The following cases and commentary, which involve inpatient insulin management, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).
Case 1: Preoperative evaluation
A 78-year-old man is evaluated in the hospital for poor glycemic control before undergoing femoral-popliteal bypass surgery. He has been on the vascular surgery ward for 3 weeks with a nonhealing foot ulcer. The patient has an extensive history of arteriosclerotic cardiovascular disease, including peripheral vascular disease, and a 20-year-history of type 2 diabetes mellitus. His most recent hemoglobin A1c value, obtained 2 months before admission, was 8.9%. His diabetes regimen consists of glipizide, 40 mg/d. While in the hospital, his plasma glucose levels have generally been in the 200 to 250 mg/dL (11.1 to 13.9 mmol/L) range. He is eating well.
In addition to stopping glipizide, which of the following is the most appropriate treatment for this patient?
A. Basal insulin and rapid-acting insulin before meals
B. Insulin infusion
C. Neutral protamine Hagedorn (NPH) insulin twice daily
D. Sliding scale regular insulin
Case 2: Pneumonia in woman with type 1 diabetes
A 23-year-old woman with type 1 diabetes mellitus is admitted to the hospital with a diagnosis of community-acquired pneumonia and lethargy. Before admission, her insulin pump therapy was discontinued because of confused mentation.
On physical examination, temperature is 37.5°C (99.5°F), blood pressure is 108/70 mm Hg, pulse rate is 100/min, and respiration rate is 24/min. There are decreased breath sounds in the posterior right lower lung. Neurologic examination reveals altered consciousness.
Laboratory studies show blood urea nitrogen, 38 mg/dL (13.6 mmol/L); creatinine, 1.4 mg/dL (123.8 µmol/L); sodium, 130 meq/L (130 mmol/L); potassium, 5.0 meq/L (5.0 mmol/L); chloride, 100 meq/L (100 mmol/L); bicarbonate, 16 meq/L (16 mmol/L); glucose, 262 mg/dL (14.5 mmol/L); and urine ketones, positive.
Which of the following is the most appropriate next step in management?
A. Add insulin glargine
B. Add neutral protamine Hagedorn (NPH) insulin
C. Implement a sliding scale for regular insulin
D. Start an insulin drip
Case 3: Severe hypoglycemia
A 35-year-old man is evaluated for hypoglycemia. He has had type 1 diabetes mellitus for 21 years and has experienced four severe episodes of hypoglycemia in the past 2 months, two of which resulted in loss of consciousness and visits to the emergency department. These episodes have occurred both overnight and during the day. He says he can no longer feel the hypoglycemia developing. He uses a blood glucose meter eight to ten times each day, and his average blood glucose level over the past month is 95 mg/dL (5.3 mmol/L); his most current hemoglobin A1c value is 5.8%. His diabetes regimen consists of insulin glargine, 22 units at night, and insulin lispro, four to eight units before meals.
Vital signs are normal. Physical examination findings are normal, with no evidence of peripheral or autonomic neuropathy.
Which of the following is the most appropriate treatment?
A. Add metformin
B. Change the insulin glargine to insulin detemir
C. Change the insulin lispro to regular insulin
D. Decrease the dosage of both insulins
Case 4: Insulin in the ICU
A 67-year-old woman is transferred to the cardiothoracic intensive care unit (ICU) after undergoing repair of an abdominal aortic aneurysm. She has a 12-year history of type 2 diabetes mellitus. Her blood glucose level on arrival at the ICU is 289 mg/dL (16.0 mmol/L). Although no longer on a cardiopulmonary bypass pump, she remains intubated and on vasopressors.
Which of the following is the best treatment to control her blood glucose level during her ICU stay?
