are performed. These procedures include pyelograms, angiograms, venograms and CT studies. The recommendation is that metformin be stopped on the day of the study and resumed once renal function normalizes 24 to 48 hours after the procedure. Because the patient is allowed nothing by mouth on the morning of the procedure, holding the glipizide is also appropriate; she is unlikely to become significantly hyperglycemic during fasting. Rosiglitazone, a thiazolidinedione, can be continued as it will not predispose the patient to hypoglycemia during fasting. Note that rosiglitazone could also be held without any untoward effect because of its long duration of action.
- Due to the potential nephrotoxicity of IV radiocontrast agents, metformin, which accumulates in renal insufficiency, should not be administered when any radiographic procedure using IV contrast agent is performed.
Correct answer: A. IV normal saline (0.9% NaCl), followed by insulin infusion
This patient presents a classic example of hyperglycemic hyperosmolar syndrome (HHS), previously referred to as hyperglycemic hyperosmolar nonketotic syndrome (HHNKS). This state develops over several days, typically due to marked hyperglycemia in the setting of a medical stress, such as infection. Free water and sodium losses can be dramatic, and patients are usually markedly volume contracted. The physical examination, especially the hypotension and tachycardia, suggests marked volume deficits in the extracellular fluid space (that is, sodium losses).
The serum sodium concentration is an excellent marker of free water deficits. Although normal on admission, the sodium concentration belies actual free water deficit, because it requires correction for the degree of hyperglycemia. Conventionally, 1.6 mEq/L of sodium should be added to the measured serum sodium for every 100 mg/dL of glucose exceeding 100 mg/dL. Therefore, in this case, the “corrected” serum sodium is actually 163 mEq/L. Such hypernatremia is indicative of significant, superimposed free water losses. Proper correction of this patient's deficits will involve repletion with both crystalloid and free water.
The restoration of vascular volume remains paramount, however. Therefore, normal saline (0.9% NaCl) should be the initial fluid of choice. IV insulin should be given to normalize this patient's blood glucose level, but only after initial expansion of the plasma volume with normal saline. If insulin is given alone or before saline, glucose levels will fall, and, as a result, water will move from the extracellular to the intracellular space. This will decrease plasma volume further and worsen hypotension. After one to two liters of normal saline, and once the vital signs improve and urine output is documented, the IV fluids should be switched to half-normal saline (0.45% NaCl). This will provide ongoing repletion of both sodium and water deficits. However, beginning with half-normal saline will not sufficiently expand the extracellular space to preserve perfusion of vital organs; this should therefore not be used as the initial IV fluid.
- In hyperglycemic hyperosmolar syndrome, restoration of vascular volume is critical; normal saline is the initial fluid of choice, even before IV insulin.
Correct answer: A. IV insulin infusion
Hyperglycemia after cardiac surgery and during critical illness is a strong predictor of adverse outcomes, including infectious complications and death. Randomized clinical trials have shown that aggressively treating hyperglycemia in this setting with IV insulin infusion reduces mortality. In a large randomized, controlled study from a European surgical intensive care unit (ICU), normalizing blood glucose (80 to 110 mg/dL) reduced ICU mortality by 42%, mainly in patients who were in intensive care for more than five days and in patients who developed infection. Aggressive control of hyperglycemia is now recommended by several professional organizations, with most recommending a blood glucose target of 110 mg/dL or less. Regular insulin by intermittent sliding scale will not allow for sufficient glycemic control in the ICU setting and has been associated with more hyperglycemic and hypoglycemic events in hospitalized patients. Insulin glargine also can only be adjusted once every 24 hours and will similarly not allow for sufficient glycemic control. Oral agents, such as glyburide, are inappropriate in this setting.
- Hyperglycemia after cardiac surgery and during critical illness is a strong predictor of adverse outcomes, including infectious complications and death.
- IV insulin infusion in hyperglycemic patients in the ICU improves outcomes.