The 1 Hour Oral Glucose Tolerance Test Predicts Development of Dysglycemia and T2DM Restricted; Files Only

Zhang, Amanda (Spring 2019)

Permanent URL: https://etd.library.emory.edu/concern/etds/5999n455n?locale=en
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Abstract

Background: Inadequate insulin secretion due to pancreatic beta cell dysfunction underlies the development and progression of type 2 diabetes (T2DM), a major public health problem. Since current methods of assessing beta cell function are time-consuming, labor- intensive, and expensive, we investigated whether the plasma glucose at 1 hour in an oral glucose tolerance test (1hOGTT) could be an equally accurate but more convenient and less costly alternative. 

Methods: The areas under receiver operating characteristic curves (ROC AUCs) were used to compare the accuracy of predicting the progression towards T2DM over 3 years in 489 participants with complete data in the European Relationship between Insulin Sensitivity

and Cardiovascular disease (RISC) Study.

Results: The ROC AUCs for 1hOGTT were 0.676 (95% CI 0.633 - 0.718) for prediction of progression from normal glucose metabolism to dysglycemia (pre-T2DM or T2DM), 0.809 (0.763-0.854) for non-high risk dysglycemia to high risk dysglycemia, and 0.910 (0.861-0.959) for non-T2DM to T2DM, all comparable or superior to more complex assessments, including the euglycemic insulin clamp, OGTT modeling, insulinogenic index, and beta cell glucose sensitivity. The findings were similar in paired analyses of data from 369-743 participants.

Conclusions: Prediction of progression toward T2DM with the simple, convenient 1hOGTT is comparable to prediction with complex and costly methods. Consideration should be given to use of the 1hOGTT for screening and to complement more complex measures in understanding mechanisms to support discovery of new treatments.

Table of Contents

Introduction...................................................................................................................................1

Glucose as a Metabolic Fuel…………………………………………………………………………………….…………….1

Regulation of Glucose Levels by Insulin……………………………………………………………………………….…1

T2DM as a Disorder of Glucose Regulation – Hyperglycemia…………………………………………………2

Natural History of Development of T2DM……………………………………………………………………………..2

Consequences of Diabetes……………………………………………………………………………………………………..4

What is Needed to Make T2DM Less of a Problem…………………………………………………………………4

Standard Analysis of Mechanisms………………………………………………………………………………………….4

We Measure Circulating Glucose Levels to Define Status……………………………………………………….6

Hypothesis………………………………………………………………………………………………………………………….…6

What is Already Known about the 1 Hour Glucose in an Oral Glucose Tolerance Test (1hOGTT).........................6

Measuring the 1hOGTT Would be Convenient, Easy, and Inexpensive……..…………………………….7

If Comparable to Standard Tests, Might Be Able to Use the 1hOGTT for Both Screening and Monitoring of Mechanisms……………7

Materials and Methods..................................................................................................................8

General Design……………………………………………………………………………………………….……………………..8

Human Subjects Considerations…………………………………………………………………………………………….8

Assessment Tools………………………………………………………………………………………………………………….9

RISC Dataset………………………………………………………………………………………………………………………..11

Data Cleaning………...................................................................................................................12

Metabolic Tests….....................................................................................................................13

Classification of Glucose Metabolism…………………………………………………………………….…………….16

Definitions of Progression toward T2DM.………….....................................................................16

Analysis of Tests to Predict an Outcome.…………......................................................................17

Receiver Operating Characteristic Analysis..............................................................................18

Analysis……………………………………………………………………………………………………………………………….19

Results..........................................................................................................................................20

Patient Characteristics………………………………………………………………….….....................................20

ROC Analysis………………………………………………………………….…......................................................20

Paired Analysis…………………………………......................................................................................24

Discussion.....................................................................................................................................28

Summary of Findings................................................................................................................28

Comparison to What is Already Known about 1hOGTT……………………………………………..…………28

What is Already Known about the 1hGCT………………………………………………………………….…………28

Limitations…………………………………………………………………………………………………………………………..29

Future Directions…………………………………………………………………………………………………………………29

Conclusions………………………………………………………………………………………………………………………….30

Table of Figures............................................................................................................................31

References....................................................................................................................................32

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