SUN-LB122 Sequential Testing to Assess Insulin Resistance in the Course of Participation in a Diabetes Prevention Program (DPP)

Abstract

Obesity has become increasingly prevalent in the United States and diabetes prevalence has increased dramatically. It is estimated that diabetes affects more than 30 million Americans (CDC, 2015). Prediabetes, a condition in which blood sugar or HbA1c levels are elevated but not to levels permitting a diagnosis of type 2 diabetes, is even more prevalent. Prediabetes precedes the development of type 2 diabetes and for this reason, has been identified as a condition at which interventions might be targeted and progression to overt diabetes might be interrupted. The publication of the initial results of the Diabetes Prevention Program (Knowler WC, 2002) demonstrated that lifestyle change and medication could substantially reduce progression to type 2 diabetes. These efforts have stimulated the CDC to implement the National Diabetes Prevention Program. Unfortunately, a substantial proportion of individuals adhering to lifestyle change or medication still progress to overt diabetes and the identification of individuals participating in a DPP at continued risk for the development of type 2 diabetes would be valuable. We designed a protocol to determine whether individuals responding appropriately to a DPP might be distinguished from individuals at continued risk for diabetes progression by sequential assessments of insulin resistance. We recently validated a multiplexed mass spectrometry assay for the measurement of intact insulin and C-peptide (Taylor SW, 2016), used this to model insulin resistance in individuals undergoing formal assessment of insulin resistance using Steady State Plasma glucose (SSPG) measurements (Abbasi F, 2018) and defined an Insulin Resistance Score (IRS) based on this data. To explore the use of this IRS in the context of an established an IRB approved protocol (Quest Testing to Assess Insulin Resistance [Q-TAIR]; Western IRB protocol # 20171395), we enrolled three cohorts totaling 40 individuals. In addition to anthropometric measurements, this protocol permitted assessment of laboratory data for fasting glucose, HbA1c, electrolytes, lipids, and the IRS at baseline, 1, 3, and 6 months, and 1 year. Data collection is complete for cohorts 1 and 2; data collection is still ongoing for cohort 3. Subjects enrolled in the individual cohorts were enrolled in individual participating practices and varied widely in the proportion offered enrollment based on laboratory test results. In keeping with expectations for adherent participants in a DPP, patients lost an average of 11 lbs. In cohorts 1 and 2, initial IRS were top or middle tertile risk in 10 of 17 patients. Importantly, normalization or improvement of laboratory test results at the conclusion of the DPP did not reflect the continued elevation of IRS risk observed in 5 of the 17 patients. These findings suggest the potential utility of the IRS in assessing changes in the degree of insulin resistance in DPP participants.