Pre-type 1 diabetes dysmetabolism: maximal sensitivity achieved with both oral and intravenous glucose tolerance testing

Abstract

Objective: To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and to identify an optimal testing strategy for detecting preclinical diabetes.

Study design: Diabetes Prevention Trial-Type 1 Diabetes (DPT-1) randomized subjects to oral (n = 372) and parenteral (n = 339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors associated with progression to diabetes were evaluated.

Results: Survival analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of first phase insulin response (FPIR) at baseline were associated with decreased diabetes-free survival. Cox proportional hazards modeling showed that baseline body mass index (BMI), FPIR, and 2-hour glucose levels were significantly associated with an increased hazard for diabetes. On testing performed within 6 months of diabetes diagnosis, 3% (1/32) had normal FPIR and normal 2-hour glucose on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR performed within 6 months of diabetes diagnosis were equivalent (76% vs 73%).

Conclusions: Most (97%) subjects had abnormal IVGTTs and/or OGTTs before the development of diabetes. The highest sensitivity is achieved using both tests.

Figure 1

A: Time to diabetes by quartile of 2-hour glucose on oral glucose tolerance testing in the Oral Insulin Prevention Trial. Subjects in the highest quartile of 2-hour glucose had a shorter diabetes free survival time compared with subjects in the lowest quartile, (p=0.0006). Quartile 1: 44 mg/dl – 92mg/dL; Quartile 2: 93mg/dL – 108 mg/dL, Quartile 3: 108 mg/dL – 120 mg/dL; Quartile 4: 121 mg/dL – 139 mg/dL. B: Time to diabetes by quartile of 2-hour glucose on oral glucose tolerance testing in the Parenteral Insulin Prevention Trial. Subjects in the highest quartile of 2-hour glucose had a shorter diabetes free survival time compared with subjects in the lowest quartile (p<0.0001). Quartile 1: 40 mg/dl – 102 mg/dL; Quartile 2: 103 mg/dL – 119mg/dL, Quartile 3: 120 mg/dL – 147 mg/dL; Quartile 4: 148mg/dL – 199 mg/dL. C: Time to diabetes by quartile of first phase insulin response on intravenous glucose tolerance testing in the Parenteral Insulin Prevention Trial. Subjects in the lowest quartile of FPIR had a shorter diabetes free survival time compared with subjects in the highest quartile, (p<0.0001). Quartile 1: 8.3 μU/mL – 52 μU/mL; Quartile 2: 53 μU/mL L – 73 μU/mL, Quartile 3: 74 μU/mL – 102 μU/mL; Quartile 4: 103 μU/mL – 325 μU/mL.

Figure 1

A: Time to diabetes by quartile of 2-hour glucose on oral glucose tolerance testing in the Oral Insulin Prevention Trial. Subjects in the highest quartile of 2-hour glucose had a shorter diabetes free survival time compared with subjects in the lowest quartile, (p=0.0006). Quartile 1: 44 mg/dl – 92mg/dL; Quartile 2: 93mg/dL – 108 mg/dL, Quartile 3: 108 mg/dL – 120 mg/dL; Quartile 4: 121 mg/dL – 139 mg/dL. B: Time to diabetes by quartile of 2-hour glucose on oral glucose tolerance testing in the Parenteral Insulin Prevention Trial. Subjects in the highest quartile of 2-hour glucose had a shorter diabetes free survival time compared with subjects in the lowest quartile (p<0.0001). Quartile 1: 40 mg/dl – 102 mg/dL; Quartile 2: 103 mg/dL – 119mg/dL, Quartile 3: 120 mg/dL – 147 mg/dL; Quartile 4: 148mg/dL – 199 mg/dL. C: Time to diabetes by quartile of first phase insulin response on intravenous glucose tolerance testing in the Parenteral Insulin Prevention Trial. Subjects in the lowest quartile of FPIR had a shorter diabetes free survival time compared with subjects in the highest quartile, (p<0.0001). Quartile 1: 8.3 μU/mL – 52 μU/mL; Quartile 2: 53 μU/mL L – 73 μU/mL, Quartile 3: 74 μU/mL – 102 μU/mL; Quartile 4: 103 μU/mL – 325 μU/mL.

Figure 1

A: Time to diabetes by quartile of 2-hour glucose on oral glucose tolerance testing in the Oral Insulin Prevention Trial. Subjects in the highest quartile of 2-hour glucose had a shorter diabetes free survival time compared with subjects in the lowest quartile, (p=0.0006). Quartile 1: 44 mg/dl – 92mg/dL; Quartile 2: 93mg/dL – 108 mg/dL, Quartile 3: 108 mg/dL – 120 mg/dL; Quartile 4: 121 mg/dL – 139 mg/dL. B: Time to diabetes by quartile of 2-hour glucose on oral glucose tolerance testing in the Parenteral Insulin Prevention Trial. Subjects in the highest quartile of 2-hour glucose had a shorter diabetes free survival time compared with subjects in the lowest quartile (p<0.0001). Quartile 1: 40 mg/dl – 102 mg/dL; Quartile 2: 103 mg/dL – 119mg/dL, Quartile 3: 120 mg/dL – 147 mg/dL; Quartile 4: 148mg/dL – 199 mg/dL. C: Time to diabetes by quartile of first phase insulin response on intravenous glucose tolerance testing in the Parenteral Insulin Prevention Trial. Subjects in the lowest quartile of FPIR had a shorter diabetes free survival time compared with subjects in the highest quartile, (p<0.0001). Quartile 1: 8.3 μU/mL – 52 μU/mL; Quartile 2: 53 μU/mL L – 73 μU/mL, Quartile 3: 74 μU/mL – 102 μU/mL; Quartile 4: 103 μU/mL – 325 μU/mL.

Figure 2

A: First phase insulin response over time to diabetes including all subjects who developed diabetes and all intravenous glucose tolerance tests. B: Fasting glucose over time to diabetes, including all subjects who developed diabetes and all oral glucose tolerance tests. C: 2-hour glucose over time to diabetes, including all subjects who developed diabetes and all oral glucose tolerance tests.

Figure 2

A: First phase insulin response over time to diabetes including all subjects who developed diabetes and all intravenous glucose tolerance tests. B: Fasting glucose over time to diabetes, including all subjects who developed diabetes and all oral glucose tolerance tests. C: 2-hour glucose over time to diabetes, including all subjects who developed diabetes and all oral glucose tolerance tests.

Figure 2

A: First phase insulin response over time to diabetes including all subjects who developed diabetes and all intravenous glucose tolerance tests. B: Fasting glucose over time to diabetes, including all subjects who developed diabetes and all oral glucose tolerance tests. C: 2-hour glucose over time to diabetes, including all subjects who developed diabetes and all oral glucose tolerance tests.