Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 60-year-old man variable 2-hour postprandial blood glucose is evaluated during a routine follow-up examination. He has type 2 diabetes mellitus. Review of his blood glucose log demonstrates fasting blood glucose values ranging from 120 to 160 mg/dL (6.7-8.9 mmol/L) and variable 2-hour postprandial blood glucose values ranging from 50 to 190 mg/dL (2.8-10.5 mmol/L). His overnight blood glucose values range from 120 to 140 mg/dL (6.7-7.8 mmol/L). He is unable to detect hypoglycemia. The patient is concerned about hyperglycemia, and he desires to reach an HbA1c level of less than 7%.

Medical history is significant for diabetic retinopathy, peripheral neuropathy, hypertension, and hyperlipidemia. Medications are neutral protamine Hagedorn (NPH) insulin, regular insulin, losartan, chlorthalidone, metformin, rosuvastatin, and aspirin.

On physical examination, blood pressure is 125/82 mm Hg and pulse rate is 80/min. BMI is 24. Retinal examination demonstrates nonproliferative retinopathy. His lower extremities have diminished sensation to a 10-g monofilament and vibration with a 128-Hz tuning fork.

HbA1c level is 7.2%, and the results of all other laboratory studies are normal.

Which of the following is the most appropriate treatment of this patient’s diabetes?

A. Continue current insulin and metformin doses
B. Continue current insulin, increase metformin dose
C. Decrease meal-time insulin, add pramlintide
D. Decrease meal-time insulin, continue metformin

MKSAP Answer and Critique

The correct answer is D. Decrease meal-time insulin, continue metformin.

This patient should decrease his meal-time insulin and continue metformin. He has hypoglycemic unawareness secondary to a diminished counterregulatory response that has developed in the setting of repeated episodes of hypoglycemia. His hypoglycemia occurs in the postprandial state, thus the meal-time insulin should be decreased to allow permissive hyperglycemia for 2 to 3 weeks. Permissive hyperglycemia is defined as allowing an increase in blood glucose values to the level at which no further episodes of hypoglycemia occur. Using less stringent glycemic goals during this period will provide the body an opportunity to reset the counterregulatory response to hypoglycemia to a more appropriate blood glucose range, if possible. Although developing mutual HbA1c goals with the patient is important, hypoglycemia in this scenario precludes reaching his goal safely. Once he no longer has hypoglycemia, changes to the meal-time insulin doses or to meal content and volume can be evaluated to fine-tune his regimen while avoiding hypoglycemia.

Continuing the current regimen places the patient at increased risk for continued hypoglycemia in the setting of hypoglycemic unawareness.

Increasing the metformin dose may improve insulin sensitivity and decrease hepatic gluconeogenesis, which could improve the hyperglycemia and/or worsen the hypoglycemia. An increased metformin dose does not address the serious complication of hypoglycemic unawareness, which must be corrected first.

Pramlintide could decrease the HbA1c to the patient’s goal; however, hypoglycemia is a side effect of pramlintide in conjunction with insulin use. This may further increase the risk of hypoglycemia in this scenario. Pramlintide is an amylin mimetic that decreases glucagon secretion and increases satiety by decreasing gastric emptying. Pramlintide should be considered when the intended reduction in HbA1c is modest and the desired effects are a reduction in both weight and postprandial hyperglycemia.

Key Point

• Treatment for hypoglycemic unawareness is to reduce the insulin dose and allow permissive hyperglycemia at all times for several weeks to provide the body an opportunity to reset the counterregulatory response to hypoglycemia to a more appropriate blood glucose range.

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