Biomarkers in Exhaled Breath of Glucose Fluctuation in Type 1 Diabetes

The investigators are investigating the "biochemical fingerprint" of hypoglycemia (low blood sugar) in the breath of people with type 1 diabetes.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Type 1 Diabetes Mellitus; Volatile Organic Compounds
• Intervention / Treatment: Diagnostic test: Collect exhaled breath during low and normal blood sugar

Detailed Description

The investigators aim through the use of proton-transfer-reaction mass spectrometry to perform comprehensive breath analysis to identify compounds of interest associated with glucose fluctuations. More than 500 different volatile organic compounds can be detected in human breath. Compounds such as ethane, pentane and isoprene (hydrocarbons), as well as acetone, acetaldehyde, methanol, ethanol, 2-propanol (oxygen-containing compounds), are most likely to be relevant and measurable in our study population. Hydrocarbons are stable end-products of lipid peroxidation and show only low solubility in blood and therefor are excreted into breath within minutes of their formation in tissues. There is evidence for increased hydrocarbon production in states of oxidative stress. Oxygen-containing compounds such as acetone/acetaldehyde (ketones) are also clinically relevant in the measurement of insulin deficient states of catabolism in patients with diabetes. A previous study of exhaled isoprene was found to be elevated during hypoglycemia. This study aims to expand on this to characterize the full range of changes in concentrations of volatile organic compounds in human breath during glucose fluctuations.

Characterizing this "biochemical fingerprint" of hypoglycemia may provide clues about what so-called diabetes alert dogs are detecting as well as improve our understanding of hypoglycemia, the physiology behind hypoglycemia unawareness, and potentially identify a novel non-invasive measure of blood glucose.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Johnson City, Tennessee, United States, 37604
      • Mountain States Health Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 78 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

People with type 1 diabetes between age 5-80.

Description

Inclusion Criteria:

• Have a diagnosis of type 1 diabetes
• No current or planned tobacco/nicotine use including vaping during the study
• Are not pregnant or planning to become pregnant during the study timeframe

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute and relative change in concentration of measured volatile organic compounds in human breath in subjects with type 1 diabetes during hypoglycemia compared to euglycemia measured by proton-transfer-reaction time-of-flight mass spectrometry.	Detectable difference in volatile organic compounds (anticipate up to 120-150 different ion signals to be assessed) in human breath during low blood sugar (<70 mg/dL) compared to normal blood sugar (70-180). As this is a 'hypothesis generating' pilot study, the investigators are observing what compounds are present and in what concentrations -- this is the reason for nonspecific outcome measures	Until three low blood sugar events have occured with breath samples collected during low blood sugar and upon recovery to normal blood sugar; expected 1-2 weeks but allowed up to 1 month to complete sample collection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize relationship of concentration of all measurable VOCs (anticipate 120-150 ion signals) by proton-transfer-reaction time-of-flight mass spectrometry across the spectrum of glycemia.	Statistically-significant (P<0.05) differences in concentration of volatile organic compounds in human breath in subjects with type 1 diabetes across the spectrum of glycemia (very low <54 mg/dL), low (55-69), in target (70-180), high (181-250), very high(>250))	up to 1 month
Identify differences in patterns of exhaled VOCs in people who have hypoglycemia unawareness	Statistically significant (P<0.05) differences in patterns of exhaled VOCs between subjects with and without hypoglycemia unawareness identified by standardized hypoglycemia unawareness survey tools	up to 1 month

Collaborators and Investigators

• Sponsor: East Tennessee State University
• Collaborators: Mountain States Health Alliance
• Investigators: Principal Investigator: Evan Los, MD, East Tennessee State Univerisity

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): August 30, 2018
• Study Completion (Actual): August 30, 2018

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: February 14, 2018
• First Posted (Actual): February 15, 2018

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
• Other Study ID Numbers: 0817.5f

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No