Salivary Transcriptome Biomarkers for Early Diabetes Detection

Study Overview
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Brief Summary
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A PRoBE design study will be used to obtain saliva from patients before undergoing blood study evaluation for screening at risk patients for the presence of undiagnosed pre-diabetes of type II diabetes. Pre-specified saliva biomarkers will be evaluated along with multi-marker models for their discriminatory value for distinguishing patients with normal glucose metabolism from those with disease. Appropriate housekeeping genes will also be incorporated to allow for the measurement of relative gene expression.

Detailed Description
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Prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) methods will be employed to collect saliva and evaluate transcriptome markers for early pre-diabetes and type II diabetes identification. At risk patients will have fasting blood glucose and insulin levels measured along with hemoglobin A1c and 2 hour post-prandial glucose levels. Saliva samples will be stored and will be analyzed after pre-specifying a panel of mRNAs and a multi marker model for validation. The pre-specified mRNAs and multi-marker model will be determined after analysis of data from a currently ongoing case-control study. After analyzing the data from this prior trial a validation plan will be locked before analysis of the prospectively collected specimens. Pre-diabetes will be defined based on abnormal glucose tolerance tests. Insulin resistance will be calculated as HOMA IR. The diagnostic value of the salivary transcriptome for will be compared with that of hemoglobin A1c and fasting blood glucose for the detection of pre-diabetes, insulin resistance and type II diabetes.

Official Title
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Salivary Transcriptome Biomarkers for Early Diabetes Detection

Conditions
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Pre-diabetes, Type II Diabetes, Insulin Resistance

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with unknown glucose metabolism status and Requiring clinically driven screening for abnormal glucose metabolism and Outpatient status Exclusion Criteria: Patients on treatment for abnormal glucose metabolism including diet and drug therapy Patients with a prior diagnosis of abnormal glucose metabolism Patients on treatment with corticosteroids

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Normal glucose metabolism<br>Normal fasting blood glucose, 2 hour post prandial glucose, hemoglobin A1c and HOMA IR | |
| Pre-diabetes<br>Abnormal glucose tolerance tests and/or insulin resistance with fating blood glucose and hemoglobin A1c below type II diabetes levels | |
| Type II diabetes<br>Hemoglobin A1c 6.5% or greater, fasting blood glucose >125 mg/dl or 2 hour post-prandial blood glucose 200 mg/ml or greater | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A multi marker test score based on a pre-specified model is measured in each patient. The test score is on a scale of 0 to 1.0 and relates to the probability of disease. | The area under the ROC curve is used to determine the overall performance of the model at the completion of the study. An area over 0.7 is considered clincially significant. | At study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-specified mRNA marker Ct values from PCR analysis will be measured in individual patients | The performance of each individual marker will be determined at study completion my comparing median values between groups by nonparametric analysis. A p value of less than or equal to 0.05 is considered significant. | At study entry | 
| Housekeeping gene Ct values on PCR analysis will be measured in individual patients | The performance of these genes will be determined based on stability within and between groups utilizing the NormFinder program. Stability values of < 0.2 will be considered significant. | At study entry |