A. Insulin glargine, once daily
B. Intravenous insulin infusion
C. Neutral protamine Hagedorn (NPH) insulin, twice daily
D. Regular insulin administered on a sliding scale
Case 5: Hypoglycemia and hip fracture
A 67-year-old woman is seen for a follow-up visit. Three weeks ago, she had a predawn episode of hypoglycemia on the way to the bathroom that caused her to fall, fracturing her hip. The patient has had type 2 diabetes mellitus for more than 20 years and has repeatedly had mild hypoglycemic episodes since the diagnosis. Although well tolerated to this point, these episodes have become increasingly frequent over the past 6 months. Her current medications are neutral protamine Hagedorn (NPH) insulin, 20 units, and regular insulin, 5 units, both injected before breakfast and supper. A review of her glucose log shows blood glucose readings ranging between 70 and 150 mg/dL (3.9 and 8.3 mmol/L) when fasting and 50 and 250 mg/dL (2.8 and 13.9 mmol/L) during the day. Her last measured hemoglobin A1c value was 7.8%.
Which of the following changes should be made to her diabetes regimen?
A. Change her medications to oral metformin and sitagliptin
B. Change her medications to insulin glargine and insulin lispro
C. Decrease the dosages of NPH and regular insulin by 10%
D. Increase her caloric intake
Case 6: Hyperglycemia with no history of diabetes
A 42-year-old man is evaluated in the surgical intensive care unit after surgery for a bowel obstruction. He presented yesterday to the emergency department for a 2-day history of fever, confusion, and abdominal pain. On examination, the patient's temperature was 38.4°C (101.1°F). Cardiac examination was normal; examination of the lungs revealed diffuse bilateral crackles. The abdomen was diffusely and markedly tender, with rebound and guarding. Leukocyte count was 18,400/µL (18.4 × 109/L) with 80% segmented neutrophils and 6% band forms. In the emergency department, his plasma glucose concentration was 205 mg/dL (11.4 mmol/L); the patient has no history of diabetes mellitus. Chest radiograph showed pulmonary edema, and the patient was hospitalized; imipenem/cilastatin was started, and he was taken to surgery. The patient was found to have a bowel obstruction with perforation and contamination of the peritoneal cavity. After surgery, the plasma glucose concentration is 300 mg/dL (16.7 mmol/L).
Which of the following is the most appropriate management of the patient's hyperglycemia?
A. Any insulin regimen that follows a sliding scale
B. Intravenous insulin drip
C. Subcutaneous intermediate-acting basal insulin
D. Subcutaneous long-acting basal insulin
Answers and commentary
Correct answer: A. Basal insulin and rapid-acting insulin before meals.
This patient has uncontrolled diabetes mellitus during an acute medical illness requiring hospitalization. Although current data does not demonstrate improved clinical outcomes with better glycemic control in patients on general hospital wards, such treatment likely improves outcomes in the intensive care unit. Recent ACP guidelines recommend maintaining blood glucose levels between 140 to 200 mg/dL (7.8 to 11.1 mmol/L) as a reasonable goal for patients in the ICU. Thus, a basal-bolus insulin regimen consisting of a long- or intermediate-acting insulin and a rapid-acting insulin analogue before meals is recommended for this hospitalized patient with diabetes mellitus. Such an approach allows for a more easily titratable regimen and can conveniently be held during diagnostic testing or procedures when nutritional intake is interrupted.
Insulin infusions are difficult to administer outside the intensive care unit in most hospitals; therefore, initiating one is not the best treatment for this patient and may not even be necessary to obtain good glycemic control.
A regimen of neutral protamine Hagedorn (NPH) insulin twice daily will likely improve glycemic control but is not as easily titratable as a basal-bolus correction and does not provide for premeal coverage to prevent postprandial glucose spikes.
Sliding scale regular insulin has been associated with increased hyperglycemic and hypoglycemic excursions and has been found to result in inferior glycemic control compared with a basal-bolus correction regimen in hospitalized patients. Initiating this approach is therefore inappropriate.
- Current data do not demonstrate improved clinical outcomes after treatment to achieve better glycemic control in patients on general hospital wards, but such treatment has been shown to improve outcomes in critically ill patients in the intensive care unit.
Correct answer: D. Start an insulin drip.
