Biomarkers in Exhaled Breath of Glucose Fluctuation in Type 1 Diabetes

Completed

• Conditions: Hypoglycemia; Volatile Organic Compounds; Type 1 Diabetes Mellitus

• Registration Number: NCT03435198
• Lead Sponsor: East Tennessee State University

Brief Summary

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

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 Timeline

• Study First Submitted: 2018-01-30
• Study First Submitted QC: 2018-02-14
• Study First Posted: 2018-02-15
• Study Start: 2018-03-01
• Primary Completion: 2018-08-30
• Study Completion: 2018-08-30
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-13
• Last Update Posted: 2019-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.	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	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

Secondary Outcome Measures

Name	Time	Method
Identify differences in patterns of exhaled VOCs in people who have hypoglycemia unawareness	up to 1 month	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
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.	up to 1 month	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))

Trial Locations

Locations (1)

Mountain States Health Alliance; 🇺🇸 Johnson City, Tennessee, United States