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

A 49-year-old man seeks advice on ways to prevent the development of type 2 diabetes mellitus because of a strong family history (mother, sister, and brother) of the disease. History is significant for hypertension, for which he takes losartan and amlodipine in the morning.

On physical examination, temperature is 37.2 °C (99.0 °F), blood pressure is 125/84 mm Hg, pulse rate is 80/min, and respiration rate is 16/min. BMI is 22. There is no S₄ gallop.

Laboratory studies show a fasting plasma glucose level of 104 mg/dL (5.7 mmol/L), a HbA1c level of 5.9%, and a urine albumin-creatinine ratio of 45 mg/g.

According to a study published in the February 2016 Diabetologia, which is an appropriate management option that may reduce this patient’s risk of type 2 diabetes?

A. Add a thiazide diuretic
B. Move the losartan to bedtime
C. Recommend a low fat diet
D. Recommend weight loss

MKSAP Answer and Critique

The correct answer is B. Move the losartan to bedtime.

Based on a recent study, moving this patient’s losartan dosage to bedtime is an appropriate management option that may reduce his risk of developing type 2 diabetes mellitus. He is at high risk for the development of type 2 diabetes; he has hypertension, a strong family history of diabetes, and newly diagnosed chronic kidney disease as defined by the increase in albuminuria. In a recently published randomized controlled trial, 2012 patients with hypertension but without type 2 diabetes were prospectively randomized to take all their hypertensive medications in the morning or at least one of the medicines at bedtime. There was an improvement in overnight blood pressure and a significantly lower incidence of new-onset type 2 diabetes with a hazard ratio of 0.43 (0.31, 0.61). This was especially true when the medication taken at bedtime was an ACE inhibitor, angiotensin receptor blocker, or nebivolol, the beta-blocker used in the study. The mechanism of action is unknown. The authors note that activation of the renin aldosterone angiotensin system (RAAS), which occurs at night, is known to result in an increase in hepatic glucose release and a decrease in insulin sensitivity. They suggest that the lower incidence of new-onset type 2 diabetes may be secondary to blockade of the RAAS with ACE inhibitors, angiotensin receptor blockers, or nebivolol, which has a regulatory effort on the RAAS.

There is no need to add a thiazide diuretic. His office blood pressure is adequately controlled, and thiazide-induced hypokalemia may decrease insulin secretion.

Although the Mediterranean diet has been associated with a decrease in the development of type 2 diabetes, in the Women’s Health Initiative Dietary Modification Trial, subjects assigned to a low-fat diet developed type 2 diabetes at a similar rate to those assigned to a usual diet.

There are no data to support weight loss in a person who is at ideal body weight.

Key Point

• According to a recently published randomized controlled trial, bedtime ingestion of hypertension medication (especially an ACE inhibitor, angiotensin receptor blocker, or beta-blocker) may help to reduce the risk of new-onset type 2 diabetes mellitus.

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