This patient should be started on an insulin drip. Discontinuation of insulin pump therapy resulted in inadequate insulin coverage; as a result, the patient developed diabetic ketoacidosis, as evidenced by the plasma glucose level of 262 mg/dL (14.5 mmol/L), positive urine ketones, and an anion gap. It is imperative to recognize that patients with insulin-deficient diabetes mellitus can develop ketoacidosis with only moderate glucose elevations. This patient should now be started on an insulin drip in a monitored setting. Intravenous insulin infusion is usually the preferred method of insulin delivery in an emergency because dehydration may be severe (which decreases subcutaneous absorption) and rapid titration of insulin may be required. Her plasma glucose level should be measured every 1 to 2 hours and adjustments made to the insulin infusion, as required, to gradually normalize her glucose level and reverse the ketoacidosis. After the metabolic abnormalities have been corrected and the patient is ready to be transferred to subcutaneous administration of insulin (usually when the patient starts eating), intravenous and subcutaneous insulin administration need to be overlapped to avoid rebound ketoacidosis. Short-acting or rapid-acting insulins should be given for 1 to 2 hours or intermediate or long-acting insulins for 2 to 3 hours before terminating the insulin infusion to ensure adequate overlap.
Insulin glargine and neutral protamine Hagedorn (NPH) insulin are long-acting preparations that do not provide the flexibility needed to aggressively treat diabetic ketoacidosis.
The use of sliding scale insulin will not allow for adequate insulin coverage, and the ketoacidosis can be expected to progress.
- Ketoacidosis can develop in insulin-deficient patients with only moderate plasma glucose elevations; an insulin drip is the most effective treatment of diabetic ketoacidosis.
Correct answer: D. Decrease the dosage of both insulins.
This patient's dosage of insulin should be decreased. Hypoglycemia is a major rate-limiting step in achieving tight glycemic control in patients with diabetes mellitus, in particular those treated with insulin. Repeated episodes of hypoglycemia are associated with a condition known as “hypoglycemia unawareness,” especially in type 1 diabetes. In this condition, the body no longer responds to mild hypoglycemia with typical symptoms (diaphoresis, tachycardia, anxiety, and tremor). Instead, neuroglycopenic symptoms, such as confusion, personality changes, and loss of consciousness, become the first manifestation of hypoglycemia. Hypoglycemia unawareness clearly relates to the frequency and severity of hypoglycemic events. In this manner, hypoglycemia begets further hypoglycemia.
Hypoglycemia unawareness can be diminished in this patient by decreasing the dosages of insulin glargine and insulin lispro by approximately 20% until his blood glucose level increases and hypoglycemia is avoided. This step allows the brain to adapt to the new ambient glycemia so that the normal adrenergic responses to hypoglycemia can be reestablished. Once this occurs, an intensification of the insulin therapy can be retried, but if problems redevelop, a permanently increased blood glucose target will be necessary.
Metformin is not approved for use in patients with type 1 diabetes mellitus. Furthermore, the addition of metformin to this patient's insulin regimen without reducing the dosage of insulin will not prevent hypoglycemia or improve hypoglycemic unawareness.
Unless the insulin dosage is concurrently decreased, simply changing the type of basal insulin from insulin glargine to insulin detemir is unlikely to increase blood glucose levels and prevent hypoglycemia.
Substituting regular insulin for the rapid-acting insulin analogue insulin lispro may actually exacerbate the incidence of hypoglycemia by delayed action on the blood glucose level. The duration of action of regular insulin is significantly longer than that of insulin lispro, with substantial insulin activity present 4 to 6 hours after injection.
- Hypoglycemia unawareness can be diminished by decreasing the dosage of insulin and scrupulously avoiding hypoglycemia.
Correct answer: B. Intravenous insulin infusion.
The intensive control of glucose levels in hospitalized patients during critical illness has garnered substantial attention over the past decade. Whereas the precise target remains controversial, a recent ACP guideline recommends blood glucose levels between 140 and 200 mg/dL (7.8 and 11.1 mmol/L) as a reasonable goal. In the setting of an intensive care unit (ICU), this is best and most safely achieved through the use of intravenous insulin. Intravenous delivery of insulin allows for more rapid titration and does not rely on subcutaneus absorption, which may be diminished or delayed in patients with cardiogenic shock or other critical illnesses associated with poor peripheral circulation.
