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Poor Glycemic Control and Insulin Resistance Associated with Vascular Endothelial Dysfunction

Poor glycemic control is associated with the occurrence of morning blood pressure surge (MBPS), which is thought to be involved in the development of vascular dysfunction….

Early morning blood pressure surge (MBPS), defined as an increase in blood pressure that occurs from night to early morning, has been recognized as a relevant measure when predicting cardiovascular risk. Available data support this concept by showing that cardiac events occur most often in the morning. In diabetes patients, insulin resistance and poor glycemic control are thought to activate sympathetic activity and subsequently cause MBPS. In hypertensive patients with even greater MBPS, an increased number of macrophages, T cells, and TNF-α are seen in atherosclerotic plaques taken from the carotid artery. These elevated levels are not seen in those without exaggerated MBPS, suggesting that MBPS may be associated with vascular injury in patients with hypertension.

A study by Yoda, K. et al. was designed to determine whether poor glycemic control, by causing MBPS, can accelerate vascular injury in diabetes patients.

The study had two primary aims: to evaluate the association of insulin resistance and glycemic control with MBPS, and to evaluate the association between MBPS and vascular endothelial dysfunction. The latter would be assessed by measuring endothelium-dependent flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD). Fifty patients were included in the study, which took place from October 2011-November 2012. All patients were required to have T2DM, and were excluded if they had renal dysfunction, secondary DM, liver disease, or CVD. The patients varied significantly in what medications they were using to treat their diabetes and/or hypertension, with some of the patients also being on statin therapy. Noninvasive ambulatory blood pressure monitoring was done in a hospital setting for each patient for a period of 24h. MBPS was determined by subtracting the lowest SBP from the morning SBP. FMD and NMD were measured between 9am and 10am. HOMA-R (Homeostasis model assessment ratio) was used to assess insulin sensitivity in patients not using insulin. HbA1C, LDL cholesterol, HDL-cholesterol, and triglyceride levels were also measured.

Results showed FPG, HbA1C and TG levels to positively correlate with MBPS. For participants not using insulin, when HOMA-R replaced TG levels as a marker of insulin resistance, HOMA-R was found to be a significant factor contributing to MBPS. With regards to the study’s second aim, MBPS and HbA1C were found to negatively correlate with FMD. This was seen when MBPS was significantly lower in patients with normal FMD that in those with impaired FMD. SBP was found to negatively correlate with FMD as well as NMD. The multiple regression analysis showed only MBPS to associate with FMD in a negative manner. None of the factors in the multiple regression analysis were found to correlate with NMD.

The results of this study show that higher HbA1C levels, as well as TG levels or HOMA-R as a measure of insulin resistance, are associated with higher MBPS in type 2 diabetes patients. Furthermore, MBPS was found to be associated in a negative manner with FMD. These relationships suggest that poor glycemic control or insulin resistance can ultimately result in the development of vascular endothelial dysfunction by way of increased MBPS. In diabetics, it is hypothesized that insulin resistance may cause MBPS by stimulating sympathetic activity, or that insulin-stimulated reabsorption of sodium in the renal tubule may contribute to MBPS. Also, insulin resistance may have a stimulatory effect on the HPA axis in the early morning hours. As this was a cross-sectional study, the results are limited as all measurements were taken at a single point in time, and it is therefore hard to identify relationships among insulin resistance, poor glycemic control, and MBPS. Further research is needed to understand these relationships in greater detail.

Practice Pearls:
  • Poor glycemic control and insulin resistance were found to be associated with increased morning blood pressure surge (MBPS), which is a predictor of cardiovascular risk.
  • MBPS is associated in a negative manner with brachial artery flow-mediated dilation (FMD).
  • MBPS should be a target for preventing vascular damage in patients with T2DM.

Yoda, K. et al. "Association Between Glycemic Control and Morning Blood Pressure Surge With Vascular Endothelial Dysfunction in Type 2 Diabetic Patients" Diabetes Care. 2014; 37:644-650.