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Dosing antihypertensives before sleep instead of upon waking lowered risk of incident diabetes in a randomized trial.

And, in fact, sleeping BP -- but not daytime or 48-hour ambulatory BP -- was found to be a significant predictor of new-onset diabetes and may be a novel target for prevention, a research team led by , of the University of Vigo, Spain, and colleagues reported in .

During a median follow-up of 5.9 years, 171 study participants developed diabetes. Incidence of new-onset diabetes was significantly lower in the bedtime group (4.8%) versus the daytime group (12%) (P<0.001).

After adjusting for factors including fasting glucose, waist circumference, and chronic kidney disease, the investigators found the bedtime group was 57% less likely to develop diabetes (HR 0.43; 95% CI 0.31-0.61; P<0.001).

Medications that block the renin-angiotensin-aldosterone system (RAAS), such as angiotensin receptor blockers (ARBs) and ACE inhibitors, had the strongest antidiabetic effect, Hermida and colleagues reported.

"Activation of the renin-angiotensin-aldosterone system (RAAS) and consequent elevations of angiotensin II and aldosterone contributes to increased hepatic glucose release and decreased insulin sensitivity," the investigators wrote. They added that the RAAS follows a circadian rhythm, becoming active during sleep.

"Accordingly, in addition to BP-lowering, RAAS blockade might also serve as an effective strategy to control impaired glucose and insulin tolerance," they said.

The prospective study included more than 2,000 hypertensive patients enrolled in the Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events (MAPEC) study. Their average age was 53, and they were roughly half men and half women.

Participants were randomized to a bedtime group, which took the entire daily dose of one or more of their hypertension medications before bed, and a daytime group, which took all their hypertension medications upon waking.

Blood pressure was assessed annually in both groups by daytime clinic measurement and by 48-hour ambulatory blood pressure (ABP) monitoring. Blinded investigators assessed the development of new-onset diabetes.

All classes of hypertension drugs showed some protective effect against diabetes in the bedtime group, but the strongest effect was found for ARBs (HR 0.39; 95% CI 0.22-0.69; P<0.001), ACE inhibitors (HR 0.31; 95% CI 0.12-0.79; P=0.015), and beta blockers (HR 0.35; 95% CI 0.14-0.85; P=0.021).

Several assessments of blood pressure were significantly lower in the bedtime group versus the daytime group, including the mean sleeping systolic BP (109.6 ±13.9 mmHg versus 114.4 ± 15.2 mmHg; P<0.001), the percentage of decline in sleeping systolic BP (12% versus 9%; P<0.001), and the percentage of those whose sleeping BP was controlled (72% versus 59%; P<0.001).

In a separately published analysis of the trial in the same journal, the investigators reported that mean sleeping systolic BP as measured by ambulatory monitoring was a significant and independent predictor of new-onset diabetes. For each 1-standard deviation elevation in mean sleeping systolic BP, the risk of diabetes increased by almost 30% (HR 1.28; 95% CI 1.10-1.45; P<0.001).

Daytime BP measured in the clinic or by ambulatory monitoring did not predict new-onset diabetes, the investigators said.

The research team concluded that "lowering asleep BP, a novel therapeutic target requiring ABP evaluation, could be a significant method for reducing new-onset diabetes risk."

"As a summary of all these findings, ambulatory BP monitoring is needed not only for proper diagnosis of hypertension and quantification of cardiovascular risk, but also, within this context, for evaluation of the individual's risk of developing diabetes, rendering ambulatory BP a cost-effective technique that should be recommended in all adults, as recently proposed by the ," Hermida told 番茄社区app via email.

"Finally, changing the time of ingestion of hypertension medications, a zero-cost intervention, has been shown to reduce cardiovascular morbidity and mortality and, in keeping with the new findings reported in Diabetologia, also significantly reduces the risk of developing diabetes," Hermida said.

"This study reinforces the importance of taking hypertension medication at night, particularly drugs that have an anti-renin effect -- ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists," , of Tulane University in New Orleans, said in an interview with 番茄社区app.

"We have known for some time that dosing at night is preferable for a lot of drugs, in particular drugs that modulate the RAAS. People don't realize that renin goes up at night," Giles said.

"Hypertension specialists know this. But the average person in the field, I don't think they're aware of this," Giles said.

From the American Heart Association:

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