If it appears that ongoing insulin is required once this patient is ready for transfer to a general ward, she should be transitioned to an injectable regimen involving long- or intermediate-acting and rapid-acting insulins. Oral agents can be restarted before discharge as long as renal function is normal and no contraindications exist.
Insulin glargine, the dosage of which is typically adjusted every 2 to 3 days until optimal glycemic control is achieved, cannot quickly guarantee adequate control during the 1 to 2 days that this patient is likely to be in the ICU. For similar reasons, using neutral protamine Hagedorn (NPH) insulin twice daily is unlikely to be the best treatment.
Although the dosage of regular insulin can be adjusted more frequently when administered on a sliding scale, this approach to glycemic control is considered inadequate because insulin is provided only when hyperglycemia becomes established. This method is not proactive enough to result in acceptable glycemic control during an ICU stay.
- Glycemic control is best achieved in the intensive care unit with an intravenous insulin infusion.
Correct answer: B. Change her medications to insulin glargine and insulin lispro.
Basal and rapid-acting insulin analogues, when dosed properly, reduce the risk of hypoglycemia. Current choices of long- or intermediate-acting basal insulins include insulin glargine, insulin detemir, and neutral protamine Hagedorn (NPH) insulin. The optimal basal insulin should be peakless and have a 24-hour duration of action. Both insulin glargine and, to a lesser extent, insulin detemir meet these requirements. NPH insulin, on the other hand, does not and is usually administered twice daily because its duration of action typically extends only 12 to 18 hours with a peak of activity at 4 to 8 hours after administration, which can precipitate hypoglycemic episodes at other times. In one study, the risk of hypoglycemia was significantly higher during the overnight hours in patients taking NPH insulin versus insulin glargine at bedtime. An ideal prandial insulin has a brisk peak and a short overall duration of action to properly cover postprandial glucose excursions. Such pharmacokinetics are found with the rapid-acting insulin analogues lispro, aspart, and glulisine. In contrast, regular insulin has a duration of action of 6 to 8 hours and so is not an optimal prandial product.
She should be encouraged to switch to a regimen of four injections of insulin per day, with a once daily injection of a basal insulin, such as insulin glargine, and mealtime injections of a rapid-acting analogue, such as insulin lispro.
Patients with advanced type 2 diabetes mellitus who are on insulin should not be transferred to oral agents because the need for insulin suggests an already significant insulin deficiency that oral agents are unlikely to overcome. Glycemic control would inevitably deteriorate.
Decreasing the dosage of NPH and regular insulin may diminish her overnight hypoglycemic episodes but would also result in higher blood glucose levels. Therefore, this change in the patient's diabetes regimen is not appropriate.
Increasing caloric intake to combat hypoglycemia is rarely indicated. Ideally, the insulin regimen should be adjusted on the basis of the patient's nutritional intake, not vice-versa.
- Unlike older insulin formulations, which have nonphysiologic pharmacokinetic profiles and thus increase the risk of hypoglycemia, basal and rapid-acting insulin analogues, when dosed properly, reduce the risk.
Correct answer: B. Intravenous insulin drip.
Glucose control in critically ill patients is now practiced widely. Hyperglycemia is believed to contribute to various physiologic derangements, such as inflammation and coagulopathy, that should be controlled in the septic patient. The exact range and goal for target glucose levels have been controversial. A recent ACP guideline recommends blood glucose levels between 140 and 200 mg/dL (7.8 and 11.1 mmol/L) as a reasonable goal for intensive care patients.
Continuous intravenous insulin is the most effective method for adequate glycemic control in these patients. Subcutaneous regular insulin based on a sliding scale and intermediate-acting or long-acting basal insulin do not offer the best acute titration of glucose in intensive care unit patients who may have volatile glucose levels. Furthermore, current guidelines emphasize the need to reconsider the widespread use of regular insulin sliding scales, which often result in labile glucose control, as the sole antihyperglycemic therapy in hospitalized patients. Instead, more active, physiologic insulin regimens are advisable.
- Continuous intravenous insulin is the most effective method for adequate glycemic control in critically ill patients.