Arterial Stiffness in Type I Diabetes Mellitus

Acute Effect of a Mixed Meal With and Without Extra Insulin on Arterial Stiffness, a Prospective Randomized Study.

Using radial artery tonometry to study arterial stiffness, the plan is to study a cohort of 65 children with Type I diabetes mellitus. This prospective, crossover study will help determine if there is an acute increase in arterial stiffness in children with Type I diabetes mellitus who do not give extra insulin to cover a meal. This will give more support to show why it is so critical to bolus every time they eat and to bolus on time to decrease cardiovascular consequences of poorly controlled diabetes. The hypothesis is that giving insulin before a meal compared to not giving insulin before a meal will be associated with lower arterial stiffness in children with type I diabetes.

Study Overview

• Status: Completed
• Conditions: Arterial Stiffness in Youth With Type 1 Diabetes
• Intervention / Treatment: Drug: Pre-meal bolus; Drug: No meal bolus

Detailed Description

The subject will fast overnight (nothing to eat or drink for at least 8 hours). The subject will be asked to drink a mixed meal replacement drink (Boost) and will be randomized (like flipping a coin) to bolus insulin for the "meal" or to not bolus insulin using their standard insulin dose. Glucose will be monitored with a finger prick before they drink the meal replacement, 1 hour later and finally 2 hours after drinking the meal replacement.

Stiffness of the blood vessel of the wrist will be determined using radial tonometry. Radial tonometry is safe and does not hurt. A pen like probe is placed on the blood vessel of the wrist. When the machine reads a good wave form the computer will calculate the stiffness of the blood vessel. This test will be done along with the glucose checks; before drinking the meal replacement drink, and 1 and 2 hours after drinking the meal replacement drink.

During the next study visit, the subject will repeat the exact same study described above. However, this time they will receive the other insulin assignment they were assigned during the first study (either bolus or no bolus).

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

University of Florida diabetes clinic and the Florida Camp for Children and Youth with Diabetes. Subjects had type 1 diabetes for at least one year, were using a basal-bolus insulin regimen, and were not taking oral hypoglycemic agents or antihypertensive drugs.

Description

Inclusion Criteria:

• Type 1 diabetes based on clinical history
• Basal-bolus insulin regimen
• Duration of diabetes greater than 1 year
• Blood glucose 65-200 mg/dL fasting

Exclusion Criteria:

• Use of metformin or any other hypoglycemic agents besides insulin
• Use of anti-hypertensives
• Caffeine or smoking within the past 24 hours

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pre-meal bolus then No meal bolus; A meal replacement drink (Boost) and bolus of rapid insulin will be given to this group. Glucose will be monitored with a finger prick before they drink the meal replacement, 1 hour later and finally 2 hours after drinking the meal replacement. Stiffness of the blood vessel of the wrist will be determined using radial tonometry and will be done at the same time as the glucose monitoring. Then 3 months later A meal replacement drink (Boost) will be given but the subject will not receive a meal bolus. Glucose will be monitored with a finger prick before they drink the meal replacement, 1 hour later and finally 2 hours after drinking the meal replacement. Stiffness of the blood vessel of the wrist will be determined using radial tonometry and will be done at the same time as the glucose monitoring	Drug: Pre-meal bolus; Long acting insulin as scheduled per usual routine PLUS rapid/ short acting (bolus) prior to Boost; Drug: No meal bolus; Long Acting insulin as scheduled per usual routine (given once daily)
No meal bolus then Pre-meal bolus; A meal replacement drink (Boost) will be given but the subject will not receive a meal bolus. Glucose will be monitored with a finger prick before they drink the meal replacement, 1 hour later and finally 2 hours after drinking the meal replacement. Stiffness of the blood vessel of the wrist will be determined using radial tonometry and will be done at the same time as the glucose monitoring. Then 3 months later meal replacement drink (Boost) and bolus of rapid insulin will be given to this group. Glucose will be monitored with a finger prick before they drink the meal replacement, 1 hour later and finally 2 hours after drinking the meal replacement. Stiffness of the blood vessel of the wrist will be determined using radial tonometry and will be done at the same time as the glucose monitoring	Drug: Pre-meal bolus; Long acting insulin as scheduled per usual routine PLUS rapid/ short acting (bolus) prior to Boost; Drug: No meal bolus; Long Acting insulin as scheduled per usual routine (given once daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the Difference Between Acute Effect of a Mixed Meal on Radial Artery Stiffness in Subjects With Type I Diabetes Mellitus Who do and Who do Not Take an Additional Bolus of Insulin.	Determine the difference between acute effect of a mixed meal on radial artery stiffness in subjects with type I diabetes mellitus who do and who do not take an additional bolus of insulin. Radial tonometry is used to calculate the augmentation index (AI). AI is expressed as a percentage of the pulse pressure and represents the difference between the first and second peaks of the central arterial waveform. The stiffer the artery the more positive elevation of the AI and the machine will indicate stiffness using a color indicator (green less stiff and red being stiff). AI is measured using the SphygmoCor VX version 7.01 (AtCor Medical, Syndey, Australia). AI will be corrected to a heart rate of 75 to eliminate differences related to heart rate variation.	From baseline to one hour then 2 hours

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Diabetes Action Research and Education Foundation
• Investigators: Principal Investigator: Michael Haller, MD, University of Florida

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: August 8, 2014
• First Submitted That Met QC Criteria: August 14, 2014
• First Posted (Estimate): August 18, 2014

Study Record Updates

• Last Update Posted (Estimate): February 6, 2017
• Last Update Submitted That Met QC Criteria: December 12, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: children; adolescents; young adults; healthy; type I diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: IRB201400553; 00093792 (Other Identifier: University of Florida)