Pioglitazone shift circadian rhythm of blood pressure from non-dipper to dipper type in type 2 diabetes mellitus

Eur J Clin Invest. 2007 Sep;37(9):709-14. doi: 10.1111/j.1365-2362.2007.01854.x.

Abstract

Background: Insulin resistance significantly correlated with a non-dipper type of essential hypertension. Thiazolidinediones (TZD), oral hypoglycaemic agents that act as insulin sensitizers, have been demonstrated in multiple in vivo and in vitro studies to possess antihypertensive properties. This study examined the efficacy of TZD therapy with pioglitazone at transforming the circadian rhythms of blood pressure from a non-dipper to a dipper type.

Materials: We examined 31 patients with type 2 diabetes mellitus during both a baseline period and a period of treatment with pioglitazone. Patients received 15 mg day(-1) pioglitazone for four weeks and 30 mg day(-1) for 12 weeks. Twenty-four hour ambulatory blood pressure monitoring (ABPM) and laboratory data (blood tests for cardiovascular risk factors) were obtained at the beginning and end of the study.

Results: In non-dippers (n = 16), but not dippers (n = 15), we observed a significant interaction between pioglitazone therapy and nocturnal falls in systolic and diastolic blood pressure. This examination indicated that the magnitude of the nocturnal blood pressure fall was affected by pioglitazone therapy. In non-dippers, but not dippers, a significant correlation was observed between the percent decrease in nocturnal BP and the homeostasis model assessment (HOMA) index (r = 0.774, P = 0.0007).

Conclusions: The present study demonstrated that pioglitazone can restore the nocturnal BP declines in parallel to reductions in the HOMA index, suggesting that insulin resistance may play an important role in the genesis of circadian BP rhythms. TZD-based treatment may thus have the additional therapeutic advantage of reducing the risk of cardiovascular complications by transforming the circadian rhythm of BP.

MeSH terms

  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Blood Glucose / analysis
  • Blood Pressure / drug effects
  • Blood Pressure Monitoring, Ambulatory / methods
  • Circadian Rhythm / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Angiopathies / drug therapy*
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance / physiology
  • Male
  • Middle Aged
  • Pioglitazone
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use*
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Blood Glucose
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Pioglitazone