Clinical Trial: Differing Levels of Hypoglycemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Mechanisms of Hypoglycemia Associated Autonomic Dysfunction, Differing Levels of Hypoglycemia

Brief Summary: Hypoglycemia can produce a spectrum of pro-inflammatory and pro-atherothrombotic changes. To date no studies appear to have investigated the effects of differing levels of hypoglycemia on the vasculature and pro-atherothrombotic balance during hypoglycemia in healthy man. The specific aim of our study will be to determine the effects of differing levels of hypoglycemia on in-vivo vascular biologic mechanisms in a healthy population.

Detailed Summary: Recent large randomized multicenter trials have investigated the effects of lowering blood glucose levels towards normal in both inpatient and ambulatory care/community settings. All studies have reported increasing prevalence and incidence of hypoglycemia as glucose levels approach normal. In fact, the occurrence of hypoglycemia was so problematic that some hospital based studies were halted and the target recommendations for glucose levels in critically unwell patients have been increased. Similarly three recent large glucose control and complications trials in type 2 diabetes mellitus (DM) have reported significantly high rates of hypoglycemia in intensively treated type 2 DM individuals. In two of these studies (VADT, ADVANCE) there was a highly significant association between severe hypoglycemia (glucose low enough to cause neurologic impairment) and serious cardiac events and increased death. Furthermore, in two studies performed in the USA (VADT, ACCORD), severe hypoglycemia occurring in the standard/conventionally treated group produced even more serious adverse cardiac effects as compared to the intensively treated group. The in-vivo mechanism(s) responsible for the above findings could not be identified from the above studies. Surprisingly there is very limited data available regarding the effects of hypoglycemia on in-vivo vascular biology. Previously, in vitro work has determined that epinephrine, norepinephrine, growth hormone, glucagon, and corticosteroids (all counterregulatory hormones) can have vascular biologic effects (platelet aggregation, fibrinolytic balance, increases in pro-inflammatory markers and changes in endothelial function). Three recent studies from my own and other laboratories performed in healthy volunteers and type 1 DM have demonstrated that hypoglycemia can produce a spectrum of pro-inflammatory and pro-atherothrombotic changes. Novel preliminary data from my lab has also demonstrated that hypoglycemia can impair endothelial fun
Sponsor: University of Maryland

Current Primary Outcome: Flow mediated vasodilation of brachial artery measurements (mean maximum % change) [ Time Frame: 120 minutes (pre) clamp and 240 minutes (post) clamp ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of Maryland

Dates:
Date Received: May 8, 2015
Date Started: July 2015
Date Completion: December 2017
Last Updated: February 9, 2017
Last Verified: February 2017