Isotope-Labeled Breath Test for Insulin Resistance

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Solution Overview

Problem

Current methods for diagnosing diabetes and insulin resistance, particularly in prediabetic stages, are invasive, burdensome for patients, and lack sensitivity, with existing breath tests unable to accurately detect sugar/fatty acid combustion ratios or insulin resistance in conditions like liver cirrhosis.

Innovation Solution

A composition combining isotope-labeled C12-38 fatty acid with isotope-labeled glucose in a labeled C-breath test to measure the sugar/fatty acid combustion ratio and insulin resistance by determining the ratio of labeled CO2 to unlabeled CO2 in expired air, allowing for accurate judgment of insulin resistance and energy source usage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If glucose tolerance test using glucose is performed, then diabetes can be diagnosed, but test subjects are restrained for several hours and blood is repeatedly collected, imposing great physical burden

Engineering Contradiction:
Improvediagnosis accuracyVSAvoidphysical burden on test subjects
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces the mechanical/invasive blood collection system with a breath analysis system. Instead of repeatedly collecting blood samples to measure glucose levels, the invention measures labeled CO2 in expired breath to assess glucose metabolism and insulin resistance, thereby eliminating the physical burden of repeated blood draws while maintaining diagnostic reliability

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces labeled CO2 in breath as an intermediary marker to indirectly measure glucose metabolism. Rather than directly measuring blood glucose levels through invasive means, the system uses the metabolic byproduct (labeled CO2) that can be non-invasively detected in breath, serving as a mediator between the metabolic process and the measurement

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If glucose tolerance test is performed, then diabetes diagnosis is possible, but test subjects must be restrained for several hours

Engineering Contradiction:
Improvediagnosis accuracyVSAvoidtest duration
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The invention replaces the time-consuming glucose tolerance test protocol with a rapid breath analysis method. By measuring labeled CO2 excretion in breath, the system can assess glucose metabolism and insulin resistance in a fraction of the time required for traditional glucose tolerance testing, significantly reducing the time subjects must spend in the testing facility

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If HbA1C or fructosamine testing is performed, then diabetes diagnosis is possible, but results cannot be known until the next hospital visit, lacking rapidity

Engineering Contradiction:
Improvediagnosis accuracyVSAvoidresult availability time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent replaces laboratory-based HbA1C and fructosamine testing with an immediate breath analysis system. By measuring labeled CO2 in real-time using breath sampling, the invention provides rapid results that are available during the same visit, eliminating the waiting period associated with laboratory processing and enabling same-day diagnosis and intervention

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

4Ease of operation

If urine glucose test or fasting blood glucose level test is performed, then screening is simple, but sensitivity is low and many diabetic cases are missed

Engineering Contradiction:
Improvetest simplicityVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent uses labeled CO2 in breath as an intermediary marker that provides higher sensitivity than direct glucose measurement. By tracking the metabolic fate of labeled glucose through CO2 excretion, the system can detect subtle metabolic abnormalities and insulin resistance that are missed by conventional urine glucose or fasting blood glucose tests, while maintaining operational simplicity

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the measurement parameter from direct glucose concentration to labeled CO2 excretion rate. This parameter transformation enables detection of metabolic dysfunction at an earlier stage, increasing sensitivity for detecting prediabetes and insulin resistance while keeping the testing procedure simple and non-invasive

Inventive Principle:
Principle #35Parameter changes

5Measurement precision

If indirect calorimetry for detecting saccharide/lipid combustion ratio is used, then prognosis of liver cirrhosis can be determined, but the method has little practicability and cannot easily grasp nutritional status

Engineering Contradiction:
Improvenutritional status detection accuracyVSAvoidmethod practicability
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces complex indirect calorimetry equipment with a simplified breath analysis system. By measuring labeled CO2 from metabolized substrates, the invention can determine saccharide/lipid combustion ratios using straightforward breath sampling and analysis, making the method practical for routine clinical use while maintaining the ability to accurately assess nutritional status and prognosis in liver cirrhosis patients

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This method enables rapid and accurate measurement of sugar/fatty acid combustion ratios and insulin resistance, providing a more sensitive diagnostic tool for diabetes and related conditions, such as borderline diabetes and liver cirrhosis, with less physical burden on patients.

Implementation Method 1

a C12-38 fatty acid or a salt thereof labeled with at least one isotope of C, wherein the C12-38 fatty acid or a salt thereof is converted in the body into labeled CO2 gas that is excreted in expired air

Methodology Applied
Scientific EffectIsotope labeling: Radioactive Tracing

Data Source

PatentEP2975400B1Composition for use in a method for measuring sugar/fatty acid combustion ratio
Publication Date: 2019.09.04 OTSUKA PHARM CO LTD
  • EP2975400B1 patent drawingFigure 1~2(B)
  • EP2975400B1 patent drawingFigure 3(A)~4(B)
  • EP2975400B1 patent drawingFigure 5(A)~6(B)

AI summary

This invention provides a method for measuring insulin resistance of a test subject, and a composition suitably used for the method. A method for measuring insulin resistance of a test subject comprising steps (a) and (b) below, the method using a composition for measuring insulin resistance comprising, as an active ingredient, a C12-38 fatty acid labeled with at least one isotope of C, wherein the C12-38 fatty acid is converted in the body into labeled carbon dioxide that is excreted in expired air, (a) intravenously administering the composition to a test subject and collecting expired air; and (b) determining the ratio of labeled CO2 amount to unlabeled CO2 amount contained in the expired air or the ratio of labeled CO2 amount to total CO2 amount contained in the expired air.