Adverse Effects of Systemic Hypoglycemia Exposure on Endothelial Function in Humans

NCT01660009 | Terminated

• 1 other identifier: MCW-MEW3
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Prior work suggests exposure to low glucose levels (hypoglycemia) is associated with increased cardiovascular risk. However, whether there is a causal relationship between cardiovascular events and hypoglycemia remains unclear with conflicting data in the literature. In this study, we plan to study whether acute exposure of patients to clinically relevant (50-60 milligrams/deciliter) levels of hypoglycemia induces or worsens blood vessel endothelial dysfunction- a key 1st step in the development of heart attacks and strokes. This will be determined in humans both with and with type 2 diabetes.

Conditions

Type 2 Diabetes

Keywords

Endothelial Function; Hypoglycemia; Mitochondria

Outcome Measures

Primary Outcomes (1)

• Flow induced Dilation of the Brachial Artery (FMD%)

  1 hour

Secondary Outcomes (3)

• Measurement of total and phosphorylated endothelium-derived NO synthase expression in radial artery endothelial cells.

  1 hour

• Measurement of mitochondrial membrane potential

  1 hour

• Mitochondrial superoxide production

  1 hour

Study Arms (2)

Hypoglycemia First

EXPERIMENTAL

Individuals will undergo a hyperinsulinemic hypoglycemic clamp in their 1st study visit after passing screening, and a euglycemic clamp in their second visit.

Other: Glycemic clamping

Euglycemia First

EXPERIMENTAL

Individuals will undergo a hyperinsulinemic euglycemic clamp in their 1st study visit after passing screening, and a euglycemic clamp in their second visit.

Other: Glycemic clamping

Interventions

Glycemic clamping OTHER

During hypoglycemic clamping, individuals will have a blood glucose level of 50-60 mg/dL for approximately 1 hour prior to outcome measurements. During euglycemic clamping, individuals will have a blood glucose level of 85-99 mg/dL for approximately 1 hour prior to outcome measurements.

Euglycemia First; Hypoglycemia First

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult age 21 or older
• If on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase reductase therapy, must be on a stable dose for at least 6 weeks prior to enrollment
• Diagnosis of type 2 diabetes by a physician as defined by the American Diabetes Association standard criteria: 1) Fasting Plasma glucose at or above 126 mg/dL 2) a two-hour value in an oral glucose tolerance test at or above 200 mg/dL, or 3) a random plasma glucose concentration 200 mg/dL in the presence of symptoms, or 4) glycosylated hemoglobin greater than or equal to 6.5%.
• Score of \< 4 using the Gold method for assessing hypoglycemia awareness
• Adult age 21 or older
• No evidence of metabolic syndrome or diabetes, hypertension (BP≥140/90), or high cholesterol (LDL≥160) at the time of screen.

You may not qualify if:

• History of stroke, peripheral arterial disease, or coronary artery disease (as defined by the presence of at least one coronary stenosis ≥ 40% on angiography or by confirmed history of myocardial infarction by standard criteria)
• Evidence of other evident major illness including chronic renal insufficiency(plasma creatinine \> 1.4 for women or 1.5 for men), liver disease (aspartate aminotransferase or alanine aminotransferase greater than 2.5 x normal), and cancer currently undergoing therapy or had therapy for cancer within 1 year of enrollment.
• Pregnancy as determine by urinary pregnancy test
• Subjects on warfarin, oral anti-thrombin inhibitors, or thienopyridines
• Subjects who have had changes to dosing of thiazolidinedione, dipeptidyl peptidase-4 (DPP-4) inhibitor, or metformin therapy within 6 weeks of enrollment.
• Failed Allen's test in both arms - unable to safely place an arterial line
• Glucose reading of \< 50 mg/dL and/or episodes of symptomatic hypoglycemia requiring the assistance of another person for recovery in the 2 years prior to enrollment.
• History of hypoglycemic convulsions
• Current fluoxetine therapy (known to interfere with neuroendocrine response to hypoglycemia)
• Glycosylated hemoglobin over 8.5%
• On aldosterone antagonist therapy at the time of enrollment
• On insulin therapy at the time of screening.
• History of allergy to local anesthetic injection like lidocaine.
• Age below 21.
• On medication for cholesterol or blood pressure.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypoglycemia

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Michael E Widlansky, MD, MPH

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2012
• First Posted: August 8, 2012
• Study Start: June 1, 2012
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: August 14, 2017

Record last verified: 2015-04

Locations

US (1)